Asociacion Medica de Puerto Rico

Transcription

B LETIN
Médico-Científico de
la Asociación Médica
de Puerto Rico
Coronary Levels Of Angiotensin-Ii And Endothelin-I In Diabetic
Patients With And Without CoronaryArtery Disease
Interventional Nephrology In Puerto Rico: A Four Year
Experience
Brugada Syndrome In Puerto Rico: A Case Series
Primary Venous Thromboembolism And Malignancy, Is There Any
Relationship?
Intravenous Ascorbic Acid And Hydrogen Peroxide In The
Management Of Patients With Chikungunya
Quality Of Life In Patients With Differentiated Thyroid Cancer
At The General Endocrinology Clinics Of The University Hospital
Of Puerto Rico
Clinical And Radiological Indicators Of Severity In Patients With
Acute Pancreatitis
Celiac Trunk And Branches Dissection Due To Energy Drink
Consumption And Heavy Resistance Exercise: Case Report And
Review Of Literature
Worsening Gradient Of Aortic Stenosis With Treatment Of
Pulmonary Arterial Hypertension In Scleroderma
Uncommon Cause Of Life-Threatening Retroperitoneal
Hemorrhage In A Healthy Young Hispanic Patient:Splenic
Arte
Artery Aneurysm Rupture
Atraumatic Bilateral Femoral Neck Fractures In A
Premenopausal Female With Hypovitaminosis D (Cover Pic)
Small Cell Carcinoma Of The Uterine Cervix: A Case Report And
Literature Review
Handlebar Hernia: Case Report And Literature Review
Should We Revisit Anticoagulation Guidelines During Thyroid
Storm?
Año 107 Nro. 1
BOLETIN
CONTENIDO
Médico Científico de la Asociación Médica de Puerto Rico
Año 107 Número 1 - Enero a Marzo de 2015
3
President’s Message
Wanda Velez Andujar MD
Original articles
5
Coronary Levels Of Angiotensin-Ii And Endothelin-I In Diabetic Patients With And Without Coronary
Artery Disease
Pablo I. Altieri Md, José M. Marcial Md, Héctor L. Banchs Md, Nelson Escobales Phd, María Crespo Phd, Wilma González Bs
8
Interventional Nephrology In Puerto Rico: A Four Year Experience
Rafael Baez Md, Jose Betancourt Md, Hector J. Diaz Md, Anmelys Rivera Md, Javier Monserrate Md, Tania Ramírez Md, Martin Gorrochategui, Md, Carlos Rivera Bermudez Md, Francisco Torre Leon Md, Jose L. Cangiano Md, Facp, Fah
12
Brugada Syndrome In Puerto Rico: A Case Series
Héctor Banchs-Viñas Md, Norwin Rivera Md , Héctor Banchs-Pieretti Md, Pablo Altieri Md
16
Primary Venous Thromboembolism And Malignancy, Is There Any Relationship?
Luis Cotto Santana Md, William Caceres Perkins Md
20
Intravenous Ascorbic Acid And Hydrogen Peroxide In The Management Of Patients With Chikungunya
Victor Marcial-Vega Md, Idxian Gonzalez-Terron, Thomas Edward Levy Md
25
Quality Of Life In Patients With Differentiated Thyroid Cancer At The General Endocrinology Clinics Of
The University Hospital Of Puerto Rico
Mónica A. Vega-Vázquez Md, Loida González-Rodríguez Md, Eduardo J. Santiago-Rodríguez Mph,Anette Garcés-Domínguez Md,Lee-Ming Shum Md, Maribel Tirado-Gómez Md, Margarita Ramírez-Vick Md
33
Clinical And Radiological Indicators Of Severity In Patients With Acute Pancreatitis
Jorge Álvarez Md,Pablo Castro Md, Maria Fernández Md, Beatriz Mcmullen Md, Carmen Rodríguez Md, Jorge Vera Md
Case Report
Medicine
is a
science.
Keeping people healthy
is an
art.
Over a decade reaching this balance.
38
Celiac Trunk And Branches Dissection Due To Energy Drink Consumption And Heavy Resistance Exercise:
Case Report And Review Of Literature
Wilma González Bs, Pablo I. Altieri Md, Enrique Alvarado Md, Héctor L. Banchs MdEdgar Colón MdNelson Escobales Ph, María Crespo Phd
41
Worsening Gradient Of Aortic Stenosis With Treatment Of Pulmonary Arterial Hypertension In Scleroderma
Daniel A. Pietras Md, Francisco R. Lopez Md, Reynerio Pérez Md, Angel López-Candales Md, Jean Elwing Md
45
Uncommon Cause Of Life-Threatening Retroperitoneal Hemorrhage In A Healthy Young Hispanic Patient: Splenic Artery Aneurysm Rupture
Luis A. Figueroa-Jiménez Md, Amy Lee González-Márquez Md, Luis Negrón-García Md, Francisco Rosas-Soler, Md, Aixa
Dones-Rodríguez Md, Mayknoll De La Paz-López, Md; Mónica Santiago-Casiano Md, Edwin Rodrίguez-Cruz Md, William Cáceres-Pérkins, Facp; Luis Báez-Díaz, Facp
51
Atraumatic Bilateral Femoral Neck Fractures In A Premenopausal Female With Hypovitaminosis D
Giovanni Paraliticci Md, David Rodríguez-Quintana Md, Ariel Dávila Md, Antonio Otero-López Md
55
Small Cell Carcinoma Of The Uterine Cervix: A Case Report And Literature Review
Pilar E. Silva-Meléndez Md, Pedro F. Escobar Md, Héctor Silva Md, Sylvia Gutiérrez Md, Manuel Rodríguez Md
58
Handlebar Hernia: Case Report And Literature Review
Luisa Angel Buitrago Md, Humberto Lugo-Vicente Md
62
Should We Revisit Anticoagulation Guidelines During Thyroid Storm?
Andrew W. Petersen Md, Gisela D. Puig-Carrión Md, Angel López-Candales Md
Catalogado en Cumulative Index e Index Medicus Listed in Cumulative
Index and Index Medicus
No.
ISSN-0004-4849.
Registrado en Latindex
-Sistema Regional de Información en Línea para
Revistas Científicas de
América Latina, el Caribe,
España y Portugal
OFICINAS ADMINISTRATIVAS:
Asociación Médica de Puerto Rico
PO Box 9387 • SANTURCE, Puerto Rico 00908-9387
Tel 787-721-6969 • Fax: 787- 724-5208 - Email: secretaria@asocmedpr.org
ANUNCIOS EN BOLETIN, WEBSITEy NEWSLETTER:
Tel.: (787) 721-6939 Ext. Informártica - itsupport@asocmedpr.org - Web Site: www.asocmedpr.org
Ilustración digital de cubierta y diseño gráfico realizados por Juan Laborde-Crocela en la Oficina de
Informática de la AMPR. Impreso en los talleres gráficos digitales de la Asociación Médica de Puerto
Rico - E-mail:itsupport@asocmedpr.org
Asociacion Medica de Puerto Rico
Junta de Directores 2014/2015
Dra. Wanda G. Vélez Andújar
President
Dr. Ricardo Marrero Santiago
President Elect
Dr. Natalio J. Izquierdo Encarnación
Inmediate Past President
Dr. Luis A. Román Irizarry
Treasurer
Dra. Ilsa Figueroa Secretary
Dr. Arturo Arché Matta
Vicepresident
Dr. Raúl A. Yordán Rivera
Vicepresident
Dr. Jaime M. Díaz Hernández
Vicepresident
Dr. Benigno López López
House of Delegates President
Dr. Eliud López Vélez
House of Delegates Vicepresident
Dr. Gonzalo González Liboy
AMA Delegate
Dr. Rolance G. Chavier Roper
AMA Delegate
Dr. Luis A. Lugo Medina
Alt. Delegate AMA
Dr. Rafael Fernández Feliberti
Alt. Delegate AMA
Dra. Mildred R. Arché
Central District President
Dr. Pedro J. Zayas Santos
East District President
Dr. Rubén Rivera Carrión
South District President
Council of Political and Legislative Issues
Luis J. Lugo Vélez, MD
Affiliation and Credentials Committee
Rafael Fernández Feliberti, MD
President’s Message
The Health Systems in the United States and Puerto Rico will transform itself through fostering
Health Information Technology (HIT), which the Federal Government is implementing. To accomplish this endeavor the Electronic Health Records (EHR) need to be implemented. This system will
provide for medical services patient oriented, well-coordinated and focused on prevention.
Right now we are close to the deadline for physicians to use Electronic Health Records (EHR) if they
participate of Medicare and/or Medicaid. For the past immediate years the Federal Government
has been promoting the EHR’s use and awarded incentives to stimulate all physicians involved to
become knowledgeable on the subject and to acquire adequate meaningful use. After the deadline,
Medicare will penalize providers not using EHR appropriately.
To make a wise decision to select which EHR is best suitable for you, it is imperative that you know
which criteria apply to your specialty, your needs and your responsibilities to guarantee privacy and
secured information about your patients. You must know that Electronic Health Records are above
Electronic Medical Records. The EHR System allows you to interchange, integrate and process
patient’s information with different providers caring for the patient with the same privacy, accuracy
and information protection of regular records in compliance with the Health Insurance Portability
and Accountability Act, HIPAA.
Given that we as physicians are the ultimate responsible for our patient’s health, it is imperative we
assume leadership on the matter and give our patient’s the opportunity to benefit of participating of
the EHR System.
The Puerto Rico Medical Association has much expertise on the matter. We have been very much
involved in the HIT-EHR System from the very beginning. It will be our pleasure to give any and all
of you the assistance you might still need on the subject.
Do not forget, the EHR is here to stay. It is indispensable in the 21st Century Medical Practice.
There is no turning back!
Institute of Continuing Medical Education
Judith Román, MD
BOLETIN Editors Board Chief
Rafael Rodríguez Mercado MD
Wanda G Vélez Andújar, MD
PRMA President
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 3
ROYAL MASTERPIECE
TERRA PINK
NATURAL
Original Articles/Articulos Originales
CORONARY LEVELS OF ANGIOTENSIN-II AND
ENDOTHELIN-I IN DIABETIC PATIENTS WITH AND
WITHOUT CORONARY ARTERY DISEASE
Department of Medicine and Physiology, University of Puerto
Rico, Medical Sciences Campus, San Juan, Puerto Rico.
b
Cardiovascular Center of Puerto Rico and the Caribbean,
San Juan, Puerto Rico.
*Corresponding author: Pablo I. Altieri MD - Box 8387, Humacao, Puerto Rico 00792. E-mail: altierip@prtc.net
a
Pablo I. Altieri MDab*, José M. Marcial MDa,
Héctor L. Banchs MDab, Nelson Escobales
PhDa, María Crespo PhDa, Wilma González BSa
ABSTRACT
Two groups of patients were studied to find out the levels of angiotensin-II and endothelin-I in
the coronary and peripheral circulation. Group A consisted of eight patients with diabetes mellitus Type 2 and coronary artery disease; and Group B with diabetes mellitus without coronary
artery disease. Significant differences were found between Group A and B in the levels of both
peptides peripherally and intracoronary. This shows the importance of these peptides in the
origin of coronary artery disease and progression of the disease in diabetics with coronary artery
disease.
Index words: coronary, level, angiotensin, endothelin, diabetic, artery, disease
INTRODUCTION
For more than a century, the path
to understand coronary artery
disease (CAD) has culminated in
a perspective in which inflammation is a fundamental mechanism
of the disease. Chronic renin-angiotensin axis (RAS) activation,
mainly through the effects of
Angiotensin II (Ang-II), leads to
hypertension and perpetuates
a cascade of pro-inflammatory,
prothrombotic, and atherogenic
effects associated with end-organ
damage. The inhibition of action
and reduction in the production of
Ang-II has been mainstay therapy
to reduce the progression of hypertension and the atherosclerotic
process (1-16).
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Ang-II will activate Endothelin-I
(ET1) release by endothelial cells
(17). This peptide is a potent vasoconstrictor, but also induces
leukocyte adhesion, monocyte
chemotaxis, platelet aggregation,
stimulate the production of cytokines, promotes differentiation
processes in vascular cells and
has marked mitogenic properties
that facilitate proliferation of endothelial and vascular muscle cells
(18). Both plasma Ang-II and ET1
levels are elevated in patients with
advanced atherosclerosis and
congestive heart failure.
There exists a possibility in the
future that peripheral plasma AngII and ET1 levels might serve as
practical clinical as well as pathogenetic markers for the extent of
coronary disease. However, no
experiments have explored the
levels of these peptides in the human coronary artery circulation
itself. The association between
Ang-II, ET and progression of CAD
suggest that these peptides could
play an even more active role in
the etiology of coronary atherosclerosis inside the coronary arteries. The objectives of our study
were to quantify Ang-II and ET-1
levels in the coronary artery circulation in diabetic patients with
CAD, and correlate these levels
with the degree of CAD and compare with similar patients without
CAD.
MATERIALS AND METHODS
Two groups were studied and
compared the levels of the two
peptides with CAD. Group A consisted of eight patients with Diabetes Mellitus Type 2 (DMT2) and
Coronary Heart Disease (CHD).
Group B consisted of ten patients
with DMT2, but without CAD (control group). Right heart catheterization was done, a catheter was
positioned at the level of the origin
of the coronaries arteries and another at the end of the coronary sinus (CS) considered the coronary
artery efflux. 10 ml of blood was
collected and immediately centrifuged. The plasma was kept at
-20ºC of the temperature. Analysis of the ET1 was done using radioimmunoassay and angiotensin
II using Immunoassay techniques.
This was followed by coronary angiography. CAD was categorized
as mild, moderate or severe. Mild
was defined as less than 50% of
obstruction in any major artery.
Moderate to severe was defined
as more than 50% of obstruction
in any major artery or previous
history of interventional or surgical management. Variables were
compared using the student’s
t-test. The Ang-II and ET1 levels
were reported as mean and standard deviation. Significant values
were considered with a p < 0.05.
RESULTS
In Group A, the levels of Ang-II in
the CS were similar to those in the
aorta (46 ± 18 pg/ml vs. 35 ± 15
pg/ml, respectively) and non-significant. These values were significantly higher when compared
to Group B levels (10 ± 2 pg/ml,
P <0.001) when the patients were
grouped according the severity
of coronary disease. The Ang-II
levels were 42% lower in the mild
disease group when compared
to those with moderate to severe
disease (29 ± 2 vs. 52 ± 8 pg/ml,
respectively). The ET1 levels of
Group A at the aortic and CS were
similar (13 ± 6; 14 ± 4 pg/ml). The
levels in Group B at the aortic and
CS were (3 ± 1; 5 ± 2 pg/ml). This
difference was statistically significant P<0.001.
DISCUSSION
The RAS is a complicated and
essential system in the regulation
of vascular homeostasis (1-16).
Angiotensin II (Ang-II) is cleaved
from angiotensin I (Ang-I) by angiotensin converting enzyme
(ACE), which is localized on the
surface of endothelial cells and
in the media and adventia of the
aorta (16); a soluble form of ACE
is also found in plasma. Ang-I is
formed from angiotensinogen,
which is secreted from the liver and
cleaved by renin, which in turn is
found in the juxtaglomerular cells
in the kidney. The traditional RAS
inhibitors, angiotensin-converting
enzyme inhibitors (ACE inhibitors)
and angiotensin receptor blockers
(ARB), target the main RAS axis
described above. However, there
are additional enzymes associated with the production of Ang-II,
such as Cathepsin-G (7), as well
as other. More novel angiotensin
molecules that serve as potential
therapeutic targets: the ACE2/Ang
(1–9) axis is a new and important
pathway to compensate for the
vasoconstrictive and hyper proliferative RAS axis. A direct mechanism implicated in the production
of these distinctive angiotensin
molecules involves ACE2, a novel
component of the RAS that converts Ang-I to Ang-(1-9) and AngII
to Ang-(1-7), a peptide with vasodilator and anti-proliferative properties. The induction of ACE2 not
only holds therapeutic promise by
producing the anti-inflammatory
Ang-(1-7), but also by reducing
Ang-II levels, thereby conferring a
twofold protection against cardiovascular remodeling from ongoing
hypertension and inflammation (116).
Concomitant to the progression of
the RAS, hyperglycemia promotes
the deposition of advanced glycation end products (AGEs) that are
formed from the non-enzymatic
glycation of proteins and lipids after contact with reducing sugars
(17). The accumulation of AGEs is
an important factor in the development and progression of vascular
injury in diabetes-associated atherosclerosis (9). Both hyperglycemia and induction of the main RAS
axis will increase oxidative stress
and increase the rate of the atherosclerotic process that ultimately end in apoptosis and necrosis of
myocytes (9), hence propagating
the deleterious effects of inflammation, insulin resistance and endothelial dysfunction (15).
The inhibition of the RAS by ACE
inhibitors and ARBs has been
mainstay therapy to reduce the
onset and/or progression of hypertension, left ventricular dysfunction, diabetic renal disease and
atherosclerosis (18). For example,
inhibitors of the RAS seem to be
more effective than other medications in stopping the progression of dilated cardiomyopathy
in hamsters that have an inherited mutation that predisposes to
such a disease. In rodents, pharmacological or genetic disruption
of RAS action prevents weightgain, promotes insulin sensitivity
and relieves hypertension (8-9),
suggesting that ACE inhibitors or
ARBs may present an effective
treatment for MetS in humans. In
addition, when obese individuals
lose weight, both adipose tissue
mass and systemic RAS activity
are reduced. An increase in adipose tissue angiotensinogen has
been reported in diet-induced
obesity: further evidence that lifestyle changes are integral to targeting the underlying mechanisms
of MetS (9-10).
6 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
Systemic inflammation (15) is a
fundamental process in the development of cardiovascular disease
in patients with MetS. This process starts with the activation of
the neuro-hormonal system. Data
shows elevated intra-coronary
levels of Ang-II and endothelin-I
(E-I) in some patients with Diabetes Mellitus Type 2 (DMT2). We
measured these peptides in 8 patients with DMT2 and concomitant
MetS, normal coronary arteries
and sub-normal ejection fraction
(49 ± 5%), and discovered that the
levels of Ang-II and E-I were elevated in the CS (coronary efflux)
and aorta of these patients when
compared to the control group,
which consisted of 10 cases with
DMT2 but without MetS that were
catheterized and found to have
normal coronary arteries and a
normal ejection fraction. In the
former, MetS group, Ang-II levels
inside the coronary sinus and aorta were 46 ± 18 and 35 ± 15 pg/
ml, respectively, while Ang-II levels were 10 ± 2 pg/ml inside both
chambers of the control group
(P < 0.001). Furthermore, in the
group with MetS, the E-I levels inside the coronary sinus and aorta
were elevated at 14 ± 4 and 13 ±
6 pg/ml in both chambers, respectively, compared to 3 ± 1 pg/ml
inside both chambers of the control group (P < 0.001). This shows
that some diabetic Type 2 patients
with Mets the activation of Ang-II
and E-1 are a primordial process
leading to atherosclerotic heart
disease leading to severe coronary artery disease with its consequences. This brings the idea that
these peptides have an extremely important role, in the origin of
the atherosclerotic process, more
pronounced in diabetic patients,
especially producing inflammation
that is a crucial mechanism in the
progression of this disease. Also,
we are in process of evaluating
the role of essential fatty acids
(resolving, protectins, maresins)
in the atherosclerotic process.
REFERENCES
(1) Rocha VZ, Libby P. Obesity, inflammation and atherosclerosis. Nat Rev. Cardiol. 2009; 6: 399-409.
(2) Fukai T. Endothelial GTPCH in ENOS uncoupling and atherosclerosis. Artherioscler Thromb Vasc Biol 2007; 27: 1493-5.
(3) Ridker PM. Inflammation C-reactive protein and cardiovascular disease. Cir Res. 2014; 114: 594-595.
(4) Tedqui A, Mallat Z. Cytokines in atherosclerosis pathogenic
and regulatory pathways. Physiol Rev 2006; 86: 515-81.
(5) Hussein AA, Gottdiener JS, Bartz TM, Sotoodehnia N, et al.
Heart rhythm 2013; 10: 1425-1432.
(6) Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive
protein and other markers of inflammations in women. N Engl J
Med 2000; 342: 836-43.
(7) Fuster V, Badimon JJ, Chesebro JH. The pathogenesis of
coronary artery disease and acute coronary syndrome. N Engl J
Med. Part 1 and 2, 1992: 326, 242-50, 310-8.
(8) de Kloet, AD, Krause EG, Wood SC. The renin angiotensin
system and metabolic syndrome. Physiol Behav 2010; 100: 525534.
(9) Boustany CM et al. Activation of the systemic in rats with diet-induced obesity and hypertension Am J Physiology 2004; 287:
943-49.
(10) Altieri P, Alvarado S, Banchs H, Escobales N, Crespo M. The
role of angiotensin II and endothelin I in the cardiomyopathy of
diabetic patients. J Investigative Med 2012; 81.
(11) Heeneman S, Sluimer J, Daeman Mat Jap. Angiotensin converting enzyme and vascular remodeling. Circ Res. 2007; 101:
441-45.
(12) Highsmith RF. Endothelin-molecular biology, physiology and
pathology. Humana Press- 1998.
(13) Ferri C, et al. Angiotensin II increases the release of endothelin cells, but does not regulate its circulating levels. 1999; 96:
261-270.
(14) Patel VB, Robbins MA & Topol EJ. C-reactive protein: a
‘golden marker’ for inflammation and coronary artery disease.
Cleve Clin J Med 2001; 68: 521-524, 527-534.
(15) Hansson, GK. Inflammation, atherosclerosis and coronary
disease. N Engl J Med 2005; 352: 1685-1695.
(16) Ferrario, CM. Role of angiotensin II in cardiovascular disease therapeutic implications of more than a century of research.
J Renen Angiotensin Aldosterone Syst 2006; 7: 3-14.
(17) Iwanaga Y, et al. Differential effects of angiotensin II versus
endothelin-1 inhibitions in hypertrophic left ventricular myocardium during transition to heart failure. Circulation 2001; 107: 606612.
(18) Luscher, TF & Burton, M. Endothelins and endothelin receptors antagonists: therapeutic consideration for a novel class of
cardiovascular drugs. Circulation 2000; 102: 2434-2440.
(19) Roig E. et al. Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive
heart failure. Eur Heart J 2000; 21: 53-57.
(20) Zouridakis, EG, et. al. Increased plasma endothelin levels in
angina patients with rapid coronary artery disease progression.
Eur Heart J 2001; 22: 1578-1584.
(21) Zeiher, AM, Ihling, C, Pistorius, K, et al. Increased tissue endothelin immunoreactivity in atherosclerotic lesion associated with
acute coronary syndromes. Lancet 1994; 344: 1405-1406.
(22) Bannenberf G, Serham C IV. Specialized pro-resolving lipid
mediator in the inflammatory response: An update. Biochim Biophys Acta 2010; 1801(12):1260-73.
RESUMEN
Dos grupos de pacientes fueron estudiados para encontrar los niveles de angiotensina II y endotelina I en la circulación coronaria y periférica. El Grupo A consistió
de ocho pacientes con diabetes mellitus Tipo 2 y enfermedad coronaria; y el Grupo
B 10 pacientes con diabetes mellitus sin enfermedad coronaria. Se encontraron
diferencias significativas entre el grupo A y B en los niveles de ambos péptidos
periféricamente e intra-coronaria. Esto muestra la importancia de estos péptidos en
el origen de la enfermedad coronaria y progresión de la enfermedad en diabéticos
con enfermedad coronaria.
INTERVENTIONAL NEPHROLOGY IN PUERTO RICO:
A Four Year Experience
Nephrology Section, Internal Medicine Department, University
of Puerto Rico School of Medicine, San Juan, Puerto Rico.
b
Internal Medicine Residency Program, University of Puerto Rico
School of Medicine.
c
University of Puerto Rico School of Medicine
d
Vascular Access Unit, Auxilio Mutuo Hospital, San Juan, Puerto
Rico.
*Corresponding
author:
Jose
L.
Cangiano
MD
313
Domenech
Avenue,
Suite 101, San Juan, Puerto Rico 00918. E-mail: jlcangiano@
yahoo.com
a
Rafael Baez M,Jose Betancourt MDb, Hector J. Diaz MDb, Anmelys Rivera MDb, Javier
Monserrate MDc, Tania Ramírez MDa, Martin
Gorrochategui, MDd, Carlos Rivera Bermudez MDa, Francisco Torre Leon MDa, Jose L.
Cangianoa* MD, FACP, FAHA
ABSTRACT
Puerto Rico is one of the most prevalent areas covered by Medicare in need of renal replacement therapy for which interventional procedures are performed. A cumulative analysis of this
management is reported in patients during the period between June 2007 and August 2010.
Experience accumulated with 3755 surgical patients revealed that 58% had intravascular catheters, 28% had arteriovenous fistulas, 15% had arteriovenous grafts, and 2% without vascular access. Procedures performed in these patients were: catheter introduction in 1990 cases
(33%), angioplasty in 751 cases (20%), angiography in 450 cases (12%), thrombectomy in 413
cases (11%) and venous mapping in 151 cases (4%). The success rates of these procedures
were evaluated by analysis of the Society of Interventional Radiology (SIR) criteria for Lifeline
Vascular Access. Using SIR definition of success rate for at least one session that includes “declots”, placement of catheters and angioplasty, our results revealed an average of 98.2% overall
success rate greater than the standard value KDOQI/SIR (> 85% ). This study has documented
for four years the success rate of Vascular Interventional Nephrology Center at Auxilio Mutuo
Hospital. In order to maintain this success rate is necessary to further evaluate its effectiveness
and, most importantly, the development of an educational program for vascular access in patients with chronic kidney disease prior to placement in dialysis units.
Index words: interventional, nephrology, Puerto Rico, experience
INTRODUCTION
Puerto Rico continues to be one
of the most prevalent areas covered by Medicare in need of renal
replacement therapy. In 2009, a
report from the Network Council
on Renal Disease of New Jersey, revealed that in Puerto Rico
4470 cases received dialysis with
a prevalent rate of 1,126 persons
per million (ppm); a total growth
of +3.58%. On the other hand,
the incidence rate was reported
to be 345 ppm with 1,370 new
cases (1). The total growth for
2000-2009 was +2.41% (USA it
was +2.0%). The main causes of
End Stage Renal Disease (ESRD)
in Puerto Rico are diabetes mellitus and hypertension. Of the
1370 new cases, 911 (67%) were
diabetic and 200 (15%) hypertensive. An increased frequency
has been reported with diabetes
+3.04% and hypertension +3.75%.
Additionally, one of the main concerns of this report was the high
mortality in Puerto Rico as compared to USA mainland (23.4% vs.
20.3% respectively). In looking for
solutions to this vexing problem
in our island, the Network Council
has provided great support to identify the reasons involved for disparity in mortality outcome. Several recommendations have been
provided to strengthen the renal
community in Puerto Rico. Among
them the Network has strengthened support for the development
of Centers of Excellence for procedures needed in this type of
patients, such as Vascular Access
Units. With this purpose in mind,
on February 2005 an Interventional Nephrology Unit for Vascular
Access was established in Auxilio
Mutuo Hospital in San Juan, Puerto Rico. An initial report of this experience has been published (2).
It was the first and has remained
the only unit to be serviced by a
group of interventional nephrologists on an outpatient basis. Before its establishment, vascular
access problems were referred
mainly to vascular surgeons and/
or interventional radiologists. It
is now accepted that nephrologists are well suited for training
and development of skills for
performing invasive procedures
because of their knowledge of renal replacement therapy. In addition, one of the main advantages
of the interventional progress by
nephrologists is that it has minimized delays in performing the
procedures, hospitalizations and
the use of temporary catheters
therefore improving the quality of
care for the chronic kidney disease patient. At present, there are
three trained interventional nephrologists with excellent procedural skills participating in this program. The procedures performed
at this center include angiograms,
percutaneous balloon angioplasty,
thrombectomies, tunneled hemodialysis catheter placement and
venous mapping. A cumulative
analysis is herein reported in 3755
patients intervened for the period between June 2007 to August
2010. Our data was compiled and
analyzed by Lifeline Vascular Access.
RESULTS
Our four year experience in an Interventional Nephrology Vascular
Access unit in San Juan in 3755
patients intervened revealed that
58% of the patients had intravascular catheters, 28% arteriovenous fistulas, 15% arteriovenous
grafts and 2% no vascular access. The procedures performed
in these patients included: 1990
(33%) catheter placement, 751
(20%) angioplasty, 450 (12%) angiogram, 413 (11%) thrombectomy, and 151 (4%) vein mapping
(see Figure 1). Figure 2 shows the
reasons for referrals in our group
of patients. Catheter exchange
(29%) was the most common reason, followed by clotted arteriovenous fistula (23%), malfunctioning
fistula (21%), change of modality
(17%), arteriovenous fistula stenosis (6%), vein mapping (3%)
and no vascular access (1%).
Figure 3 depicts the procedure
success rate as analyzed by SIR
(Society of Interventional Radiology) criteria from Lifeline Vascular Access. Using SIR definition
of success rate for at least one
session including declots, catheter placements and angioplasties,
our results revealed an average of
98.2% of overall success rate exceeding the KDOQI/SIR standard
Figure 1: Shows the procedures performed. Each column depicts the
number of patients with the respective percentage.
53%
1990
20%
12%
11%
4%
751
450
413
151
Figure 2: Shows the reason for referral of the 3755 patients in the study.
Each column depicts the number of patients with the respective percentage.
21%
794
29%
23%
857
1091
17%
636
6%
220
1%
36
value (= or > 85%). Taking into
consideration the SIR threshold
for complications being 5%, we
observed a minimal complication
rate in our procedures of 0.45%,
which is significantly below the established threshold.
DISCUSSION
This retrospective study reports
the four-year experience in an
3%
121
Interventional Nephrology Vascular Access Unit in San Juan
Puerto Rico after establishment in
2004. A total of 3,755 cases were
performed during the study period from 2007 to 2010.The period
studied was from 2007 to 2010.
The procedures were catheter
placement, angioplasty, angiograms, thrombectomy, and vein
mapping. Most of the complications of tunneled catheter placement are related to the experience
Figure 3: Shows the procedure success rate. Each column depicts the
number of patients with the respective percentage.
disease patients prior to placement in dialysis units.
99%
REFERENCES
SIR/KDOQI = 85%
98%
of the operator and the use of ultrasound guidance for cannulation of
the vein. Blind insertion may result
in complication rates as high as
5.9% (4). Complications observed
include pneumothorax, hemothorax, hemomediastinum, recurrent
laryngeal nerve palsy, or bleeding which may require exploration
and/or blood transfusion. Our Vascular Unit uses ultrasonogram and
fluoroscopic guidance for cannulation of veins and the success rate
was 95.4%. The complication for
tunneled catheters was acceptable with minimal complications
were observed, most of them mild
or moderate hematomas.
Venous stenosis may be a hazardous lesion to treat. Angioplasty is
not always successful. The main
complication associated to angioplasty is venous rupture (5,6)
with an incidence between 1.7%
to 3.8% (7,8). The most common
lesion producing venous stenosis
is intimal fibromuscular dysplasia.
The interventionist must be careful
in avoiding the tear of veins. In our
study, no episodes of venous rupture were reported and the majority of complications were minimal,
mostly related to the development
of grade 1 and 2 hematomas.
Thrombectomy was also successful in our team. Large series
of thrombectomies have reported
a success ratio of 95% in 1176
98%
98%
cases (9,10). However, success
rates for cardiovascular thrombectomies have been from 62% to
95% (11,12). The most common
complication associated to thrombectomy has been vein rupture
resulting in hematomas. On the
other hand, the major complication related to thrombectomy is
peripheral vascular embolization.
Some studies have reported this
complication to be as high as 6%
(13). In our current experience, no
peripheral arterial embolization
was reported.
The safety and efficacy of vascular
access related procedures were
also demonstrated in our study.
Complications were minimal and
reported as 0.45% not affecting
the well being of the patient. The
overall success rate of 98.2% by
the SIR criteria is well above the
standard SIR criteria of 85% and
compares to many Vascular Centers throughout the United States.
In conclusion, this four-year study
has documented the success rate
of the Interventional Nephrology
Vascular Center at the Auxilio Mutuo Hospital. This progress has
been well accepted by our nephrologists and patients. In order
to maintain this successful rate we
need to continue assessing its effectiveness and, most important,
develop a vascular access educational program with chronic kidney
1.Report from Network Council on Renal
Disease of New Jersey. Puerto Rico Data;
2009
2. Torre León F, Rivera Bermúdez C,
Hernández V, Silva J, Santiago Delpín E.
Interventional Nephrology in Puerto Rico.
Semin Dial 2006;19:176-9
3. Sacks D, McClenny TE, Cardella JF,
Lewis CA, Society of Interventional Radiology Clinical Practice Guidelines J
Vasc Interv Radiol 2003; 14:S199–S202
4. Bour ES, Weaver AS, Yang HC, Gifford
RR. Experience with the double lumen Silastic catheter for hemoaccess. Surg Gynecol Obstet. 1990 Jul;171(1):33-9.
5. Beathard GA. Management of complications of endovascular dialysis access procedures Semin Dial. 2003 JulAug;16(4):309-13
6. Pappas JN, Vesely TM. Vascular rupture during angioplasty of hemodialysis
raft-related stenosis J Vasc Access. 2002
Jul-Sep;3(3):120-6
7. Rundback JH, Leonardo RF, Poplausky
MR, Rozenblit G. Venous rupture complicating hemodialysis access angioplasty:
percutaneous treatment and outcomes
in seven patients AJR Am J Roentgenol. 1998 Oct;171(4):1081-4
8. Raynaud AC, Angel CY, Sapoval
MR, Beyssen B, Pagny JY, Auguste M.
Treatment of hemodialysis access rupture during PTA with Wallstent implantation J Vasc Interv Radiol. 1998 MayJun;9(3):437-42
9. Beathard GA, Welch BR, Maidment HJ.
Mechanical thrombolysis for the treatment
of thrombosed hemodialysis access grafts
Radiology. 1996 Sep;200(3):711-6
10. Sharafuddin MJ, Kadir S, Joshi
SJ, Parr D. Percutaneous balloon-assisted aspiration thrombectomy of clotted
hemodialysis access grafts J Vasc Interv
Radiol. 1996 Mar-Apr;7(2):177-83.
11. Overbosch EH, Pattynama PM, Aarts
HJ, Schultze Kool LJ, Hermans J, Reekers JA. Occluded hemodialysis shunts:
Dutch multicenter experience with the
hydrolyser catheter Radiology. 1996
Nov;201(2):485-8.
12. Trerotola SO, Vesely TM, Lund
GB, Soulen MC, Ehrman KO, Cardella JF.
Treatment of thrombosed hemodialysis
access grafts: Arrow-Trerotola percutaneous thrombolytic device versus pulsespray thrombolysis. Arrow-Trerotola Percutaneous Thrombolytic Device Clinical
Trial. Radiology. 1998 Feb;206(2):403-14
13. Lazzaro CR, Trerotola SO, Shah
H, Namyslowski J, Moresco K, Patel N.
Modified use of the arrow-trerotola percutaneous thrombolytic device for the
treatment of thrombosed hemodialysis
access grafts. J Vasc Interv Radiol. 1999
Sep;10(8):1025-31.
RESUMEN
Puerto Rico es una de las zonas de mayor prevalencia de enfermedad crónica renal, cubiertas por Medicare, en necesidad de intervenciones quirúrgicas. Un análisis acumulativo
de estas intervenciones y tratamientos se informa en este documento en 3,755 pacientes
durante el período comprendido entre junio de 2007 y agosto de 2010. Nuestra experiencia
en 3,755 pacientes reveló que al 58% se le realizó inserción de catéteres intravasculares,
28% creación de fístulas arteriovenosas, y 15% tuvieron injertos arteriovenosos. Los procedimientos realizados en estos pacientes fueron los siguientes: implantación de catéter en
1990 casos (33%), angioplastia en 751 casos (20%), angiograma en 450 casos (12%), trombectomía en 413 casos (11%) y mapa venoso en 151 casos (4%). La tasa de éxito de los
procedimientos se evalúa por análisis de SIR (Sociedad de Radiología Intervencional) por
criterios de Acceso Vascular “Lifeline”. Usando la definición SIR nuestros resultados revelaron un promedio de 98.2% de tasa de éxito global superior al valor KDOQI/SIR estándar (>
85%). Este estudio ha documentado la tasa de éxito del Centro Vascular Intervencionista de
Nefrología del Hospital Auxilio Mutuo superando lo establecido por SIR. Con el fin de mantener esta tasa de éxito es necesario seguir evaluando su eficacia y, lo más importante, el
desarrollo de un programa educativo de acceso vascular en pacientes con enfermedad renal
crónica antes de admitirse en las unidades de diálisis.
BRUGADA SYNDROME IN PUERTO RICO:
A Case Series
Héctor Banchs-Viñas MDa
Norwin Rivera MDb
Héctor Banchs-Pieretti MDa
Pablo Altieri MDa*
University of Puerto Rico School of Medicine, Department of
Medicine, Cardiology Section. San Juan, Puerto Rico.
Veterans Affairs Caribbean Healthcare System, Department of
Medicine, San Juan, Puerto Rico.
*Corresponding author: Pablo I. Altieri MD - Box 8387, Humacao, Puerto Rico 00792. E-mail: altierip@prtc.net
a
b
ABSTRACT
Brugada syndrome (BrS) is characterized by ST-segment changes in the right precordial
ECG leads and a high incidence of sudden death in patients with structurally normal
hearts. Life-threatening ventricular arrhythmias are the hallmark of Brugada syndrome.
The incidence and prevalence of BrS in Puerto Rico, to our knowledge, has never been
studied and there is only one case report of BrS in Puerto Rico in the literature. We review three cases of BrS in Puerto Rican patients who presented to our institution with
syncope reviewing the literature.
Index words: brugada, syndrome, Puerto Rico, case, series
INTRODUCTION
Brugada Syndrome (BrS) is a hereditary cardiac channelopathy
that predisposes affected individuals to ventricular arrhythmias.
BrS is associated with sudden
cardiac death in otherwise healthy
individuals and is characterized
by ST-segment elevation in the
right precordial ECG leads and a
high incidence of sudden death in
patients with structurally normal
hearts [1]. It is difficult to estimate
the true prevalence of the disease
in the general population because
the ECG pattern can be dynamic and is often concealed [2]. The
clinical diagnosis of BrS is made
when a type 1 BrS ECG pattern
occurs in association with a personal history of syncope secondary to ventricular tachycardia (VT)
or ventricular fibrillation (VF), or a
history of aborted sudden cardiac
death. This diagnostic electrocardiographic pattern has a worldwide prevalence in the general
population of 1 of 1,000 individuals, representing a relevant health
care issue [3]. The mainstay treatment in BrS is implantation of a
cardioverter defibrillator (ICD).
The incidence and prevalence of
BrS in Puerto Rico, to our knowledge, has never been studied and
there is only one case report of
BrS in Puerto Rico in the literature
[1]. We review three cases of BrS
in Puerto Rican patients who presented to our institution with syncope reviewing the literature.
Case History 1
A 62 year-old man with past history of arterial hypertension and
type 2 diabetes mellitus was at a
pre-operative evaluation for elective non-cardiac surgery when
he had sudden onset of cramping pain on his left shoulder
followed by loss of consciousness
for approximately one minute. Vital signs after the event were normal except for a temperature of
39°C. ECG performed after he
regained consciousness revealed
ST segment elevation in leads
V1-V3 (see Figure 1), and he was
taken emergently to the cardiac
catheterization laboratory due to
suspected STEMI. Coronary angiography showed normal coronary
arteries with no obstructive lesions.
The left ventriculogram showed
preserved left ventricular systolic function. Transthoracic echocardiography showed no structural abnormalities with normal
Figure 1. Electrocardiogram showing coved ST segment elevations
from v1-v3 consistent with type 1 Brugada pattern
left ventricular ejection fraction.
Upon further questioning he denied past episodes of syncope,
loss of consciousness, seizure
activity, a history of arrhythmias
and family history of sudden cardiac death. He also denied alcohol,
cigarette or drug abuse. Laboratory studies, including complete
blood count, serum chemistries,
hepatic and renal function tests,
were within normal limits. Troponin I, CK-MB and myoglobin levels were also within normal limits.
Based on clinical presentation
and electrocardiographic findings Figure 2: Initial ECG showing type 1 Brugada pattern with coved ST-seghe was diagnosed with Brugada ment elevation descend with upward convexity, T-wave inversion and ≥
syndrome and an ICD was im- 2mm J-point elevation in V2-V3.
planted. He was discharge home
without complications.
Case History 2
A 29-year-old man with history of
bronchial asthma presented to the
emergency department with retrosternal chest pain of three hours
duration and loss of consciousness. Pain was described as
10/10 in intensity, oppressive, and
non-radiating. Chest pain started after an episode of emotional
stress, after which he suddenly
lost consciousness for approximately three minutes, regaining
consciousness spontaneously. By
the time he arrived to the emergency department all symptoms
had resolved.
Review of systems was remarkable for three episodes of sudden
loss of consciousness in the past
year. These episodes were not associated with exertion and he did
not seek medical care at that time.
He denied palpitations, history of
heart disease, cardiac surgery,
shortness of breath, diaphoresis,
seizures, or family history of SCD.
He admitted to recent cocaine
abuse including the day of the
event. Physical examination and
vital signs were unremarkable.
Initial complete blood count and
serum chemistries were within
normal limits, including potassium
levels. Troponin, creatine kinase
(CK-MB) and myoglobin were all
negative. A 12-lead ECG (see Figure 2) showed ST-segment elevation in the right precordial leads
Figure 3: Follow up ECG showing resolution if the Brugada pattern
(V1-V3), initially diagnosed as
an antero-septal acute myocardial infarction. Closer inspection
showed coved ST-segment elevation of more than 2 mm in the
right precordial leads (V1-V3) with
T-wave inversion compatible with
type 1 Brugada pattern. A follow
up ECG (see Figure 3) showed
resolution of the Brugada pattern.
2D-Echocardiogram showed normal left ventricle systolic and diastolic function with 60% ejection
fraction, normal cardiac chambers
dimensions with no structural abnormalities. Due to history of recent and recurring syncope of
unexplained cause, and the presence of type 1 Brugada pattern on
ECG, an implantable cardioverter-defibrillator (ICD) to treat ventricular arrhythmias and prevent
SCD was offered but he declined
this option.
Case History 3
A 62 year-old man with past history
of multiple myeloma was brought
to the emergency department after experiencing an episode of
sudden loss of consciousness
while driving in heavy traffic. A bystander started cardiopulmonary
resuscitation until paramedics arrived, intubated him and took him
to the nearest emergency department. Upon arrival to the emergency room ECG revealed coved
ST elevations in leads V1-V3 (see
Figure 4). He had six episodes of
ventricular tachycardia with hemodynamic deterioration that required electrical cardioversion. He
was transferred to our institution
with a suspected STEMI for emergent cardiac catheterization. Coronary angiography showed no significant lesions and transthoracic
Figure 4. Marked coved ST segment elevations and negative T wave of
right precordial leads in a patient with Brugada Syndrome.
Figure 5: The 3 recognized ECG patterns seen in Brugada Syndrome.
echocardiography revealed no
structural abnormalities and normal left ventricular ejection fraction. Medical history was negative
for previous episodes of syncope,
arrhythmias and family history of
sudden cardiac death. Laboratory
workup revealed mild leukocytosis and Troponin I elevation with
normal serum chemistries, renal
and liver function. Based on the
ECG findings and a history of syncope and ventricular tachycardia
the diagnosis of BrS was made
and the patient received an ICD
for secondary prevention. He was
extubated without complications
and discharged home in stable
condition.
DISCUSSION
Brugada syndrome (BrS) was
first described in 1992 as a disease that predisposes apparently
healthy individuals to sudden cardiac death [3]. It is as an autosomal dominant inherited arrhythmic
disorder characterized by ST elevation with successive negative
T waves in the right precordial
leads without structural cardiac abnormalities [4]. The ECG
changes can be dynamic and
sometimes are concealed and
may be observed only in certain
situations, such as fever, intoxication, vagal stimulation, electrolyte
imbalance and with some drugs
(sodium channels blockers) that
may unmask a Brugada pattern
[5]. There are three recognized
ECG patterns seen in BrS, but
only the type 1 pattern is considered diagnostic (see Figure 5). In
individuals presenting with patterns 2 and 3 provocative maneuvers must be performed in order
to unmask the type 1 pattern. Although most cases of BrS display
right precordial ST-segment elevation, isolated cases of ST-segment elevation in the inferior and
left precordial leads have been reported in Brugada-like syndromes
[2]. It is important to recognize the
Brugada ECG pattern and to be
aware that patients with BrS may
be initially diagnosed with STEMI.
Life-threatening ventricular arrhythmias are the hallmark of Brugada syndrome and are thought to
arise as a result of accelerated inactivation of the sodium channels
and predominance of transient
outward potassium current to generate a voltage gradient in the right
ventricular layers. This gradient
triggers VT/VF possibly through
a phase 2 reentrant mechanism
[5,9]. Patients are at risk for sudden cardiac death (SCD) due to
ventricular arrhythmias, which can
be the first manifestation of the
disease, and often occur at rest
and at night [2]. The syndrome
manifests predominantly in men in
the third and fourth decades of life
[10]. Roughly 15% to 20% of the
patients with BrS have mutations
at the alpha subunit of the sodium
channel gene (SCN5A) but recent
studies have linked the syndrome
to mutations in the genes that encode the α and β subunit of the
calcium channel and the gene that
encodes glycerol-3-phosphate dehydrogenase 1-like enzyme (GPD1L)[6,7]. Brugada phenotype has
been reported to be up to 8 to 10
times more prevalent in men than
in women and hormonal influence
might play a role in the phenotypic
manifestations of BrS [6]. Patients
with BrS have an increased incidence of atrial arrhythmias with
atrial fibrillation being the most
common, found in 11% to 14%
of patients [4,7]. Enhanced duration of atrial action potential and
increased intra-atrial conduction
time may contribute to the genesis of atrial arrhythmias in BrS [7].
In patients with BrS and a history
of aborted SCD or syncope secondary to VT/VF, an implantable
cardioverter defibrillator (ICD) is
the first line therapy and is the
only proven effective treatment for
the disease [2]. For patients with
recurrent VT/VF and ICD shocks,
adjunctive medical with quinidine
may be required for suppression
of ventricular arrhythmias [4].
REFERENCES
1. Martínez H, Montano L, Rodríguez-Ospina L, et al. A case of Brugada Syndrome
in a 63 y/o man with chest pain. Bol Asoc
Med PR. 2008 Oct-Dec: 100(4):86-8
2. Antzelevitch C, Brugada P, Borggrefe
M, et al.Brugada Syndrome: Report of
the Second Consensus Conference: Endorsed by the Heart Rhythm Society and
the European Heart Rhythm Association.
Circulation. 2005; 111:659-670.
3. Priori SG, Gasparini M, Napolitano C,
et al. Risk Stratification in Brugada Syndrome. Results of the PRELUDE Registry. J Am Coll Cardiol.2012;59:37-45.
4. Mizusawa Y, Wilde AA. Brugada Syndrome. Circ Arrhythm Electrophysiol.
2012;5:606-616.
5. De Luna AB, Brugada J, Baranchuk A,
et al. Current electrocardiographic criteria
for diagnosis of Brugada pattern: a consensus report. J Electrocardiol. 2012; 45:
433-442.
6. Benito B, Sarkozy A, Mont L, et al. Gender Differences in Clinical Manifestations
of Brugada Syndrome. J Am Coll Cardiol
2008; 52: 1567-73.
7. Francis J, Antzelevitch C. Atrial Fibrillation and Brugada Syndrome. J Am Coll
Cardiol.2008;51:1149-53.
8. Wilde AA, Antzelevitch C, Borggrefe
M,et al.Proposed Diagnostic Criteria for
the Brugada Syndrome Consensus Report. Circulation.2002;106:2514-2519.
9. Nagase S, Kusano KF, Morita H, et al.
Longer Repolarization in the Epicardium
at the Right Ventricular Outflow Tract
Causes Type 1 Electrocardiogram in patients with Brugada Syndrome. J Am Coll
Cardiol 2008; 51:1154-61.
10. Prystowsky EN, Padanilam BJ, Joshi
S, Fogel RI. Ventricular Arrhythmias in the
Absence of Structural Heart Disease. J
Am Coll Cardiol. 2012;59:1733-44.
RESUMEN
El Síndrome de Brugada es un desorden cardiaco hereditario
que causa arritmias ventriculares en personas sin enfermedad estructural cardiaca. Este síndrome puede causar muerte
súbita y tiene un patrón hereditario autosómico dominante
causando mutaciones en los canales de iones del corazón,
predisponiendo a los individuos con la mutacion a arritmias
ventriculares. El tratamiento para esta condición consiste en
la implantación de un desfibrilador cardiaco. El Síndrome de
Brugada no ha sido estudiado en Puerto Rico y a nuestro
entender solo existe en la literatura un reporte de caso del
Síndrome de Brugada en Puerto Rico. En este artículo presentamos tres casos de Sindrome de Brugada que fueron
atendidos en el Centro Cardiovascular de Puerto y hacemos
una revisión de la literatura.
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Primary venous thromboembolism and malignancy, is
there any relationship?
Department of Internal Medicine San Juan City Hospital, San Juan, Puerto Rico.
Hematology-Oncology Department, VA Caribbean System and San Juan City Hospital, San Juan, Puerto Rico.
*Corresponding author: Luis Cotto Santana MD – Internal Medicine Department, San
Juan City Hospital, San Juan, Puerto Rico 00926. E-mail: luiscottosantana@gmail.
com
a
b
Luis Cotto Santana MDa*
William Caceres Perkins MDb
ABSTRACT
Deep venous thrombosis and pulmonary embolism can be the first manifestation of cancer. In light of this association screening for cancer has been proposed in patients with
primary VTE to identify an undiagnosed malignancy. Method: Descriptive, retrospective
record review that includes 3244 patients from VA San Juan Caribbean system with diagnosis of lung (small and non-small cell), prostate, colon, rectum, liver, stomach, esophagus, pancreas and breast cancer, lymphoma or leukemia from 2005 to 2010 evaluated for
primary VTE during five years prior to their malignancy diagnosis. Secondary outcomes
evaluated were age and staging at the time of VTE diagnosis. The inclusion criteria were
veterans with age 21 years old or more and with diagnosis of the above mentioned malignancies. The exclusion criteria were pregnancy five years to the diagnosis of malignancy, history of coagulopathy or use of anticoagulation at moment of the diagnosis of
malignancy. Results: 3244 records were reviewed. From the 2858 that met the inclusion
criteria 22 (8%) had history of VTE five years before their malignancy, most of them (14%)
with diagnosis of pancreatic malignancy. After we studied VTE by site of malignancy:
7% of pancreatic, 0.8% of prostate, 0.5% of colon, 0.6% of bladder, 0.8% of liver, 0.4% of
lung, 1.1% of rectal cancer patients but none with leukemia, stomach, esophagus, breast
cancer had VTE. Regarding patients with advanced metastatic cancer at the moment of
their diagnosis, only 13% had a prior event of VTE. Conclusion: Although at this point
there is no clear indication to screen for malignancy in patients presenting primary VTE
our results point out an increased number of VTE in patients with subsequent pancreatic
cancer. More research is needed before further recommendations on cancer screening in
patients with VTE.
Index words: primary, venous, thromboembolism, malignancy
INTRODUCTION
Deep venous thrombosis and
pulmonary embolism, collectively
termed venous thromboembolism
(VTE), can be the first manifestation of cancer. It has been speculated that the development of VTE
result from interactions between
multiple genetic and environmental risk factors. Unprovoked (or
primary) VTE is defined as a principal diagnosis of VTE during admission in patients without history
of cancer or hospitalization in the
previous six months. Provoked (or
secondary) VTE is defined as a diagnosis of VTE that occur during
hospitalization or in patients
requiring hospitalization within 90
days of one surgical procedure,
trauma or hospitalization, patients
with immobilization for more than
7 days, using oral contraceptive
or hormone replacement therapy
as well as those in the postpartum
period (1, 2). Several inherited
or acquired coagulation defects
have been identified as VTE risk
factors over the past year (3). On
the other hand and in light of its
association with malignancies,
a more extensive screening for
cancer has been proposed in
patients with primary VTE. Identifying previously undiagnosed
cancer in patients with VTE may
be important for several reasons
including diagnosis at a curable
stage (4). Some retrospective
studies suggested that limited
cancer screening (careful medical
history, physical examination and
basic blood work) was adequate
to detect most cases of undiagnosed cancer in patient with VTE
(3). They also found that the highest percent of diagnosis of cancer
was six month after an episode
of VTE (3). The main objective
of this research is to identify the
most common type of malignancies that present after a primary
VTE in order to establish screening guidelines for those patients.
METHOD
Data and study sample
The IRB office at Veterans Affair
Caribbean System in San Juan,
Puerto Rico approved this study.
The tumor data registry center in
VA Hospital, San Juan P.R. was
reviewed for veterans 18 years
of age or older with diagnosis of
lung (small and non-small cell),
prostate, colon, rectum, liver,
stomach, esophagus, pancreas and breast cancer, lymphoma and leukemia from January
1, 2005 to December 31, 2010.
Those electronic medical records
were evaluated for an admission
diagnosis of primary VTE during
five years prior to the diagnosis of
malignancy.
Primary VTE was defined as a
VTE in patients without history
of cancer or hospitalization in the
previous 6 months. Provoked (or
secondary) VTE was defined as a
VTE during a hospitalization or in
patients requiring hospitalization
within 90 days of a surgical procedure, trauma or hospitalization,
patients with immobilization for
more than 7 days, using oral contraceptive or hormone replacement therapy as well as those in
the postpartum period. Patients
were excluded if they had a diagnosis of malignancy prior to January 1, 2005, history of coagulopathy or pregnancy five years prior
to the diagnosis of malignancy.
excluded based on exclusion criteria. One hundred fourteen were
on anticoagulation at moment of
the diagnosis of malignancy and
272 had a prior diagnosis of malignancy between 2005 and 2010.
Of the 2859 patients that met the
inclusion criteria, 1559(54%) had
prostate cancer, 432(15%) colon cancer, 234(8%) lung cancer,
164(5%) bladder cancer, 17(5%)
breast cancer, 132(4%) hepatic
cancer, 82(2%) gastric cancer,
42(1%) pancreatic cancer, 89(3%)
rectal cancer, 44(1%) esophageal
cancer and 64(2%) had leukemia.
(see Figure 1)
Twenty-one cases (0.7%) of primary VTE were identified from
those patients meeting our inclusion criteria. They occurred
as follows: 13 (0.83%) of those
with prostate cancer, 2(0.5%) of
those with colon cancer, 1(0.6%)
of those with bladder cancer,
1(0.8%) of those with hepatic
cancer, 3(7%) of those with pancreatic cancer, 1(1.1%) of those
with rectal cancer and none of
those with gastric, lung, esophageal, breast cancer or leukemia
patients had an event of primary
VTE in the five years prior their
diagnosis of malignancy (see
Figure 2).
Figure 1. Number of patients evaluated by type of malignancies
included in the research.
Validation of diagnosis
Diagnosis of primary VTE was
confirmed after reviewing anticoagulation clinics record and/or imaging studies.
Statistics
Descriptive statistics were used to
analyze the collected data. RESULTS
Three thousand two hundred forty four patients had a diagnosis of
lung (small and non-small cell),
prostate, colon, rectum, liver,
stomach, esophagus, pancreas
and breast cancer, lymphoma and
leukemia within January 1, 2005
to December 31, 2010. Three
hundred eighty six (12%) were
Figure 2. Percent of patients with VTE within five years prior to their
diagnosis of malignancy
Most patients with primary VTE
(95%) presented lower extremity
deep vein thrombosis (DVT) and
1 (5%) had atrial thrombi. There
was no upper extremity DVT or
pulmonary embolism identify in
our population.
Regarding time of presentation
of VTE before the diagnosis malignancy, 9 patients (43%) were
diagnosed at 0-6 months interval,
none within 7-12 months, 3(14%)
within 13-18 months, 2(9%) within
19 to 24 months, 2(9%) within 25
to 36 months, 3(14%) within 37
to 48 months and 2(9%) 49 to 60
months interval prior to their diagnosis of malignancy (see Figure
3). Staging at the time of diagnosis of malignancy confirmed metastasis in 4 (19%) patients with
previous primary VTE and none
in 16(76%) patients. One (5%)
patient had no documented metastatic status (see Figure 4).
6- Chew, H. et al; Incidence of venous thromboembolism and its effect on survival among patients with common cancers, Annals of
Internal medicine, vol. 166, Feb 2006, pags. 458 – 464.
7- Nordstrom M, Lindblad B, Anderson H, et al Deep venous thrombosis and occult malignancy: an epidemiological study.
8- Cornuz J, Pearson SD, Creager MA, et al. Importance of findings on the initial evaluation for cancer in patients with symptomatic
idiopathic deep venous thrombosis.
RESUMEN
Figure 3. Percent of number of patients by time interval between diagnosis of primary VTE and malignancy
DISCUSSION
White R. et al described an increase in primary VTE in patients
with leukemia, non-Hodgkin lymphoma and pancreatic, ovarian, stomach, renal cell and lung
cancer, most of them within four
months prior to the diagnosis of
malignancy (1). In accordance
with their findings, most of primary VTE in our population occurred in patients with pancreatic
cancer. Interestingly, the time interval from the primary VTE and
the diagnosis of malignancy also
occurred within six months.
On the contrary the metastatic
status of our population at moment of diagnosis was much
lower in relation with the patients
studied by White (1). This finding
and the low percent of patients
with malignancy who had a previous diagnosis of primary VTE
in our population are most likely related to our small sample
population.
Other researchers
previously studied other secondary outcomes of our study. For
example, although some suggest
that an upper extremity DVT is a
common presentation in patients
with malignancy (5), there were
Figure 4. Percent of patient metastatic status at moment of diagnosis of
malignancy in patient with primary VTE.
no events of upper extre mity
DVT reported in our population.
Chew et al, (6) report a high prevalence of pulmonary embolism
(PE) associated with abdominal
cavity malignancies particularly
ovarian, biliary or stomach cancer. In contrast to their finding
there were no cases of pulmonary embolism in our population.
Although some author recommend an aggressive and extensive screening for cancer in patients that present with a primary
VTE(2) more studies are needed
before establish guidelines or
recommend screening studies for
malignancy (7, 8).
REFERENCES
1- White R. et al; Incidence of Idiopathic
Deep Venous thrombosis and secondary
thromboembolism among ethnic groups
in California, Annals of Internal Medicine,
Vol 128, Num 9, Pags 737-740. May 1998
2- White R. et al; Incidence of venous
thromboembolism in the year before the
diagnosis of cancer in 528 693 adults,
Annals of Internal Medicine, Vol 165, Aug
8/22, 2005, pags 1782-1787
3- Jan-Leedert P, Nic J., Veeger, et al;
The pathogenesis of venous thromboembolism: Evidence for multiple interrelated causes. Annals of internal medicine
2006, vol 145, number 11, pags 807-815
4- Carrier M., Le Gal M., Wells P. et al;
Systematic reviews: The trousseau syndrome revised: should we screen extensively for cancer in patients with venous
thromboembolism?, Annals of internal
medicine, vol 149, num 5, pags. 323-333.
5- Kucher, Nils MD; Deep-vein thrombosis of the upper extremities, The new England journal of medicine 2011; 364:8619, pags 861-869
Trombosis venosa profunda y embolia pulmonar, llamados colectivamente tromboembolismo venoso (TEV), puede ser la primera manifestación de cáncer. Dada esta asociación se ha
tratado de proponer un método de cernimiento para malignidad en pacientes que presentan
con un TEV con el propósito de identificar alguna malignidad no diagnosticada. Método: Es
un estudio descriptivo, retrospectivo, monocéntrico de revisión de expedientes clínicos que
incluyó 3244 pacientes del Hospital Veterano en San Juan P.R. con diagnósticos de cáncer
de pulmón (de célula pequeña y no pequeña), próstata, colon, recto, hígado, estómago, páncreas, seno, linfoma y leucemia entre 2005 y 2012. Dichos expedientes se evaluaron para un
evento de TEV en los cinco años previos a su diagnóstico de malignidad. Resultados secundarios del estudio fueron edad y estadio de la enfermedad al momento de su diagnóstico. Los pacientes debían ser veteranos, mayores de 21 años con un diagnóstico de cáncer
de los previamente mencionados entre 1 de enero de 2005 y 31 de diciembre de 2010. Los
criterios de exclusión fueron un estado de embarazo en los 5 años previos a su diagnóstico
de malignidad, historial previo de alguna coagulopatía, alguna malignidad preexistente o
tratamiento de anticoagulación al momento del diagnóstico de la malignidad. Resultados:
Se evaluaron 3244 expedientes. De los 2858 expedientes que cumplieron los criterios de
inclusión 22 (0.8%) tuvieron un evento de TEV en los cinco años previos a su diagnóstico
de malignidad; la mayoría (14%) con un diagnóstico de cáncer de páncreas. Al evaluar los
casos de TEV según la malignidad: 7% de páncreas, 0.8% de próstata, 0.5% de colon, 0.6%
de vejiga, 0.8% de hígado, 0.4% de pulmón y 1.1% cáncer de recto, pero ninguno de los pacientes con cáncer de estómago, esófago, seno o leucemia tuvieron un evento de TEV. En
relación al estadio metastático al momento de diagnóstico, sólo 13% de los pacientes con
historial previo de TEV tenían un estado metastático avanzado al momento de su diagnóstico de malignidad. Conclusión: Aunque en este momento no existe una indicación clara para
recomendar cernimiento de malignidad en pacientes que presentan con un TEV, nuestros
resultados apuntan a un numero aumentado de paciente con TEV a los cuales subsecuentemente se le diagnostica cáncer de páncreas. Se necesitan mas investigaciones para establecer guías de cernimiento para cáncer en los pacientes que presentan con un TEV.
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Cursos especiales.
INTRAVENOUS ASCORBIC ACID AND HYDROGEN
PEROXIDE IN THE MANAGEMENT OF PATIENTS WITH
CHIKUNGUNYA
Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico.
San Juan Bautista School of Medicine, School of Public Health, Caguas, Puerto
Rico.
c
Memorial Hospital, Colorado Springs, Colorado.
Corresponding author: Victor Marcial-Vega MD - 122 Eleanor Roosevelt, Interior,
San Juan, Puerto Rico, 00918. E-mail: marcialvegamd@aol.com
a
b
Victor Marcial-Vega MDa*
Idxian Gonzalez-Terronb
Thomas Edward Levy MDc
Authors acknowledge Solynet Baez, Alin Blanchet, Milagros Monge, RN, for their care
of the patients in this study
ABSTRACT
Chikungunya is a viral illness characterized by severe joint pains, which may persist for
months to years. There is no effective treatment for this disease. We treated 56 patients
with moderate to severe persistent pains with a single infusion of ascorbic acid ranging
from 25-50 grams and hydrogen peroxide (3 cc of a 3% solution) from July to October
2014. Patients were asked about their pain using the Verbal Numerical Rating Scale-11 immediately before and after treatment. The mean Pain Score before and after treatment was
8 and 2 respectively (60%) (p < 0.001); and 5 patients (9%) had a Pain Score of 0. The use
of intravenous ascorbic acid and hydrogen peroxide resulted in a statistically significant
reduction of pain in patients with moderate to severe pain from the Chikungunya virus
immediately after treatment. Index words: intravenous, ascorbic, acid, hydrogen, peroxide, chikungunya
INTRODUCTION
Chikungunya is a viral illness
characterized by an acute viral
syndrome, typically lasting a few
days to a week, followed by a
chronic and extremely painful involvement of the joints which can
last four months to 5 years in up
to 33% of the patients. There is
no cure for this disease and the
only available treatment is symptomatic and supportive [1-6].
The Puerto Rico Department of
Health has reported by November 2014 (10th Month of epidemic) 18,109 suspected cases and
3,385 confirmed cases (total of
21,494) with most cases reported
during the month of July. No effective treatment has been reported for this condition [7].
The purpose of this work was to
determine whether intravenous
vitamin c and hydrogen peroxide
were effective against the pain
caused by the Chikungunya virus. During the beginning of the
present epidemic of Chikungunya
in Puerto Rico, we administered
intravenous ascorbic acid and
hydrogen peroxide to 56 patients
complaining of severe pains due
to their clinical diagnosis seen at
Marcial Integrative Medical Center. This is a review of the results
of the pain control in this population.
All 22 patients with influenza who
received intravenous 3 cc of
0.3% solution of hydrogen peroxide followed by 20 grams of
ascorbic acid, including a suspected case of viral meningo-encephalitis, have responded dramatically within three hours with
complete resolution of at least
50% of symptoms, and with no
side effects[8].
The use of ascorbic acid as an
effective antiviral has been documented as early as 1949 when
Frederick R. Klenner, MD, the
first doctor to publish in peer reviewed journals, documented the
ability of vitamin C to reliably cure
many different acute infectious
diseases and reliably neutralize
any toxin treated, when sufficiently dosed and administered for a
long enough period of time [9],
the cure of 60 out of patients with
polio within 4 days of ascorbic
acid administration intramuscularly and orally [10], and the cure
of advanced polio and its associated flaccid paralysis with ascorbic acid in 1951 [11].
The purpose of this review was
to determine whether the administration of intravenous vitamin C
and hydrogen peroxide is associated with a reduction and/or elimination of the chronic persistent
pain due to Chikungunya immediately after treatment.
MATERIALS AND METHOD
Study design
All patients came to the Marcial Integrative Medicine Center in San Juan
during the 2014 Chikungunya epidemic in Puerto Rico. They all had
the initial acute clinical picture, which
included all or some of the following
symptoms: fevers, chills, rash, weakness, malaise, fatigue, headaches.
All patients had the most important
clinical feature of persistent, moderate to severe joint pains that interfered significantly with activities of
daily living.
for each patient indicating that this
was not a proven method of treatment for this condition and the possible side effects of it. We have observed from experience that the most
common side effect is hypoglycemia
that can be prevented in all patients
by instructing them to eat before and
during the infusion.
Statistical Analysis
We used the SPSS IBM 22 statistics
package. The relation between Vitamin C + hydrogen peroxide and Pain
score was plotted in two histograms
and frequency tables. Comparison
of parameters before and after the
treatment was performed by Wilcoxon Signed Rank 2 sample test. A p
value ≤ 0.001 was considered as statistically significant.
They underwent an evaluation that
included review of blood-work, history taking, pertinent physical exam
and detailed determination of the
pain in each joint using the Numeric
Rating Scale-11. Each patient had a RESULTS
calculated average Pain Score that
was obtained adding all individual A total of 56 patients were available
areas of pain and dividing among
the number of affected sites. All patients were instructed to eat within
two hours before the infusion and to
snack liberally during the procedure.
for analysis. They were 14 males
(25%) and 42 females (75%). Patients at the 25 percentile of Pain
Score, or who reported lesser intensity pain had a pre-treatment score
of 7. This was reported as a 2 Post
treatment for a reduction on the Pain
Score of 71%. The median pre-treatment Pain Score for the group was 8
and this was reduced to 2 post-treatment for a reduction of 75%. The average Pain Score pre-treatment for
at the 75 Percentile, or associated
with more severe pain was 8 and to
a reduction post-treatment of 4 for a
reduction of the Pain Score of 60%.
The range of reduction of the Pain
Score was from 60-71% for the most
and least affected patients respectively. Five of the patients (5/56)
or 9% had a complete response to
treatment or complete disappearance of pain after treatment. Three of
the patients, or 5%, had no response
to treatment (see Table 1).
Effect of Vitamin C and hydrogen peroxide on Chikungunya
patients
Two infusions were injected in 56 patients: 100 cc Normal Saline with 3 cc
of a 3% solution of hydrogen peroxide, 500 mg of magnesium chloride
and 1000 micrograms of methylcobalamin followed by 500 cc of sterile
water or lactated Ringer’s solution
with 20 to 50 grams of ascorbic acid,
B complex (thiamine 100 mg, riboflavin 2mg, pyridoxine 2mg, dexpanthenol 2mg, niacinamide 100 mg), 100
milligrams of thiamine and 100 milligrams of pyridoxine. All were slowly
infused intravenously over a 2-4 hour
period. Patients were then evaluated
after the infusion to determine their
overall Pain Score post-treatment
using the Verbal Numerical Rating
Scale-11. The evaluated variable
was the pain intensity from a scale of
0-10 (0 meaning no pain and 10 the
worst pain experienced).
Forty-two (42/56=75%) of the patients received 25-30 grams of
ascorbic acid. Seven, 6, 5 and 3
patients received 30 grams, 20
grams, 50 grams and 40 grams respectively.
Written informed consent was obtained
Table 1 Frequency Table of Pain Score before and after treatment.
No patients discontinued their
participation in the study because
of adverse reactions to the treatment. No adverse side effects
were observed in any patient.
The scores of pain showed significant improvement (p < 0.001)
after the treatment (see Figure
1). The results of the Wilcoxon
Signed Rank test show that this
treatment improves quality of life
in patients with Chikungunya (see
Figure 2).
Figure 2: Results of Wilcoxon
Signed Rank test.
DISCUSSION
Our protocol has shown that the
use of intravenous hydrogen peroxide and ascorbic acid is safe
and strongly associated with a
more than 61% post-infusion reduction of pain in patients affected with Chikungunya virus related
arthralgias.
These results are consistent with
previous in-vitro research which
has shown that ascorbic acid inactivates the polio [21], herpes Figure 1A: Histogram of Pain Score before the treatment
[22], vaccinia [24], tobacco mosaic [25], bacteriophage [26-29],
entero [30], influenza [31] and rabies [32] viruses.
They are also consistent with previous clinical research showing
ascorbic acid can resolve polio
[9-11,33,34], its associated flaccid paralysis [10], acute hepatitis
[35-38], viral encephalitis [39-42],
measles (simple and complicated) [43], mumps (simple and
complicated) [44], chickenpox
[45], influenza [46] and rabies in
guinea pigs.
Since there is no effective treatment for severe debilitating Chikungunya related pains [47], and
because there is an epidemic in
Puerto Rico at the present moment, intravenous vitamin C and
hydrogen peroxide may be considered as a safe and viable alternative to manage these patients
effectively. Randomized controlled studies need to be done to
further explore this question. We
are in the process of reviewing
our clinical data to determine the
longer range apparent effect of Figure 2B: Histogram of Pain Score after the treatment.
this modality on Pain Scores
and to determine if more infusions
and/or higher doses will be more
effective.
REFERENCES
1. Pialoux G, Gaüzère BA, Jauréguiberry S, Strobel M. Chikungunya, an epidemic arbovirosis. Lancet Infect Dis.
2007;7:319–27
2. Fourie ED, Morrison JG. Rheumatoid
arthritic syndrome after chikungunya fever. S Afr Med J. 1979; 56:130–2.
3. Kennedy AC, Fleming J, Solomon L.
Chikungunya viral arthropathy: A clinical
description. J Rheumatol. 1980; 7:231–6.
4. Brighton SW, Prozesky OW, de la
Harpe AL. Chikungunya virus infection.
A retrospective study of 107 cases. S Afr
Med J. 1983; 63:313–5.
5. Sam IC, AbuBakar S. Chikungunya virus infection. Med J
Malaysia 2006; 61:264-9.
6. Mohan A. Chikungunya fever: clinical
presentation and
principles of management. Indian J Med
Res 2006 (in press).
7. Puerto Rico Department of Health,
Weekly Report of (October 22-28, 2014)
of Chikungunya Epidemic (Week 43)
8. Marcial-Vega, VA, 2013, Presented
at the XIIth Health Symposium of the
Ana G Mendez University System, July
19, 2013, Marriott Hotel, San Juan, Puerto Rico, Integrative Medicine: Its Role
in The Management of Cancer, Autism,
Degenerative Neurological Conditions,
Influenza and other Chronic Conditions:
A New Paradigm In Medicine, (In Press)
9. Frederick R. Klenner, M.D., F.C.C.P,
Journal of Applied Nutrition Vol. 23, No’s
3 & 4, Winter ,1971, 1, Observations On
the Dose and Administration of Ascorbic
Acid When Employed Beyond the Range
Of A Vitamin In Human Pathology
Frederick R. Klenner, M.D., F.C.C.P.
10. Klenner, F.R., The Treatment of Poliomyelitis and Other Viral Diseases with
Vitamin C, Southern Medicine and Surgery, July1949, 209 11. Klenner, F.R. Massive Doses of Vitamin C and the Virus Diseases, Journal
of Southern Medicine and Surgery, April
1951, Vol.113, No.4, pp.101-107
12. Wilson MK, Baguley BC, Wall C,
Jameson MB, Findlay MP. Review of
high-dose intravenous vitamin C as
ananticancer agent. Asia Pac J Clin Oncol. 2014 Mar; 10(1):22-37. doi: 10.1111/
ajco.12173. Review. PubMed PMID:
24571058.
13. Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity
of chemotherapy. Sci Transl Med. 2014
Feb 5; 6(222):222ra18.
14. Parrow NL, Leshin JA, Levine M. Parenteral ascorbate as a cancer therapeutic: a reassessment based on pharmacokinetics. Antioxid Redox Signal. 2013
Dec 10; 19(17):2141-56. doi: 10.1089/
ars.2013.5372. Epub 2013 Jun 19. Review. PubMed PMID: 23621620;
15. Efficacy of improved hydrogen peroxide against important healthcare-associated pathogens. Rutala WA, Gergen MF,
Weber DJ. Infect Control Hosp Epidemi
ol. 2012 Nov; 33(11):1159-61.
16. [Hydrogen peroxide treatment for
vaginal trichomoniasis. 1955]. González
Ramos M. Ginecol Obstet Mex. 2010
Jun; 78(6):329-31.
17. Marcial-Vega, VA, 2013, Presented at
the XIIth Health Symposium of the Ana
G Mendez University System, July 19,
2013, Marriott Hotel, San Juan, Puerto Rico, Integrative Medicine: It’s Role
in The Management of Cancer, Autism,
Degenerative Neurological Conditions,
Influenza and other Chronic Conditions:
A New Paradigm In Medicine. (Submitted
for publication)
18. Marcial-Vega, VA, 2014, Integrative
Medicine in the Management of Breast
and other Cancers, Presented at the
First Multidisciplinary Breast Symposium
of the Sociedad Puertorriqueña de Senología, Aug.23, 2014, Embassy Suites
Hotel, Carolina, Puerto Rico.
19.A naturopathic cause of portal venous
gas embolism. Hydrogenperoxide ingestion causing significant portal venous gas
and stomach wall thickening.Fok MC,
Zwirewich C, Salh BS. Gastroenterology.
2013 Mar; 144(3):509, 658-9.
20. Shallenberger, Frank, M.D, President
of the American Academy of Ozonetherapy, Nov. 2014, Personal Communication
21. Jungeblut, CW, Inactivation of Poliomyelitis virus in vitro by crystalline vitamin
C (ascorbic acid): J Exp Med. 1935 Sep
30; 62(4):517-19.
22. Holden; Molloy: Further experiments
on the inactivation of herpes virus by vitamin C (l-ascorbic acid). Journal of Immunology 33:251-257, 1937
23. Kligler and Bernkopf: Inactivation of
vaccinia virus by ascorbic acid and glutathione. Nature 139:965-966, 1937,
24. Turner G (1964) Inactivation of vaccinia virus by ascorbic acid. J Gen Microbiol 35:75-80
25. Lojkin M (1936) A study of ascorbic
acid as an inactivating agent of tobacco
mosaic virus. Contr B o y c e
Thompson Inst Pl Res 8:455
26. Lominski (1936) Inactivation du
bacteriophage par l’acide delta containing single-stranded DNA by ascorbic
acid. J Nutr Sci Viascorbique. C r Seanc
Soc Biol 122:176
27. Murata, A, : Mechanism of inactivation
of bacteriophage deltaA containing single-stranded DNA by ascorbic acid. J Nutr
Sci Vitaminol (Tokyo). 1975;21(4):261-9.
28. Morgan, AR (1976) The mechanism
of DNA strand breakage by vitamin C and
superoxide and the protective roles of
catalase and superoxide dismutase. Nucleic Acids Res. 1976 May;3(5):1139-49.
29. Richter, HE (1982) Rapid inactivation
of bacteriophage T7 by ascorbic acid is
repairable. Biochim Biophys Acta. 1982
Apr 26;697(1):25-30.
30. Salo, RJ (1978) Inactivation of enteroviruses by ascorbic acid and sodium
bisulfite. Appl Environ Microbiol. 1978
Jul;36(1):68-75.
31. Cheng, LL (2012) [An in vitro study on
the pharmacological ascorbate treatment
of influenza virus]. [Article in Chinese]
Zhonghua Jie He He Hu Xi Za Zhi. 2012
Jul;35(7):520-3.
32. Amato G (1937) Azione dell’acido
ascorbico sul virus fisso della rabia e sulla tossina tetanica. Giornale di Batteriologia, Virologia et Immunologia (Torino)
19:843-847
33. Greer, 1955, Med Times. 1955 Nov;
83(11):1160-1. Vitamin C in acute poliomyelitis.
34. Baur, H, Poliomyelitis therapy with
ascorbic acid: Helv Med Acta., 1952 Oct;
19(4-5):470-4.
35. Dalton, WL, Massive Doses of Vitamin C in the treatment of Viral Diseases:
J Indiana State Med Assoc., 1962 Aug;
55:1151-4.
36. Cathcart, 1981 [7321921] (Reported
that he never had a single case of acute
viral hepatitis fail to respond to properly dosed IVC, and that he never had a
VC-treated hepatitis patient subsequently
develop chronic hepatitis)
37. Orens, S, Hepatitis B—A ten Day
“Cure”. A personal History: Bull Phila Cty
Dent Socc., 1983 Mar; 48(6):4-5.
38. (1974) Klenner FR. Significance of
high daily intake of ascorbic acid in preventive medicine. Journal of the International Academy of Preventive Medicine
1:45-69
Vitamin C repeatedly cured cases of viral
encephalitis, many presenting in coma:
39. (July 1949) Klenner FR. The treatment of poliomyelitis and other virus diseases with vitamin C. Southern Medicine
& Surgery 111:209-214 [18147027]
40. (April 1951) Klenner FR. Massive
doses of vitamin C and the virus diseases. Southern Medicine & Surgery
103:101-107 [14855098]
41. (1953) Klenner FR. Observations of
the dose and administration of ascorbic
acid when employed beyond the range of
a vitamin in human pathology. Journal of
Applied Nutrition 23:61-88
43. Klenner, FR : The Treatment of Poliomyelitis and Other Virus Diseases
With Vitamin C, South Med Surg. 1949
Jul;111(7):209-14.
44. Herpes infections, acute (chickenpox) Dainow, 1943 68 197; Zureick, 1950
[14908970]; (1974) Klenner 1: 45
45. Influenza (flu, including H1N1 swine
flu); 60 Minutes report, New Zealand,
2010); see www.peakenergy.com
46. Banic, S, ; Prevention of Rabies By Vitamin C, Nature. 1975 Nov
13;258(5531):153-4.
47. Centers for Disease Control and Prevention: Chikungunya virus
http://www.cdc.gov/chikungunya/symptoms/index.html
Ehr Timeline
RESUMEN
Chikungunya es una enfermedad viral caracterizada
por dolor severo en el área
de las coyunturas que puede
persistir por meses o años.
Manejamos56 pacientes con
dolor moderado-severo persistente con una infusión
sencilla de ácido ascórbico
entre rangos de 25-50 gramos
y peróxido de hidrógeno (3 cc
de una solución de 3%) entre
Julio a Octubre del 2014. A
los pacientes se les preguntó
acerca de su dolor utilizando la Escala de Valoración
Numérica Verbal-11 inmediatamente antes y después del
tratamiento. La Puntuación
de Dolor promedio antes y
después del tratamiento fue 8
y 2 respectivamente (60%) (p
< 0.001) y en 5 pacientes (9%)
la Puntuación de Dolor bajó a
0. El uso de ácido ascórbico
y peróxido de hidrógeno intravenoso está asociado con
una reducción estadísticamente significativa de dolor
en pacientes con dolor moderado a severo debido al virus
del Chikungunya inmediatamente después de la infusión.
QUALITY OF LIFE IN PATIENTS WITH
DIFFERENTIATED THYROID CANCER AT THE
GENERAL ENDOCRINOLOGY CLINICS OF
THE UNIVERSITY HOSPITAL OF PUERTO RICO
University of Puerto Rico Medical Sciences Campus, Department of Medicine, Endocrinology, Diabetes and Metabolism Section, San Juan, Puerto
Rico.
b
Puerto Rico Clinical and Translational Research Consortium.
c
University of Puerto Rico Medical Sciences Campus, Department of Internal Medicine, San Juan, Puerto Rico.
d
University of Puerto Rico Medical Sciences Campus, Department of Medicine, Hematology and Oncology Section, San Juan, Puerto Rico.
*Corresponding author: Margarita Ramírez-Vick, MD- PO Box 365067 San
Juan, Puerto Rico 00936-5067. Email: mramirezvick@gmail.com
Presented during the poster session of the 83rd Annual Meeting of the
American Thyroid Association held in San Juan, Puerto Rico.
a
ABSTRACT
Differentiated thyroid cancer (DTC) can compromise the quality of life of patients. Our
purpose is to investigate if the quality of life, in a cohort of patients in Puerto Rico, is affected by the diagnosis and/or treatment modalities received for DTC. Methods: This is
a cross-sectional study of 75 subjects with DTC. A Spanish version of the University Of
Washington Quality Of Life Questionnaire was used, including multiple aspects of physical and social functioning. Descriptive and bivariate analysis between domain scores and
variables of interest were performed. Results: 82.7% of the patients reported that their
health was the same or better than it was before treatment. The mean composite score
obtained was 82.3, reflecting an overall little effect on quality of life. Patients diagnosed
with DTC at an age of ≥45 years reported a significantly better score on the pain domain
when compared with those diagnosed earlier (p < 0.05). Patient who received >150 mCi
of radioiodine had a tendency towards a worse score on the same domain (p=0.05). Conclusions: Our cohort reported an overall minimal effect on the quality of life of patients
with DTC. Future treatment strategies should include periodic quality of life evaluations,
in order to tailor therapy in this growing population.
Index words: quality, life, differentiated, thyroid, cancer, University, Hospital, Puerto Rico
INTRODUCTION
Thyroid carcinoma is the most
common malignancy of the endocrine system [1-4]. Thyroid cancer can be classified according to
its histological features [4], with
the most common type being the
differentiated thyroid carcinoma
(DTC). Arising from thyroid follicular epithelial cells, DTC includes
papillary carcinoma, follicular carcinoma, and the less frequently
found Hurthle cell carcinoma. It is
more common in females and is
often asymptomatic. The age of diagnosis is an important prognostic
factor; thyroid cancer in older persons (more than 45 years of age
Mónica A. Vega-Vázquez MDa
Loida González-Rodríguez MDa
Eduardo J. Santiago-Rodríguez MPHb
Anette Garcés-Domínguez MD0
Lee-Ming Shum MDc
Maribel Tirado-Gómez MDd
Margarita Ramírez-Vick MDa*
is associated with a worse prognosis [4,5]. Other important risk
factors include a history of head
and neck irradiation, male gender,
large nodule size, focal tumor fixation or invasion to lymph node
and the presence of metastasis,
among others [4,5].
The incidence of thyroid cancer
is rising worldwide [6]. Within the
United States, the incidence of
thyroid cancer has increased from
3.6 to 8.7 per 100,000 from 1973
to 2002, representing a 2.4-fold
increase [7]. Further studies found
that this was mostly due to the diagnosis of papillary thyroid cancer,
although its mortality has remained
stable during this period [7]. An
estimate reported by the American
Cancer Society in 2014 resulted in
62,980 new cases of thyroid cancer in the United States [8]. The
explanation for this increasing
trend is still under investigation;
however it is thought that it could
be related to new diagnostic modalities, such as the introduction
of ultrasound and fine needle aspiration of thyroid gland [7,9]. Data
gathered from the Central Cancer
Registry of Puerto Rico revealed
that the overall incidence rate for
thyroid cancer in Puerto Rico has
also increased from 3.0 to 7.0 per
100,000 population, with an annual
percentage change of 5.3% during
years 1985 to 2004 [10].
neck cancer settings [23,24].
The treatment for DTC mainly consists of surgical management, in
some cases it is followed by the
use of radioactive iodine (I131 )
[11] and lifelong supplementation
with levothyroxine at a dose to suppress thyrotropin levels [12-16]. Although treatment for thyroid cancer
is generally well tolerated, it can
often result in multiple short and
long term complications. Complications reported with thyroidectomy mainly include physical or functional impairments, including voice
and discomfort during swallowing
and recurrent laryngeal nerve injury [17]. Radioactive iodine ablation
therapy has also been associated
with acute and long-term complications within thyroid cancer patients. Acute risks associated with
radioactive iodine include nausea, vomiting, ageusia, salivary
swelling and pain [18]. Long-term
complications include recurrent
sialoadenitis, xerostomia, dental
caries, pulmonary fibrosis, nasolacrimal outflow obstruction and
second primary malignancy [18].
Given the repercussions that the
diagnosis and treatment of thyroid
carcinoma may have in our patients, and its worldwide increase
in prevalence, several researchers have taken the task to study
the impact on the quality of life in
different populations with variable
outcomes.
Although DTC generally has a favorable prognosis with long-term
survival rate of 90% [5,20,25], the
primary goal of our study is to investigate, through the UW-QOL
questionnaire, if the quality of life
of patients with the diagnosis of
DTC is affected in a cohort of patients within Puerto Rico. To our
knowledge this is the first study in
the Puerto Rican population to assess the quality of life of patients
with DTC.
Quality of life questionnaires are
useful tools developed to evaluate
patient well-being, mainly throughout the individual’s own perception
of life [19,20]. Among the tools developed for quality of life assessment in patients with cancer, the
University of Washington Quality
of Life (UW-QOL) questionnaire
is a validated, accurate and internationally accepted survey instrument [21]. The UW-QOL was first
described in 1993 by Hasan and
Weymuller [22] and was specifically designed to assess quality of
life in patients with head and neck
malignancy. The questionnaire
provides a simple measurement of
health-related quality of life and it
has been shown to be suitable for
use in a wide variety of head and
Each patient underwent a face-toface interview in order to obtain sociodemographic information, past
and present medical history. Other
data including weight, height, body
mass index, thyroid stimulating
hormone (TSH) level, cancer histopathology type, tumor size, time
of diagnosis, remission state, and
treatment received for cancer were
obtained by reviewing the medical
records. Tumor staging at the time
of cancer diagnosis, was classified
according to American Joint Cancer Committee (AJCC) TNM system [26].
PATIENTS AND METHODS
A cross-sectional study of 75 consenting subjects attending the
General Endocrinology Clinics of
the University Hospital of Puerto Rico was performed. Subjects
meeting the inclusion criteria were
invited to participate on our study
after their follow-up medical evaluation. In order to participate, subjects must have met the following
inclusion criteria: 1) should be 21
years or older; and 2) must have
been previously diagnosed with
differentiated thyroid cancer. Subjects were excluded from the study
if: 1) were unable to complete
the questionnaire, and 2) if they
had history of other types of head
and neck cancer. The Institutional Review Board of the University
of Puerto Rico, Medical Sciences
Campus approved this study.
After data collection, subjects were
asked to complete a Spanish version of the UW-QOL questionnaire
[27]. The first part of the UW-QOL
questionnaire consists of 12 multiple choice questions, designed
to address the following domains:
pain, appearance, activity, recreation, chewing, swallowing,
speech, shoulder, taste, saliva, humor and anxiety [3, 21,23]. Scores
for these questions can range from
0 to 100, with 100 indicating the
best level of function. Scores for the
questionnaire were done according to the UW-QOL questionnaire
guidance; higher scores reflect a
better QOL and higher functioning. An overall composite score
was calculated using the mean of
all domains included in the questionnaire. Two additional subscale
scores were computed, which included the physical function and
the social function subscale. The
physical subscale includes the
average scores for the domains
of chewing, swallowing, speech,
taste, saliva, and appearance; and
the social-emotional function subscale includes the average score
for anxiety, mood, pain, activity,
recreation and shoulder domains.
As a general agreement for scoring, from 75-100 will be graded as
having little effect in quality of life,
from 50-74 having a relative effect on quality of life and less than
50 points as having an important
effect on quality of life [21]. The
UW-QOL questionnaire also includes three additional questions
concerning patients’ perception of
global health-related quality of life.
The statistical analysis was performed using the statistical package Stata 12.1 version. A descriptive analysis of the demographic,
clinical and treatment variables,
as well as the quality of life scores
was performed. Categorical variables were reported as frequencies and percentages, and continuous variables were reported
as mean ± standard deviation. To
assess the relationship between
each of the twelve domains on the
UW-QOL questionnaire and independent variables, such as age
of diagnosis, sex, type of surgery,
radioiodine treatment and tumor
size, the Mann-Whitney or Kruskal-Wallis tests were used. Results
were considered significant at p
values below 0.05.
RESULTS
A total of 75 subjects with differentiated thyroid cancer were recruited
for the study cohort. The mean age
of the group was 51.5 ± 13.3 years
(range, 24-87 years) and 84%
were female. Forty-eight percent
of patients were diagnosed with
cancer at an age younger than 45
years old and 52% were diagnosed
at an age older than 45 years. The
most frequently encountered histopathology type of thyroid cancer
was the papillary carcinoma, seen
in 96% of the subjects; followed by
follicular thyroid cancer, reported
in 2.7% of the study population. At
the time of diagnosis, 70.7% of the
subjects were classified as Stage
I, 6.7 % as Stage II, 12% as Stage
III and 5.3% as Stage IV. As documented in the medical records,
the size of the tumor was reported
as less than 1 cm in 25 subjects
(37.3%), between 1 and 2 cm in 25
subjects (37.3%) and larger than 2
cm in 17 individuals (25.4%). Table
1 summarizes the demographics
and characteristics of our study
population.
Most of our study subjects underwent total thyroidectomy (98.7%).
Adjuvant lymph node dissection
was done only in twenty-four subjects (32%). Sixty-eight (90.7%)
patients received levothyroxine
for TSH suppression therapy. Sixty-six (88%) subjects in the cohort received radioactive iodine
treatment for adjuvant remnant
ablation therapy. Patients receiving radioactive therapy were then
divided into low-dose (150 mCi or
less, n=40) and high-dose (more
than 150 mCi, n= 14) of the total
therapeutic dose of radioiodine received, defined as the summation
of all doses greater than 30 mCi.
The elapsed period of time since
the radioiodine therapy was also Table 1: Demographics and Clinical
classified into recent exposure in the study
(12 months or less, n= 15) and
long-time exposure (more than 12 associated variables (see Table 3),
months, n= 51). Table 2 summariz- the age of diagnosis had an effect
es treatment-related characteris- on the pain domain score. Subtics of our cohort.
jects diagnosed younger (less than
45 years old) showed significantly
In the evaluation of the relationship worse scores on the domain than
between the quality of life domains their counterparts (p=0.02). Meanwith clinical profile and treatment while patients who received high
Profile of the 75 subjects included
therapeutic radioiodine doses had
a tendency toward a worse score
on the same domain (p=0.05). Of
the subjects diagnosed with DTC
at an age younger than 45 years,
36.1% underwent treatment with
radioiodine at a cumulative dose
higher than 150 mCi, while 2.6%
of those diagnosed at 45 years of
age or older received a cumulative
radioiodine doses higher than150
mCi (Fisher’s exact test: p<0.001);
which could account for the unexpectedly lower scores seen in the
pain domain for the patients diagnosed younger. In regard to the relationship among the other quality
of life domains with clinical profile
and treatment variables, no other
significant association was found. Regarding the UW-QOL question
on overall health-related quality of
life, 82.7% of the patients reported that their health was the same
or better than it was before treatment. The calculated UW-QOL
mean composite score was 82.3
± 15.1. For the physical subscale
the mean score was 87.9 ± 14.1.
The social-emotional subscale
mean score was 77.0 ± 19.4. (see
Figure 1). These computed results
are all associated with an overall
little effect on the cohort quality of
life.
DISCUSSION
The purpose of this study was to
evaluate quality of life in a cohort
of DTC patients in Puerto Rico.
We found that the overall quality
of life score, assessed by the UWQOL questionnaire, was minimally
affected after the diagnosis and
treatment for differentiated thyroid
cancer in our cohort; although we
did found a slightly lower overall composite score than the one
reported by Almeida et al [21]. In
our study, patients who were diagnosed at an age younger than 45
years showed significantly worse
scores on the pain domain than
their counterparts. Meanwhile patients who received a cumulative
therapeutic radioiodine dose of
more than 150 mCi had a tendency toward a worse score on the
same domain. In our cohort, the
patients who received higher cumulative radioiodine doses were
those diagnosed before 45 years
of age, which could account for the
unexpectedly lower scores seen
in the pain domain of the subjects
diagnosed younger. In general,
patients with DTC usually received
radioiodine therapy for remnant or
Table 3: Bivariate analysis of the relationship between quality of life domains with clinical profile and treatment associated variables
Table 2: Differentiated thyroid cancer treatment-related characteristics
of the 75 subjects included in the study
adjuvant ablation of residual tissue.
However, appropriate patient selection and therapeutic doses used
for radioiodine therapy are still uncertain and recently have been
under debate. Especially in the
low risk for recurrence population
and because higher cumulative
doses of RAI have been associated to acute and long term complications, the minimum effective
dose, if any, should be given.
We did not observe the significant
reduction in quality of life in the recreation domain described by Dingle et.al, among patients exposed
to higher cumulative doses of radioiodine [3]. Nor did we observe
the effect of higher cumulative radioiodine doses with worse scores
on the domains of swallowing,
chewing, speech, shoulder, taste
or anxiety reported by Almeida
et.al [21]. In our study population,
we did not find any association between gender, tumor size, type of
surgery, or time since radioiodine
therapy with the twelve domains
scores included in the UW-QOL
questionnaire.
cross-sectional design, thus no
baseline questionnaire before
treatment or during follow up period was obtained. Second, the
questionnaire was given in a faceto-face setting which could have
introduced some information bias,
as patients’ answers might be exThere are some limitations in aggerated in an attempt to seek
our study. First, our study had a more physician attention at the
Figure 1: Composite score, physical and social-emotional subscales. The composite score is
the average score of the twelve domains included in the University of Washington Quality of Life
Questionnaire. The physical subscale is the average of the domains of chewing, swallowing,
speech, taste, saliva, and appearance; and the social subscale includes the average scores for
anxiety, mood, pain, activity, recreation and shoulder domains.
clinic. Third, some clinical data
was obtained from medical chart,
which are not designed for research purposes and may have
had missing information. Fourth,
TSH levels and thyroglobulin
panel were not measured the
same day that the questionnaire
was administered, thus we were
unable to make associations between quality of life domains with
TSH levels or thyroglobulin presence.
Given the low mortality associated to thyroid cancer, health care
providers tend to regard differentiated thyroid cancer somewhat
indifferently when compared
with other types of cancer [1].
However a systematic review
from 1997 to 2010 done by Husson et.al has shown that patients with differentiated thyroid
cancer can have a similar or
slightly worse health related quality of life compared with the normative population [6]. Thyroid
cancer survivors have reported
some specific medical problems
after cancer treatment and follow-up tests, which can have a
direct negative impact on their
current and long-term quality of
life [6]. Although the treatment
of differentiated thyroid cancer is
generally associated with a good
prognosis, some studies have
shown that quality of life domains
can be affected by treatment and
its side effects. Future treatment
strategies should include periodic quality of life assessment and
evaluation of long-term side effect of therapies, in order to tailor
therapy in this growing population
of patients. The multidisciplinary
approach in a cancer patient
should not only target cancer remission and/or increasing patient
survival, but should also attempt
to preserve or provide an adequate quality of life for these patients and their families. It should
be mandatory to investigate potential factors that may affect
quality of life in thyroid cancer
patients, in order to develop tools
that may help improve their quality of life in the nearby future within this population.
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ACKNOWLEDGMENTS
This publication was made possible by
grants from the National Center for Research Resources (U54 RR 026139)
and the National Institute on Minority
Health and Health Disparities (8U54 MD
007587-03), a component of the National
Institutes of Health.
RESUMEN
El propósito de nuestro estudio es
investigar si la calidad de vida, de
un grupo de pacientes en Puerto
Rico, se ve afectada por el diagnóstico y/o modalidades de tratamiento recibido luego del diagnóstico de cáncer diferenciado de
tiroide. Métodos: Se trata de un
estudio transversal de 75 sujetos
con cáncer diferenciado de tiroide,
donde se utilizó una versión en español del cuestionario de calidad
de vida de la Universidad de Washington. Este instrumento incluye
múltiples aspectos del funcionamiento físico y social que impactan
la calidad de vida de los sujetos.
Se realizó un análisis descriptivo
y bivariado de las puntuaciones
obtenidas en el cuestionario y las
variables de interés relacionadas
al cáncer diferenciado de tiroide.
Resultado: 82.7% de los pacientes informaron de que su salud era
igual o mejor de lo que era antes
del diagnostico y tratamiento del
cáncer diferenciado de tiroide. El
promedio de la puntuación compuesta obtenida en el cuestionario
fue de 82.3, lo que refleja un efecto
mínimo sobre la calidad de vida en
estos pacientes. Sin embargo, los
sujetos diagnosticados con cáncer
diferenciado de tiroide a una edad
de ≥45 años reportaron una puntuación significativamente mejor en el
dominio del dolor en comparación
con los diagnosticados a edades
mas tempranas (p < 0.05). Los paciente que recibieron > 150 mCi de
yodo radiactivo mostraron una tendencia hacia una peor puntuación
en la misma categoría de dolor (p=
0.05). Conclusiones: Nuestro grupo
de pacientes con cáncer diferenciado de tiroide reportaron en general
un efecto mínimo en su calidad de
vida. Sin embargo, futuras intervenciones de tratamiento deben incluir
instrumentos que de forma periódica evalúen la calidad de vida de estos pacientes.
CLINICAL AND RADIOLOGICAL INDICATORS OF
SEVERITY IN PATIENTS WITH ACUTE PANCREATITIS
Bella Vista Hospital Family Medicine Program, Mayaguez, Puerto Rico.
*Corresponding author: Beatriz McMullen MD – 1201 NW 16th Street, Miami, Florida, USA
33125. E-mail: beatriz.mcmullen@gmail.com
a
Jorge Álvarez MDa
Pablo Castro MDa
Maria Fernández MDa
Beatriz McMullen MDa*
Carmen Rodríguez MDa
Jorge Vera MDa
ABSTRACT
The purpose of this study was to estimate the degree of association between clinical (Ranson criteria) and radiological variables (Abdominal CT scan) with degree of severity in
patients with a diagnosis of acute pancreatitis. Method: All patients discharged with the
diagnosis of acute pancreatitis from January 1, 2010 through December 31, 2012 in a community hospital were selected (N = 174). The following variables were studied: sex; age;
weight; height; admission and discharge dates; presence of several chronic conditions;
laboratory results included in Ranson criteria; abdominal CT category; outcome, including fatality, surgery, and other complications. Analysis included descriptive statistics and
Risk-Ratios for complications for different groups of subjects, using clinical and radiological criteria. Results: The incidence rate of complications, including fatality, surgery
and organ failure was 36.2%. Factors that showed significant associations with the risk of
complication on crude analysis were gallbladder disease with a RR = 1.78 (95% CI: 1.22,
2.60) and abnormal abdominal CT with a RR = 1.85 (95% CI: 1.11, 3.07). With multivariate
analysis, gallbladder disease, abnormal abdominal CT, and presence of 3 or more Ranson’s criteria showed increased risk for complications, but the results did not reach statistical significance. Discussion: The factors that seemed to be associated with increased
rate of complications in subjects with acute pancreatitis were gallbladder disease, abnormal abdominal CT, and 3 or more Ranson’s criteria. The results did not show statistical
significance probably because of low statistical power of the study.
Index words: clinical, radiological, indicators, severity, acute, pancreatitis
INTRODUCTION
emboli, hypoperfusion, vasculitis), accounts for a significant percentcystic fibrosis, and Reye’s syn- age of admissions to hospitals. At
Acute pancreatitis is an inflamma- drome. (4).
Bella Vista Hospital between 2010
tion of the pancreas that usually
and 2012, there were 24,768 hosoccurs as a result of gallstones or This is a disease capable of wide pitalized patients; acute pancreatialcohol abuse. These are the two clinical variation, ranging from mild tis was responsible for 1% of those
most common causes of acute pan- discomfort to severe pain and pros- admissions.
creatitis, accounting for 60-80% of tration. Moreover, the inflammatocases. Other causes include blunt ry process may remain localized in There are currently controversies
trauma to the abdomen, iatrogenic the pancreas, spread to regional regarding which factors or criteria
trauma (postoperative trauma or tissues, or even involve remote or- are better predictors of a poor outprocedures like endoscopic retro- gan systems. (5) The majority of come from this disease. The most
grade cholangiopancreatography), cases of acute pancreatitis do not common method of assessing sehypertriglyceridemia, hypercalce- cause complications nonetheless verity and prognosis of patients
mia, drugs such as rosuvastatin a small percentage may develop with acute pancreatitis is the use of
and sitaglipin (1, 2), infections such an illness with complications that clinical criteria that were described
as mumps or leptospirosis (3), require intensive care. In all cas- by Ranson as far back as 1974 (6).
congenital anomalies (pancreas es it is essential to determine the These clinical criteria are used to
divisum, choledochocele), ampul- cause and if at all possible to try to calculate a severity score based
lary or pancreatic tumors, vascular prevent acute pancreatitis and its on factors identified at admisabnormalities (atherosclerotic
complications. Acute pancreatitis
sion (age, white blood cell count,
blood glucose, AST, LDH) and
within 48 hours of admission (serum calcium, hematocrit change,
oxygen, BUN, base deficit, and
fluid sequestration). More recently, Balthazar described a system
of classifying the severity of acute
pancreatitis, based in findings of
an abdominal CT scan. According
to this system: Class A = normal
pancreas; Class B = enlargement
of pancreas; Class C = inflammatory changes in pancreas; Class D
= ill-defined single fluid collection;
Class E = two or more poorly defined fluid collections. (7)
The objective of this study was
to describe the characteristics of
patients admitted with acute pancreatitis in a community hospital
and to estimate the degree of association between clinical (Ranson
criteria) and radiological variables
(Abdominal CT scan) with prognosis in patients with a diagnosis of
acute pancreatitis.
METHOD
This was a retrospective cohort
study conducted in a community hospital located in Mayagüez,
Puerto Rico. The investigators
obtained all necessary authorizations from the hospital’s administration and from Ponce School
of Medicine and Health Sciences’
Institutional Review Board (IRB
130312-II). All patients discharged
with the diagnosis of acute pancreatitis from January 1, 2010 through
December 31, 2012 in the mentioned hospital were selected (N =
174). Investigators systematically
reviewed the hospital records of
these subjects and extracted data
including the following variables:
sex; age; weight; height; admission and discharge dates; presence of diabetes mellitus, arterial
hypertension, chronic obstructive
pulmonary disease, and cholelithiasis; evidence of excessive alcohol
intake; Laboratory test results on
admission, including white blood
cell count, blood glucose, AST,
serum calcium, pO2, hematocrit,
blood urea nitrogen, serum creatinine, and blood CO2; and outcome, including fatality, surgery,
organ failure or death. Abdominal
computed tomography (CT) scan
findings were classified in four
groups according to criteria defined previously by Balthazar (7)
Normal abdominal CT scans were
classified as “A”. Abnormal abdominal CT scans were classified as
“B” if only pancreatic swelling was
reported. A “C” classification was
given when the scan showed fluid
collection, and “D” was used when
there was evidence of severe abnormalities such as hemorrhage.
Investigators did the data analysis
using Epiinfo®, which is a statistical software produced by the Centers for Disease Control (CDC).
Statistical analysis included distribution frequencies of demographic variables and co-morbid
conditions. Means and frequency
distributions for different laboratory
abnormalities and abdominal CT
categories were estimated. The
analysis also included estimation
of risks for several complications
and comparison of these risks for
different groups of subjects. These
comparisons were expressed in
terms of risk-ratios and their respective 95% confidence intervals.
The adjusted hazard ratios of complications for different factors were
calculated using a Cox Proportional Hazards model.
RESULTS
Figure 1 shows the sex distribution
of the 174 subjects in the study, of
which 51% were female and 49%
were male. The mean age was
59.5 years (SD = 17.8), with a median age of 63 years and a range
of 17-94 years. Figure 2 shows the
age distribution by groups; the majority of subjects were 60 years of
age or older. Figure 3 shows the
distribution of subjects by groups
according to their Body Mass Index (BMI). The majority of subjects
were overweight or obese. The
mean number of days of hospital
stay was 7 days (SD = 5.1) with a
median stay of 5 days and a range
of 1-32 days. A total of 36 subjects
(21%) were admitted from 7-14
days; 13 subjects (7%) were admitted for more than 14 days.
hypertension, 46.0% for diabetes
mellitus and 31.0% for gallbladder disease. Table 1 shows these
results and the prevalence rates
of other conditions. Results of abdominal CT scans were classified
in four categories as described
in the Method section. Figure 4
shows the distribution of abdominal
CT scan results by group. Only 114
subjects had abdominal CT scans.
For the remaining data analysis all
abnormal CT scans (categories B,
C and D) were grouped together.
The prevalence rate of abnormal
abdominal CT’s was 35.1%. Table 2 shows the prevalence rates
in the study subjects of different
clinical criteria, including abnormal
laboratory results that have been
implicated in the past as having
prognostic value in patients with
pancreatitis. These criteria are
among those described by Ranson
but not all of these criteria were
available in this study population.
Table 3 shows the incidence rate
of different complications. The
most frequent complication was
surgery (20.1%) followed by renal
failure (9.8%). Four subjects in
this study died during the course
of hospitalization, for a case-fatality rate of 2.3%. The combined
incidence rate for any complication
was 36.2%.
Individuals with complications had
a mean hospital stay of 8.6 days
(SD = 5.8); individuals without
complications had a mean hospital
stay of 6.0 days (SD = 4.5). The
difference of their mean stays was
2.6 days (95% CI: 0.9, 4.3), which
was statistically significant.
Table 4 shows results from the
crude analysis of the risk of having an outcome with complications
comparing groups of individuals
with and without different exposures. Factors that showed significant associations with the risk
of complication on crude analysis
were gallbladder disease with a
RR = 1.78 (95% CI: 1.22, 2.60)
and abnormal abdominal CT with a
RR = 1.85 (95% CI: 1.85). Having
three or more of the clinical RanPrevalence rates of chronic con- son’s criteria present also showed
ditions were 63.2% for arterial a tendency for increased risk of
Figura 2
Figura 1
Figura 4
Figura 3
Tabla 1
Tabla 2
complications, although the result
was not statistically significant,
with a RR = 1.58 (95% CI: 0.66,
3.74). Since many of these clinical
and radiological factors may coexist in the same individuals and
serve as confounders one another,
these three factors were included
in a multivariate analysis or Cox
Proportional Hazards Model in order to estimate their adjusted Hazard Ratios for complications. In this
analysis, the three factors included
continued to show a tendency for
increased risk for complications,
but the results did not reach statistical significance. These results
are shown in Table 5.
DISCUSSION
Tabla 3
The incidence of acute pancreatitis varies in different countries and
can be developed as the results of
many factors. In the United States
the incidence of this disease ranges from 13 to 45/100,000 persons,
per year. Causal factors of acute
pancreatitis are many, but the most
RESUMEN
frequent causes are gallstones
and alcohol (8). Studies suggest
that the incidence of pancreatitis
has increased in Europe and USA
in the past years (9).
The patient profile of the subjects
in this study reveals a similar prevalence of both sexes. The majority
of patients were 60 years or older. There was a high prevalence
of co-morbidities such as obesity, hypertension, and diabetes
mellitus. The overall incidence of
complications was 36.2%. These
complications included necrosis, hemorrhage, infection, organ
failure and death. As anticipated,
patients with complications had
longer hospital stays than patients
without complications.
Ranson’s criteria and other severity scoring systems such as Computed Tomography (CT) Severity
Index have been developed to
predict the likelihood of adverse
outcomes, including fatality, in patients with acute pancreatitis. Early evaluation and risk stratification
for patients with acute pancreatitis are important to differentiate
patients with mild versus severe
disease and those who need intensive care treatment (10).
Attempts have been made to determine whether clinical or radiological criteria are better predictors of poor prognosis in these
patients.
Bollen and collaborators found
that the Balthazar system of abdominal CT classification was a
better predictor of poor prognosis
than other classification systems
based on CT findings, but they did
not find a difference between this
system and several others based
on clinical criteria in their ability
to predict severity (11). Bota and
her co-investigators developed a
clinical severity score system –
they called Prediction Pancreatic
Severity Score – that was able to
predict a poor outcome with 75%
accuracy (12). In another recent
study C- Reactive Protein (CRP)
levels were found to be good
predictors of pancreatic necrosis
and Ranson scores were better
Tabla 4
Tabla 5
predictors of case fatality (13). In
a very recent study, Brand and
collaborators established that
contrast-enhanced abdominal CT
was useful to predict a poor outcome, but the study included only
subjects with necrotizing pancreatitis (14).
In our study the factors that
showed a tendency to be associated with the risk of complications were the presence of three
or more Ranson’s criteria’s and
abnormalities in Abdominal CT
Scan. However, none of the associations were statistically significant, more likely due the size
of the group and subsequent lack
of statistical power. Another limitation of this study was that not all of
Ranson’s criteria were available in
the medical records.
REFERENCES
1. Chintanaboina JK, Gopavaram D. Recurrent Acute Pancreatitis Probably Induced by Rosuvastatin Therapy: A Case
Report. Case Reports in Medicine. 2012:
2012: 4 pages (E pub)
2. Sue M , Yoshihara A, Kuboki K, Hiroi N,
Yoshino G. A case of severe acute necrotizing pancreatitis after administration of
sitagliptin. Clin Med Insights Case Rep.
2013; 6:23-7.
3. Popa D , Vasile D, Ilco A. Severe acute
pancreatitis - a serious complication
of leptospirosis. J Med Life. 2013 Sep
15;6(3):307-9.
4. Tenner S. Baillie J, DeWitt J, Vege
SS. American College of Gastroenterology Guideline: Management of Acute
Pancreatitis. Am J Gastroenterol 2013;
108:1400–1415.
5. Bradley EL. A Clinically Based Classification System for Acute Pancreatitis.
Summary of the International Symposium
on Acute Pancreatitis, Atlanta, GA,
September 11 through 13, 1992. Arch
Surg 1993;128:586–90.
6. Ranson JH, Rifkind KM, Roses DF,
Fink SD, Eng K, Spencer FC. Prognostic
signs and the role of operative management in acute pancreatitis. Surg Gynecol
Obstet. 1974 Jul;139(1):69-81.
7. Balthazar E. Acute pancreatitis: Assessment of severity with clinical and CT
evaluation. Radiology 2002; 223:603-613.
8. Dhiraj Yadav and Albert B. Lowenfels,
The Epidemiology of Pancreatitis and
Pancreatic Cancer, Gastroenterology. Jun
2013; 144(6): 1252–1261.
9. Roberts SE, Akbari A, Thorne K, Atkinson M, Evans PA, The incidence of
acute pancreatitis: impact of social
deprivation, alcohol consumption, seasonal and demographic factors, Alimentary Pharmacology and Therapeutic. 2013
Sep; 38(5): 539-48.
10. Carroll J, Herrick B, Gipson T, Lee S.,
Acute Pancreatitis: Diagnosis, Prognosis,
and Treatment, American Family Physician. 2007 May 15; 75(10):1513-1520.
11. Bollen TL , Singh VK, Maurer R,
Repas K, van Es HW, Banks PA, Mortele KJ. A comparative evaluation of radiologic and clinical scoring systems in
the early prediction of severity in acute
pancreatitis. Am J Gastroenterol. 2012
Apr;107(4):612-9.
12. Bota S, Sporea I, Sirli R, et al. Predictive factors for severe evolution in acute
pancreatitis and a new score for predicting a severe outcome. Annals of Gastroenterology 2013; 26: 156-162
13. Khanna AK, Meher S, Prakash S, Tiwary SK, Singh U, Srivastava A, Dixit VK.
Comparison of Ranson, Glasgow, MOSS,
SIRS, BISAP, APACHE-II, CTSI Scores,
IL-6, CRP, and Procalcitonin in Predicting
Severity, Organ Failure, Pancreatic Necrosis and Mortality in Acute Pancreatitis.
HPB Surgery 2013; 2013: 10 pages (E
pub)
14. Brand M , Götz A, Zeman F, Bet al.
Acute necrotizing pancreatitis: laboratory,
clinical, and imaging findings as predictors of patient outcome. AJR Am J Roentgenol. 2014 Jun;202(6):1215-31.
Continue...
El propósito de este estudio
fue estimar el grado de asociación entre criterios clínicos
(Ranson) y radiológicos (TC
abdominal) con el grado de
severidad en pacientes con
pancreatitis aguda. Método;
Todos los pacientes dados
de alta con un diagnóstico de
pancreatitis aguda en un hospital de comunidad entre el
1ro de enero de 2012 al 31
de diciembre de 2012 fueron
seleccionados (N = 174). Las
siguientes variables fueron
estudiadas: sexo, edad, peso,
estatura, fechas de admisión y
alta, presencia de varias condiciones crónicas, resultados de
laboratorio, categoría de TC
abdominal, letalidad, cirugía y
otras complicaciones. El análisis incluyó estadísticas descriptivas y razones de riesgo
para diferentes complicaciones
para diferentes grupos de sujetos, usando criterios clínicos
y radiológicos. Resultados: La
tasa de incidencia de complicaciones, incluyendo letalidad,
cirugía y fallo de órganos fue
36.2%. Factores que tuvieron
asociaciones significativas con
el riesgo de complicaciones al
hacer análisis crudos fueron
enfermedad de la vesícula con
un RR = 1.78 (IC 95%: 1.22,
2.60) y una TC abdominal
anormal con un RR = 1.85 (IC
95%: 1.11, 3.07). Con análisis
multivariado, la enfermedad de
la vesícula, una TC abdominal
anormal y la presencia de 3
o más criterios de Ranson tuvieron una tendencia a un mayor riesgo de complicaciones,
pero los resultados no fueron
estadísticamente
significativos. Discusión: Los factores
que parecieron estar asociados con un aumento en riesgo
de complicaciones en sujetos
con pancreatitis aguda fueron
enfermedad de la vesícula,
una TC abdominal anormal y
la presencia de 3 o más criterios de Ranson. Los resultados
no demostraron significación
estadística probablemente por
un poder estadístico bajo del
estudio.
Case Report/Reporte de Casos
CELIAC TRUNK AND BRANCHES DISSECTION DUE
TO ENERGY DRINK CONSUMPTION AND HEAVY
RESISTANCE EXERCISE:
Case Report and Review of Literature
Wilma González BSa
Pablo I. Altieri MDac*
Enrique Alvarado MDb
Héctor L. Banchs MDac
Edgar Colón MDb
Nelson Escobales PhDa
María Crespo PhDa
A
Department of Medicine and Physiology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
b
Department of Diagnostic Radiology, University of Puerto Rico, School of Medicine, Medical
Sciences Campus, San Juan, Puerto Rico.
c
Cardiovascular Center of Puerto Rico and the Caribbean, San Juan, Puerto Rico.
*Corresponding author: Pablo I. Altieri MD - Box 8387, Humacao, Puerto Rico 00792. E-mail:
altierip@prtc.net
a
ABSTRACT
Higher doses and consumption of energy drinks leads to cardiovascular effects and potential consequences. Principal components found in energy drinks such as caffeine,
guarana and taurine has been related to dilatation, aneurysm formation, dissection and
ruptures. There is no evidence showing an integration of these components and its effects in endothelium and aortic walls due to higher levels of pressure during exercises.
We report a case of a 44 years male with celiac trunk and branches dissection due to
long-term consumption of energy drinks and intense exercise routine. Our proposition
relates cell and vessel walls alterations including elasticity in endothelial wall due to higher blood pressure, resistance by intense exercise routine and long-term consumption of
energy drinks.
Index words: celiac, trunk, branches, dissection, energy, drink, consumption, exercise
INTRODUCTION
Energy drinks (ED) consumptions
have been related in recent years
to cardiovascular disease events
but little evidence exists showing
its hemodynamic side effects (1).
Critical analysis has been studied
to present the effects of ED components with extensive exercise routine and its cardiovascular effects.
We present a case of a 44 years
old male with a history of long-term
ED consumption and intense exercise routine that used cross training and heavy resistance bands.
Case History
The patient is a 44 years old male
with no previous history of any cardiovascular disease, presenting
severe epigastric pain and dizziness. The pain started during exercise while using weight training
and heavy resistance bands in a
cross training program, persisting
for several hours. Prior to exercise,
the patient drank an ED based on
caffeine and guarana as stimulants. A computed tomography angiography (CTA) of the abdomen
and pelvis was performed during
his evaluation (see Figure 1). It
showed a small linear filling defect
(intimal flap) in the celiac trunk, approximately 1.2 cm distal to the origin, with a fusiform aneurysmal dilatation and tortuosity of the vessel
distal to the identified flap. The CTA
showed also tortuous dilatation of
the common hepatic artery and a
stenotic region with discontinuity
of lumen in the proximal splenic artery, 1.6 cm distal to its origin, with
distal reconstitution by collateral
circulation. No abdominopelvic solid organ abnormalities were presented. The patient was observed
closely. Follow up CTA showed no
further changes. The patient was
advised to stop using of ED and
B
Figure 1. Abdominopelvic CT angiogram (CTA) showing
dissection of the celiac trunk. (a) Axial maximum intensity projection (MIP) image at the level of the celiac trunk
showing a linear filling defect (yellow arrow) representing
the intimal flap. Note the large caliber of the common hepatic artery (blue arrow). The splenic artery (black arrow)
shows an area of proximal severe stenosis and discontinuity of the lumen. (b) 3-dimensional volume rendering frontal image of the upper abdominal aorta showing an area of
severe stenosis and discontinuity in the proximal splenic
artery (white arrow). (CA: celiac artery, CH: common hepatic artery, SMA: superior mesenteric artery, RRA: right
renal artery, LRA: left renal artery).
stop the intensive exercise routine.
DISCUSSION
Higher aortic wall stress involved
in strenuous exercise routine could
lead to aortic dilatation, aneurysm
formation, aortic dissection, and
ruptures (2). This associations are
based on higher levels of pressure over 300 mmHg versus normal level between 180-220 mmHg
presented in heavy trainings that
deteriorate properties of the aortic lumen and increases the risk to
dissects (3). The necessity to enhance performance in heavy training routine exercises has improve
the usage of stimulants such as energy drinks (ED), but its consumption could lead to potential health
consequences. These relations
are based on ED principal content
of excessive caffeine, taurine, and
guarana doses, long-term exposure, and its biochemical effects
. The use of caffeine has been
related to cell swelling, catecholamine excess, endothelium-dependent flow mediated dilatation,
modulation of glucose levels, higher cholesterol, arterial hypertension, cell wall and arterial stiffness,
cardiac arrhythmias, coronary artery disease, abnormal stimulation
of the central nervous system, and
death (4-7). Combination of principal components in ED may lead
to apoptotic cell pathways such as
lower basal levels of free radical
generation, membrane blebbing,
cell shrinkage, catecholamine excess, cleaved caspase-3 positivity,
removal of intracellular reactive oxygen species, acid-base disorders,
seizure, and insulin sensitivity (89).
ED’s principal components have
been related with aortic dissection
and aortic aneurysm (10, 11), but
there’s no evidence showing this
effects by the integration of ED’s
components, consumption of high
doses of caffeine, and the stress in
vessel walls during extensive exercise routine. The effect of these
additives has been reported to increase epinephrine and endurance
during exercise (12). Thus, higher
doses of ED has not been reported
as a secondary factor during exercise routines that could contribute to stress limit in vessel walls.
During exercise, acute rises in BP
has been related to vessel walls by
deteriorating aortic wall and producing aneurysmal enlargement
(3). Riles & Lin (13) have reported
a 45-year-old man with arterial dissection, similar to our patient’s, related to weight lifting and its effects
in blood pressure. Also, the relation between root dilatation during
weight training routines in youth
population (11) and acute aortic dissection activity due to weight lifting
(10) has been reported. The main
factors related to aortic dissection
have been reported as degeneration in the intima media thickness
related to collagen content, elastin, and hypertensive activity (14).
We proposed a relationship in the
intervention of elasticity in endothelial vessel walls, strengthen by
ED’s effects in higher blood pressure, and a combination of cell and
vessel wall alterations due to the
pressure exerted by heavy resistance bands with long term consumption of caffeine-based ED.
Individuals who show aneurysmal
formation or aortic dilatation should
be warned to the use of these components in heavy training. Also,
those who are using heavy training exercises should consider prior
screening and a broader knowledge of possible side effects of
these additives.
REFERENCES
and clinical understanding provide an opportunity to save young lives. J Cardiovasc
Surg (Torino) 2010; 51(5): 669-81.
(12) Heckman MA, Sherry K, De Mejia
EG. Energy drinks: an assessment of
their market size, consumer demographics, ingredients profile, functionality, and
regulations in the United States. Compr
Rev Food Sci Food Saf 2010; 9: 303–17.
(13) Riles TS, Lin JC. Celiac artery dissection from heavy weight lifting. J Vasc Surg
2011; 53(6): 1714-5.
(14) Aziz F, Penupolu S, Alok A, Doddi S,
Abed M. Peripartum acute aortic dissection: A case report & review of literature. J
Thorac Dis 2011; 3(1) 65-7.
(3) Mayerick C, Carré F, Elefteriades J.
Aortic dissections and sport: physiologic
and clinical understanding provide an opportunity to save young lives. J Cardiovasc
Surg 2010; 51(5): 669-81.
(4) Wolk BJ, Ganetsky M, Babu KM. Toxicity of energy drinks. Curr Opin Pediatr
2012; 24(2): 243-51.
(5) Dworzański W, Opielak G, Burdan F.
Side effects of caffeine. Pol Merkur Lekarski 2009; 27(161): 357-61.
(6) Eudy AE, Gordon LL, Hockaday BC, et
al. Efficacy and safety of ingredients found
in preworkout supplements. Am J Health
Syst Pharm 2013; 70(7): 577-88.
(7) Doerner J, Kuetting D, Naehle CP,
Schild HH, Thomas DK. Caffeine and taurine containing energy drink improves systolic left-ventricular contractility in healthy
volunteers assessed by strain analysis
using cardiac magnetic resonance tagging
(CSPAMM). Radiological Society of North
America 2013, Chicago, USA.
(8) Zeidán-Chuliá F, Gelain DP, Kolling EA,
et al. Major components of energy drinks
(caffeine, taurine, and guarana) exert cytotoxic effects on human neuronal SH-SY5Y
cells by decreasing reactive oxygen species production. Oxid Med Cell Longev
2013; 2013:791-795.
(9) Trabulo D, Marques S, Pedroso E. Caffeinated energy drink intoxication. Emerg
Med J 2011; 28: 712-14.
(10) Hatzaras I, Tranquilli M, Coady M, Barrett PM, Bible J, Elefteriades JA. Weight
lifting and aortic dissection: more evidence
for a connection. Cardiology 2007; 107(2):
103-6.
(11) Mayerick C, Carré F, Elefteriades J.
Aortic dissection and sport: physiologic
Department of Internal Medicine, University of Cincinnati, College of Medicine, Cincinnati, Ohio.
b
Cardiovascular Division, University of Cincinnati, College of Medicine, Cincinnati, Ohio.
c
Pulmonary Division, University of Cincinnati, College of Medicine, Cincinnati, Ohio.
d
Cardiovascular Medicine Division, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
*Corresponding author: Angel López-Candales, MD, PO Box 365067, San Juan, Puerto Rico 00936-5067. Email: angel.lopez17@upr.edu
a
Daniel A. Pietras MDa
Francisco R. Lopez MDb
Reynerio Pérez MDc
Angel López-Candales MDc*
Jean Elwing MDd
ABSTRACT
(1) Jonjev ZS, Bala G. High-energy drinks
may provoke aortic dissection. Coll Antropol 2013; 37 Suppl 2: 227-9.
(2) Erbel R, Alfonso F, Boileau C, et al. Diagnosis and management of aortic dissection. Eur Heart J 2001; 22(18): 1642-81.
WORSENING GRADIENT OF AORTIC STENOSIS WITH
TREATMENT OF PULMONARY ARTERIAL HYPERTENSION IN SCLERODERMA
RESUMEN
Dosis altas y el consumo de
bebidas energéticas conduce a efectos cardiovasculares con sus posibles consecuencias.
Componentes
principales en las bebidas
energéticas como la cafeína,
guaraná y taurina se ha relacionado con la dilatación,
formación de aneurismas,
disección y rupturas; aunque
no existe evidencia mostrando una integración de estos
componentes y sus efectos
en endotelio y paredes aórticas debido a altos niveles de
presión en los ejercicios. Divulgamos un caso de un varón
de 44 años con disección del
tronco celíaco y sus ramas
debido al largo plazo de consumo de bebidas energéticas
y rutina de ejercicio intenso.
Nuestra propuesta refiere a
la célula y alteraciones de las
paredes de los vasos arteriales incluyendo la elasticidad
en la pared endotelial debido
a la presión arterial más alta,
resistencia de rutina de ejercicio intenso y consumo a largo plazo de energía bebidas
Systemic sclerosis (SSc) can cause interstitial lung and pulmonary vascular disease that
can induce pulmonary arterial hypertension (PAH). It is well known that severe PAH may
reduce left ventricular preload and decrease diastolic filling with the potential of reducing forward flow. We present a case in which a patient with SSc and symptomatic PAH
required direct pulmonary vasodilator therapy for treatment of elevated pulmonary pressures. On follow-up echocardiogram, while improvement in right ventricular function
and reduction in estimated pulmonary pressures were noted; worsening of aortic valve
gradients was also found. Cardiac hemodynamics of pulmonary vasodilator therapy is
discussed and the literature is reviewed.
Index words: gradient, aortic, stenosis, pulmonary, hypertension, scleroderma
INTRODUCTION
Pulmonary arterial hypertension is
a frequent complication of systemic sclerosis. Even though survival
in systemic sclerosis complicated
by pulmonary arterial hypertension remains poor; early diagnosis and treatment may improve
outcomes since worsening hemodynamic factors are associated
with reduced survival. In this case
report we review treatment with a
pulmonary vasodilator resulting in
improvement in right sided function; however, uncovered the true
severity of a previously unrecognized valvular abnormality. Further
evidence is provided to review cardiac hemodynamics and explain
why aortic stenosis was uncovered
while treating this patient.
Case History
A 58-year-old male with systemic sclerosis (SSc) presented with
dyspnea on exertion, lethargy,
and fatigue. A transthoracic echocardiogram (TTE) showed normal
left ventricular systolic function,
pulmonary arterial hypertension
(PAH) and mild aortic stenosis (AS)
with a mean valve gradient of 16
mmHg. A right heart catheterization confirmed severe elevation in
pulmonary artery (PA) pressures
(70/25 mmHg with mean PA 45
mmHg), decreased pulmonary
capillary wedge pressure (PCWP)
(8 mmHg), high pulmonary vascular resistance (453 dyn·s/cm5) and
increased transpulmonary gradient
(37 mmHg) were noted, confirming
an intrinsic right-sided cause for
this patient pulmonary hypertension. Pre-capillary etiology of PH
was further supported by exercise
hemodynamics (supine bike) with
23 mmHg increase in mPA without
increase in wedge and a mild AS
gradient. Vasodilator therapy was
initiated.
A repeat echocardiogram obtained
eight months after starting PA vasodilator therapy showed a decreased in PA systolic pressures
of nearly 50% from baseline (36
mmHg) while the mean aortic valve
gradient had increased from 21 to
32 mmHg as seen in Figure 1. As
expected, RV systolic function had
significantly improved as demonstrated by the increase in strain
generation using velocity vector
imaging (Figure 2A and B). Similarly, left ventricular myocardial
systolic velocities as well as strain
generation were also significantly
increased by the velocity vector imaging technique as seen in Figure
2C-F.
DISCUSSION
PAH is a frequent complication of
SSc and likely due to proliferative
arterial pulmonary microangiopathy (1-4). Even though survival in
SSc complicated by PAH remains
poor, despite currently available
treatment options, and the prognosis for patients with interstitial
lung disease associated PAH is
particularly grim, early diagnosis
and treatment may improve outcomes since worsening hemodynamic factors are associated with
reduced survival (5).
Figure 2: (A) Velocity vector imaging of
RV segments during the initial study and
(B) on the follow up study. Please note
the significant increase in peak systolic
RV strain generation. (C) Baseline and
(D) follow-up velocity vector imaging of
LV segments demonstrating velocity
curves. Please note how the systolic
velocity has doubled (solid arrow). (E)
Baseline and (F) follow-up velocity vector imaging curves showing strain generation of the same LV segments. Similarly, please note that the peak systolic
LV strain generation has also doubled
(broken arrow).
Figure 1: Initial and follow-up aortic, peak aortic and LVOT systolic velocities as well as tricuspid regurgitation
Doppler signals. Please note, a significant increase in aortic velocity when compared to LVOT, suggesting
worsening aortic stenosis calculation as a result of increased forward flow in the follow-up study. In addition,
the follow-up study shows a lower maximal velocity of the tricuspid regurgitation signal, suggesting improvement in pulmonary hypertension as a result of therapy.
This particular case not only highlights a basic hemodynamic principle between improved right
ventricular ejection as a result of
vasodilator therapy; thus increasing forward flow; but also of enhanced myocardial mechanics.
Not only we speculate that these
two mechanisms directly contributed to unmasking the true AS severity; but provide direct proof of
this hemodynamic and mechanical
principle. The latter can be clearly
appreciated with the use of velocity
vector imaging. The use of direct
pulmonary vasodilator therapy significantly improved myocardial dynamics as seen in Figure 2. Specifically, a significant increase in peak
systolic strain generation not only
was documented in the RV, but
also in the LV.
It is well known that systole and
diastole result in shortening and
elongation of the myocardium, respectively. This cyclical change in
shape (deformation) allows the use
of strain to quantify cardiac function. Lagrangian strain, or simply
strain, is defined as the change in
myocardial fiber length and it has
been used to objectively quantitative myocardial contractility (6).
Lack of recognition of this basic
mechanical principle proven by
velocity vector imaging could have
been wrongly interpreted as PAH
progression and/or therapy failure
if there was any reappearance of
symptoms. In our patient, there
we no new symptoms; worsening
of the aortic valve gradients was
simply discovered on a follow-up
surveillance study. Therefore, no
additional changes were done to
his PAH regimen and at that time
no other intervention was recommended as development of severe
AS was not anticipated given the
advanced nature of his underlying
condition.
To our knowledge not only this is
the first case reporting documentation of worsening in AS severity
as a direct result of improving right
and left ventricular mechanics with
direct pulmonary vasoactive therapy; but also of the objective documentation of improvement myocardial mechanics with this form of
therapy.
REFERENCES
1. Sitbon O, Humbert M, Jais X, et al. Longterm response to calcium channel blockers
in idiopathic pulmonary arterial hypertension. Circulation 2005;111:3105-3111.
2. Hachulla E, Gressin V, Guillevin L, et al.
Early detection of pulmonary arterial hypertension in systemic sclerosis: a French
nationwide prospective multicenter study.
Arthritis Rheum 2005;52:3792–3800.
3. Mukerjee D, St George D, Coleiro B, et
al. Prevalence and outcome in systemic
sclerosis associated pulmonary arterial
hypertension: application of a registry approach. Ann Rheum Dis 2003;62:1088–
1093.
4. Phung S, Strange G, Chung LP, et al.
Prevalence of pulmonary arterial hypertension in an Australian scleroderma population: screening allows for earlier diagnosis.
Intern Med J 2009;39:682–691.
5. Mathai SC, Hummers LK, Champion HC,
Wigley FM, Zaiman A, Hassoun PM, Girgis
RE. Survival in pulmonary hypertension
associated with the scleroderma spectrum
of diseases: impact of interstitial lung disease. Arthritis Rheum 2009;60:569-577.
6. Huang SJ, Orde S. From speckle tracking echocardiography to torsion: research
tool today, clinical practice tomorrow. Curr
Opin Crit Care. 2013;19:250-257.
RESUMEN
La esclerosis sistémica puede
causar enfermedad pulmonar
intersticial y de la vasculatura
pulmonar produciendo hipertensión pulmonar arterial. Se
reconoce que esta hipertensión
pulmonar puede reducir la precarga ventricular izquierda y
disminuir la presión diastólica
de llenado reduciendo el flujo
del corazón. Discutimos el caso
de un paciente con esclerosis
sistémica e hipertensión pulmonar sintomática que requirió
terapia vasodilatadora directa
pulmonar para el manejo de su
presión pulmonar elevada. En
ecocardiogramas de seguimientos mientras se noto una mejora
en la función ventricular derecha y reducción en la presión
pulmonar, ocurrió un deterioro
en el gradiente de presión de
la válvula aortica. La hemodinámica cardiaca de la terapia
de vasodilatación pulmonar se
discute y la literatura en esta
condición se revisa.
Asociación Médica
de Puerto Rico
UNCOMMON CAUSE OF LIFE-THREATENING
RETROPERITONEAL HEMORRHAGE IN A HEALTHY
YOUNG HISPANIC PATIENT: SPLENIC ARTERY
ANEURYSM RUPTURE
Internal Medicine Department, San Juan City Hospital, San
Juan, Puerto Rico.
b
Hematology–Medical Oncology Section, VA Caribbean
Healthcare System and San Juan City Hospital, San Juan,
Puerto Rico.
c
Interventional Vascular Section,Cardiovascular Medical Center of Puerto Rico, San Juan, Puerto Rico
*Corresponding author: Luis A. Figueroa-Jiménez MD - Internal Medicine Department, San Juan City Hospital, CMMS #79
PO Box 70344, San Juan, Puerto Rico 00936-8344. Email:
md.lfigueroa@gmail.com
a
Objetivos
La Asociación Médica de Puerto Rico es fundada en el año de
1902, cuando por aquel entonces, el insigne doctor Manuel
Quevedo Báez ve la necesidad de aglutinar a la profesión médica puertorriqueña en un núcleo para la defensa de la colectividad y así fomentar el contínuo progreso de la ciencia y el
arte de la medicina y el mejoramiento de la salud del pueblo de
Puerto Rico. Tras vencer incontables dificultades e inconvenientes naturales de la época, se celebró la asamblea constituyente
el día 21 de septiembre de 1902, en el salón de sesiones de la
Cámara de Delegados en la ciudad de San Juan.
MEMBRESIAS
ABSTRACT
Splenic artery aneurysms (SAA) are a rare life threatening clinical diagnosis. We present
a case of a young Hispanic woman with an aneurysm of the middle branch of the splenic artery and active leakage. The defect was embolized with complete resolution of the
retroperitoneal bleeding. Physicians should be aware of this rare entity especially when
female patients presents complaining of severe epigastric pain with associated hypovolemic shock.
Index words: retroperitoneal hemorrhage, young Hispanic, women, splenic, artery, aneurysm, rupture
INTRODUCTION
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MEMBRESIAS
P.O.BOX 9387
SAN JUAN, PR 00908-9387
Luis A. Figueroa-Jiménez MDa*, Amy Lee
González-Márquez MDa, Luis Negrón-García
MDb, Francisco Rosas-Soler, MDa, Aixa Dones-Rodríguez MDa, Mayknoll De la Paz-López,
MDb; Mónica Santiago-Casiano MDb, Edwin
Rodrίguez-Cruz MDc, William Cáceres-Pérkins,
FACPb; Luis Báez-Díaz, FACPb
present a case of a young Hispanic woman with an aneurysm of the
Splenic artery aneurysms (SAA) middle branch of the splenic artery
are a rare life-threatening clinical and active leakage.
diagnosis. They may either be due
to congenital defects or acquired Case History
conditions such as atherosclerosis
formation (1). The specific etiolog- A 19-year-old woman without hisic factors are in relation with an- tory of any systemic illness was
giodysplasia, portal hypertension, brought to the urgency room with
pregnancy and atherosclerosis (2). the complaint of diffuse abdominal
The prevalence of SAA ranges from pain of 24 hours of evolution. She
0.1% to 2% (3). Although SAA are described the pain as of sudden
considered rare, they remain the onset, initially located in the left upmost common (50%–75%) among per quadrant, blunt in quality, gradall visceral aneurysms. Predomi- ually progressing to 10 out of 10 in
nance among women is found with intensity, radiating to the back. Exa ratio of 4:13. SAA are important acerbated by movement and parto recognize, considering that in tially alleviated by the supine posiacute settings, patients who pres- tion. There was no association to
ent with ruptured or symptomatic food ingestion, sick contacts, drug
SAA, are exposed to a life-threat- use, or trauma. Pain was accomening condition with hemodynamic panied by the sensation of abdomcollapse and high mortality. Up to inal fullness. She denied allergies,
25% may be complicated by rup- fever, chills, night sweats, nausea
ture (2). Retrospective studies or vomiting, and changes in bowel
have shown that women with SAA or voiding habits. No past similar
rupture are exposed to a high mor- episodes of abdominal pain were
tality rate of 70% to 90% (3). We reported. She had no previous
hospitalizations or any past surgeries. Did not travel recently, nor
was sexually active. Family history
was non-contributory. Except for
occasional spontaneous bruising,
mild gum bleeding and self-limited
epistaxis, the rest of the review of
systems was negative.
On physical examination, patient
was in acute distress and ill appearing. She was alert and fully oriented. Vital signs were remarkable
for hypotension (98/60 mmHg) and
tachycardia (96 bpm). Conjunctival
pallor and dry oral mucosa were evident. No extra-heart sounds, murmurs or gallops were noted. Lung
fields were clear to auscultation.
Abdominal auscultation revealed
hypoactive bowel sounds. Percussion was dull in both upper abdominal quadrants. Palpation of a bulging or mass-like area located to the
left upper quadrant elicited severe
pain 10/10 in intensity. Spleen size
could not be determined. Scrutiny
was negative as well as Murphy’s
sign, McBurney’s point tenderness,
illiopsoas sign, Rovsing’s sign, and
Cullen’s sign. Scattered discrete
ecchymosis were found in bilateral lower extremities. There was no
evidence of any gross neurological
deficits.
Laboratories showed a complete
metabolic panel within normal limits. Complete blood count disclosed
WBC count of 15,000/μL, hemoglobin 9.4g/dL, hematocrit 27.2%,
and platelet count of 235,000/
μL. Coagulation panel; PT, PTT
and INR were within normal limits, except for a prolonged bleed- Figure 1: Abdominopelvic CT Scan: Large left retroperitoneal hematoing time. Urine analysis revealed ma, causing severe mass effect upon the adjacent celiac trunk, splenic
microscopic hematuria. Follow up artery/vein, pancreas, spleen and left kidney.
laboratories revealed hemoglobin
levels in decreasing trend; from 9.4
g/dL to 5.3 g/dL in a period of 24
hours. The patient received analgesia and multiple packed RBCs
transfusions.
An abdominopelvic CT-scan revealed the presence of a large
left retroperitoneal space hematoma causing severe mass effect
upon the adjacent celiac trunk,
splenic artery and vein, pancreas,
spleen and left kidney (see Figure
1). Findings were suggestive of
a small outpouching of the distal
splenic vein or artery with an acute
over chronic left retroperitoneal
hematoma, worrisome for the pos- Figure 2: Abdominopelvic MRI: Large encapsulated retroperitoneal
sibility of aneurysmal rupture with hemorrhage
active bleeding. In addition, a left
perinephric space hemorrhage and
distal transverse colon wall hematoma were described. Due to these
life-threatening findings an immeFigure 3: Abdiate more extensive workup was
dominal
arperformed besides clinical and heteriogram:
modynamic stabilization of the paDownward
tient.
displacement
into the pelvic
An abdominal MRI revealed findregion of the
ings compatible with a large 18 cm
left kidney and
in craniocaudal dimension and 15
adjacent struccm in transverse dimension encaptures with comsulated hemorrhage in the left side
promise
of
of the abdomen, which could be
blood flow secretroperitoneal in location or disondary to mass
secting within the mesentery (see
effect. (upper
Figure 2). The source of bleeding
arrow: towards
was not identified. Abdominal ultrathe right kidney,
sound disclosed a large left retroarrow
below:
peritoneal mass with thick septapointing out the
tions and avascular compartments,
displacement of
findings suggested a lymphovasthe left kidney)
cular malformation.
Figure 4: Abdominal arteriogram: Identification of the splenic artery aneurysm located in the middle
splenic branch.
Figure 5: Abdominal arteriogram/ Catheterism: Figure 6: Splenic catheterism: Status-post emCatheter device reached the splenic aneurysm, bolization of the middle and 3rd branch of splenic artery. Disclosed blockade of splenic aneuready for embolization techniques.
rysm leakage and blood flow after placement of
vascular plugs proximal to the aneurysm (Amplatzer® vascular occluders; St. Jude MedicalMN, USA).
Radiographic findings prompted
immediate surgical evaluation.
General surgery, as well as interventional radiologist specialists
analyzed the case, however invasive strategies were disregarded
upon consideration of a possible
concomitant coagulopathic process. Also, considering the worrisome findings in the history of
spontaneous self-limited mucosal
bleeding in addition to a prolonged
bleeding time, the possibility of a
bleeding disorder was very likely.
However, von Willebrand factor,
ristocetin cofactor activity, factor
VII, VIII activity, D-dimers and fibrinogen levels were all within normal limits, so a hemostasis disorder was excluded.
performed by cardiovascular intervention service revealing an
aneurysm of the middle branch of
the splenic artery with active leakage (see Figure 4). Embolization
with Amplatzer® vascular occluders (St. Jude Medical- MN, USA)
were done to the middle and third
branch of the splenic arteries with
complete resolution of the retroperAn abdominal arteriogram was itoneal bleeding (see Figure 6).
The patient was discharge home
within one-week with follow up at
outpatient clinics. Re-evaluation
with imaging studies disclosed persistence of the large capsulated
retroperitoneal hematoma but the
patient remains asymptomatic. No
further medical actions have been
taken.
DISCUSSION
Splenic artery aneurysms (SAA)
are rare and remain an insidious
entity. Retrospective reviews of
nonselective angiograms have
provided the most reliable incidence estimate of approximately
0.8% (3). The pathogenesis of SAA
has only been partially elucidated.
Histologic examinations have variously demonstrated internal and
external lamina disruption, fibrodysplasia of the media, subendothelial thickening, and accretion of
glycosaminoglycans in the subintimal layer and media (4). Commonly listed risk factors and associated
diseases include atherosclerosis,
autoimmune conditions (eg, lupus,
vasculitides), collagen vascular
diseases, pancreatitis, and portal
hypertension (2). There is a higher
prevalence of SAA among women.
The influence of hormonal factors
on arterial structure has been speculated but not confirmed (4, 5).
Retrospective analysis suggests
there is an inverse correlation of
SAA calcification and initial aneurysm size. The more calcification
presents in the SAA, the smaller
the SAA at presentation (6). However, calcification cannot be correlated with SAA rupture, a protective role against aneurysm growth
may exist. One study suggests that
may be that eggshell calcification
early in aneurysm development
will prevent expansion of the aneurysm (6).
Rupture is the most fatal clinical
presentation of SAA. Life-threatening rupture results in severe
abdominal pain and hypovolemic
shock as we reported in our case
presentation. There is an absence
of convincing evidence predicting
the risk of SAA rupture. Size of the
SAA is not clearly associated with
risk of rupture (3). Data shows that
cases with rupture SAA presented
with massive blood collection within peritoneal cavity and retroperitoneal space. These cases usually
undergo exploration laparotomy, to
identify the source of bleeding and
further splenectomy is performed
following the ligation of the splenic
artery proximal to the lesion (7).
SAA may be treated via open or
endovascular methods. The treatment of SAA depends on its location
over the splenic artery. The favored
method of treatment at present is
embolization (5). When embolization is difficult or contraindicated
by the proximity of the aneurysm
to the spleen (with risk of splenic
infarction) the options are open or
laparoscopic surgery with ligation
of the splenic artery, excision of the
aneurysm with re-anastomosis of
the artery or splenectomy with removal of the aneurysm (5). In our
case embolization was successfully done after the patient was hemodynamically stable. Embolization
of the SAA could be performed
when preservation of the native
artery is not required (8). The goal
is to achieve complete occlusion of
the vessel beyond the aneurysmal
neck first and then proximal to the
lesion to avoid back bleeding into
the lesions through gastroepiploic,
pancreatic, or gastric collaterals
(8). In summary, treatment options
are dictated by the anatomic location, the age of the patient, the
physiologic and clinical conditions
(9).
SAA rupture may become a relevant differential diagnosis of intraperitoneal hemorrhage and sudden death, respectively. Physicians
should be aware of this rare entity, especially when patients present to the emergency department
complaining of severe epigastric
pain with associated hypovolemic
shock more concerning in the female population. Future studies
must continue to focus on risk factors for rapid growth and further
delineation of SAA natural history,
which could ultimately identify patients who would benefit from early
prophylactic intervention.
alimenta
REFERENCES
1. Betal D, Khangura JS, Swan PJ, Mehmet V: Spontaneous ruptured splenic artery aneurysm: a case report, Cases Journal 2009;2:7150.
tu vida
2. Abbas MA, Stone WM, Fowl RJ: Splenic artery aneurysms; Two decades experience at Mayo Clinic, Ann Vasc Surg
2002;16:442-449.
3. Berceli SA: Hepatic and splenic artery aneurysms, Semin Vasc Surg
2005;18:196-201.
“Ensure me brinda los nutrientes que
necesito todos los días para ayudar a
mantenerme activa y con energía.”
4. Sadat U, Dar O, Walsh S, Varty K:
Splenic artery aneurysms in pregnancy: a
systematic review, Int J Surg 2008;6:261265.
5. Matsumoto K, Ohgami M, Shirasingi
N, Nohga K, Kitajima M: A first case report of the successful laparoscopic repair
of a splenic artery aneurysm, Surgery
1997;121:462–4.
6. Lakin RO, Bena JF, Sarac TP, et al: The
contemporary management of splenic artery aneurysms, J Vasc Surg 2011;53:95865.
7. Trastek VF, Pairolero PC, Joyce JW,
Hollier LH, Bernatz PE: Splenic artery aneurysms, Surgery 1982; 91:694-9.
8. Zhu X, Tam MDBS, Pierce G, et al: Utility
of the Amplatzer vascular plugs in splenic
artery embolization: comparison in conventional coil technique, Cardiovasc Intervent Radiol 2011;34:522-531.
9. Ikeda O, Tamura Y, Nakasone Y, et al:
Nonoperative management of unruptured
visceral artery aneurysms: treatment by
transcatheter coil embolization, J Vasc
Surg 2008;47:1212-1219.
C
M
Y
CM
MY
CY
CMY
K
RESUMEN
Aneurismas en la arteria esplénica son un raro y potencialmente diagnóstico mortal
clínico. Presentamos el caso
de una mujer joven con un
aneurisma de la rama intermedia de la arteria esplénica
y sangrado activo. Se realizaron técnicas de embolización
de forma exitosa. En este reporte queremos demostrar la
importancia de una identificación temprana de esta rara
identidad especialmente en
mujeres con dolor abdominal
y shock hipovolémico.
Si consumes 2 botellas
*
de Vitaminas y Minerales
*Del valor diario recomendado de 24 vitaminas y minerales.
Usarlo como parte de una alimentación saludable y un plan de ejercicios.
© 2015 Abbott Laboratories Inc. APR-150270 LITHO en P.R.
Mi secreto para ayudar
a manejar la diabetes es
ATRAUMATIC
BILATERAL
FEMORAL
NECK
FRACTURES IN A PREMENOPAUSAL FEMALE WITH
HYPOVITAMINOSIS D
Department of Orthopedic Surgery, School of Medicine, University of Puerto
Rico, Medical Sciences Campus. San Juan, Puerto Rico.
*Corresponding author: Antonio Otero-López MD - Department of Orthopedics,
UPR Medical Sciences Campus, PO Box 365067, San Juan, Puerto Rico 009365067. E-mail: drantiniootero@onelinkpr.net
a
Giovanni Paraliticci MDa
David Rodríguez-Quintana MDa
Ariel Dávila MDa
Antonio Otero-López MDa*
ABSTRACT
Bilateral femur neck fractures in young adult patients are very rare in atraumatic circumstances. We report a young premenopausal female with osteomalacia secondary
to vitamin D deficiency and spontaneous bilateral femur neck fractures. Patient had no
reported risk factors for osteomalacia but hypovitaminosis D was noted on laboratory
evaluation. Osteomalacia secondary to low serum levels of vitamin D may lead to stress
and fragility fractures. Identification and treatment of at risk patients may decrease the
incidence of stress fractures and its possible complications.
Index words: atraumatic, bilateral, femoral fractures, premenopausal, female, hypovitaminosis
Nutrición Avanzada
3 en 1
Manejo de Azúcar en Sangre
con
CARB STEADY®
ULTRA
Salud del Corazón**
Apoyo Inmunológico†
Disponibles en:
Vainilla y Chocolate
MARCA
E
A Toda Hora,
Nutrición y Diabetes en Control
* Entre los médicos que recomiendan los productos nutricionales a sus pacientes con diabetes. ** Con fitoesteroles a base de plantas
† Excelente fuente de antioxidantes (vitaminas C, E y selenio)
Use bajo supervisión médica como parte de un plan de manejo de diabetes. © 2014 Abbott Laboratories Inc. APR-140009 Litho en P.R.
IC O S
ED
M
R EC OM
N
#
*
DA
R
DA P O
INTRODUCTION
Bilateral femur neck fractures in
premenopausal females or young
adult males occur in one of two
scenarios, either high-energy trauma or secondary to metabolic disorders. Reports exist of two Japanese individuals with bilateral and
unilateral femoral neck fractures
secondary to hypovitaminosis D
(1, 2). In these cases both patients
showed poor dietary habits and alcoholism. Most reports in the literature of atraumatic bilateral femur
fractures have documented causes
of osteomalacia, including oncogenic osteomalacia, malabsorption, chronic steroid use, pregnancy and alcoholism, among others
(3,4,5,6).
Low levels of Vitamin D have been
documented in normal/healthy individuals as well as in the orthopedic
patient population seen on everyday orthopedic practice (7). We
present a young adult premenopausal female with atraumatic bilateral femoral neck fracture. This
patient had normal laboratory values except for very low serum level
of vitamin D3. Our patient was notified and consented for presentation of her case in the literature.
Case History
femoral neck fractures she was
then referred to our clinic for further
This is the case of a 46-year-old evaluation and management.
female patient with progressive
bilateral hip pain. Her hip symp- The patient was 160 cm tall and
toms began twenty-two days prior her weight was 66 kg (body mass
to presenting at our clinic at the index; 25.9). She had a past medPuerto Rico Medical Center. She ical history of hypothyroidism that
reported her bilateral hip pain as was well controlled with levothydeveloping insidiously and asso- roxine sodium 50 micrograms daiciated with gradual bilateral knee ly (TSH – 2.04). She denied other
pain. Symptoms did improve after medical conditions or medication
a short course of physical therapy treatments. She had no history of
and non-steroidal anti-inflammato- trauma, seizures, or bone metary drugs. Given some improvement bolic diseases. Both her family and
in her pain she continued with her dietary history were also unremarkPT regimen as directed by her pri- able.
mary physician who documented
negative findings on pelvis and bi- Upon arrival at our clinic patient had
lateral knee radiographs.
pain on inguinal area upon ambulation and associated antalgic gait.
During this second stage of phys- Both hips had decreased range of
ical therapy she developed wors- motion secondary to pain. Radioening bilateral thigh pain with ra- graphs and computerized tomodiation to both her gluteal and hip gram (CT) showed possible stress
regions. At this time, her hip pain fractures of bilateral femoral necks
was 7/10 on visual analogue scale and no looser’s zones on pubic
(VAS) with marked limitation of her rami or femoral cortex (see Figures
daily activities. At this time, her pri- 1 & 2). Pelvic MRI did show evimary physician ordered further ra- dence of non-displaced acute bilatdiographic workup, which included eral femoral neck stress fractures
radiographs, computerized tomog- (see Figure 3). Dual-energy x-ray
raphy (CT) scan, and pelvic mag- absorptiometry showed lumbar
netic resonance imaging (MRI). Af- spine Z score -1.4, femoral neck Z
ter imaging results showed bilateral score 1.3, totals hip Z score -0.1.
FRAX score for major osteoporotic Figure 1: Preoperative anteroposterior radiograph of the bilateral hip
fracture and hip fracture were 2.6% joints. There are no looser’s zones in the pubic rami or stress fractures
and < 0.1% respectively. apparent in this examination.
Laboratory results displayed normal values of total serum calcium (9.6 mg/dL; reference range,
9-10.5 mg/dL), serum phosphorus
(3.7 mg/dL; reference range, 3-4.5
mg/dL), and alkaline phosphatase
(71 IU/L; reference range, 36-92
IU/L). Serum level of 1,25(OH)2vitamin D3 was decreased (18.3 pg/
mL; reference range, 15-80 pg/mL).
The serum albumin was normal
(4.1 g/dL; reference range, 3.5-5.1
g/dL). Her PTH level at most recent
follow up was 23pq/ml (reference
range, 16-64pq/mL).
Given previous failure of conservative management and symptoms of
severe bilateral hip pain we recommended and internal fixation with
two cannulated hip screws for both
hips (see Figures 4). Decision for
internal fixation versus arthroplasty
was made given the non-displaced
nature of the fractures. At the time
of surgery and given the possibility of osteomalacia a tricortical biopsy of the ilium was obtained. It
showed no histologic evidence of
osteomalacia. She was started on
daily oral calcium and vitamin D
supplements (50,000 Units). Partial
weight bearing was allowed with
assistive devices 60 days postoperatively. Complete weight bearing
was not allowed until 90 days postoperatively at which time patient
had complete radiographic healing
apparent on radiographs. Follow up
laboratories showed improvement
in hypovitaminosis D (Vitamin D3 =
47.26 ng/mL) following two months
of oral supplements. Our patient
was able to return to her activities
of daily living without assistance
three months post operatively.
DISCUSSION
Vitamin D has received considerable attention in recent years,
because of studies demonstrating inadequate levels in otherwise
healthy populations (5,6). Recent
recommendations of the International Osteoporosis Foundation
and Osteoporosis Canada show
that optimum levels vitamin D
Figure 2: Preoperative coronal (a) and sagittal (b) tomographic images
showing bilateral femoral necks with vertical sclerotic lesions. Noted
how lesions are on tension side of the bone.
Figure 3: Preoperative T1 (a) and T2 Fat Suppression (b) magnetic resonance imaging (MRI) showing bilateral femoral neck fractures
Hypovitaminosis D may result in
osteomalacia, a metabolic bone
condition resulting in weak demineralized bone. Long termed
hypovitaminosis D may result in
spontaneous fractures secondary
to this poorly mineralized weakened bone. Multiple risk factors for
hypovitaminosis D exist such as:
decrease sun exposure, obesity,
dietary deficiency, malabsorption,
medication-induced, breast-feeding, cholesterol-lowering agents,
genetic disorder, anti-seizure medication, and hyperthyroidism. None
of these risk factors were identified
in our patient.
Orthopedic surgeons and physicians in general should be aware of
these increasing trends in Vitamin
D deficiency. Similar to the American Academy of Orthopedic Surgeons move towards better osteoporosis awareness and prevention
of fragility fracture, screening and
early recognition of high risk patients with vitamin D deficiency and
osteomalacia can decrease the incidence of morbid hip fractures.
Figure 4: Postoperative radiograph showing bilateral cannulated screw
fixation of femoral neck fractures.
In the present case, the patient had
no history of major trauma or any
known risk factors for osteomalacia. Her presenting symptoms of
insidious atraumatic bilateral thigh/
inguinal pain imply a fragility fracture secondary to possible bone
mineral deficiency. Laboratory data
did not demonstrate any abnormality in the serum levels of calcium, phosphorus, or bone alkaline
phosphatase, but she did have a
low serum level of 1,25 (OH)2vitamin D3. Moreover, radiographs
did not show typical features of osteomalacia such as Looser's zone,
but addition of CT scan did show
sclerotic vertical lines on both femoral necks implying healing stress
fractures. Given normal dietary and
other lifestyle habits the cause of
the low serum level of vitamin D in
this case is still not clear.
To our knowledge, a previous report exists in the literature of bilateral femur fractures in a patient
with low levels of vitamin D. This
report was in an Asian patient with
dietary deficiencies and alcoholism
(1). Our patient underwent bilateral internal fixation with cannulated
screws given the early recognition
and non-displaced fracture pattern.
Further delay in treatment may
have led to displacement of the
fractures and hip replacement surgery. With this, we think that prevention and early diagnosis seem
of paramount importance to prevent occurrence and displacement
of hip stress fractures on patients
with osteomalacia.
The increasing incidence of hypovitaminosis D in the general population will lead to an increase in
reported incidence of fragility fractures.. Femoral neck fractures, as
in this case, require early diagnosis
to prevent morbidities associated
with fragility fractures. Given the
previously reported elevated rate
of undiagnosed hypovitaminosis D,
preventive medicine with screening
and oral vitamin D supplementation
should be implemented by primary care physicians and orthopedic
specialists.
REFERENCES
RESUMEN
1. Nagao S1, Ito K, Nakamura I. Spontaneous bilateral femoral neck fractures associated with a low serum level of vitamin
D in a young adult. J Arthroplasty. 2009
Feb; 24(2):322.e1-4.
2. Ohishi H1, Nakamura Y, Kishiya M, Toh
S. Spontaneous femoral neck fracture associated with a low serum level of vitamin
D. J Orthop Sci. 2013 May; 18(3):496-9.
3. Rajeev A. Bilateral spontaneous inter-trochanteric fractures of proximal femurs. Int J
Surg Case Rep. 2014; 5(5):246-8.
4. Baki ME1, Uygun H, Arı B, Aydın H. Bilateral femoral neck insufficiency fractures
in pregnancy. Eklem Hastalik Cerrahisi.
2014
5. Carter T1, Nutt J, Simons A. Bilateral
femoral neck insufficiency fractures secondary to vitamin D deficiency and concurrent corticosteroid use--a case report. Arch
Osteoporos. 2014;9:172
6. Sivas F1, Günesen O, Ozoran K, Alemdaroğlu E. Osteomalacia from Mg-containing antacid: a case report of bilateral hip fracture. Rheumatol Int. 2007
May;27(7):679-81
7. Patton CM1, Powell AP, Patel AA. Vitamin D in orthopedics. J Am Acad Orthop
Surg. 2012 Mar; 20(3):123-9.
8. Hanley DA, Cranney A, Jones G, Whiting SJ, Leslie WD, Guidelines Committee
of the Scientific Advisory Council of Osteoporosis Canada: Vitamin D in adult health
and disease: A review and guideline statement from Osteoporosis Canada (summary). CMAJ 2010; 182():1315-1319.
9. Dawson-Hughes B, Mithal A, Bonjour J-P, et al: IOF position statement:
Vitamin D recommendations for older
adults. Osteoporos Int 2010; 21():11511154. 10. Caro Y, Negron V, Palacios C. Association between Vitamin D Levels and Blood
Pressure in a Group of Puerto Ricans. PR
Health Sci J.Sep 2012; 31(3):123-129.
Las fracturas bilaterales de cuello femoral en jóvenes adultos son inusuales en circunstancias no traumáticas. En este
reporte presentamos un paciente con osteomalacia sin factores de riesgo por historial y fracturas bilaterales de cuello
femoral. En nuestra evaluación preoperatoria se identificaron
niveles disminuidos de vitamina D. Osteomalacia secundaria a niveles bajos de vitamina D puede llevar a fracturas de
estrés o fragilidad. El tratamiento de esta condición debe ser
preventivo. La identificación con tratamiento temprano de
pacientes a riesgo puede prevenir complicaciones mayores
asociadas con fracturas de estrés en la cadera.
SMALL CELL CARCINOMA OF THE UTERINE CERVIX:
A Case Report and Literature Review
St. Luke Episcopal Hospital and the Ponce School of Medicine, Ponce, Puerto Rico.
*Corresponding author: Pedro F. Escobar MD - 100 Grand Paseos Blvd, Suite 112, PMB
236 San Juan, PR 00926. Email: escobarp@me.com
a
Pilar E. Silva-Meléndez MDa
Pedro F. Escobar MDa*
Héctor Silva MDa
Sylvia Gutiérrez MDa
Manuel Rodríguez MDa
ABSTRACT
Small cell carcinoma of the uterine cervix is a rare and aggressive extra-pulmonary
variant of small cell tumors. This carcinoma of the cervix comprises less than 5% of all
cervical carcinomas and is known to be highly undifferentiated. It is associated with a
poor prognosis and characterized by premature distant nodal involvement. The survival
rate at all stages ranges from 17% to 67%. We describe the case of a 41 years old female
patient with a rare, and aggressive, clinical stage IB2 small cell neuroendocrine carcinoma of the cervix. The goal of this case report is to describe this rare pathology and
contribute information to the scant available data.
Index words: small, cell, carcinoma, uterine, cervix
INTRODUCTION
CONVIERTASE EN PROVEEDOR
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Dra. Victoria Michelen
Small cell carcinoma of the uterine
cervix (SCC) is a highly malignant
extra-pulmonary variant of small
cell malignancy (1, 2). This rare
uterine cervix carcinoma variant is
histopathologically indistinguishable from its pulmonary counterpart (1). The incidence is estimated to be around 3% of all uterine
cervix malignancies. The exact
numbers are not precise due to nomenclature disagreement leading
to histopathologic misdiagnoses.
The diagnosis of small cell carcinoma of the uterine cervix might be
overestimated. However, Reagan
established specific histopathologic criteria for its classification.
These are: predominance of uniformly organized small basophilic
cells, high nuclear-cellular ratio,
presence of opaque or coarsely
granular chromatin, cell and nuclear size uniformity, and elevated
mitotic index (3).
Small cell carcinoma of the cervix
is known to be highly undifferentiated and with a poor prognosis.
The tumor is characterized by increased invasion of lymphatics,
distant metastasis, and dismal survival rates. Weed et al found dis-
studied patients, with a 93% mortality rate 5 years after diagnosis
(2). Chemotherapy has been used
for metastatic disease in multiple
combinations with some response.
However, the regimen, timing and
duration of chemotherapy remain
controversial (1). Some authors
also argue in favor of prophylactic
brain irradiation due to high risk
of brain metastases. Small case
series of patients with adequate
small cell carcinoma diagnosis are
not sufficient to establish a standard of care. Current treatments
have been extrapolated from pulmonary small cell carcinoma treatment regimens (4). We describe
the case of a 41 years old female
patient with a rare, and aggressive,
clinical stage IB2 small cell neuroendocrine carcinoma of the cervix.
The goal of this case report is to
describe this rare pathology and
contribute information to the scant
available data.
The study design is a retrospective record review analysis. The
medical records available at the
Saint Luke's Episcopal Hospital
and private clinic were reviewed
and proceed with data collection in
accordance to HIPAA regulations.
The Ponce School of Medicine
Review Board (IRB) approved the
study.
Case History
This is the case of a 41 yearsold-female G3P3A0 with the chief
complaint of foul smelling, bloody,
vaginal discharge, inter-menstrual bleeding, and pelvic discomfort of four months duration. She
denies fever or chills. The patient
had regular menstrual cycles and
no previous history of similar episodes. She is currently sexually
active. Five years ago she was
treated with a loop electrosurgical
excision procedure for a cervical
intraepithelial neoplasia grade 3.
Two years later she had cryosurgery of the cervix due to a lowgrade lesion. The subsequent Pap
smear evaluations were negative.
The last evaluation was one year
prior to current complains. Upon
examination, a 4 centimeters exophytic, necrotic mass on the posterior cervical lip was identified
(see Figure 1). Cervical punch biopsies were taken and reported as
small cell carcinoma of the cervix
(see Figure 2). Endometrial biopsy was performed and reported as
normal proliferative endometrium.
The clinical staging for this patient
DISCUSSION
Figure 1. Uterine cervix exophytic mass.
Pioneer studies of cervical cancer were performed by Reagan
classifying uterine cervix cancer into three groups based on
histopathology. These were: keratinizing carcinoma, large cell
non-keratinizing carcinoma, and
small cell carcinoma. The latter
has distinct and specific histopathologic findings. The lack of
standardization for differentiating
between the groups led Reagan,
in 1959, to establish specific histopathologic criteria for identifying a small cell carcinoma of the
uterine cervix. Our case meets
these criteria, presenting with
predominance of uniformly organized small basophilic cells, high
nuclear-cellular ratio, and elevated mitotic index (see Figure 2a)
(3). The immunohistochemistry
favored a small cell carcinoma
diagnosis with positive staining
for the characteristic immunohistochemical markers: synaptophysin, Chromogranin A, neurofilament, and neuron-specific
enolase (Figure 2b, 2c, 2d, and
2e). Although immunohistochemical markers are not part of the
criteria for diagnosis of small cell
carcinoma of the cervix, they are
frequently used to guide it. The
most frequent markers used are:
Chromogranin A, synaptophysin,
and neuron-specific enolase (5).
In addition, immunohistochemical staining was positive for ki-67,
which correlates with the characteristic high mitotic rate of this
malignancy (see Figure 2f).
Figure 2. Histopathology of Small cell carcinoma. a) Hematoxylin and
Eosin stain, b)Synaptophysin, c)Chromogranin A, d)Neurofilment, e)Neu- The incidence of small cell carcinoma of the cervix is rare, comrospecific enolase, and f)Ki-67.
prising less than 5% of all cervical
is IB2. Abdomino-pelvic CT scan three cycles of Cisplastin and Etopo- carcinomas (1). Moreover, this
evaluation showed inhomogenous side. Upon follow up evaluation with malignancy comprises 0.9% of all
solid mass in the right adnexa as Abdomino-Pelvic CT scan showed invasive cervical carcinomas (5).
well as multiseptated cystic lesion enlarged bilateral periaortic and peri- It is an extra-pulmonary variant of
in the left adnexa with prominent caval lymph nodes with largest lymph small cell carcinoma and it is hisuterine cervix and retroperitoneal nodes along psoas muscle extend- topathologically indistinguishable
lymphadenopathy. Physical exam, ing from renal vessels into the pelvis, from its pulmonary counterpart.
imagining and pathologic findings pelvic large conglomeration of lymph Extensive studies have been perguide our referral to chemothera- nodes and cervix with thick mucosa formed to determine adequate
py and radiotherapy. She received and presence of inhomogeneous management, but the scarcity of
cases limits the investigations. Due
to these previously mentio ned limitations, extrapolation of treatment
regimens used in the treatment of
lung small cell carcinoma is currently being used for the treatment of
small cell carcinoma of the uterine
cervix. The role of surgery in this
type of malignancy is a cause for dispute. Various retrospective analysis
have found increased survival rates
with either radical hysterectomy or
hysterectomy alone (4,8). In contrast, large studies investigated the
role of surgery and found no change
in outcome, but did find decreased
survival in the surgical management
group (7). Furthermore, several
studies have found increased brain
metastases and many argued in favor of prophylactic brain irradiation
due to high risk of brain metastases.
Liao et al. studied prognostic factors
for this type of carcinoma and identified the positivity of chromogranin,
an advanced FIGO stage, and increased tumor mass as poor prognostic factors of survival (6). Cohen
et al. found that early-stage disease
is an independent prognostic factor
(4). However, the survival is dismal
even in early stage disease with a
5-year survival of 37%. Human papilloma virus (HPV) has a well-known
role in development of carcinoma of
the cervix. The emerging data suggests that HPV also has a role in the
development of small cell carcinoma
of the cervix, with HPV genotypes
16 and 18 being most commonly
associated. Interestingly, genotype
18 seems to be more prevalent in
small cell carcinoma in contrast to
squamous cell carcinoma (5). Our
patient did not present with high-risk
HPV serotypes.
In conclusion, the main outcome of
this case report is reinforcing the
need to have more studies and case
reports of small cell carcinoma of
the uterine cervix in order to develop the most appropriate guidelines
of treatment and a standard of care
for this rare malignancy. Additional
data is still needed in order to establish standardized and effective treatment modalities for this pathology.
Consideration should be given to
this rare malignancy aiming to identify effective treatment modalities.
REFERENCES
1. Viswanathan AN, Deavers MT, Jhingran
A, et al. Small cell neuroendocrine carcinoma of the cervix: outcome and patterns of
recurrence. Journal of Gynecology Oncology. 2004;93:27-33.
2. Weed JC, Graff AT, Shoup B, et al. Small
Cell Undifferentiated (Neuroendocrine)
Carcinoma of the Uterine Cervix. Journal of the American College of Surgeons.
2003;197:44-51.
3. Wentz WB, Reagan JW. Survival in cervical cancer with respect to cell type. Cancer. 1959; 12: 384-388.
4. Cohen JG, Kapp DS, Shin JY, et al. Small
cell carcinoma of the cervix: treatment and
survival outcomes of 188 patients. American Journal of Obstetrics and Gynecology.
2010; 203: 347 e1-e6.
5. Atienza-Amores M, Guerini-Rocco E,
Soslow RA, et al. Small cell carcinoma of
the gynecologic tract: A multifaceted spectrum of lesions. Journal of Gynecology Oncology. 2014;134:410-418.
6. Liao LM, Zhang X, Ren YF, et al. Chromogranin A (CgA) as poor prognostic factor in patients with small cell carcinoma
of the cervix: results of a retrospective
study of 293 patients. PLOS ONE. 2012;
7(4):e33674.
7. Wang KL, Chang TC, Jung SM, et al.
Primary treatment and prognostic factors
of small neuroendocrine carcinoma of the
uterine cervix: A Taiwanese Gynecologic
Oncology group study. European Journal
of Cancer. 2012; 48:1484-1494.
8. Boruta II DM,Schorge JO, Duska LA,
et al. Multimodality therapy in early-stage
neuroendocrine carcinoma of the uterine
cervix. Journal of Gynecology Oncology.
2013; 129: 135-139.
RESUMEN
El carcinoma de células pequeñas
en el cuello del útero es raro y agresivo, es una variante extra-pulmonar de los carcinomas de células
pequeñas. Este tipo de carcinoma
del cuello del útero compone menos
de 5% de todas las malignidades
del cuello del útero, se conoce por
ser altamente no diferenciado. Se
asocia con un pronóstico pobre
y es caracterizado por invasión a
distancia del sistema linfático. La
sobrevida en todos los estadíos
va de un 17% a un 67%. El caso
presentado es de una fémina de 41
años de edad con un carcinoma de
células pequeñas en el cuello del
útero. La meta de este reporte de
caso es compartir la presentación
clínica, hallazgos y evolución de la
enfermedad para contribuir a entender mejor esta rara malignidad
del cuello del útero.
WWW.ASOCMEDPR.ORG
solid lesion. Patient was schedule to change chemotherapy regimen but was lost to follow-up.
HANDLEBAR HERNIA:
Case Report and Literature Review
Luisa Angel Buitrago MDa
Humberto Lugo-Vicente MDa*
Department and Residency of Pediatrics, San Juan City Hospital, San Juan, Puerto Rico.
bSection of Pediatric Surgery, Department of Surgery, UPR School of Medicine,
San Juan, Puerto Rico.
*Corresponding author: Humberto Lugo-Vicente MD – PO Box 10426, San Juan,
Puerto Rico 00922. E-mail: titolugo@coqui.net
a
ABSTRACT
Handlebar hernia is a rare traumatic abdominal wall hernia occurring after blunt trauma.
We report a case of an adolescent patient with a traumatic rectus muscle abdominal wall
hernia produced by injury with the bicycle handlebar. The skin abrasion caused by the
trauma and a swelling reproduced after a Valsalva maneuver suggested the diagnosis.
Traumatic wall hernias after blunt trauma should be repaired primarily to avoid complications.
Index words: handlebar, hernia, rectus, abdominis
INTRODUCTION
Traumatic abdominal wall hernias
caused by bicycle handle are rare.
The criteria to identify a traumatic
hernia include absence of previous
hernia in the same area, evidence
of abdominal wall injury and immediate or delayed development of a
hernia. There are approximately
forty cases reported in the literature [1,2]. This abdominal wall injury is caused by a direct trauma
with an object with small surface
area like a bicycle handlebar with
sufficient force to damage the abdominal wall, but not the skin. We
present a case of an adolescent
male with a traumatic handlebar
hernia after a fall from a bicycle.
Case History
This is a 14-year-old-male patient
with no history of systemic illness
presenting to the emergency department one day after losing control of his bicycle and falling into
the handlebar. He complained of
a lump on his right abdomen with
mild intermittent non-radiating pain
in the area of the protruding bulge
with coughing. In general the patient was in no acute distress with
normal vital signs for age, clear
lung to auscultation, normal heart
rate and rhythm no murmur or
gallop. At abdominal evaluation
the patient had a right supra-umbilical abrasion, with an obvious
abdominal wall hernia visualized
in his right rectus abdominal muscle after a Valsalva maneuver, with
no rebound or tenderness to palpation (see Figure 1 & 2). Laboratories (CBC, BMP, PT, PTT, INR)
were within the normal range. Abdominal Ultrasound followed by a
CT-Scan of abdomen with contrast
showed a rectus abdominal wall
rupture with omental protrusion
within the defect (see Figure 3 &
4). During surgery a five cm defect
due to rupture of the transverse
fascia of the right rectus abdominis
was identified (see Figure 5). The
hernial defect was repaired using
approximation of the medial rectus
muscle to the midline with anterior
fascia transverse closure using interrupted absorbable sutures (see
Figure 6). He followed an uneventful postoperative course.
identified the relationship of blunt
injury with the handlebar of the bicycle and the development of an
abdominal hernia in 1980 [3,7].
DICUSSSION
There are three types of TAWH
categorized in 1988 by Wood and
Robyn; Type I is a small defect
caused by blunt injury of low energy trauma such as a bicycle handlebar. Type II is a larger defect
caused by high-energy blunt trauma from motor vehicles crash or
from a height, and type III is a larger defect involving intraabdominal
bowel herniation as described in
deceleration injuries [1,4,5]. Most
traumatic abdominal wall hernias
in children are Type 1, also called
handlebar hernias due to the common nature of the accident. The
criteria to identify a traumatic hernia include absence of previous
hernia in the same area, evidence
of abdominal wall injury and immediate or delayed development of a
hernia, with or without presence of
peritoneum [1].
Traumatic abdominal wall hernias (TAWH) are caused by a force
strong enough to damage the abdominal wall, but not to damage
the more elastic skin [1-8]. Selvy
first described TAWH in 1906, and
the term handlebar hernia was introduced when Dimyan and Robb
There are approximately forty
cases of TAWH reported in the
literature, the more common presentation is a hernia in the lower
abdomen in males with a an average age of 9.5 years (range from 5
to 14 years). Risk factors associated with the development of a TAWH
in children include risk behavior, not
using protective equipment and poor
handling experience [2,6,7]. Although
the majority of cases reported in the
literature have a lower abdominal
trauma usually in the right side lateral
to the rectus sheath or over the linea
alba, a few cases were reported after
upper abdominal trauma and even
thoracic defects [1,3,6].
Intra-abdominal trauma is more common with
upper abdominal trauma and type II
TWAH [6,8]. Our case patient was a
14 years adolescent with a supra-umbilical handlebar abrasion and hernia
observed when performing the Valsalva maneuver.
The diagnosis of handlebar hernia is
clinical made by history and physical
examination, however some cases
reported discovery of a hernial defect during laparoscopy evaluation for
blunt abdominal trauma not seen at
physical examination [1,5]. Patients
usually present to the emergency department with abdominal bulge tender at palpation and overlaying skin
contusion or handlebar imprinting
abrasion that is not always present,
but when is present increased risk of
abdominal trauma has been reported
[3-6,8,9]. When signs of acute abdomen or hemorrhagic shock are present serious intra-abdominal injury
should have to be considered. In our
case although the patient has handlebar imprinting abrasion, there were no
signs of hemorrhagic shock or acute
abdomen such as, abdominal distention, rigidity, absent bowel sound, tenderness with rebound and guarding
which make us think about associated
intra abdominal injury.
Figure 1: Abdominal abrasion caused by handlebar injury.
Diagnosis of handlebar hernia should
be confirmed with imaging studies.
The most important studies are abdominal X-ray, ultrasound and CT
scan. Abdominal CT-Scan helps us
determine if other intra-abdominal injuries like intestinal perforation, liver,
spleen or pancreatic rupture are present [1, 3, 6].
Although laparoscopy repair and conservative management has been reported, the literature recommendsopen
surgical repair with closing of all layers
and use of prosthetic material when
defect is large as definitive treatment to
avoid complications like incarceration
and bowel ischemia [1, 3, 5, 6, 9-11].
Figure 2: Abdominal bulge caused during Valsalva maneuver.
When CT scan is inconclusive,
laparoscopy
evaluation of solid organ,
diaphragm and small
bowel injury is very useful. With intra-abdominal
injuries exploratory laparotomy is necessary for
repaired of such injuries
[1, 4]. In our case abdominal ultrasound and
CT scan help confirm the
diagnosis of abdominal
wall hernia since no intra-abdominal injury was
found. Because there
were neither clinical
signs nor intra-abdominal injury reported on the
CT-Scan, laparoscopy
was not perform and the
defect was closed by primary repair without the
need of prosthetic material.
Handlebar injury should
be included within the
differential diagnose at
the moment of evaluating abdominal trauma
with small surface object. Parent education
about adequate cloth
and protective equipFigure 3: Ultrasound demonstrating the rectus abdominis wall defect with omen- ment, including using
a vest for protecting
tum.
Figure 4: CT-Scan showing the rectus
abdominis wall defect.
Figure 5: Hernial defect during surgery
abdomen when cycling, is a
method to prevent and ameliorate such injury. Traumatic
wall hernias after blunt trauma
should be repaired primarily to
avoid future complications.
REFERENCES
1. Goliath J., Mittal V. and McDonough J. Traumatic Handlebar Hernia: A Rare Abdominal
Wall Hernia pediatric surgery
2004; 1531-5037
2. Klimek P.M., Lutz T., Zanchariou Z., Kessler U., Berger
S. Handlebar injuries in children Pediatric Surguery 2013;
29:269-273
3. Rathore A., Simpson B.,
Diefenbach A. Traumatic abdominal wall hernias: an emerging trend in handlebar injuries
Journak of Pediatric Surgery
2012; 47:1410-1413
4. Kubalak G. Hanlerbar hernia: Case repot and review of
literature The journal of trauma
1994; 0022-5284
5. Linuma Y., Yamazaki Y., Hirose Y., et al. A case of a traumatic abdominal wall hernia
that could not be identified until
exploratory laparoscopy was
performed Pediatric Surgery int
2005; 21:54-57
6. Yan J., Wood J., Bevan C.,
Cheng W., Wilson G. Traumatic
abdominal wall hernia- a case
report and literature review
Journal of Pediatric Surgery
2011, 46:1642-1645
7.Ku bota A., Shono J., Yonekura T., et al Handlebar hernia:
case report and review of pediatric cases Pediatric Surgery
Int. 1999, 15:411-412
8. Mancel B., Aslam A. Traumatic abdominal wall hernia: an
unusual bicycle handlebar injury Pediatric Surgery Int 2003;
19:746-747
9. Decker S., Engelmann C.,
Krettek C., Muller C. Traumatic abdominal wall hernia after
blunt abdominal trauma caused
by a handlebar in children: A
well-visualized case report Surgery 2012; 151:899-900
Figure 6: Surgical closure hernial defect.
10. Matsou S., Okada S., Matsumata T. Successful conservative treatment of a bicycle-handlebar hernia: report of a case Surgery Today 2007;
37(4):349-51
11. Upasani A., Bouhadiba N. Pediatric abdominal wall hernia following
handlebar injury: should we diagnose more and operated less? BMJ Case
Report 2013; 10.1136
RESUMEN
La hernia de manubrio es una hernia abdominal traumática rara que ocurre después de trauma romo. Reportamos
el caso de un adolescente con una hernia traumática en su
musculo recto luego de trauma romo con el manubrio de
su bicicleta. La abrasión en la piel y el abultamiento que
ocurrió en el área del recto abdominal con la maniobra de
Valsalva sugirieron el diagnostico. Las hernias traumáticas abdominal deben ser reparadas primariamente para
evitar futuras complicaciones.
SHOULD WE REVISIT ANTICOAGULATION
GUIDELINES DURING THYROID STORM?
Andrew W. Petersen MDa
Gisela D. Puig-Carrión MDb
Angel López-Candales MDc*
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
b
Department of Internal Medicine University of Puerto Rico School of Medicine, San
Juan, Puerto Rico.
c
Cardiovascular Medicine Division , University of Puerto Rico School of Medicine, San
Juan, Puerto Rico.
*Corresponding Author: Angel López-Candales MD - University of Puerto Rico School
of Medicine, Medical Sciences Building, PO Box 365067, San Juan, Puerto Rico 009365067.
E-mail: angel.lopez17@upr.edu
a
ABSTRACT
Thyroid storm is a rare but potentially catastrophic disease expression of thyrotoxicosis
with well-recognized cardiovascular manifestations such as heart failure and atrial fibrillation. Even though some studies have found an increased risk of cardiac thrombus formation and subsequent thromboembolism in these patients, the use of anticoagulation
to prevent thromboembolic sequelae of thyrotoxic atrial fibrillation remains unclear. We
present a patient presenting with new onset dilated cardiomyopathy and resistant atrial
fibrillation with thyroid storm that had a large left atrial appendage clot. Case particulars
are discussed and the literature reviewed.
Index words: anticoagulation, guidelines, thyroid, storm
INTRODUCTION
and concomitant weight loss.
Thyrotoxic (or thyroid) storm (or
thyrotoxic crisis) is defined as a
life-threatening condition caused
by the exaggerated clinical manifestation of thyrotoxicosis. Although it is difficult to estimate the
exact incidence of this condition;
it is believed that thyroid storm
accounts for < 1–2% of hospital
admissions (1). If left untreated,
it has a high reported mortality,
ranging between 20% and 50%
(2).
On physical exam, her heart rate
was 174 and irregular, blood pressure was 126/98 mmHg, respiratory rate was 36 per minute, and
temperature was 96.9 F. She was
somewhat anxious and diaphoretic, in no distress, and had a slight
elevation in her jugular venous
pressure noted with bibasilar rales.
No ventricular gallops or murmurs
were appreciated, but her point of
maximal impulse was hyperkinetic
and apically displaced. A 2+ bilateral pitting edema was noted as
well as horizontal nystagmus and
a fine resting tremor. Electrocardiogram showed atrial fibrillation
with a rapid ventricular response
with a rate of 184. Initial blood
workup was unremarkable with
the exception of her BNP that was
1277 pg/ml (<450), TSH 0.02 mIU/L (0.45-4.5), Free T4 > 7.0 ng/dl
(0.61-1.76). Her thyrotropin receptor antibodies were found to be elevated at 18.91 IU/L (0-1.75) confirming the diagnosis of Grave’s
disease.
Thyroid storm is mediated not
only by an acute and rapid rise in
levels of circulating thyroid hormone, but also by enhanced cellular response to thyroid hormone
(1). Specific effects of the thyroid
hormone on the cardiovascular
system have been well characterized. Sinus tachycardia is the
most common manifestation of
thyrotoxicosis, but atrial fibrillation is the most clinically relevant
complication, occurring in an estimated 5% to 15% of patients with
hyperthyroidism (3). In contrast,
transesophageal echocardiogram
was performed. This not only
confirmed left ventricular dilatation with global hypokinesis and
severely reduced ejection fraction
(see Figures 1A and 1B), but also
identified the presence of a 7 mm
thrombus with significant spontaneous echo contrast within the left
atrial appendage (see Figures 2A
and 2B). Because of the significant risk of embolization intravenous heparin and Warfarin were
immediately initiated. The patient
responded to standard heart failure therapy with Lisinopril, Toprol
XL and required Furosemide as
well. She was discharged home
and has done remarkably well.
On her six month follow-up appointment, she was euthyroid and
in normal sinus rhythm. Repeat
transesophageal echocardiogram
not only showed normal left ventricular cavity size and ejection
fraction of 60% (see Figures 3A
and 3B); but also showed complete dissolution of her left atrial
appendage clot (see Figure 4).
DISCUSSION
Thyroid hormone is an important
regulator of cardiac function and
cardiovascular hemodynamics. It
is well established that triiodothyronine, (T3), the physiologically
active form of thyroid hormone,
binds to nuclear receptor proteins
and mediates the expression of
several important cardiac genes.
Genomic pathway alterations include transcriptional activation
and repression of target genes
encoding structural and functional
regulatory proteins of intracellular
calcium handling, such as calcium
activated ATPase and its inhibitory cofactor phospholamban (6,
7). Thyroid hormone also causes
nongenomic alterations of cardiac
inotropism and chronotropism, as
well as causes an acute reduction in peripheral vascular resistance by promoting relaxation in
vascular smooth muscle (8). Excess thyroid hormone causes an
increase in sympathetic tone and
a decrease in parasympathetic
tone resulting in tachycardia and a
widened pulse pressure. Through
stimulation of erythropoietin secretion there is an increase in
overall blood volume and preload.
These clinically result in an increase in cardiac output (6, 7). Alterations in tissue responsiveness
to catecholamines via modulation
of adrenergic receptor expression
or possible postreceptor modifications in the submembranic signaling pathways have also been implicated in clinical manifestation of
excess thyroid hormone (1).
As previously discussed, the development of atrial fibrillation occurs in 5 to 15 percent of patients
with hyperthyroidism (7). A higher
prevalence of atrial fibrillation is
noted among older patients with
known or suspected underlying organic heart disease (9). Treatment
of hyperthyroidism is frequently
associated with reversion to sinus
rhythm approximately over a period of 8 to 10 weeks once patients
have returned to a euthyroid state
(10). This reversibility has resulted in the use of anticoagulation
to prevent systemic embolization
while in hyperthyroid associated
Figure 1A: Transesophageal gastric view taken at the level of the
papillary muscles showing the left ventricle in end-diastole.
Figure1B: Transesophageal gastric view taken at the level of the
papillary muscles showing the left ventricle in end-systole.
atrial fibrillation to remain controversial (7).
It is well established that while atrial fibrillation increases the risk of
stroke; the absolute rate of stroke
depends on age and comorbid
conditions (11). Furthermore, the
use of a classification scheme
such as CHADS2 has been validated to help physicians make decisions regarding antithrombotic
use in patients with this atrial dysrhythmia (11). Hyperthyroidism
However, we believe that the interaction between thyrotoxicosis and
cerebrovascular events needs to
be revisited, particularly when the
thyroid hormone is now known to
shorten activated partial thromboplastin time, increase fibrinogen
levels, and increase factor VIII and
factor X activity (13, 14). These
coagulation abnormalities have
been linked to stroke in patients
with thyrotoxicosis even while in
normal sinus rhythm (5). Furthermore, alterations in hemostatic
mechanisms and platelet activation, as well as inflammation and
growth factor changes have been
well described in patients with
atrial fibrillation (15). Finally, the
presence of dilated cardiac chambers and reduced systolic function
have also been implicated in the
activation of inflammatory and
neuroendocrine pathways, leading to endothelial dysfunction and
a prothrombotic state with dysregulated platelets and activation of
the coagulation cascade (16).
Figure 2A: Midesophageal view showing the left atrium and left atrial
appendage (LAA). In this view the black arrow demonstrates the presence of a echodense mass, suggestive of a clot within the LAA.
Given the significant clot burden
that was demonstrated in our patient, it was determined that she
would clinically benefit from anticoagulation. She was started on
intravenous Heparin and bridged
to Warfarin successfully. On follow up, six months after her initial
presentation even though she has
continued to struggle with alcohol
abuse as well as anxiety and depression; her left ventricular function returned to normal and there
was complete resolution of the
clot.
Figure 3A: Transesophageal gastric showing the left ventricle in end-diastole.
Early recognition of the clinical
manifestations of hyperthyroidism
is critical to the proper diagnosis
and management of thyroid storm.
Similarly important is to recognize
the potential for cardiovascular
involvement. More importantly,
this case highlights an unresolved
treatment issue in these patients
with regards to anticoagulation in
hyperthyroid patients with atrial
fibrillation. A large scale prospective study is needed to revisit this
critically important clinical dilemma, as in our case, it stands to
reason that there was a significant
benefit to anticoagulation therapy. REFERENCES
Figure 2B: Midesophageal view showing the left atrium and left atrial
appendage (LAA). In this view the black arrow shows the clot while the
broken white arrow shows the presence of spontaneous echo contrast
(sluggish blood flow in early stages of clot formation) within the LAA. In
both images, both mitral valve leaflets (denoted by the white arrows)
and part of the left ventricle are also seen.
1. Sarlis NJ, Gourgiotis L. Thyroid
emergencies. Rev Endocr Metab
Disord. 2003; 4: 129-136.
2. Burch HB, Wartofsky L.
Life-threatening
thyrotoxicosis.
Thyroid storm. Endocrinol Metab
Clin North Am. 1993; 22: 263-277.
3. Petersen P, Hansen JM. Stroke
in thyrotoxicosis with atrial fibrillation. Stroke 1988;19(1):15-8.
4. Dahl P, Danzi S, Klein I. Thyrotoxic
Figure 3B: Transesophageal gastric view showing the left ventricle in end-systole. Please note smaller left ventricular end-diastolic as well as systolic dimensions when compared with Figure 1A and B not only suggestive of resolution of
left ventricular cavity dilatation, but also of improvement in left ventricular systolic
function.
RESUMEN
Figure 4: Midesophageal view showing the left atrium and left atrial
appendage (LAA). In this view there is no spontaneous echo contrast or clot shown suggesting resolution of the blood stasis not that
the patient is in normal sinus rhythm.
cardiac disease. Curr Heart Fail
Rep 2008;5(3):170-6.
5. Traube E, Coplan NL. Embolic
risk in atrial fibrillation that arises
from hyperthyroidism: review of
the medical literature. Tex Heart
Inst J. 2011; 38: 225-228.
6. Klein I, Danzi S. Thyroid disease and the heart. Circulation.
2007 Oct 9;116(15):1725-35
7. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001; 344:501509.
8. Fazio S, Palmieri EA, Lombardi
G, et al. Effects of thyroid hormone
on the cardiovascular system. Recent Prog Horm Res. 2004; 59:
31-50.
9. Nordyke RA, Gilbert FI Jr, Harada ASM. Graves’ disease: influence of age on clinical findings.
Arch Intern Med 1988; 148: 626631.
10. Nakazawa HK, Sakurai K,
Hamada N, et al. Management of
atrial fibrillation in the post-thyrotoxic state. Am J Med 1982; 72:
903-906.
11. Gage BF, Waterman AD, Shannon W, et al. Validation of clinical
classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation.
JAMA. 2001; 285: 2864-2870.
12. Petersen P, Hansen JM. Stroke
in thyrotoxicosis with atrial fibrillation. Stroke. 1988; 19: 15-18.
13. Franchini M, Montagnana M,
Manzato F, et al. Thyroid dysfunction and hemostasis: an issue still
unresolved. Semin Thromb Hemost 2009; 35: 288-294.
14. Erem C, Ersoz HO, Karti SS,
et al. Blood coagulation and fibrinolysis in patients with hyperthyroidism. J Endocrinol Invest 2002;
25: 345-350.
15. Watson T, Shantsila E, Lip GY.
Mechanisms of thrombogenesis
in atrial fibrillation: Virchow’s triad
revisited. Lancet. 2009; 373: 155166.
16. Bhatia RS, Ouzounian M, Tu
JV, et al. Anticoagulation in patients with heart failure. Cardiovasc Hematol Agents Med Chem.
2009; 7: 193-197.
La tormenta tiroidea
es una condición rara
pero
potencialmente
catastrófica en la expresión de tirotoxicosis con reconocidas manifestaciones
cardíacas, tales como
insuficiencia cardiaca
y fibrilación auricular.
Aun cuando algunos
estudios han documentado un aumento no
solamente en el riesgo
de formación de trombos; sino también de
eventos tromboembólicos de origen cardíaco
en estos pacientes, el
uso de anticoagulantes para prevenir esta
secuelas
tromboembólicas en casos de fibrilación auricular asociados
tirotóxicosis
no están bien definido.
Describimos el caso
de una paciente fémina que se presenta con
cardiomiopatía dilatada, fibrilación atrial
resistente y coágulos
en su aurícula atrial
como consecuencia de
tormenta tiroidea. Los
particulares del caso
se discuten y la literatura actual se revisa.
DESCUENTO ESPECIAL
A MIEMBROS DE LA AMPR
Desde 1902
apoyando
a la clase médica
y a los futuros profesionales de salud.
Creando
eventos y jornadas de educación
y permitiendo la publicación de investigaciones
en nuestro
nuest
BOLETIN

Asociacion Medica de Puerto Rico

Transcription

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