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1.
Clin Exp Emerg Med ; 11(1): 100-105, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38018071

RESUMO

Extracorporeal membrane oxygenation (ECMO) has been increasingly employed in the emergency department for patients with a potentially reversible cause of cardiac arrest. We present the case of a young female patient with an in-hospital cardiac arrest who was found to have severe right heart strain on point-of-care ultrasound (POCUS), suggesting a massive pulmonary embolism. Rapid bedside diagnosis using ultrasound expedited bedside cannulation and initiation of ECMO as a bridge to surgical thrombectomy, and ultimately the patient survived with full neurologic function. With its ready availability and increasing acceptance by consultants, POCUS should be incorporated into cardiac arrest algorithms as the standard of care to rule in thrombotic and obstructive causes of cardiac arrest.

2.
World J Microbiol Biotechnol ; 40(1): 10, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37947912

RESUMO

Melanin is a brown-black pigment with significant roles in various biological processes. The tyrosinase enzyme catalyzes the conversion of tyrosine to melanin and has promising uses in the pharmaceutical and biotechnology sectors. This research aims to purify and immobilize the tyrosinase enzyme from Pseudomonas sp. EG22 using cellulose-coated magnetic nanoparticles. Various techniques were utilized to examine the synthesized nanoparticles, which exhibited a spherical shape with an average diameter of 12 nm and a negative surface potential of - 55.7 mV with a polydispersity index (PDI) of 0.260. Comparing the immobilized magnetic tyrosinase enzyme with the free enzyme, the study's findings showed that the immobilized tyrosinase enzyme had optimal activity at a pH of 6 and a temperature of 35 °C, and its activity increased as the concentration of tyrosine increased. The study investigated the antibacterial and anticancer bioactivity of the enzyme's melanin product and found that it exhibited potential antibacterial activity against a multi-drug resistant strain including S. aureus and E. coli. The produced melanin also demonstrated the potential to decrease cell survival and induce apoptosis in initiation cells.


Assuntos
Nanopartículas de Magnetita , Monofenol Mono-Oxigenase , Melaninas , Celulose , Nanopartículas de Magnetita/química , Pseudomonas , Escherichia coli , Staphylococcus aureus , Enzimas Imobilizadas/química , Tirosina , Antibacterianos/farmacologia
4.
JTCVS Open ; 12: 30-36, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36590711

RESUMO

Objectives: Computed tomography angiography (CTA) is the imaging modality most frequently used to diagnosis type A aortic dissection for chest pain with a high degree of sensitivity and specificity. False negative and positive errors in diagnosis are infrequent. Despite initial negative imaging studies for dissection, surgeons must consider early operation in patients with recent onset chest pain in the presence of an ascending aortic aneurysm. Methods: We report 4 cases (2004-2021) of patients with a mean age of 51.25 years (male:female = 3:1) who presented with chest pain. Two had a history of syncope. On computed tomography angiography, all had an ascending aortic aneurysm and no dissection flap. Three had thickening of the ascending aorta and 1 had a chronic type B dissection. On echocardiography, aortic regurgitation was moderate-severe in 2 patients, 2 had a pericardial effusion, and none had a definitive dissection flap. All were operated on because of the surgeon's concern for the association of chest pain and an ascending aortic aneurysm. The Institutional Review Board at George Washington University Committee on Human Research has determined that the research is exempt from review under Department of Health and Human Services regulatory category 4 (#FWA00005945). The project as described in the application may proceed without further oversight by the Office of Human Resources on September 9, 2022. Results: The diagnosis of type A aortic dissection was made at operation (3 on median sternotomy and 1 after aortotomy). All patients did well. One patient who had peripheral cannulation (no malperfusion) and severe coagulopathy developed a compartment syndrome and postoperatively required a below-knee amputation. Conclusions: Surgeons must maintain a high index of suspicion for aortic dissection when patients present with chest pain and are found to have an ascending aortic aneurysm even in the absence of initial, classic features of dissection on computed tomography angiography. Improvements in imaging techniques and analysis are required.

5.
ASAIO J ; 67(10): 1097-1099, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34324444

RESUMO

COVID-19 can be associated with acute respiratory distress syndrome, which increases the likelihood of morbidity and mortality. Ventilator-induced lung injury is a known complication of mechanical ventilation (MV) and can further compound lung injury and recovery. Escalation to extracorporeal membrane oxygenation can be required in patients who deteriorate on MV. We report our experience with complete avoidance of MV using an ECMO First strategy deployed in an awake nonintubated COVID-19 patient with severe pneumonia.


Assuntos
COVID-19/terapia , Oxigenação por Membrana Extracorpórea/métodos , Lesão Pulmonar/terapia , Síndrome do Desconforto Respiratório/terapia , Oxigenação por Membrana Extracorpórea/efeitos adversos , Humanos , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , SARS-CoV-2 , Lesão Pulmonar Induzida por Ventilação Mecânica/etiologia , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle
6.
J Surg Res ; 258: 345-351, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33069392

RESUMO

INTRODUCTION: Although the numbers of older adults in the US are rapidly increasing, there is sparse recent data on the use and outcomes of coronary artery bypass grafting (CABG) among this population. We aimed to evaluate the characteristics and outcomes of older adults undergoing CABG and to measure temporal trends. MATERIALS AND METHODS: Using data from the National Inpatient Sample (2005-2014), patients aged 85 y and older who underwent CABG were selected. Demographic, clinical, and hospital characteristics were extracted. Outcomes measured were hospital mortality, hospital length of stay, discharge home, and operative complications. Patients were grouped by 2-year increments. Differences in clinical characteristics and outcomes over time were evaluated using trend analyses. RESULTS: There were 60,124 patients included in the cohort. The mean age was 86.8 y with majority being men (61%), white (88%), and treated in teaching hospitals (61%). Over the study period, the annual surgical volume decreased from 6689 in 2005/06 to 5150 in 2013/14. Mortality decreased from 8.5% to 5.5% (P-trend <0.001) and mean hospital length of stay decreased from 13.9 d to 12.0 d (P-trend <0.001), whereas the rate of discharge home remained stable (14.1% versus 11.6%, P-trend = 0.056). Compared with patients in 2005/06, those in 2013/14 had higher comorbidities [diabetes: 27.6% versus 17.3%; chronic kidney disease: 29.8% versus 9.2%; peripheral artery disease: 7.5% versus 6.0%; and hypertension: 83.7% versus 64.5% (all P-trend <0.001)]. CONCLUSIONS: CABG volumes are decreasing among older adults, and comorbidity burden is increasing, but outcomes are improving. These data may indicate improved preoperative optimization and better perioperative care processes.


Assuntos
Ponte de Artéria Coronária/tendências , Idoso de 80 Anos ou mais , Comorbidade , Ponte de Artéria Coronária/mortalidade , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia
7.
J Card Surg ; 35(4): 930-933, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32069370

RESUMO

The indications for extracorporeal membrane oxygenation (ECMO) are expanding. Postobstructive pulmonary edema, also known as negative pressure pulmonary edema, can result in severe respiratory compromise and acute respiratory distress syndrome. We present a case of a 26-year-old female with laryngeal papillomatosis and laryngospasm after direct laryngoscopy, who developed severe NPPE refractory to mechanical ventilator support, which was successfully treated with veno-venous ECMO.


Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Neoplasias Laríngeas/cirurgia , Papiloma/cirurgia , Complicações Pós-Operatórias/terapia , Edema Pulmonar/terapia , Adulto , Feminino , Humanos , Neoplasias Laríngeas/complicações , Laringismo/complicações , Laringismo/cirurgia , Papiloma/complicações , Pressão , Índice de Gravidade de Doença , Resultado do Tratamento
8.
J Heart Lung Transplant ; 38(4): 433-439, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30744940

RESUMO

BACKGROUND: Bleeding and need for blood products are major complications associated with extracorporeal membrane oxygenation (ECMO) use. This study evaluated bleeding complications with low and standard heparinization protocols in the maintenance of venoarterial (VA)-ECMO. METHODS: A retrospective comparison was performed of 2 methods of heparinization in a contemporaneous series of adult patients supported with VA-ECMO at Rush University Medical Center, between November 2011 and November 2016. CentriMag (Thoratec, Pleasanton, CA) pumps, Quadrox (Maquet, Wayne, NJ) oxygenators, and heparin-bonded circuitry were used in all patients. Group 1 was a control group of 50 patients who had ECMO support with an initiation dose of 5,000 U of heparin, followed by standard heparinization at a goal activated clotting time of 180 to 220 seconds. Group 2 comprised 52 adult patients supported with a "low heparin protocol" ECMO, receiving a standard heparin bolus of 5,000 U for cannulation but without subsequent, ongoing heparin administration. Acuity of illness was similar in both groups as assessed by the Mortality Probability Model (59% in Group 1 vs 62.9% in Group 2, p = 0.08). Data were submitted to the Extracorporeal Life Support Organization prospectively. Clots in the circuit, limb ischemia, oxygenator failure, and embolic complications were recorded. RESULTS: Weaning off ECMO was successful in 26 patients (50%) in Group 2 compared with 18 (36%) in Group 1 (p = 0.05). Hemorrhage from the cannulation site occurred in 11 (21%) in Group 2 vs 21 (42%) in Group 1 and from the surgical site in 11 (21%) in Group 2 vs 18 (36%) in Group 1. Severe bleeding complications were higher in the control group (Group 1, 32%) compared with Group 2 (11.5%; p = 0.012). CONCLUSIONS: Maintenance with low heparin is safe in patients supported by VA-ECMO. This strategy may reduce risk of severe bleeding and associated complications.


Assuntos
Anticoagulantes/administração & dosagem , Oxigenação por Membrana Extracorpórea/efeitos adversos , Hemorragia/etiologia , Heparina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Artérias , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Veias , Adulto Jovem
9.
Ann Thorac Surg ; 106(6): 1766, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30107144
10.
Regen Med ; 12(8): 969-982, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29215316

RESUMO

Stem/progenitor cell-based therapy has been extensively studied for angiomyogenic repair of the ischemic heart by regeneration of the damaged myocytes and neovascularization of the ischemic tissue through biological bypassing. Given their inherent ability to assume functionally competent endothelial phenotype and release of broad array of proangiogenic cytokines, endothelial progenitor cells (EPCs)-based therapy is deemed as most appropriate for vaculogenesis in the ischemic heart. Emulating the natural repair process that encompasses mobilization and homing-in of the bone marrow and peripheral blood EPCs, their reparability has been extensively studied in the animal models of myocardial ischemia with encouraging results. Our literature review is a compilation of the lessons learned from the use of EPCs in experimental animal models with emphasis on the in vitro manipulation and delivery strategies to enhance their retention, survival and functioning post-engraftment in the heart.


Assuntos
Células Progenitoras Endoteliais/citologia , Modelos Animais , Infarto do Miocárdio/terapia , Miocárdio/citologia , Neovascularização Fisiológica , Humanos
11.
Ann Thorac Surg ; 103(1): e97-e99, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28007290

RESUMO

Aortic root reconstruction in the setting of redo aortic valve procedures or infective endocarditis may be technically challenging, particularly because of variable destruction or distortion of the left ventricular outflow tract. Homograft aortic root replacement is an excellent option for aortic root abscesses but is limited by homograft availability. We describe a simple technique of a bioprosthetic valved conduit constructed on the table using a Dacron (DuPont, Wilmington, DE) skirt below the valve. The use of the Dacron skirt facilitates easy reconstruction of the left ventricular outflow tract.


Assuntos
Valva Aórtica/cirurgia , Bioprótese , Procedimentos Cirúrgicos Cardíacos/métodos , Próteses Valvulares Cardíacas , Ventrículos do Coração/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Polietilenotereftalatos , Humanos , Desenho de Prótese
12.
J Radiol Case Rep ; 10(8): 1-11, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27761189

RESUMO

We present a case in which intraocular silicone injection for complex retinal detachment resulted in migration and distribution of silicone along the intracranial visual pathway, and ultimately throughout the ventricular system. Misinterpretation of this material as intracranial hemorrhage on outside computed tomography imaging delayed emergent repair of a Type A aortic dissection until the diagnosis was made on repeat imaging. A discussion of this case and salient computed tomography and magnetic resonance imaging characteristics of silicone is provided.


Assuntos
Aneurisma Aórtico/diagnóstico por imagem , Dissecção Aórtica/diagnóstico por imagem , Migração de Corpo Estranho/diagnóstico por imagem , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/diagnóstico por imagem , Descolamento Retiniano/tratamento farmacológico , Silicones/efeitos adversos , Dissecção Aórtica/cirurgia , Aneurisma Aórtico/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Hemorragias Intracranianas/cirurgia , Imageamento por Ressonância Magnética , Síndrome de Marfan/complicações , Pessoa de Meia-Idade , Silicones/administração & dosagem , Tomografia Computadorizada por Raios X
13.
Tex Heart Inst J ; 42(6): 558-60, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26664311

RESUMO

Endometrial stromal sarcoma metastases usually occur within the pelvis and rarely involve the great vessels or the heart. We present the case of a 55-year-old woman who was referred for endovascular therapy to treat presumed thrombosis of the inferior vena cava. The suspected thrombus was recalcitrant to endovascular removal with use of an AngioVac venous drainage device. Results of an intraprocedural transvenous biopsy revealed the mass to be the intravascular extension of an endometrial stromal sarcoma. The patient underwent surgical excision of the tumor, and, shortly thereafter, a hysterectomy and salpingo-oophorectomy. This complex case highlights both the rarity of malignancy masquerading as caval thrombus and the importance of multispecialty collaboration.


Assuntos
Neoplasias do Endométrio/patologia , Neoplasias Cardíacas/patologia , Sarcoma do Estroma Endometrial/secundário , Neoplasias Vasculares/secundário , Veia Cava Inferior/patologia , Biópsia , Erros de Diagnóstico , Neoplasias do Endométrio/cirurgia , Feminino , Átrios do Coração/patologia , Neoplasias Cardíacas/cirurgia , Humanos , Histerectomia , Pessoa de Meia-Idade , Invasividade Neoplásica , Ovariectomia , Flebografia/métodos , Valor Preditivo dos Testes , Salpingectomia , Sarcoma do Estroma Endometrial/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Neoplasias Vasculares/cirurgia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgia , Trombose Venosa/diagnóstico
14.
BMJ Case Rep ; 20152015 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-26243540

RESUMO

Aortic thoracic dissection (AD) is a serious cardiovascular disease. According to the Stanford classification; type A involves the ascending aorta and type B the descending distal to the left subclavian artery. Neurological complications secondary to AD are devastating. Ischaemic stroke and hypoxic encephalopathy are early-recognised complications of type A as the arch vessels can be involved AD. Although, late ischaemic stroke had been reported in 1.4-5% of patients with type B dissection, early stroke is very unusual as it cannot be simply explained by AD anatomical pathogenesis. We report two patients who presented with type B AD complicated by early ischaemic strokes. Work-up revealed significant cardiomyopathies in both patients but with left ventricle thrombus in one. In both patients the strokes were felt to be of cardioembolic origin.


Assuntos
Aneurisma da Aorta Torácica/diagnóstico , Dissecção Aórtica/classificação , Dissecção Aórtica/diagnóstico , Acidente Vascular Cerebral/complicações , Adulto , Aorta , Ecocardiografia Transesofagiana , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Artéria Subclávia , Tomografia Computadorizada por Raios X
15.
J Pak Med Assoc ; 56(6): 267-72, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16827250

RESUMO

OBJECTIVES: To describe the distribution of over weight and body mass index, waist circumference and waist/ hip ratio, correlate obesity measures to coronary heart disease risk factors in comparison to Pakistan National Survey (PNS). METHODS: The Metroville Health Study (MHS) was an urban risk factor reduction intervention study in Metroville Karachi. Base line data was used which was not a random sample. Demographic data including serum cholesterol, glucose, haemoglobin, and blood pressure were collected. RESULTS: In MHS high cholesterol was 16% and 24% in men and women respectively, and 25% had hypertension. Self-reported diabetes was 8%, over-weight/obesity 34% and 49% for men and women, compared to 16% and 25% for PNS, while high risk waist-hip ratio (WHR) was present in 41% and 72% of men and women respectively. Under-weight in Metroville men was 12% and 9% in women, compared to 26% and 27% in PNS. The anthropometry variables were significantly correlated with each other while weight was significantly correlated with TC and waist circumference (WC). CONCLUSION: Obesity was alarmingly prevalent in urban Metroville in comparison to PNS. Cardio Vascular Disease (CVD) risk factors were prevalent in Metroville and TC and WC were significantly correlated with obesity measures. For prevention of increasing CVD in urban communities, targeted programs of intervention are required.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , National Institutes of Health (U.S.) , Adolescente , Adulto , Fatores Etários , Antropometria , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Relações Comunidade-Instituição , Diabetes Mellitus Tipo 2/etiologia , Feminino , Humanos , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Paquistão/epidemiologia , Prevalência , Fatores de Risco , Estados Unidos , Saúde da População Urbana
16.
Int Surg ; 90(3): 148-50, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16466003

RESUMO

Cellular cardiomyoplasty using various types of donor cells is now validated by a large number of experimental studies. We report a case of cellular cardiomyoplasty performed on a beating heart using autologous skeletal myoblasts, thus combining the efficacy of both procedures. Approximately 2.5 g of rectus femoris muscle tissue biopsy was taken from the patient and cultured using a patented procedure to generate human myoblasts. The cell type and the purity of the cell culture were ascertained by immunostaining for human desmin expression. Under direct vision and stabilization with the Octopus III tissue stabilizer, 3.70 x 10(8) myoblasts in 3 ml of the patient's own serum were injected into the myocardium in 20 sites on the anterior wall and near the apex on the posterior wall, in and around the infarcted areas. In this case report, this procedure was found to be a safe and viable option, with improvement in cardiac function.


Assuntos
Cardiomioplastia/métodos , Mioblastos Esqueléticos/transplante , Infarto do Miocárdio/cirurgia , Células Cultivadas , Ponte de Artéria Coronária sem Circulação Extracorpórea , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo
17.
Mol Ther ; 9(1): 14-23, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14741773

RESUMO

The incidence of heart failure is achieving epidemic proportions. Adult human myocytes cannot regenerate because these cells do not re-enter the cell cycle. In patients with heart failure, myoblast transplantation is emerging as a potential therapeutic option to augment the function of remaining myocytes. Both skeletal myoblasts and autologous bone marrow cell transplantation, after intensive preclinical experimental animal studies, have entered phase I safety studies in humans. Most of these clinical trials have involved small groups of patients and cell transplantation was carried out as an adjunct to coronary revascularization. Preliminary results show that the procedure is safe and leads to improved myocardial function. This paper reviews and summarizes the outcome of these phase I trials involving skeletal myoblast transplantation.


Assuntos
Baixo Débito Cardíaco/terapia , Mioblastos Esqueléticos/transplante , Animais , Ásia/epidemiologia , Baixo Débito Cardíaco/epidemiologia , Baixo Débito Cardíaco/etiologia , Transplante de Células/efeitos adversos , Transplante de Células/mortalidade , Ensaios Clínicos Fase I como Assunto , Europa (Continente)/epidemiologia , Humanos , Mioblastos Esqueléticos/fisiologia , Transplante Autólogo , Estados Unidos/epidemiologia
18.
Circ Res ; 91(1): 25-31, 2002 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-12114318

RESUMO

Interactions between integrins and growth factor receptors play a critical role in the development and healing of the vasculature. This study mapped two binding domains on fibronectin (FN) that modulate the activity of the angiogenic factor, vascular endothelial growth factor (VEGF). Using solid-phase assays and surface plasmon resonance analysis, we identified two novel VEGF binding domains within the N- and C-terminus of the FN molecule. Native FN bound to VEGF enhanced endothelial cell migration and mitogen-activated protein (MAP) kinase activity, but FN that is devoid of the VEGF binding domains failed to do so. Coprecipitation studies confirmed a direct physical association between VEGF receptor-2 (Flk-1) and the FN integrin, alpha5beta1, which required intact FN because FN fragments lacking the VEGF binding domains failed to support receptor association. Thrombin-activated platelets released intact VEGF/FN complexes, which stimulated endothelial cell migration and could be inhibited by soluble high affinity VEGF receptor 1 and antibodies to alpha5beta1 integrin. This study demonstrates that FN is potentially a physiological cofactor for VEGF and provides insights into mechanisms by which growth factor receptors and integrins cooperate to influence cellular behavior.


Assuntos
Fatores de Crescimento Endotelial/metabolismo , Endotélio Vascular/metabolismo , Fibronectinas/metabolismo , Linfocinas/metabolismo , Sítios de Ligação , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Fatores de Crescimento Endotelial/química , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Ativação Enzimática , Proteínas da Matriz Extracelular/farmacologia , Fibronectinas/química , Humanos , Linfocinas/química , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fragmentos de Peptídeos/farmacologia , Ligação Proteica , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptores de Fibronectina/metabolismo , Receptores de Vitronectina/metabolismo , Trombina/farmacologia , Fator A de Crescimento do Endotélio Vascular , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular , Vitronectina/farmacologia
20.
Turk J Haematol ; 19(3): 349-89, 2002 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-27264974

RESUMO

Sepsis, a systemic inflammatory syndrome, is a response to infection and when associated with multiple organ dysfunction is termed, severe sepsis. It remains a leading cause of mortality in the critically ill. The response to the invading bacteria may be considered as a balance between proinflammatory and antiinflammatory reaction. While an inadequate proinflammatory reaction and a strong antiinflammatory response could lead to overwhelming infection and death of the patient, a strong and uncontrolled proinflammatory response, manifested by the release of proinflammatory mediators may lead to microvascular thrombosis and multiple organ failure. Endotoxin triggers sepsis by releasing various mediators including tumor necrosis factor-alpha and interleukin-1(IL-1). These cytokines activate the complement and coagulation systems, release adhesion molecules, prostaglandins, leukotrienes, reactive oxygen species and nitric oxide (NO). Other mediators involved in the sepsis syndrome include IL-1, IL-6 and IL-8; arachidonic acid metabolites; platelet activating factor (PAF); histamine; bradykinin; angiotensin; complement components and vasoactive intestinal peptide. These proinflammatory responses are counteracted by IL-10. Most of the trials targeting the different mediators of proinflammatory response have failed due a lack of correct definition of sepsis. Understanding the exact pathophysiology of the disease will enable better treatment options. Targeting the coagulation system with various anticoagulant agents including antithrombin, activated protein C (APC), tissue factor pathway inhibitor (TFPI) is a rational approach. Many clinical trials have been conducted to evaluate these agents in severe sepsis. While trials on antithrombin and TFPI were not so successful, the double-blind, placebo-controlled, phase III trial of recombinant human activated protein C worldwide evaluation in severe sepsis (PROWESS) was successful, significantly decreasing mortality when compared to the placebo group. Better understanding of the pathophysiologic mechanism of severe sepsis will provide better treatment options. Combination antithrombotic therapy may provide a multipronged approach for the treatment of severe sepsis.

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