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1.
J Vasc Surg ; 75(1): 38-46, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34197944

RESUMEN

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) has become first-line therapy for complicated acute type B aortic dissection (aTBAD). However, the strategy for optimal proximal landing zone remains to be determined. We compared early outcomes and late aortic-related adverse events in patients undergoing TEVAR for complicated aTBAD with endograft deployment in proximal landing zone 2 vs 3. METHODS: We performed a retrospective chart review of adult patients undergoing TEVAR for complicated aTBAD within 6 weeks of diagnosis from January 2008 to December 2018. We excluded patients with connective tissue disorders and prior type A repair. Patients were divided into landing zone 2 TEVAR (Z2T) and zone 3 TEVAR (Z3T) groups. Z2 patients were divided between left subclavian artery (LSA) revascularization (Z2R) vs LSA coverage without revascularization (Z2C). Groups were compared for the need for aortic reintervention within 36 months of initial admission and freedom from aortic-related adverse events and mortality (AREM), defined as the need for aortic reintervention, aortic-related death, or rupture. RESULTS: Eighty-three patients underwent TEVAR for complicated aTBAD within a mean of 4.1 ± 7.8 days; 89.5% of patients had less than 2 cm of healthy proximal descending thoracic aorta. The landing zone was Z3T in 35 patients and 48 underwent Z2T: 10 Z2C and 38 Z2R. There were no differences between Z2T and Z3T in time from diagnosis to TEVAR, demographics, comorbidities, and diameter aortic measurements. The 30-day survival was 87.8%-89.5% for Z2R, 88.6% for Z3, and 80.0% for Z2C (P = .610). The postoperative spinal cord ischemia rate was 3.7%-2.7% for Z2R, 0% for Z3T, and 20.0% for Z2C (P = .012). The postoperative thoracic aortic rupture was 2.2% in Z2 and 0 in Z3. The need for aortic reintervention at 36 months after TEVAR was lower for Z2T (10.4%) vs Z3T (31.4%; P = .025). Freedom from AREM at 36 months was higher in Z2T vs Z3T (87.5% vs 68.6%; P = .048). The freedom from proximal reintervention was higher in Z2T (95.8%) compared with Z3T (80.0%; P = .019). Z3T deployment was predictive for AREM (odd ratio, 3.648; 95% confidence interval, 1.161-11.465; P = .027) and need for proximal reintervention (odds ratio, 5.542; 95% confidence interval, 1.062-28.927; P = .042). CONCLUSIONS: Most patients with aTBAD have less than 2 cm of proximal healthy descending thoracic aorta. In patients treated for complicated aTBAD, Z2T is associated with a lower need for aortic reintervention and aortic-related adverse events than Z3T. Patients may benefit from a more aggressive proximal landing zone with similar perioperative morbidity when Z2T is done with LSA revascularization.


Asunto(s)
Angioplastia/métodos , Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/métodos , Complicaciones Posoperatorias/epidemiología , Anciano , Disección Aórtica/etiología , Angioplastia/efectos adversos , Angioplastia/instrumentación , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/complicaciones , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Stents/efectos adversos , Arteria Subclavia/cirugía , Resultado del Tratamiento
2.
J Vasc Surg ; 75(2): 464-472.e2, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34506888

RESUMEN

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) is increasingly utilized in the management of acute type B aortic intramural hematoma (TBIMH). Optimal timing for intervention has not been described. The aim of this study was to evaluate TEVAR timing on postoperative aortic remodeling. METHODS: A retrospective chart review was performed on patients who underwent TEVAR for TBIMH from January 2008 to September 2018. Imaging was reviewed pre- and postoperatively. Primary data points included true lumen diameter (TLD) and total aortic diameter (TAD) at the site of maximal pathology. Primary endpoint was aortic remodeling evidenced by a TAD/TLD ratio closest to 1.0. Secondary outcome was occurrence of aortic-related adverse events and mortality (AREM): aortic rupture, aortic-related death, progression to dissection, or need for aortic reintervention within 12 months. Patients undergoing emergent TEVAR (within 24 hours, 'eTEVAR') were compared with the remainder - delayed TEVAR ('dTEVAR'). RESULTS: We analyzed 71 patients that underwent TEVAR for TBIMH; 25 underwent emergent TEVAR and 46 patients underwent dTEVAR (median, 5.5 days; range, 2-120 days). There were no differences in demographics and comorbidities, and patients did not differ in presenting IMH thickness (12.6 ± 3.1 vs 11.3 ± 4.1 mm; P = .186) nor presenting TAD/TLD ratio (1.535 ± 0.471 vs 1.525 ± 0.397; P = .928) for eTEVAR and dTEVAR groups, respectively. eTEVAR patients had larger average presenting maximal descending aortic diameter (45.8 ± 14.3 vs 38.2 ± 7.5 mm; P = .018) and higher incidence of penetrating aortic ulcer on presenting computed tomography angiography (52.0% vs 21.7%; P = .033). Thirty-day mortality was 2 of 25 (8.0%) for eTEVAR and 2 of 45 (4.4%) for dTEVAR (P = .602). Postoperative aortic remodeling was more complete in the dTEVAR group (1.23 ± 0.12 vs 1.33 ± 0.15; P = .004). Case-control matching (controlling for presenting descending aortic diameter and penetrating aortic ulcer) on 30 patients still showed better aortic remodeling in the dTEVAR group (1.125 ± 0.100 vs 1.348 ± 0.42; P < .001). The incidence of AREM was higher in the eTEVAR (6/25; 24.0%) group compared with the dTEVAR group (2/46; 4.3%). At 12 months, freedom from AREM was higher in the dTEVAR group (95.7% vs 76.0%; P = .011). Postoperative TAD/TLD ratio was the best predictor for late aortic-related adverse events (area under the receiver operator characteristic = 0.825; P = .003). CONCLUSIONS: TEVAR for acute TBIMH within 24 hours of admission is associated with lower aortic remodeling and higher occurrence of late AREM. Delaying TEVAR when clinically possible could improve aortic remodeling and aortic-related outcomes.


Asunto(s)
Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/complicaciones , Rotura de la Aorta/cirugía , Procedimientos Endovasculares/métodos , Hematoma/etiología , Remodelación Vascular , Anciano , Disección Aórtica/diagnóstico , Disección Aórtica/cirugía , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/fisiopatología , Aneurisma de la Aorta Torácica/complicaciones , Aneurisma de la Aorta Torácica/diagnóstico , Rotura de la Aorta/complicaciones , Rotura de la Aorta/diagnóstico , Aortografía , Prótesis Vascular , Angiografía por Tomografía Computarizada , Femenino , Estudios de Seguimiento , Hematoma/diagnóstico , Humanos , Masculino , Periodo Posoperatorio , Estudios Retrospectivos , Resultado del Tratamiento
3.
J Vasc Surg ; 71(4): 1088-1096, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32063446

RESUMEN

OBJECTIVE: Intramural hematoma (IMH) is on the spectrum of acute aortic syndrome, but optimal management is poorly understood. The aim of this study was to evaluate outcomes of patients with type B IMH (TBIMH) after best medical therapy (BMT) and to assess for risk factors associated with failure of BMT. METHODS: This is a single-institution retrospective chart review of all patients with TBIMH between January 2008 and December 2017. Failure of BMT was defined as any of the following end points: aortic rupture, aorta-related death, aortic enlargement to at least 55 mm or growth of >10 mm within 12 months, or need for surgical aortic intervention for failed BMT. RESULTS: We identified 92 patients, of whom 25 received emergent thoracic endovascular aortic repair; 67 patients were initially managed with BMT, and of these, 32 underwent thoracic endovascular aortic repair within 14 days for early BMT failure. Two additional patients had early BMT failure; one died of aortic rupture due to retrograde type A dissection, and one patient was advised to undergo repair but did not comply and was lost to follow-up. Fourteen patients (20.9%) received endovascular therapy for late failure of BMT after the initial hospitalization. Medical management was successful in 19 patients (28.4%), although 5 patients had aortic enlargement but below the threshold for elective repair (maximal aortic diameter of 55 mm). On univariate analysis, presenting IMH thickness and growth of IMH thickness were risk factors for BMT failure. On multivariate analysis, presenting IMH thickness was the sole predictive risk factor for medical therapy failure (odds ratio, 1.083; 95% confidence interval, 1.021-1.149; P = .008), with an odds ratio of 6.810 (95% confidence interval, 1.921-24.146; P = .002) with a presenting IMH thickness of ≥8.0 mm, which was the calculated IMH thickness cutoff value with highest sensitivity and specificity to predict failure of BMT (area under the receiver operating characteristic curve = 0.795; P = .001; J = 0.62). CONCLUSIONS: BMT for TBIMH is associated with a high failure rate and need for interventions. IMH thickness on admission is the most reliable factor to predict failure of BMT.


Asunto(s)
Enfermedades de la Aorta/terapia , Hematoma/terapia , Anciano , Aorta Torácica , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/mortalidad , Progresión de la Enfermedad , Procedimientos Endovasculares , Femenino , Hematoma/diagnóstico por imagen , Hematoma/mortalidad , Humanos , Masculino , Estudios Retrospectivos , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Insuficiencia del Tratamiento
4.
J Cutan Pathol ; 44(6): 523-529, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28256051

RESUMEN

BACKGROUND: Dermatopathologists assess wounds secondary to trauma, infection, or oncologic resection that can be challenging to reconstruct. OASIS Ultra, an extracellular matrix, has been described for use in chronic and burn wounds. The aim of this pilot study is to assess wound healing in post-traumatic and infective wounds treated with OASIS using histological markers of repair. MATERIALS AND METHODS: Adults with traumatic, infective or iatrogenic wound defects with size precluding primary closure were eligible. Half the wound was randomly assigned to receive OASIS plus standard therapy; the other half received standard of care (SOC) therapy. During dressing changes, standardized-scale photographs were taken and biopsies obtained. Histologic sections were reviewed for degree of acute inflammation and extent of tissue repair. Neutrophils, edema, hemorrhage, necrosis, fibroblasts, collagen density and neovascularization were semi-quantitatively assessed. RESULTS: Forty-four skin biopsies from 7 patients with 10 acute wounds met eligibility criteria. Histologically, OASIS samples demonstrated improved acute inflammation scores compared to SOC. No patients experienced OASIS-related complications. OASIS-treated wound halves trended toward more wound contraction and improved tissue repair. CONCLUSION: Our scoring system aids histopathological wound assessment. Treatment of critical-sized, post-traumatic, acute wounds with OASIS resulted in decreased inflammation, and potentially more advanced wound healing, compared to SOC.


Asunto(s)
Quemaduras , Matriz Extracelular , Cicatrización de Heridas , Heridas y Lesiones , Adulto , Anciano , Anciano de 80 o más Años , Vendajes , Biopsia , Quemaduras/metabolismo , Quemaduras/patología , Quemaduras/terapia , Enfermedad Crónica , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Femenino , Humanos , Masculino , Proyectos Piloto , Heridas y Lesiones/metabolismo , Heridas y Lesiones/patología , Heridas y Lesiones/terapia
5.
J Surg Res ; 193(1): 316-23, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25016441

RESUMEN

BACKGROUND: Trauma represents a significant public health burden, and hemorrhage alone is responsible for 40% of deaths within the first 24 h after injury. Noncompressible hemorrhage accounts for the majority of hemorrhage-related deaths. Thus, materials which can arrest bleeding rapidly are necessary for improved clinical outcomes. This preliminary study evaluated several self-expanding hydrophobically modified chitosan (HM-CS) foams to determine their efficacy on a noncompressible severe liver injury under resuscitation. METHODS: Six HM-CS foam formulations (HM-CS1, HM-CS2, HM-CS3, HM-CS4, HM-CS5, and HM-CS6) of different graft types and densities were synthesized, characterized, and packaged into spray canisters using dimethyl ether as the propellant. Expansion profiles of the foams were evaluated in bench testing. Foams were then evaluated in vitro, interaction with blood cells was determined via microscopy, and cytotoxicity was assessed via live-dead cell assay on MCF7 breast cancer cells. For in vivo evaluation, rats underwent a 14 ± 3% hepatectomy. The animals were treated with either: (1) an HM-CS foam formulation, (2) CS foam, and (3) no treatment (NT). All animals were resuscitated with lactated Ringer solution. Survival, total blood loss, mean arterial pressures (MAP), and resuscitation volume were recorded for 60 min. RESULTS: Microscopy showed blood cells immobilizing into colonies within tight groups of adjacent foam bubbles. HM-CS foam did not display any toxic effects in vitro on MCF7 cells over a 72 h period studied. Application of HM-CS foam after hepatectomy decreased total blood loss (29.3 ± 7.8 mL/kg in HM-CS5 group versus 90.9 ± 20.3 mL/kg in the control group; P <0.001) and improved survival from 0% in controls to 100% in the HM-CS5 group (P <0.001). CONCLUSIONS: In this model of severe liver injury, spraying HM-CS foams directly on the injured liver surface decreased blood loss and increased survival. HM-CS formulations with the highest levels of hydrophobic modification (HM-CS4 and HM-CS5) resulted in the lowest total blood loss and highest survival rates. This pilot study suggests HM-CS foam may be useful as a hemostatic adjunct or solitary hemostatic intervention.


Asunto(s)
Quitosano/farmacología , Hemorragia/etiología , Hemorragia/terapia , Hemostáticos/farmacología , Ensayo de Materiales , Heridas y Lesiones/complicaciones , Animales , Vendajes , Bovinos , Quitosano/química , Modelos Animales de Enfermedad , Hemostáticos/química , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Hígado/irrigación sanguínea , Hígado/lesiones , Células MCF-7 , Masculino , Proyectos Piloto , Ratas Sprague-Dawley , Resucitación
6.
Heart Surg Forum ; 16(3): E150-1, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23803239

RESUMEN

We describe the case of a 54-year-old woman with a postinfarction ventricular septal defect (VSD) and ventricular free wall rupture who was stabilized with a percutaneous ventricular assist device (pVAD) to allow for myocardial infarct stabilization. Following the rupture of the right ventricular free wall and cardiopulmonary arrest on hospital day 10, pVAD support was promptly converted to extracorporeal membrane oxygenation (ECMO) support for stabilization. After surgical repair was completed, pVAD support was continued for 4 days to allow recovery. The patient was discharged on postoperative day 11 and is alive and well 4 years later. Postinfarction VSD with free wall rupture may be salvaged with pVAD and ECMO support.


Asunto(s)
Oxigenación por Membrana Extracorpórea/métodos , Defectos del Tabique Interventricular/terapia , Corazón Auxiliar , Infarto del Miocardio/terapia , Rotura Septal Ventricular/terapia , Terapia Combinada , Femenino , Defectos del Tabique Interventricular/diagnóstico , Defectos del Tabique Interventricular/etiología , Humanos , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Resultado del Tratamiento , Rotura Septal Ventricular/diagnóstico , Rotura Septal Ventricular/etiología
7.
Heart Surg Forum ; 16(3): E155-7, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23803241

RESUMEN

The incidence of cardiac rupture complicating myocardial infarction has declined since the introduction of thrombolytic therapy. Despite the advances in the management of myocardial infarction, cardiac rupture remains an important cause of death among infarction-related fatalities. We discuss a patient who presented to our hospital with myocardial infarction and who subsequently developed a complex ventricular septal rupture, for which surgical repair was not feasible. Implantation of a CardioWest Total Artificial Heart (SynCardia Systems) allowed for immediate hemodynamic stabilization and served as a bridge to transplantation.


Asunto(s)
Defectos del Tabique Interventricular/etiología , Defectos del Tabique Interventricular/cirugía , Trasplante de Corazón , Corazón Artificial , Infarto del Miocardio/complicaciones , Rotura Septal Ventricular/etiología , Rotura Septal Ventricular/cirugía , Terapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/cirugía , Resultado del Tratamiento
8.
J Vasc Surg Cases Innov Tech ; 8(2): 175-178, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35391996

RESUMEN

A 65-year-old woman had presented with a ruptured type B intramural hematoma associated with a right-sided aortic arch aneurysm, a large Kommerell diverticulum (KD) and an aberrant left subclavian artery (LSA). She underwent total aortic arch replacement with elephant trunk, thoracic endovascular aortic repair, and LSA ligation distal to the left vertebral artery. She subsequently developed a brisk type II endoleak into the KD via retrograde flow from the left vertebral artery. Percutaneous access of the left internal mammary artery with coil embolization of the proximal LSA and KD was performed. At 5 years, computed tomography angiogram showed complete thoracic aortic remodeling without an endoleak. The results from the present case have illustrated the novel use of the left internal mammary artery as an alternative access for LSA embolization in patients with type II endoleak and limited access options.

9.
ACS Biomater Sci Eng ; 5(5): 2563-2576, 2019 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-33405762

RESUMEN

Internal bleeding is an injury that can be difficult to localize and effectively treat without invasive surgeries. Injectable polymeric nanoparticles have been developed that can reduce clotting times and blood loss, but they have yet to incorporate sufficient diagnostic capabilities to assist in identifying bleeding sources. Herein, polymeric nanoparticles were developed to simultaneously treat internal bleeding while incorporating tracers for visualization of the nanoparticles by standard clinical imaging modalities. Addition of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate (DiD; a fluorescent dye), biotin functionality, and gold nanoparticles to hemostatic polymeric nanoparticles resulted in nanoparticles amenable to imaging with near-infrared (NIR) imaging, immunohistochemistry, and X-ray computed tomography (CT), respectively. Following a lethal liver resection injury, visualization of accumulated nanoparticles by multiple imaging methods was achieved in rodents, with the highest accumulation observed at the liver injury site, resulting in improved survival rates. Tracer addition to therapeutic nanoparticles allows for an expansion of their applicability, during stabilization by first responders to diagnosis and identification of unknown internal bleeding sites by clinicians using standard clinical imaging modalities.

11.
J Spec Oper Med ; 18(4): 34-35, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30566722

RESUMEN

BACKGROUND: Care of trauma casualties in an austere environment presents many challenges, particularly when evacuation is not immediately available. Man-packable medical supplies may be consumed by a single casualty, and resupply may not be possible before evacuation, particularly during prolonged field care scenarios. We hypothesized that unmanned aerial drones could successfully deliver life-sustaining medical supplies to a remote, denied environment where vehicle or foot traffic is impossible or impractical. METHODS: Using an unmanned, rotary- wing drone, we simulated delivery of a customizable, 4.5kg load of medical equipment, including tourniquets, dressings, analgesics, and blood products. A simulated casualty was positioned in a remote area. The flight was preprogrammed on the basis of grid coordinates and flew on autopilot beyond visual range; data (altitude, flight time, route) were recorded live by high-altitude Shadow drone. Delivery time was compared to the known US military standards for traversing uneven topography by foot or wheeled vehicle. RESULTS: Four flights were performed. Data are given as mean (± standard deviation). Time from launch to delivery was 20.77 ± 0.05 minutes (cruise speed, 34.03 ± 0.15 km/h; mean range, 12.27 ± 0.07 km). Medical supplies were delivered successfully within 1m of the target. The drone successfully returned to the starting point every flight. Resupply by foot would take 5.1 hours with an average speed of 2.4km/h and 61.35 minutes, with an average speed of 12 km/h for a wheeled vehicle, if a rudimentary road existed. CONCLUSION: Use of unmanned drones is feasible for delivery of life-saving medical supplies in austere environments. Drones repeatedly and accurately delivered medical supplies faster than other methods without additional risk to personnel or manned airframe. This technology may have benefit for austere care of military and civilian casualties.


Asunto(s)
Aeronaves/instrumentación , Equipos y Suministros , Medicina Militar , Tecnología de Sensores Remotos/instrumentación , Estudios de Factibilidad , Humanos
13.
J Am Coll Surg ; 226(6): 1030-1035, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29501782

RESUMEN

BACKGROUND: Bile spillage (BS) occurs frequently during laparoscopic cholecystectomy, yet its impact on postoperative outcomes remains unknown. We hypothesized that BS increases the risk of surgical site infections (SSI) after laparoscopic cholecystectomy. STUDY DESIGN: Patients older than 18, who were admitted to an academic hospital for a laparoscopic (or laparoscopic converted to open) cholecystectomy, from May 2010 to March 2017, were prospectively included. Open cholecystectomies were excluded. Patients were assessed clinically during hospitalization and 2 to 4 weeks after discharge. We compared those who had BS during the operation with those who did not. Our primary endpoint was the rate of SSI. Stepwise logistic regression was used to identify independent predictors of SSI. RESULTS: Of 1,001 patients, 49.9% underwent laparoscopic cholecystectomy for acute cholecystitis, 20.9% for symptomatic cholelithiasis or biliary colic, 12.8% for gallstone pancreatitis, and 16.4% for other indications. Bile was spilled intraoperatively in 591 patients (59.0%), with hydrops noted in 10.5% and empyema in 14.6% of them. In 202 (20.2%) patients, BS was accompanied by stone spillage. Patients with BS were older (median age of 52 vs 42, p < 0.001) and were more frequently male (44.8% vs 27.8%, p < 0.001). Conversion to open was more likely in operations with BS (13.0% vs 4.4%, p < 0.001). Bile spillage was associated with a higher SSI rate (7.1% vs 2.4%, p = 0.001) and longer hospital stay (median of 3 vs 2 days, p < 0.001). In the multivariable analysis, BS, conversion to open, and American Society of Anesthesiologists (ASA) score > 2 were independent predictors of SSI (odds ratios: 2.29, 2.46, and 2.1 respectively, p < 0.05). CONCLUSIONS: Bile spillage is associated with SSI, and surgeons should take extra caution to avoid it during laparoscopic cholecystectomy.


Asunto(s)
Bilis , Colecistectomía Laparoscópica , Colecistitis/cirugía , Infección de la Herida Quirúrgica/etiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo
14.
J Med Chem ; 50(17): 4113-21, 2007 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-17665896

RESUMEN

A wide variety of pathogens have acquired antimicrobial resistance as an inevitable evolutionary response to the extensive use of antibacterial agents. In particular, one of the most widely used antibiotic structural classes is the beta-lactams, in which the most common and the most efficient mechanism of bacterial resistance is the synthesis of beta-lactamases. Class C beta-lactamase enzymes are primarily cephalosporinases, mostly chromosomally encoded, and are inducible by exposure to some beta-lactam agents and resistant to inhibition by marketed beta-lactamase inhibitors. In an ongoing effort to alleviate this problem a series of novel 4-substituted trinems was designed and synthesized. Significant in vitro inhibitory activity was measured against the bacterial beta-lactamases of class C and additionally against class A. The lead compound LK-157 was shown to be a potent mechanism-based inactivator. Acylation of the active site Ser 64 of the class C enzyme beta-lactamase was observed in the solved crystal structures of two inhibitors complexes to AmpC enzyme from E. cloacae. Structure-activity relationships in the series reveal the importance of the trinem scaffold for inhibitory activity and the interesting potential of the series for further development.


Asunto(s)
Antibacterianos/síntesis química , Azetidinas/síntesis química , Proteínas Bacterianas/antagonistas & inhibidores , Farmacorresistencia Bacteriana , Compuestos Heterocíclicos con 3 Anillos/síntesis química , Inhibidores de beta-Lactamasas , Acilación , Antibacterianos/química , Azetidinas/química , Proteínas Bacterianas/química , Sitios de Unión , Cristalografía por Rayos X , Enterobacter cloacae/enzimología , Compuestos Heterocíclicos con 3 Anillos/química , Modelos Moleculares , Estructura Molecular , Estereoisomerismo , Relación Estructura-Actividad , beta-Lactamasas/química
15.
JAMA Surg ; 152(6): 574-580, 2017 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-28273299

RESUMEN

Importance: Hemostatic resuscitation has been shown to be beneficial for patients with trauma, but there is little evidence that it is equally beneficial for bleeding patients without trauma. The practice of a high transfusion ratio of fresh frozen plasma (FFP) to red blood cells (RBCs) has spread to other surgical and medical fields. Objective: To identify whether ratio-based resuscitation in patients without trauma is associated with improved survival. Design, Setting, and Participants: This study is a retrospective review of all massive transfusions provided in an urban academic hospital from January 1, 2009, through December 31, 2012. Massive transfusion was defined as the transfusion of at least 10 U of RBCs in the first 24 hours after a patient's admission to the operating room, emergency department, or intensive care unit. All patients who received massive transfusions within the study period and survived more than 30 minutes after hospital arrival were counted (n=865). Patients were grouped into those with trauma and those without trauma. Sources of data included the Research Patient Data Registry, patients' medical records, and blood bank records. All data collection occurred between April 26, 2013, and April 26, 2015. Data analysis took place from April 27, 2015, and June 22, 2016. Main Outcomes and Measures: Examination of FFP:RBC transfusion ratios for patients without trauma. Results: There were 865 massive transfusion events that occurred within 4 years, transfusing 16 569 U of RBCs, 13 933 U of FFP, 5228 U of cryoprecipitate, and 22 635 U of platelets. Most of these transfusions were received by patients without trauma (767 [88.7%]), by men (582 [67.3%]), and for intraoperative bleeding (544 [62.9%]). The FFP:RBC ratios of survivors and nonsurvivors were nearly identical: the ratio for survivors was 1:1.5 (interquartile range [IQR], 1:1.1-1:2.2) and for nonsurvivors was 1:1.4 (IQR, 1:1.1-1:1.9; P = .43). Among the 767 patients without trauma, there was no difference in the adjusted odds ratio (aOR) for 30-day mortality when comparing the high FFP:RBC ratio vs the low FFP:RBC ratio subgroups (aOR, 1.10; 95% CI, 0.72-1.70; P = .65). In vascular surgery, the aOR for death favored the high FFP:RBC ratio subgroup (aOR, 0.16; 95% CI, 0.03-0.79; P = .02). However, in general surgery and medicine, the aOR for death favored the low FFP:RBC ratio subgroup; general surgery: aOR, 4.27 (95% CI, 1.28-14.22; P = .02); medicine: aOR, 8.48 (95% CI, 1.50-47.75; P = .02). Conclusions and Relevance: High FFP:RBC transfusion ratios are applied mostly to patients without trauma, who account for nearly 90% of all massive transfusion events. Thirty-day survival was not significantly different in patients who received a high FFP:RBC ratio compared with those who received a low ratio.


Asunto(s)
Transfusión Sanguínea , Transfusión de Eritrocitos , Hemorragia/terapia , Técnicas Hemostáticas , Plasma/citología , Resucitación/métodos , Centros Médicos Académicos , Adulto , Anciano , Estudios de Cohortes , Femenino , Hemorragia/etiología , Hemorragia/mortalidad , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Quirófanos , Estudios Retrospectivos , Tasa de Supervivencia
16.
Inflammation ; 40(4): 1264-1274, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28493077

RESUMEN

Hemorrhage is a common cause of death in the battlefield. Valproic acid (VPA) has been associated with improved outcomes in multiple models of trauma, when combined with isotonic fluid resuscitation. However, isotonic fluid administered in this setting is logistically impractical and may be associated with complications. In this study, we sought to evaluate the feasibility and immunologic impact of combining VPA treatment with low-volume hypertonic saline (HTS). In vivo: female Yorkshire swine were subjected to hemorrhage (40% total blood volume) and polytrauma (rib fracture and delayed liver injury). Animals were kept in shock for 30 minutes and resuscitated with (1) normal saline (NS, 3× hemorrhaged volume), (2) HTS (7.5% saline, 4 mL/kg), or (3) HTS + VPA (4 mg/kg; 150 mg/kg; n = 3/cohort). After 18 hours of observation, animals were euthanized and the lungs evaluated for acute injury and expression of myeloperoxidase (MPO) and caveolin-1 (Cav-1). In vitro: human umbilical vein endothelial cells (HUVECs) were exposed to anoxic conditions (5% CO2, 95% N2) for 16 hours in (1) normosmotic, (2) hyperosmotic (400 mOsm), or (3) hyperosmotic + VPA (4 mM) media. Immunohistochemistry and Western blots were performed to determine Cav-1 expression. Lungs from VPA-treated animals demonstrated decreased acute injury, MPO expression, and endothelial expression of Cav-1 when compared to lungs from animals resuscitated with NS or HTS alone. Similarly, HUVECs cultured in hyperosmotic media containing VPA demonstrated decreased expression of Cav-1. This study demonstrates that combined treatment with VPA and HTS is a viable strategy in hemorrhagic shock and polytrauma. Attenuation of lung injury following VPA treatment may be related to modulation of the inflammatory response.


Asunto(s)
Lesión Pulmonar/prevención & control , Traumatismo Múltiple/tratamiento farmacológico , Solución Salina Hipertónica/uso terapéutico , Choque Hemorrágico/tratamiento farmacológico , Ácido Valproico/uso terapéutico , Animales , Caveolina 1/análisis , Células Cultivadas , Femenino , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Lesión Pulmonar/diagnóstico , Lesión Pulmonar/tratamiento farmacológico , Traumatismo Múltiple/etiología , Peroxidasa/análisis , Resucitación/métodos , Porcinos
17.
J Trauma Acute Care Surg ; 82(2): 263-269, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27893647

RESUMEN

BACKGROUND: Although cervical spine CT (CSCT) accurately detects bony injuries, it may not identify all soft tissue injuries. Although some clinicians rely exclusively on a negative CT to remove spine precautions in unevaluable patients or patients with cervicalgia, others use MRI for that purpose. The objective of this study was to determine the rates of abnormal MRI after a negative CSCT. METHODS: Blunt trauma patients who either were unevaluable or had persistent midline cervicalgia and underwent an MRI of the C-spine after a negative CSCT were enrolled prospectively in eight Level I and II New England trauma centers. Demographics, injury patterns, CT and MRI results, and any changes in cervical spine management as a result of MRI imaging were recorded. RESULTS: A total of 767 patients had MRI because of cervicalgia (43.0%), inability to evaluate (44.1%), or both (9.4%). MRI was abnormal in 23.6% of all patients, including ligamentous injury (16.6%), soft tissue swelling (4.3%), vertebral disc injury (1.4%), and dural hematomas (1.3%). Rates of abnormal neurological signs or symptoms were not different among patients with normal versus abnormal MRI. (15.2 vs. 18.8%, p = 0.25). The c-collar was removed in 88.1% of patients with normal MRI and 13.3% of patients with an abnormal MRI. No patient required halo placement, but 11 patients underwent cervical spine surgery after the MRI results. Six of the eleven had neurological signs or symptoms. CONCLUSIONS: In a select population of patients, MRI identified additional injuries in 23.6% of patients despite a normal CSCT. It is uncertain if this is a true limitation of CT technology or represents subtle injuries missed in the interpretation of the scan. The clinical significance of these abnormal MRI findings cannot be determined from this study group. LEVEL OF EVIDENCE: Therapeutic study, level IV.


Asunto(s)
Vértebras Cervicales/lesiones , Imagen por Resonancia Magnética/métodos , Traumatismos Vertebrales/diagnóstico por imagen , Heridas no Penetrantes/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , New England , Estudios Prospectivos , Tomografía Computarizada por Rayos X
18.
Am J Surg ; 211(4): 656-663.e4, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26860622

RESUMEN

BACKGROUND: Intraoperative blood product transfusions carry risk but are often necessary in emergency general surgery (EGS). METHODS: We queried the American College of Surgery-National Surgical Quality Improvement Program database for EGS patients (2008 to 2012) at 2 tertiary academic hospitals. Outcomes included rates of high packed red blood cell (pRBC) use (estimated blood loss:pRBC < 350:1) and high fresh frozen plasma (FFP) use (FFP:pRBC >1:1.5). Patients were then stratified by exposure to high blood product use. Stepwise logistic regression was performed. RESULTS: Of 992 patients, 33% underwent EGS. Estimated blood loss was similar between EGS and non-EGS (282 vs 250 cc, P = .288). EGS patients were more often exposed to high pRBC use (adjusted odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.11 to 3.66) and high-FFP use (OR = 2.75, 95% CI: = 1.10 to 6.84). High blood product use was independently associated with major nonbleeding complications (high pRBC: OR = 1.73, 95% CI = 1.04 to 2.91; high FFP: OR = 2.15, 95% CI = 1.15 to 4.02). CONCLUSIONS: Despite similar blood loss, EGS patients received higher rates of intraoperative blood product transfusion, which was independently associated with major complication.


Asunto(s)
Pérdida de Sangre Quirúrgica/prevención & control , Urgencias Médicas , Transfusión de Eritrocitos/efectos adversos , Cirugía General , Plasma , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Boston , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo
19.
J Trauma Acute Care Surg ; 79(1): 39-46; discussion 46-7, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26091312

RESUMEN

BACKGROUND: Noncompressible abdominal bleeding accounts for significant mortality in both military and civilian populations. There is an emergent need for a temporary hemostatic intervention whenever surgical care is not immediately available. Our team previously described a self-expanding polyurethane foam for the treatment of exsanguinating abdominal hemorrhage. The objective of this study was to translate a safe and effective swine dose into an appropriate human dose through foam administration in recently deceased humans with representative tissue compliance. METHODS: With institutional review board oversight and informed consent at three centers, terminal patients were identified. Within 3 hours of death, the abdomen was accessed, and fluid was added to simulate hemorrhage. Foam was percutaneously administered using a prototype delivery system at multiple doses (45, 55, 65, 75, and 100 mL). Intra-abdominal pressure was monitored for 15 minutes, and then, foam was removed via laparotomy to assess abdominal tissue contact. RESULTS: Twenty-one recently deceased patients ranging in age from 20 years to 92 years and body mass index from 18 kg/m to 39 kg/m were enrolled in the study. Foam was administered at a mean (SD) of 146 (34) minutes after death. Three subjects were screen failures, and three subjects were excluded from the analysis because of experimental errors. Change in intra-abdominal pressure and semiquantitative organ contact were used as surrogates to compare findings between humans and swine. Doses of 45, 55, and 65 mL resulted in peak pressures of 37 (20), 28 (8.1), and 33 (20) mmHg, respectively, within the acceptable range established in swine studies. Foam deployments of 75 mL and 100 mL exceeded acceptable pressures defined in swine. Higher foam doses tended to improve contact with the diaphragm, paracolic gutters, and liver. CONCLUSION: The use of recently deceased humans demonstrates a novel approach to device evaluation in representative human anatomy, particularly when tissue compliance is critical. Sixty-five milliliters was determined to be the clinically appropriate dose for foam treatment in bleeding human patients.


Asunto(s)
Exsanguinación/terapia , Hemostáticos/administración & dosificación , Poliuretanos/administración & dosificación , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
20.
ASAIO J ; 60(5): 529-32, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25010911

RESUMEN

Mortality for patients presenting with acute myocardial infarction (AMI) complicated by ventricular septal defect (VSD) and cardiogenic shock is very high even with surgical repair. We report our experience regarding utilization of TandemHeart, a percutaneous ventricular assist device (pVAD) as an adjunct to the treatment of these patients. Retrospective case series study design included a total of 11 patients with post-AMI VSD and severe refractory cardiogenic shock who received pVAD support at our institution. Three patients underwent immediate surgical repair and received pVAD support for postcardiotomy cardiogenic shock for 2, 4, and 7 days, respectively. However, all three died. The other eight patients had pVAD implanted prior to surgical repair in order to rest the myocardium before operation. Hemodynamics improved immediately after pVAD placement, and after receiving pVAD support for 7 ± 3 days, they underwent surgical VSD repair. Their total pre- and post-surgical pVAD support was 14 ± 4 days. All eight survived 30 days postoperatively. At 6 months postsurgery overall survival rate was 75%. Our small series of these critically ill patients shows a trend toward better survival after immediate pVAD placement to stabilize the patient and allow for myocardial maturation before surgical VSD repair.


Asunto(s)
Defectos del Tabique Interventricular/cirugía , Corazón Auxiliar , Infarto del Miocardio/cirugía , Femenino , Defectos del Tabique Interventricular/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Estudios Retrospectivos , Choque Cardiogénico/mortalidad , Choque Cardiogénico/cirugía , Resultado del Tratamiento
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