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1.
Clin Infect Dis ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38959299

RESUMEN

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute diverticulitis. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2.
Clin Infect Dis ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963816

RESUMEN

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for obtaining cultures of intra-abdominal fluid in patients with known or suspected intra-abdominal infection. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

3.
Clin Infect Dis ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963815

RESUMEN

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute intra-abdominal abscess. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

4.
Clin Infect Dis ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963819

RESUMEN

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute appendicitis. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

5.
Clin Infect Dis ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963820

RESUMEN

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute cholecystitis or acute cholangitis. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

6.
Clin Infect Dis ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963817

RESUMEN

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for obtaining blood cultures in patients with known or suspected intra-abdominal infection. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

7.
Clin Infect Dis ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963047

RESUMEN

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides a recommendation for risk stratification according to severity of illness score. The panel's recommendation is based upon evidence derived from systematic literature reviews and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

8.
Clin Infect Dis ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38965057

RESUMEN

As the first part of an update to the clinical practice guideline on the diagnosis and management of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America, the panel presents twenty-one updated recommendations. These recommendations span risk assessment, diagnostic imaging, and microbiological evaluation. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

9.
J Surg Res ; 295: 95-101, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38000260

RESUMEN

INTRODUCTION: Applying to general surgery residency is undoubtedly a competitive process. Participation in scholarly activity (SCA) has been cited as a criterion when selecting applicants for interview and in the ranking process. This study aims to evaluate the association between gender of applicants to surgery residency and SCA and to characterize trends in SCAs over time. METHODS: We analyzed the SCA of applicants interviewed at a general surgery residency program over 6-interview cycles (2016-2021). Eight SCA categories were included: (1) Poster Presentation, (2) Oral Presentation, (3) Peer-Reviewed (PR) Journal Articles/Abstracts, (4) PR Journal Articles/Abstracts (Other than Published), (5) PR Online Publication, (6) PR Book Chapter, (7) Nonpeer reviewed Online Publication, and (8) Other Articles/Scientific Monograph. RESULTS: Of a total of 335 interviewed applicants, 288 (86%) had at least one count of SCA. Overall, no difference between male and female applicants was noticed (n = 178, 84.8% versus n = 110, 88%, P = 0.409) and no change in percentage of SCA over the six cycles (P = 0.239). The most reported SCAs were poster presentations (n = 242, 72.2%), oral presentations (n = 159, 47.5%), PR journal articles/abstracts (n = 159, 47.5%). Female applicants have marginally higher median (interquartile range) for SCAs compared to male applicants (5 [3, 8] versus 4 [3, 8], P value 0.272). CONCLUSIONS: No association between gender and SCA among applicants for general surgery residency positions was observed. While more than three-fourths of applicants have at least one SCA, only a small fraction of applicants were published. Students should be made aware of the importance of SCA early in graduate medical education.


Asunto(s)
Cirugía General , Internado y Residencia , Humanos , Masculino , Femenino , Educación de Postgrado en Medicina , Cirugía General/educación
10.
Clin Infect Dis ; 77(9): e46-e56, 2023 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-37738671

RESUMEN

In the past decade, the prevalence of multidrug-resistant gram-negative (MDR-GN) bacterial infections has increased significantly, leading to higher rates of morbidity and mortality. Treating these infections poses numerous challenges, particularly when selecting appropriate empiric therapy for critically ill patients for whom the margin for error is low. Fortunately, the availability of new therapies has improved the treatment landscape, offering safer and more effective options. However, there remains a need to establish and implement optimal clinical and therapeutic approaches for managing these infections. Here, we review strategies for identifying patients at risk for MDR-GN infections, propose a framework for the choice of empiric and definitive treatment, and explore effective multidisciplinary approaches to managing patients in the hospital while ensuring a safe transition to outpatient settings.


Asunto(s)
Antibacterianos , Infecciones por Bacterias Gramnegativas , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Hospitales
11.
J Surg Res ; 279: 285-295, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35802943

RESUMEN

INTRODUCTION: Appropriate faculty supervision and conditional independence of residents during training are required for autonomous and independent postgraduate practice. However, there is a growing concern that competence for transition to independent practice is not universally met. We hypothesize that surgery residents play a significant and active role in achieving their own independent status. METHODS: Over seven academic years (July 2014 through June 2021), 46 surgeons supervised and intraoperatively assessed the performance of 51 residents using validated Objective Structured Assessment of Technical Skill (OSATS) and Zwisch Operative Autonomy (ROA) assessments. Resident readiness to perform procedures independently (RRI) was graded as yes, no, or not applicable. Data were analyzed using descriptive statistics with categorical variables reported as frequencies and percentages. RESULTS: A total of 1657 elective procedures were performed by residents supervised by faculty. Association between RRI and postgraduate year (PGY), OSATS scores, ROA, resident and faculty gender, and case complexity was analyzed. Results indicated positive correlation between RRI and summative OSATS score (r = 0.510, P < 0.001), PGY (r = 0.535, P < 0.001) and ROA (r = 0.473, P < 0.001). Percentage of overall RRI increased from 7% at PGY1 to 87.4% at PGY5. Meaningful autonomy ratings increased from 23.6% at PGY1 to 92.5% at PGY5. Variations in ratings was observed when considering case category and complexity. CONCLUSIONS: RRI increases with years of training with variation when considering the specialty/The Accreditation Council for Graduate Medical Education procedure category and the complexity of cases. Specialty fellowships are a viable option to address the gap in The Accreditation Council for Graduate Medical Education categories when residency alone cannot reach appropriate independence. Residents' technical skills play a crucial role in evaluating RRI and granting operative autonomy.


Asunto(s)
Cirugía General , Internado y Residencia , Cirujanos , Competencia Clínica , Educación de Postgrado en Medicina/métodos , Evaluación Educacional/métodos , Cirugía General/educación , Humanos
12.
J Surg Res ; 259: 97-105, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33279849

RESUMEN

BACKGROUND: The spleen is an important contributor to the uncontrolled, excessive release of proinflammatory signals during sepsis that leads to the development of tissue injury and diffuse end-organ dysfunction. Therapeutic pulsed ultrasound (pUS) has been shown to inhibit splenic leukocyte release and reduce cytokine production in other inflammatory disease processes. We hypothesized that pUS treatment inhibits spleen-derived inflammatory responses and increases survival duration in rats with severe intra-abdominal sepsis leading to septic shock. MATERIALS AND METHODS: Rats with intra-abdominal sepsis, induced by cecal ligation and incision, underwent abdominal washout, intra-peritoneal administration of cefazolin, and then either no further treatment (control), splenectomy, or pUS of the spleen. Animals were observed for the primary endpoint of survival duration. RESULTS: Survival curves were significantly different for all groups (P < 0.01). Median survival increased from 9.5 h in control rats to 19.8 h in pUS rats and 35.0 h in splenectomy rats (P < 0.01). At 4 h after cecal ligation and incision, the pUS group had decreased splenic contraction and leukocyte count (P = 0.03) compared with control, indicating reduced exodus of splenic leukocytes. In addition, elevation in plasma TNF-α and MCP-1 was significantly attenuated in the pUS group (P < 0.05 versus control). Splenic ß2 adrenergic receptor levels and phosphorylated Akt were significantly more elevated in the pUS group (P < 0.01 versus control). CONCLUSIONS: pUS significantly prolonged the survival duration of rats with severe intra-abdominal sepsis. This treatment may be an effective, noninvasive therapy that dampens detrimental immune responses during septic shock by activating ß2 adrenergic receptor-Akt phosphorylation in the cholinergic anti-inflammatory pathway.


Asunto(s)
Leucocitos/inmunología , Choque Séptico/terapia , Bazo/efectos de la radiación , Esplenectomía , Terapia por Ultrasonido/métodos , Acetilcolina/metabolismo , Animales , Modelos Animales de Enfermedad , Humanos , Mediadores de Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Recuento de Leucocitos , Leucocitos/metabolismo , Fosforilación/inmunología , Fosforilación/efectos de la radiación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Receptores Adrenérgicos beta 2/metabolismo , Choque Séptico/sangre , Choque Séptico/inmunología , Transducción de Señal/inmunología , Transducción de Señal/efectos de la radiación , Bazo/citología , Bazo/metabolismo , Bazo/cirugía , Ondas Ultrasónicas
13.
Cerebrovasc Dis ; 50(2): 141-146, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33423033

RESUMEN

BACKGROUND: We sought to investigate the effect of obesity and BMI on functional outcome and rate of symptomatic intracranial hemorrhage (sICH) in a large sample of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT). METHODS: In a single-center retrospective, but prospectively collected data, study of patients with AIS treated with IVT in a 10-year period, patients were placed into groups based on their BMI defined as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (<30 kg/m2). The rate of sICH and discharge modified Rankin Scale (mRS) were compared between the groups using logistic regression analysis. RESULTS: In a total of 834 patients who received IVT for AIS during a 10-year period, 224 (27.0%) were obese. Obese patients did not have a higher rate of sICH after IVT for AIS on the unadjusted or adjusted analysis (adjusted OR 0.95, 95% CI 0.48-1.88). We did not find an association between obesity and poor functional outcome at discharge (adjusted OR 0.76, 95% CI 0.53-1.09). CONCLUSIONS: After adjusting for confounding factors such as age, baseline National Institute of Health Stroke Scale (NIHSS), and comorbidities, obesity was not associated with an unfavorable functional outcome at discharge nor with a higher risk of sICH in patients with AIS treated with IVT.


Asunto(s)
Índice de Masa Corporal , Fibrinolíticos/administración & dosificación , Obesidad/complicaciones , Terapia Trombolítica , Anciano , Anciano de 80 o más Años , Femenino , Fibrinolíticos/efectos adversos , Humanos , Infusiones Intravenosas , Hemorragias Intracraneales/inducido químicamente , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Obesidad/diagnóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Terapia Trombolítica/efectos adversos , Resultado del Tratamiento
14.
Transpl Infect Dis ; 23(1): e13458, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32894634

RESUMEN

Hepatitis B virus (HBV) can be transmitted from organ donor to recipient, but details of transmission events are not widely published. The Disease Transmission Advisory Committee (DTAC) evaluated 105 cases of potential donor derived transmission events of HBV between 2009-2017. Proven, probable or possible transmission of HBV occurred in 25 (23.8%) cases. Recipients of liver grafts were most commonly infected (20 of 21 exposed recipients) compared to 9 of 21 exposed non-hepatic recipients. Eleven of 25 donors were HBV core antibody (HBcAb) positive/HBV surface antigen (HBsAg) negative and infected 8/20 recipients. Of the 10 liver recipients and 1 liver-kidney recipient who received organs from these donors: six were not given antiviral prophylaxis, two developed infection after antiviral prophylaxis was discontinued, two developed HBV while on lamivudine prophylaxis, one was on antiviral prophylaxis and did not develop HBV viremia or antigenemia. One recipient of a HBcAb positive/HBsAg negative kidney developed active HBV infection. Unexpected donor-derived transmission of HBV was a rare event in reports to DTAC, but was often detected in the recipient late post-transplant. Six of 11 recipients (54.5%) of a liver from a HBcAb positive donor did not receive prophylaxis; all of these were potentially preventable with the use of anti-viral prophylaxis.


Asunto(s)
Hepatitis B , Obtención de Tejidos y Órganos , Comités Consultivos , Anticuerpos contra la Hepatitis B , Antígenos del Núcleo de la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B/inmunología , Humanos , Donantes de Tejidos
15.
Acta Neurol Scand ; 144(6): 663-668, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34314036

RESUMEN

OBJECTIVES: Safety of intravenous thrombolysis (IVT) within 3-4.5 hours of stroke onset in patients ≥80 years is still disputable. We evaluated the association of symptom onset-to-treatment time (SOTT) with the symptomatic intracranial hemorrhage (sICH), poor outcome, and mortality in patients≥80 years. MATERIALS AND METHODS: In a retrospective study, patients treated with IVT following stroke were registered. Outcomes were poor outcome (mRS>2), sICH/ECASS-2, and in-hospital mortality. We compared the patients≥80 years who received IVT within 3 hours with those receiving IVT within 3-4.5 hours. We further compared the patients who were <80 years with those ≥80 years and SOTT of 3-4.5 hours. RESULTS: Of 834 patients, 265 aged over 80. In those above 80 and in multivariable analysis, the associations of SOTT with poor outcome (aOR: 1.401, CI: 0.503-3.903, p=0.519), sICH (aOR=2.50, CI=0.76-8.26, p= 0.132) and mortality (aOR=1.12, CI=0.39-3.25, p= 0.833) were not significant. 106 patients received IVT within 3-4.5 hours. In multivariable analysis, the associations of age (≥80 versus <80) with poor outcome (aOR=1.87, CI=0.65-5.37, p=0.246), sICH (aOR=0.65, CI=0.14-3.11, p=0.590), and mortality (aOR=0.87, 95% CI=0.16-4.57, p=0.867) were not significant in patients with SOTT of 3-4.5 hours. CONCLUSION: IVT within 3-4.5 hours in patients ≥80 years is not associated with increased sICH, poor outcome, and mortality compared to the early time window, and also compared to the younger patients in 3-4.5 hours window period. The decision of IVT administration in this age group should not be made solely on the basis of stroke onset timing.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Administración Intravenosa , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Humanos , Estudios Retrospectivos , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Resultado del Tratamiento
16.
J Stroke Cerebrovasc Dis ; 30(5): 105678, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33640783

RESUMEN

INTRODUCTION: Current guidelines allow the administration of intravenous recombinant tissue plasminogen activator (IV r-tPA) to warfarin-treated patients with acute ischemic stroke (AIS) who have an international normalized ratio (INR) of ≤1.7. However, concerns remain about the safety of using IV r-tPA in this situation due to a conceivable risk of symptomatic intracranial hemorrhage (sICH), lack of dedicated randomized controlled trials and the conflicts in the available data. We aimed to determine the risk of sICH in warfarin-treated patients with subtherapeutic INR who received IV r-tPA for AIS in our large volume comprehensive center. METHODS: Patients who had received IV r-tPA for AIS in a 9.6-year period were retrospectively investigated (n = 834). Patients taking warfarin prior to presentation were identified (n = 55). One patient was excluded due to elevated INR beyond the acceptable range for IV r-tPA treatment. Because of the significant difference in the sample size (54 vs 779), warfarin group was matched with 54 non-warfarin patients adjusted for independent risk factors for sICH (age, admission NIHSS, history of diabetes). Good outcome was defined as mRS of 0-2 on discharge and sICH was defined as an ICH causing increase in NIHSS ≥4 or death. Warfarin-treated group was further dichotomized based on INR (1-1.3 vs 1.3-1.7) and safety and outcome measures were compared between resultant groups. RESULTS: No significant difference was found between warfarin-treated and the non-warfarin groups in terms of chance of good outcome on discharge (27.8% in warfarin group vs 26.4% in non-warfarin group; p-value >0.05), or the rate of occurrence of sICH (3.7% in warfarin group vs 11.1% in non-warfarin group; p-value >0.05). Furthermore, rate of sICH (5.1% in patients with INR <1.3 versus 0.0% in patients with INR 1.3-1.7; p-value >0.05) or chance of good outcome on discharge (28.2% of patients with INR <1.3 versus 26.7% in patients with INR 1.3-1.7; p-value >0.05) were not found to be different after the warfarin-treated group was dichotomized. CONCLUSION: Administration of IV r-tPA for AIS in warfarin-treated patients with subtherapeutic INR <1.7 does not increase the risk of sICH.


Asunto(s)
Anticoagulantes/uso terapéutico , Monitoreo de Drogas , Fibrinolíticos/administración & dosificación , Relación Normalizada Internacional , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Terapia Trombolítica , Activador de Tejido Plasminógeno/administración & dosificación , Warfarina/uso terapéutico , Administración Intravenosa , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Hemorragia Cerebral/inducido químicamente , Toma de Decisiones Clínicas , Bases de Datos Factuales , Femenino , Fibrinolíticos/efectos adversos , Humanos , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/mortalidad , Masculino , New York , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/mortalidad , Factores de Tiempo , Activador de Tejido Plasminógeno/efectos adversos , Resultado del Tratamiento , Warfarina/efectos adversos
17.
Int J Mol Sci ; 22(18)2021 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-34575994

RESUMEN

Global hypothermia prolongs survival in rats with intraabdominal feculent sepsis by inhibiting inflammatory responses. We hypothesized that topical neck cooling (TNC) has similar benefits. Septic shock was induced by cecal ligation and incision (CLI) in Sprague Dawley rats. Rats were randomized to sham laparotomy, control with CLI, CLI with TNC, or vagotomy at the gastroesophageal junction before CLI and TNC. Two more groups underwent peritoneal washout with and without TNC two hours after CLI. TNC significantly lowered neck skin temperature (16.7 ± 1.4 vs. 30.5 ± 0.6 °C, p < 0.05) while maintaining core body normothermia. TNC rats recovered from anesthesia 70 min earlier than the control (p < 0.05). Three hours following CLI, the control and vagotomy with TNC groups had significantly more splenic contraction, fewer circulating leukocytes and higher plasma IL-1ß, IL-10 and TNF-α levels than TNC rats (p < 0.05). TNC prolonged survival duration after CLI by a median of four hours vs. control (p < 0.05), but no benefit was seen if vagotomy preceded TNC. Peritoneal washout alone increased survival by 3 h (9.2 (7.8-10.5) h). Survival duration increased dramatically with TNC preceding washout, to a 56% survival rate (>10 days). TNC significantly prolonged the survival of rats with severe intraabdominal sepsis by inhibiting systemic proinflammatory responses by activating vagal anti-inflammatory pathways.


Asunto(s)
Hipertermia Inducida , Choque Séptico , Nervio Vago , Animales , Citocinas/sangre , Ratas , Ratas Sprague-Dawley , Choque Séptico/sangre , Choque Séptico/terapia
18.
Ann Neurol ; 85(1): 125-136, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30450637

RESUMEN

OBJECTIVE: Agonism of protease-activated receptor (PAR) 1 by activated protein C (APC) provides neuro- and vasculoprotection in experimental neuroinjury models. The pleiotropic PAR1 agonist, 3K3A-APC, reduces neurological injury and promotes vascular integrity; 3K3A-APC proved safe in human volunteers. We performed a randomized, controlled, blinded trial to determine the maximally tolerated dose (MTD) of 3K3A-APC in ischemic stroke patients. METHODS: The NeuroNEXT trial, RHAPSODY, used a novel continual reassessment method to determine the MTD using tiers of 120, 240, 360, and 540 µg/kg of 3K3A-APC. After intravenous tissue plasminogen activator, intra-arterial mechanical thrombectomy, or both, patients were randomized to 1 of the 4 doses or placebo. Vasculoprotection was assessed as microbleed and intracranial hemorrhage (ICH) rates. RESULTS: Between January 2015 and July 2017, we treated 110 patients. Demographics resembled a typical stroke population. The MTD was the highest-dose 3K3A-APC tested, 540 µg/kg, with an estimated toxicity rate of 7%. There was no difference in prespecified ICH rates. In exploratory analyses, 3K3A-APC reduced ICH rates compared to placebo from 86.5% to 67.4% in the combined treatment arms (p = 0.046) and total hemorrhage volume from an average of 2.1 ± 5.8 ml in placebo to 0.8 ± 2.1 ml in the combined treatment arms (p = 0.066). INTERPRETATION: RHAPSODY is the first trial of a neuroprotectant for acute ischemic stroke in a trial design allowing thrombectomy, thrombolysis, or both. The MTD was 540 µg/kg for the PAR1 active cytoprotectant, 3K3A-APC. A trend toward lower hemorrhage rate in an exploratory analysis requires confirmation. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02222714. ANN NEUROL 2019;85:125-136.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/cirugía , Proteína C/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Activador de Tejido Plasminógeno/administración & dosificación , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico por imagen , Terapia Combinada/métodos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Método Simple Ciego , Accidente Cerebrovascular/diagnóstico por imagen
19.
Cerebrovasc Dis ; 49(5): 503-508, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32927457

RESUMEN

AIM: The aim of this was to study the effects of statins and their intensity on symptomatic intracranial hemorrhage (sICH) and outcome after IV thrombolysis (IVT) for acute ischemic stroke (AIS). METHODS: We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with IVT for AIS in our center in a 10-year period. Patients were further characterized as any statin users versus non-users on admission to the emergency department. Statins were categorized in high intensity or low intensity statin based on its propensity to reduce lower low-density cholesterol by ≥45% or <45%, respectively. Safety and discharge modified Rankin Score were compared between statin users versus non-users and also between high-intensity versus low-intensity groups. RESULTS: A total of 834 patients received IVT for AIS in our center during a 10-year period. Multivariate models were adjusted for age, NIH Stroke Scale at admission, INR, and history of DM and atrial fibrillation. There was no association between odds of sICH and any statin use (OR = 0.52 [0.26-1.03], p = 0.06). In multivariate model, any statin use was not associated with odds of poor outcome (Table 4: OR = 1.01 [0.79-1.55], p = 0.57). There was no significant association between odds of sICH among patients on high-intensity statin compared to low intensity statin (multivariate model OR = 0.39 [0.11-1.40], p = 0.15). There was 47% reduced odds of poor outcome among patients on high-intensity statin as compared to low-intensity statin (OR = 0.53[0.32-0.88] p = 0.01). However, this significant association was lost in the multivariate model (OR = 0.60 [0.35-1.05], p = 0.07). CONCLUSION: Our study does not show any significant association between risk of sICH and poor outcome after IVT for patients on prior statin therapy. We also did not find significant association between the risk of sICH and poor outcome after IVT and the intensity of the stain used.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Dislipidemias/tratamiento farmacológico , Fibrinolíticos/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Administración Intravenosa , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico , Dislipidemias/diagnóstico , Femenino , Fibrinolíticos/efectos adversos , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Hemorragias Intracraneales/inducido químicamente , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Terapia Trombolítica/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
20.
Liver Transpl ; 25(7): 1043-1053, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31063679

RESUMEN

The appropriate duration of surgical antibiotic prophylaxis in orthotopic liver transplantation (OLT) in the presence of significant iatrogenic immunosuppression is unclear. We hypothesized that 72 hours of perioperative antibiotic prophylaxis would decrease rates of surgical site infection (SSI) in OLT patients when compared with intraoperative antibiotic prophylaxis alone. OLT recipients were randomized to receive either intraoperative antibiotics only (short antibiotics [SAs]) or 72 hours of perioperative antibiotics (extended antibiotics [EAs]). A total of 102 patients were randomized: 51 to the EA group and 51 to the SA group. Rates of SSI and nosocomial infection (NI) in the SA group were 19% and 17%, respectively, compared with 27% (SSI; P = 0.36) and 22% (NI; P = 0.47) in the EA group, although these differences were not statistically significant. Intensive care unit (ICU) length of stay (LOS), hospital LOS, 30-day mortality, and time to infection were also similar between the 2 groups. Patients developing infections had longer ICU LOS and hospital LOS and a higher association with reoperation, endoscopic retrograde cholangiopancreatography, and 30-day readmission. In conclusion, extending perioperative antibiotics to 72 hours from intraoperative dosing alone in OLT patients does not appear to decrease the incidence of SSI or NI. The results from this pilot trial with 60% power suggest that it is acceptable for OLT recipients to receive intraoperative antibiotic prophylaxis alone.


Asunto(s)
Antibacterianos/uso terapéutico , Profilaxis Antibiótica/métodos , Infección Hospitalaria/epidemiología , Trasplante de Hígado/efectos adversos , Infección de la Herida Quirúrgica/epidemiología , Infección Hospitalaria/etiología , Infección Hospitalaria/prevención & control , Esquema de Medicación , Femenino , Humanos , Incidencia , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Trasplante de Hígado/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Atención Perioperativa/métodos , Proyectos Piloto , Reoperación/estadística & datos numéricos , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control , Factores de Tiempo , Resultado del Tratamiento
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