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1.
Clin Infect Dis ; 79(Supplement_3): S109-S112, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-38959299

RESUMO

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 on 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.


Assuntos
Diverticulite , Infecções Intra-Abdominais , Complicações Infecciosas na Gravidez , Humanos , Gravidez , Feminino , Diverticulite/diagnóstico por imagem , Adulto , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/diagnóstico por imagem , Complicações Infecciosas na Gravidez/diagnóstico , Doença Aguda , Diagnóstico por Imagem/métodos , Diagnóstico por Imagem/normas
2.
Clin Infect Dis ; 79(Supplement_3): S88-S93, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963047

RESUMO

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 on 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.


Assuntos
Infecções Intra-Abdominais , Humanos , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/microbiologia , Adulto , Medição de Risco , Criança , Gravidez , Feminino , Estados Unidos , Índice de Gravidade de Doença
3.
Clin Infect Dis ; 79(Supplement_3): S113-S117, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963815

RESUMO

This article 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 article, the panel provides recommendations for diagnostic imaging of suspected acute intra-abdominal abscess. The panel's recommendations are based on 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.


Assuntos
Abscesso Abdominal , Infecções Intra-Abdominais , Humanos , Gravidez , Feminino , Adulto , Abscesso Abdominal/diagnóstico por imagem , Abscesso Abdominal/microbiologia , Criança , Infecções Intra-Abdominais/diagnóstico por imagem , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/microbiologia , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Diagnóstico por Imagem/normas
4.
Clin Infect Dis ; 79(Supplement_3): S123-S126, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963816

RESUMO

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 on 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 Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.


Assuntos
Infecções Intra-Abdominais , Humanos , Gravidez , Infecções Intra-Abdominais/microbiologia , Infecções Intra-Abdominais/diagnóstico , Feminino , Adulto , Criança , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/diagnóstico , Estados Unidos
5.
Clin Infect Dis ; 79(Supplement_3): S118-S122, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963817

RESUMO

This article 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 guideline, the panel provides recommendations for obtaining blood cultures in patients with known or suspected intra-abdominal infection. The panel's recommendations are based on 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.


Assuntos
Hemocultura , Infecções Intra-Abdominais , Humanos , Gravidez , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/microbiologia , Feminino , Adulto , Criança , Hemocultura/normas , Hemocultura/métodos , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/microbiologia , Estados Unidos
6.
Clin Infect Dis ; 79(Supplement_3): S94-S103, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963819

RESUMO

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 (IDSA). In this paper, the panel provides recommendations for diagnostic imaging of suspected acute appendicitis. The panel's recommendations are based on 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.


Assuntos
Apendicite , Infecções Intra-Abdominais , Humanos , Apendicite/diagnóstico por imagem , Gravidez , Feminino , Adulto , Criança , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/diagnóstico por imagem , Infecções Intra-Abdominais/microbiologia , Complicações Infecciosas na Gravidez/diagnóstico , Diagnóstico por Imagem/métodos , Diagnóstico por Imagem/normas , Doença Aguda , Estados Unidos
7.
Clin Infect Dis ; 79(Supplement_3): S104-S108, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963820

RESUMO

This article is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intraabdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this article, the panel provides recommendations for diagnostic imaging of suspected acute cholecystitis and acute cholangitis. The panel's recommendations are based on 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 Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.


Assuntos
Colangite , Colecistite Aguda , Infecções Intra-Abdominais , Humanos , Colangite/diagnóstico por imagem , Gravidez , Feminino , Adulto , Colecistite Aguda/diagnóstico por imagem , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/diagnóstico por imagem , Criança , Complicações Infecciosas na Gravidez/diagnóstico , Diagnóstico por Imagem/métodos , Diagnóstico por Imagem/normas , Masculino
8.
Clin Infect Dis ; 79(Supplement_3): S81-S87, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965057

RESUMO

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 21 updated recommendations. These recommendations span risk assessment, diagnostic imaging, and microbiological evaluation. The panel's recommendations are based on 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.


Assuntos
Infecções Intra-Abdominais , Humanos , Gravidez , Feminino , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/microbiologia , Adulto , Criança , Medição de Risco , Diagnóstico por Imagem/métodos , Diagnóstico por Imagem/normas , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/microbiologia , Estados Unidos
9.
J Surg Res ; 295: 95-101, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38000260

RESUMO

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.


Assuntos
Cirurgia Geral , Internato e Residência , Humanos , Masculino , Feminino , Educação de Pós-Graduação em Medicina , Cirurgia Geral/educação
10.
J Surg Res ; 303: 224-232, 2024 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-39374565

RESUMO

INTRODUCTION: The search for an optimal drug delivery system capable of addressing a wide range of wounds and defects in regenerative medicine remains a challenge. Blood clots (BCs) have been implicated as a promising candidate due to their natural occurrence, autologous nature, and potential for tissue repair. The aim of this study is to investigate BC as a vehicle for antibiotic delivery and its effectiveness in infection control. METHODS: BCs derived from murine and porcine models were used to study the in vitro release of gentamicin and vancomycin over a 7-d period. Moreover, BCs conjugated with mesenchymal stem cells and these antibiotics were assessed for antimicrobial activity via microdilution and agar well diffusion, and quantification of vascular endothelial growth factor release through enzyme-linked immunosorbent assay. RESULTS: Conjugated BCs maintained a sustained release of gentamicin and vancomycin throughout the 7-d period. Functional tests confirmed antimicrobial activity with zones of inhibition comparable to antibiotic controls. Vascular endothelial growth factor quantification revealed a pronounced and sustained release, especially from BCs conjugated with male mesenchymal stem cells, suggesting a gender influence on therapeutic outcomes. This sex-specific variance underscores the need for tailored therapeutic approaches in regenerative medicine applications. CONCLUSIONS: We demonstrated the remarkable potential of BC as a drug delivery system through sustained antibiotic and growth factor release, both of which are key in preventing infection and promoting tissue regeneration. The ease and cost effectiveness of BC preparation as well as its favorable federal regulatory profile support the potential translational application of BCs as a natural biomaterial in regenerative medicine.

11.
Clin Infect Dis ; 77(9): e46-e56, 2023 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-37738671

RESUMO

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.


Assuntos
Antibacterianos , Infecções por Bactérias Gram-Negativas , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Hospitais
12.
J Surg Res ; 279: 285-295, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35802943

RESUMO

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.


Assuntos
Cirurgia Geral , Internato e Residência , Cirurgiões , Competência Clínica , Educação de Pós-Graduação em Medicina/métodos , Avaliação Educacional/métodos , Cirurgia Geral/educação , Humanos
13.
J Surg Res ; 259: 97-105, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33279849

RESUMO

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.


Assuntos
Leucócitos/imunologia , Choque Séptico/terapia , Baço/efeitos da radiação , Esplenectomia , Terapia por Ultrassom/métodos , Acetilcolina/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Contagem de Leucócitos , Leucócitos/metabolismo , Fosforilação/imunologia , Fosforilação/efeitos da radiação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Receptores Adrenérgicos beta 2/metabolismo , Choque Séptico/sangue , Choque Séptico/imunologia , Transdução de Sinais/imunologia , Transdução de Sinais/efeitos da radiação , Baço/citologia , Baço/metabolismo , Baço/cirurgia , Ondas Ultrassônicas
14.
Cerebrovasc Dis ; 50(2): 141-146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33423033

RESUMO

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.


Assuntos
Índice de Massa Corporal , Fibrinolíticos/administração & dosagem , Obesidade/complicações , Terapia Trombolítica , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Infusões Intravenosas , Hemorragias Intracranianas/induzido quimicamente , AVC Isquêmico/complicações , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Terapia Trombolítica/efeitos adversos , Resultado do Tratamento
15.
Transpl Infect Dis ; 23(1): e13458, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32894634

RESUMO

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.


Assuntos
Hepatite B , Obtenção de Tecidos e Órgãos , Comitês Consultivos , Anticorpos Anti-Hepatite B , Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/imunologia , Humanos , Doadores de Tecidos
16.
Acta Neurol Scand ; 144(6): 663-668, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34314036

RESUMO

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.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Resultado do Tratamento
17.
J Stroke Cerebrovasc Dis ; 30(5): 105678, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33640783

RESUMO

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.


Assuntos
Anticoagulantes/uso terapêutico , Monitoramento de Medicamentos , Fibrinolíticos/administração & dosagem , Coeficiente Internacional Normatizado , AVC Isquêmico/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Varfarina/uso terapêutico , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Hemorragia Cerebral/induzido quimicamente , Tomada de Decisão Clínica , Bases de Dados Factuais , Feminino , Fibrinolíticos/efeitos adversos , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , AVC Isquêmico/mortalidade , Masculino , New York , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento , Varfarina/efeitos adversos
18.
Int J Mol Sci ; 22(18)2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34575994

RESUMO

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.


Assuntos
Hipertermia Induzida , Choque Séptico , Nervo Vago , Animais , Citocinas/sangue , Ratos , Ratos Sprague-Dawley , Choque Séptico/sangue , Choque Séptico/terapia
19.
Ann Neurol ; 85(1): 125-136, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30450637

RESUMO

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.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/cirurgia , Proteína C/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Terapia Combinada/métodos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Método Simples-Cego , Acidente Vascular Cerebral/diagnóstico por imagem
20.
Cerebrovasc Dis ; 49(5): 503-508, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32927457

RESUMO

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.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Dislipidemias/diagnóstico , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hemorragias Intracranianas/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
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