Preclinical Studies on Mechanisms Underlying the Protective Effects of Propranolol in Traumatic Brain Injury: A Systematic Review.

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity amongst trauma patients. Its treatment is focused on minimizing progression to secondary injury. Administration of propranolol for TBI maydecrease mortality and improve functional outcomes. However, it is our sense that its use has not been universally adopted due to low certainty evidence. The literature was reviewed to explore the mechanism of propranolol as a therapeutic intervention in TBI to guide future clinical investigations. Medline, Embase, and Scopus were searched for studies that investigated the effect of propranolol on TBI in animal models from inception until June 6, 2023. All routes of administration for propranolol were included and the following outcomes were evaluated: cognitive functions, physiological and immunological responses. Screening and data extraction were done independently and in duplicate. The risk of bias for each individual study was assessed using the SYCLE's risk of bias tool for animal studies. Three hundred twenty-three citations were identified and 14 studies met our eligibility criteria. The data suggests that propranolol may improve post-TBI cognitive and motor function by increasing cerebral perfusion, reducing neural injury, cell death, leukocyte mobilization and p-tau accumulation in animal models. Propranolol may also attenuate TBI-induced immunodeficiency and provide cardioprotective effects by mitigating damage to the myocardium caused by oxidative stress. This systematic review demonstrates that propranolol may be therapeutic in TBI by improving cognitive and motor function while regulating T lymphocyte response and levels of myocardial reactive oxygen species. Oral or intravenous injection of propranolol following TBI is associated with improved cerebral perfusion, reduced neuroinflammation, reduced immunodeficiency, and cardio-neuroprotection in preclinical studies.

Liver transplantation with donation after medical assistance in dying: Case series and systematic review of the literature.

Medical assistance in dying (MAiD) has been a legally approved practice in Canada since 2016. Only recently have patients undergoing MAiD also been considered as donors for liver transplantation (LT). This study aimed to evaluate a case series of LT outcomes for recipients with MAiD donors and was paired with a systematic literature review of studies assessing the efficacy of MAiD-associated liver donation. A retrospective chart review of patients registered within the LT Registry at London Health Sciences Centre (LHSC) in London, Ontario, Canada, that had received MAiD donor LT was conducted to develop a case series. Descriptive statistics were produced based on available patient outcomes information. The systematic review included euthanasia due to MAiD being a term exclusive to Canada. Case series had a 100% 1-year graft survival rate, with 50% of patients experiencing early allograft dysfunction but having no significant clinical outcome. A single case of postoperative biliary complication was reported. Median warm ischemic time ranged from 7.8-13 minutes among case series and literature reviews. Utilization of donation after circulatory death allografts procured after MAiD appears to be promising. Mechanisms associated with potential impact in postoperative outcomes include relatively lower warm ischemic time relative to donation after circulatory death Maastricht III graft recipients.

Diagnostic sensitivity of pleural fluid cytology in malignant pleural effusions: systematic review and meta-analysis.

BACKGROUND: Pleural fluid cytology is an important diagnostic test used for the investigation of pleural effusions. There is considerable variability in the reported sensitivity for the diagnosis of malignant pleural effusions (MPE) in the literature. OBJECTIVE: The purpose of this review is to determine the diagnostic sensitivity of pleural fluid cytology for MPE, both overall and by tumour type, to better inform the decision-making process when investigating pleural effusions. DATA SOURCES: A literature search of EMBASE and MEDLINE was performed by four reviewers. Articles satisfying inclusion criteria were evaluated for bias using the QUADAS-2 tool. DATA EXTRACTION: For quantitative analysis, we performed a metaanalysis using a binary random-effects model to determine pooled sensitivity. Subgroup analysis was performed based on primary cancer site and meta-regression by year of publication. SYNTHESIS: Thirty-six studies with 6057 patients with MPE were included in the meta-analysis. The overall diagnostic sensitivity of pleural fluid cytology for MPE was 58.2% (95% CI 52.5% to 63.9%; range 20.5%-86.0%). There was substantial heterogeneity present among studies (I2 95.5%). For primary thoracic malignancies, sensitivity was highest in lung adenocarcinoma (83.6%; 95% CI 77.7% to 89.6%) and lowest in lung squamous cell carcinoma (24.2%; 95% CI 17.0% to 31.5%) and mesothelioma (28.9%; 95% CI 16.2% to 41.5%). For malignancies with extrathoracic origin, sensitivity was high for ovarian cancer (85.2%; 95% CI 74.2% to 96.1%) and modest for breast cancer (65.3%; 95% CI 49.8% to 80.8%). CONCLUSIONS: Pleural fluid cytology has an overall sensitivity of 58.2% for the diagnosis of MPE. Clinicians should be aware of the high variability in diagnostic sensitivity by primary tumour type as well as the potential reasons for false-negative cytology results.PROSPERO registration numberCRD42021231473.

Venous and Arterial Thrombosis in Ambulatory and Discharged COVID-19 Patients: A Systematic Review and Meta-analysis.

Introduction Venous and arterial thromboses are frequently observed complications in patients with severe novel coronavirus disease 2019 (COVID-19) infection who require hospital admission. In this study, we evaluate the epidemiology of venous and arterial thrombosis events in ambulatory and postdischarge patients with COVID-19 infection. Materials and Method EMBASE and MEDLINE were searched up to July 21, 2021, in addition to other sources. We included studies that assessed the epidemiology of venous and arterial thrombosis events in ambulatory and postdischarge COVID-19 patients. Results A total of 16 studies (102,779 patients) were identified. The overall proportion of venous thromboembolic events in all patients, that is, ambulatory and postdischarge, was 0.80% (95% confidence interval [CI]: 0.44-1.28), 0.28% (95% CI: 0.07-0.64), and 1.16% (95% CI: 0.69-1.74), respectively. Arterial events occurred in 0.75% (95% CI: 0.27-1.47) of all patients, 1.45% (95% CI: 1.10-1.86) of postdischarge patients, and 0.23% (95% CI: 0.019-0.66) of ambulatory patients. The pooled incidence rate estimates per 1,000 patient-days for VTE events were 0.06 (95% CI: 0.03-0.08) and 0.12 (95% CI: 0.07-0.19) for outpatients and postdischarge, respectively, whereas for arterial events were 0.10 (95% CI: 0-0.30) and 0.26 (95% CI: 0.16-0.37). Conclusion This study found a low risk of venous and arterial thrombi in ambulatory and postdischarge COVID-19 patients, with a higher risk in postdischarge patients compared with ambulatory patients. This suggests that regular universal thromboprophylaxis in these patient populations is probably not necessary.

Effect of Needle Size on Diagnosis of Sarcoidosis with Endobronchial Ultrasound-guided Transbronchial Needle Aspiration: Systematic Review and Meta-Analysis.

Background: Sarcoidosis is a multisystem disease characterized by noncaseating granulomatous inflammation that most commonly involves the lungs. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become an invaluable tool in the assessment of patients with mediastinal and/or hilar lymphadenopathy. Objective: It has been hypothesized that use of the larger 19-gauge (G) needle with EBUS-TBNA improves diagnostic sensitivity in sarcoidosis. However, it is unclear whether the existing literature supports this supposition. Data Sources: A literature search of Embase and Medline was performed by two reviewers. Included articles were evaluated for bias using the QUADAS-2 tool. Data Extraction: For quantitative analysis, we performed a meta-analysis using a binary random-effects model to determine pooled sensitivity. Subgroup analysis was performed based on needle size, use of rapid on-site evaluation (ROSE), study design, and prevalence of sarcoidosis in study group. Synthesis: Sixty-five studies with a total of 4,242 patients were included in the meta-analysis. Overall pooled sensitivity for diagnosis of sarcoidosis was 83.99% (95% confidence interval [CI], 81.22-86.53) among all studies. The 19G subgroup had a significantly higher sensitivity (93.73%; 95% CI, 89.72-97.74%; I2 = 0.00%; P < 0.01) compared with the 21G subgroup (84.61%; 95% CI, 78.80-90.42%; I2 = 69.83%), 22G subgroup (84.07%; 95% CI, 80.90-87.24%; I2 = 85.21%) or unspecified 21G/22G subgroup (78.85%; 95% CI, 70.81-86.90%; I2 = 84.47%). There were no significant differences with use of ROSE or prevalence of sarcoidosis or by study design. Conclusions: The use of 19G needles during EBUS-TBNA had the highest diagnostic sensitivity based on available studies. Further randomized controlled trials using 19G needles should be considered in patients with suspected sarcoidosis.

Bleeding Risk in Nonvalvular Atrial Fibrillation Patients Receiving Direct Oral Anticoagulants and Warfarin: A Systematic Review and Meta-Analysis of Observational Studies.

Introduction In randomized trials in atrial fibrillation (AF) patients on direct oral anticoagulants (DOACs) have a lower risk of bleeding compared with warfarin. However, data from randomized trials may not extrapolate to general population. We aimed to determine the risk of bleeding in patients on DOACs in observational studies. Materials and Methods Observational studies from 1990 to January 2019 were included. A pooled effect hazard ratio (HR) was calculated with a random effects model using the generic inverse variance method. Subgroup analyses according to previous anticoagulants exposure, study type, funding source, and DOAC type (direct thrombin inhibitors vs. factor Xa inhibitors) were conducted. Results A total of 35 studies comprising 2,356,201 patients were included. The average pooled HR for observational data was 0.78 (95% confidence interval [CI] 0.71, 0.85). There were no statistically significant differences in pooled HR by previous exposure to anticoagulants, DOAC type (direct thrombin vs. factor Xa inhibitors), study type, and funding source. Among patients receiving factor Xa inhibitors, patients on apixaban had a lower risk of bleeding compared with warfarin (HR 0.60, 95% CI 0.50, 0.71, p < 0.001) in contrast to those on rivaroxaban (HR 0.98, 95% CI 0.91, 1.06, p = 0.60). Conclusion In observational studies, AF patients on DOACs experience less bleeding events compared with warfarin; however, apixaban and dabigatran, but not rivaroxaban, have a lower risk of bleeding than warfarin.

Post-thrombotic syndrome and recurrent thromboembolism in patients with upper extremity deep vein thrombosis: A systematic review and meta-analysis.

INTRODUCTION: There is limited data on the occurrence of complications in patients with upper extremity deep vein thrombosis (UEDVT). AIMS: We aimed to determine the frequency of post-thrombotic syndrome (PTS), thrombosis recurrence and major bleeding (MB) in patients with UEDVT. MATERIAL AND METHODS: We conducted a systematic review of the literature including studies from 1970 onwards. We included observational studies, randomized trials, or cases series including >20 patients. We calculated pooled proportions using a random effects model. Subgroup analyses according to etiology and treatment modality were conducted. RESULTS: A total of 62 studies comprising 3550 patients were included. The pooled proportions for PTS and recurrence were 19.4% (95% CI 11.3-27.6) and 7.5% (95% CI 4.1-10.9), respectively. With a mean follow up of 6 months, the proportion of PTS was higher in patients with primary (unprovoked) UEDVT compared to secondary, whereas recurrence was higher in secondary UEDVT. PTS was more frequent in patients treated with anticoagulation alone compared to thrombolysis or surgical decompression. The pooled proportion for MB was 5.0% (95% CI 0.3-9.7) after anticoagulation alone and 3.8% (95% CI: 2.4-5.8%) after thrombolysis and/or surgery. CONCLUSIONS: This study suggests that UEDVT is associated with significant rates of PTS and recurrence and its treatment has a relatively low risk of major bleeding. Differences exist depending on etiology and treatment modality.

Ketamine-Propofol Versus Propofol Alone for Procedural Sedation in the Emergency Department: A Systematic Review and Meta-analysis.

OBJECTIVES: Propofol is an agent commonly used for procedural sedation and analgesia (PSA) in the emergency department (ED), but it can cause respiratory depression and hypotension. The combination of ketamine-propofol (K-P) is an alternative that theoretically provides a reduction in adverse events compared to propofol. The primary objective of this review was to determine if K-P has a lower frequency of adverse respiratory events in patients undergoing PSA in the ED than propofol alone. Secondary objectives were to compare the proportion of overall adverse events, sedation time, procedure time, and recovery time between K-P and propofol. METHODS: Electronic searches of Medline, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL were conducted and reference lists were hand-searched. Randomized controlled trials (RCTs) published in English comparing the use of K-P to propofol alone for PSA in the ED were included. RESULTS: Six RCTs were included with a combined total of 932 patients (K-P = 520, propofol = 412). Five RCTs reported the proportion of adverse respiratory events; the pooled estimate revealed fewer adverse respiratory events with K-P compared to propofol (29.0% vs. 35.4%; risk ratio [RR] = 0.82; 95% confidence interval [CI] = 0.68 to 0.99). There was no significant difference with respect to the proportion of overall adverse events (38.8% vs. 42.5%; RR = 0.88; 95% CI = 0.75 to 1.04). Procedure time was similar when the groups were compared. CONCLUSIONS: The premise of combining ketamine with propofol is based on the many synergies that theoretically exist between these two agents. In this study, K-P had a lower frequency of adverse respiratory events in patients undergoing PSA in the ED compared to propofol alone.

The effect of loss to follow-up on treatment of blunt traumatic thoracic aortic injury.

OBJECTIVE: Loss to follow-up (LTFU) can be a major difficulty for any clinical research study. The objective of this systematic review was to assess the extent of LTFU and its potential effect in studies of adult trauma patients with blunt thoracic aortic injuries (BTAIs). METHODS: Studies comparing management of BTAIs were systematically reviewed. Duplicate independent review was used for study selection, data abstraction, and critical appraisals. RESULTS: Thirty-six studies were included for synthesis, of which 94.1% applied a retrospective cohort design to prospective institutional databases. The mean LTFU at 1 year was 26.5% ± 31.6% for endovascular repair and 20.6% ± 34.2% for open repair groups. Not having a surgical/interventional specialist as a first or senior author was associated with a 39.7% higher LTFU at 1 year (P = .002). Studies with a higher risk of bias, later publication year, or North American origin were associated with a significantly higher risk for LTFU at 1 year (P ≤ .001). Nearly half of included studies assessed in-hospital outcomes exclusively. Only 38.2% explicitly reported LTFU data. Eight studies explicitly described the method of dealing with LTFU: eight used survival analysis and one used a national Social Security Death Index. Sensitivity analyses using plausible worst-case LTFU scenarios resulted in 14% to 17% of studies changing direction of effect. CONCLUSIONS: There is significant LTFU in trauma studies comparing operative methods for BTAIs. LTFU is generally handled and reported suboptimally, and sensitivity analyses suggest that study results are sensitive to differential LTFU. This has implications for the evidence-based choice of the operative method. Some protective factors that may aid in reducing LTFU were identified, one of which was involvement of a surgical or interventional specialist as a key author.