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BACKGROUND: Mortality for patients receiving extracorporeal membrane oxygenation (ECMO) for COVID-19 increased over the course of the pandemic. We investigated the association between immunomodulators and mortality for patients receiving ECMO for COVID-19. METHODS: We retrospectively analysed the Extracorporeal Life Support Organisation registry from 1 January, 2020, through 31 December, 2021, to compare the outcomes of patients who received no immunomodulators, only corticosteroids, only other immunomodulators (selective interleukin blockers, janus-kinase inhibitors, convalescent plasma, and intravenous immunoglobulin), and a combination of corticosteroids and other immunomodulators administered either before or during ECMO. We used Cox regression models to estimate survival time until 90 days. We estimated the propensity score of receiving different immunomodulators using multinomial regression, and incorporated these scores into the regression models. RESULTS: We included 7181 patients in the final analysis; 6169 patients received immunomodulators either before or during ECMO. The 90-day survival was 58.1% (95%-CI 55.1-61.2%) for patients receiving no immunomodulators, 50.7% (95%-CI 49.0-52.5%) for those receiving only corticosteroids, 62.2% (95%-CI 57.4-67.0%) for those receiving other immunomodulators, and 48.5% (95%-CI 46.7-50.4%) for those receiving corticosteroids and other immunomodulators. Compared to patients without immunomodulators, patients receiving either corticosteroids alone (HR: 1.13, 95%-CI 1.01-1.28) or with other immunomodulators (HR: 1.21, 95%-CI: 1.07-1.54) had significantly shorter survival time, while patients receiving only other immunomodulators had significantly longer survival time (HR: 0.79, 95%-CI: 0.66-0.96). The receipt of immunomodulators (across all three groups) was associated with an increase in secondary infections. CONCLUSIONS: In this cohort study, we found that immunomodulators, in particular corticosteroids, were associated with significantly higher mortality amongst patients receiving ECMO for COVID-19, after adjusting for potential confounding variables and propensity score. In addition, patients receiving corticosteroids with or without other immunomodulators had longer ECMO runs, which has potential implications for resource allocation. While residual confounding likely remains, further studies are required to evaluate the timing of immunomodulators and better understand the possible mechanisms behind this association, including secondary infections.
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BACKGROUND: Fifty years since its inception, Light's criteria have aided in classifying pleural effusions (PEs) as exudates if 1 or more criteria are met. Thoracic ultrasound (US) emerges as a non-invasive technique for point of care use especially if pleural procedures are contemplated. OBJECTIVE: We aimed to develop a score based on radiological and US features that could separate exudates from transudates without serum and pleural fluid biochemical tests necessary for Light's criteria. METHODS: A prospective review of consecutive patients with PE who underwent thoracocentesis was performed. CXRs were evaluated for laterality followed by US for echogenicity, pleural nodularity, thickening and septations. PE was classified as exudate or transudate according to Light's criteria and corroborated with albumin gradient. A score combining radiological and US features was developed. RESULTS: We recruited 201 patients with PE requiring thoracocentesis. Mean age was 64 years, 51% were females, 164 (81.6%) were exudates, and 37 (18.4%) were transudates. Assigning 1-point for Diaphragmatic nodularity, Unilateral, Echogenicity, Pleural Thickening and Septations, DUETS ranged from 1 to 5. DUETS ≥2 indicated high likelihood for exudate (PPV 98.8%, NPV 100%) with 1% misclassification versus 6.9% using Light's criteria (p < 0.001). CONCLUSION: DUETS separated exudates from transudates with good accuracy, and could obviate paired serum and pleural fluid tests necessary for Light's criteria computation. Our study reflected real world practice where DUETS performed better than Light's criteria for PE that arose from more than one disease processes, and in the evaluation of patients with PE who have received diuretics.
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The optimal pharmacological prophylaxis for venous thromboembolism (VTE) after hip or knee arthroplasty is uncertain. We conducted a systematic review and network meta-analysis to compare the efficacy and safety of various medications. We searched multiple databases for randomized clinical trials (RCTs) comparing medications (including factor Xa inhibitors, factor IIa inhibitor, warfarin, unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], aspirin, pentasaccharide) for VTE prophylaxis post-arthroplasty. Outcomes included any postoperative VTE identified with screening, major bleeding, and death. We used LMWH as the main comparator for analysis and performed trial sequential analysis (TSA) for each pairwise comparison. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessments, Developments and Evaluations). We analyzed 70 RCTs (55,841 participants). Factor Xa inhibitors decreased postoperative VTE significantly compared with LMWH (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.44-0.68, high certainty). Pentasaccharides probably reduce VTE (OR: 0.61, 95% CI: 0.36-1.02, moderate certainty), while the factor IIa inhibitor dabigatran may reduce VTE (OR: 0.75, 95% CI: 0.40-1.42, low certainty). UFH probably increases VTE compared with LMWH (OR: 1.31, 95% CI: 0.91-1.89, moderate certainty), and other agents like warfarin, aspirin, placebo, and usual care without thromboprophylaxis increase VTE (high certainty). Factor Xa inhibitors may not significantly affect major bleeding compared with LMWH (OR: 1.06, 95% CI: 0.81-1.39, low certainty). No medications had a notable effect on mortality compared with LMWH (very low certainty). TSA suggests sufficient evidence for the benefit of factor Xa inhibitors over LMWH for VTE prevention. Compared with LMWH and aspirin, factor Xa inhibitors are associated with reduced VTE after hip or knee arthroplasty, without an increase in bleeding and likely no impact on mortality.
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Objective: Though frailty is associated with mortality, its impact on long-term survival after an ICU admission with COVID-19 is unclear. We aimed to investigate the association between frailty and long-term survival in patients after an ICU admission with COVID-19. Design Setting and Participants: This registry-based multicentre, retrospective, cohort study included all patients ≥16 years discharged alive from the hospital following an ICU admission with COVID-19 and documented clinical frailty scale (CFS). Data from 118 ICUs between 01/01/2020 through 31/12/2020 in New Zealand and 31/12/2021 in Australia were reported in the Australian and New Zealand Intensive Care Society Adult Patient Database. The patients were categorised as 'not frail' (CFS 1-3), 'mildly frail' (CFS 4-5) and 'moderately-to-severely frail' (CFS 6-8). Main Outcome Measures: The primary outcome was survival time up to two years, which we analysed using Cox regression models. Results: We included 4028 patients with COVID-19 in the final analysis. 'Moderately-to-severely frail' patients were older (66.6 [56.3-75.8] vs. 69.9 [60.3-78.1]; p < 0.001) than those without frailty (median [interquartile range] 53.0 [40.1-64.6]), had higher sequential organ failure assessment scores (p < 0.001), and less likely to receive mechanical ventilation (p < 0.001) than patients without frailty or mild frailty. After adjusting for confounders, patients with mild frailty (adjusted hazards ratio: 2.31, 95%-CI: 1.75-3.05) and moderate-to-severe frailty (adjusted hazards ratio: 2.54, 95%-CI: 1.89-3.42) had higher mortality rates than those without frailty. Conclusions: Frailty was independently associated with shorter survival times to two years in patients with severe COVID-19 in ANZ following hospital discharge. Recognising frailty provides individualised patient intervention in those with frailty admitted to ICUs with severe COVID-19. Clinical trial registration: Not applicable.
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OBJECTIVES: A nontrivial number of patients in ICUs experience persistent critical illness (PerCI), a phenomenon in which features of the ICU course more consistently predict mortality than the initial indication for admission. We aimed to describe PerCI among patients with critical illness caused by COVID-19, and these patients' short- and long-term outcomes. DESIGN: Multicenter retrospective cohort study. SETTING: Australian and New Zealand Intensive Care Society Adult Patient Database of 114 Australian ICUs between January 1, 2020, and March 31, 2022. PATIENTS: Patients 16 years old or older with COVID-19, and a documented ICU length of stay. EXPOSURE: The presence of PerCI, defined as an ICU length of stay greater than or equal to 10 days. MEASUREMENTS: We compared the survival time up to 2 years from ICU admission using time-varying robust-variance estimated Cox proportional hazards models. We further investigated the impact of PerCI in subgroups of patients, stratifying based on whether they survived their initial hospitalization. MAIN RESULTS: We included 4961 patients in the final analysis, and 882 patients (17.8%) had PerCI. ICU mortality was 23.4% in patients with PerCI and 6.5% in those without PerCI. Patients with PerCI had lower 2-year (70.9% [95% CI, 67.9-73.9%] vs. 86.1% [95% CI, 85.0-87.1%]; p < 0.001) survival rates compared with patients without PerCI. Patients with PerCI had higher mortality (adjusted hazards ratio: 1.734; 95% CI, 1.388-2.168); this was consistent across several sensitivity analyses. When analyzed as a nonlinear predictor, the hazards of mortality were inconsistent up until 10 days, before plateauing. CONCLUSIONS: In this multicenter retrospective observational study patients with PerCI tended to have poorer short-term and long-term outcomes. However, the hazards of mortality plateaued beyond the first 10 days of ICU stay. Further studies should investigate predictors of developing PerCI, to better prognosticate long-term outcomes.
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BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) may reduce mortality and improve neurological outcomes in patients with cardiac arrest. We updated our existing meta-analysis and trial sequential analysis to further evaluate ECPR compared to conventional CPR (CCPR). METHODS: We searched three international databases from 1 January 2000 through 1 November 2023, for randomised controlled trials or propensity score matched studies (PSMs) comparing ECPR to CCPR in both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). We conducted an updated random-effects meta-analysis, with the primary outcome being in-hospital mortality. Secondary outcomes included short- and long-term favourable neurological outcome and survival (30 days-1 year). We also conducted a trial sequential analysis to evaluate the required information size in the meta-analysis to detect a clinically relevant reduction in mortality. RESULTS: We included 13 studies with 14 pairwise comparisons (6336 ECPR and 7712 CCPR) in our updated meta-analysis. ECPR was associated with greater precision in reducing overall in-hospital mortality (OR 0.63, 95% CI 0.50-0.79, high certainty), to which the trial sequential analysis was concordant. The addition of recent studies revealed a newly significant decrease in mortality in OHCA (OR 0.62, 95% CI 0.45-0.84). Re-analysis of relevant secondary outcomes reaffirmed our initial findings of favourable short-term neurological outcomes and survival up to 30 days. Estimates for long-term neurological outcome and 90-day-1-year survival remained unchanged. CONCLUSIONS: We found that ECPR reduces in-hospital mortality, improves neurological outcome, and 30-day survival. We additionally found a newly significant benefit in OHCA, suggesting that ECPR may be considered in both IHCA and OHCA.
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Reanimação Cardiopulmonar , Humanos , Reanimação Cardiopulmonar/métodos , Oxigenação por Membrana Extracorpórea/métodos , Parada Cardíaca/terapia , Parada Cardíaca/mortalidade , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/mortalidadeRESUMO
BACKGROUND: The association between frailty and short-term and long-term outcomes in patients receiving elective surgery for cancer remains unclear, particularly in those admitted to the ICU. METHODS: In this multicentre retrospective cohort study, we included adults ≥16 yr old admitted to 158 ICUs in Australia from January 1, 2018 to March 31, 2022 after elective surgery for cancer. We investigated the association between frailty and survival time up to 4 yr (primary outcome), adjusting for a prespecified set of covariates. We analysed how this association changed in specific subgroups (age categories [<65, 65-80, ≥80 yr], and those who survived hospitalisation), and over time by splitting the survival information at monthly intervals. RESULTS: We included 35,848 patients (median follow-up: 18.1 months [inter-quartile range: 8.3-31.1 months], 19,979 [56.1%] male, median age 69.0 yr [inter-quartile range: 58.8-76.0 yr]). Some 3502 (9.8%) patients were frail (defined as clinical frailty scale ≥5). Frailty was associated with lower survival (hazard ratio: 1.72, 95% confidence interval [CI]: 1.59-1.86 compared with clinical frailty scale ≤4); this was concordant across several sensitivity analyses. Frailty was most strongly associated with mortality early on in follow-up, up to 10 months (hazard ratio: 1.39, 95% CI: 1.03-1.86), but this association plateaued, and its predictive capacity subsequently diminished with time up until 4 yr (1.96, 95% CI: 0.73-5.28). Frailty was associated with similar effects when stratified based on age, and in those who survived hospitalisation. CONCLUSIONS: Frailty was associated with poorer outcomes after an ICU admission after elective surgery for cancer, particularly in the short term. However, its predictive capacity with time diminished, suggesting a potential need for longitudinal reassessment to ensure appropriate prognostication in this population.
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Fragilidade , Neoplasias , Adulto , Idoso , Humanos , Masculino , Feminino , Fragilidade/epidemiologia , Idoso Fragilizado , Estudos de Coortes , Estudos Retrospectivos , Austrália/epidemiologia , Hospitalização , Unidades de Terapia Intensiva , Neoplasias/cirurgiaRESUMO
PURPOSE: Cardiogenic shock is associated with high mortality. In refractory shock, it is unclear if mechanical circulatory support (MCS) devices improve survival. We conducted a network meta-analysis to determine which MCS devices confers greatest benefit. METHODS: We searched MEDLINE, Embase, and Scopus databases through 27 August 2023 for relevant randomized controlled trials (RCTs) and propensity score-matched studies (PSMs). We conducted frequentist network meta-analysis, investigating mortality (either 30 days or in-hospital) as the primary outcome. We assessed risk of bias (Cochrane risk of bias 2.0 tool/Newcastle-Ottawa Scale) and as sensitivity analysis reconstructed survival data from published survival curves for a one-stage unadjusted individual patient data (IPD) meta-analysis using a stratified Cox model. RESULTS: We included 38 studies (48,749 patients), mostly reporting on patients with Society for Cardiovascular Angiography and Intervention shock stages C-E cardiogenic shock. Compared with no MCS, extracorporeal membrane oxygenation with intra-aortic balloon pump (ECMO-IABP; network odds ratio [OR]: 0.54, 95% confidence interval (CI): 0.33-0.86, moderate certainty) was associated with lower mortality. There were no differences in mortality between ECMO, IABP, microaxial ventricular assist device (mVAD), ECMO-mVAD, centrifugal VAD, or mVAD-IABP and no MCS (all very low certainty). Our one-stage IPD survival meta-analysis based on the stratified Cox model found only ECMO-IABP was associated with lower mortality (hazard ratio, HR, 0.55, 95% CI 0.46-0.66). CONCLUSION: In patients with cardiogenic shock, ECMO-IABP may reduce mortality, while other MCS devices did not reduce mortality. However, this must be interpreted within the context of inter-study heterogeneity and limited certainty of evidence.
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Coração Auxiliar , Choque Cardiogênico , Humanos , Choque Cardiogênico/terapia , Pontuação de Propensão , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: We aimed to conduct a systematic review and meta-analysis to assess the effects of anemia and anemia severity on patient outcomes in cardiac surgery and determine whether preoperative treatments confer postoperative benefit. SOURCE: We searched four international databases for observational and randomized studies published until 1 October 2022. Study quality was assessed via Newcastle-Ottawa scores and the Cochrane Risk-of-Bias 2 tool and certainty of evidence was rated with the Grading of Recommendations, Assessment, Development and Evaluations approach. We conducted random-effects meta-analyses for our primary outcome of mortality, for secondary outcomes including length of stay (LOS) in the hospital and intensive care unit, and for postsurgical complications. As part of a secondary analysis, we analyzed short-term preoperative anemia treatments and conducted trial sequential analysis of randomized trials to assess the efficacy of these treatment programs. PRINCIPAL FINDINGS: We included 35 studies (159,025 patients) in our primary meta-analysis. Preoperative anemia was associated with increased mortality (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.2 to 2.9; P < 0.001, high certainty). Study-level meta-regression revealed lower hemoglobin levels and studies with lower proportions of male patients to be associated with increased risk of mortality. Preoperative anemia was also associated with an increase in LOS and postsurgical complications. Our secondary analysis (seven studies, 1,012 patients) revealed short-term preoperative anemia treatments did not significantly reduce mortality (OR, 1.1; 95% CI, 0.65 to 1.9; P = 0.69). Trial sequential analysis suggested that there was insufficient evidence to conclude if treatment programs yield any benefit or harm. CONCLUSIONS: Preoperative anemia is associated with mortality and morbidity after cardiac surgery. More research is warranted to test the efficacy of current anemia treatment programs. STUDY REGISTRATION: PROSPERO (CRD42022319431); first submitted 17 April 2023.
RéSUMé: OBJECTIF: Notre objectif était de mener une revue systématique et une méta-analyse pour évaluer les effets de l'anémie et de la gravité de l'anémie sur les devenirs des patient·es en chirurgie cardiaque et déterminer si les traitements préopératoires conféraient un bénéfice postopératoire. SOURCES: Nous avons réalisé des recherches dans quatre bases de données internationales pour en extraire des études observationnelles et randomisées publiées jusqu'au 1er octobre 2022. La qualité des études a été évaluée à l'aide des scores de Newcastle-Ottawa et de l'outil Cochrane 2 sur le risque de biais, et la certitude des données probantes a été évaluée selon l'approche GRADE (Grading of Recommendations, Assessment, Development and Evaluations). Nous avons réalisé des méta-analyses à effets aléatoires pour notre critère d'évaluation principal de mortalité, pour les critères d'évaluation secondaires, notamment la durée du séjour à l'hôpital et à l'unité de soins intensifs, et pour les complications postopératoires. Dans le cadre d'une analyse secondaire, nous avons examiné les traitements préopératoires de l'anémie à court terme et effectué une analyse séquentielle d'études randomisées afin d'évaluer l'efficacité de ces modalités de traitement. CONSTATATIONS PRINCIPALES: Nous avons inclus 35 études portant sur 159 025 patient·es dans notre méta-analyse. L'anémie préopératoire était associée à une augmentation de la mortalité (rapport de cotes [RC], 2,5; intervalle de confiance [IC] à 95 %, 2,2 à 2,9; P < 0,001, certitude élevée). La méta-régression au niveau de l'étude a révélé que des taux d'hémoglobine plus faibles et des études avec des proportions plus faibles de patients masculins étaient associées à un risque accru de mortalité. L'anémie préopératoire était également associée à une augmentation de la durée de séjour et des complications postopératoires. Notre analyse secondaire (sept études, 1012 patient·es) a révélé que les traitements préopératoires de l'anémie à court terme ne réduisaient pas significativement la mortalité (RC, 1,1; IC 95 %, 0,65 à 1,9; P = 0,69). L'analyse séquentielle des études a suggéré qu'il n'y avait pas suffisamment de données probantes pour conclure si les modalités de traitement entraînaient un bénéfice ou un préjudice. CONCLUSION: L'anémie préopératoire est associée à la mortalité et à la morbidité après une chirurgie cardiaque. D'autres recherches sont justifiées pour tester l'efficacité des programmes actuels de traitement de l'anémie. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42022319431); première soumission le 17 avril 2023.
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Anemia , Procedimentos Cirúrgicos Cardíacos , Humanos , Masculino , Anemia/complicações , Anemia/epidemiologia , Anemia/terapia , Tempo de Internação , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Unidades de Terapia IntensivaRESUMO
Artificial intelligence (AI) and its application in classification of blood cells in the peripheral blood film is an evolving field in haematology. We performed a rapid review of the literature on AI and peripheral blood films, evaluating the condition studied, image datasets, machine learning models, training set size, testing set size and accuracy. A total of 283 studies were identified, encompassing 6 broad domains: malaria (n = 95), leukemia (n = 81), leukocytes (n = 72), mixed (n = 25), erythrocytes (n = 15) or Myelodysplastic syndrome (MDS) (n = 1). These publications have demonstrated high self-reported mean accuracy rates across various studies (95.5% for malaria, 96.0% for leukemia, 94.4% for leukocytes, 95.2% for mixed studies and 91.2% for erythrocytes), with an overall mean accuracy of 95.1%. Despite the high accuracy, the challenges toward real world translational usage of these AI trained models include the need for well-validated multicentre data, data standardisation, and studies on less common cell types and non-malarial blood-borne parasites.
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Leucemia , Malária , Humanos , Inteligência Artificial , Eritrócitos , Leucócitos , Malária/diagnósticoRESUMO
BACKGROUND: Recent advances in cancer therapeutics have improved outcomes, resulting in increasing candidacy of patients with metastatic cancer being admitted to intensive care units (ICUs). A large proportion of patients also have frailty, predisposing them to poor outcomes, yet the literature reporting on this is scarce. We aimed to assess the impact of frailty on survival in patients with metastatic cancer admitted to the ICU. METHODS: In this retrospective registry-based cohort study, we used data from the Australia and New Zealand Intensive Care Society Adult Patient (age ≥16 years) database to identify patients with advanced (solid and haematological cancer) and a documented Clinical Frailty scale (CFS) admitted to 166 Australian ICUs. Patients without metastatic cancer were excluded. We analysed the effect of frailty (CFS 5-8) on long-term survival, and how this effect changed in specific subgroups (cancer subtypes, age [<65 years or ≥65 years], and those who survived hospitalisation). Because estimates tend to cluster within centres and vary between them, we used Cox proportional hazards regression models with robust sandwich variance estimators to assess the effect of frailty on survival time up to 4 years after ICU admission between groups. FINDINGS: Between Jan 1, 2018, and March 31, 2022, 30â026 patients were eligible, and after exclusions 21â174 patients were included in the analysis; of these, 6806 (32·1%) had frailty, and 11â662 (55·1%) were male, 9489 (44·8%) were female, and 23 (0·1%) were intersex or self-reported indeterminate sex. The overall survival was lower for patients with frailty at 4 years compared with patients without frailty (29·5% vs 10·9%; p<0·0001). Frailty was associated with shorter 4-year survival times (adjusted hazard ratio 1·52 [95% CI 1·43-1·60]), and this effect was seen across all cancer subtypes. Frailty was associated with shorter survival times in patients younger than 65 years (1·66 [1·51-1·83]) and aged 65 years or older (1·40 [1·38-1·56]), but its effects were larger in patients younger than 65 years (pinteraction<0·0001). Frailty was also associated with shorter survival times in patients who survived hospitalisation (1·49 [1·40-1·59]). INTERPRETATION: In patients with metastatic cancer admitted to the ICU, frailty was associated with poorer long-term survival. Patients with frailty might benefit from a goal-concordant time-limited trial in the ICU and will need suitable post-intensive care supportive management. FUNDING: None.
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Fragilidade , Segunda Neoplasia Primária , Neoplasias , Idoso , Humanos , Masculino , Feminino , Idoso Fragilizado , Estudos de Coortes , Estudos Retrospectivos , Austrália/epidemiologia , Unidades de Terapia Intensiva , Neoplasias/terapia , Sistema de RegistrosRESUMO
Heart failure is a global health concern with significant implications for healthcare systems. Left ventricular assist devices (LVADs) provide mechanical support for patients with severe heart failure. However, the placement of the LVAD outflow graft within the aorta has substantial implications for hemodynamics and can lead to aortic insufficiency during long-term support. This study employs computational fluid dynamics (CFD) simulations to investigate the impact of different LVAD outflow graft locations on aortic hemodynamics. The introduction of valve morphology within the aorta geometry allows for a more detailed analysis of hemodynamics at the aortic root. The results demonstrate that the formation of vortex rings and subsequent vortices during the high-velocity jet flow from the graft interacted with the aortic wall. Time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI) indicate that modification of the outflow graft location changes mechanical states within the aortic wall and aortic valve. Among the studied geometric factors, both the height and inclination angle of the LVAD outflow graft are important in controlling retrograde flow to the aortic root, while the azimuthal angle primarily determines the rotational direction of blood flow in the aortic arch. Thus, precise positioning of the LVAD outflow graft emerges as a critical factor in optimizing patient outcomes by improving the hemodynamic environment.
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BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and clinical trials are conflicting and the factors influencing outcome have not been well established. METHODS: We conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach. FINDINGS: We included 29 observational and randomized studies involving 7,397 patients. Factors with moderate or high certainty of association with increased survival with favourable functional outcome include pre-arrest patient factors, such as younger age (odds ratio (OR) 2.13, 95% CI 1.52 to 2.99) and female sex (OR 1.37, 95% CI 1.11 to 1.70), as well as intra-arrest factors, such as shockable rhythm (OR 2.79, 95% CI 2.04 to 3.80), witnessed arrest (OR 1.68 (95% CI 1.16 to 2.42), bystander CPR (OR 1.55, 95% CI 1.19 to 2.01), return of spontaneous circulation (OR 2.81, 95% CI 2.19 to 3.61) and shorter time to cannulation (OR 1.14, 95% CI 1.17 to 1.69 per 10 minutes). INTERPRETATION: The findings of this review confirm several clinical concepts wellestablished in the cardiac arrest literature and their applicability to the patient for whom ECPR is considered - that is, the impact of pre-existing patient factors, the benefit of timely and effective CPR, as well as the prognostic importance of minimizing low-flow time. We advocate for the thoughtful consideration of these prognostic factors as part of a risk stratification framework when evaluating a patient's potential candidacy for ECPR.
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Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Feminino , Parada Cardíaca Extra-Hospitalar/terapia , Prognóstico , Razão de Chances , Estudos RetrospectivosRESUMO
BACKGROUND: With ideal mean arterial pressure (MAP) targets in resuscitated out-of-hospital cardiac arrest (OHCA) patients unknown, we performed a meta-analysis of randomised controlled trials (RCTs) to compare the effects of higher versus lower MAP targets. METHODS: We searched four databases until 1 May 2023 for RCTs reporting the effects of higher MAP targets (>70 mmHg) in resuscitated OHCA patients and conducted random-effects meta-analyses. The primary outcome was mortality while secondary outcomes were neurological evaluations, arrhythmias, acute kidney injury, and durations of mechanical ventilation and ICU stay. We conducted inverse-variance weighted strata-level meta-regression against a proportion of non-survivors to assess differences between reported MAPs. We also conducted a trial sequential analysis of RCTs. RESULTS: Four RCTs were included. Higher MAP was not associated with reduced mortality (OR: 1.09, 95%-CI: 0.84 to 1.42, p = 0.51), or improved neurological outcomes (OR: 0.99, 95%-CI: 0.77 to 1.27, p = 0.92). Such findings were consistent despite additional sensitivity analyses. Our robust variance strata-level meta-regression revealed no significant associations between mean MAP and the proportion of non-survivors (B: 0.029, 95%-CI: -0.023 to 0.081, p = 0.162), and trial sequential analysis revealed no meaningful survival benefit for higher MAPs. CONCLUSIONS: A higher MAP target was not significantly associated with improved mortality and neurological outcomes in resuscitated OHCA patients.
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BACKGROUND: Although outcomes of patients after cardiac arrest remain poor, studies have suggested that extracorporeal cardiopulmonary resuscitation (ECPR) might improve survival and neurological outcomes. We aimed to investigate any potential benefits of using ECPR over conventional cardiopulmonary resuscitation (CCPR) in patients with out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). METHODS: In this systematic review and meta-analysis, we searched MEDLINE via PubMed, Embase, and Scopus from Jan 1, 2000, to April 1, 2023, for randomised controlled trials and propensity-score matched studies. We included studies comparing ECPR with CCPR in adults (aged ≥18 years) with OHCA and IHCA. We extracted data from published reports using a prespecified data extraction form. We did random-effects (Mantel-Haenszel) meta-analyses and rated the certainty of evidence using the Grading of Recommendations, Assessments, Developments, and Evaluations (GRADE) approach. We rated the risk of bias of randomised controlled trials using the Cochrane risk-of-bias 2.0 tool, and that of observational studies using the Newcastle-Ottawa Scale. The primary outcome was in-hospital mortality. Secondary outcomes included complications during extracorporeal membrane oxygenation, short-term (from hospital discharge to 30 days after cardiac arrest) and long-term (≥90 days after cardiac arrest) survival with favourable neurological outcomes (defined as cerebral performance category scores 1 or 2), and survival at 30 days, 3 months, 6 months, and 1 year after cardiac arrest. We also did trial sequential analyses to evaluate the required information sizes in the meta-analyses to detect clinically relevant reductions in mortality. FINDINGS: We included 11 studies (4595 patients receiving ECPR and 4597 patients receiving CCPR) in the meta-analysis. ECPR was associated with a significant reduction in overall in-hospital mortality (OR 0·67, 95% CI 0·51-0·87; p=0·0034; high certainty), without evidence of publication bias (pegger=0·19); the trial sequential analysis was concordant with the meta-analysis. When considering IHCA only, in-hospital mortality was lower in patients receiving ECPR than in those receiving CCPR (0·42, 0·25-0·70; p=0·0009), whereas when considering OHCA only, no differences were found (0·76, 0·54-1·07; p=0·12). Centre volume (ie, the number of ECPR runs done per year in each centre) was associated with reductions in odds of mortality (regression coefficient per doubling of centre volume -0·17, 95% CI -0·32 to -0·017; p=0·030). ECPR was also associated with an increased rate of short-term (OR 1·65, 95% CI 1·02-2·68; p=0·042; moderate certainty) and long-term (2·04, 1·41-2·94; p=0·0001; high certainty) survival with favourable neurological outcomes. Additionally, patients receiving ECPR had increased survival at 30-day (OR 1·45, 95% CI 1·08-1·96; p=0·015), 3-month (3·98, 1·12-14·16; p=0·033), 6-month (1·87, 1·36-2·57; p=0·0001), and 1-year (1·72, 1·52-1·95; p<0·0001) follow-ups. INTERPRETATION: Compared with CCPR, ECPR reduced in-hospital mortality and improved long-term neurological outcomes and post-arrest survival, particularly in patients with IHCA. These findings suggest that ECPR could be considered for eligible patients with IHCA, although further research into patients with OHCA is warranted. FUNDING: None.