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BACKGROUND: Identifying candidates for extracorporeal cardiopulmonary resuscitation (eCPR) is challenging, and novel predictive markers are urgently needed. Hyperfibrinolysis is linked to tissue hypoxia and is associated with poor outcomes in out-of-hospital cardiac arrest (OHCA). Rotational thromboelastometry (ROTEM) can detect or rule out hyperfibrinolysis, and could, therefore, provide decision support for initiation of eCPR. We explored early detection of hyperfibrinolysis in patients with refractory OHCA referred for eCPR. METHODS: We analysed ROTEM results and resuscitation parameters of 57 adult patients with ongoing OHCA who presented to our ICU for eCPR evaluation. RESULTS: Hyperfibrinolysis, defined as maximum lysis ≥15%, was present in 36 patients (63%) and was associated with higher serum lactate, lower arterial blood pH, and increased low-flow intervals. Of 42 patients who achieved return of circulation, 28 had a poor 30-day outcome. The incidence of hyperfibrinolysis was higher in the poor outcome group compared with patients with good outcomes (75% [21 of 28] vs 7.1% [1 of 14]; P<0.001). The ratio of EXTEM A5 to lactate concentration showed good predictive value in detecting hyperfibrinolysis (AUC of 0.89 [95% confidence interval 0.8-1]). CONCLUSIONS: Hyperfibrinolysis was common in patients with refractory cardiac arrest, and was associated with poor prognosis. The combination of high lactate with early clot firmness values, such as EXTEM A5, appears promising for early detection of hyperfibrinolysis. This finding could facilitate decisions to perform eCPR, particularly for patients with prolonged low-flow duration but lacking hyperfibrinolysis.
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Reanimação Cardiopulmonar , Fibrinólise , Parada Cardíaca Extra-Hospitalar , Tromboelastografia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Tromboelastografia/métodos , Reanimação Cardiopulmonar/métodos , Prognóstico , Idoso , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/sangue , Parada Cardíaca Extra-Hospitalar/complicações , Fibrinólise/fisiologia , Oxigenação por Membrana Extracorpórea/métodos , Adulto , Ácido Láctico/sangue , Estudos RetrospectivosRESUMO
OBJECTIVES: This study aims to describe physicians' perspectives on the use of computed tomography (CT) in patients with sepsis. METHODS: In January 2022, physicians of a large European university medical center were surveyed using a web-based questionnaire asking about their views on the role of CT in sepsis. A total of 371 questionnaires met the inclusion criteria and were analyzed using work experience, workplace, and medical specialty of physicians as variables. Chi-square tests were performed. RESULTS: Physicians considered the ability to detect an unknown focus as the greatest benefit of CT scans in sepsis (70.9%, n = 263/371). Two clinical criteria - "signs of decreased vigilance" (89.2%, n = 331/371) and "increased catecholamine demand" (84.7%, n = 314/371) - were considered highly relevant for a CT request. Elevated procalcitonin (82.7%, n = 307/371) and lactate levels (83.6%, n = 310/371) were consistently found to be critical laboratory values to request a CT. As long as there is evidence of infection in one organ region, most physicians (42.6%, n = 158/371) would order a CT scan based on clinical assessment. Combined examination of the chest, abdomen, and pelvis was favored (34.8%, n = 129/371) in cases without clinical clues of an infection source. A time window of ≥ 1-6 h was preferred for both CT examinations (53.9%, n = 200/371) and CT-guided interventions (59.3%, n = 220/371) in patients with sepsis. CONCLUSION: Despite much consensus, there are significant differences in attitudes towards the use of CT in septic patients among physicians from different workplaces and medical specialties. Knowledge of these perspectives may improve patient management and interprofessional communication. KEY POINTS: Despite interdisciplinary consensus on the use of CT in sepsis, statistically significant differences in the responses are apparent among physicians from different workplaces and medical specialties. The detection of a previously unknown source of infection and the ability to plan interventions and/or surgery based on CT findings are considered key advantages of CT in septic patients. Timing of CT reflects the requirements of specific disciplines.
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Médicos , Sepse , Humanos , Sepse/diagnóstico por imagem , Sepse/etiologia , Centros Médicos Acadêmicos , Tomografia Computadorizada por Raios X , Inquéritos e QuestionáriosRESUMO
Purpose: Prognosis of sarcoma patients is improving, with a better understanding of sarcomagenesis revealing novel therapeutic targets. However, aggressive chemotherapy remains an essential part of treatment, bearing the risk of severe side effects that require intensive medical treatment. Available data on the characteristics and clinical outcome of sarcoma patients admitted to intensive care units (ICU) are sparse. Patients and Methods: We performed a retrospective analysis of sarcoma patients admitted to the ICU from 2005 to 2022. Patients ≥18 years with histologically proven sarcoma were included in our study. Results: Sixty-six patients were eligible for analysis. The following characteristics had significant impact on overall survival: sex (p=0.046), tumour localization (p=0.02), therapeutic intention (p=0.02), line of chemotherapy (p<0.001), SAPS II score (p=0.03) and SOFA score (p=0.02). Conclusion: Our study confirms the predictive relevance of established sepsis and performance scores in sarcoma patients. For overall survival, common clinical characteristics are also of significant value. Further investigation is needed to optimize ICU treatment of sarcoma patients.
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BACKGROUND: Increasing evidence suggests that secondary sclerosing cholangitis (SSC), which can lead to cirrhosis or liver failure, may be a hepatobiliary long-term complication of COVID-19. The aim of this study was to estimate the frequency and outcome of this COVID-19 sequela and to identify possible risk factors. METHODS: This observational study, conducted at University Hospital Charité Berlin and Unfallkrankenhaus Berlin, Germany, involved hospitalized patients with COVID-19 pneumonia, including 1082 ventilated COVID-19 patients. We compared COVID-19 patients who developed SSC with a COVID-19 control group by univariate and multivariate analyses. RESULTS: SSC occurrence after COVID-19 was observed exclusively in critically ill patients with invasive ventilation, albeit with extreme clustering among them. One in every 43 invasively ventilated COVID-19 patients developed this complication. Risk factors preceding the development of secondary sclerosing cholangitis in critically ill COVID-19 patients (SSC-CIP) were signs of systemic reduced blood oxygen supply (e.g., low PaO2/FiO2, ischemic organ infarctions), multi-organ failure (high SOFA score) at admission, high fibrinogen levels and intravenous ketamine use. Multivariate analysis confirmed fibrinogen and increased plasma lactate dehydrogenase as independent risk factors associated with cholangiopathy onset. The 1-year transplant-free survival rate of COVID-19-associated SSC-CIP was 40%. CONCLUSIONS: COVID-19 causes SSC-CIP in a substantial proportion of critically ill patients. SSC-CIP most likely develops due to severe tissue hypoxia and fibrinogen-associated circulatory disturbances. A significant increase of patients with SSC-CIP is to be expected in the post-COVID era.
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COVID-19 , Colangite Esclerosante , Humanos , Colangite Esclerosante/complicações , Colangite Esclerosante/terapia , Estado Terminal , COVID-19/complicações , Cirrose Hepática/complicações , FibrinogênioRESUMO
Heterogeneous light-driven catalysis is a cornerstone of sustainable energy conversion. Most catalytic studies focus on bulk analyses of the hydrogen and oxygen evolved, which impede the correlation of matrix heterogeneities, molecular features, and bulk reactivity. Here, we report studies of a heterogenized catalyst/photosensitizer system using a polyoxometalate water oxidation catalyst and a model, molecular photosensitizer that were co-immobilized within a nanoporous block copolymer membrane. Via operando scanning electrochemical microscopy (SECM), light-induced oxygen evolution was determined using sodium peroxodisulfate (Na2 S2 O8 ) as sacrificial electron acceptor. Ex situ element analyses provided spatially resolved information on the local concentration and distribution of the molecular components. Infrared attenuated total reflection (IR-ATR) studies of the modified membranes showed no degradation of the water oxidation catalyst under the reported light-driven conditions.
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BACKGROUNDResults of many randomized trials on COVID-19 convalescent plasma (CCP) have been reported, but information on long-term outcome after CCP treatment is limited. The objectives of this extended observation of the randomized CAPSID trial are to assess long-term outcome and disease burden in patients initially treated with or without CCP.METHODSOf 105 randomized patients, 50 participated in the extended observation. Quality of life (QoL) was assessed by questionnaires and a structured interview. CCP donors (n = 113) with asymptomatic to moderate COVID-19 were included as a reference group.RESULTSThe median follow-up of patients was 396 days, and the estimated 1-year survival was 78.7% in the CCP group and 60.2% in the control (P = 0.08). The subgroup treated with a higher cumulative amount of neutralizing antibodies showed a better 1-year survival compared with the control group (91.5% versus 60.2%, P = 0.01). Medical events and QoL assessments showed a consistent trend for better results in the CCP group without reaching statistical significance. There was no difference in the increase in neutralizing antibodies after vaccination between the CCP and control groups.CONCLUSIONThe trial demonstrated a trend toward better outcome in the CCP group without reaching statistical significance. A predefined subgroup analysis showed a significantly better outcome (long-term survival, time to discharge from ICU, and time to hospital discharge) among those who received a higher amount of neutralizing antibodies compared with the control group. A substantial long-term disease burden remains after severe COVID-19.Trial registrationEudraCT 2020-001310-38 and ClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health).
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COVID-19 , Humanos , COVID-19/terapia , COVID-19/etiologia , SARS-CoV-2 , Qualidade de Vida , Capsídeo , Seguimentos , Imunização Passiva/efeitos adversos , Anticorpos Neutralizantes , Anticorpos AntiviraisRESUMO
While New Public Management practices (NPM) have been adopted in academia and higher education over the past two decades, this paper is investigating their role in a specifically socio-philosophical way: The preeminent question is what organization of science is likely to make science and research work well in the context of a complex society. The starting point is an obvious intuition: that academia would be "economized" by NPM (basically, that something is coming from the outside and is disturbing the inside). Habermas provides a sophisticated theorization for this intuition. In contrast, the thesis advanced here is that we should consider NPM potentially problematic-but not for descending from economics or administration outside academia. It is because NPM often cannot help research and science to function well. In this (rather "essayistic" than strictly deductive) consideration, I will therefore tentatively discuss an alternative approach that takes up critical intuitions while transposing them into a different setting. If we understand science and research as a form of life, a different picture emerges that can still bring immanent standards to bear, but at the same time compose them more broadly. This outlines a socio-philosophical critique of NPM. Accordingly, the decisive factor is not NPM's provenance. What is decisive is that it addresses some organizational problems while at the same time creating new ones. At the end, an outlook is sketched on how the specific situation of NPM allows some hypotheses on academy's [by "academy", I am referring to the whole research community (like "academia")] future organization. Ex negativo, it seems likely that qualitative evaluation criteria and creative freedom will have to play a greater role.
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Morbidity and mortality of COVID-19 is increased in patients with inborn errors of immunity (IEI). Age and comorbidities and also impaired type I interferon immunity were identified as relevant risk factors. In patients with primary antibody deficiency (PAD) and lack of specific humoral immune response to SARS-CoV-2, clinical disease outcome is very heterogeneous. Despite extensive clinical reports, underlying immunological mechanisms are poorly characterized and levels of T cellular and innate immunity in severe cases remain to be determined. In the present study, we report clinical and immunological findings of 5 PAD patients with severe and fatal COVID-19 and undetectable specific humoral immune response to SARS-CoV-2. Reactive T cells to SARS-CoV-2 spike (S) and nucleocapsid (NCAP) peptide pools were analyzed comparatively by flow cytometry in PAD patients, convalescents and naïve healthy individuals. All examined PAD patients developed a robust T cell response. The presence of polyfunctional cytokine producing activated CD4+ T cells indicates a memory-like phenotype. An analysis of innate immune response revealed elevated CD169 (SIGLEC1) expression on monocytes, a surrogate marker for type I interferon response, and presence of type I interferon autoantibodies was excluded. SARS-CoV-2 RNA was detectable in peripheral blood in three severe COVID-19 patients with PAD. Viral clearance in blood was observed after treatment with COVID-19 convalescent plasma/monoclonal antibody administration. However, prolonged mucosal viral shedding was observed in all patients (median 67 days) with maximum duration of 127 days. PAD patients without specific humoral SARS-CoV-2 immunity may suffer from severe or fatal COVID-19 despite robust T cell and normal innate immune response. Intensified monitoring for long persistence of SARS-CoV-2 viral shedding and (prophylactic) convalescent plasma/specific IgG as beneficial treatment option in severe cases with RNAemia should be considered in seronegative PAD patients.
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COVID-19 , Interferon Tipo I , Doenças da Imunodeficiência Primária , Anticorpos Antivirais , COVID-19/terapia , Humanos , Imunidade Humoral , Imunização Passiva , RNA Viral , SARS-CoV-2 , Linfócitos T , Soroterapia para COVID-19RESUMO
BACKGROUND: We compared filter survival and citrate-induced complications during continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in COVID-19 and Non-COVID-19 patients. METHODS: In this retrospective study we included all consecutive adult patients (n = 97) treated with RCA-CRRT. Efficacy and complications of RCA-CRRT were compared between COVID-19 and Non-COVID-19 patients. RESULTS: Mean filter run-time was significantly higher in COVID-19 patients compared to Non-COVID-19 patients (68.4 (95%CI 67.0-69.9) vs. 65.2 (95%CI 63.2-67.2) hours, respectively; log-rank 0.014). COVID-19 patients showed significantly higher activated partial thromboplastin time (aPTT) throughout the CRRT due to intensified systemic anticoagulation compared to Non-COVID-19 patients (54 (IQR 45-61) vs. 47 (IQR 41-58) seconds, respectively; p < 0.001). A significantly higher incidence of metabolic alkalosis, hypercalcemia and hypernatremia, consistent with reduced filter patency and citrate overload, was observed in COVID-19 patients compared to Non-COVID-19 patients (19.1% vs. 12.7%, respectively; p = 0.04). These metabolic disarrangements were resistant to per-protocol adjustments and disappeared after replacement of the CRRT-filter. CONCLUSIONS: RCA-CRRT in COVID-19 patients with intensified systemic anticoagulation provides an adequate filter lifespan. However, close monitoring of the acid-base balance appears warranted, as these patients tend to develop reduced filter patency leading to a higher incidence of citrate overload and metabolic disturbances. TRIAL REGISTRATION (LOCAL AUTHORITY): EA1/285/20 (Ethikkommission der Charité - Universitätsmedizin Berlin); date of registration 08.10.2020.
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COVID-19 , Terapia de Substituição Renal Contínua , Anticoagulantes/efeitos adversos , Citratos , Ácido Cítrico/efeitos adversos , Estado Terminal , Humanos , Estudos Retrospectivos , SARS-CoV-2RESUMO
INTRODUCTION: Hyperlactatemia is a regular condition in the intensive care unit, which is often associated with adverse outcomes. Control of the triggering condition is the most effective treatment of hyperlactatemia, but since this is mostly not readily possible, extracorporeal renal replacement therapy (RRT) is often tried as a last resort. The present study aims to evaluate the factors that may contribute to the decision whether to start RRT or not and the potential impact of the start of RRT on the outcome in patients with severe lactic acidosis (SLA) (lactate ≥5 mmol/L). MATERIALS AND METHODS: We conducted a retrospective single-center cohort analysis over a 3-year period including all patients with a lactate level ≥5 mmol/L. Patients were considered as treated with RRT because of SLA if RRT was started within 24 h after reaching a lactate level ≥5 mmol/L. RESULTS: Overall, 90-day mortality in patients with SLA was 34.5%. Of the 1,203 patients who matched inclusion/exclusion criteria, 11% (n = 133) were dialyzed within 24 h. The propensity to receive RRT was related to the lactate level and to the SOFA renal and cardio score. The most frequently used modality was continuous RRT. Patients who were started on RRT versus those who did not have 2.3 higher odds of mortality, even after adjustment for the propensity to start RRT. CONCLUSIONS: Our analysis confirms the high mortality rate of patients with SLA. It adds that odds for mortality is even higher in patients who were started on RRT versus not. We suggest keeping an open mind to the factors that may influence the decision to start dialysis and bear in mind that without being a bridge to correction of the underlying condition, dialysis is unlikely to affect the outcome.
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Acidose Láctica , Injúria Renal Aguda , Hiperlactatemia , Acidose Láctica/etiologia , Acidose Láctica/terapia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Humanos , Unidades de Terapia Intensiva , Ácido Láctico , Diálise Renal , Terapia de Substituição Renal , Estudos RetrospectivosRESUMO
Recently, porous photocatalytically active block copolymer membranes were introduced, based on heterogenized molecular catalysts. Here, we report the integration of the photosensitizer, i. e., the light absorbing unit in an intermolecular photocatalytic system into block copolymer membranes in a covalent manner. We study the resulting structure and evaluate the orientational mobility of the photosensitizer as integral part of the photocatalytic system in such membranes. To this end we utilize transient absorption anisotropy, highlighting the temporal reorientation of the transition dipole moment probed in a femtosecond pump-probe experiment. Our findings indicate that the photosensitizer is rigidly bound to the polymer membrane and shows a large heterogeneity of absolute anisotropy values as a function of location probed within the matrix. This reflects the sample inhomogeneity arising from different protonation states of the photosensitizer and different intermolecular interactions of the photosensitizers within the block copolymer membrane scaffold.
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Fármacos Fotossensibilizantes , Polímeros , Fenômenos Químicos , PorosidadeRESUMO
BACKGROUNDCOVID-19 convalescent plasma (CCP) has been considered a treatment option for COVID-19. This trial assessed the efficacy of a neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment.METHODSPatients (n = 105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. The primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21.ResultsThe primary outcome occurred in 43.4% of patients in the CCP group and 32.7% in the control group (P = 0.32). The median time to clinical improvement was 26 days in the CCP group and 66 days in the control group (P = 0.27). The median time to discharge from the hospital was 31 days in the CCP group and 51 days in the control group (P = 0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies, the primary outcome occurred in 56.0% of the patients (vs. 32.1%), with significantly shorter intervals to clinical improvement (20 vs. 66 days, P < 0.05) and to hospital discharge (21 vs. 51 days, P = 0.03) and better survival (day-60 probability of survival 91.6% vs. 68.1%, P = 0.02) in comparison with the control group.ConclusionCCP added to standard treatment was not associated with a significant improvement in the primary and secondary outcomes. A predefined subgroup analysis showed a significant benefit of CCP among patients who received a larger amount of neutralizing antibodies.Trial registrationClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health): ZMVI1-2520COR802.
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COVID-19/terapia , SARS-CoV-2 , Idoso , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/uso terapêutico , COVID-19/imunologia , COVID-19/fisiopatologia , Terapia Combinada , Estudos Cross-Over , Feminino , Humanos , Imunização Passiva/efeitos adversos , Imunização Passiva/métodos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Resultado do Tratamento , Soroterapia para COVID-19RESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) induces lung injury of varying severity, potentially causing severe acute respiratory distress syndrome (ARDS). Pulmonary injury patterns in COVID-19 patients differ from those in patients with other causes of ARDS. We aimed to explore the frequency and pathogenesis of cavitary lung lesions in critically ill patients with COVID-19. Retrospective study in 39 critically ill adult patients hospitalized with severe acute respiratory syndrome coronavirus 2 including lung injury of varying severity in a tertiary care referral center during March and May 2020, Berlin/Germany. We observed lung cavitations in an unusually large proportion of 22/39 (56%) COVID-19 patients treated on intensive care units (ICU), including 3/5 patients without mechanical ventilation. Median interquartile range (IQR) time between onset of symptoms and ICU admission was 11.5 (6.25-17.75) days. In 15 patients, lung cavitations were already present on the first CT scan, performed after ICU admission; in seven patients they developed during a subsequent median (IQR) observation period of 48 (35-58) days. In seven patients we found at least one cavitation with a diameter > 2 cm (maximum 10 cm). Patients who developed cavitations were older and had a higher body mass index. Autopsy findings in three patients revealed that the cavitations reflected lung infarcts undergoing liquefaction, secondary to thrombotic pulmonary artery branch occlusions. Lung cavitations appear to be a frequent complication of severely ill COVID-19 patients, probably related to the prothrombotic state associated with COVID-19.
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COVID-19/patologia , Pulmão/patologia , Embolia Pulmonar/patologia , Idoso , COVID-19/complicações , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/etiologia , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificaçãoRESUMO
BACKGROUND: Cardiac injury associated with cytokine release frequently occurs in SARS-CoV-2 mediated coronavirus disease (COVID19) and mortality is particularly high in these patients. The mechanistic role of the COVID19 associated cytokine-storm for the concomitant cardiac dysfunction and associated arrhythmias is unclear. Moreover, the role of anti-inflammatory therapy to mitigate cardiac dysfunction remains elusive. AIMS AND METHODS: We investigated the effects of COVID19-associated inflammatory response on cardiac cellular function as well as its cardiac arrhythmogenic potential in rat and induced pluripotent stem cell derived cardiomyocytes (iPS-CM). In addition, we evaluated the therapeutic potential of the IL-1ß antagonist Canakinumab using state of the art in-vitro confocal and ratiometric high-throughput microscopy. RESULTS: Isolated rat ventricular cardiomyocytes were exposed to control or COVID19 serum from intensive care unit (ICU) patients with severe ARDS and impaired cardiac function (LVEF 41±5%; 1/3 of patients on veno-venous extracorporeal membrane oxygenation; CK 154±43 U/l). Rat cardiomyocytes showed an early increase of myofilament sensitivity, a decrease of Ca2+ transient amplitudes and altered baseline [Ca2+] upon exposure to patient serum. In addition, we used iPS-CM to explore the long-term effect of patient serum on cardiac electrical and mechanical function. In iPS-CM, spontaneous Ca2+ release events were more likely to occur upon incubation with COVID19 serum and nuclear as well as cytosolic Ca2+ release were altered. Co-incubation with Canakinumab had no effect on pro-arrhythmogenic Ca2+ release or Ca2+ signaling during excitation-contraction coupling, nor significantly influenced cellular automaticity. CONCLUSION: Serum derived from COVID19 patients exerts acute cardio-depressant and chronic pro-arrhythmogenic effects in rat and iPS-derived cardiomyocytes. Canakinumab had no beneficial effect on cellular Ca2+ signaling during excitation-contraction coupling. The presented method utilizing iPS-CM and in-vitro Ca2+ imaging might serve as a novel tool for precision medicine. It allows to investigate cytokine related cardiac dysfunction and pharmacological approaches useful therein.
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Anticorpos Monoclonais Humanizados/farmacologia , Arritmias Cardíacas , Tratamento Farmacológico da COVID-19 , COVID-19 , Sinalização do Cálcio/efeitos dos fármacos , Miócitos Cardíacos , SARS-CoV-2/metabolismo , Adulto , Idoso , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patologia , COVID-19/complicações , COVID-19/metabolismo , COVID-19/patologia , Cálcio/metabolismo , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos , Ratos Sprague-Dawley , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/patologiaRESUMO
PURPOSE: Chronic obstructive pulmonary disease (COPD) is a risk factor for acquiring multiple drug resistant bacteria. The main objective of this analysis was to question a beneficial outcome in the routine use of antipseudomonal antibiotics in the empiric treatment of severe AECOPD in Intensive Care Unit patients. MATERIAL AND METHODS: We report a retrospective, observational cohort study in adult patients with severe AECOPD admitted to ICU at a tertiary care university hospital. Antibiotic treatment on admission as well as microbiology samples were analyzed. The influence of SOFA score at admission, age, sex and antibiotic choice upon survival was investigated by multivariable analysis. RESULTS: 437 patients were included. Mean age was 68 years (±10), 46.5% were female. 271/437 patients (62%) were initially treated with antibiotics covering Pseudomonas aeruginosa. Overall, positive microbiology samples were found in 107 patients (24.5%). P. aeruginosa was only found in 3.7%. There was no significant difference in 30-day ICU mortality after adjusting for age, sex and severity of illness (20.4% ± 11.6 in patients with Pseudomonas inactive antibiotics versus 29.3% ± 10.8 in patients with PAA, p=0.113). CONCLUSIONS: Empiric use of antipseudomonal antibiotics did not result in improved ICU survival in this retrospective analysis.
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Antibacterianos , Doença Pulmonar Obstrutiva Crônica , Adulto , Idoso , Antibacterianos/uso terapêutico , Feminino , Humanos , Unidades de Terapia Intensiva , Pseudomonas aeruginosa , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos RetrospectivosRESUMO
COVID 19 is associated with a hypercoagulable state and frequent thromboembolic complications. For how long this acquired abnormality lasts potentially requiring preventive measures, such as anticoagulation remains to be delineated. We used viscoelastic rotational thrombelastometry (ROTEM) in a single center cohort of 13 critical ill patients and performed follow up examinations three months after discharge from ICU. We found clear signs of a hypercoagulable state due to severe hypofibrinolysis and a high rate of thromboembolic complications during the phase of acute illness. Three month follow up revealed normalization of the initial coagulation abnormality and no evidence of venous thrombosis in all thirteen patients. In our cohort the coagulation profile was completely normalized three months after COVID-19. Based on these findings, discontinuation of anticoagulation can be discussed in patients with complete venous reperfusion.
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Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea , Tratamento Farmacológico da COVID-19 , COVID-19 , Tromboelastografia , Tromboembolia , Trombose Venosa , Idoso , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/patologia , COVID-19/sangue , COVID-19/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Tromboembolia/tratamento farmacológico , Tromboembolia/patologia , Trombose Venosa/tratamento farmacológico , Trombose Venosa/patologiaRESUMO
With an urgent need for bedside imaging of coronavirus disease 2019 (COVID-19), this study's main goal was to assess inter- and intraobserver agreement in lung ultrasound (LUS) of COVID-19 patients. In this single-center study we prospectively acquired and evaluated 100 recorded ten-second cine-loops in confirmed COVID-19 intensive care unit (ICU) patients. All loops were rated by ten observers with different subspeciality backgrounds for four times by each observer (400 loops overall) in a random sequence using a web-based rating tool. We analyzed inter- and intraobserver variability for specific pathologies and a semiquantitative LUS score. Interobserver agreement for both, identification of specific pathologies and assignment of LUS scores was fair to moderate (e.g., LUS score 1 Fleiss' κ = 0.27; subpleural consolidations Fleiss' κ = 0.59). Intraobserver agreement was mostly moderate to substantial with generally higher agreement for more distinct findings (e.g., lowest LUS score 0 vs. highest LUS score 3 (median Fleiss' κ = 0.71 vs. 0.79) or air bronchograms (median Fleiss' κ = 0.72)). Intraobserver consistency was relatively low for intermediate LUS scores (e.g. LUS Score 1 median Fleiss' κ = 0.52). We therefore conclude that more distinct LUS findings (e.g., air bronchograms, subpleural consolidations) may be more suitable for disease monitoring, especially with more than one investigator and that training material used for LUS in point-of-care ultrasound (POCUS) should pay refined attention to areas such as B-line quantification and differentiation of intermediate LUS scores.
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COVID-19/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Sistemas Automatizados de Assistência Junto ao Leito , SARS-CoV-2 , COVID-19/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Variações Dependentes do Observador , Estudos Prospectivos , UltrassonografiaRESUMO
BACKGROUND: Patients with COVID-19 seem to be prone to the development of arrhythmias. The objective of this trial was to determine the characteristics, clinical significance and therapeutic consequences of these arrhythmias in COVID-19 patients requiring intensive care unit (ICU) treatment. METHODS AND RESULTS: A total of 113 consecutive patients (mean age 64.1 ± 14.3 years, 30 (26.5%) female) with positive PCR testing for SARS-CoV2 as well as radiographically confirmed pulmonary involvement admitted to the ICU from March to May 2020 were included and observed for a cumulative time of 2321 days. Fifty episodes of sustained atrial tachycardias, five episodes of sustained ventricular arrhythmias and thirty bradycardic events were documented. Sustained new onset atrial arrhythmias were associated with hemodynamic deterioration in 13 cases (35.1%). Patients with new onset atrial arrhythmias were older, showed higher levels of Hs-Troponin and NT-proBNP, and a more severe course of disease. The 5 ventricular arrhythmias (two ventricular tachycardias, two episodes of ventricular fibrillation, and one torsade de pointes tachycardia) were observed in 4 patients. All episodes could be terminated by immediate defibrillation/cardioversion. Five bradycardic events were associated with hemodynamic deterioration. Precipitating factors could be identified in 19 of 30 episodes (63.3%), no patient required cardiac pacing. Baseline characteristics were not significantly different between patients with or without bradycardic events. CONCLUSION: Relevant arrhythmias are common in severely ill ICU patients with COVID-19. They are associated with worse courses of disease and require specific treatment. This makes daily close monitoring of telemetric data mandatory in this patient group.
Assuntos
COVID-19 , Idoso , Arritmias Cardíacas/diagnóstico , Eletrocardiografia , Feminino , Humanos , Unidades de Terapia Intensiva , Pessoa de Meia-Idade , RNA Viral , SARS-CoV-2RESUMO
INTRODUCTION: Acute kidney injury (AKI) is an important complication in COVID-19, but its precise etiology has not fully been elucidated. Insights into AKI mechanisms may be provided by analyzing the temporal associations of clinical parameters reflecting disease processes and AKI development. METHODS: We performed an observational cohort study of 223 consecutive COVID-19 patients treated at 3 sites of a tertiary care referral center to describe the evolvement of severe AKI (Kidney Disease: Improving Global Outcomes stage 3) and identify conditions promoting its development. Descriptive statistics and explanatory multivariable Cox regression modeling with clinical parameters as time-varying covariates were used to identify risk factors of severe AKI. RESULTS: Severe AKI developed in 70 of 223 patients (31%) with COVID-19, of which 95.7% required kidney replacement therapy. Patients with severe AKI were older, predominantly male, had more comorbidities, and displayed excess mortality. Severe AKI occurred exclusively in intensive care unit patients, and 97.3% of the patients developing severe AKI had respiratory failure. Mechanical ventilation, vasopressor therapy, and inflammatory markers (serum procalcitonin levels and leucocyte count) were independent time-varying risk factors of severe AKI. Increasing inflammatory markers displayed a close temporal association with the development of severe AKI. Sensitivity analysis on risk factors of AKI stage 2 and 3 combined confirmed these findings. CONCLUSION: Severe AKI in COVID-19 was tightly coupled with critical illness and systemic inflammation and was not observed in milder disease courses. These findings suggest that traditional systemic AKI mechanisms rather than kidney-specific processes contribute to severe AKI in COVID-19.
RESUMO
Drugs intoxications often lead to severe vasoplegia and cardiogenic shock, and VA-ECMO represents a viable therapy option. However, as cardiopulmonary support is not contributing to the removal of the causal agent from the blood, detoxification by a new hemoadsorption device (CytoSorb) could represent a potential therapeutic tool due to its highly efficient elimination capacity of endogenous but also exogenous hydrophobic substances for which otherwise no effective antidote exist. In this case series, four anecdotal cases of acute intoxications requiring VA-ECMO support used as extracorporeal cardiopulmonary resuscitation after intoxication-induced out-of-hospital cardiac arrest (OHCA) are presented, who were additionally treated with CytoSorb hemoadsorption in combination with renal replacement therapy. Combined treatment was associated with a considerable decrease in plasma levels of the overdosed drugs. Additionally, the combination of applied techniques was safe, practical, and technically feasible with no adverse or any device-related side effects documented during or after the treatment sessions. Based on the reported dramatic decline in drug levels during treatment, that fits in the device's characteristics, we strongly suggest to further investigate the potentially lifesaving role of CytoSorb therapy in patients with acute intoxications requiring multiple organ support techniques.