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BACKGROUND AND AIMS: COVID-19 vaccination has proved to be effective to prevent symptomatic infection and severe disease even in immunocompromised patients including liver transplant patients. We aim to assess the impact of COVID-19 vaccination on the mortality and development of severe and critical disease in our center. METHODS: A retrospective cohort study of LT patients in a reference center between March 2020 and February 2022. Demographic data, cirrhosis etiology, time on liver transplantation, immunosuppressive therapies, and vaccination status were recorded at the time of diagnosis. Primary outcome was death due to COVID-19, and secondary outcomes included the development of severe COVID-19 and intensive care unit (ICU) requirement. RESULTS: 153 of 324 LT recipients developed COVID-19, in whom the main causes of cirrhosis were HCV infection and metabolic-associated fatty liver disease. The vaccines used were BNT162b2 (48.6%), ChAdOx1 nCoV-19 (21.6%), mRNA-1273 vaccine (1.4%), Sputnik V (14.9%), Ad5-nCoV-S (4.1%) and CoronaVac (9.5%). Case fatality and ICU requirement risk were similar among vaccinated and unvaccinated LT patients (adjusted relative case fatality for vaccinated versus unvaccinated of 0.68, 95% CI 0.14-3.24, p = 0.62; adjusted relative risk [aRR] for ICU requirement of 0.45, 95% CI 0.11-1.88, p = 0.27). Nonetheless, vaccination was associated with a lower risk of severe disease (aRR for severe disease of 0.32, 95% CI 0.14-0.71, p = 0.005). CONCLUSIONS: Vaccination reduces the risk of severe COVID-19 in LT patients, regardless of the scheme used. Vaccination should be encouraged for all.
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Vacinas contra COVID-19 , COVID-19 , Transplante de Fígado , Humanos , Vacina de mRNA-1273 contra 2019-nCoV , Vacina BNT162 , ChAdOx1 nCoV-19 , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Cirrose Hepática , México/epidemiologia , Estudos Retrospectivos , Transplantados , VacinaçãoRESUMO
Portal hypertension may have major consequences on the pulmonary vasculature due to the complex pathophysiological interactions between the liver and lungs. Portopulmonary hypertension (PoPH), a subset of group 1 pulmonary hypertension (PH), is a serious pulmonary vascular disease secondary to portal hypertension, and is the fourth most common subtype of pulmonary arterial hypertension. It is most commonly observed in cirrhotic patients; however, patients with noncirrhotic portal hypertension can also develop it. On suspicion of PoPH, the initial evaluation is by a transthoracic echocardiogram in which, if elevated pulmonary pressures are shown, patients should undergo right heart catheterization to confirm the diagnosis. The prognosis is extremely poor in untreated patients; therefore, management includes pulmonary arterial hypertension therapies with the aim of improving pulmonary hemodynamics and moving patients to orthotopic liver transplantation (OLT). In this article, we review in detail the epidemiology, pathophysiology, process for diagnosis, and most current treatments including OLT and prognosis in patients with PoPH. In addition, we present a diagnostic algorithm that includes the current criteria to properly select patients with PoPH who are candidates for OLT.
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The use of immunosuppressive medications for solid organ transplantation is associated with cardiovascular, metabolic, and oncologic complications. On the other hand, the development of graft rejection is associated with increased mortality and graft dysfunction. Liver transplant recipients can withdraw from immunosuppression without developing graft injury while preserving an adequate antimicrobial response - a characteristic known as immunotolerance. Immunotolerance can be spontaneously or pharmacologically achieved. Contrary to the classic dogma, clinical studies have elucidated low rates of true spontaneous immunotolerance (no serologic or histological markers of immune injury) among liver transplant recipients. However, clinical, serologic, and tissue biomarkers can aid in selecting patients in whom immunosuppression can be safely withdrawn. For those who failed an immunosuppression withdrawal trial or are at high risk of rejection, pharmacological interventions for immunotolerance induction are under development. In this review, we provide an overview of the mechanisms of immunotolerance, the clinical studies investigating predictors and biomarkers of spontaneous immunotolerance, as well as the potential pharmacological interventions for inducing it.
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Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Imunossupressores/efeitos adversos , Terapia de Imunossupressão , Tolerância Imunológica , Biomarcadores/metabolismo , Rejeição de Enxerto/tratamento farmacológicoAssuntos
COVID-19 , Insuficiência Respiratória , Humanos , Posicionamento do Paciente , Decúbito Ventral , SARS-CoV-2 , VigíliaRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0245772.].
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Throughout the COVID-19 pandemic, thousands of temporary ICUs have been established worldwide. The outcomes and management of mechanically ventilated patients in these areas remain unknown. OBJECTIVES: To investigate mortality and management of mechanically ventilated patients in temporary ICUs. DESIGN SETTING AND PARTICIPANTS: Observational cohort study in a single-institution academic center. We included all adult patients with severe COVID-19 hospitalized in temporary and conventional ICUs for invasive mechanical ventilation due to acute respiratory distress syndrome from March 23, 2020, to April 5, 2021. MAIN OUTCOMES AND MEASURES: To determine if management in temporary ICUs increased 30-day in-hospital mortality compared with conventional ICUs. Ventilator-free days, ICU-free days (both at 28 d), hospital length of stay, and ICU readmission were also assessed. RESULTS: We included 776 patients (326 conventional and 450 temporary ICUs). Thirty-day in-hospital unadjusted mortality (28.8% conventional vs 36.0% temporary, log-rank test p = 0.023) was higher in temporary ICUs. After controlling for potential confounders, hospitalization in temporary ICUs was an independent risk factor associated with mortality (hazard ratio, 1.4; CI, 1.06-1.83; p = 0.016).There were no differences in ICU-free days at 28 days (6; IQR, 0-16 vs 2; IQR, 0-15; p = 0.5) or ventilator-free days at 28 days (8; IQR, 0-16 vs 5; IQR, 0-15; p = 0.6). We observed higher reintubation (18% vs 12%; p = 0.029) and readmission (5% vs 1.6%; p = 0.004) rates in conventional ICUs despite higher use of postextubation noninvasive mechanical ventilation (13% vs 8%; p = 0.025). Use of lung-protective ventilation (87% vs 85%; p = 0.5), prone positioning (76% vs 79%; p = 0.4), neuromuscular blockade (96% vs 98%; p = 0.4), and COVID-19 pharmacologic treatment was similar. CONCLUSIONS AND RELEVANCE: We observed a higher 30-day in-hospital mortality in temporary ICUs. Although both areas had high adherence to evidence-based management, hospitalization in temporary ICUs was an independent risk factor associated with mortality.
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OBJECTIVE: Describe the histological findings of minimally ultrasound-guided invasive autopsies in deceased patients with severe SARS-CoV-2 and compare the diagnostic yield with open autopsies. DESIGN: Observational post-mortem cohort study. Minimally invasive ultrasound-guided autopsies were performed in fourteen deceased patients with a confirmed diagnosis of SARS-CoV-2 pneumonia. Histological and clinical findings of lung, kidney, and liver tissue are described and contrasted with those previously reported in the literature. SETTING: Single-center COVID-19 reference center in Mexico City. RESULTS: Fourteen minimally invasive autopsies revealed a gross correlation with open autopsies reports: 1) Lung histology was characterized mainly by early diffuse alveolar damage (12/13). Despite low lung compliances and prolonged mechanical ventilation, the fibrotic phase was rarely observed (2/13). 2) Kidney histopathology demonstrated acute tubular injury (12/13), interstitial nephritis (11/13), and glomerulitis (11/13) as the predominant features 3) Liver histology was characterized by neutrophilic inflammation in all of the cases, as well as hepatic necrosis (8/14) despite minimal alterations in liver function testing. Hepatic steatosis was observed in most cases (12/14). SARS-CoV-2 positivity was widely observed throughout the immunohistochemical analysis. However, endothelitis and micro thrombosis, two of the hallmark features of the disease, were not observed. CONCLUSION: Our data represents the largest minimally invasive, ultrasound-guided autopsy report. We demonstrate a gross histological correlation with large open autopsy cohorts. However, this approach might overlook major histologic features of the disease, such as endothelitis and micro-thrombosis. Whether this represents sampling bias is unclear.
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COVID-19RESUMO
Background: Antimalarial drugs were widely used as experimental therapies against COVID-19 in the initial stages of the pandemic. Despite multiple randomized controlled trials demonstrating unfavorable outcomes in both efficacy and adverse effects, antimalarial drugs are still prescribed in developing countries, especially in those experiencing recurrent COVID-19 crises (India and Brazil). Therefore, real-life experience and pharmacovigilance studies describing the use and side effects of antimalarials for COVID-19 in developing countries are still relevant. Objective: To describe the adverse effects associated with the use of antimalarial drugs in hospitalized patients with COVID-19 pneumonia at a reference center in Mexico City. Methods: We integrated a retrospective cohort with all adult patients hospitalized for COVID-19 pneumonia from March 13th, 2020, to May 17th, 2020. We compared the baseline characteristics (demographic and clinical) and the adverse effects between the groups of patients treated with and without antimalarial drugs. The mortality analysis was performed in 491 patients who received optimal care and were not transferred to other institutions (210 from the antimalarial group and 281 from the other group). Results: We included 626 patients from whom 38% (n = 235) received an antimalarial drug. The mean age was 51.2 ± 13.6 years, and 64% were males. At baseline, compared with the group treated with antimalarials, the group that did not receive antimalarials had more dyspnea (82 vs. 73%, p = 0.017) and cyanosis (5.3 vs. 0.9%, p = 0.009), higher respiratory rate (median of 28 vs. 24 bpm, p < 0.001), and lower oxygen saturation (median of 83 vs. 87%, p < 0.001). In the group treated with antimalarials, 120 patients had two EKG evaluations, from whom 12% (n = 16) prolonged their QTc from baseline in more than 50 ms, and six developed a ventricular arrhythmia. Regarding the trajectories of the liver function tests over time, no significant differences were found for the change in the mean value per day between the two groups. Among patients who received optimal care, the mortality was 16% (33/210) in those treated with antimalarials and 15% (41/281) in those not receiving antimalarials (RR 1.08, 95% 0.75-1.64, and adjusted RR 1.12, 95% CI 0.69-1.82). Conclusion: The adverse events in patients with COVID-19 treated with antimalarials were similar to those who did not receive antimalarials at institutions with rigorous pharmacological surveillance. However, they do not improve survival in patients who receive optimal medical care.
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BACKGROUND: As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has remained in Latin America, Mexico has become the third country with the highest death rate worldwide. Data regarding in-hospital mortality and its risk factors, as well as the impact of hospital overcrowding in Latin America has not been thoroughly explored. METHODS AND FINDINGS: In this prospective cohort study, we enrolled consecutive adult patients hospitalized with severe confirmed COVID-19 pneumonia at a SARS-CoV-2 referral center in Mexico City from February 26th, 2020, to June 5th, 2020. A total of 800 patients were admitted with confirmed diagnosis, mean age was 51.9 ± 13.9 years, 61% were males, 85% were either obese or overweight, 30% had hypertension and 26% type 2 diabetes. From those 800, 559 recovered (69.9%) and 241 died (30.1%). Among survivors, 101 (18%) received invasive mechanical ventilation (IMV) and 458 (82%) were managed outside the intensive care unit (ICU); mortality in the ICU was 49%. From the non-survivors, 45.6% (n = 110) did not receive full support due to lack of ICU bed availability. Within this subgroup the main cause of death was acute respiratory distress syndrome (ARDS) in 95% of the cases, whereas among the non-survivors who received full (n = 105) support the main cause of death was septic shock (45%) followed by ARDS (29%). The main risk factors associated with in-hospital death were male sex (RR 2.05, 95% CI 1.34-3.12), obesity (RR 1.62, 95% CI 1.14-2.32)-in particular morbid obesity (RR 3.38, 95%CI 1.63-7.00)-and oxygen saturation < 80% on admission (RR 4.8, 95%CI 3.26-7.31). CONCLUSIONS: In this study we found similar in-hospital and ICU mortality, as well as risk factors for mortality, compared to previous reports. However, 45% of the patients who did not survive justified admission to ICU but did not receive IMV / ICU care due to the unavailability of ICU beds. Furthermore, mortality rate over time was mainly due to the availability of ICU beds, indirectly suggesting that overcrowding was one of the main factors that contributed to hospital mortality.