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1.
EClinicalMedicine ; 40: 101099, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34490415

RESUMO

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. Methods: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). Findings: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. Interpretation: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. Funding: Funded by Roche Sequencing Solutions, Inc.

2.
J Clin Anesth ; 68: 110099, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33120302

RESUMO

STUDY OBJECTIVE: Delirium is frequently observed in the postoperative and intensive care unit (ICU) population. Due to the multifactorial origin of delirium and according to international guidelines (e.g., American Geriatrics Society; Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) guideline), there are several but no incontestable options for prevention and symptomatic treatment. The purpose of the Baden PRIDe (Prevention and Reduction of Incidence of postoperative Delirium) trial was to determine whether postoperative cognitive dysfunction and delirium could be prevented by the combination of possible preventive agents such as haloperidol and ketamine. In addition, pre- and postoperative levels of the biomarkers cortisol, neuron specific enolase (NSE) and S100ß were measured to investigate their dynamics in delirious and non-delirious patients after surgery. DESIGN: The Baden PRIDe Trial was an investigator-initiated, phase IV, two-centre, randomised, placebo-controlled, double-blind clinical trial. SETTING: Perioperative care. PATIENTS: 182 adult patients that underwent elective or emergency surgery under general or combined (i.e., general and regional) anaesthesia. INTERVENTIONS: Pre-anaesthetic, pharmacologic prevention of postoperative brain dysfunction with haloperidol, ketamine, and the combination of both vs. placebo. MEASUREMENTS: Assessment of cognitive performance pre- and postoperatively with the MMSE, the DOS, the Nursing Delirium Screening Scale (Nu-DESC) or the Intensive Care Delirium Screening Checklist (ICDSC) during ICU stay. MAIN RESULTS: None of the three study arms - haloperidol, ketamine, or both drugs combined - was significantly superior to placebo for prevention of postoperative brain dysfunction and delirium (P = 0.39). Measured levels of postoperative cortisol were significantly higher in delirious patients. S-100ß levels were significantly higher in all postoperative outcome groups (cognitive impairment, delirium, no cognitive decline), whereas postoperative NSE levels declined in all groups. CONCLUSIONS: The study results offer no possibility for a novel recommendation for prevention of postoperative cognitive decline including delirium. Perioperative S-100ß trajectories in patients with cognitive deterioration suggest affection of glial cells in particular. TRIAL REGISTRATION: ClinicalTrials.govNCT02433041; registered on April 7, 2015.


Assuntos
Disfunção Cognitiva , Delírio , Ketamina , Adulto , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Delírio/prevenção & controle , Método Duplo-Cego , Haloperidol/efeitos adversos , Humanos
3.
Hum Pathol ; 42(2): 285-90, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21106224

RESUMO

From 2006 to 2009, Switzerland experienced the highest measles incidence rate in Central and Western Europe. This increased occurrence of measles cases is mainly due to insufficient vaccination of the Swiss population over a period of many years. Acute appendicitis is a rare complication of measles infection. To date, 25 cases of measles-associated appendicitis have been documented in the English literature. Sixteen (64.0%) of the 25 patients had developed appendicitis in the prodromal stage of measles before skin rash appeared. This article describes the unusual histopathologic findings of measles-associated appendicitis in a 19-year-old non-measles-vaccinated man in the transitional phase from prodromal to full-blown disease and provides a comprehensive review of the literature.


Assuntos
Apendicite/patologia , Sarampo/patologia , Doença Aguda , Apendicite/cirurgia , Apendicite/virologia , Humanos , Masculino , Sarampo/complicações , Vírus do Sarampo/genética , Vírus do Sarampo/isolamento & purificação , RNA Viral/análise , Adulto Jovem
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