Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Caracterização fenotípica e funcional de subpopulações de linfócitos t reguladores (TREG) Na reação tipo 2 (ENL) da hanseníase

Made available in DSpace on 2018-06-12T17:45:03Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) katherine_castro_ioc_mest_2018.pdf: 2095605 bytes, checksum: 8a1dca03e2bf9f2be6702a351cc4623a (MD5)Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.O Eritema Nodoso Leproso (ENL) é uma manifestação aguda e sistêmica, que ocorre de forma súbita, podendo ser grave e levar pacientes de hanseníase ao óbito. O episódio reacional é observado em cerca da metade dos pacientes multibacilares (MB), principalmente na forma lepromatosa polar (LL) e sua gênese pode ocorrer em qualquer momento do tratamento poliquimioterápico, inclusive antecedendo o mesmo. Incapacidades físicas associadas ao ENL são fonte de extremo sofrimento e retirada do mercado de trabalho de grande parte dos pacientes. No ENL ocorre progressão da resposta imune celular para um cenário reativo e ainda pouco compreendido. Assim, esse trabalho se propôs a caracterizar fenotípica e funcionalmente os linfócitos Treg CD4+ e CD8+ periféricos, tanto ex vivo, quanto em resposta ao M. leprae (ML), de 12 pacientes com ENL, cujos dados foram comparados com 8 pacientes LL e 10 voluntários sadios (VS) de área endêmica para a hanseníase, todos moradores do Rio de Janeiro. A frequência dessas células e sua atividade funcional foram avaliadas através da análise ex vivo da expressão de CTLA-4 e da determinação da frequência in vitro de células produtoras de TGF-\03B2 e IL-10, por citometria de fluxo multiparamétrica Ademais, a produção de citocinas em sobrenadante (SN) de culturas de células mononucleares periféricas (PBMC) frente ao ML, através de ensaio imunoenzimático (ELISA). Uma redução significativa das células Treg CD4+ ex vivo foi observada nos pacientes com ENL (p<0,001), além do envolvimento restrito de CTLA-4 em suprimir resposta ao ML em todos os grupos. A análise in vitro também demonstrou a redução significativa (p<0,0001) das Treg CD4+ no grupo ENL, com inalteração de suas frequências mesmo após estímulo com ML. A avaliação da atividade funcional in vitro revelou que as Treg CD4+ produtoras de TGF-\03B2 estão significantemente reduzidas nos pacientes com ENL em relação ao grupo LL (p<0,05), enquanto as Treg CD4+/IL-10+ não diferiram entre os grupos. De acordo com o estudo, as Treg CD8+ não estão envolvidas na gênese do ENL. Por fim, o grupo ENL apresentou níveis significativamente aumentados na produção de IL-6 por PBMC em comparação aos outros grupos, tanto em culturas não estimuladas (NE), quanto em resposta ao ML (p<0,05). O trabalho revelou ainda níveis mais elevados de produção de IL-17, IL-23 e IFN-\03B3 em PBMC no grupo ENL em comparação ao outro grupo LL, embora sem significância. Os dados obtidos sugerem uma mudança transitória na regulação da resposta imune mantida por células Treg CD4+ no ENL, como observado na forma LL, tornando o microambiente permissivo para a instalação do processo reacional.Erythema Nodosum Leprosum (ENL) is an acute and systemic manifestation, which occurs suddenly, can be severe and lead leprosy patients to death. Reactional episodes are observed among the half of multibacillary (MB) patients, mainly into the polar lepromatous (LL) form, beginning at any time of the multidrug therapy, and even before the treatment. Physical disabilities associated to ENL are the source of extreme suffering and absence from work in most of cases. ENL occurs in progression of the cellular immune response associated with a reactive and still poorly understood scenario. Thus, this work aimed to characterize phenotypic and functionally Treg cells CD4+ and CD8+, ex vivo and in response to M. leprae (ML), from 12 ENL patients, which were compared to 8 LL and 10 healthy volunteers (VS) from leprosy endemic areas, all residents in the city of Rio de Janeiro. The functional activity and frequencies of these cells were evaluated by ex vivo analysis of CTLA-4 expression and the in vitro frequency of TGF-\03B2 and IL-10 producing cells, through multiparametric flow cytometry In addition, the production of cytokines in supernatant (SN) from peripheral blood mononuclear cell (PBMC) cultures was investigated against ML antigens by enzyme-linked immunosorbent assay (ELISA). Ex vivo significant reduction of Treg CD4+ frequency was observed to ENL patients (p<0,001), and low implication of CTLA-4 in suppressing response was noted in all groups. In vitro analysis also demonstrated decrease of Treg CD4+ in the ENL group (p<0,0001), without change of the frequencies, even after stimulation with ML. In vitro functional activity evaluation revealed that the frequency of Treg CD4+ producing TGF-\03B2 were significantly reduced among ENL patients compared to LL (p<0,05) and Treg CD4+/ IL-10+ did not differ significantly between groups. According to the study, Treg CD8+ are not implicated in the genesis of ENL. Finally, the ENL group had significant increased IL-6 levels production by PBMC compared to other groups, in non-stimulated (NE) cultures and in response to ML (p<0,05). The study also showed increase levels of IFN-\03B3, IL-17 and IL-23 in PBMC from ENL group in comparison to LL, although not significant. These data suggest a transient change in the regulation of the immune response maintained by Treg CD4+ in ENL, making the microenvironment permissive for the installation of the reactional process

Increased oxidative stress in elderly leprosy patients is related to age but not to bacillary load.

BackgroundLeprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy.Methodology/principal findings87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase.Conclusions/significanceWe conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease