Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

The impact of stapling technique and surgeon specialism on anastomotic failure after right?sided colorectal resection: an international multicentre, prospective audit

Aim There is little evidence to support choice of technique and configuration for stapled anastomoses after right hemicolectomy and ileocaecal resection. This study aimed to determine the relationship between stapling technique and anastomotic failure. Method Any unit performing gastrointestinal surgery was invited to contribute data on consecutive adult patients undergoing right hemicolectomy or ileocolic resection to this prospective, observational, international, multicentre study. Patients undergoing stapled, side?to?side ileocolic anastomoses were identified and multilevel, multivariable logistic regression analyses were performed to explore factors associated with anastomotic leak. Results One thousand three hundred and forty?seven patients were included from 200 centres in 32 countries. The overall anastomotic leak rate was 8.3%. Upon multivariate analysis there was no difference in leak rate with use of a cutting stapler for apical closure compared with a noncutting stapler (8.4% vs 8.0%, OR 0.91, 95% CI 0.54–1.53, P = 0.72). Oversewing of the apical staple line, whether in the cutting group (7.9% vs 9.7%, OR 0.87, 95% CI 0.52–1.46, P = 0.60) or noncutting group (8.9% vs 5.7%, OR 1.40, 95% CI 0.46–4.23, P = 0.55) also conferred no benefit in terms of reducing leak rates. Surgeons reporting to be general surgeons had a significantly higher leak rate than those reporting to be colorectal surgeons (12.1% vs 7.3%, OR 1.65, 95% CI 1.04–2.64, P = 0.04). Conclusion This study did not identify any difference in anastomotic leak rates according to the type of stapling device used to close the apical aspect. In addition, oversewing of the anastomotic staple lines appears to confer no benefit in terms of reducing leak rates. Although general surgeons operated on patients with more high?risk characteristics than colorectal surgeons, a higher leak rate for general surgeons which remained after risk adjustment needs further exploration

Relationship between method of anastomosis and anastomotic failure after right hemicolectomy and ileo-caecal resection: an international snapshot audit

Aim: The anastomosis technique used following right-sided colonic resection is widely variable and may affect patient outcome. This study aimed to assess the association between leak and anastomosis technique (stapled vs handsewn). Method: This was a prospective, multicentre, international audit including patients undergoing elective or emergency right hemicolectomy or ileo-caecal resection operations over a 2-month period in early 2015. The primary outcome measure was the presence of anastomotic leak within 30\ua0days of surgery, determined using a prespecified definition. Mixed effects logistic regression models were used to assess the association between leak and anastomosis method, adjusting for patient, disease and operative cofactors, with centre included as a random-effect variable. Results: This study included 3208 patients, of whom 78.4% (n\ua0=\ua02515) underwent surgery for malignancy and 11.7% (n\ua0=\ua0375) underwent surgery for Crohn's disease. An anastomosis was performed in 94.8% (n\ua0=\ua03041) of patients, which was handsewn in 38.9% (n\ua0=\ua01183) and stapled in 61.1% (n\ua0=\ua01858). Patients undergoing handsewn anastomosis were more likely to be emergency admissions (20.5% handsewn vs 12.9% stapled) and to undergo open surgery (54.7% handsewn vs 36.6% stapled). The overall anastomotic leak rate was 8.1% (245/3041), which was similar following handsewn (7.4%) and stapled (8.5%) techniques (P\ua0=\ua00.3). After adjustment for cofactors, the odds of a leak were higher for stapled anastomosis (adjusted OR\ua0=\ua01.43; 95% CI: 1.04\u20131.95; P\ua0=\ua00.03). Conclusion: Despite being used in lower-risk patients, stapled anastomosis was associated with an increased anastomotic leak rate in this observational study. Further research is needed to define patient groups in whom a stapled anastomosis is safe

The relationship between method of anastomosis and anastomotic failure after right hemicolectomy and ileo-caecal resection: an international snapshot audit.

BACKGROUND: Anastomosis technique following right sided colonic resection is widely variable and may affect patient outcomes. This study aimed to assess the association between leak and anastomosis technique (stapled versus handsewn) METHODS: This was a prospective, multicentre, international audit including patients undergoing elective or emergency right hemicolectomy or ileo-caecal resection operations over a two-month period in early 2015. The primary outcome measure was the presence of anastomotic leak within 30 days of surgery, using a pre-specified definition. Mixed effects logistic regression models were used to assess the association between leak and anastomosis method, adjusting for patient, disease and operative cofactors, with centre included as a random effect variable. RESULTS: This study included 3208 patients, of whom 78.4% (n=2515) underwent surgery for malignancy and 11.7% (n=375) for Crohn's disease. An anastomosis was performed in 94.8% (n=3041) of patients, which was handsewn in 38.9% (n=1183) and stapled in 61.1% (n=1858) cases. Patients undergoing handsewn anastomosis were more likely to be emergency admissions (20.5% handsewn versus 12.9% stapled) and to undergo open surgery (54.7% versus 36.6%). The overall anastomotic leak rate was 8.1% (245/3041), which was similar following handsewn (7.4%) and stapled (8.5%) techniques (p=0.3). After adjustment for cofactors, the odds of a leak were higher for stapled anastomosis (adjusted odds ratio 1.43, 95% confidence interval 1.04-1.95, p=0.03). DISCUSSION: Despite being used in lower risk patients, stapled anastomosis was associated with an increased anastomotic leak rate in this observational study. Further research is needed to define patient groups in whom a stapled anastomosis is safe. This article is protected by copyright. All rights reserve