SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Should ambulatory appendectomy become the standard treatment for acute appendicitis?

Abstract Background Appendectomy is increasingly performed as a ‘short stay’ or ‘ambulatory’ procedure, yet there is no consensus for selection of patients with acute appendicitis for ambulatory surgery (AS). We aimed to compare characteristics and outcomes of complicated and uncomplicated appendectomies performed in ambulatory vs. conventional settings, and to determine factors associated with unexpected re-consultations and re-hospitalizations. Methods The authors reviewed a consecutive series of 185 laparoscopic appendectomies. Whenever possible, patients were offered AS, defined as ‘discharge on the same working day.’ Multivariable regressions were performed to determine associations of unexpected re-consultations and re-hospitalizations with surgery type (ambulatory or conventional) and patient characteristics (age, gender, obesity, symptoms, appendicolith, perforations, appendix diameter, serologic results, American Society of Anesthesiologists score, and Saint-Antoine score). Results From the initial cohort, 117 patients (63.2%) were eligible for AS, of which 8 had peri- or post-operative contraindications. Therefore, 109 patients (58.9%) were operated by AS, with median length of stay 8.5 h (range, 3.3–20.5). Ambulatory cases had a lower incidence of complications (11.9%) than conventional cases (25.0%) (p = 0.029). Uni- and multi-variable regressions revealed that unexpected re-consultations were not significantly associated with any of the pre- or peri-operative variables but that unexpected re-hospitalizations were 4 times more likely for patients with appendicolith (OR, 4.32; p = 0.04). Conclusions Ambulatory surgery could be considered as a standard procedure for both complicated and uncomplicated acute appendicitis. Appendicolith was found to be an independent risk factor for unexpected re-hospitalization and should therefore trigger closer monitoring

Short-term Outcomes of Ambulatory Colectomy for 157 Consecutive Patients

International audienceTo evaluate short-term outcomes of laparoscopic colectomy for selected consecutive patients in an ambulatory setting at two institutions.BACKGROUND:Several studies showed that an enhanced recovery protocol for colorectal surgery reduces postoperative morbidity and mortality, and shortens the length of hospital stay. The development of such a program has allowed us to gradually reduce the length of stay for colorectal surgery, until ambulatory management.METHODS:Between February, 2013 and December, 2016, all patients scheduled for elective laparoscopic colectomy and meeting rigorous criteria for ambulatory surgery were included. Outcome was prospectively studied.RESULTS:One hundred fifty-seven patients (70 women) with a median age of 61 years (range 25-82 years) were included. The ambulatory rate for colectomy was 30.5%. Median operative time and length of in-hospital stay were 95 minutes (range 45-232 minutes) and 10.0 hours (range 7-14.7 hours), respectively. The admission rate was 7.0% due to operative difficulties (4 patients), medical reasons (4 patients), and social reasons (3 patients). Outcomes for these patients were uneventful and the median length of hospital stay was 3.1 days (range 1-14 days). An unscheduled consultation was necessary for 30 patients (20.5%). Nine patients required readmission (6.1%), of whom 6 required reoperation (3.8%). The overall 30-day morbidity rate was 24.8%. The mortality rate was 0%.CONCLUSIONS:This is the first case of consecutive patients undergoing ambulatory colectomy for malignant or benign disease. We demonstrated the feasibility, safety, and reproducibility of outpatient colectomy for selected patients. In our experience, 30% of patients scheduled for elective colectomy can be managed in an ambulatory setting

History of multiple sclerosis in 2 successive pregnancies: A French and Italian cohort

Objective: To evaluate the risk of relapses during pregnancy and in the first 3 months after delivery in 2 successive pregnancies in a cohort of French and Italian women with multiple sclerosis (MS). Methods: A total of 93 women were included if they had had 2 pregnancies followed prospectively after MS onset between January 1993 and 2013. The association of a relapse during pregnancy or the first postpartum trimester in pregnancy 1 and pregnancy 2 was evaluated by univariate logistic regression. Results: A majority of women did not experience any exacerbation in the 3 months after delivery (31.2% and 23.7%, respectively, relapsed after pregnancy 1 and 2; p 0.32). A total of 7.6% had a relapse after both pregnancies. The risk of relapse after pregnancy 2 was not associated with the number of relapses in the prepregnancy year (odds ratio [OR] 1.52 [0.57-4.05]) or during pregnancy (OR 1.57 [0.52-4.79]) or with the occurrence of a relapse after pregnancy 1 (OR 0.86 [0.29-2.50]). Conclusions: Our work provides original data on the evolution of successive pregnancies in MS, showing a similar (and even lower) disease activity in the second pregnancy. There was no correlation of activity in successive pregnancies. Therefore, counseling of women with MS who consider having a second baby should be the same as for the first one

History of multiple sclerosis in 2 successive pregnancies: A French and Italian cohort

Objective: To evaluate the risk of relapses during pregnancy and in the first 3 months after delivery in 2 successive pregnancies in a cohort of French and Italian women with multiple sclerosis (MS). Methods: A total of 93 women were included if they had had 2 pregnancies followed prospectively after MS onset between January 1993 and 2013. The association of a relapse during pregnancy or the first postpartum trimester in pregnancy 1 and pregnancy 2 was evaluated by univariate logistic regression. Results: A majority of women did not experience any exacerbation in the 3 months after delivery (31.2% and 23.7%, respectively, relapsed after pregnancy 1 and 2; p 0.32). A total of 7.6% had a relapse after both pregnancies. The risk of relapse after pregnancy 2 was not associated with the number of relapses in the prepregnancy year (odds ratio [OR] 1.52 [0.57-4.05]) or during pregnancy (OR 1.57 [0.52-4.79]) or with the occurrence of a relapse after pregnancy 1 (OR 0.86 [0.29-2.50]). Conclusions: Our work provides original data on the evolution of successive pregnancies in MS, showing a similar (and even lower) disease activity in the second pregnancy. There was no correlation of activity in successive pregnancies. Therefore, counseling of women with MS who consider having a second baby should be the same as for the first one

Overweight is associated to a better prognosis in metastatic colorectal cancer: A pooled analysis of FFCD trials

IF 7.191 (2017)International audienceBACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI <18.5). Interaction tests were performed between BMI effect and sex, age and the addition of antiangiogenics to chemotherapy.RESULTS:The rate of BMI ≥25 patients was 41.5%, ranging from 37.6% (1991-1999 period) to 41.5% (2000-2006 period) and 44.8% (2007-2013 period). Comparison of overweight patients versus normal BMI range patients revealed a significant improvement of median overall survival (OS) (18.5 versus 16.3 months, HR = 0.88 [0.80-0.98] p = 0.02) and objective response rate (ORR) (42% versus 36% OR = 1.23 [1.01-1.50] p = 0.04) but a comparable median progression-free survival (PFS) (7.8 versus 7.2 months, HR = 0.96 [0.87-1.05] p = 0.35). Subgroup analyses revealed that overweight was significantly associated with better OS in men. OS and PFS were significantly shorter in thin patients.CONCLUSION:Overweight patients had a prolonged OS compared with normal weight patients with mCRC. The association of overweight with better OS was only observed in men. The pejorative prognosis of BMI <18.5 was confirmed.Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserve