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

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Different HBsAg decline after 3 years of therapy with entecavir in patients affected by chronic hepatitis B HBeAg-negative and genotype A, D and E

The role of measurement of hepatitis B "s" antigen (HBsAg) during the therapy with oral nucleos(t)ide analogues is still debatable. The HBsAg declines after 3 years of therapy with entecavir (ETV) was investigated among patients affected by hepatitis B virus (HBV), e antigen (HBeAg)-negative and genotypes A, D and E. A prospective cohort of 123 patients was enrolled consecutively from April 2007 to May 2010 with at least 3 years of treatment with ETV. Patients with chronic HBV infection, HBeAg-negative, naive for previous treatment and with virological response to ETV were included in the study. HBsAg level and HBV-DNA were tested every 3 months during the first year of treatment, then every 6 months for a time of at least 3 years. After 3 years, HBsAg decline was 0.77\u2009log\u2009IU/ml, 0.65\u2009log\u2009IU/ml, 0.45 respectively; A versus D (P\u2009=\u20090.012), A versus E (P\u2009<\u20090.001), D versus E (P\u2009<\u20090.001). In the multivariate linear regression analysis only the HBV genotype was predictive of HBsAg decline after 3 years of treatment (P\u2009<\u20090.001). The expected time to HBsAg loss was 15.6 years for the A genotype, 17 years for D, 24.6 years for E (P\u2009<\u20090.001). The treatment with ETV leads the different kinetics in HBsAg decline among genotypes A, D and E; the expected time of HBsAg loss was significantly higher in E genotype compared to A and D genotype

Role of CYP27B1+2838 promoter polymorphism in the treatment of chronic hepatitis B HBeAg negative with PEG-interferon

In HBV-infected patients, the vitamin D deficiency has been related to chronic liver diseases, progression of hepatic fibrosis and poor response to the treatment. The CYP27B1 gene, which encodes the 1-??-hidroxylase and involved in the 1,25-dihydroxyvitamin D synthesis, was recently associated to type-1 diabetes, autoimmune disorders and treatment response in HCV. Then, we aimed to investigate the role of CYP27B1 polymorphisms in HBV treatment with PEG-IFN. We retrospectively enrolled 190 patients with chronic hepatitis B HBeAg negative treated for 48 weeks with PEG-IFN ??-2a. We examined the role of rs4646536 CYP27B1 SNP (CYP27B1+2838) according to virological and serological response. Our results showed that the TT genotype of CYP27B1+2838 was significantly prevalent in patients with end-of-therapy virological response (37.6%) vs CT/CC (9.4%) (P < 0.001). Virological relapse was prevalent in patients with CT/CC genotype (12.6%) vs TT genotype (2.1%) (P < 0.001). TT genotype was also related to HBsAg loss (P = 0.004) and anti-HBs appearance (P = 0.002). In the multivariate analysis, the TT genotype resulted to be a good positive predictor of sustained virological response (OR = 5.632, IC = 1.938-16.368, P = 0.001) and serological response (OR = 6.161, IC = 1.856-20.457, P = 0.003). The CYP27B1+2838 polymorphism may be useful as pretreatment factor to selection of patients with higher probability of response to therapy

Second-look digital breast tomosynthesis (SL-DBT) in assessing incidental findings (IFs) at contrast-enhanced magnetic resonance imaging (CE-MRI) in patients with newly diagnosed breast cancer

Purpose: To test if SL-DBT, i.e. the re-evaluation of DBT images after CEMRI, helps assessing IFs at CE-MRI in patients with newly diagnosed breast cancer. Methods and Materials: Two experienced readers in consensus retrospectively reviewed the examinations of 43 patients who underwent DBT and CE-MRI from May 2012 to January 2013, looking for a DBT correlate of IFs at CE-MR. Standard of reference was histology for CE-MRI suspicious findings (ACR-BIRADS-3-5) and imaging follow-up for CE-MRI non-suspicious findings (ACR-BIRADS-1-2). Fisher exact test was used. Results: A total of 32 CE-MRI IFs were detected in 24 patients: 18 BIRADS-2 and 14 BIRADS-3-5. A DBT correlate was found in 12/24 IFs (38%) overall, 8/14 (57%) MR-BIRADS-3-5 and 4/18 (22%) MR-BIRADS-2 IFs, with borderline significance (p=0.080). Malignancy was histologically confirmed for 10/14 CE-MRI IFs; 6 of these 10 additional malignancies (60%) had a DBT correlate with suspicious features: 3 invasive lobular; 2 ductal carcinoma in situ; and 1 invasive ductal. A significantly lower rate of DBT correlate (6/22, 27%), was found for non-suspicious CE-MRI IFs, all with benign features (p=0.005). Conclusion: A DBT correlate was more frequent for malignant than for benign CE-MRI IFs. SL-DBT has the potential to confirm more than 50% of suspicious CE-MR IFs. However, the absence of a DBT correlate does not warrant to avoid MR-guided biopsy