Determinants of SARS-CoV-2 receptor gene expression in upper and lower airways

The recent outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic. One week after initial symptoms develop, a subset of patients progresses to severe disease, with high mortality and limited treatment options. To design novel interventions aimed at preventing spread of the virus and reducing progression to severe disease, detailed knowledge of the cell types and regulating factors driving cellular entry is urgently needed. Here we assess the expression patterns in genes required for COVID-19 entry into cells and replication, and their regulation by genetic, epigenetic and environmental factors, throughout the respiratory tract using samples collected from the upper (nasal) and lower airways (bronchi). Matched samples from the upper and lower airways show a clear increased expression of these genes in the nose compared to the bronchi and parenchyma. Cellular deconvolution indicates a clear association of these genes with the proportion of secretory epithelial cells. Smoking status was found to increase the majority of COVID-19 related genes including ACE2 and TMPRSS2 but only in the lower airways, which was associated with a significant increase in the predicted proportion of goblet cells in bronchial samples of current smokers. Both acute and second hand smoke were found to increase ACE2 expression in the bronchus. Inhaled corticosteroids decrease ACE2 expression in the lower airways. No significant effect of genetics on ACE2 expression was observed, but a strong association of DNA- methylation with ACE2 and TMPRSS2- mRNA expression was identified in the bronchus.</p

Textbook outcome as a composite outcome measure in non-small-cell lung cancer surgery

Contains fulltext : 231430.pdf (Publisher’s version ) (Open Access

Variability of Active Cervical Range of Motion Within and Between Days in Healthy Participants:A Prospective Observational Study

OBJECTIVE: The purpose of this study was to determine the intraday and interday variability and systematic change over the day of active cervical range of motion (aCROM) measurements in asymptomatic persons using a clinically applicable measurement device. METHODS: A prospective observational study was performed. Sixteen adults (8 men and 8 women, median age 51 years) without neck pain in the last 3 months were recruited in 2 physiotherapy practices. Active cervical range of motion was estimated using the Apple iPhone application "3D Range of Motion." Measurements were performed 3 times a day for 7 days and spread over a period of 3 weeks. Mean values of aCROM were calculated. Intraday and interday variability was estimated by calculating limits of agreement. RESULTS: The limits of agreement for intraday variability ranged from ±12.1° for left rotation to ±15.5° for total rotation. For interday variability, the limits of agreement ranged from ±14.2° for right rotation to ±20.1° for total rotation. No systematic change over the day was found. CONCLUSION: This study showed substantial intraday and interday variability of aCROM measurements in asymptomatic people. No trend toward an increased or decreased aCROM was observed during the course of the day. When interpreting aCROM values, clinicians should consider the degree of variation in aCROM measurements over time

Safety of elective colorectal cancer surgery:Non-surgical complications and colectomies are targets for quality improvement

Background Mortality following severe complications (failure-to-rescue, FTR) is targeted in surgical quality improvement projects. Rates may differ between colon- and rectal cancer resections. Methods Analysis of patients undergoing elective colon and rectal cancer resections registered in the Dutch Surgical Colorectal Audit in 2011-2012. Severe complication- and FTR rates were compared between the groups in univariate and multivariate analysis. Results Colon cancer (CC) patients (n = 10,184) were older and had more comorbidity. Rectal cancer (RC) patients (n = 4,906) less often received an anastomosis and had more diverting stomas. Complication rates were higher in RC patients (24.8% vs. 18.3%, P <0.001). However, FTR rates were higher in CC patients (18.6% vs. 9.4%, P <0.001). Particularly, FTR associated with anastomotic leakage, postoperative bleeding, and infections was higher in CC patients. Adjusted for casemix, CC patients had a twofold risk of FTR compared to RC patients (OR 1.89, 95% CI 1.06-3.37). Conclusions Severe complication rates were lower in CC patients than in RC patients; however, the risk of dying following a severe complication was twice as high in CC patients, regardless of differences in characteristics between the groups. Efforts should be made to improve recognition and management of postoperative (non-)surgical complications, especially in colon cancer surgery. J. Surg. Oncol. 2014 109:???-???. (c) 2013 Wiley Periodicals, Inc

Yield of Screening for COVID-19 in Asymptomatic Patients Before Elective or Emergency Surgery Using Chest CT and RT-PCR (SCOUT): Multicenter Study

OBJECTIVE: To determine the yield of preoperative screening for COVID-19 with chest CT and RT-PCR in patients without COVID-19 symptoms. SUMMARY OF BACKGROUND DATA: Many centers are currently screening surgical patients for COVID-19 using either chest CT, RT-PCR or both, due to the risk for worsened surgical outcomes and nosocomial spread. The optimal design and yield of such a strategy are currently unknown. METHODS: This multicenter study included consecutive adult patients without COVID-19 symptoms who underwent preoperative screening using chest CT and RT-PCR before elective or emergency surgery under general anesthesia. RESULTS: A total of 2093 patients without COVID-19 symptoms were included in 14 participating centers; 1224 were screened by CT and RT-PCR and 869 by chest CT only. The positive yield of screening using a combination of chest CT and RT-PCR was 1.5% [95% confidence interval (CI): 0.8-2.1]. Individual yields were 0.7% (95% CI: 0.2-1.1) for chest CT and 1.1% (95% CI: 0.6-1.7) for RT-PCR; the incremental yield of chest CT was 0.4%. In relation to COVID-19 community prevalence, up to ∼6% positive RT-PCR was found for a daily hospital admission rate >1.5 per 100,000 inhabitants, and around 1.0% for lower prevalence. CONCLUSIONS: One in every 100 patients without COVID-19 symptoms tested positive for SARS-CoV-2 with RT-PCR; this yield increased in conjunction with community prevalence. The added value of chest CT was limited. Preoperative screening allowed us to take adequate precautions for SARS-CoV-2 positive patients in a surgical population, whereas negative patients needed only routine procedures

Yield of Screening for COVID-19 in Asymptomatic Patients Before Elective or Emergency Surgery Using Chest CT and RT-PCR (SCOUT): Multicenter Study

OBJECTIVE: To determine the yield of preoperative screening for COVID-19 with chest CT and RT-PCR in patients without COVID-19 symptoms. SUMMARY OF BACKGROUND DATA: Many centers are currently screening surgical patients for COVID-19 using either chest CT, RT-PCR or both, due to the risk for worsened surgical outcomes and nosocomial spread. The optimal design and yield of such a strategy are currently unknown. METHODS: This multicenter study included consecutive adult patients without COVID-19 symptoms who underwent preoperative screening using chest CT and RT-PCR before elective or emergency surgery under general anesthesia. RESULTS: A total of 2093 patients without COVID-19 symptoms were included in 14 participating centers; 1224 were screened by CT and RT-PCR and 869 by chest CT only. The positive yield of screening using a combination of chest CT and RT-PCR was 1.5% [95% confidence interval (CI): 0.8-2.1]. Individual yields were 0.7% (95% CI: 0.2-1.1) for chest CT and 1.1% (95% CI: 0.6-1.7) for RT-PCR; the incremental yield of chest CT was 0.4%. In relation to COVID-19 community prevalence, up to ∼6% positive RT-PCR was found for a daily hospital admission rate >1.5 per 100,000 inhabitants, and around 1.0% for lower prevalence. CONCLUSIONS: One in every 100 patients without COVID-19 symptoms tested positive for SARS-CoV-2 with RT-PCR; this yield increased in conjunction with community prevalence. The added value of chest CT was limited. Preoperative screening allowed us to take adequate precautions for SARS-CoV-2 positive patients in a surgical population, whereas negative patients needed only routine procedures