Background Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov , NCT04384926 . Findings Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include...

Background The coronavirus disease 2019 (COVID‐19) pandemic caused disruptions in treatment for cancer. Less is known about its impact on new cancer diagnoses, where delays could cause worsening long‐term outcomes. This study quantifies decreases in encounters related to prostate, lung, bladder and colorectal cancers, procedures that facilitate their diagnosis, and new diagnoses of those cancers in the COVID era compared to pre‐COVID era. Methods All encounters at Veterans' Affairs facilities nationwide from 2016 through 2020 were reviewed. The authors quantified trends in new diagnoses of cancer and in procedures facilitating their diagnosis, from January 1, 2018 onward. Using 2018 to 2019 as baseline, reductions in procedures and new cancer diagnoses in 2020 were estimated. Calculated absolute and percentage differences in annual volume and observed‐to‐expected volume ratios were calculated. Heat maps and funnel plots of volume changes were generated. Results From 2018 through 2020, there were 4.1 million cancer‐related encounters, 3.9 million relevant procedures, and 251,647 new cancers diagnosed. Compared to the annual averages in 2018 through 2019, colonoscopies in 2020 decreased by 45% whereas prostate biopsies, chest computed tomography scans, and cystoscopies decreased by 29%, 10%, and 21%, respectively. New cancer diagnoses decreased by 13% to 23%. These drops varied by state and continued to accumulate despite reductions in pandemic‐related restrictions. Conclusion The authors identified substantial reductions in procedures used to diagnose cancer and subsequent reductions in new diagnoses of cancer across the United States because of the COVID‐19 pandemic. A nomogram is provided to identify and resolve these unmet health care needs and avoid worse long‐term cancer outcomes. Lay Summary The disruptions due to the COVID‐19 pandemic have led to substantial reductions in new cancers being diagnosed. This study quantifies those reductions in a national health care system and offers a method for understanding the backlog of cases and the resources needed to resolve them.

Previous studies have shown that gene therapy with inducible nitric oxide synthase (iNOS) protects against myocardial infarction at 3 days after gene transfer. However, the long-term effects of iNOS gene therapy on myocardial ischemic injury and cardiac function are unknown. To address this issue, we used a recombinant adenovirus 5 (Ad5) vector (Av3) with deletions of the E1, E2a, and E3 regions, which enables long-lasting recombinant gene expression for at least 2 mo due to lack of inflammation. Mice received intramyocardial injections in the left ventricular (LV) anterior wall of Av3/LacZ (LacZ group) or Av3/iNOS (iNOS group); 1 or 2 mo later, they were subjected to myocardial infarction (30-min coronary occlusion followed by 4 h of reperfusion). Cardiac iNOS gene expression was confirmed by immunoblotting and activity assays at 1 and 2 mo after gene transfer. In the iNOS group, infarct size (percentage of risk region) was significantly reduced (P < 0.05) both at 1 mo (24.2 ± 3.4%, n = 6, vs. 48.0 ± 3.6%, n = 8, in the LacZ group) and at 2 mo (23.4 ± 3.1%, n = 8, vs. 36.6 ± 2.4%, n = 7). The infarct-sparing effects of iNOS gene therapy were as powerful as those observed 24 h after ischemic preconditioning (23.1 ± 3.4%, n = 10). iNOS gene transfer had no effect on LV function or dimensions up to 8 wk later (echocardiography). These data demonstrate that iNOS gene therapy mediated by the Av3 vector affords long-term (2 mo) cardioprotection without inflammation or adverse functional consequences, a finding that provides a rationale for further preclinical testing of this therapy. Keywordsnitric oxide synthase; cardiac function; mouse Although ischemic preconditioning (PC) is known to be a powerful cardioprotective adaptation, it has not yet found clinical application. The late phase of PC would appear particularly suitable for therapeutic exploitation because it is underlain by the upregulation of cardioprotective genes, which, if expressed chronically, could conceivably induce a longlasting PC state (3, 4). Among these genes, the inducible isoform of nitric oxide (NO) synthase (iNOS) has been studied most thoroughly. Extensive evidence over the past decade demonstrates that iNOS is an obligatory mediator of the protection afforded by late PC induced by various stimuli, including ischemia, physical exercise, and various pharmacological agents (1-3, 5). Therefore, upregulation of iNOS appears to be a final common pathway whereby diverse stimuli induce a shift of the heart to a defensive clinically to protect the ischemic myocardium, it is important to determine whether chronic overexpression of iNOS in the myocardium is cardioprotective.In this regard, a number of experimental and clinical results have been interpreted to suggest that enhanced production of NO via iNOS is detrimental to the myocardium (13,20). Increased iNOS activity has been reported in ventricular tissue from patients with dilated cardiomyopathy (6). Increased iNOS activity has also been found in myocarditis, ischemic heart disease, valv...

This pilot study indicates that the use of CGM values in hospitalized patients can be successfully transmitted to a monitoring device in the nursing station, improving patient surveillance in insulin treated patients with diabetes.