The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Ozone exposure is associated with acute changes in inflammation, fibrinolysis, and endothelial cell function in coronary artery disease patients

Abstract Background Air pollution is a major risk factor for cardiovascular disease, of which ozone is a major contributor. Several studies have found associations between ozone and cardiovascular morbidity, but the results have been inconclusive. We investigated associations between ozone and changes across biological pathways associated with cardiovascular disease. Methods Using a panel study design, 13 participants with coronary artery disease were assessed for markers of systemic inflammation, heart rate variability and repolarization, lipids, blood pressure, and endothelial function. Daily measurements of ozone and particulate matter (PM2.5) were obtained from central monitoring stations. Single (ozone) and two-pollutant (ozone and PM2.5) models were used to assess percent changes in measurements per interquartile ranges of pollutants. Results Per interquartile increase in ozone, changes in tissue plasminogen factor (6.6%, 95% confidence intervals (CI) = 0.4, 13.2), plasminogen activator inhibitor-1 (40.5%, 95% CI = 8.7, 81.6), neutrophils (8.7% 95% CI = 1.5, 16.4), monocytes (10.2%, 95% CI = 1.0, 20.1), interleukin-6 (15.9%, 95% CI = 3.6, 29.6), large-artery elasticity index (−19.5%, 95% CI = −34.0, −1.7), and the baseline diameter of the brachial artery (−2.5%, 95% CI = −5.0, 0.1) were observed. These associations were robust in the two-pollutant model. Conclusions We observed alterations across several pathways associated with cardiovascular disease in 13 coronary artery disease patients following ozone exposures, independent of PM2.5. The results support the biological plausibility of ozone-induced cardiovascular effects. The effects were found at concentrations below the EPA National Ambient Air Quality Standards for both ozone and PM2.5

Additional file 1: Table S1. of Ozone exposure is associated with acute changes in inflammation, fibrinolysis, and endothelial cell function in coronary artery disease patients

Percent changes of measured factors with ambient ozone concentrations. Effect estimates (95% CI) were log-transformed, correspond to changes per IQR of ozone, and were adjusted for season, temperature, and humidity. Effect estimates for SumPSD, LF:HF, LF, HF, FMD, and CRP were also adjusted for the 5dMA barometric pressure. LAIE = large artery elasticity index; SAEI = small artery elasticity index; FMD = flow-mediated dilatation; BAD = baseline artery diameter; SBP = systolic blood pressure; DBP = diastolic blood pressure; tPA = tissue plasminogen factor; PAI-1 = plasminogen activator inhibitor-1; vWF = von Willebrand factor; IL = interleukin; TNF = tumor necrosis factor; CRP = C-reactive protein; SAA = serum amyloid A; sICAM = soluble intercellular adhesion molecule; sVCAM = soluble vascular adhesion molecule; HDL = high density lipoprotein; LDL = low density lipoprotein; LF = low frequency; HF = high frequency; PSD = power spectrum density; SDNN = standard deviation of the normal-to-normal; rMSSD = root-mean squared of successive differences. *p value < 0.10 for the percent change from the mean of the measured outcome per unit IQR of exposure, **p value < 0.05 for the percent change from the mean of the measured outcome per unit IQR of exposure. (DOCX 21 kb

A genome-wide trans-ethnic interaction study links the PIGR-FCAMR locus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic.

Air pollution is a worldwide contributor to cardiovascular disease mortality and morbidity. Traffic-related air pollution is a widespread environmental exposure and is associated with multiple cardiovascular outcomes such as coronary atherosclerosis, peripheral arterial disease, and myocardial infarction. Despite the recognition of the importance of both genetic and environmental exposures to the pathogenesis of cardiovascular disease, studies of how these two contributors operate jointly are rare. We performed a genome-wide interaction study (GWIS) to examine gene-traffic exposure interactions associated with coronary atherosclerosis. Using race-stratified cohorts of 538 African-Americans (AA) and 1562 European-Americans (EA) from a cardiac catheterization cohort (CATHGEN), we identify gene-by-traffic exposure interactions associated with the number of significantly diseased coronary vessels as a measure of chronic atherosclerosis. We found five suggestive (P<1x10-5) interactions in the AA GWIS, of which two (rs1856746 and rs2791713) replicated in the EA cohort (P < 0.05). Both SNPs are in the PIGR-FCAMR locus and are eQTLs in lymphocytes. The protein products of both PIGR and FCAMR are implicated in inflammatory processes. In the EA GWIS, there were three suggestive interactions; none of these replicated in the AA GWIS. All three were intergenic; the most significant interaction was in a regulatory region associated with SAMSN1, a gene previously associated with atherosclerosis and B cell activation. In conclusion, we have uncovered several novel genes associated with coronary atherosclerosis in individuals chronically exposed to increased ambient concentrations of traffic air pollution. These genes point towards inflammatory pathways that may modify the effects of air pollution on cardiovascular disease risk

Manhattan Plot of Interaction P-values for EA GWIS.

<p>Manhattan plot of interaction P-values for the EA GWIS. Though no interactions achieved genome-wide significance (red line) interactions on chromosome 11 (<i>CAPRIN1</i>), 18, and 21 (<i>SAMSN1</i> open chromatin region) exceeded the suggestive significance threshold (blue line).</p

LocusZoom Plot of <i>FCAMR-PIGR</i> locus for African-Americans.

<p>LD is calculated relative to the most significant variant rs1856746. LD across the three most significant variants within the region is substantial however all other variants in the region show little correlation with rs291096 despite the relatively low recombination rate across the region. For plotting 1000 Genomes data is used (population AFR) in genome build hg19.</p

GWIS interactions with P < 1x10^-5.

<p>GWIS interactions with P < 1x10^-5.</p

LocusZoom Plot of Open Chromatin Region Downstream of <i>SAMSN1</i> for EA GWIS.

<p>Overall the LD across the region is modest to low supporting the hypothesis that the interaction association signal is coming from rs2822693 or an untyped variant in high LD with it, likely restricted to the region between the two recombination peaks. For plotting 1000 Genomes data was used (population = EUR) in genome build hg19.</p