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

Genetic analysis of synaptotagmin 2 in spontaneous and Ca(2+)-triggered neurotransmitter release

Synaptotagmin 2 resembles synaptotagmin 1, the Ca(2+) sensor for fast neurotransmitter release in forebrain synapses, but little is known about synaptotagmin 2 function. Here, we describe a severely ataxic mouse strain that harbors a single, destabilizing amino-acid substitution (I377N) in synaptotagmin 2. In Calyx of Held synapses, this mutation causes a delay and a decrease in Ca(2+)-induced but not in hypertonic sucrose-induced release, suggesting that synaptotagmin 2 mediates Ca(2+) triggering of evoked release in brainstem synapses. Unexpectedly, we additionally observed in synaptotagmin 2 mutant synapses a dramatic increase in spontaneous release. Synaptotagmin 1-deficient excitatory and inhibitory cortical synapses also displayed a large increase in spontaneous release, demonstrating that this effect was shared among synaptotagmins 1 and 2. Our data suggest that synaptotagmin 1 and 2 perform equivalent functions in the Ca(2+) triggering of action potential-induced release and in the restriction of spontaneous release, consistent with a general role of synaptotagmins in controlling ‘release slots' for synaptic vesicles at the active zone

The role of Schmidt 'Antonovka' in apple scab resistance breeding

'Antonovka' has long been recognised as a major source of scab (Venturia inaequalis) resistance useful for apple breeding worldwide. Both major gene resistances in the form of the Rvi10 and Rvi17 and quantitative resistance, collectively identified as VA, have been identified in different accessions of 'Antonovka'. Most of the 'Antonovka' scab resistance used in apple-breeding programmes around the world can be traced back to Schmidt 'Antonovka' and predominantly its B VIII progenies 33,25 (PI 172623), 34,6 (PI 172633), 33,8 (PI 172612) and 34,5 (PI 172632). Using genetic profile reconstruction, we have identified "common 'Antonovka' " as the progenitor of the B VIII family, which is consistent with it having been a commercial cultivar in Poland and the single source of scab resistance used by Dr. Martin Schmidt. The major 'Antonovka' scab resistance genes mapped to date are located either very close to Rvi6, or about 20-25 cM above it, but their identities need further elucidation. The presence of the 139 bp allele of the CH-Vf1 microsatellite marker known to be associated with Rvi17 (Va1) in most of the 'Antonovka' germplasm used in breeding suggests that it plays a central role in the resistance. The nature and the genetic relationships of the scab resistance in these accessions as well as a number of apple cultivars derived from 'Antonovka', such as, 'Freedom', 'Burgundy' and 'Angold', are discussed. The parentage of 'Reglindis' is unclear, but the cultivar commercialised as 'Reglindis' was confirmed to be an Rvi6 cultivar