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The naked mole rat (NMR), Heterocephalus glaber, the longest-living rodent1, provides a unique opportunity to explore how evolution has shaped adult stem cell (ASC) activity with increasing lifespan. Using cumulative BrdU labelling and a quantitative imaging approach to track intestinal ASCs (Lgr5+) in NMRs over time in their native in vivo state, we show adaptations to living in near-anaerobic2, food-deprived3 subterranean environment, has necessitated an expanded pool of Lgr5+ cells, which exhibit slower division rates compared to short-lived mice, but have similar turnover as humans. Unlike human LGR5+ cells at the crypt base (LGR5+CBC) that slow down their division rates by entering quiescence(G0) 4, NMR Lgr5+CBC cells in both the small intestine and the colon transit slowly through the active cell cycle (G1 to M) by prolonging arrest at G1 and/or G2. The inverse correlation between ASC division rates and lifespan appears to be specific to Lgr5+CBC/LGR5+CBC cells as this relationship is not seen for cells outside the crypt base. Our data provide an explanation for the observed anticorrelation between somatic mutation rates and longevity in mammals5, with ASC lineages in longer-lived organisms turning over slowly to possibly mitigate ASC exhaustion and reduce mutation rates for long-term tissue maintenance. Finally, we also observe an expanded pool of differentiated cells in NMRs that confer enhanced protection and function to the intestinal mucosa which is able to detect any chemical imbalance in the luminal environment efficiently, triggering a robust anti-proliferative, pro-apoptotic response within the stem cell zone.

ObjectiveEndoscopic resection (ER) often involves referral to tertiary centres with high volume practices. Lesions can be subject to prior manipulation and mischaracterisation of features required for accurate planning, leading to prolonged or cancelled procedures. As potential solutions, repeating diagnostic procedures is burdensome for services and patients, while even enriched written reports and still images provide insufficient information to plan ER. This project sought to determine the frequency and implications of polyp mischaracterisation and whether the use of telestration might prevent it.Design/methodA retrospective data analysis of ER referrals to four tertiary centres was conducted for the period July–December 2019. Prospective telestration with a novel digital platform was then performed between centres to achieve consensus on polyp features and ER planning.Results163 lesions (163 patients; mean age 67.9±12.2 y; F=62) referred from regional hospitals, were included. Lesion site was mismatched in 11 (6.7%). Size was not mentioned in the referral in 27/163 (16.6%) and incorrect in 81/136 (51.5%), more commonly underestimated by the referring centre (ConclusionsPolyp mischaracterisation is a frequent feature of ER referrals, but could be corrected by the use of telestration between centres. Our study involved expert-to-expert consensus, so extending to ‘real-world’ referring centres would offer additional learning for a digital pathway.

Aims Evaluating the effect of Covid-19 on case selection and perioperative outcomes of emergency laparotomies across South West London (SWL). Methods A retrospective cohort study including all emergency laparotomies performed at three SWL-based NHS hospitals from 01/04/2020-31/12/2020 (i.e., “pandemic” cohort; from the first national lockdown), versus a “pre-pandemic” cohort (01/04/2019-31/12/2019). Data was extracted from the NELA database and hospital records, and analysed by two independent clinicians. Results 414 patients met the inclusion criteria. 17.6% fewer (227 vs. 187) laparotomies were performed during the pandemic period. There were no significant sociodemographic differences between cohorts (mean age 64.5 vs. 62.7 years, p = 0.284; M:F ratio 1:1.154 vs. 1:0.928, p = 0.221). Pre-operative NELA risk scores were higher before the pandemic (mean 13.05% vs. 9.55%, p = 0.020). The commonest indication for laparotomy in both cohorts was small bowel obstruction (32.6% vs. 37.4%), treated most commonly with adhesiolysis. Postoperatively, fewer patients received HDU/ITU care during the pandemic than before (ward-based recovery 4.7% vs. 13.8%, HDU/ITU recovery 93.4% vs. 79.4%, χ2=15.4, p Conclusions The overall reduction in emergency laparotomies observed during the pandemic period was potentially secondary to tighter case selection guided by objective risk stratification. Fewer patients were recovered postoperatively on HDU/ITU, and patients were generally discharged from hospital earlier. Such trends in perioperative care served to support organizational prioritization in response to Covid-19 service provision.

Aims Recent case reports have described occult gastrointestinal perforation secondary to Covid-related microcirculatory thromboembolic phenomena. This study aims to evaluate the effect of Covid-19 on the incidence of gastrointestinal perforations across South West London (SWL). Methods A retrospective cohort study included all patients with gastrointestinal perforations presenting to three SWL-based NHS hospitals from 01/04/2020-31/12/2020 (i.e. “pandemic” cohort; from the first national lockdown), versus a representative “pre-pandemic” cohort (01/04/2019-31/12/2019). Data was extracted from the hospital coding records, patient case-notes, and the NELA database, and analysed by two independent clinicians. Results A total of 448 patients were included. 9.3% more (214 vs. 234, p = 0.286) gastrointestinal perforations presented during the pandemic period than beforehand. Comparing both periods, there were no significant differences between the numbers of colonic diverticular perforations (183 vs. 185), gastrojejunal ulcer perforations (1 per period), and terminal ileal perforations (1 per period). There were 78% more peptic ulcer perforations (9 vs. 16) and 55% more gallbladder perforations (20 vs. 31) during the pandemic period, although no overall significant difference was derived at the 95% confidence interval (Χ2=3.458, p = 0.484). Conclusions While there was no significant overall increase in spontaneous gastrointestinal perforation during Covid-19, this study clearly suggests increased rates of peptic and gallbladder perforations. Larger-scale epidemiological data are warranted to ascertain whether this is secondary to increased consumption of alcohol, non-steroidal anti-inflammatory medication or other pro-ulcerative drug regimes during the pandemic. Further data will also be vital to highlight delays in investigation and/or presentation resulting in these increased perforation rates.

Saliva represents an ideal matrix for diagnostic biomarker development as it is readily available and requires no invasive collection procedures. However, salivary RNA is labile and rapidly degrades. Previous attempts to isolate RNA from saliva have yielded poor quality and low concentrations. Here we compare collection and processing methods and propose an approach for future studies. The effects of RNA stabilisers, storage temperatures, length of storage and fasting windows were investigated on pooled saliva samples from healthy volunteers. Isolated RNA was assessed for concentration and quality. Bacterial growth was investigated through RT-PCR using bacterial and human primers. Optimal conditions were implemented and quality controlled in a clinical setting. The addition of RNAlater increased mean RNA yield from 4912 ng/μl to 15,473 ng and RNA Integrity Number (RIN) from 4.5 to 7.0. No significant changes to RNA yield were observed for storage at room temperature beyond 1 day or at -80 °C. Bacterial growth did not occur in samples stored at ambient temperature for up to a week. There was a trend towards higher RNA concentration when saliva was collected after overnight fasting but no effect on RIN. In the clinic, RNA yields of 6307 ng and RINs of 3.9 were achieved, improving on previous reports. The method we describe here is a robust, clinically feasible saliva collection method using preservative that gives high concentrations and improved RINs compared to saliva collected without preservative.