Two-year outcomes of conservatively managed appendicitis during the COVID-19 pandemic-a multicentre cohort study.

PURPOSE: During the COVID-19 pandemic, the new RCSEng guidelines resulted in appendicitis being more commonly managed conservatively to avoid aerosol-generating procedures. This resulted in shorter hospital stays without increased short-term complications. The 2-year outcomes of this change, specifically recurrence and re-admission rates remain unknown. METHODS: We conducted a multicentre, prospective, observational study including all adult patients treated as appendicitis after the implementation of the new surgical guidelines during the COVID-19 pandemic. Outcomes included initial management failure, re-admission rate, appendicitis recurrence, and interval appendicectomy. A historical cohort prior to the COVID-19 pandemic was used for comparison. Patients were followed up for 2-years post index admission. Categorical and continuous variables were compared using Fisher's exact test and Student's T or Mann-Whitney U tests as appropriate. RESULTS: Sixty-three and 79 patients with appendicitis were included from four NHS trusts, before (A) and after (B) the new intercollegiate guidelines respectively. Operative management was used less frequently in cohort B (28/79 vs 52/63; p<0.001). More patients re-presented in cohort B (14/79 vs 3/63; p=0.020), but not when comparing only those managed conservatively (2/11 vs 13/52; p=1.000). A similar trend was observed for appendicitis recurrence although without statistical significance (2/63 vs 9/79; p=0.112); with loss of trend when comparing those managed conservatively-only (2/11 vs 9/52; p=1.000). Among all patients, four (2.8%) were found to have underlying neoplasia of which three were initially managed conservatively (3/63; 4.8%). CONCLUSION: Conservative management of appendicitis has previously been shown to have short-term benefits in expedited hospital discharge without early complications. The present study shows it has a higher readmission and appendicitis recurrence rates. The risks of this alongside missed/delayed management of neoplasia needs to be considered alongside the benefits including avoidance of aerosol-generating general anaesthesia and laparoscopy during the COVID-19 pandemic or similar future health crises. Small case numbers limit analysis.

Glue versus mechanical mesh fixation in laparoscopic inguinal hernia repair: meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: The optimal choice for mesh fixation in laparoscopic inguinal hernia repair (LIHR) has not been well established. This review compared the effects of glue versus mechanical mesh fixation in LIHR on incidence of chronic postoperative inguinal pain (CPIP) and other secondary outcomes, including acute pain, seroma, haematoma, hernia recurrence and other postoperative complications. METHODS: A systematic review of English/non-English studies using MEDLINE, the Cochrane Library, OpenGrey, OpenThesis and Web of Science, and searching bibliographies of included studies was completed. Search terms included laparoscopic, hernia, fibrin glue, Tisseel, Tissucol, cyanoacrylate, Glubran and Liquiband. Only RCTs comparing mechanical with glue-based fixation in adult patients (aged over 18 years) that examined CPIP were included. Two authors independently completed risk-of-bias assessment and data extraction against predefined data fields. All pooled analyses were computed using a random-effects model. RESULTS: Fifteen RCTs met the inclusion criteria; 2777 hernias among 2109 patients were assessed. The incidence of CPIP was reduced with use of glue-based fixation (risk ratio (RR) 0.36, 95 per cent c.i. 0.19 to 0.69; P = 0.002), with moderate heterogeneity that disappeared with sensitivity analysis (8 d.f.) for patient-blinded studies (RR 0.43, 0.27 to 0.86). Trial sequential analysis provided evidence for a relative risk reduction of at least 25 per cent. The incidence of haeamtoma was reduced by using glue-based fixation (RR 0.29, 0.10 to 0.82; P = 0.02) with no significant effects on seroma formation or hernia recurrence (RR 1.07, 0.46 to 2.47; P = 0.88). CONCLUSION: Glue-based mesh fixation appears to reduce the incidence of CPIP and haematoma after LIHR compared with mechanical fixation, with comparable recurrence rates.

Design, synthesis, and biological evaluation of aryl piperazines with potential as antidiabetic agents via the stimulation of glucose uptake and inhibition of NADH:ubiquinone oxidoreductase.

The management of blood glucose levels and the avoidance of diabetic hyperglycemia are common objectives of many therapies in the treatment of diabetes. An aryl piperazine compound 3a (RTC1) has been described as a promoter of glucose uptake, in part through a cellular mechanism that involves inhibition of NADH:ubiquinone oxidoreductase. We report herein the synthesis of 41 derivatives of 3a (RTC1) and a systematic structure-activity-relationship study where a number of compounds were shown to effectively stimulate glucose uptake in vitro and inhibit NADH:ubiquinone oxidoreductase. The hit compound 3a (RTC1) remained the most efficacious with a 2.57 fold increase in glucose uptake compared to vehicle control and micromolar inhibition of NADH:ubiquinone oxidoreductase (IC50 = 27 µM). In vitro DMPK and in vivo PK studies are also described, where results suggest that 3a (RTC1) would not be expected to provoke adverse drug-drug interactions, yet be readily metabolised, avoid rapid excretion, with a short half-life, and have good tissue distribution. The overall results indicate that aryl piperazines, and 3a (RTC1) in particular, have potential as effective agents for the treatment of diabetes.