Aims With the evolving landscape of acute upper GI bleeding (AUGIB) management, a comprehensive understanding of changing clinical outcomes becomes imperative. This report presents findings from the 2022 UK-wide multi-centre AUGIB audit, drawing comparisons to the previous 2007 study. [1]

BACKGROUND AND OBJECTIVES:The role of various genetic markers including alpha synuclein, Parkin, etc., is known in the pathogenesis of Parkinson's disease (PD). Novel genetic markers including paraoxonase 1 (PON1) have also been linked to PD pathogenesis in recent studies. The PON1 L55M allele carriers may have defective clearance of environmental toxins and may result in increased susceptibility to PD. Hence, we studied the role of PON1 L55M polymorphism in PD among a North Indian population. MATERIALS AND METHOD:Seventy-four PD patients and 74 age- and sex-matched controls were recruited in this hospital-based case-control study. Baseline characteristics were recorded using structured questionnaire. DNA was extracted from 3-4 ml of venous blood, followed by PCR and restriction digestion. PON1 L55M genotypes were visualized as bands: LL (177 bp), LM (177, 140 bp) and MM (140,44 bp) on 3% agarose gel. Mann-Whitney U test and Chi-squared test were used for comparing two groups of skewed and categorical variables, respectively. Measures of strength of association were calculated by binary regression analysis. P value < 0.05 was considered as significant. RESULTS:Parkinson's disease patients had significantly higher exposure to pesticides (12.2%; P (organophosphate exposure) < 0.001) and well water drinking (28.4%; P = 0.006) compared to controls. Frequency distribution of LL, LM, MM genotypes was 67.5% (50/74), 28.4% (21/74), and 4.1% (3/74), respectively, for cases and 72.6% (54/74), 26% (19/74) and 1.4% (1/74), respectively, for controls. PON1 L55M genotype distribution between Parkinson's disease cases and controls was not significant (P = 0.53). PON1 L55M polymorphism was not associated with PD after adjusting for confounders by binary regression analysis. CONCLUSION:There was no significant association between PON1 L55M polymorphism and PD. Larger population-based studies would be required from India before drawing any definite conclusions.

Background: To assess the prevalence of gustatory (taste) dysfunction in Long COVID-19 patients, along with the type of dysfunction and the time taken for its resolution. Methods: This is a retrospective observational study based on patients presenting to a specialist smell clinic being run as a part of long COVID clinic in an ENT department in a regional hospital in UK. Out of all these patients presenting to this clinic, the ones with taste problems with or without smell problems were included in this study and analysed from electronic patient records. Their taste dysfunction was described along with the follow up period to look at the resolution of symptoms and the time taken for the resolution. Results: 70% of the patients had hypogeusia, 22% had dysgeusia and 8% had ageusia. 52% of the patients showed partial resolution of taste dysfunction, 28 % showed complete resolution and 16% had no improvement in a follow up period of 29 months. Overall, the taste problems lasted for an average of 19.3 ± 7.51 months. Conclusions: From our study, we concluded there is a significant burden of taste dysfunction among the long COVID patients in addition to the smell dysfunction, and despite slow recovery, many of the patients are expected to recover months after the initial infection. Nevertheless, this adds to the distress of the patient as they are unable to enjoy their food during this time which can have negative effects on the quality of life of these patients.

Surface flattening in medical imaging has seen widespread use in neurology and more recently in cardiology to describe the left ventricle using the bull's-eye plot. The method is particularly useful to standardize the display of functional information derived from medical imaging and catheter-based measurements. We hypothesized that a similar approach could be possible for the more complex shape of the left atrium (LA) and that the surface flattening could be useful for the management of patients with atrial fibrillation (AF). We implemented an existing surface mesh parameterization approach to flatten and unfold 3D LA models. Mapping errors going from 2D to 3D and the inverse were investigated both qualitatively and quantitatively using synthetic data of regular shapes and computer tomography scans of an anthropomorphic phantom. Testing of the approach was carried out using data from 14 patients undergoing ablation treatment for AF. 3D LA meshes were obtained from magnetic resonance imaging and electroanatomical mapping systems. These were unfolded using the developed approach and used to demonstrate proof-of-concept applications, such as the display of scar information, electrical information and catheter position. The work carried out shows that the unfolding of complex cardiac structures, such as the LA, is feasible and has several potential clinical uses for the management of patients with AF.

Oesophageal gastro-intestinal stromal tumours (GISTs) are rare, accounting for less than five percent of all GIST, with the majority of these occurring at the oesophago-gastric junction (OGJ). Due to the anatomical location and size of these tumours at presentation, surgical resection is often a major undertaking. Neoadjuvant treatment with tyrosine kinase inhibitors, such as Imatinib mesylate, have the potential to downstage such tumours, thereby limiting the extent of subsequent surgical resection. This may therefore reduce any potentially associated morbidity and mortality. We report the case of a 75-year-old gentleman who presented with a large OGJ GIST, which presented with dysphagia. The tumour was deemed too large for local excision due to the risk of compromising the lumen at the OGJ in attempting to obtain a clear resection margin. Given the patient’s co-morbidity, oesophagectomy or total gastrectomy was deemed too major an undertaking. Therefore, endoscopic biopsies were obtained with a view to possible neoadjuvant therapy. These confirmed DOG-1 and Exon-11 mutations, suggesting sensitivity to Imatinib mesylate. A standard dose regime of 400mg daily for a planned 36-month course was commenced. Subsequent imaging showed a substantial decrease in tumour bulk and the decision was made to perform a local excision. A local enucleation procedure was performed, and the patient made a sound recovery. Post-operative histology of resected tumour showed almost complete tumour regression. This significant response to neoadjuvant Imatinib mesylate therapy demonstrates clear potential for its use in similar cases, where radical resection would cause significant morbidity and risk mortality.

We thank Drs White and Regan for their comments [1] regarding our article [2]. Unfortunately, most of the markers of insulin resistance mentioned in their correspondence, namely HOMA-IR, HOMA2 and QUICKI, are not available in the UK Biobank. Therefore, this exposure, even if we had wanted to include it, would require another dataset to address this research question. In terms of addressing upstream causes of elevated HbA1c, we did adjust for BMI and comorbidity in our model to isolate the causal effect of elevated HbA1c. Concerning their point about our agreement to ‘pre-operative testing of surgical patients for hyperinsulinaemia as well as hyperglycaemia and HbA1c glycation’, we have two main concerns. First, we wonder whether using surrogate measures of insulin resistance in everyday practice is feasible. We must consider the added cost to the NHS, the availability of the tests in hospital laboratories, the turnaround times of these investigations in the short pre-operative assessment window and, of course, the ability of all clinicians to interpret the results. Indeed, interpretation of results relies on clinically relevant thresholds, which brings us to our second concern. While there is a large amount of observational data on glucose and HbA1c and postoperative outcomes, there is a relative paucity of evidence for markers of hyperinsulinaemia and postoperative complications. This is an area that is no doubt important, but requires further assessment to elucidate its clinical relevance.

INTRODUCTION:It is currently unknown which method of cystic duct closure is most effective at reducing the risk of bile leak after laparoscopic cholecystectomy. The aims of this work were to determine the most common closure methods used in the UK and review available evidence on which method has the lowest risk of bile leak.METHODS:We conducted an online survey through the Association of Upper Gastrointestinal Surgeons (AUGIS). We also undertook a systematic review using PubMed, EMBASE, MEDLINE and the Cochrane Library for studies that compared different methods for cystic duct occlusion and reported postoperative bile leak.FINDINGS:There was significant variation in practice between consultant surgeons. For routine laparoscopic cholecystectomy metal clips were used most (64%) followed by locking polymer clips (33%) and suture ties (3%). In cases of a dilated cystic duct, preferences were locking polymer clips (60%), suture ties (30%) and metal clips (5%). We included six studies in our review with a total of 8,011 patients. Metal clips were associated with an increased odds of bile leak compared with locking polymer clips (OR 5.66, 95% CI 1.13-28.41, p=0.04) or suture ties (OR 4.17, 95% CI 0.72-24.31, p=0.12). Most studies were retrospective, unlikely to be adequately powered, and vulnerable to selection bias.CONCLUSIONS:Limited available evidence suggests that metal clips have the highest risk of bile leak, but results are not strong enough to recommend a change in current clinical practice. A trial is now required to determine the best method of cystic duct closure.

Abstract Introduction The British Society of Gastroenterology (BSG) guidelines on the management of acute idiopathic pancreatitis (AIP) state the incidence of idiopathic cases to be no more than 30%. However, before a firm diagnosis of AIP is made, Endoscopic Ultrasound (EUS) may be used to determine occult causes. This approach may help prevent recurrent attacks which may evolve into chronic pancreatitis. Method Retrospective analysis over a one-year period of cases of AIP in a tertiary referral centre was performed to see the incidence of AIP and the role of EUS. Patients with an identifiable cause for pancreatitis were excluded, leaving only those who had received a diagnosis of AIP and the diagnostic value of EUS was examined. Results Of the 101 patients diagnosed with AIP, 19% (n=19) underwent an EUS successfully. 79% (n=15) had no underlying cause of pancreatitis identified on EUS. In the remaining 21% of cases (n=4), microlithiasis, ductal stones, and pus requiring drainage were common findings. Of these patents, only 1 was referred for surgery. In the patient group with negative findings on EUS, 4% were unaffected, 2% were referred for surgery, 2% died and 7% had recurrent episodes of pancreatitis. Conclusions The results of this study show that EUS is a valuable modality in patients with suspected AIP, with a positive diagnostic rate of 21%. Therefore, we propose EUS needs to be included in the investigative pathway of all suspected AIP. Although EUS is a relatively scarce resource, further research is required to establish guidelines for the investigation of suspected AIP.

Summary The aim of our study was to clarify the association between glycated haemoglobin (HbA 1c ) and postoperative outcomes in people without an existing diagnosis of diabetes. Half a million adults were recruited into the UK Biobank prospective cohort study between March 2006 and October 2010. We divided participants into three groups: no diagnosis of diabetes and HbA 1c < 42 mmol.mol −1 ; no diagnosis of diabetes and elevated HbA 1c (≥ 42 mmol.mol −1 with no upper limit); and prevalent diabetes (regardless of HbA 1c concentration) at recruitment. We followed up participants by linkage with routinely collected hospital data to determine any surgical procedures undertaken after recruitment and the associated postoperative outcomes. Our main outcome measure was a composite primary outcome of 30‐day major postoperative complications and 90‐day all‐cause mortality. We used logistic regression to estimate the odds of the primary outcome by group. We limited analyses to those who underwent surgery within one year of recruitment (n = 26,653). In a combined effects logistic regression model, participants not known to have diabetes with HbA 1c ≥ 42 mmol.mol −1 had increased odds of the primary outcome (OR [95% CI] 1.43 [1.02–2.02]; p = 0.04), when compared with those without diabetes and HbA 1c < 42 mmol.mol −1 . This effect was attenuated and no longer statistically significant in a direct effects model with adjustment for hyperglycaemia‐related comorbidity (OR [95% CI] 1.37 [0.97–1.93]; p = 0.07). Elevated pre‐operative HbA 1c in people without diabetes may be associated with an increased risk of complications, but the association is likely confounded by end‐organ comorbidity. In contrast to previous evidence, our findings suggest that to prevent adverse postoperative outcomes, optimisation of pre‐existing morbidity should take precedence over reducing HbA 1c in people without diabetes.

AbstractObjectiveThe ENT run through pilot was introduced in 2018 to improve early recruitment to the specialty. This study aimed to understand what makes a successful interview applicant and the experience of the run through trainees during the specialty trainee one and specialty trainee two years.MethodA questionnaire survey was sent to all ENT run through trainees.ResultsTwenty-three trainees responded. Of the successful candidates, 74 per cent held additional degrees prior to application. The median core surgical interview rank was 27 (range: 3–174). Trainees felt that being on the run through pilot had increased ENT trainer engagement.ConclusionThe ENT run through posts are highly competitive, and holding an additional degree may improve applicant success. The pilot programme has been successful by increasing trainer engagement at this critical stage of training. These results will enable development of the pilot programme and provide valuable information for those applying to an ENT run through post.

Purpose: A metaplasia-dysplasia-carcinoma sequence is the most plausible carcinogenic pathway for gallbladder cancer. Although the incidence of gallbladder is increasing, very little is known about its precancerous lesions. This study explored the temporal changes in the prevalence of low-grade dysplasia (LGD), high-grade dysplasia (HGD) and gallbladder adenocarcinoma and associated risk factors. Method: We retrospectively identified 5 835 consecutive patients who underwent cholecystectomy at a single academic teaching hospital between January 2011 and March 2020. Patients were grouped according to histology as: no dysplasia; LGD; HGD; and adenocarcinoma. Fitted linear models estimated temporal trends in prevalence and mean age for all histological outcomes. Logistic regression models estimated associated risk factors. Results: The prevalence of LGD was 1.47%, HGD 0.17% and adenocarcinoma 0.19%. Prevalence for all diseases increased over time, and mean age at diagnoses decreased over time. The mean age at diagnoses for LGD was 57 years, HGD 63 years and adenocarcinoma 77 years. In a multivariate logistic regression model, with no dysplasia as the reference group, female gender increased the odds of LGD (OR 4.57, 95% CI 3.07-10.10, p=<0.0001). BMI was not associated with the risk of LGD, HGD or adenocarcinoma. Conclusion: Our data suggests the prevalence of precancerous gallbladder lesions are increasing in younger patients. Although a risk factor for cholelithiasis, BMI was not associated with disease progression. If occurring in a dysplasia-carcinoma sequence, mean age of diagnoses suggests a progression period of 20 years. Further research is required to explain both the significant sex disparity and potential environmental risk factors for gallbladder dysplasia.

INTRODUCTION:It is clear that a proportion of patients continue to suffer long-lasting symptoms following acute infection with coronavirus disease 2019 (COVID-19). Persistent olfactory dysfunction is one of the commonest complaints reported in the condition colloquially known as long COVID (now known as post-acute sequelae of SARS-CoV-2 infection (PASC)). The prevalence, risk factors and clinical course of long COVID olfactory dysfunction are not yet well understood. At present, the main stay of treatment is olfactory training. Quantitative olfactory testing and impacts on patient quality of life have not been widely studied. This study describes our experiences at Wrightington, Wigan and Leigh Teaching Hospitals, UK (WWL) of establishing a COVID-19 smell clinic, along with preliminary data on patient demographics, baseline smell test scores and quality of life questionnaire scores before olfactory training.METHODS:We piloted a COVID-19 smell clinic. We recorded patient demographics and clinical characteristics then performed clinical assessment of each patient. Quantitative measurements of olfactory dysfunction were recorded using the University of Pennsylvania Smell Identification Test (UPSIT). We measured the impact of olfactory dysfunction on patient quality of life using the validated English Olfactory Disorders Questionnaire (eODQ).RESULTS:20 patients participated in the clinic. 4 patients were excluded from analysis due to missing data. Median age was 35 years. 81% (n=13) of the participants were female. 50% (n=8) of patients suffered with a combination of anosmia/ageusia and parosmia, whilst 43% (n=7) of patients suffered with anosmia/ageusia without parosmia. Almost all the patients registered UPSIT scores in keeping with impaired olfaction. Patient scores ranged from 22 to 35, with the median score at 30. All patients reported that their olfactory dysfunction had an impact on their quality of life. The median eODQ score reported was 90, with scores ranging from 42 to 169 out of a maximum of 180.CONCLUSION:We have demonstrated that it is simple and feasible to set up a COVID-19 smell clinic. The materials are inexpensive, but supervised completion of the UPSIT and eODQ is time-consuming. Patients demonstrate reduced olfaction on quantitative testing and experience significant impacts on their quality of life as a result. More research is needed to demonstrate if olfactory training results in measurable improvements in smell test scores and quality of life.

Osteoarthritis (OA) is a leading pathological condition resulting in the degeneration and destruction of articular cartilage. The presence of inherent mesenchymal progenitor cells (MPCs) within the articular cartilage has led to explore the possible reparative mechanisms to regenerate and restore the functional and mechanical properties of hyaline cartilage. The present in vitro study was aimed to identify and characterize the MPCs derived from OA cartilage. MPCs derived from the explant culture of OA cartilage were analyzed in terms of cellular and biological properties, and multilineage differentiation abilities. Upon cell surface marker analysis, MPCs were CD73+, CD90+, CD166+, CD146-, CD34-, CD45-, and HLA-DR-, whose expression defines stemness and chondroprogenitor status. MPCs exhibited a higher proliferative index and limited or no senescence activity till later passages. Trilineage differentiation towards osteogenesis, adipogenesis, and chondrogenesis was observed with cytochemical staining and also by mRNA expression of lineage-specific markers by RT-qPCR. The results showed that OA cartilage harbors a viable pool of MPCs with greater chondrogenic potential. These cell niches could serve as a superior cell source for cartilage regeneration due to their committed progeny and hence could prevent heterotypic cartilage formation. [ J Adv Biotechnol Exp Ther 2021; 4(2.000): 200-209]

Purpose: Cholecystectomy is one of the most performed operations in general surgery, yet evidence is currently lacking regarding the most effective method of securing the cystic duct to reduce the risk of bile leak. Whilst non-locking, metallic, clips are very commonly used, observational evidence suggests that clips with a locking mechanism reduce the risk of bile leak from the cystic duct compared to non-locking clips. However, such studies are small and unlikely to be adequately powered. Therefore, there is uncertainty in clinical practice regarding the most effective method of bile duct closure. The aim of this review was to pool available observational data to improve the effect estimate of current evidence and help inform surgical practice. Methods: We undertook a systematic search of PubMed, EMBASE, MEDLINE and the Cochrane Library from date of inceptions to 23rd July 2020 for articles that compared the use of locking and non-locking clips and reported the incidence of early postoperative bile leak from the cystic duct. Results: A total of 6 studies were deemed eligible for inclusion. Three of these studies reported data suitable for inclusion in a meta-analysis. Meta-analysis estimated that non-locking clips were associated with an increased odds of bile leak from the cystic duct compared to locking clips OR=9.59 (95% CI 1.74-52.81). However, most studies were small and retrospective and unlikely to be adequately powered, this is reflected in the imprecision of the pooled effect estimate. Conclusions: There is low level evidence suggesting that locking clips may reduce the risk of cystic duct leak after cholecystectomy compared to the use of non-locking clips. An adequately powered prospective study, preferably a randomised controlled trial, is required to determine the best method of cystic duct closure during cholecystectomy.

Recreational physical activity has been shown to protect against the development of oesophageal adenocarcinoma as well as gastroesophageal reflux disease (GORD), but such effects have not been demonstrated for non-recreational activity. We examined whether high levels of occupational physical activity (heavy manual labour or physical work) were associated with the risk of oesophageal adenocarcinoma as well as its sequential precursor diseases: gastroesophageal reflux disease, reflux oesophagitis and Barrett’s oesophagus. In this population-based prospective cohort study, participants aged between 37 to 73 years were recruited from 22 regions across the United Kingdom. Baseline occupational information (job type and levels of heavy manual activity) was assessed using both questionnaires and verbal interviews. Incident cases were identified by linkage with routinely collected hospital inpatient and cancer registry data for England, Scotland and Wales. Primary clinical outcomes were GORD without oesophagitis, GORD with oesophagitis (reflux oesophagitis), Barrett’s oesophagus and oesophageal adenocarcinoma. The effects of heavy manual activity on disease risk were estimated using Cox proportional hazard regression adjusted for multiple risk factors and stratified by socioeconomic status. Between 2006 and 2010, 502 men and 524 women were enrolled. Main analyses were limited to the working population with a full set of variables of interest (n=266, 453). Compared to jobs with low levels of heavy manual activity, high-level jobs had increased hazard ratios (HRs) for GORD (1.20, 95% CI 1.11-1.30), reflux oesophagitis (1.17, 95% CI 1.04-1.31) and Barrett’s oesophagus (1.13, 95% CI 0.98-1.32), but not oesophageal adenocarcinoma (0.91 95% CI 0.54-1.56). High levels of occupational heavy manual activity could be used as a new risk factor for GORD and reflux oesophagitis, the precursor diseases of oeosphageal adenocarcinoma.

Abstract Recreational physical activity has been shown to protect against the development of oesophageal adenocarcinoma as well as gastroesophageal reflux disease (GORD), but such effects have not been demonstrated for non-recreational activity. We examined whether high levels of occupational physical activity (heavy manual labour or physical work) were associated with the risk of oesophageal adenocarcinoma as well as its sequential precursor diseases; gastroesophageal reflux disease (GORD), reflux oesophagitis and Barrett’s oesophagus. Methods In this population-based prospective cohort study, participants aged between 37 to 73 years were recruited from 22 regions across the United Kingdom. Baseline occupational information of job type and levels of heavy manual activity was assessed using both questionnaires and verbal interviews. Incident cases were identified by linkage with routinely collected hospital inpatient and cancer registry data for England, Scotland and Wales. Primary clinical outcomes were GORD without oesophagitis, GORD with oesophagitis (reflux oesophagitis), Barrett’s oesophagus and oesophageal adenocarcinoma. The effects of heavy manual activity on disease risk were estimated using Cox proportional hazard regression. Results Between 2006 and 2010, 502 524 men and women were enrolled. Main analyses were limited to the working population with a full set of variables of interest (n = 266 453). Compared to jobs with low levels of heavy manual activity, high level jobs had increased hazard ratios (HRs) for GORD (1.20, 95% CI 1.11–1.30), reflux oesophagitis (1.17, 95% CI 1.04–1.31) and Barrett’s oesophagus (1.13, 95% CI 0.98–1.32), but not oesophageal adenocarcinoma (0.91 95% CI 0.54–1.56). Conclusion High levels of occupational heavy manual activity could be used as a risk factor for GORD and reflux oesophagitis, the precursor diseases of Barrett’s oesophagus and oesophageal adenocarcinoma.