Development and validation of a novel Barrett's oesophagus patient reported outcome measure (B-PROM).

Background: Patients with Barrett's oesophagus (BO) carry significant cancer worry, burden of symptoms, and lack disease-specific knowledge. Currently there is no validated BO patient reported outcome measure (PROM) to measure these factors for use in clinical practice and research, hence the aim of this study was to devise a novel, validated BO-specific tool, B-PROM. Methods: Literature review, quantitative and qualitative research informed the initial item generation. The item bank was refined through a modified Delphi process between May and August 2021. The PROM was then tested through cognitive interviews and validated via multicentre testing between September 2021 and February 2023 with the aim to create a succinct tool which addresses the key important factors to BO patients and has strong psychometric properties. Findings: B-PROM covers key themes of disease-specific knowledge, trust in clinicians, burden of symptoms, cancer worry and burden of surveillance. Validation results from 387 participants (response rate 40.8%) showed 93.3% of participants completed >95% of B-PROM. All individual items scored a completion rate of >95%. Mean completion time was 5 mins 34s for a sample group. Nineteen items showed a ceiling effect, 3 items showed a floor effect. Internal consistency overall demonstrated a Cronbach Alpha of 0.846, while predetermined subsections showed Cronbach alphas of 0.335, 0.718, 0.736, and 0.896. Inter-item analysis found 2 pairs of items with strong correlation, with only 6 items correlating weakly. Item-total correlation showed 19 items correlated well. Exploratory Factor analysis (EFA) with principal component analysis produced 5 components with Eigenvalues >1 of which 4/5 had satisfactory Cronbach alphas. Test-retest reliability showed no significant differences across single and average measures (p ≤ 0.001). Interpretation: B-PROM is the first BO-specific PROM to be systematically evaluated. Validation findings show strong internal consistency, short completion time, low missingness and excellent test-retest reliability. Funding: Medtronic Limited ISR-2016-1077.

Dedicated service for Barrett's oesophagus surveillance endoscopy yields higher dysplasia detection and guideline adherence in a non-tertiary setting in the UK: a 5-year comparative cohort study.

Objective: Barrett's oesophagus (BO) endoscopic surveillance is performed to varying quality, dedicated services may offer improved outcomes. This study compares a dedicated BO service to standard care, specifically dysplasia detection rate (DDR), guideline adherence and use of advanced imaging modalities in a non-tertiary setting. Design/method: 5-year retrospective comparative cohort study comparing a dedicated BO endoscopy service with surveillance performed on non-dedicated slots at a non-tertiary centre in the UK. All adult patients undergoing BO surveillance between 1 March 2016 and 1 March 2021 were reviewed and those who underwent endoscopy on a dedicated BO service run by endoscopists with training in BO was compared with patients receiving their BO surveillance on any other endoscopy list. Endoscopy reports, histology results and clinic letters were reviewed for DDR and British society of gastroenterology guideline adherence. Results: 921 BO procedures were included (678 patients). 574 (62%) endoscopies were on a dedicated BO list vs 348 (38%) on non-dedicated.DDR was significantly higher in the dedicated cohort 6.3% (36/568) vs 2.7% (9/337) (p=0.014). Significance was sustained when cases with indefinite for dysplasia were excluded: 4.9% 27/533 vs 0.9% 3/329 (p=0.002). Guideline adherence was significantly better on the dedicated endoscopy lists.Factors associated with dysplasia detection in regression analysis included visible lesion documentation (p=0.036), use of targeted biopsies (p=<0.001), number of biopsies obtained (p≤0.001). Conclusions: A dedicated Barrett's service showed higher DDR and guideline adherence than standard care and may be beneficial pending randomised trial data.

Robustness to Transformations Across Categories: Is Robustness Driven by Invariant Neural Representations?

Deep convolutional neural networks (DCNNs) have demonstrated impressive robustness to recognize objects under transformations (e.g., blur or noise) when these transformations are included in the training set. A hypothesis to explain such robustness is that DCNNs develop invariant neural representations that remain unaltered when the image is transformed. However, to what extent this hypothesis holds true is an outstanding question, as robustness to transformations could be achieved with properties different from invariance; for example, parts of the network could be specialized to recognize either transformed or nontransformed images. This article investigates the conditions under which invariant neural representations emerge by leveraging that they facilitate robustness to transformations beyond the training distribution. Concretely, we analyze a training paradigm in which only some object categories are seen transformed during training and evaluate whether the DCNN is robust to transformations across categories not seen transformed. Our results with state-of-the-art DCNNs indicate that invariant neural representations do not always drive robustness to transformations, as networks show robustness for categories seen transformed during training even in the absence of invariant neural representations. Invariance emerges only as the number of transformed categories in the training set is increased. This phenomenon is much more prominent with local transformations such as blurring and high-pass filtering than geometric transformations such as rotation and thinning, which entail changes in the spatial arrangement of the object. Our results contribute to a better understanding of invariant neural representations in deep learning and the conditions under which it spontaneously emerges.

Synthesis of a Ag/rGO nanocomposite using Bos taurus indicus urine for nitroarene reduction and biological activity.

The present study develops a unique in situ synthesis of a catalytically and biologically active Ag/reduced graphene oxide (rGO) nanocomposite. Herein, we employed Bos taurus indicus urine to synthesize a Ag/rGO nanocomposite in an environmentally benign, facile, economical, and sustainable manner. The elemental composition analysis reveals the presence of Ag, O and C elements. The scanning electron micrograph shows the formation of spherical silver in nanoform whereas rGO is found to be flake shaped with a wrinkled nature. The synthesized nanomaterial and its composite shows a positive catalytic effect in simple organic transformation for the reduction of nitroarene compounds. Investigations were conducted into the catalytic effectiveness of the prepared nanomaterials for diverse nitroarene reduction. Then, using NaBH4 at 25 °C, the catalytic roles of Ag and the Ag/rGO nano-catalyst were assessed towards the catalytic reduction of several environmental pollutants such as 2-, 3- and 4-nitroaniline and 4-nitrophenol into their respective amino compounds. To test their catalytic performance, bio-mimetically synthesized Ag NPs were thermally treated at 200 °C and compared with the Ag/rGO nanocomposite. Furthermore, biomedical applications such as the antibacterial and antioxidant properties of the as-prepared nanomaterials were investigated in this study.

Bos taurus (A-2) urine assisted bioactive cobalt oxide anchored ZnO: a novel nanoscale approach.

In this study, a novel synthetic method for cobalt oxide (Co3O4) nanoparticles using Bos taurus (A-2) urine as a reducing agent was developed. In addition to this ZnO nanorods were produced hydrothermally and a nanocomposite is formed through a solid-state reaction. The synthesized materials were characterized through modern characterization techniques such as XRD, FE-SEM with EDS, DLS, zeta potential, FT-IR, Raman spectroscopic analysis, and TGA with DSC. The free radical destructive activity was determined using two different methods viz. ABTS and DPPH. The potential for BSA denaturation in vitro, which is measured in comparison to heat-induced denaturation of egg albumin and results in anti-inflammatory effects of nanomaterial was studied. All synthesized nanomaterials have excellent antibacterial properties, particularly against Salmonella typhi and Staphylococcus aureus. The composite exhibits excellent antioxidant and anti-inflammatory activities in comparison to pure nanomaterials. This reveals that these nanomaterials are advantageous in medicine and drug administration.

Biogenic synthesis of silver anchored ZnO nanorods as nano catalyst for organic transformation reactions and dye degradation.

In this study, we are reporting biogenic synthesis of silver nanoparticles and hydrothermal synthesis of zinc oxide nanoparticles. Using convenient mechanical milling methods, nanocomposites with superior photocatalytic and catalytic properties are synthesized. Herein, we have adopted a green, eco-friendly, and economical route for the synthesis of Ag nanoparticles using Zingiber officinalae rhizome extract in an aqueous solution. The synthesized materials were characterized using UV-Vis spectroscopy, XRD, SEM & FE-SEM, FT-IR, Raman, and a particle size analyzer with zeta potential analysis. The photocatalytic activities of Ag, ZnO and their composites were studied by observing the degradation of methylene blue and crystal violet dyes under natural sunlight. Then the catalytic efficacies of synthesized nanoparticles for various organic transformation reactions were studied. Ag-ZnO nanocomposites were predicted to have improved photocatalytic activity and organic transformation reactions, allowing them to be used in environmental remediation applications.

Bio-mimetic synthesis of catalytically active nano-silver using Bos taurus (A-2) urine.

Herein we have synthesized silver nanoparticles (Ag NPs) using liquid metabolic waste of Bos taurus (A-2 type) urine. Various bio-molecules present in cow urine, are effectively used to reduce silver (Ag) ions into silver nanoparticles in one step. This is bio-inspired electron transfer to Ag ion for the formation of base Ag metal and is fairly prompt and facile. These nanoparticles act as a positive catalyst for various organic transformation reactions. The structural, morphological, and optical properties of the as-synthesized Ag NPs are widely characterized by X-ray diffraction spectroscopy, ultraviolet-visible spectroscopy, scanning electron microscope, Fourier transmission infra-red spectroscopy, and atomic force microscopy. The as-synthesized bio-mimetic Ag NPs show potential activity for several reduction reactions of nitro groups. The Ag NPs were also used for degradation of hazardous dyes such as Methylene blue and Crystal violet with good degradation rate constant.

Fulminant myocarditis as an early presentation of SARS-CoV-2.

Myocarditis is well known to be caused by viral infections such as Coxsackie virus group B, human herpes virus 6 and parvovirus B19. However, during the current emerging outbreak of SARS-CoV-2, there have been few case reports describing myocarditis as a possible presentation. In our case report we describe, early cardiac manifestations of SARS-CoV-2 in a UK District General Hospital. A 44-year-old Caucasian woman without any comorbidities presented with SARS-CoV-2 related fulminant myocarditis without initial respiratory symptoms. Patient underwent treatment with milrinone and methylprednisolone that showed reduction in myocardial inflammation and significantly improved myocardial contractility. This was then followed by a second phase of SARS-CoV-2 associated pneumonia and renal failure requiring ventilatory support and haemofiltration. Although, not described in the literature, we have found conjunctive use of milrinone and methylprednisolone effective in patient with SARS-CoV-2 fulminant myocarditis.

Endoscopic resection of early squamous neoplasia of the oesophagus: long-term follow-up in a UK population from a tertiary hospital.

AIM: To review the efficacy and outcomes of endoscopic resection in the diagnosis and treatment of oesophageal squamous dysplasia and early neoplasia. METHODS: This was a retrospective study between May 2012-2018. Twenty-one patients were treated with or considered for treatment with endoscopic resection at a tertiary hospital in the UK. The primary outcome was curative resection, defined as histologically proven complete resection of the lesion with deep/vertical margin ≥1 mm from neoplasia. Secondary outcomes were changes in staging from endoscopic resection histology, whether there was a complete reversal of dysplasia at 12-months or the latest endoscopic follow-up and 5-year overall survival rate. RESULTS: Seventeen patients (mean age = 66.5 years) with 20 lesions (35% en-bloc; 65% piecemeal resections) had endoscopic resection performed. Complete resection was achieved in 90% of lesions by endoscopic criteria, but this was confirmed in fewer lesions histologically. Curative resection was achieved histologically in 60% of lesions (11 patients) and noncurative resection in 40% of lesions (6 patients). Changes in staging from endoscopic resection histology were found in 79.2% of lesions (41.7% upstaged; 37.5% downstaged). No patients were found to have recurrence at their 12-month endoscopic follow-up. Eight of the 11 patients (72.7%) with curative resection remained clear of dysplasia/neoplasia throughout their follow-up (mean, 24.3 months; median, 19 months). The five-year overall survival rate was 64%. CONCLUSION: In UK, endoscopic resection is useful in the management of early squamous neoplasia both for staging and (by piecemeal endoscopic resection in elderly unfit) for medium- to long-term disease clearance.

Long-term follow-up of endoscopic submucosal dissection of gastric dysplasia and early neoplasia in a United Kingdom Caucasian population - a tertiary centre experience.

Introduction: Endoscopic submucosal dissection (ESD) is extensively performed for the treatment of early gastric cancer (EGC) in the Eastern countries due to its favourable outcomes compared to gastrectomy in terms of lower complication rates, shorter hospital stays, better quality of life, with similar 5-year survival rate. Yet, its use is still limited in the UK.Aim: A long-term follow-up study to evaluate the outcome of ESD in the treatment of EGC in a Caucasian population at a tertiary referral centre in the United Kingdom.Methods: Data for the 35 Caucasian patients, who underwent ESD in a tertiary referral centre between May 2012 and June 2017 were collected. The selected patients were followed-up until May 2018. Curative resection (CR) and survival rates were used to measure the efficacy of ESD.Results: ESD was attempted on 46 lesions and completed on 37. En-bloc and CR rates of 57% and 19% were achieved, respectively. 24% of the lesions were non-CR and 57% were indefinite for non-CR/CR and 41% of the lesions showed change in histological grade post-ESD. Complete reversal of dysplasia/neoplasia was seen in 60% of the 'indefinite' group and 100% of the CR group at latest FU (18 months, mean). Recurrence was seen in 23% of the patients at latest FU. Seventy-one months' survival rate was 77%, while the disease-specific mortality was 0%.Conclusions: This study demonstrates the positive long-term outcome of ESD for gastric neoplasia in a UK Caucasian population, encouraging further development and implementation of ESD in the UK.

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Pilot Study of Cannabidiol-rich Botanical Extract in the Symptomatic Treatment of Ulcerative Colitis.

Background: Cannabidiol (CBD) exhibits anti-inflammatory properties that could improve disease activity in inflammatory bowel disease. This proof-of-concept study assessed efficacy, safety and tolerability of CBD-rich botanical extract in ulcerative colitis (UC) patients. Methods: Patients aged 18 years or older, with left-sided or extensive UC, Mayo scores of 4-10 (endoscopy scores ≥1), and on stable 5-aminosalicylic acid dosing, were randomized to 10-weeks' CBD-rich botanical extract or placebo capsules. The primary endpoint was the percentage of patients in remission after treatment. Statistical testing was 2-sided, using a 10% significance level. Results: Patients were less tolerant of CBD-rich botanical extract compared with placebo, taking on average one-third fewer capsules, and having more compliance-related protocol deviations (principally insufficient exposure), prompting identification of a per protocol (PP) analysis set. The primary endpoint was negative; end of treatment remission rates were similar for CBD-rich botanical extract (28%) and placebo (26%). However, PP analysis of total and partial Mayo scores favoured CBD-rich botanical extract (P = 0.068 and P = 0.038, respectively). Additionally, PP analyses of the more subjective physician's global assessment of illness severity, subject global impression of change, and patient-reported quality-of-life outcomes were improved for patients taking CBD-rich botanical extract (P = 0.069, P = 0.003, and P = 0.065, respectively). Adverse events (AEs) were predominantly mild/moderate with many in the CBD-rich botanical extract group potentially attributable to the ∆9-tetrahydrocannabinol content. A greater proportion of gastrointestinal-related AEs, indicative of UC worsening, was seen on placebo. Conclusion: Although the primary endpoint was not reached, several signals suggest CBD-rich botanical extract may be beneficial for symptomatic treatment of UC.

Effect of diagnosis, surveillance, and treatment of Barrett's oesophagus on health-related quality of life.

Barrett's oesophagus is a chronic precancerous condition that predisposes patients to the development of oesophageal adenocarcinoma, which, once invasive, carries a poor prognosis. This likelihood of a negative outcome has led to the development of robust surveillance and treatment pathways. The true effect of Barrett's oesophagus on life expectancy and the efficacy of long-term surveillance remains under debate. With these uncertainties and no reliable methods of individual risk stratification, patients must be continually monitored and thus carry the burden of this chronic disease. In this Review, we summarise the major findings concerning the patients' perspective of this disease and its care pathways. Health-related quality of life (HRQoL) measurement has become a valuable metric to assess the effects of disease, the quality of health-care delivery, and treatment efficacy across various disease settings. Research to date has shown significant reductions in HRQoL scores related to Barrett's oesophagus compared with controls from the general population. The scores of patients with Barrett's oesophagus seem to be similar to those of patients with gastro-oesophageal reflux disease. Symptom control appears to be important, but not the only factor, in maximising HRQoL. Most researchers have used generic and disease-specific HRQoL instruments because there are few outcome measures that are validated and reliable in patients with Barrett's oesophagus. These methodologies potentially overlook crucial unmeasured areas that are specific to patients with Barrett's oesophagus. Historically, follow-up care has left some patients with insufficient understanding of the disease, inaccurate perceptions of cancer risk, and an unnecessary psychological burden. A greater understanding of the prevalence of these factors and identification of follow-up needs specific to these patients will help to shape future health-care delivery and improve patient experience.

The anatomy of Rouviere's sulcus as seen during laparoscopic cholecystectomy: A proposed classification.

INTRODUCTION: Although Rouviere's sulcus is being increasingly mentioned as the first landmark to be seen so as to begin dissection during laparoscopic cholecystectomy to prevent bile duct injuries, the anatomy of the sulcus has not been described in clear and simple terms. OBJECTIVES: To define the detailed anatomy of Rouviere sulcus as seen during laparoscopic surgery in simple terms for the surgeons to refer to and begin their dissection from this, always staying above this sulcus in order to eliminate bile duct injury. METHODS: 100 recordings of laparoscopic cholecystectomy were analysed to define the anatomy of the Rouviere's sulcus. RESULTS: Majority of the sulci (71) were seen as a deep sulcus and were labelled as simply the 'sulcus'. This was further seen to be of two types - open (60) or closed (11). Some of the sulci (23) were small and so narrow and shallow as to be labelled as a 'slit'. Rarely, the sulcus was found to be fused and represented by a white fusion line (6 cases), and this was simply labelled as a 'scar'. CONCLUSIONS: The Rouviere's sulcus can now be defined in three simple terms - a deep sulcus, or a slit or a scar. We recommend that as a first step in laparoscopic cholecystectomy, the surgeon must look for this reference point (whether it is in the form of a scar, or a slit or a real sulcus) which will be the plane of the main bile duct, and thus avoid any dissection below this point in order to eliminate any danger to the bile duct during surgery.

Laryngopyocele: Presenting with pressure symptom.

Laryngocele is a rare, benign dilatation of the laryngeal saccule that may extend internally into the airway or externally through the thyrohyoid membrane. When it is secondarily infected, it is called laryngopyocele, which is even rarer. Many laryngoceles are asymptomatic; sometimes, they may cause a cough, hoarseness, stridor, sore throat and may present as a swelling on one or both sides of the neck. Laryngocele may be associated with supraglottic squamous cell carcinoma. Computed tomography scan is the most effective imaging method for diagnosis. Surgery is the treatment of choice. A case of large mixed laryngopyocele in a 75-year-old male is described together with surgical management and follow-up. A review of the literature is also presented.

Therapeutic hypothermia after cardiac arrest in Long QT syndrome: Could it be an adjunctive treatment to prevent dysrhythmias?

Therapeutic hypothermia has been used for neuroprotection following cardiac arrest presenting with ventricular tachycardia or ventricular fibrillation regardless of underlying cause. Long QT syndrome is a cause for polymorphic ventricular tachycardia, and we know that therapeutic hypothermia increases the QT interval. We managed a 27-year-old woman, who was 10 weeks post-partum, who collapsed secondary to ventricular fibrillation at home. Bystander cardiopulmonary resuscitation was started with successful resuscitation after a rescue shock from paramedics. On hospital admission, her computerised tomography head, computerised tomography pulmonary angiogram and echocardiography did not show any abnormality. Her baseline electrocardiogram showed prolonged QTc interval of 504 ms without ischaemic changes. After intubation and ventilation, she was treated with therapeutic hypothermia for 48 h. She had a further episode of polymorphic ventricular tachycardia requiring rescue shock just prior to starting therapeutic hypothermia in hospital. No dysrhythmias occurred during therapeutic hypothermia, although the QTc further increased. After stopping the therapeutic hypothermia, she had two further ventricular tachycardia episodes. After commencement of beta blockers, she remained free of arrhythmias, and an implantable cardioverter defibrillator was implanted, she has recovered without any neurological deficit. Ventricular dysrhythmias caused by prolongation of the QT interval during or after therapeutic hypothermia are not well understood. There has been a report of a patient also having ventricular dysrhythmia 2 h after re-warming post therapeutic hypothermia and also a report of arrhythmia free period during therapeutic hypothermia in a long QT syndrome patient; both these features are present in our patient. Re-warming is not usually known to cause any arrhythmias; however, it could be a problem in those with long QT syndrome. Whether therapeutic hypothermia has a place in helping to control ventricular dysrhythmias needs further study.

Cannabis use amongst patients with inflammatory bowel disease.

BACKGROUND: Experimental evidence suggests the endogenous cannabinoid system may protect against colonic inflammation, leading to the possibility that activation of this system may have a therapeutic role in inflammatory bowel disease (IBD). Medicinal use of cannabis for chronic pain and other symptoms has been reported in a number of medical conditions. We aimed to evaluate cannabis use in patients with IBD. METHODS: One hundred patients with ulcerative colitis (UC) and 191 patients with Crohn's disease (CD) attending a tertiary-care outpatient clinic completed a questionnaire regarding current and previous cannabis use, socioeconomic factors, disease history and medication use, including complimentary alternative medicines. Quality of life was assessed using the short-inflammatory bowel disease questionnaire. RESULTS: A comparable proportion of UC and CD patients reported lifetime [48/95 (51%) UC vs. 91/189 (48%) CD] or current [11/95 (12%) UC vs. 30/189 (16%) CD] cannabis use. Of lifetime users, 14/43 (33%) UC and 40/80 (50%) CD patients have used it to relieve IBD-related symptoms, including abdominal pain, diarrhoea and reduced appetite. Patients were more likely to use cannabis for symptom relief if they had a history of abdominal surgery [29/48 (60%) vs. 24/74 (32%); P=0.002], chronic analgesic use [29/41 (71%) vs. 25/81 (31%); P<0.001], complimentary alternative medicine use [36/66 (55%) vs. 18/56 (32%); P=0.01] and a lower short inflammatory bowel disease questionnaire score (45.1±2.1 vs. 50.3±1.5; P=0.03). Patients who had used cannabis [60/139 (43%)] were more likely than nonusers [13/133 (10%); P<0.001 vs. users] to express an interest in participating in a hypothetical therapeutic trial of cannabis for IBD. CONCLUSION: Cannabis use is common amongst patients with IBD for symptom relief, particularly amongst those with a history of abdominal surgery, chronic abdominal pain and/or a low quality of life index. The therapeutic benefits of cannabinoid derivatives in IBD may warrant further exploration.

Natural history of azathioprine-associated lymphopenia in inflammatory bowel disease patients: a prospective observational study.

INTRODUCTION: Azathioprine (AZA) is commonly used in inflammatory bowel disease (IBD) patients. Lymphopenia is a recognized effect of this treatment, but lymphopenia-related complications in IBD patients have not been widely reported. The incidence and progression of AZA-induced lymphopenia in IBD patients is not well described. There is no consensus on its optimal management in this group. AIMS AND METHODS: We assessed the incidence and progression of lymphopenia and its related complications in a cohort of IBD patients over a 14-month period in two large tertiary gastroenterology units. Analysis of prospectively collected data was performed. RESULTS: Fifty-two patients were studied prospectively with a median age of 34 years. Eighteen patients (34.6%) developed lymphopenia (<1.0×10(9)/l) during the course of treatment and 10 of them had severe lymphopenia (<0.6×10(9)/l). Lymphopenia lasted on average 85.4 days and spontaneously resolved in 13 patients. No lymphopenia related-complications were documented. Patients treated with steroids had a significantly higher rate of lymphopenia (83.3 vs. 44.1%, P=0.0083). CONCLUSION: Lymphopenia is common among IBD patients treated with AZA. However, it did not seem to be associated with a higher risk of opportunistic infections and spontaneously resolved in the majority of cases.