The Fatty Liver, Cirrhosis, and Liver Cancer Study (TENDENCY): Protocol for a Multicenter Case-Control Study.

BACKGROUND: Hepatocellular cancer (HCC) is associated with high mortality, and early diagnosis leads to better survival. Patients with cirrhosis, especially due to nonalcoholic fatty liver disease and viral hepatitis, are at higher risk of developing HCC and form the main screening group. The current screening methods for HCC (6-monthly screening with serum alpha fetoprotein and ultrasound liver) have low sensitivity; hence, there is a need for better screening markers for HCC. OBJECTIVE: Our study, TENDENCY, aims to validate the novel screening markers (methylated septin 9, urinary volatile organic compounds, and urinary peptides) for HCC diagnosis and study these noninvasive biomarkers in liver disease. METHODS: This is a multicenter, nested case-control study, which involves comparing the plasma levels of methylated septin 9 between confirmed HCC cases and patients with cirrhosis (control group). It also includes the comparison of urine samples for the detection of HCC-specific volatile organic compounds and peptides. Based on the findings of a pilot study carried out at University Hospital Coventry & Warwickshire, we estimated our sample size to be 308 (n=88, 29% patients with HCC; n=220, 71% patients with cirrhosis). Urine and plasma samples will be collected from all participants and will be frozen at -80 °C until the end of recruitment. Gas chromatography-mass spectrometry will be used for urinary volatile organic compounds detection, and capillary electrophoresis-mass spectrometry will be used for urinary peptide identification. Real-time polymerase chain reaction will be used for the qualitative detection of plasma methylated septin 9. The study will be monitored by the Research and Development department at University Hospital Coventry & Warwickshire. RESULTS: The recruitment stage was completed in March 2023. The TENDENCY study is currently in the analysis stage, which is expected to finish by November 2023. CONCLUSIONS: There is lack of effective screening tests for hepatocellular cancer despite higher mortality rates. The application of more sensitive plasma and urinary biomarkers for hepatocellular cancer screening in clinical practice will allow us to detect the disease at earlier stages and hence, overall, improve HCC outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44264.

'It's All Downhill from Here': A Scoping Review of Sports-Related Concussion (SRC) Protocols in Downhill Mountain Biking (DHI), with Recommendations for SRC Policy in Professional DMB.

INTRODUCTION: Downhill mountain biking (DHI) is a form of cycling and does not currently have a specific sports-related concussion (SRC) assessment. OBJECTIVE: To review the extent, range and nature of research investigating SRC in DMB, provide a summary of key literature findings relating to its identification and management, and then develop a SRC protocol specific to DMB. DESIGN: Scoping review as per recognised methods. SETTING: Literature-based. The following databases were searched: MEDLINE, EMBASE, Scopus and Web of Science, with no restrictions on date. Results were limited to the English language. PARTICIPANTS: Six articles were included in the review from 64 identified articles. The article had to specifically include an analysis of adult downhill riders for inclusion. OUTCOME MEASURES: Study type, study group (amateur/professional), concussion incidence, concussion assessment and recommendations. MAIN RESULTS: Concussion incidence was identified as between 5-23%. No study outlined a trackside assessment of cyclists or a protocol for return to play where SRC was identified. Several authors identified that riders often continued to participate despite the presence of a concussion. No sport-specific SRC assessment was determined for DHI, and a SRC assessment was therefore developed. CONCLUSIONS: This review illustrates the lack of studies and formal protocol in SRC assessment for DHI. In light of this, we propose a three-stage framework specific to the sport to best identify a concussion and act where appropriate while minimising disruption to competition. This framework involves assessing the cyclist on the 'sideline', a second assessment post-event in the medical room and a third assessment the following day. A SRC consensus meeting specific for DHI is suggested with an identified need for updated guidance from UCI, requiring possible rule changes for the sport.

How do changes in flow magnitude due to hydropower operations affect fish abundance and biomass in temperate regions? A systematic review.

BACKGROUND: Altering the natural flow regime, an essential component of healthy fluvial systems, through hydropower operations has the potential to negatively impact freshwater fish populations. Establishing improved management of flow regimes requires better understanding of how fish respond to altered flow components, such as flow magnitude. Based on the results of a recent systematic map on the impacts of flow regime changes on direct outcomes of freshwater or estuarine fish productivity, evidence clusters on fish abundance and biomass responses were identified for full systematic review. The primary goal of this systematic review is to address one of those evidence clusters, with the following research question: how do changes in flow magnitude due to hydropower operations affect fish abundance and biomass? METHODS: This review follows the guidelines of the Collaboration for Environmental Evidence. It examined commercially published and grey literature originally identified during the systematic map process and a systematic search update. All articles were screened using an a priori eligibility criteria at two stages (title and abstract, and full-text) and consistency checks were performed at all stages. All eligible articles were assessed for study validity and specifically designed data extraction and study validity tools were used. A narrative synthesis included all available evidence and meta-analysis using the standardized mean difference (Hedges' g) was conducted where appropriate. REVIEW FINDINGS: A total of 133 studies from 103 articles were included in this systematic review for data extraction and critical appraisal. Most studies were from North America (60%) and were conducted at 146 different hydropower dams/facilities. Meta-analysis included 268 datasets from 58 studies, separated into three analyses based on replication type [temporal (within or between year replication) or spatial]. Fish abundance (226 datasets) and biomass (30 datasets) had variable responses to changes in flow magnitude with estimated overall mean effect sizes ranging from positive to negative and varying by study design and taxa. In studies with temporal replication, we found a detectable effect of alterations to the direction of flow magnitude, the presence of other flow components, sampling methods, season, and fish life stage. However, we found no detectable effect of these moderators for studies with spatial replication. Taxonomic analyses indicated variable responses to changes in flow magnitude and a bias towards salmonid species. CONCLUSIONS: This synthesis did not find consistent patterns in fish abundance or biomass responses to alterations or changes in flow magnitude. Fish responses to flow magnitude alterations or changes were highly variable and context dependent. Our synthesis suggests that biotic responses may not be generalizable across systems impacted by hydroelectric power production and operations, where specific features of the system may be highly influential. Site-specific and adaptive management may be necessary. To improve study validity and interpretability, studies with long-term continuous monitoring, and both temporal and spatial replication are needed. When this gold standard is unfeasible, studies should strive, at minimum, to maximize replication within both intervention and comparator groups for either temporal or spatial designs. To further address knowledge gaps, studies are needed that focus on non-salmonids, multiple seasons, and systems outside of North America. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13750-021-00254-8.

How long do percutaneous endoscopic gastrostomy feeding tubes last? A retrospective analysis.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes allow for long-term enteral feeding. Disk-retained PEG tubes may be suitable for long-term usage without planned replacement, but data on longevity are limited. We aimed to assess the rates and predictors of PEG longevity and post-PEG mortality. DESIGN: Single-centred retrospective cohort study of patients with disk-retained (Freka) PEG tubes. METHODS: All patients undergoing PEG between 2010 and 2013 were identified, and retrospective analysis of outcomes until 2017 (median 1062 days) was performed. Time-to-event data were plotted using Kaplan-Meier curves, with predictors of survival derived from multivariate Cox-regression analyses. RESULTS: 277patients were studied, with a median age of 74 years (IQR 59-82). PEG tube failure occurred in 17.4%, due to: buried bumper syndrome (7.0%), split/broken tube (6.3%), peristomal infection (1.8%) and dislodged tube (1.1%). PEG tube longevity was 95.1% (1 year) and 68.5% (5 year), with age <70 (HR 2.65, 95% CI 1.25 to 5.62, p=0.011) being predictive of PEG failure. Post-PEG mortality was 10.5% (30 day), 35.4% (1 year) and 59.7% (5 year). Age ≥70 was associated with mortality (HR 2.79, 95% CI 1.92 to 4.05, p<0.001), whereas PEG failure (HR 0.46, 95% CI 0.27 to 0.77, p=0.003) and elective PEG removal (HR 0.23, 95% CI 0.08 to 0.64, p=0.005) were associated with reduced mortality. CONCLUSIONS: 68.5% of PEG tubes remain intact after 5 years. Younger age was associated with earlier PEG failure, whereas younger age, PEG replacement and elective PEG tube removal were associated with improved survival. These data may inform future guidance for elective PEG tube replacements.

Intubation failure during gastroscopy: incidence, predictors and follow-up findings.

BACKGROUND: Intubation failure (IF) occurs when an endoscopist is unable to progress via the oropharynx into the upper oesophagus. AIM: To assess incidence and aetiology of IF and predictors of structural pharyngeal abnormalities in patients with IF. METHODS: All gastroscopies (n=26,130) performed in our centre, between August 2010 and August 2016 were retrospectively reviewed. Barium radiology and repeat gastroscopy findings were evaluated for structural causes of IF. Patients were categorised into 'failure to tolerate' and 'failure to progress' based on endoscopy reports. RESULTS: The incidence of IF was 0.95%. Rates of IF varied with endoscopist specialty (p=0.021), but not with patient age, sex or sedation dose. Among cases of IF, structural pharyngeal abnormalities were detected on barium radiology in 28.9%, consisting of cricopharyngeal hypertrophy and/or Zenker's diverticulum in 73.2%. 'Failure to progress' predicted pharyngeal pathology in 55.6%. Predictors of structural causes on barium radiology following IF included: age >/=65 (OR 4.0, 95% CI: 1.8-8.9, p<0.001); indication of dysphagia (OR 5.5, 95% CI: 2.5-11.8, p<0.001), and failure of endoscopic progression (OR 5.2, 95% CI: 2.3-12.0, p<0.001). CONCLUSION: Patients with IF should be investigated owing to the high risk of underlying pathology, particularly if associated with age >/=65, dysphagia, and failure of endoscopic progression. We propose that IF rates of <1% could be used as a quality indicator in gastroscopy.

The 2015 upper gastrointestinal "Be Clear on Cancer" campaign: its impact on gastroenterology services and malignant and premalignant diagnoses.

OBJECTIVE: To assess the impact of the upper gastrointestinal 'Be Clear on Cancer' campaign launched by Public Health England between January and February 2015 on open-access gastroscopy referrals, incidence of target diagnoses (oesophagogastric cancer and Barrett's oesophagus), cancer staging at presentation, 1-year survival and cost per additional diagnosis. DESIGN: We performed a retrospective study of patients referred for 2-week-wait (2WW), open-access endoscopy 3 months following the campaign with diagnoses, endoscopic findings, staging and 12-month survival compared with data from corresponding months in 2014. SETTING: Three adjacent National Health Service trusts in the West Midlands with a combined population of 1.34 million in 2015. RESULTS: 2WW open-access referrals increased by 48% (95% CI 1.35 to 1.61, p<0.001). The proportion of target diagnoses fell from 6.7% to 6.1% (p=0.62). There were no significant overall increases in target diagnoses (OR 1.35, 95% CI 0.95 to 1.92, p=0.11) or cancer (OR 1.30, 95% CI 0.80 to 2.07, p=0.36). There was no change in tumour, node, metastasis (TNM) staging for oesophageal or gastric cancer. Overall 1-year survival did not alter significantly (HR 1.10, 95% CI 0.56 to 2.19, p=0.76). DISCUSSION: The 'Be Clear on Cancer' campaign led to a 48% increase in demand for 2WW gastroscopies but did not significantly affect the incidence of target diagnoses, cancer staging or 1-year survival.

Does the presence of a trainee compromise success of biliary cannulation at ERCP?

BACKGROUND AND STUDY AIMS: Findings in the literature are conflicting on whether trainee involvement in endoscopic retrograde cholangiopancreatography (ERCP) procedures is detrimental to cannulation success rates. We addressed this in a prospective study, where cannulation success with or without trainee presence was the primary outcome measure. PATIENTS AND METHODS: We prospectively recorded data on 2 senior endoscopists and their trainees over an 18-month period for ERCPs in patients with a virgin ampulla. Presence or absence of a trainee at ERCP procedures was pragmatic, reflecting their other service or training commitments or annual leave. For trainee presence, the training protocol allowed them 6 minutes of supervised time in which to achieve biliary cannulation after reaching the ampulla. Study outcome measures included cannulation success, time to cannulation, technique, whether this was achieved independently by the trainee, and complications. RESULTS: There were 219 procedures recorded and analyzed (134 with a trainee, 85 without). Three trainees were involved. Selective biliary cannulation was achieved in 201 (92 %) of cases. When a trainee was present, cannulation was successful in 122/134 procedures (91 %), compared to 79/85 (93 %) with a senior endoscopist alone ( P  = 0.8, Fisher's exact test). Mean time to biliary cannulation with a trainee present was 7 minutes, compared with 5 minutes with no trainee. Mean time for successful independent cannulation by the trainee was 4 minutes, and 9 minutes for a consultant following a trainee's attempt. There were no serious adverse events. CONCLUSION: Our study shows that with this training protocol, involvement of a trainee on a routine secondary care ERCP list does not impair biliary cannulation success, and does not prolong a subsequent attempt by the senior endoscopist if initially unsuccessful. These findings support the involvement of trainees in routine ERCP lists with this training protocol.

A functional extracellular matrix biomaterial derived from ovine forestomach.

Extracellular matrix (ECM) based biomaterials have an established place as medical devices for wound healing and tissue regeneration. In the search for biomaterials we have identified ovine forestomach matrix (OFM), a thick, large format ECM which is biochemically diverse and biologically functional. OFM was purified using an osmotic process that was shown to reduce the cellularity of the ECM and aid tissue delamination. OFM produced using this technique was shown to retain residual basement membrane components, as evidence by the presence of laminin and collagen IV. The collagenous microarchitecture of OFM retained many components of native ECM including fibronectin, glycosaminoglycans, elastin and fibroblast growth factor basic. OFM was non-toxic to mammalian cells and supported fibroblast and keratinocyte migration, differentiation and infiltration. OFM is a culturally acceptable alternative to current collagen-based biomaterials and has immediate clinical applications in wound healing and tissue regeneration.

Piperacillin-tazobactam versus ciprofloxacin plus amoxicillin in the treatment of infective episodes after liver transplantation.

An optimum antimicrobial regimen for bacterial infection after orthotopic liver transplantation has not been identified. In this prospective 4 year study of patients undergoing liver transplantation, patients were randomized to receive either piperacillin-tazobactam (112 patient episodes) or ciprofloxacin plus amoxicillin (105 patient episodes) for empirical treatment of infective episodes in the first 3 months after transplant. Metronidazole was added to the ciprofloxacin-amoxicillin regimen where anaerobic infection was suspected. Patient groups were comparable with respect to clinical, biochemical and haematological parameters. At the 72 h primary efficacy end-point, the overall response rate for the intention-to-treat group was 74/112 (66.1%) for piperacillin-tazobactam and 63/105 (60.0%) for ciprofloxacin plus amoxicillin (P=0.399); the corresponding figures for the per-protocol (PP) group were 73/82 (89.0%) (piperacillin-tazobactam) and 61/80 (76.3%) (ciprofloxacin plus amoxicillin) (P=0.038). At the end-of-study assessment, 58.9% of episodes in the piperacillin-tazobactam group had a successful clinical outcome, compared with 50.5% in the ciprofloxacin plus amoxicillin group (P=0.222); the corresponding figures for the PP group were 83.5% (piperacillin-tazobactam) and 68.8% (ciprofloxacin plus amoxicillin) (P=0.038). Staphylococci and aerobic Gram-negative bacilli were the predominant pathogens in both groups. Bacteria resistant to the study drugs were encountered, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and multiply-resistant Klebsiella spp. Empirical monotherapy with piperacillin-tazobactam is an effective treatment for infective episodes in liver transplant patients.