bluuebunny/crossref_metadata_2025_split huggingface dataset:
Major variation in hepatocellular carcinoma treatment and outcomes in England: a retrospective cohort study
Authors: Beecroft Sue , O’Connell Matthew , Nassar Ayman , Noon Katie , Pollock Kevin G , Palmer Dan , Cross Timothy J S 
Published: May 2022

ObjectiveHepatocellular carcinoma (HCC) is increasingly incident in England, while survival remains poor with regional disparities. We aimed to explore the differences in HCC treatment across different geographical regions and to examine the impact on cancer survival.MethodsIncident HCC cases and treatment were identified from the English Hospital Episode Statistics (2016–2017) and then a subset by National Health Service (NHS) regions. Treatment was grouped into curative, palliative and untreated. Median survival was estimated to date of death in the national statistics.ResultsThe median observed survival was 8.6 months (95% CI 7.5 to 9.9) across all 2160 HCC cases, 52.1 months (CI 50.5, not reached) in 449 (20.8%) treated with curative intent, 21.0 months (CI 18.5 to 24.5) after other cancer-specific treatment in 449 (20.8%), and 2.3 months (CI 2.1 to 2.6) in 1262 (58.4%) untreated. Across NHS regions, <50% of cases received treatment (30.4%–49.6%), while between 14.2% and 27.7% had curative treatment. The 3-year survival was similar (23.5%–29.7%), except in the London region (40.0%).ConclusionMajority of HCC cases in England are untreated and survival remains low, with variation in outcomes in regions with similar incident rates. A deeper exploration of regional treatments and screening practice is required to improve early detection and survival.
Development and validation of the scale for measuring biopsychosocial approach of family physicians to their patients
Authors: Makivić Irena , Klemenc-Ketiš Zalika 
Published: May 2022

ObjectiveWhile other models focus more on disease and pathophysiology, the biopsychosocial approach emphasises the importance of human health and disease in their fullest contexts. If we are to gain an insight into physical and psychological health needs, and address them quickly and adequately, it is important that we recognise them already at the family practice stage. An approach that assesses needs at patient level could also be seen as patient-centred care, which is one of the key elements of high-quality care. To the best of our knowledge, no scale for measuring the biopsychosocial approach of family physicians has yet been developed.DesignThe aim of this study was to develop and validate a scale that measures the biopsychosocial approach of family physicians to their patients through the Delphi and validation process.SettingThe scale was developed through the Delphi study and validated by means of significant statistical methods. Pearson’s correlation coefficient, Cronbach’s alpha, the intracorrelation coefficient, the Spearman-Brown coefficient and exploratory factor analysis were applied.ParticipantsFive family physicians took part in a brainstorming process and 24 family medicine experts took part in the Delphi study. For the first part of the validation process, there were 31 family medicine trainees in the first group and 32 in the second group. For the last part of the validation process, 164 family physicians completed the scale.ResultThrough the Delphi study, 39 final items covering three areas within the biopsychosocial approach were identified. Construct validity was high, with positive linear correlation and good face validity. The intraclass correlation coefficient for test–retest reliability was 0.862. The Spearman-Brown coefficient was the highest (0.931) on an even and odd division. Factor rotation showed that three factors on 35 items explained 39.5% of variances. The final internal consistency on 35 items was 0.911.ConclusionThe developed scale measures the biopsychosocial dimension of family physicians’ work with high Cronbach’s alpha measures and good validity.
Tacrolimus-binding protein FKBP8 directs myosin light chain kinase-dependent barrier regulation and is a potential therapeutic target in Crohn’s disease
Authors: Zuo Li , Kuo Wei-Ting , Cao Feng , Chanez-Paredes Sandra D , Zeve Daniel , Mannam Prabhath , Jean-François Léa , Day Anne , Vallen Graham W , Sweat Yan Y , Shashikanth Nitesh , Breault David T , Turner Jerrold R 
Published: May 2022

ObjectiveIntestinal barrier loss is a Crohn’s disease (CD) risk factor. This may be related to increased expression and enzymatic activation of myosin light chain kinase 1 (MLCK1), which increases intestinal paracellular permeability and correlates with CD severity. Moreover, preclinical studies have shown that MLCK1 recruitment to cell junctions is required for tumour necrosis factor (TNF)-induced barrier loss as well as experimental inflammatory bowel disease progression. We sought to define mechanisms of MLCK1 recruitment and to target this process pharmacologically.DesignProtein interactions between FK506 binding protein 8 (FKBP8) and MLCK1 were assessed in vitro. Transgenic and knockout intestinal epithelial cell lines, human intestinal organoids, and mice were used as preclinical models. Discoveries were validated in biopsies from patients with CD and control subjects.ResultsMLCK1 interacted specifically with the tacrolimus-binding FKBP8 PPI domain. Knockout or dominant negative FKBP8 expression prevented TNF-induced MLCK1 recruitment and barrier loss in vitro. MLCK1-FKBP8 binding was blocked by tacrolimus, which reversed TNF-induced MLCK1-FKBP8 interactions, MLCK1 recruitment and barrier loss in vitro and in vivo. Biopsies of patient with CD demonstrated increased numbers of MLCK1-FKBP8 interactions at intercellular junctions relative to control subjects.ConclusionBinding to FKBP8, which can be blocked by tacrolimus, is required for MLCK1 recruitment to intercellular junctions and downstream events leading to immune-mediated barrier loss. The observed increases in MLCK1 activity, MLCK1 localisation at cell junctions and perijunctional MLCK1-FKBP8 interactions in CD suggest that targeting this process may be therapeutic in human disease. These new insights into mechanisms of disease-associated barrier loss provide a critical foundation for therapeutic exploitation of FKBP8-MLCK1 interactions.
Hepatic p63 regulates glucose metabolism by repressing SIRT1
Authors: Gonzalez-Rellan Maria J , Novoa Eva , da Silva Lima Natalia , Rodriguez Amaia , Veyrat-Durebex Christelle , Seoane Samuel , Porteiro Begoña , Fondevila Marcos F , Fernandez Uxia , Varela-Rey Marta , Senra Ana , Iglesias Cristina , Escudero Adriana , Fidalgo Miguel , Guallar Diana , Perez-Fernandez Roman , Prevot Vincent , Schwaninger Markus , López Miguel , Dieguez Carlos , Coppari Roberto , Frühbeck Gema , Nogueiras Ruben 
Published: May 2022

Objectivep63 is a transcription factor within the p53 protein family that has key roles in development, differentiation and prevention of senescence, but its metabolic actions remain largely unknown. Herein, we investigated the physiological role of p63 in glucose metabolism.DesignWe used cell lines and mouse models to genetically manipulate p63 in hepatocytes. We also measured p63 in the liver of patients with obesity with or without type 2 diabetes (T2D).ResultsWe show that hepatic p63 expression is reduced on fasting. Mice lacking the specific isoform TAp63 in the liver (p63LKO) display higher postprandial and pyruvate-induced glucose excursions. These mice have elevated SIRT1 levels, while SIRT1 knockdown in p63LKO mice normalises glycaemia. Overexpression of TAp63 in wild-type mice reduces postprandial, pyruvate-induced blood glucose and SIRT1 levels. Studies carried out in hepatocyte cell lines show that TAp63 regulates SIRT1 promoter by repressing its transcriptional activation. TAp63 also mediates the inhibitory effect of insulin on hepatic glucose production, as silencing TAp63 impairs insulin sensitivity. Finally, protein levels of TAp63 are reduced in obese persons with T2D and are negatively correlated with fasting glucose and homeostasis model assessment index.Conclusions.These results demonstrate that p63 physiologically regulates glucose homeostasis.
British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults
Authors: Dhar Anjan , Haboubi Hasan N , Attwood Stephen E , Auth Marcus K H , Dunn Jason M , Sweis Rami , Morris Danielle , Epstein Jenny , Novelli Marco R , Hunter Hannah , Cordell Amanda , Hall Sharon , Hayat Jamal O , Kapur Kapil , Moore Andrew Robert , Read Carol , Sami Sarmed S , Turner Paul J , Trudgill Nigel J 
Published: May 2022

BackgroundEosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE.MethodsThe Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance.ResultsFifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research.ConclusionsThese comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.
Longitudinal changes of thoracic aortic diameters in the general population aged 55 years or older
Authors: Thijssen Carlijn G E , Mutluer Ferit O , van der Toorn Janine E , Bons Lidia R , Gökalp Arjen L , Takkenberg Johanna JM , Mokhles Mostafa M , van Kimmenade Roland R J , Vernooij Meike W , van der Lugt Aad , Budde Ricardo P J , Roos-Hesselink Jolien W , Kavousi Maryam , Bos Daniel 
Published: May 2022

ObjectiveLongitudinal data on age-related changes in the diameters of the thoracic aorta are scarce. To better understand normal variation and to identify factors influencing this process, we aimed to report male-female-specific and age-specific aortic growth rate in the ageing general population and identify factors associated with growth rate.MethodsFrom the prospective population-based Rotterdam Study, 943 participants (52.0% females, median age at baseline 65 years (62–68)) underwent serial non-enhanced cardiac CT. We measured the diameters of the ascending (AA) and descending aorta (DA) at two time points and expressed absolute and relative differences. Linear mixed effects analysis was performed to identify determinants associated with change in aortic diameters.ResultsMean AA diameter at baseline was 37.3±3.6 mm in male population and 34.7±3.2 mm in female population, mean DA diameter was 29.6±2.3 in male population and 26.9±2.2 mm in female population. The median absolute change in diameters during follow-up (mean scan interval 14.1±0.3 years) was 1 mm (0–2) for both the AA and DA. Absolute change per decade in AA diameter was significantly larger in males than in females (0.72 mm/decade (0.00–1.43) vs 0.70 mm/decade (0.00–1.41), p=0.006), as well as absolute change in AD diameter (0.71 mm/decade (0.00–1.42) vs 0.69 mm/decade (0.00–1.36), p=0.008). There was no significant difference between male and female population in relative change of their aortic diameters during follow-up. Age, male sex, higher body mass index (BMI) and higher diastolic blood pressure (DBP) showed a statistically significant independent association with increase in AA and DA diameters over time.ConclusionsSome degree of increase in thoracic aortic diameters is typical in both men and women of an aging population. Factors associated with this change in thoracic aortic diameters were sex, age, BMI and DBP.
Fractional flow reserve versus angiography alone in guiding myocardial revascularisation: a systematic review and meta-analysis of randomised trials
Authors: Elbadawi Ayman , Sedhom Ramy , Dang Alexander T , Gad Mohamed M , Rahman Faisal , Brilakis Emmanouil S , Elgendy Islam Y , Jneid Hani 
Published: May 2022

BackgroundRandomised trials evaluating the efficacy and safety of fractional flow reserve (FFR)-guided versus angiography-guided revascularisation among patients with obstructive coronary artery disease (CAD) have yielded mixed results.AimsTo examine the comparative efficacy and safety of FFR-guided versus angiography-guided revascularisation among patients with obstructive CAD.MethodsAn electronic search of MEDLINE, SCOPUS and Cochrane databases without language restrictions was performed through November 2021 for randomised controlled trials that evaluated the outcomes of FFR-guided versus angiography-guided revascularisation. The primary outcome was major adverse cardiac events (MACE). Data were pooled using a random-effects model.ResultsThe final analysis included seven trials with 5094 patients. The weighted mean follow-up duration was 38 months. Compared with angiography guidance, FFR guidance was associated with fewer number of stents during revascularisation (standardised mean difference=−0.80; 95% CI −1.33 to −0.27), but no difference in total hospital cost. There was no difference between FFR-guided and angiography-guided revascularisation in long-term MACE (13.6% vs 13.9%; risk ratio (RR) 0.97, 95% CI 0.85 to 1.11). Meta-regression analyses did not reveal any evidence of effect modification for MACE with acute coronary syndrome (p=0.36), proportion of three-vessel disease (p=0.88) or left main disease (p=0.50). There were no differences between FFR-guided and angiography-guided revascularisation in the outcomes all-cause mortality (RR 1.16, 95% CI 0.80 to 1.68), cardiovascular mortality (RR 1.27, 95% CI 0.50 to 3.26), repeat revascularisation (RR 0.99, 95% CI 0.81 to 1.21), recurrent myocardial infarction (RR 0.92, 95% CI 0.74 to 1.14) or stent thrombosis (RR 0.61, 95% CI 0.31 to 1.21).ConclusionAmong patients with obstructive CAD, FFR-guided revascularisation did not reduce the risk of long-term adverse cardiac events or the individual outcomes. However, FFR-guided revascularisation was associated with fewer number of stents.PROSPERO registration numberCRD42021291596.
Perioperative outcomes and readmissions following cardiac operations in kidney transplant recipients
Authors: Madrigal Josef , Richardson Shannon , Hadaya Joseph , Verma Arjun , Tran Zachary , Sanaiha Yas , Benharash Peyman 
Published: May 2022

ObjectiveAlthough kidney transplant (KTx) recipients are at significant risk for cardiovascular disease, outcomes following cardiac operations have been examined in limited series. The present study thus aimed to assess the impact of KTx on in-hospital perioperative outcomes and readmissions in a nationally representative cohort.MethodsAll adults undergoing elective coronary artery bypass grafting, valve repair/replacement or a combination thereof were identified from the 2010–2018 Nationwide Readmissions Database. Patients were stratified by history of KTx. Transplant-capable centres were defined as hospitals performing at least one KTx annually. To perform risk-adjustment in assessing outcomes, multivariable regression models were developed.ResultsOf an estimated 1 407 351 patients included for analysis, 0.2% (n=2849) were KTx recipients. Compared with the general cardiac surgical population, patients with prior KTx experienced higher adjusted odds of in-hospital mortality (adjusted OR (AOR) 2.44, 95% CI 1.72 to 3.47, p<0.001) and perioperative complication (AOR 1.67, 95% CI 1.44 to 1.94, p<0.001). Additionally, KTx was independently associated with greater readmission rates within 30 days (AOR 1.96, 95% CI 1.65 to 2.34, p<0.001) with kidney injury contributing significantly to the burden of rehospitalisation (4.6 vs 1.8%, p=0.005). In a subpopulation comprised of only KTx recipients, treatment at a transplant-capable centre reduced odds of kidney injury with non-transplant hospitals as reference (AOR 0.65, 95% CI 0.43 to 0.98, p=0.037).ConclusionsKidney transplant recipients undergoing cardiac operations encounter significant risks compared with the general surgical population. Referral to transplant-capable centres should be explored to improve outcomes and to preserve allograft function in this population.
Estimates of road traffic deaths in Tanzania
Authors: Mbugua Leah Watetu , Mitra Sudeshna , Neki Kazuyuki , Gutierrez Hialy , Balasubramaniyan Ramshankar , Winer Mercer , Roberts Jaeda , Vos Theo , Hamilton Erin , Naghavi Mohsen , Harrison James E , Job Soames , Bhalla Kavi 
Published: May 2022

IntroductionThere is considerable uncertainty in estimates of traffic deaths in many sub-Saharan African countries, with the Global Burden of Disease (GBD) and the Global Status Report on Road Safety (GSRRS) reporting widely differing estimates. As a case study, we reviewed and compared estimates for Tanzania.MethodsWe estimated the incidence of traffic deaths and vehicle ownership in Tanzania from nationally representative surveys. We compared findings with GBD and GSRRS estimates.ResultsTraffic death estimates based on the 2012 census (9382 deaths; 95% CI: 7565 to 11 199) and the 2011–2014 Sample Vital Registration with Verbal Autopsy (8778; 95% CI: 7631 to 9925) were consistent with each other and were about halfway between GBD (5 608; 95% UI: 4506 to 7014) and WHO (16 252; 95% CI: 13 130 to 19 374) estimates and more than twice official statistics (3885 deaths in 2013). Surveys and vehicle registrations data show that motorcycles have increased rapidly since 2007 and now comprise 66% of vehicles. However, these trends are not reflected in GBD estimates of motorcycles in the country, likely resulting in an underestimation of motorcyclist deaths.ConclusionReducing discrepancies between GBD and GSRRS estimates and demonstrating consistency with local epidemiological data will increase the legitimacy of such estimates among national stakeholders. GBD, which is the only project that models the road-user distribution of traffic deaths in all countries, likely severely underestimates motorcycle deaths in countries where there has been a recent increase in motorcycles. Addressing police under-reporting and strengthening surveillance capacity in Tanzania will allow a better understanding of the road safety problem and better targeting of interventions.
Postmortem survey of haemoglobin A1c, non-alcoholic steatohepatitis and liver fibrosis within a general population
Authors: Klaric Kristina-Ana , Parai Jacqueline Louise , Kepron Charis Anthea , Walker Alfredo Eugene , Milroy Christopher Mark 
Published: May 2022

AimsNon-alcoholic steatohepatitis (NASH), fatty liver disease and fibrosis are associated with diabetes mellitus and obesity. Previous autopsy series have reported prevalence of fatty liver disease to be 11%–24%. Recent studies, using imaging and serology, suggest a prevalence of 20%–35%, NASH of 5% and advanced fibrosis of 2%–3%. We examined the prevalence of NASH and liver fibrosis in a general autopsy population.MethodsA cross-sectional study of consecutive, adult, medicolegal autopsies over a 1-year period was conducted. Liver sections were scored for fibrosis, inflammation and steatosis using a modified NASH scoring system. Stepwise logistic regression was used to identify associations between NASH or moderate/severe fibrosis and several clinicopathological parameters, including postmortem haemoglobin A1c (HbA1c).ResultsOf 376 cases, 86 (22.9%) were classified as NASH. Prevalence of diabetes mellitus, body mass index (BMI) and postmortem HbA1c were significantly higher in NASH cases (39.5%, 32.3 kg/m2and 6.88%) than non-NASH cases (12.1%, 27.0 kg/m2and 5.73%). Decedents with moderate/severe fibrosis (6.9%) had higher prevalence of diabetes, BMI and HbA1c (50%, 31.4 kg/m2and 6.7%) compared with those with no/mild fibrosis (16%, 28 kg/m2and 5.9%). HbA1c ≥7% was found to be an independent predictor of NASH (OR 5.11, 95% CI 2.61 to 9.98) and advanced fibrosis (OR 3.94, 95% CI 1.63 to 9.53).ConclusionsNASH and advanced fibrosis were higher in our general adult autopsy population compared with previously published estimates. This is a large series with histological evaluation showing that HbA1c >7.0% is independently associated with NASH and advanced fibrosis.
Indirect impact of the COVID-19 pandemic and its containment measures on social inequalities in hospital utilisation in Italy
Authors: Di Girolamo Chiara , Gnavi Roberto , Landriscina Tania , Forni Silvia , Falcone Manuele , Calandrini Enrico , Cesaroni Giulia , Russo Antonio , Leoni Olivia , Fanizza Caterina , Allotta Alessandra , Costa Giuseppe , Spadea Teresa 
Published: May 2022

BackgroundThe pandemic may undermine the equity of access to and utilisation of health services for conditions other than COVID-19. The objective of the study is to evaluate the indirect impact of COVID-19 and lockdown measures on sociodemographic inequalities in healthcare utilisation in seven Italian areas.MethodsIn this multicentre retrospective study, we evaluated whether COVID-19 modified the association between educational level or deprivation and indicators of hospital utilisation and quality of care. We also assessed variations in gradients by sex and age class. We estimated age-standardised rates and prevalence and their relative per cent changes comparing pandemic (2020) and pre-pandemic (2018–2019) periods, and the Relative Index of Inequalities (RIIs) fitting multivariable Poisson models with an interaction between socioeconomic position and period.ResultsCompared with 2018–2019, hospital utilisation and, to a lesser extent, timeliness of procedures indicators fell during the first months of 2020. Larger declines were registered among women, the elderly and the low educated resulting in a shrinkage (or widening if RII <1) of the educational gradients for most of the indicators. Timeliness of procedures indicators did not show any educational gradient neither before nor during the pandemic. Inequalities by deprivation were nuanced and did not substantially change in 2020.ConclusionsThe socially patterned reduction of hospital utilisation may lead to a potential exacerbation of health inequalities among groups who were already vulnerable before the pandemic. The healthcare service can contribute to contrast health disparities worsened by COVID-19 through more efficient communication and locally appropriate interventions.