Probiotic treatment with viable α-galactosylceramide-producing Bacteroides fragilis reduces diabetes incidence in female nonobese diabetic mice.

BACKGROUND: We aimed to investigate whether alpha-galactosylceramide (α-GalCer)-producing Bacteroides fragilis could induce natural killer T (NKT) cells in nonobese diabetic (NOD) mice and reduce their diabetes incidence. METHODS: Five-week-old female NOD mice were treated orally with B. fragilis, and islet pathology and diabetes onset were monitored. Immune responses were analyzed by flow cytometry and multiplex technology. Effects of ultraviolet (UV)-killed α-GalCer-producing B. fragilis and their culture medium on invariant NKT (iNKT) cells were tested ex vivo on murine splenocytes, and the immunosuppressive capacity of splenocytes from B. fragilis-treated NOD mice were tested by adoptive transfer to nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. RESULTS: B. fragilis reduced the diabetes incidence from 69% to 33% and the percent of islets with insulitis from 40% to 7%, which doubled the serum insulin level compared with the vehicle-treated control mice. Furthermore, the early treatment reduced proinflammatory mediators in the serum, whereas the proportion of CD4+ NKT cell population was increased by 33%. B. fragilis growth media stimulated iNKT cells and anti-inflammatory M2 macrophages ex vivo in contrast to UV-killed bacteria, which had no effect, strongly indicating an α-GalCer-mediated effect. Adoptive transfer of splenocytes from B. fragilis-treated NOD mice induced a similar diabetes incidence as splenocytes from untreated NOD mice. CONCLUSIONS: B. fragilis induced iNKT cells and M2 macrophages and reduced type 1 diabetes in NOD mice. The protective effect seemed to be more centered on gut-pancreas interactions rather than a systemic immunosuppression. B. fragilis should be considered for probiotic use in individuals at risk of developing type 1 diabetes.

Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments.

BACKGROUND: Fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like donor variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) with FMT or FVT hinder their wider clinical application in treating less acute diseases. METHODS: To overcome these challenges, we developed methods to broaden FVT's clinical application while maintaining efficacy and increasing safety. Specifically, we employed the following approaches: (1) chemostat-fermentation to reproduce the bacteriophage FVT donor component and remove eukaryotic viruses (FVT-ChP), (2) solvent-detergent treatment to inactivate enveloped viruses (FVT-SDT), and (3) pyronin-Y treatment to inhibit RNA virus replication (FVT-PyT). We assessed the efficacy of these processed FVTs in a C. difficile infection mouse model and compared them with untreated FVT (FVT-UnT), FMT, and saline. RESULTS: FVT-SDT, FVT-UnT, and FVT-ChP reduced the incidence of mice reaching the humane endpoint (0/8, 2/7, and 3/8, respectively) compared to FMT, FVT-PyT, and saline (5/8, 7/8, and 5/7, respectively) and significantly reduced the load of colonizing C. difficile cells and associated toxin A/B levels. There was a potential elimination of C. difficile colonization, with seven out of eight mice treated with FVT-SDT testing negative with qPCR. In contrast, all other treatments exhibited the continued presence of C. difficile. Moreover, the results were supported by changes in the gut microbiome profiles, cecal cytokine levels, and histopathological findings. Assessment of viral engraftment following FMT/FVT treatment and host-phage correlations analysis suggested that transfer of phages likely were an important contributing factor associated with treatment efficacy. CONCLUSIONS: This proof-of-concept study shows that specific modifications of FVT hold promise in addressing challenges related to donor variability and infection risks. Two strategies lead to treatments significantly limiting C. difficile colonization in mice, with solvent/detergent treatment and chemostat propagation of donor phages emerging as promising approaches. Video Abstract.

Patient education in multilingual groups of cardiac patients: Mission (im)possible?

Objective: In Norway, cardiac rehabilitation with patient education is usually accessible only to patients who understand Norwegian. The Cardiac Care Class (CCC) in focus in this article is a unique healthcare service in that, via interpreting services, it provides patient education to patients with limited Norwegian proficiency (LNP). This article examines the adaptations carried out to make cardiac rehabilitation accessible to LNP patients. Methods: The data stem from a qualitative study with participant observation during interpreter-mediated CCCs and from interviews with healthcare professionals, patients, and interpreters conducted by an interdisciplinary team. The collaborative data analysis focused on identifying various forms of adaptations. Results: Providing interpreting in CCCs required organizational, logistical, and pedagogical adaptations, including having fewer class participants, engaging qualified interpreters, conducting pre-class meetings with the interpreters, and adjusting the course content and language. Communication was found to be satisfactory, although some critical issues (e.g., interpreters' working conditions) were raised. Conclusion: This study showed that interpreter-mediated CCCs can reach multilingual groups provided that the necessary adaptations are made. Innovation: This research is the first to show how a cardiac rehabilitation class in Norway is made accessible to multilingual patient groups by providing interpreting.

Prevalence of sleep-disordered breathing in children and adolescents with large horizontal maxillary overjet due to mandibular retrognathia: a case control study.

STUDY OBJECTIVES: The aim of the study was to examine the prevalence of sleep-disordered breathing (SDB) in children and adolescents with large overjet due to mandibular retrognathia compared to a control group. METHODS: In this case-control study children with large overjet ≥ 6 mm due to mandibular retrognathia (study group) were compared to a group with neutral occlusion (controls). All participants underwent respiratory polygraphy (PG) and questionnaires regarding sleepiness and snoring. Differences across groups were tested by: Chi-square, general linear model adjusted for age, sex, and body mass index (BMI), and Mann-Whitney test. Differences in results of PG were also tested by general linear model adjusted for age, sex, and BMI according to severity of mandibular retrognathia. RESULTS: Thirty-seven (19 male;18 female, median age 12.3 years) participants were included in the study group and 32 (16 male;16 female, median age 12.2 years) in the control group. No significant difference in SDB assessed by PG or questionnaires between the groups was found even though the snore index was higher in the study group (p=0.051). The snore index was higher than the parent-reported snoring. Respiration rate was significantly reduced in the study group (p=0.043), and estimated sleep time efficiency was significantly reduced in males compared to females (p<0.001). CONCLUSIONS: No significant differences in SDB were found between the groups even though the snore index was higher in the study group. The snore index of the PG was higher than the parent-reported snoring. Estimated sleep time efficiency was reduced in males. The study improves the understanding of risk of SDB in non-obese children with large overjet due to mandibular retrognathia and may contribute to an interdisciplinary approach of risk assessment of SDB in children with malocclusion. CLINICAL TRIAL REGISTRATION: NCT04964830.

Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice.

Metabolic syndrome encompasses amongst other conditions like obesity and type-2 diabetes and is associated with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat metabolic syndrome by restoring the GM; however, concerns on accidentally transferring pathogenic microbes remain. As a safer alternative, fecal virome transplantation (FVT, sterile-filtrated feces) has the advantage over FMT in that mainly bacteriophages are transferred. FVT from lean male donors have shown promise in alleviating the metabolic effects of high-fat diet in a preclinical mouse study. However, FVT still carries the risk of eukaryotic viral infections. To address this, recently developed methods are applied for removing or inactivating eukaryotic viruses in the viral component of FVT. Modified FVTs are compared with unmodified FVT and saline in a diet-induced obesity model on male C57BL/6 N mice. Contrasted with obese control, mice administered a modified FVT (nearly depleted for eukaryotic viruses) exhibits enhanced blood glucose clearance but not weight loss. The unmodified FVT improves liver pathology and reduces the proportions of immune cells in the adipose tissue with a non-uniform response. GM analysis suggests that bacteriophage-mediated GM modulation influences outcomes. Optimizing these approaches could lead to the development of safe bacteriophage-based therapies targeting metabolic syndrome through GM restoration.

Network of doctors for multimorbidity and diabetes - the NOMAD intervention: protocol for feasibility trial of multidisciplinary team conferences for people with diabetes and multimorbidity.

BACKGROUND: The prevalence of diabetes and coexisting multimorbidity rises worldwide. Treatment of this patient group can be complex. Providing an evidence-based, coherent, and patient-centred treatment of patients with multimorbidity poses a challenge in healthcare systems, which are typically designed to deliver disease-specific care. We propose an intervention comprising multidisciplinary team conferences (MDTs) to address this issue. The MDT consists of medical specialists in five different specialities meeting to discuss multimorbid diabetes patients. This protocol describes a feasibility test of MDTs designed to coordinate care and improve quality of life for people with diabetes and multimorbidity. METHODS: A mixed-methods one-arm feasibility test of the MDT. Feasibility will be assessed through prospectively collected data. We will explore patient perspectives through patient-reported outcomes (PROs) and assess the feasibility of electronic questionnaires. Feasibility outcomes are recruitment, PRO completion, technical difficulties, impact of MDT, and doctor preparation time. During 17 months, up to 112 participants will be recruited. We will report results narratively and by the use of descriptive statistics. The collected data will form the basis for a future large-scale randomised trial. DISCUSSION: A multidisciplinary approach focusing on better management of diabetic patients suffering from multimorbidity may improve functional status, quality of life, and health outcomes. Multimorbidity and diabetes are highly prevalent in our healthcare system, but we lack a solid evidence-based approach to patient-centred care for these patients. This study represents the initial steps towards building such evidence. The concept can be efficiency tested in a randomised setting, if found feasible to intervention providers and receivers. If not, we will have gained experience on how to manage diabetes and multimorbidity as well as organisational aspects, which together may generate hypotheses for research on how to handle multimorbidity in the future. ADMINISTRATIVE INFORMATION: Protocol version: 01 TRIAL REGISTRATION: NCT05913726 - registration date: 21 June 2023.

New nomenclature for fatty liver disease.

This review investigates that, in 2023, fatty liver disease underwent a name change to "steatotic liver disease" (SLD). SLD now includes metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), and metabolic and alcohol-related liver disease (MetALD). The renaming aims to better incorporate alcohol intake and metabolic risk factors into disease classification and to diminish the stigma associated with the previous nomenclature. Early identification of the patient's aetiology is important for the prognosis which can be improved by interventions against the causative risk factors.

Advancing responsible genomic analyses of ancient mollusc shells.

The analysis of the DNA entrapped in ancient shells of molluscs has the potential to shed light on the evolution and ecology of this very diverse phylum. Ancient genomics could help reconstruct the responses of molluscs to past climate change, pollution, and human subsistence practices at unprecedented temporal resolutions. Applications are however still in their infancy, partly due to our limited knowledge of DNA preservation in calcium carbonate shells and the need for optimized methods for responsible genomic data generation. To improve ancient shell genomic analyses, we applied high-throughput DNA sequencing to 27 Mytilus mussel shells dated to ~111-6500 years Before Present, and investigated the impact, on DNA recovery, of shell imaging, DNA extraction protocols and shell sub-sampling strategies. First, we detected no quantitative or qualitative deleterious effect of micro-computed tomography for recording shell 3D morphological information prior to sub-sampling. Then, we showed that double-digestion and bleach treatment of shell powder prior to silica-based DNA extraction improves shell DNA recovery, also suggesting that DNA is protected in preservation niches within ancient shells. Finally, all layers that compose Mytilus shells, i.e., the nacreous (aragonite) and prismatic (calcite) carbonate layers, with or without the outer organic layer (periostracum) proved to be valuable DNA reservoirs, with aragonite appearing as the best substrate for genomic analyses. Our work contributes to the understanding of long-term molecular preservation in biominerals and we anticipate that resulting recommendations will be helpful for future efficient and responsible genomic analyses of ancient mollusc shells.

Infections increase the risk of decompensation and death in patients with early alcohol-related liver disease.

Background & Aims: Infections are frequent in patients with cirrhosis and worsen prognosis. We evaluated the incidence of infections and their impact on decompensation and death in patients with early alcohol-related liver disease (ALD) during long-term follow-up. Methods: We performed a prospective cohort study of patients in secondary care with a history of excess alcohol intake, no prior decompensation, and with liver biopsies along with clinical investigations conducted at baseline. During follow-up, we reviewed the patients' electronic healthcare records for cases of infections, hospitalizations, transient elastography measurements, decompensations, all-cause mortality, and alcohol intake. Results: We included 461 patients with a mean age of 56±10 years (76% males; fibrosis stage F0-1/F2/F3-4 = 259/107/93 [56%/23%/20%]). During a median follow-up of 4.5 years (IQR 2.9-6.3), 134 patients (29%) developed a total of 312 infections, most frequently pneumonia (106/312, 34%) and urinary tract infections (57/312, 18%). Excessive alcohol intake during follow-up, smoking ≥30 pack years, MELD score and elevated liver stiffness during follow-up were independent predictors of infections. Patients who developed at least one infection had a significantly increased risk of subsequent decompensation (hazard ratio 4.98, 95% CI 2.47-10.03) and death (hazard ratio 8.24, 95% CI 4.65-14.59). Infections increased the risk of decompensation and death independently of baseline fibrosis stage, age, gender, and MELD score. Conclusions: Almost one-third of patients with early ALD develop an infection, which worsens their prognosis by increasing the risk of decompensation and death. The risk of infections increases with liver disease severity and ongoing harmful use of alcohol. Impact and implications: This study reveals that infections significantly worsen the prognosis of patients with early alcohol-related liver disease (ALD), increasing the likelihood of decompensation and death by up to eight times. These findings, pertinent to healthcare providers, researchers, and policymakers, emphasize the importance of early prevention and management of infections in patients with ALD, even those in early stages who may be asymptomatic. It was observed that nearly one-third of patients with early-stage ALD developed infections over 4.5 years, with risk factors including alcohol overuse, smoking, and higher MELD scores. The research underscores the critical need to incorporate these insights into clinical practice and public health policies to improve patient outcomes and mitigate the impact of infections in patients with ALD.

Loss of Cardiac Splicing Regulator RBM20 Is Associated With Early-Onset Atrial Fibrillation.

We showed an association between atrial fibrillation and rare loss-of-function (LOF) variants in the cardiac splicing regulator RBM20 in 2 independent cohorts. In a rat model with loss of RBM20, we demonstrated altered splicing of sarcomere genes (NEXN, TTN, TPM1, MYOM1, and LDB3), and differential expression in key cardiac genes. We identified altered sarcomere and mitochondrial structure on electron microscopy imaging and found compromised mitochondrial function. Finally, we demonstrated that 3 novel LOF variants in RBM20, identified in patients with atrial fibrillation, lead to significantly reduced splicing activity. Our results implicate alternative splicing as a novel proarrhythmic mechanism in the atria.

Using liver stiffness to predict and monitor the risk of decompensation and mortality in patients with alcohol-related liver disease.

BACKGROUND & AIMS: Liver stiffness measurement (LSM) is recommended for disease prognostication and monitoring. We evaluated if LSM, using transient elastography, and LSM changes predict decompensation and mortality in patients with alcohol-related liver disease (ALD). METHODS: We performed an observational cohort study of compensated patients at risk of ALD from Denmark and Austria. We evaluated the risk of decompensation and all-cause mortality, stratified for compensated advanced chronic liver disease (cACLD: baseline LSM ≥10 kPa) and LSM changes after a median of 2 years. In patients with cACLD, we defined LSM changes as (A) LSM increase ≥20% ("cACLD increasers") and (B) follow-up LSM <10 kPa or <20 kPa with LSM decrease ≥20% ("cACLD decreasers"). In patients without cACLD, we defined follow-up LSM ≥10 kPa as an LSM increase ("No cACLD increasers"). The remaining patients were considered LSM stable. RESULTS: We followed 536 patients for 3,008 patient-years-median age 57 years (IQR 49-63), baseline LSM 8.1 kPa (IQR 4.9-21.7)-371 patients (69%) had follow-up LSM after a median of 25 months (IQR 17-38), 41 subsequently decompensated and 55 died. Of 125 with cACLD at baseline, 14% were "cACLD increasers" and 43% "cACLD decreasers", while 13% of patients without cACLD were "No cACLD increasers" (n = 33/246). Baseline LSM, follow-up LSM and LSM changes accurately predicted decompensation (C-index: baseline LSM 0.85; follow-up LSM 0.89; LSM changes 0.85) and mortality (C-index: baseline LSM 0.74; follow-up LSM 0.74; LSM changes 0.70). When compared to "cACLD decreasers", "cACLD increasers" had significantly lower decompensation-free survival and higher risks of decompensation (subdistribution hazard ratio 4.39, p = 0.004) and mortality (hazard ratio 3.22, p = 0.01). CONCLUSION: LSM by transient elastography predicts decompensation and all-cause mortality in patients with compensated ALD both at diagnosis and when used for monitoring. IMPACT AND IMPLICATIONS: Patients at risk of alcohol-related liver disease (ALD) are at significant risk of progressive disease and adverse outcomes. Monitoring is essential for optimal disease surveillance and patient guidance, but non-invasive monitoring tools are lacking. In this study we demonstrate that liver stiffness measurement (LSM), using transient elastography, and LSM changes after a median of 2 years, can predict decompensation and all-cause mortality in patients at risk of ALD with and without compensated advanced chronic liver disease. These findings are in line with results from non-alcoholic fatty liver disease, hepatitis C and primary sclerosing cholangitis, and support the clinical utility of LSM, using transient elastography, for disease prognostication and monitoring in chronic liver diseases including ALD, as recommended by the Baveno VII.

Sleepiness in children with severe malocclusion compared with in children with neutral occlusion.

INTRODUCTION: The study aimed to compare daytime sleepiness in children with severe malocclusion with healthy children with neutral occlusion (controls) and to analyze associations between daytime sleepiness and craniofacial morphology in children with severe malocclusion. METHODS: In 120 children with severe malocclusion (73 girls, 47 boys; mean age, 11.96 years; mean body mass index [BMI] score, 18.97 kg/m2) and 35 controls (18 girls, 17 boys; mean age, 11.97 years; mean BMI score, 20.28 kg/m2), sleep and daytime sleepiness were recorded using Epworth Sleepiness Scale and Berlin Questionnaire. Occlusion was registered clinically, and craniofacial morphology was assessed on lateral cephalograms. Differences in daytime sleepiness and sleep between the groups and associations between daytime sleepiness and sleep and craniofacial morphology were analyzed by a general linear model adjusted for age, gender, and BMI score. RESULTS: Daytime sleepiness occurred significantly more often in children with malocclusion than in control subjects (P = 0.015). There was a tendency for children with malocclusion to feel extremely tired during the day more often than controls (P = 0.054). There was no significant difference between the groups in sleeping hours during night-time, but the amount of sleep was negatively associated with age (P <0.001) and BMI score (P = 0.004). Only maxillary inclination was significantly associated with daytime sleepiness (P = 0.043). CONCLUSIONS: Daytime sleepiness occurred significantly more often in children with severe malocclusion than in those with neutral occlusion, and the association between daytime sleepiness and craniofacial morphology may exist. The results might prove valuable in interdisciplinary collaboration between medical doctors and orthodontists in diagnostics, prevention, and treatment of children at risk for sleep-disordered breathing.

Oro-facial function and quality of life in children and adolescents with large horizontal maxillary overjet-A case-control study.

BACKGROUND: Large horizontal maxillary overjet (overjet) is associated with reduced bite force (BF) and number of contacts, which influence the chewing effectivity (CE). Oral health, oro-facial function (OF) and malocclusion have great impact on psychological well-being and quality of life (QoL). OBJECTIVES: The aims of the study were to examine OF, temporomandibular disorders (TMD), BF, CE, QoL and well-being in children and adolescents with large overjet. METHODS: The study was a case-control study including healthy children with large overjet in the study group compared to a control group of healthy children with neutral occlusion, all 9-14 years old. OF was examined by use of Nordic Orofacial Test-Screening (NOT-S), Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and registration of morphological and functional occlusion. QoL and well-being were examined using KIDSCREEN-10 and Strengths and Difficulties Questionnaire. RESULTS: The study and control groups included 37 and 32 participants, respectively. Significantly increased NOT-S score (p < .001) and reduced BF (p = .011), numbers of contacts (p < .001) and CE (p = .005) were found in the study group. BF, numbers of contacts and CE were negatively associated with erupting canines and premolars. No significant difference was found in age, gender, dental eruption, TMD diagnosis or QoL between the groups. Significantly increased emotional symptoms (p = .007), hyperactivity (p = .043) and total difficulties score (p = .009) were found in the study group. CONCLUSION: The study group showed higher NOT-S score and reduced BF, number of contacts and CE. No difference in QoL were found between the groups, although reduced well-being and increased emotional symptoms, hyperactivity and total difficulties were found in the study group.

Pressure ulcer point prevalence, classification, locations, and preventive measures: Insights from a Norwegian nursing home survey.

OBJECTIVE: To report data from a point pressure ulcer (PU) prevalence survey on prevalence, PU categories, locations and preventive interventions at one Norwegian nursing home. METHODS: A cross-sectional research design was used. One nursing home in Norway participated in the prevalence survey in 2020. The data were collected on one selected day. A total of 74 out of 88 residents (84.1%) participated. Descriptive statistical analyses were run. RESULTS: The overall prevalence of PUs was 27% amongst all participants in the nursing home, who together had a total of 57 PUs categorised as category I-III. One major finding was that the most common site of the PUs was on the residents' toes. Interestingly, the prevalence of PUs in the residents' sacrum was considerably low. The most frequently used PU preventive interventions were foam chair cushions, nutritional supplements and pressure-reducing heel protection. CONCLUSION: This study identified a high prevalence of PUs, predominantly on residents' toes. Although preventive strategies were implemented, their application appeared limited. Implementing obligatory care packages and annual nationwide PU surveys might be worth considering in municipalities.

Validation of the new nomenclature of steatotic liver disease in patients with a history of excessive alcohol intake: an analysis of data from a prospective cohort study.

BACKGROUND: Steatotic liver disease is a new overarching term that includes metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related steatotic liver disease (MetALD), and alcohol-related liver disease (ALD). We aimed to validate the prognostic importance of MASLD, MetALD, and ALD as steatotic liver disease subclasses. METHODS: Between April 18, 2013, and Sept 17, 2018, we prospectively recruited patients aged 18-75 years with current or previous excessive alcohol intake (>24 g/day for women and >36 g/day for men) for at least a year and no previous hepatic decompensation from the Department of Gastroenterology and Hepatology at Odense University Hospital (Odense, Denmark). Participants were followed up until Sept 15, 2022. Here, we characterise these patients according to steatotic liver disease subclasses. We classified patients as having MASLD, MetALD, or ALD in accordance with the nomenclature definitions, on the basis of metabolic comorbidity and self-reported average alcohol intake in the 3 months leading up to inclusion. Histological scoring was done by a pathologist who was masked to the clinical data. We compared prognoses between classes using Cox regression analyses on hepatic decompensation and overall mortality as the two outcome measures. Patients not meeting the criteria for steatotic liver disease were classified as no steatotic liver disease and served as a reference group. FINDINGS: We enrolled 446 patients with a history of excessive alcohol intake were included in this analysis (334 [75%] were male and 112 [25%] were female; median age 56 years [SD 10]). Cirrhosis was present in 58 (13%), and 435 (98%) had at least one cardiometabolic risk factor. 321 (72%) met steatotic liver disease criteria and 125 (28%) did not have steatotic liver disease, meaning no evident liver steatosis and no significant fibrosis (≥F2). Of the 321 patients with steatotic liver disease, six (2%) were identified as having ALD due to the absence of cardiometabolic risk factors. The remaining 315 (98%) patients presented with at least one cardiometabolic risk factor. Of these patients, 153 (49%) had MASLD, 76 (24%) had MetALD, and 86 (27%) had ALD. During follow-up, 67 (15%) of 446 patients decompensated and 97 (22%) died (median follow-up 70 months [IQR 53-94]). Patients with steatotic liver disease had a significantly higher risk of hepatic decompensation and overall mortality than those without steatotic liver disease, independent of age, sex, and liver stiffness. The risk of decompensation increased in a stepwise manner from MASLD (hazard ratio 4·73 [95% CI 1·03-21·6]), through MetALD (7·69 [1·66-35·6]), to ALD (10·2 [2·24-46·4]). Similarly, overall mortality increased from MASLD (HR 2·30 [95% CI 1·08-4·90]), through MetALD (2·94 [1·31-6·58]), to ALD (3·57 [1·64-7·80]), independent of age, sex, and liver stiffness. INTERPRETATION: Steatotic liver disease and its subclasses portend distinct prognoses. There is a need to specify how historical alcohol intake should be integrated into the nomenclature and risk stratification of steatotic liver disease. FUNDING: EU Horizon 2020 Research and Innovation Program.

Screening for Fibrosis Promotes Lifestyle Changes: A Prospective Cohort Study in 4796 Individuals.

BACKGROUND AND AIMS: Early detection of liver fibrosis is believed to promote lifestyle changes. We evaluated self-reported changes in alcohol intake, diet, exercise, and weight after participating in a screening study for liver fibrosis. METHODS: We conducted a prospective screening study of individuals at risk of alcohol-related liver disease (ALD) or metabolic dysfunction-associated steatotic liver disease (MASLD). We provided lifestyle advice to all participants and evaluated lifestyle changes by questionnaires after 1 week and 6 months, with re-examination of a subgroup after 2 years. RESULTS: A total of 1850 at risk of ALD and 2946 at risk of MASLD were included, of whom 383 (8%) were screening positive (transient elastography ≥8 kPa). A total of 84% replied to the 6-month questionnaire. In ALD participants, excessive drinking decreased from 46% to 32% after 6 months. Only 15% reported increased drinking, without differences between screening positive and negative individuals (P = .698). In high-risk drinkers, a positive screening test predicted abstinence or decreased alcohol use after 6 months (odds ratio, 2.45; 95% confidence interval, 1.32-4.57; P = .005). After 2 years, excessive drinking decreased from 52% to 41% in a subgroup of 752 individuals and a positive screening test predicted abstinence or decreased alcohol use after 2 years (odds ratio, 1.84; 95% confidence interval, 1.09-3.11, P = .023). MASLD participants showed similar improvements: 35% improved their diet, 22% exercised more, and 13% reported a weight loss ≥5% after 6 months. CONCLUSIONS: Screening for liver fibrosis is associated with sustained improvements in alcohol consumption, diet, weight, and exercise in at-risk ALD and MASLD. The changes are most pronounced in screening positive participants but not limited to this group.

Conflictos de intereses financieros en las revisiones sistemáticas: asociación con los resultados, las conclusiones y la calidad metodológica / Financial conflicts of interest in systematic reviews: associations with results, conclusions, and methodological quality

Las prácticas de tratamiento de los pacientes se basan a menudo en la investigación clínica. Las revisiones sistemáticas son un tipo de investigación clínica fundamental. Cuando se han realizado varios estudios similares (es decir, estudios que investigan las mismas cuestiones de investigación utilizando métodos similares), estos pueden identificarse y analizarse en una revisión sistemática.Así, las revisiones sistemáticas resumen los estudios existentes y proporcionan una visión general de un campo de investigación específico. Por lo tanto, pueden tener una gran influencia en las decisiones sobre la atención al paciente y es esencial que sean fiables.A veces, las revisiones sistemáticas están financiadas por empresas con un interés económico en los resultados y las conclusiones de la revisión. Por ejemplo, porque producen un medicamento o dispositivo investigado en la revisión. En otras ocasiones, las revisiones sistemáticas son llevadas a cabo por investigadores con un interés financiero personal en un resultado específico. Por ejemplo, cuando el investigador actúa como consultor de la empresa que produce una intervención que es evaluada en la revisión. Estos conflictos de intereses financieros pueden repercutir en la forma en que se realizan las revisiones sistemáticas y se informa de ellas. La Revisión Metodológica Cochrane se centra en los conflictos de intereses financieros relacionados con las empresas de medicamentos o dispositivos en las revisiones sistemáticas. El objetivo principal fue investigar el grado en que las revisiones sistemáticas con conflictos de intereses financieros presentan los resultados de la revisión y sacan conclusiones más favorables que las revisiones sistemáticas sin dichos conflictos de intereses financieros. (AU)