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Due to their bacterial ancestry, many components of mitochondria share structural similarities with bacteria. Release of molecular danger signals from injured cell mitochondria (mitochondria-derived damage-associated molecular patterns, mito-DAMPs) triggers a potent inflammatory response, but their role in fibrosis is unknown. Using liver fibrosis resistant/susceptible mouse strain system, we demonstrate that mito-DAMPs released from injured hepatocyte mitochondria (with mtDNA as major active component) directly activate hepatic stellate cells, the fibrogenic cell in the liver, and drive liver scarring. The release of mito-DAMPs is controlled by efferocytosis of dying hepatocytes by phagocytic resident liver macrophages and infiltrating Gr-1(+) myeloid cells. Circulating mito-DAMPs are markedly increased in human patients with non-alcoholic steatohepatitis (NASH) and significant liver fibrosis. Our study identifies specific pathway driving liver fibrosis, with important diagnostic and therapeutic implications. Targeting mito-DAMP release from hepatocytes and/or modulating the phagocytic function of macrophages represents a promising antifibrotic strategy. Progressive fibrosis is a driver of morbidity and mortality in many chronic liver diseases, but the underlying mechanisms are incompletely understood. Here, the authors show that mitochondria-derived damage-associated molecular patterns are released from injured hepatocytes and can trigger fibrogenic activation of hepatic stellate cells.

Background The use of feedback has been integral to medical student learning, but rigorous evidence to evaluate its education effect is limited, especially in the role of patient feedback in clinical teaching and practice improvement. The aim of the Patient Teaching Associate (PTA) Feedback Study was to evaluate whether additional written consumer feedback on patient satisfaction improved consultation skills among medical students and whether multisource feedback (MSF) improved student performance. Methods In this single site, double-blinded randomised controlled trial, 71 eligible medical students from two universities in their first clinical year were allocated to intervention or control and followed up for one semester. They participated in five simulated student-led consultations in a teaching clinic with patient volunteers living with chronic illness. Students in the intervention group received additional written feedback on patient satisfaction combined with guided self-reflection. The control group received usual immediate formative multisource feedback from tutors, patients and peers. Student characteristics, baseline patient-rated satisfaction scores and tutor-rated consultation skills were measured. Results Follow-up assessments were complete in 70 students attending the MSF program. At the final consultation episodes, both groups improved patient-rated rapport ( P  = 0.002), tutor-rated patient-centeredness and tutor-rated overall consultation skills ( P  = 0.01). The intervention group showed significantly better tutor-rated patient-centeredness ( P  = 0.003) comparing with the control group. Distress relief, communication comfort, rapport reported by patients and tutor-rated clinical skills did not differ significantly between the two groups. Conclusions The innovative multisource feedback program effectively improved consultation skills in medical students. Structured written consumer feedback combined with guided student reflection further improved patient-centred practice and effectively enhanced the benefit of an MSF model. This strategy might provide a valuable adjunct to communication skills education for medical students. Trial registration Australian New Zealand Clinical Trials Registry Number ACTRN12613001055796 .

Nonalcoholic fatty liver disease (NAFLD) is a major public health problem worldwide and the most common chronic liver disease. NAFLD currently affects approximately one in every four people in the United States, and its global burden is expected to rise in the next decades. Despite being a prevalent disease in the general population, only a minority of patients with NAFLD will develop nonalcoholic steatohepatitis (NASH) with advanced liver fibrosis (stage 3‐4 fibrosis) and liver‐related complications. Certain populations, such as patients with type 2 diabetes mellitus (T2DM), are recognized to be at the highest risk for developing NASH and advanced fibrosis. Both the American Diabetes Association and the European Association for the Study of Diabetes recommend screening of all T2DM for NAFLD. Incorporating a simple noninvasive algorithm into the existing diabetic care checklists in the primary care practice or diabetologist’s office would efficiently identify patients at high risk who should be referred to specialists. The proposed algorithm involves a first‐step annual fibrosis‐4 score (FIB‐4) followed by vibration‐controlled transient elastography (VCTE) for those with indeterminate or high‐risk score (FIB‐4 ≥1.3). Patients at low‐risk (FIB‐4 <1.3 or VCTE <8 kPa) can be followed up by primary care providers for lifestyle changes and yearly calculation of FIB‐4, while patients at high risk (FIB‐4 ≥1.3 and VCTE ≥8 kPa) should be referred to a liver‐specialized center. Conclusion: Patients with T2DM or prediabetes should be screened for NASH and advanced fibrosis. The proposed simple algorithm can be easily incorporated into the existing workflow in the primary care or diabetology clinic to identify patients at high risk for NASH and advanced fibrosis who should be referred to liver specialists.

Metabolic syndrome (MetS) represents a cluster of obesity and insulin resistance-related comorbidities. Abdominal obesity, hypertension, elevated triglyceride and glucose levels are components of MetS and may have a negative effect on cognitive function, but few cognitive studies have examined the combined risk severity. We sought to determine which specific cognitive abilities were associated with MetS in older adults at risk of cognitive decline. Cross-sectional study. 108 AIBL Active participants with memory complaints and at least one cardiovascular risk factor. Cardiovascular parameters and blood tests were obtained to assess metabolic syndrome criteria. The factors of MetS were standardized to obtain continuous z-scores. A battery of neuropsychological tests was used to evaluate cognitive function. Higher MetS z-scores were associated with poorer global cognition using ADAS-cog (adjusted standardized beta=0.26, SE 0.11, p<0.05) and higher Trail Making B scores (adjusted beta=0.23, SE 0.11, p<0.05). Higher MetS risk was related to lower cognitive performance. Combined risk due to multiple risk factors in MetS was related to lower global cognitive performance and executive function. A higher MetS risk burden may point to opportunities for cognitive testing in older adults as individuals may experience cognitive changes.

Correction to: BMC Health Services Research (2025) 25:873 https://doi.org/10.1186/s12913-025-12969-2 In this article, the authors reported Errors in the Abstract and in the footnote of Table 5. Additional benefits for patients included increased access to specialist advice through the and reduced face-to-face contact due to use of a digital platforms minimising unnecessary hospital visits for patients. Additional benefits for patients included increased access to specialist advice through the Wound Care Command Centre™ and reduced face-to-face contact due to use of a digital platform minimising unnecessary hospital visits for patients. Anna Cohen4 Show authors BMC Health Services Research volume 25, Article number: 1206 (2025) Cite this article 175 Accesses Metrics details The Original Article was published on 01 July 2025 Correction to: BMC Health Services Research (2025) 25:873 https://doi.org/10.1186/s12913-025-12969-2 In this article, the authors reported Errors in the Abstract and in the footnote of Table 5. Additional benefits for patients included increased access to specialist advice through the and reduced face-to-face contact due to use of a digital platforms minimising unnecessary hospital visits for patients. Additional benefits for patients included increased access to specialist advice through the Wound Care Command Centre™ and reduced face-to-face contact due to use of a digital platform minimising unnecessary hospital visits for patients.

Background Chronic wounds pose considerable financial challenges for healthcare systems globally, with most cases requiring hospital care and extended lengths of stay, particularly due to delayed access to treatment. To address this, Sydney Local Health District (LHD) in Australia launched the Wound Care Command Centre™ in 2023, utilising a digital application for timely access to wound care and to reduce the burden on hospitals. This study evaluates the cost consequences of this Centre by comparing healthcare service use under this new model of care compared to service use under standard clinical practice after one year of operation to determine savings to the health system. Methods Admitted patient, non-admitted and emergency department patient records relating to chronic wounds between 2018 and 2024 were analysed to determine service use costs, number of chronic wound admissions, length of stay, non-admitted services and emergency department presentations. Regression was used to control for patient mix, and records from a neighbouring LHD utilising the standard clinical care model was used as a control for this study. Results We estimated that with the Wound Care Command Centre™, in 2023 there were up to 97 chronic wound admissions prevented, 943 hospital days averted due to earlier discharges, 308 more non-admitted service events and 208 more emergency department presentations in Sydney LHD, compared to expected levels under standard clinical practice models. This was consistent with reduced prevalence of complex cellulitis admissions in Sydney LHD and partial shifting of care from admitted to outpatient settings. Reduced hospital admissions and earlier discharges were estimated to total between $3.2 M to $4.8 M and costs of non-admitted and emergency department services were estimated to total $264k. After accounting for $1.3 M operational costs for the Command Centre over 2023, net savings were between $1.7 M to $3.3 M. Conclusions The Wound Care Command Centre™ reduced hospital admissions by 97 individuals and shortened hospital length of stays by 1.1 day, resulting in savings up to $3.3 M for Sydney LHD. Additional benefits for patients included increased access to specialist advice through the Wound Care Command Centre™ and reduced face-to-face contact due to use of a digital platform minimising unnecessary hospital visits for patients.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and its prevalence continues to rise. Fibrosis‐4 index (FIB‐4) has been shown to be a prognostic marker of liver‐related outcomes in patients with NAFLD. We analyzed data from TriNetX global federated research network, combining data on 30 million patients. Patients were categorized into three diagnostic groups: NAFLD, nonalcoholic steatohepatitis (NASH), and at risk of NASH. Primary outcome was all‐cause mortality, and secondary outcomes included progression to NASH, development of cirrhosis, end‐stage liver disease, hepatocellular carcinoma (HCC), and liver transplantation. A total of 442,277 subjects (1.5% of the cohort) were assessed, and 81,108 were retained for analysis. Median follow‐up was 34.8 months (interquartile range 12.2). FIB‐4 was < 1.3 in 52.3% patients and ≥ 2.67 in 11.4% patients. In multivariate analysis, FIB‐4 ≥ 2.67 was significantly and independently associated with all‐cause mortality (hazard ratio [HR] 2.49, 95% confidence interval [CI] 2.20‐2.82, P < 0.001) as well as with progression to NASH (HR 5.78, 95% CI 4.72‐7.07, P < 0.001), cirrhosis (HR 2.04, 95% CI 1.86‐2.24, P < 0.001), end‐stage liver disease (HR 1.86, 95% CI 1.68‐2.05, P < 0.001), HCC (HR 3.66, 95% CI 2.71‐4.94, P < 0.001), and liver transplantation (HR 7.98, 95% CI 4.62‐13.79, P < 0.001). Conclusion: In a real‐world nationwide database, FIB‐4 ≥ 2.67 was a strong predictor of both all‐cause mortality and liver‐related adverse outcomes independently of the baseline diagnostic group and common risk factors. Our findings indicate that FIB‐4 could play a role as a risk‐stratification tool for a population health approach. Significant underdiagnosis of both NAFLD/NASH and NASH cirrhosis in electronic medical records was observed.

Nonalcoholic fatty liver disease (NAFLD) is closely associated with an increased risk of cardiovascular disease. We aimed to determine whether the fibrosis-4 index (FIB-4) can identify patients with NAFLD at highest risk of cardiovascular events. We analyzed data from 81,108 patients with (i) a diagnosis of NAFLD, (ii) nonalcoholic steatohepatitis (NASH), or (iii) at risk (RISK) of NASH. The outcome of interest was major adverse cardiovascular events (MACE) defined by myocardial infarction, hospitalization for unstable angina or heart failure, and coronary revascularization. The mean age was 62 years, and 49.6% were men. Among 67,273 patients without previous cardiovascular disease, 9,112 (13.5%) experienced MACE over median follow-up of 3 years. In univariate analysis, a FIB-4 ≥2.67 was a significant predictor of MACE overall (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.63-2.04, P < 0.001) and across all baseline groups. After adjusting for established cardiovascular risk factors, FIB-4 ≥2.67 remained the strongest predictor of MACE overall (adjusted HR [aHR] 1.80, 95% CI 1.61-2.02, P < 0.001) and was consistently associated with myocardial infarction (aHR 1.46, 95% CI 1.25-1.70, P < 0.001), hospitalization for unstable angina (aHR 1.24, 95% CI 1.03-1.49, P = 0.025), hospitalization for heart failure (aHR 2.09, 95% CI 1.86-2.35, P < 0.001), coronary artery bypass graft (aHR 1.65, 95% CI 1.26-2.17, P < 0.001), and percutaneous coronary intervention (aHR 1.72, 95% CI 1.21-2.45, P = 0.003). In a large, real-world cohort of patients with NAFLD, NASH, or at RISK of NASH, the FIB-4 score was the strongest independent predictor of MACE, beyond established cardiovascular risk factors and baseline liver diagnosis.

The complications of Nonalcoholic Fatty Liver Disease (NAFLD) are dependent on the presence of advanced fibrosis. Given the high prevalence of NAFLD in the US, the optimal evaluation of NAFLD likely involves triage by a primary care physician (PCP) with advanced disease managed by gastroenterologists. We compared the cost-effectiveness of fibrosis risk-assessment strategies in a cohort of 10,000 simulated American patients with NAFLD performed in either PCP or referral clinics using a decision analytical microsimulation state-transition model. The strategies included use of vibration-controlled transient elastography (VCTE), the NAFLD fibrosis score (NFS), combination testing with NFS and VCTE, and liver biopsy (usual care by a specialist only). NFS and VCTE performance was obtained from a prospective cohort of 164 patients with NAFLD. Outcomes included cost per quality adjusted life year (QALY) and correct classification of fibrosis. Risk-stratification by the PCP using the NFS alone costs $5,985 per QALY while usual care costs $7,229/QALY. In the microsimulation, at a willingness-to-pay threshold of $100,000, the NFS alone in PCP clinic was the most cost-effective strategy in 94.2% of samples, followed by combination NFS/VCTE in the PCP clinic (5.6%) and usual care in 0.2%. The NFS based strategies yield the best biopsy-correct classification ratios (3.5) while the NFS/VCTE and usual care strategies yield more correct-classifications of advanced fibrosis at the cost of 3 and 37 additional biopsies per classification. Risk-stratification of patients with NAFLD primary care clinic is a cost-effective strategy that should be formally explored in clinical practice.

Lack of physical activity is a risk factor for dementia, however, the utility of interventional physical activity programs as a protective measure against brain atrophy and cognitive decline is uncertain. Here we present the effect of a randomized controlled trial of a 24-month physical activity intervention on global and regional brain atrophy as characterized by longitudinal voxel-based morphometry with T1-weighted MRI images. The study sample consisted of 98 participants at risk of dementia, with mild cognitive impairment or subjective memory complaints, and having at least one vascular risk factor for dementia, randomized into an exercise group and a control group. Between 0 and 24 months, there was no significant difference detected between groups in the rate of change in global, or regional brain volumes.