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176 papers

Changes in Inpatient Coding for Hepatic Encephalopathy After Introduction of ICD-10 Code K76.82.

Goble SR et al. · Jul 1, 2026

An ICD-10 code specific for hepatic encephalopathy (HE), K76.82, was introduced in October of 2022. We aimed to assess changes in HE documentation following the introduction of this code. Using the National Inpatient Sample, we compared utilization of ICD-10 codes historically used to identify HE before and after K76.82. From 2016 to 2021, 20.0% of cirrhosis hospitalizations included a non-specific HE code, decreasing to 4.7% in 2023. K76.82 was used in 20.3% of hospitalizations in 2023. The introduction of K76.82 has dramatically changed the documentation of HE, and future studies assessing HE trends and outcomes need to account for these changes.

Medicine

Early Versus Late Wake-Up Call After Out-Of-Hospital Cardiac Arrest: Protocol for a Multicenter Randomized Comparison Within the Danish Out-of-Hospital Cardiac Arrest (DANOHCA) Trial.

Grejs AM et al. · Jul 1, 2026

Background Survivors of out-of-hospital cardiac arrest (OHCA) who remain comatose after return of spontaneous circulation are routinely sedated and mechanically ventilated during early post-resuscitation care. Although prolonged sedation has traditionally been considered necessary, contemporary normothermia-based temperature control allows earlier wake-up call. The optimal timing of an early wake-up call remains unknown and may influence overall mortality, neurological recovery, duration of mechanical ventilation, and length of hospital stay. Methods The Danish Out-of-Hospital Cardiac Arrest (DANOHCA) trial (clinicaltrials.gov identifier: NCT05895838; and euclinicaltrials.eu, identifier: 2024-515,997-28-00) is an investigator-initiated, multicenter, randomized clinical trial using a 2 × 2 × 2 × 2 factorial design evaluating four interventions in patients resuscitated from OHCA. The present protocol describes the comparison of an early versus late wake-up call strategy. Adult patients (≥ 18 years) with presumed cardiac-cause of OHCA, sustained return of spontaneous circulation, and persistent unconsciousness on intensive care unit admission are randomized 1:1 to early wake-up call (≤ 6 h after randomization) or late wake-up call (28-36 h after randomization). Wake-up call includes interruption of sedation, assessment of neurology, and may be followed by extubation if predefined neurological and respiratory criteria are fulfilled. The primary endpoint is days alive and out of hospital within 30 days after randomization. Analyses will follow a modified intention-to-treat principle. Perspectives Optimizing post-resuscitation care remains a cornerstone in managing comatose cardiac arrest survivors and improving outcomes. We hypothesize that sedation for 28-36 h leads to more days alive outside of the hospital in 30 days compared to sedation for ≤ 6 h. Trial registration EudraCT number: 2016-003265-26; EU CTIS no 2024-515997-28-00; ClinicalTrials.gov identifier: NCT05895838.

Medicine

Effects of a 4-Week Multi-Exercise Isometric Resistance Training Programme on Resting and Ambulatory Blood Pressure in Normotensive Adults.

Wright BH et al. · Jul 1, 2026

Isometric resistance training (IRT) can reduce resting and ambulatory blood pressure (AmBP) yet established exercise methods lack versatility and may present with participation barriers. An isometric training band (ITB) has been identified as an alternative modality; however, its long-term effects on resting and ambulatory blood pressure (BP) remains unknown. This study assessed the effects of the ITB on resting BP and AmBP following 4 weeks of IRT. Forty-two normotensive adults (22 male, 20 female; mean ± SD, age 31 ± 14 years, systolic [sBP], 120 ± 5 mmHg, diastolic [dBP], 72 ± 7 mmHg), were randomised to a control (CON), isometric handgrip (IHG) or ITB group. Resting (systolic, diastolic, mean arterial BP and heart rate [HR]) and AmBP (24-h, daytime and night-time) were measured pre- and post-4 weeks of supervised IRT (4 x 2-min contractions at 30% MVC [IHG] or 4 x 2-min contractions at CR-10 values equivalent to 30% MVC [ITB]). Resting sBP was reduced for IHG (-4.6 mmHg, p 0.05 across all measures). These findings suggest 4 weeks of IRT using the ITB can elicit reductions in resting BP and night-time AmBP in normotensives comparable to IHG, indicating the ITB may offer a practical and cost-effective alternative to established interventions.

Medicine

Herpes Simplex Virus Hepatitis: An Overlooked Cause of Acute Liver Failure Across a Broad Spectrum of Immunocompromise.

Mondelli MU et al. · Jul 1, 2026

Background and aims Herpes simplex virus (HSV) infection is common worldwide, but hepatic involvement is rare. HSV hepatitis is an uncommon yet frequently catastrophic cause of acute hepatitis and acute liver failure (ALF), accounting for Methods We describe three cases of HSV hepatitis presenting with distinct risk profiles and clinical manifestations and review the diagnostic and therapeutic challenges associated with this condition. Results Clinical presentation was nonspecific in all cases, and mucocutaneous lesions were absent or delayed, contributing to diagnostic uncertainty. All patients exhibited marked aminotransferase elevation with relatively modest hyperbilirubinemia ("anicteric hepatitis"), frequently accompanied by cytopenias and coagulopathy. Delayed recognition was associated with rapid clinical deterioration, whereas earlier initiation of intravenous acyclovir was associated with biochemical and clinical improvement. Diagnosis was established using polymerase chain reaction-based detection of HSV DNA in blood and tissue samples. Conclusions HSV hepatitis remains an under-recognized cause of ALF across a broad spectrum of immunocompromised and seemingly immunocompetent patients. Given the narrow therapeutic window and favourable safety profile of acyclovir, empiric intravenous antiviral therapy should be considered in patients with ALF of indeterminate aetiology while diagnostic testing is pending, particularly in high-risk clinical settings. Increased awareness of this overlooked diagnosis may improve outcomes and prevent avoidable mortality.

Medicine

Diabetic Foot Ulceration in Dialysis-Dependent End-Stage Kidney Disease: A Systematic Review of Epidemiology, Clinical Outcomes and Mortality Risk.

Lim JZM et al. · Jul 1, 2026

Background Diabetic foot ulceration (DFU) and lower limb complications are highly prevalent in people with end-stage kidney disease (ESKD), particularly those receiving dialysis; however, the overall burden and outcomes remain incompletely characterised. This systematic review with narrative synthesis aimed to summarise study characteristics and evidence on the epidemiology of DFU in ESKD, including incidence, prevalence, wound healing outcomes, and associations with lower-extremity amputation (LEA) and mortality. Methods MEDLINE (via PubMed), EMBASE and the Cochrane Database of Systematic Reviews were searched from inception to 31 January 2026 for longitudinal and cross-sectional studies, including registry data, in adults with ESKD or on dialysis. Outcomes included DFU epidemiology, wound healing, revascularisation, LEA and mortality. Results The review included 64 observational studies. In dialysis-dependent populations, DFU incidence is high and increases with advancing renal impairment, often preceding dialysis initiation. Evidence on whether dialysis initiation itself increases DFU risk is limited and heterogeneous, although observational cohorts suggest a temporal association with haemodialysis initiation, particularly within the first 2 years. Data comparing haemodialysis and peritoneal dialysis are scarce. Wound healing outcomes were variable, with earlier recurrence observed, although multidisciplinary care improved healing, largely driven by perfusion and ulcer severity rather than renal function alone. Although based on observational and heterogeneous data, dialysis-dependent ESKD was frequently identified as an independent predictor of LEA after adjustment for confounders, with coexisting peripheral arterial disease, a key determinant of adverse limb outcomes. Mortality risk appeared to compound following amputation, with observational data suggesting high post-amputation mortality (approaching 50% at 2 years and 70% at 5 years), consistent with a shift towards limb loss rather than increased DFU occurrence. Interpretation is limited by study heterogeneity, observational design, limited long-term data on healing and recurrence, and inadequate stratification by dialysis modality. Conclusions Current evidence underscores substantial gaps in understanding the natural history and optimal management of diabetic foot disease in dialysis-dependent ESKD. Future research should prioritise well-designed prospective studies to delineate dialysis-specific risk pathways, incorporate robust stratification by dialysis modality, and evaluate interventions targeting ischaemia and limb preservation. Standardisation of outcome reporting, particularly for healing durability and recurrence, will be essential to enable meaningful comparisons and guide the development of tailored multidisciplinary care models for this high-risk population.

Medicine

Acute HEV Infection Is a Relevant Cause of Decompensation and ACLF in Patients With Liver Cirrhosis.

Dinkelborg K et al. · Jul 1, 2026

Background and aims Hepatitis E virus (HEV) infection is very frequent in Europe with more than 2 million annual infections. Patients with liver cirrhosis may face an increased risk of suffering from acute-on-chronic liver failure (ACLF) due to HEV infection. We explored the consequences and prevalence of HEV infection in individuals with liver cirrhosis. Methods We retrospectively analysed the clinical outcome of all consecutive patients who were hospitalized at our center due to acute HEV infection and analysed their outcome between 2014 and 2024. Next, we tested 249 sera from 184 cirrhotic patients during individual episodes of acute hepatic decompensation for anti-HEV IgM and HEV-RNA to analyse the relevance of acute HEV infection as a triggering event. Finally, we established a single center cohort of patients with advanced liver cirrhosis, and assessed the anti-HEV IgG seroprevalence (n = 332). Results Over the past decade, 32 patients with liver cirrhosis who were hospitalized due to acute HEV infection were identified. Among these patients, 16 (50%) developed ACLF, resulting in five fatalities (31.3%) and three individuals (18.8%) requiring liver transplantation for survival. Of 249 sera obtained during acute hepatic decompensation, 11 (4.4%) were either HEV-RNA positive (n = 2) and/or anti-HEV IgM positive (n = 10), linking HEV infection to these acute decompensations. Screening of patients with liver cirrhosis for anti-HEV IgG showed that 67.2% of patients (223/332) were anti-HEV negative and thus at potential risk for future HEV infection. Conclusions Patients with advanced liver cirrhosis are at risk of acute HEV infection, which is a relevant cause of hepatic decompensation and ACLF with high mortality in these patients. Trial registration DRKS00010664; NCT04801290.

Medicine

Aging and Western Diet Synergistically Impair Hepatic Thyroid Hormone Signaling to Promote Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Mice.

Zhang X et al. · Jul 1, 2026

Metabolic dysfunction-associated steatotic liver disease (MASLD) is primarily driven by a Western-style diet and exacerbated with aging, yet underlying mechanisms remain unclear. Given the essential role of thyroid hormone (TH) in MASLD progression, we hypothesized that impaired intrahepatic TH action during aging promotes MASLD progression and severity of MASH with fibrosis. We evaluated hepatic TH metabolism in young (18-24 weeks) and old (108-120 weeks) C57BL/6J mice fed either a normal chow diet (NCD) or a Western diet with fructose (WDF) for 8 weeks. Liver histology, metabolic parameters, inflammatory and fibrotic markers, intrahepatic thyroxine (T4) and triiodothyronine (T3) concentrations, and activities of deiodinase enzymes (Dio1 and Dio3) were measured. Additionally, an in vitro hepatocyte senescence model using AML12 cells was employed to assess age-related alterations in deiodinase expression and the therapeutic efficacy of resmetirom (an FDA-approved thyromimetic). Aging and WDF synergistically exacerbated hepatic inflammation and fibrosis, accompanied by significant reductions in intrahepatic T4 and T3. Aging markedly decreased Dio1 activity, which converts T4 to active T3, whereas WDF partially restored Dio1 in old mice. Conversely, Dio3 activity, responsible for TH inactivation, increased with age but exhibited age-dependent differential responses to WDF, findings mirrored in senescent hepatocytes. Notably, resmetirom significantly reduced senescence markers, inhibited senescence-associated secretory phenotype (SASP) genes, inflammasome activation, endoplasmic reticulum (ER) stress, and activated autophagy. Collectively, our findings demonstrate that aging and stress by a Western-style diet synergistically impair hepatic TH signaling, accelerating MASLD progression. Furthermore, resmetirom improved hepatic senescence, highlighting its potential therapeutic repurposing for aging-associated hepatic pathologies, including MASLD.

Medicine

Clinical Remission of an Unresectable Presumptive Haemangiosarcoma in a Dog Treated With Toceranib, Piroxicam, and Propranolol: A Case Report.

Park WD. · Jul 1, 2026

Haemangiosarcoma (HSA) is a highly aggressive vascular tumour in dogs, characterised by rapid growth, early metastasis, and poor prognosis despite conventional treatment with surgery and doxorubicin-based chemotherapy. A 14-year-old spayed female Maltese (4.14 kg) was presented with progressive abdominal distension and anorexia. Imaging revealed a large retroperitoneal mass, and computed tomography identified a 12.1 × 8.0 × 8.5 cm heterogeneous tumour. Exploratory laparotomy confirmed the lesion was unresectable, and biopsy findings were most consistent with presumptive haemangiosarcoma (HSA) due to the small, cautery-affected specimen. Medical therapy was initiated with toceranib phosphate (10 mg every other day), followed one week later by propranolol (0.3 mg/kg twice daily) and piroxicam (0.3 mg/kg once daily). The patient was monitored every 2-4 weeks with physical examination and serial haematology and serum biochemistry. Two months after initiating therapy, the abdominal ultrasonography demonstrated tumour reduction to 4.9 × 2.7 cm, and after 7 months the mass was no longer detectable on radiographic follow-up imaging (radiography and ultrasonography). Throughout treatment, haematologic and biochemical values remained within reference intervals, no clinically significant adverse effects were observed, and the owner reported resolution of abdominal distension with improved activity. This case demonstrates that combined therapy with toceranib, propranolol, and piroxicam achieved radiographic and clinically sustained remission of unresectable canine presumptive HSA while preserving quality of life. These findings suggest that multimodal therapy targeting angiogenesis and tumour growth pathways may represent a promising alternative strategy for managing this malignancy and warrant further clinical evaluation.

Medicine

Assessment of allopurinol use in patients with chronic kidney disease and asymptomatic hyperuricemia: a retrospective cohort study.

Souza MELS et al. · Jul 1, 2026

Introduction Asymptomatic hyperuricemia (AH) is common in patients with chronic kidney disease (CKD) and has been identified as a modifiable condition. Addressing it could increase the possibilities for preventing and treating kidney injury. Objective To assess whether administering allopurinol to people with chronic kidney disease and asymptomatic hyperuricemia enhances kidney function and delays progression to kidney failure. Methods This is a retrospective cohort study with data collection from medical records at a specialized center from 2006 to 2020. Eighty people in stages 3 and 4 of CKD with AH were divided into two groups: 40 patients received allopurinol and 40 did not receive medication. Patients were followed for 24 months, with four consultations. Serum uric acid levels and creatinine-based estimated glomerular filtration rate (eGFRcr), estimated by the CKD-EPI formula, were compared within groups and between groups using mean, standard deviation, and analysis of variance (ANOVA). Results Eighty patients were included in the study. Comparing 40 patients with no treatment for hypertension with 40 patients receiving hypouricemic therapy (HUT) with allopurinol, it was observed that mean serum uric acid decreased at all review visits in the allopurinol group, and there was a significant increase in mean eGFRcr after starting allopurinol (p Conclusion Allopurinol was useful in reducing serum uric acid levels, improving kidney function, and delaying progression to kidney failure in patients with AH.

Medicine

Impact of Different Types of Sedentary Behaviour on Cognitive Function in Older Adults: A Systematic Review.

de Jesus Silva TR et al. · Jul 1, 2026

Issue addressed Sedentary behaviour (SB) is a relevant determinant of health in ageing, yet its effects on cognitive function remain inconclusive. The literature often treats SB as a homogeneous exposure, without considering that different sedentary activities may differentially affect cognitive domains. Accordingly, this study sought to identify how distinct types of SB influence cognition in older adults. Methods A systematic review was conducted and registered in PROSPERO (CRD42025637160), following PRISMA guidelines. Observational studies published between 2010 and 2025 were included if they involved participants aged 60 years or older and examined the relationship between specific types of SB and cognitive domains. Searches were performed in PubMed/MEDLINE, Web of Science and Scopus. Two independent reviewers carried out study selection, data extraction and quality assessment using Joanna Briggs Institute tools. Results The search yielded 1795 records, resulting in the inclusion of 13 studies encompassing 43 902 participants. Findings were heterogeneous: passive SB, particularly, television viewing, was more frequently associated with poorer cognitive performance. In contrast, cognitively stimulating sedentary activities involving complex tasks-such as reading, playing games and computer use-were positively associated with memory, executive function and processing speed. Some studies further suggested that cognitive engagement may mitigate potential negative effects of SB. Conclusions The findings indicate that the impact of SB on cognition depends more on the type of activity performed than on total sedentary time, underscoring the importance of context and mental demand. SO WHAT?: Identifying which types of SB are beneficial or harmful may inform health promotion strategies, encouraging older adults to replace passive SB with cognitively stimulating sedentary activities, thereby supporting healthier cognitive ageing.

Medicine