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176 papers

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

Comparative Evaluation of Smartphone-Based Fundus Imaging Systems in Dogs and Cats.

Michaud B. · Jul 1, 2026

Objective To compare the feasibility, image quality, acquisition time, and evaluator preference of four smartphone-based fundus imaging (SBFI) systems in dogs and cats using a handheld fundus camera as a reference device. Animals studied Twenty client-owned animals, including 10 dogs and 10 cats. Procedures Fundus images were obtained from 40 eyes (20 mydriatic and 20 non-mydriatic) using four SBFI systems (iExaminer Panoptic, NUN WFE-02S, OQVet, and VistaView) and a handheld infrared fundus camera (Aurora). Image acquisition success and acquisition time were recorded for each device. Image quality was independently graded using a 10-point Likert scale by a masked panel of 32 veterinary ophthalmologists. Evaluators also selected their preferred image among the four SBFI systems. Results Image acquisition was successful in all animals for all devices under both mydriatic and non-mydriatic conditions (100%). Image quality differed significantly between devices. Among SBFI systems, OQVet achieved the highest median score (7; interquartile range [IQR] 6-8), followed by VistaView (6; IQR 5-8), NUN (5; IQR 4-7), and iExaminer (4; IQR 3-5). OQVet received approximately 50% of evaluator preference votes. The reference camera achieved the highest image quality in 77.5% of imaging sets but was outperformed by OQVet (15%) and VistaView (7.5%) in some examinations. Pupil dilation did not significantly influence image quality or acquisition time. Conclusions Smartphone-based fundus imaging enables reliable retinal imaging in dogs and cats and represents an accessible option for retinal documentation and screening in veterinary practice.

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

Hypertransaminasemia Is a Marker of Severity in Children Hospitalized for Influenza.

Poeta M et al. · Jul 1, 2026

Purpose Elevated transaminases have been associated with increased severity in adult influenza cases, but data in the pediatric population are limited. This study aims to evaluate the prevalence, clinical characteristics and prognostic value of elevated transaminases in children hospitalized for influenza. Methods A multicentre retrospective cohort study was conducted on 543 children hospitalized for acute viral respiratory infections. Demographic, clinical, biochemical, radiological features, and outcome were collected and analyzed, comparing children with influenza to those with other respiratory viruses. The association between elevated transaminases and clinical severity, complications, and intensive care unit (ICU) admission was assessed. Results Among 543 children, 127 (23.4%) had laboratory-confirmed influenza, with 24.4% showing elevated transaminases versus 7.2% in noninfluenza infections (p Conclusion Elevated transaminases occur in one fourth of children hospitalized for influenza and are associated with more severe disease, systemic complications, and worse outcomes. The findings suggest that transaminase elevation reflects systemic and muscular involvement rather than primary liver injury. Monitoring transaminases provides an early, easy marker to identify children at risk of severe influenza.

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

Integrating Individual Placement Support in Early Psychosis Programs: A Necessary Step to Foster Return to Employment in First Episode Psychosis Patients.

Renda M et al. · Jul 1, 2026

Introduction Return to studies or employment, a major element of recovery after a first episode of psychosis (FEP), is out of reach of a significant proportion of patients. Specific programs such as Individual Placement Support (IPS) have been proposed to overcome this hurdle. While some early intervention programs include IPS, others must rely on IPS programs that are open to a wider range of patients. The aim of this paper was to explore the accessibility of IPS for FEP patients treated in such a context. Methods One hundred and eighty nine patients of an ongoing FEP cohort study who were treated at our program in the period where the IPS program was available and for whom sufficient data was available were included in the study. We assessed reasons for non-referral to RESSORT and compared baseline and outcome characteristics of patients who did or did not enter the program. Results A small minority of patients had access to RESSORT. Patients who entered RESSORT had better premorbid functioning and a higher degree of insight at baseline than the ones who did not enter the program. Patients who entered RESSORT had a significantly higher rate of return to premorbid PAS score, without significant difference on other dimensions of functioning. Conclusions When IPS programs are not embedded in early intervention programs, FEP patients have limited chances to access them. Integrating supported employment skills within the role of case managers may be a solution in programs where resources are lacking to develop an IPS program specifically dedicated to FEP patients.

Medicine

Validation of Risk Models for Predicting Post-SVR HCC in Real-World Surveillance Across Global Geographic Regions.

Toyoda H et al. · Jul 1, 2026

Background & aims Several clinical risk models have been proposed to stratify hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis C virus (HCV) after sustained virologic response (SVR). However, validation efforts have focused on monocentric or country-specific cohorts, and it is unclear if clinical risk models can be broadly applied to global populations. We characterised regional variation in model performance for HCC risk stratification in post-SVR patients. Methods Four HCC clinical risk models (aMAP score, FIB-4 index, GES score, and Toronto HCC risk index [THRI]) were analysed in six real-world cohorts, which included 8796 post-SVR patients from different geographic regions globally. Model discrimination was assessed using Harrel's c-statistic index. HCC incidence rates were compared across low-, intermediate-, and high-risk groups for each model. Results Distributions of patient characteristics and HCC incidence rates varied across geographic regions. Predictive performances of models were comparable within each cohort despite the model with the highest c-statistics differing by regions. Performance was lower than those from original reports overall; c-statistics of models across most regions remained below 0.70. Conclusions There remains a continued need to improve discrimination and calibration of clinical models to stratify HCC risk in post-SVR patients. Accuracy of models may differ by geographic region, underscoring the importance of external validation to assess transportability of models and suggesting no single model can be universally applied.

Medicine