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PubMed2026

Prevalence of Slowly Expanding Lesions in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Chronic active lesions (CALs) reflect chronic inflammation in multiple sclerosis (MS). Slowly expanding lesions (SELs) are CALs identified on conventional MRI by linear, concentric expansion over time, while paramagnetic rim lesions (PRLs) are CALs characterized by a paramagnetic rim on susceptibility-sensitive MRI. However, the prevalence of SELs and their overlap with PRLs remain unclear. The aims of this study were to (1) estimate the proportion of SELs among all T2 lesions and the proportion of patients with at least 1 SEL and (2) assess the proportion of SELs overlapping with PRLs. METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase on February 1, 2026, for studies evaluating SELs in MS. At least 2 authors independently assessed study eligibility. Primary outcomes were the pooled proportion of SELs among T2 lesions and the proportion of patients with at least 1 SEL. We estimated mean per-patient volumes of SELs and total T2 lesions and the proportion of SELs overlapping with PRLs. Random-effects generalized linear mixed-effects models and inverse-variance methods were used, with between-study heterogeneity assessed using τ2 and I2 and robustness using sensitivity analyses. Univariable meta-regression explored heterogeneity. PROSPERO: CRD42024603778. RESULTS: Of 5,980 records, 20 studies comprising 4,786 patients with MS were included (mean age: 43.6 ± 6.3 years; 63.7% female). Sample sizes varied by outcome. SELs accounted for 14% (95% CI 10-21) of all T2 lesions, and 78% (67-85) of patients had at least 1 SEL. After sensitivity analysis, per-patient mean volumes were 1.42 mL (0.79-2.06) for SELs and 10.6 mL (8.53-12.67) for total T2 lesions. In total, 11% (6-20) of SELs overlapped with PRLs. In subgroup analyses, proportions of SELs were similar in relapsing-remitting and progressive MS (15%), but the proportion of patients with at least 1 SEL was higher in progressive MS. Between-study heterogeneity was high across analyses with no significant sources identified. DISCUSSION: Although SELs represent a minority of T2 lesions, most patients have at least 1 SEL and a subset overlaps with PRLs, suggesting a partial correspondence between these 2 imaging markers of chronic inflammatory activity. Limitations include possible publication bias, high unexplained heterogeneity, differences in SEL identification methods, and differences in MRI time point number/timing.

Humans↗

PubMed2026

Identification and functional characterization of a novel antiviral chicken interferon-υ.

Interferons are critical mediators of antiviral immunity in vertebrates. While type IV interferon (IFN-υ) has been identified in fish and amphibians, its existence and function in chickens remained unknown. Through systematic genomic screening, we identified and cloned a novel chicken interferon gene, designated ChIFN-υ. Phylogenetic analysis placed ChIFN-υ within a distinct clade alongside zebrafish and clawed frog IFN-υ, confirming its identity as a type IV interferon, with minimal homology to classical type I, II, or III IFNs. Expression profiling revealed constitutive ChIFN-υ expression in mucosal and immune tissues of healthy chickens, exhibiting a distinct developmental shift: highest in trachea and small intestine in 1-day-old chicks, shifting to spleen and lung in 4-week-old chickens. ChIFN-υ expression was strongly upregulated following H9N2 AIV infection. Functionally, recombinant ChIFN-υ protein activated the interferon-stimulated response element (ISRE) and Mx promoter in a dose-dependent manner and significantly inhibited the replication of both vesicular stomatitis virus (VSV) and H9N2 AIV in DF-1 cells. In vivo, early treatment with exogenous ChIFN-υ significantly reduced pulmonary and tracheal viral loads and decreased oropharyngeal and cloacal virus shedding in H9N2-infected chickens. In conclusion, this study identifies and functionally characterizes the type IV interferon in chickens, elucidating the evolutionary status, regulated expression, and antiviral efficacy of ChIFN-υ. These findings highlight its potential as a candidate for developing interferon-based therapies against avian viral diseases.

Animals↗

PubMed2026

Synaptic vesicle glycoprotein 2A PET imaging in parkinsonian α-synucleinopathies: a systematic review.

Synaptic dysfunction is increasingly recognized as an early and biologically relevant component of α-synucleinopathies. However, conventional imaging biomarkers mainly assess dopaminergic dysfunction, glucose metabolism, or structural damage rather than presynaptic density itself. Synaptic vesicle glycoprotein 2A (SV2A) PET enables in vivo assessment of presynaptic terminal integrity and may provide complementary information in Parkinson's disease (PD), Parkinson's disease dementia/dementia with Lewy bodies (PDD/DLB), and multiple system atrophy (MSA). This systematic review synthesized the available evidence on SV2A-targeted PET in parkinsonian α-synucleinopathies, focusing on regional imaging patterns, clinical associations, longitudinal findings, and methodological determinants of interpretation. Seventeen reports were included. In PD, the most recurrent finding was reduced SV2A binding in the substantia nigra, although additional involvement of brainstem, caudate, striatal, thalamic, raphe, or cortical regions was reported in selected cohorts. In PDD/DLB, abnormalities appeared broader and more cortical, with evidence of association between cortical SV2A binding and cognitive performance. In MSA, one study suggested a distinct infratentorial and cerebellar pattern with potential relevance for phenotypic stratification. SV2A PET is a promising research biomarker for biological characterization of synucleinopathies. However, the field remains limited by small cohorts, methodological heterogeneity, variable quantification strategies, limited longitudinal evidence, and potential cohort overlap. Multicentre validation and harmonized protocols are required before clinical translation.

Humans↗

PubMed2026

Is There a Difference in Occurrence of Complications Between Adults With Hemoglobin SS and Hemoglobin SC Disease: An Extended Systematic Review.

Sickle cell disease (SCD) is characterized by both acute and chronic complications. The clinical manifestation of these complications differs between genotypes. Given the large amount of research already published, this systematic review aims to offer a complete overview of types of sickle cell complications between adults in the most common genotypes Hemoglobin SS (HbSS) and Hemoglobin SC (HbSC), putting options for further research into perspective. An extensive literature search was performed to study all available evidence on these complications. This review was performed according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) statement guidelines, and was performed on January 2, 2024. A total of 710 references were identified. After careful screening, 521 records were excluded based on title and abstract and other exclusion criteria. In total, 158 articles were excluded after full-text assessment. Our analysis of 31 studies highlights key differences in complications between HbSS and HbSC genotypes in sickle cell disease (SCD). Vaso-occlusive crises (VOCs) remain the most common acute complication in both genotypes. HbSS patients experience more frequent VOCs, while HbSC patients generally have a milder clinical course when it comes to acute complications. Chronic complications, particularly in the ocular and pulmonary systems, are more prevalent in HbSC patients. However, as acute complications are more common in HbSS and chronic complications more common in HbSC, both genotypes face progressive organ damage due to recurrent ischemic injury and inflammation.

Humans↗

PubMed2026

Family-Wise Error Rate Control in Clinical Trials With Overlapping Populations.

We consider clinical trials with multiple, overlapping patient populations that test multiple treatment policies specifically tailored to these populations. Such designs may lead to multiplicity issues, as false statements will affect several populations. For type I error control, often the family-wise error rate (FWER) is controlled, which is the probability to reject at least one true null hypothesis. If the joint distribution of the test statistics is known, the FWER level can be exhausted by determining critical values or adjusted-levels. The adjustment is typically done under the common ANOVA assumptions. However, the performed tests are then only valid under the rather strong assumption of homogeneous null effects, that is, when the null hypothesis applies to all subpopulations and their intersections. We show that under cancelling null effects, when heterogeneous effects cancel out in some or all subpopulations, this procedure does not provide FWER control. We also suggest different alternatives and compare them in terms of FWER control and their power.

Humans↗

PubMed2026

Nurse-led acute care post-operative interventions in adult cardiac surgery: a systematic review.

AIMS: The primary aim of this systematic review was to identify nurse-led clinical interventions evaluated in randomized controlled trials (RCTs) for adults who had undergone cardiac surgery. The secondary aim was to assess the effectiveness of these interventions on post-operative clinical and patient-reported outcomes during the acute inpatient phase. METHODS AND RESULTS: A systematic review was undertaken according to an a priori protocol using Joanna Briggs Institute (JBI) methodology and PRISMA guideline for reporting. Eligible studies were RCTs of adult (≥18 years) cardiac surgery, nurse-led inpatient interventions implemented immediately post-surgery and prior to discharge. Six databases were searched from inception to June 2025. Of 2690 records, 19 RCTs were eligible, representing 13 countries, and 3142 participants. Risk of bias varied, with only two low-risk trials. Interventions were grouped into seven domains: behavioural support; temperature management and comfort strategies; pain and symptom management; wound care; infection prevention; respiratory and pulmonary function; and post-operative recovery, mobilization, and hydration. Across these domains, nurse-led interventions were generally feasible, safe, and positively affected patient comfort, physiological stability, symptom relief, and aspects of functional recovery. CONCLUSION: Nurse-led inpatient interventions contribute meaningfully to inpatient post-operative recovery in cardiac surgery, although the broader cardiac surgical nursing scope is underrepresented in RCTs. This review provides a foundation for developing further high-quality research, peer-reviewed interdisciplinary practice guidelines, and strengthening the scope and recognition of cardiac surgical nursing as a distinct specialty. REGISTRATION: PROSPERO-CRD420251063851.

Humans↗

PubMed2026

Real-World Efficacy and Safety of Standard-of-Care Chimeric Antigen Receptor T-Cell (CART) and Bispecific T-Cell Engager (TCE) Therapies in Relapsed/Refractory Multiple Myeloma (RRMM).

We aimed to evaluate the real-world (RW) efficacy and safety of standard-of-care CART versus TCE therapies in relapsed/refractory myeloma (RRMM), to assess utilization, outcomes, and tolerability of these therapies in a RW oncology in the US. Data were derived from the US-based, electronic health record-derived deidentified Flatiron Health Research Database, 2021-2024. A total of 419 patients (CART n = 220; TCE n = 199) with a confirmed diagnosis of myeloma who received CART or TCE as a standard-of-care treatment after at least 2 prior lines of therapy were included. Patients in the CART cohort were younger, had better ECOG PS, and a higher receipt of a prior autologous stem cell transplant versus bispecific TCE cohort. In CART versus TCE cohort, the overall response rates (ORR) were 83.3% versus 66.3%, median duration of response 7.9 months versus 4.3 months, progression free survival (PFS) 13.6 months versus 10.5 months, and overall survival (OS) of 29.8 months versus 21.9 months, respectively. A higher percentage of hematologic toxicity, infections, and cytokine release syndrome (CRS) were noted in the CART versus TCE cohort. This study provides insights on the RW effectiveness of CART versus TCE in the treatment of RRMM; highlights the differences in patient selection, clinical responses, treatment duration, and toxicity profiles.

CART↗

PubMed2026

Serum Albumin on Admission: A Prognostic Marker of Morbidity and Mortality in Burns? A Systematic Review and Meta-Analysis.

Albumin is essential for maintaining oncotic pressure and vascular integrity. In burn injuries, increased capillary permeability leads to hypoalbuminemia, which is a recognized marker of poor outcomes in critical illness. However, its prognostic value in acute burn care remains underexplored. This study evaluated the prognostic value of admission serum albumin in predicting mortality, acute kidney injury (AKI), hospital and intensive care unit length of stay, ventilatory requirements, sepsis, and pulmonary infection in patients with burn injuries. A systematic search of PubMed, Scopus, Cochrane Library, Web of Science, MEDLINE, and Embase was conducted. Of 5587 studies screened, 19 were included in the systematic review and 9 in the meta-analysis. Statistical analysis was performed using RStudio, with pooled outcomes reported as odds ratios (ORs), standardized mean differences, and hierarchical summary receiver operating characteristic curves. Heterogeneity was assessed using Cochran's Q, I2, and tau2. Hypoalbuminemia on admission was significantly associated with increased mortality during admission (OR 9.51; 95% CI, 3.04-29.78; I2 49.3%). Admission hypoalbuminemia was also associated with an increased risk of AKI (OR 2.83; 95% CI, 2.49-3.22; I2 0%). Evidence for other outcomes was limited and heterogeneous. Admission serum albumin appears to be a valuable prognostic marker in patients with burn injuries, particularly for mortality and AKI. Further research is required to support its integration into burn-specific risk models, characterize albumin trends within the first 24 h postinjury, and establish optimal cut-off values.

Humans↗

PubMed2026

Associations between multiple essential trace metal concentrations and risk of hyperuricemia: insights from a central Chinese population.

Previous studies have indicated that levels of individual essential trace metals are related to hyperuricemia (HUA), but evidence on their combined effects is limited. To address this gap, the associations of individual and joint levels of 12 essential trace metals (manganese, selenium, nickel, chromium, cobalt, tin, iron, molybdenum, zinc, strontium, vanadium, and copper) with the risk of HUA were investigated in 2,021 adults recruited from Hunan Province, China. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to determine urinary metal concentrations. Logistic regression, Bayesian kernel machine regression (BKMR), and quantile g calculation (Qgcomp) were applied to evaluate the associations of single and mixture metal concentrations with HUA. Of the participants, 516 (25.53%) were diagnosed with HUA. Inverse associations were found between vanadium, chromium, manganese, iron, cobalt, selenium, strontium, and molybdenum levels and HUA, with ORs ranging from 0.63 to 0.91. Conversely, a positive association was observed between zinc concentration and HUA [OR (95% CI): 1.17 (1.01, 1.37)]. Both BKMR and Qgcomp models showed a negative overall effect of essential trace metals on HUA risk, with strontium (- 43.6%) and vanadium (- 27.8%) being the main contributors. In addition, formal interaction tests revealed significant effect modification by age for tin and by BMI for zinc. In conclusion, the levels of essential trace metals were linked to a decreased risk of HUA, and these associations were modified by age and BMI only for specific metals.

Humans↗

PubMed2026

Effectiveness of exercise-based prehabilitation on pre and postoperative outcomes of patients undergoing cardiac surgery-An umbrella review of systematic reviews.

AIMS: Individuals undergoing cardiac surgery are becoming older, frailer, and less mobile. Prehabilitation has shown to improve postoperative outcomes by optimizing preoperative physical function. This umbrella review aims to pool the systematic reviews assessing the effectiveness of exercise-based prehabilitation in cardiac surgery. METHODS AND RESULTS: The review followed the PRIOR checklist. PubMed, Embase, CINAHL, Cochrane library, Scopus, Web of science, ProQuest NAHD, ProQuest HMC, Open Grey and MedNar were searched using relevant keywords from inception to 16th December, 2024. Two reviewers screened and extracted data from the included reviews and assessed primary study overlap with the corrected covered area. Methodological quality of the reviews was evaluated with the A MeaSurement Tool to Assess systematic Reviews-2 scale. Certainty of evidence was assessed using a previously developed criteria for overview of reviews. Six systematic reviews with 30 unique trials and 6705 participants were included. The interventions assessed included breathing exercises, inspiratory muscle training, and exercise training. Prehabilitation reduced length of hospital stay, postoperative pulmonary complications, and clinically improved functional capacity with a very low to moderate certainty of evidence. However, there was uncertainty regarding the effects pertaining to adverse events and quality of life. The methodological quality of all reviews was critically low. The primary trials scored poorly in the domains of selection and detection bias. CONCLUSION: Exercise-based prehabilitation might reduce length of hospital stay and postoperative complications, and improve functional capacity. However, the quality of evidence is poor, and individual discretion is required before implementing them into practice. REGISTRATION: PROSPERO: CRD42023480100.

Humans↗

PubMed2026

Safety and Tolerability of Single and Multiple Daily Oral Doses of Dried Kratom Leaf Powder in a Randomized Trial in Healthy Volunteers.

BACKGROUND: Kratom use is rising, increasing the need for safety and tolerability studies of high-quality and well-characterized kratom products in humans. Kratom's risk-benefit ratio, recommended dose, treatment-emergent adverse events (TEAEs), abuse potential, and withdrawal require evaluation. Thus, the safety and tolerability of 4 escalating single and 15 daily dried kratom leaf powder doses in human volunteers were evaluated over 47 days in the largest controlled kratom-administration study to date. METHODS: A randomized, between-subject, double-blind, placebo-controlled, dose-escalation study of MitraLeaf kratom powder after single doses (SD), during 15 daily doses (multiple doses; MD), and a 23-day follow-up was conducted in 116 volunteers (49 MitraLeaf and 67 placebo). Twelve participants each received a SD of either 6.65, 13.3, 26.6, or 53.2 mg (n = 13) mitragynine in 500, 1000, 2000, or 4000 mg of MitraLeaf, respectively, with a 10-day follow-up. The same participants received 15 daily doses at the same concentration of SD mitragynine received, with a 27-day follow-up period. Inclusion criteria were nonsmoking healthy males and females who never used kratom or had not used kratom for ≥12 months, 18-55 years old, and BMI ≥18.5 and ≤29.9 kg/m 2 . Participants were excluded if they had known CYP3A4, CYP2D6, or CYP1A2 genetic polymorphisms. RESULTS: No serious adverse events or deaths were reported. TEAEs after SD or MD generally increased as the dose increased. Dizziness, nausea, and feeling of relaxation were the most commonly reported TEAEs after SD, and headache, feeling hot, increased alanine aminotransferase level, and nausea were most common after MD. CONCLUSIONS: This SD and first MD controlled study shows that Mitragyna speciosa -derived MitraLeaf kratom powder was safe and well tolerated at the dose ranges tested, with no evidence of meaningful abuse potential or withdrawal.

Humans↗

PubMed2026

Effect of flavored on!® nicotine pouch products on smoking behaviors: A sequential, multiple assignment, randomized controlled trial.

PURPOSE: To evaluate whether flavored versus unflavored nicotine pouch (NP) access affects cigarette reduction and smoke exposure among adults who smoke daily, and whether delayed flavor introduction affects these outcomes. METHODS: Adults who smoked ≥ 5 cigarettes/day (CPD) with interest in replacing cigarettes with NPs were enrolled in a remote, six-week, sequential multiple assignment randomized trial (n = 402 randomized; n = 400 analyzed). Participants were randomized to immediate access to seven NP flavors (Flavor), unflavored-only access for six weeks (Original), or unflavored-only for three weeks followed by flavor access (Delayed Flavor). Primary outcomes were ≥ 50% reduction in weekly mean expired-air carbon monoxide (CO) from baseline and mean CO at Week 6. Secondary outcomes included ≥ 50% CPD reduction, mean CPD, CO-verified 7-day abstinence, and incident smoke-free days. RESULTS: At Week 6, Flavor and Original did not differ in ≥ 50% CO reduction (14.3% vs 14.2%; IRR=1.0, 95% CI=0.6-1.8) or mean CO (18.3 vs 16.5 ppm; β=1.9, 95% CI=-1.3-5.0). CPD decreased across groups by Week 6, with no differences between Flavor and Original in ≥ 50% CPD reduction (50.3% vs 51.6%; IRR=1.0, 95% CI=0.8-1.2) or CO-verified abstinence (9.3% vs 8.9%; IRR=1.0, 95% CI=0.5-2.2). Flavor increased smoke-free days early, with attenuation over time. Among Week 3 non-responders, delayed flavor access increased ≥ 50% CPD reduction at Week 6 (33.3% vs 18.6%; IRR=1.8, 95% CI=1.0-3.2). CONCLUSIONS: NP access supported cigarette reduction regardless of flavor availability, but flavors may accelerate smoke-free days and improve response among individuals who do not reduce cigarette consumption with unflavored products alone.

Humans↗

PubMed2026

Safety, tolerability, pharmacokinetics, and pharmacodynamics of oral JMKX003002 in Chinese healthy participants: a randomized, double-blind, placebo-controlled, single- and multiple-ascending dose, and food-effect phase I clinical trial.

OBJECTIVE: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharma-codynamics (PD) of the sodium-hydrogen exchanger 3 (NHE3) inhibitor JMKX003002 in Chinese healthy participants. PATIENTS AND METHODS: This phase I, randomized, double-blind, placebo-controlled study included a single-ascending dose (SAD) study with seven cohorts (1 mg [n = 4] and 5, 20, 50, 75, 100, or 125 mg [n = 8]), a food-effect (FE) study with six sequence groups (25 mg twice daily, n = 4), and a multiple-ascending dose (MAD) study with two cohorts (10 mg or 20 mg twice daily, n = 10). RESULTS: JMKX003002 was well-tolerated, with mostly mild treatment-related adverse events. One Grade 3 diarrhoea occurred in each of the 50 mg and 125 mg groups. No serious adverse events were reported, and no participants discontinued or withdrew due to treatment-emergent adverse events. Most plasma samples were below the limit of quantification (0.2 ng/mL), with only transient detection of low concentrations, indicating low systemic exposure. JMKX003002 was primarily excreted in stool (79.9% recovered) and was undetectable in urine. The PD results consistently showed decreased urinary sodium and phosphorus, along with increased stool sodium and phosphorus, compared to baseline across all three studies. One day after discontinuation, stool sodium and phosphorus remained elevated relative to baseline in the MAD study. Mixed-effects model analysis in the FE study demonstrated significant food effect on stool sodium and phosphorus excretion. CONCLUSION: JMKX003002 exhibited favorable safety and tolerability with minimal systemic exposure. It effectively increased sodium and phosphorus excretion in stool. These promising findings warrant further investigation of JMKX003002 to evaluate its clinical benefits. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300070473). Registered on April 13, 2023; prospectively registered.

Adult↗

PubMed2026

Men's experiences of multiple long-term conditions and/or disability in the UK Game of Stones weight management trial: a mixed-methods evaluation.

OBJECTIVES: To explore experiences, health outcomes and retention of men with multiple long-term conditions (MLTCs) and/or disability within the Game of Stones weight management randomised controlled trial (RCT). DESIGN: Mixed-methods process evaluation within an RCT where secondary outcomes included the Weight Self-Stigma Questionnaire, EuroQol 5-Dimension 5-Level (EQ-5D-5L), EQ-5D-5L anxiety and depression subscale, Patient Health Questionnaire-4 and retention. Semistructured interviews were conducted at 12 months and analysed using the framework method. SETTING: Conducted across three UK trial centres: Belfast, Bristol and Glasgow. PARTICIPANTS: 585 men with obesity (mean (SD) age, 50.7 (13.3) years) were randomised to one of three groups: behavioural text messages with financial incentives, texts alone or waiting-list control. Interviews were conducted with 54 participants from the two intervention groups. RESULTS: 235 (40%) participants lived with MLTCs, 181 (31%) had a single condition, 167 (29%) had no conditions and 165 (29%) had a disability. Of those with MLTCs, 99 were disabled and 93 were living in deprived areas. Participants with MLTCs and/or disability were older, fewer had a degree-level qualification and fewer were in full-time work. Retention at 12 months was higher for men with disability (76%) or no long-term conditions (75%) and lower for men with diabetes (65%). Self-reported weight stigma, well-being and quality-of-life scores improved or stayed the same for men living with MLTCs in the intervention groups; however, results for anxiety and depression screening scores were inconsistent. Participant experiences indicated complex dynamic health, social and life situations which could provide motivation to lose weight for some but not others. Hospitalisation and poor mobility, with inability to exercise, were demotivating for making changes to reach weight loss targets. CONCLUSIONS: Men living with MLTCs and/or disability varied from very successful weight loss and improved health to not prioritising or feeling helped by the programme or disengagement due to immobility or diabetes. TRIAL REGISTRATION NUMBER: isrctn.org Identifier: ISRCTN91974895.

Humans↗

PubMed2026

New Evidence in Heart Failure: 2026 Update.

Heart failure (HF) remains a major cause of morbidity, mortality, impaired quality of life and healthcare expenditure worldwide. The global burden of HF continues to increase due to population aging, improved survival, and the growing prevalence of cardiovascular, renal, and metabolic comorbidities. Simultaneously, the pace of scientific progress in HF has accelerated considerably. Recent advances have refined our understanding of HF epidemiology, prognosis, and disease trajectories, including emerging concepts of HF improvement, remission, and recovery. The Second Universal Definition of HF has also updated the classification framework, moving beyond the traditional ejection fraction-based categories. HF is now broadly classified into two major phenotypes: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Novel mechanistic insights highlight the role of inflammation, immune activation, metabolic dysfunction, mitochondrial biology, and multisystem interactions in HF progression. There has also been significant progress in the characterization and management of major comorbidities, including chronic kidney disease (CKD), diabetes, obesity, atrial fibrillation (AF), pulmonary hypertension, frailty, malnutrition, and cancer. Diagnostic innovations include novel biomarkers, multi-omics technologies, artificial intelligence-based approaches, advanced imaging techniques, congestion assessment tools, and emerging digital health solutions. Important advances have occurred in specific HF aetiologies, including cardiomyopathies, cardiac amyloidosis (CA), myocarditis, arrhythmia-induced cardiomyopathy (AiCM), and Chagas cardiomyopathy. Therapeutic developments continue to reshape HF management across the spectrum of left ventricular ejection fraction. Recent evidence has focused on optimization of guideline-directed medical therapy in HFrEF, expansion of evidence-based therapies in HFpEF, and growing roles for sodium-glucose cotransporter-2 inhibitors, finerenone, incretin-based therapies, and transcatheter valve interventions. Collectively, these advances support the transition from a predominantly phenotype-based approach towards a more personalized and biologically informed model of HF care, with the potential to further improve outcomes across the entire HF spectrum.

Journal Article↗

PubMed2026

A Novel Multiple Sensory Nerve Block Combination Using Ultrasound Guidance in Knee Arthroplasty: A Randomized Clinical Trial.

INTRODUCTION: Combining adductor canal block (ACB), infiltration between the popliteal artery and posterior capsule of the knee (IPACK), and genicular nerve blocks provides motor-sparing analgesia in total knee arthroplasty (TKA). Adding nerve blocks targeting the nerve to vastus medialis, vastus intermedius, and anterior femoral cutaneous nerve may improve postoperative pain management without affecting mobility. This study evaluated the effect of an eight-nerve block combination for pain relief after TKA versus local infiltration analgesia (LIA). METHODS: Participants were randomized into intervention or standard treatment groups. The intervention group received an eight-nerve block combination using 40 mL ropivacaine, 5 mg/mL, with 75 µg of clonidine. The control group received LIA comprising 150 mL ropivacaine, 2 mg/mL, supplemented with 0.5 mg adrenaline. The primary outcome was postoperative pain intensity, measured by the numeric rating scale (NRS) at postanesthesia care unit (PACU) arrival, 1 hour, 2 hours after PACU arrival, at ward arrival, evening of surgery, morning of postoperative day 1 (POD1), and at 14:00 POD1. Statistical analysis was performed using the Mann-Whitney U test. Secondary outcomes included 48-hour oral morphine equivalent (OME) consumption and length of hospital stay (LOS). RESULTS: A total of 217 patients scheduled for TKA were randomized. No significant differences were observed in the primary outcome. NRS at rest, presented as median (IQR), did not differ between groups at any time point. At PACU arrival 0 (0-3) vs 0 (0-4), at 1 hour 2 (0-4) vs 2 (0-5), at 2 hours 2 (0-6) vs 2.5 (0-4), at ward arrival 3 (2-5) vs 3 (2-5), on the evening of POD0 4 (3-5) vs 3.5 (2-6), on the morning of POD1 4 (3-6) vs 4 (2-5), and at 14:00 POD1 3 (2-5) vs 3 (2-5) for nerve block and LIA groups, respectively (all P > .05). Exploratory secondary outcomes indicated reduced 48-hour OME consumption presented as median (IQR), 70 mg (52.5-96.3), vs 96 mg (61.3-148.8); P = .008) and shortened hospital stay, median (IQR), 1 day (1-2), vs 2 days, (1-3); P < .001) in the nerve block group compared to the LIA group. CONCLUSIONS: No differences were observed in pain scores between the eight-nerve block combination and LIA. Secondary outcomes revealed a reduction in 48-hour opioid consumption and a modestly shorter hospital stay with nerve block compared to LIA.

Humans↗

PubMed2026

Ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated non-small-cell lung cancer after disease progression on EGFR tyrosine kinase inhibitor therapy (HARMONi): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: Ivonescimab has shown clinical efficacy in non-small-cell lung cancer (NSCLC). We aimed to assess the efficacy and safety of ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated NSCLC whose disease progressed after third-generation EGFR tyrosine kinase inhibitor (TKI) therapy. METHODS: HARMONi is a randomised, placebo-controlled, double-blind, phase 3 trial done at 114 cancer centres and hospitals across Asia, Europe, and North America. Eligible patients were aged at least 18 years (upper limit: 75 years in Asia) with stage IIIB/IIIC or IV non-squamous EGFR-mutated NSCLC, disease progression after treatment with a third-generation EGFR-TKI, and an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) via a centralised interactive voice response system or interactive web response system to receive ivonescimab (20 mg/kg) or placebo plus pemetrexed (500 mg/m2) and carboplatin (target area under the curve 5 mg/mL per min) intravenously every 3 weeks. Randomisation was stratified by brain metastases status at enrolment and geographical region. The primary endpoints were progression-free survival by blinded independent radiology review committee and overall survival in the intention-to-treat population. Safety was assessed in patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov (NCT06396065), has completed enrolment, and is ongoing for treatment and follow-up. FINDINGS: From Jan 25, 2022, to Oct 1, 2024, 660 individuals were screened for eligibility; of these, 438 were enrolled and randomly assigned to receive ivonescimab plus chemotherapy or placebo plus chemotherapy (219 per group). Of enrolled patients, 257 (59%) were female and 181 (41%) were male; 306 (70%) reported race as Asian, and 105 (24%) as White. At a median follow-up of 22·3 months (95% CI 21·5-23·0), 275 progression or death events had occurred in 345 patients (129 events among 172 patients in the ivonescimab plus chemotherapy group and 146 events among 173 patients in the placebo plus chemotherapy group). Median progression-free survival was 6·8 months (95% CI 5·7-7·1) in the ivonescimab plus chemotherapy group versus 4·4 months (4·1-5·5) in the placebo plus chemotherapy group (hazard ratio [HR] 0·52; 95% CI 0·41-0·66; p<0·0001). At a median follow-up of 29·7 months (95% CI 27·7-31·0), 262 deaths occurred in 438 patients (122 in the ivonescimab plus chemotherapy group and 140 in the placebo plus chemotherapy group). Median overall survival was 16·8 months (14·3-19·0) in the ivonescimab plus chemotherapy group versus 14·0 months (12·8-15·7) in the placebo plus chemotherapy group (HR 0·79; 0·62-1·01). The most common grade 3-4 treatment-related adverse events in the ivonescimab plus chemotherapy versus the placebo plus chemotherapy group were decreased neutrophil count (42 [19%] of 218 vs 36 [17%] of 218), decreased white blood cell count (28 [13%] vs 24 [11%]), decreased platelet count (27 [12%] vs 14 [6%]), and anaemia (22 [10%] vs 27 [12%]). Serious treatment-related adverse events occurred in 61 (28%) patients in the ivonescimab plus chemotherapy group and 33 (15%) patients in the placebo plus chemotherapy group. Treatment-related adverse events led to death in four patients (disease progression, multiple organ dysfunction syndrome, and hepatic failure, each in one patient; gastrointestinal haemorrhage and pulmonary embolism in one patient) in the ivonescimab plus chemotherapy group and five patients (pneumonitis, myocardial infarction, cerebrovascular accident, cognitive disorder, and embolic stroke, each in one patient) in the placebo plus chemotherapy group. INTERPRETATION: Ivonescimab plus chemotherapy showed a clinically meaningful and statistically significant progression-free survival benefit in patients with EGFR-mutated NSCLC after progression on EGFR-TKI therapy. The clinical benefit and lack of new safety signals of ivonescimab with chemotherapy support the potential for the combination as a new treatment option in this patient population. FUNDING: Summit Therapeutics.

Humans↗

PubMed2026

Umbilical Cord-Derived Cell-Based Interventions for Bronchopulmonary Dysplasia and Related Complications in Preterm Infants: A Bayesian Sparse-Data Meta-Analysis.

Bronchopulmonary dysplasia (BPD) is a major complication of prematurity with limited disease-modifying therapies. We evaluated umbilical cord-derived cell-based interventions for BPD and related complications in preterm infants. This Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-based systematic review and meta-analysis were registered in PROSPERO. PubMed, Cochrane Library, Web of Science, CNKI, and Wanfang were searched from inception to June 14, 2026. Comparative clinical studies of umbilical cord-derived cell-based interventions in preterm infants at risk of or diagnosed with BPD were included. Outcomes included BPD, BPD severity, death, persistent pulmonary hypertension of the newborn (PPHN), patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), late-onset sepsis (LOS), and adverse events (AEs). Bayesian random-effects meta-analysis used a binomial-normal hierarchical model to estimate pooled odds ratios (ORs), 95% credible intervals (CrIs), prediction intervals, and heterogeneity. Twelve studies were included. Umbilical cord-derived cell-based interventions showed a possible protective effect on overall BPD (OR, 0.48; 95% CrI, 0.14-1.20). Stronger associations were observed for severe BPD (OR, 0.17; 95% CrI, 0.01-0.85), moderate or severe BPD (OR, 0.28; 95% CrI, 0.09-0.70), and ROP stage ≥3 (OR, 0.17; 95% CrI, 0.02-0.65). No conclusive benefit or harm was observed for death, PPHN, PDA, IVH, NEC, or LOS. No treatment-related serious AEs were identified. However, prediction intervals were generally wide, and the certainty of evidence was low to very low for most outcomes. Umbilical cord-derived cell-based interventions may reduce the risk of moderate or severe BPD in preterm infants, with an additional potential benefit for ROP stage ≥3. Current evidence remains limited, and larger randomized trials with standardized outcomes and long-term follow-up are needed.

Humans↗