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PubMed2026

Efficacy and safety of human albumin combined with furosemide in acute decompensated heart failure with hepatic dysfunction.

BACKGROUND: Congestion is the most common clinical presentation on admission of patients with acute decompensated heart failure (ADHF). Finding effective ways to alleviate congestion has become a pivotal management step. This study sought to investigate the efficacy and safety of intravenous (IV) albumin use in conjunction with furosemide in patients hospitalized for ADHF with hepatic dysfunction in terms of subjective regression of congestion symptoms and worsening renal function. METHODS: This prospective, open-label, randomized-pragmatic trial recruited 241 patients with hepatic dysfunction hospitalized for ADHF. Patients (78 years, 54% female) were assigned to receive IV albumin with furosemide or IV furosemide alone. The coprimary study endpoints were patients' global assessment of symptoms score, quantified as the area under the curve (AUC) of the score on a visual analog scale, and the change in creatinine levels over 72 hours from admission. RESULTS: The experimental treatment group demonstrated a greater improvement in patients' global assessment of symptoms scores (AUCbaseline-72 h 3,767 vs 3,457 points; P < .001) and a milder increase in creatinine levels (0.07 vs 0.18 mg/dL; P = .045) than the IV furosemide group. The length of stay was 1 day shorter (4 vs 5 days; P < .001) and the incidence of worsening renal function was lower (25% vs 38%; P = .037) in the experimental treatment group. CONCLUSIONS: In this hypothesis generating study, among patients with ADHF and hepatic dysfunction, concomitant use of IV albumin and furosemide for the first 72 hours resulted in a significant improvement in subjective perception symptoms of decongestion and a milder increase in creatinine levels than IV furosemide alone.

Aged↗

PubMed2026

GATA2 deficiency: enhancer deregulation, immune surveillance failure, and clonal evolution.

Germline mutations in GATA2 cause a syndromic inborn error of immunity characterized by cytopenia, infections, immune dysregulation, and a marked predisposition to myelodysplastic syndrome and acute myeloid leukemia. Initially defined by the DCML phenotype-dendritic cell, monocyte, B- and NK-cell deficiency-GATA2 deficiency is now recognized as a disorder of global immune-hematopoietic homeostasis. Recent multi-omics and experimental models reveal enhancer-driven inflammatory rewiring, IRF8-dependent lineage imbalance, and premature hematopoietic aging. In parallel, adaptive immune defects, including impaired B- and T-cell development and function, contribute to defective immune surveillance. These alterations not only explain susceptibility to infection but also shape clonal evolution and malignant transformation. Clinically, improved risk stratification and transplant outcomes underscore the importance of early recognition and monitoring of immune dysfunction. GATA2 deficiency thus represents a paradigm linking immune dysregulation, inflammatory stress, and cancer predisposition.

Humans↗

PubMed2026

Comparative effectiveness of torsemide vs furosemide in the management of heart failure patients: Win-ratio reanalysis of the TRANSFORM-HF trial.

BACKGROUND: Loop diuretics are widely used for managing congestion in patients with heart failure (HF). The TRANSFORM-HF trial is a multicenter randomized study that enrolled heart failure patients, comparing a strategy of torsemide vs furosemide. The time-to-event analysis demonstrated neutral effects on all-cause death at 30 months and the composite of all-cause death and first rehospitalization at 12 months. We evaluated whether a hierarchical win-ratio (WR) framework integrating mortality, recurrent hospitalization, and patient-reported health status provides additional interpretive insight. METHODS: This study is a secondary analysis of the pragmatic, multicenter, open-label, randomized TRANSFORM-HF trial, conducted across 60 US hospitals that randomized 2,859 patients hospitalized with HF to torsemide or furosemide. The primary 12-month hierarchical composite outcome was defined as (1) all-cause mortality, (2) recurrent all-cause hospitalizations, and (3) lack of improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). The primary statistical method was a WR analysis adjusting covariates via inverse probability weighting. Subgroup analyses evaluated potential heterogeneity across patient demographics and clinical characteristics. RESULTS: In the primary 12-month intention-to-treat analysis, the adjusted WR was 1.07 (95% CI, 0.98-1.16; P = .13), indicating no significant difference between torsemide and furosemide. A supplementary 30-month analysis with extended mortality follow-up yielded a similar estimate (adjusted WR, 1.06; 95% CI, 0.98-1.16; P = .14); hospitalization and KCCQ-CSS components were assessed through 12 months. As-treated sensitivity analyses were consistent with the neutral primary findings. Exploratory subgroup analyses were not adjusted for multiplicity and should be considered hypothesis-generating. CONCLUSIONS: The overall WR comparison between torsemide and furosemide showed no statistically significant difference in the primary 12-month analysis. The WR framework provided an interpretive decomposition across outcome domains but did not establish superiority of either loop diuretic strategy. All findings should be considered exploratory. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03296813, https://clinicaltrials.gov/study/NCT03296813.

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PubMed2026

ER proteostasis failure in HYOU1 deficiency alters B cells, neutrophils, and interferon signalling.

Hypoxia upregulated 1 (HYOU1) is a stress-inducible ER chaperone. We investigated 2 unrelated patients carrying biallelic HYOU1 variants and presenting with primary immunodeficiency. Patient 1, homozygous for p.Pro444His, displayed failure to thrive, hypoglycemia, B cell lymphopenia, and neutropenia. Patient 2, compound heterozygous for p.Arg262Gln and p.Pro757_Glu758insAla, exhibited recurrent infections, enteropathy, and hypogammaglobulinemia. In Patient 1, while HYOU1 transcription was preserved, the protein was severely reduced. Tunicamycin treatment of dermal fibroblasts showed a blunted unfolded protein response and defective induction of ER stress-responsive genes. Immunophenotyping showed near-absence of circulating B cells, and single-cell RNA sequencing of bone marrow identified an arrest at the pro-B cell stage. Neutrophils displayed hypogranulation and dysregulated IFN- and apoptosis-associated transcriptional signatures, unresponsive to G-CSF. HYOU1 deficiency hence results in ER stress-induced proteostasis failure that simultaneously impairs adaptive immunity through B cell developmental arrest and innate immunity through neutrophil dysfunction and IFN pathway imbalance. This work expands the spectrum of HYOU1 deficiency and further identifies ER proteostasis as a central determinant of immune homeostasis.

Journal Article↗

PubMed2026

Empagliflozin and functional aerobic capacity in individuals with increased risk of heart failure: The Empire Prevent Cardiac trial.

BACKGROUND: Higher maximal oxygen consumption (VO₂ max) is associated with lower risk of developing heart failure (HF). Empagliflozin improves VO2 max in HF with reduced ejection fraction, but the effect on VO2 max in individuals at risk of HF remain unknown. OBJECTIVE: This study aimed to evaluate the effect of 180 days treatment with empagliflozin compared to placebo on VO2 max, daily physical activity level, and quality of life (QoL) in individuals with overweight or obesity and risk of HF. METHOD: This investigator-initiated, double-blinded, randomized, placebo-controlled, multicenter trial included elderly individuals with body mass index >28 kg/m2 and at least one additional risk factor for HF, including hypertension, ischemic heart disease, stroke, or chronic kidney disease. Individuals with HF or type 2 diabetes mellitus were excluded. The primary endpoint was the mean difference in change of VO2 max. The secondary outcome was objectively measured physical activity level. QoL was an explorative outcome. RESULTS: Among 191 randomized individuals (94 empagliflozin, 97 placebo), 89% had hypertension and 66% ischemic heart disease. At baseline, 69% were male, median age was 68 years, median body mass index 31.9 kg/m², mean left ventricular ejection fraction 65 ± 9%, and mean VO₂ max 18.1 ± 4.3 mL/min/kg. Empagliflozin did not change VO2 max with an estimated treatment difference of -0.2 mL/min/kg (97.5% confidence interval -1.2 to 0.8), adjusted P = 1.00. No significant treatment differences were observed for neither daily physical activity nor QoL. CONCLUSIONS: Empagliflozin did not affect VO2 max, physical activity level, or QoL in elderly individuals with overweight or obesity and risk of HF.

Humans↗

PubMed2026

Impact of estimated total blood volume on NT-proBNP response to angiotensin receptor-neprilysin inhibition in acute heart failure: Insights from the PREMIER study.

BACKGROUND: Sacubitril/valsartan (Sac/Val) reduces N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in acute heart failure (AHF), particularly in patients with reduced ejection fraction. However, whether estimated total blood volume (TBV), calculated using anthropometric equations, is associated with heterogeneity in biomarker response remains uncertain. METHODS: This post hoc exploratory sub-analysis of the PREMIER randomized trial evaluated whether baseline estimated TBV was associated with heterogeneity in NT-proBNP reduction after Sac/Val compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) therapy. Estimated TBV was calculated using validated anthropometric equations and dichotomized at the median (4.05 L). Patients were further stratified by left ventricular ejection fraction (LVEF <40% vs ≥40%). The primary endpoint was the proportional change in NT-proBNP from baseline to Week 8. RESULTS: Among 376 patients, 372 with baseline estimated TBV data were analyzed. In the high TBV group, Sac/Val was associated with greater NT-proBNP reduction than ACEI/ARB (-56% vs -32%; ratio of change, 0.67; 95% confidence interval, 0.53-0.84; P = .001), whereas no significant difference was observed in the low TBV group (P for heterogeneity = 0.063). In patients with LVEF <40%, Sac/Val was associated with greater NT-proBNP reduction in both TBV groups. In patients with LVEF ≥40%, Sac/Val was associated with greater NT-proBNP reduction in the high TBV group, whereas the point estimate in the low TBV group numerically favored ACEI/ARB. CONCLUSIONS: In this exploratory post hoc analysis, higher estimated TBV was associated with greater NT-proBNP reduction after Sac/Val, particularly among patients with LVEF ≥40%. These findings are hypothesis-generating and require external validation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05164653; Japan Registry of Clinical Trials, jRCTs021210046.

Humans↗

PubMed2026

High-Flow Nasal Oxygen Versus Conventional Oxygen Therapy and Non-Invasive Ventilation for Acute Respiratory Failure in the Emergency Department: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis compares the use of high-flow nasal oxygen (HFNO) with conventional oxygen therapy (COT) and non-invasive ventilation (NIV) in the management of acute respiratory failure (ARF) in the emergency department (ED). A comprehensive search of relevant sources was undertaken. Randomised controlled trials (RCTs) assessing adult patients (≥ 18 years) treated in the ED for ARF and comparing HFNO to COT/NIV were included. The primary outcome was the need for endotracheal intubation and mechanical ventilation (IMV). Secondary outcomes included physiological and biochemical parameters, ICU admission, hospital length of stay, dyspnoea scores and mortality. A total of 17 RCTs (1955 patients) were included. There was a significant reduction in IMV favouring the HFNO group compared to COT and NIV (RR 0.64, 95% CI 0.47-0.88). HFNO showed significant improvements in RR, SpO2, PaO2 and Modified Borg Dyspnoea Scale. Subgroup analysis showed reduced rates of IMV with HFNO compared to COT (RR 0.61, 95% CI 0.41-0.91), but not compared to NIV (RR 0.69, 95% CI 0.42-1.14). HFNO additionally showed a reduction of IMV compared to NIV and COT in undifferentiated patients (RR 0.61, 95% CI 0.41-0.93), but not in exacerbations of COPD or acute heart failure. Ten of the 17 studies had at least some concern for risk of bias, with several analyses having notable heterogeneity. HFNO showed a significant reduction in rates of IMV, improvement in peripheral oxygen saturations, PaO2, respiratory rate and patient dyspnoea scores compared to COT and NIV.

Humans↗

PubMed2026

Adaptive proteomic remodeling and eNOS upregulation in luminal endothelium and perivascular adipose tissue of patent saphenous vein grafts after CABG.

OBJECTIVE: Long-term patency of saphenous vein grafts (SVGs) remains a significant challenge in coronary artery bypass grafting (CABG). The biological factors underlying successful human grafts are poorly understood. We aimed to characterize the structural and molecular features associated with successful graft function. METHODS: Patent and occluded SVG and internal thoracic artery (ITA) grafts were obtained from explanted hearts of CABG patients undergoing heart transplantation for end-stage heart failure not attributable to graft failure, along with freshly harvested ITA and SVG controls. Samples underwent histomorphological analysis, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics. RESULTS: Patent ITA (ITA-P) showed minimal intimal hyperplasia with medial reinforcement, whereas patent SVGs (SVG-P) had organized, α-smooth muscle actin (αSMA)-positive myofibroblast-rich neointima. Endothelial nitric oxide synthase (eNOS) was markedly upregulated in patent grafts at two sites-the luminal endothelium and adventitial microvessels within perivascular adipose tissue (PVAT)-and lost at both sites in occluded SVG (SVG-O). Adventitial CD31-positive microvessels were significantly increased in patent grafts. Proteomically, ITA-P and SVG-P shared a largely common adaptive proteome enriched in translation, RNA processing, and extracellular matrix (ECM) organization, with shared upstream activation of NR4A3, EGFR, and STAT1, and conduit-specific signatures (IGF-1/RUNX2 in ITA-P; RETN/SRC/PTGES in SVG-P). PTGES was strongly expressed in the adventitia of SVG-P. CONCLUSIONS: Patent arterial and venous bypass grafts exhibited a shared adaptive phenotype characterized by dual-site upregulation of eNOS in both the luminal endothelium and the perivascular microvessels/PVAT. In SVG-P, PTGES was co-upregulated alongside eNOS, indicating a mechanistic link between the proteomic and IHC findings. These findings highlight the perivascular compartment as a site of adaptive, eNOS-associated changes in patent vein grafts.

Humans↗

PubMed2026

Chronic neurological diseases with acute respiratory failure in a real-life cohort: insights into ICU and long-term survival-A retrospective study.

BACKGROUND: Patients with chronic neurological diseases (CND) are at increased risk of pulmonary complications that often require ICU admission. This study aimed to identify clinical factors associated with ICU mortality and long-term survival in patients with CND who developed acute respiratory failure (ARF). METHODS: This retrospective cohort study was conducted in a level III respiratory ICU. Patients with pre-existing CND admitted to the ICU with ARF were included. ICU mortality was analyzed using multivariable logistic regression. Long-term survival after ICU discharge was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mortality timing was further characterized using hazard function analysis. RESULTS: A total of 220 patients were included; the most common neurological diagnoses were dementia (37.3%), stroke (22.7%), and amyotrophic lateral sclerosis (14.1%). ICU mortality was 33.6%. Higher APACHE II scores were independently associated with increased ICU mortality (OR 1.076 per point increase; 95% CI 1.029-1.126; p < 0.001). Long-term survival differed significantly by post-discharge respiratory support strategy, with Kaplan-Meier analysis demonstrating more favorable survival patterns among patients receiving home non-invasive mechanical ventilation (NIMV) (p = 0.003). In Cox regression analysis, age, home NIMV, and feeding modality at discharge were independently associated with long-term outcomes. Survival analyses revealed an early clustering of deaths within the first months after ICU discharge, particularly among patients with dementia. CONCLUSIONS: In patients with CND, acute physiological severity was the main determinant of ICU mortality, whereas long-term survival after ICU discharge was poor, with deaths clustering within the first months thereafter. Post-discharge respiratory support and nutritional management should be individualized according to the expected clinical trajectory and patient values.

Humans↗

PubMed2026

Indications, Techniques and Complications Associated With Pterygoid Implants: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Pterygoid implants represent a graftless option for rehabilitation of patients with posterior maxillary atrophy, engaging the dense cortical bone of the pterygomaxillary complex. Despite clinical growth, a comprehensive synthesis of indications, surgical techniques, and complications is lacking. This review evaluated the prevalence of complications, implant survival rates, and marginal bone loss (MBL) associated with pterygoid implant placement. METHODS: The reporting of this review follows PRISMA 2020 guidelines. Six electronic databases (PubMed, Ovid, Scopus, WoS, CENTRAL, and Dentistry & Oral Sciences Source) were searched from 1 January 2020 to 31 December 2025. Included criteria comprised randomized and non-randomized clinical studies reporting outcomes of pterygoid implants (≥ 13 mm) in adult patients with posterior maxillary atrophy (minimum 10 implants). Risk of bias was assessed using JBI critical appraisal checklists. Proportions were pooled using the Freeman-Tukey double arcsine transformation under a random-effects model. Certainty of evidence was assessed using GRADE. RESULTS: Seventeen studies reporting 846 patients and 1915 pterygoid implants were included. The pooled survival rate was 97.9% (95% CI: 97.1%-98.6%; I2 = 0%; 14 studies) and the overall failure rate was 2.1% (95% CI: 1.4%-3.0%). Early failure rate was 0.9% (95% CI: 0.0%-3.0%; I2 = 59.5%). Late failure and MBL were summarized narratively. Certainty of evidence was low to very low. CONCLUSIONS: Pterygoid implants demonstrate excellent survival (97.9%) and low failure rates (2.1%), primarily early, supporting their reliability as a graftless solution for posterior maxillary atrophy. Complications appear infrequent though heterogeneously reported. Low evidence certainty necessitates prospective studies with standardized outcome reporting.

Humans↗

PubMed2026

Outcomes of Suture Tape-Augmented ACL Reconstruction in Patients With High Internal Rotational Tibial Subluxation: A Minimum 3-Year Cohort Study.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) using hamstring tendon (HT) autografts faces persistent challenges of graft failure, especially in patients with high internal rotational tibial subluxation (IRTS). HYPOTHESIS: Patients with high IRTS who undergo HT autograft ACLR with suture tape augmentation (STA) will have lower graft failure rates and superior clinical outcomes as compared with those without STA. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective cohort study included patients with high IRTS-defined as lateral minus medial anterior tibial subluxation >5.8 mm based on prior studies-who underwent primary ACLR using HT autografts with STA and had a minimum follow-up of 3 years. Propensity score matching (1:1) was performed to identify a control group of patients with similarly high IRTS who underwent HT ACLR without STA. Postoperative outcomes were assessed by the International Knee Documentation Committee score, Lysholm score, and Tegner activity scale, as well as by return-to-sport status and graft failure. Clinically meaningful improvements were evaluated by the minimal clinically important difference, Patient Acceptable Symptom State, and substantial clinical benefit. RESULTS: This study included 62 patients with high IRTS: 31 with STA and 31 matched controls. The mean IRTS was 6.6 mm (range, 5.9-8.9) in the STA group and 6.8 mm (range, 5.8-8.7) in the control group. The mean patient age was 32.9 years (range, 20-50), and the mean follow-up was 3.8 years (range, 3.1-5.0). At final follow-up, the STA group showed significantly higher proportions of patients achieving the minimal clinically important difference (93.5% vs 74.2%; P = .038), Patient Acceptable Symptom State (96.8% vs 74.2%; P = .012), and substantial clinical benefit (54.8% vs 25.8%; P = .020). The return-to-sport rate was also higher in the STA group (74.2% vs 48.4%; P = .037). Additionally, the STA group demonstrated a lower graft failure rate (0% vs 12.9%; P = .039). CONCLUSION: For patients with high IRTS, STA in ACLR with HT autografts is associated with improved clinical outcomes, a higher return-to-sport rate, and a lower risk of graft failure at midterm follow-up.

Humans↗

PubMed2026

Efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis: a multicenter, randomized, open-label, active-controlled, phase III trial.

BACKGROUND: This study aimed to evaluate the efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis (MHD). METHODS: In this phase III, multicenter, randomized, open-label, non-inferiority trial, patients with hyperphosphatemia on maintenance hemodialysis were randomly assigned to receive either ferric citrate or sevelamer carbonate tablets for 12 weeks. The primary endpoint was the change in serum phosphorus levels from baseline to week 12, with a non-inferiority margin of 0.32 mmol/L. Secondary endpoints included changes in serum calcium, intact parathyroid hormone, and safety assessments. RESULTS: A total of 239 patients were randomized to the ferric citrate group (n = 119) or the sevelamer carbonate group (n = 120). The mean change in serum phosphorus levels was -0.70 ± 0.50 mmol/L in the ferric citrate group and -0.61 ± 0.59 mmol/L in the sevelamer carbonate group (least squares mean difference, -0.09 mmol/L; 95% CI, -0.24 to 0.05 mmol/L; non-inferiority margin, 0.32 mmol/L). No significant inter-group differences were found in the percentage of patients achieving target phosphorus levels (49.09% vs. 48.28%, p = 0.902). Ferric citrate significantly improved iron-related parameters and hemoglobin levels. Most treatment-emergent adverse events were mild, with gastrointestinal disorders being the most common. CONCLUSIONS: Ferric citrate tablets were non-inferior to sevelamer carbonate in reducing serum phosphorus levels in hyperphosphatemia patients on maintenance hemodialysis, with the added benefit of improving iron-related anemia and a favorable safety profile.

Adult↗

PubMed2026

Percutaneous left ventricular assist device in cardiogenic shock associated with and without acute myocardial infarction: a real-world retrospective cohort study.

BACKGROUND: Percutaneous left ventricular assist devices (pLVAD, such as Impella), are increasingly used for cardiogenic shock (CS). Outcomes may differ between acute myocardial infarction-related CS (AMI-CS) and non-AMI CS due to differing pathophysiology and trajectories. METHODS: Using the USA TriNetX Network (2016-2024), we identified adults with CS treated withpLVAD. AMI-CS was defined by MI within seven days of implantation; non-AMI CS included all patients with CS not attributable to acute MI, representing heterogeneous etiologies such as decompensated cardiomyopathy, myocarditis, valvular failure, pulmonary vascular causes, and arrhythmic shock. Patients with recent coronary artery bypass graft (CABG) were excluded. Propensity matching produced two balanced cohorts (n = 2,026 each). RESULTS: Among 6,873 AMI-CS and 4,521 non-AMI CS patients, matched groups were similar (mean age 63 years, 26% female). AMI-CS had higher mortality at 30 days (hazard ratio [HR] 1.19, p = 0.002), 90 days (HR 1.13, p = 0.02), and 180 days (HR 1.14, p = 0.007). Heart failure (HF) exacerbations (HR 1.21, p < 0.001) and pulmonary edema (HR 1.23, p = 0.005) were also more common in AMI-CS. Stroke, ventricular arrhythmias, cardiac arrest, acute kidney injury, major bleeding, vascular complications, and hemodialysis were comparable. CONCLUSION: AMI-CS patients supported with pLVAD experienced higher mortality and greater HF-related morbidity than non-AMI CS.

Humans↗

PubMed2026

Orthoplastic management of open calcaneal fractures: A systematic review of flap selection and complications.

BACKGROUND: Open calcaneal fractures are rare, high-energy injuries involving extensive soft-tissue loss and comminuted bone disruption. Successful management depends on coordinated orthoplastic reconstruction to achieve stable fixation and durable coverage. Multiple flap types have been described, yet comparative outcomes remain poorly defined. METHODS: A systematic review was performed in accordance with PRISMA guidelines (PROSPERO: CRD420251138394). MEDLINE, Embase, Cochrane CENTRAL, and Scopus were searched from January 2000 to July 2025. Studies reporting flap-based reconstruction for open calcaneal fractures in adults were included. Extracted data included flap type, fixation method, follow-up duration, and complications such as infection, necrosis, vascular crises, flap loss, and amputation. RESULTS: Thirteen studies comprising 88 major flap reconstructions were analysed. Overall flap survival was 97.7%, with two failures (both muscle/myocutaneous). Fasciocutaneous flaps showed the lowest complication rates (8.3%) with no reported cases of infection, while muscle/myocutaneous flaps demonstrated cases of infection (20%) and accounted for both flap failures and the only reported amputation. Chimeric flaps were increasingly used in recent series (n = 32), achieving reliable survival but higher vascular compromise (6.3%). Osteocutaneous flaps were rare (n = 4) and primarily used for defects with bone loss, showing infection in 50% of cases. Meta-analysis was not possible due to heterogeneity and small sample sizes. CONCLUSIONS: Fasciocutaneous flaps provide reliable, low-complication coverage for clean wounds, while muscle flaps remain valuable for contamination or complex cases with extensive tissue loss. Chimeric, and osteocutaneous flaps show promise, but larger, standardised studies are needed to clarify their roles in hindfoot reconstruction.

Humans↗

PubMed2026

Targeting Gasdermins for Therapeutic Interventions in Central Nervous System Injury.

Central nervous system (CNS) injuries are the leading cause of permanent disability and premature death in adults worldwide, with their incidence continuing to rise amid social development. These injuries not only severely impair the quality of life but also impose a heavy burden on the global public health system. Current clinical interventions, such as decompression and thrombolysis, can alleviate primary injury but fail to effectively reverse the secondary neuroinflammatory damage. Traditional anti-inflammatory therapies, which cannot block the upstream source of the inflammatory cascade, have led to repeated failures in global clinical translation research over the past decades. Gasdermins were first characterized in studies of systemic inflammatory diseases. These proteins form transmembrane pores to drive the release of proinflammatory factors and inflammatory cell death, serving as key mediators of host innate immunity. Recent studies have revealed that gasdermins play critical roles in regulating the initiation and amplification of neuroinflammation following CNS injury. To clarify the therapeutic potential of gasdermins as targets for injury repair, this review systematically summarizes the structure and function of gasdermins, as well as their cell-specific activation and regulatory mechanisms. We further elaborate on their pathological roles in these injuries and the corresponding therapeutic strategies, aiming to provide a theoretical reference for basic research and clinical translation in this field.

Humans↗

PubMed2026

Continuous Intraperitoneal Insulin Infusion for People With Type 1 Diabetes: A Literature Review and International Position Statement.

Achieving glucose targets without hypoglycaemia is the treatment goal in type 1 diabetes. Structured education, intensified insulin injection regimens, continuous glucose monitoring, automated insulin delivery, and ongoing support from a multidisciplinary team all support people with type 1 diabetes to achieve this goal. Despite these advances, significant barriers to achieving optimal management remain. Continuous intraperitoneal insulin infusion has comparable or better glucose outcomes to continuous subcutaneous insulin infusion and may reduce the frequency of hypoglycaemia, including severe episodes. Intraperitoneal insulin may be considered as a treatment modality for children and adults with type 1 diabetes using optimised intensive insulin therapy for whom subcutaneous insulin has failed due to lipoatrophy, -dystrophy or -hypertrophy, local allergy, subcutaneous insulin resistance or co-existing skin conditions. Failure of subcutaneous insulin may result in recurrent or unexplained severe hypoglycaemia or hyperglycaemia. Intraperitoneal insulin may also be considered as a treatment modality for people with type 1 diabetes with severe needle-phobia, and for those being considered for islet cell or pancreatic transplantation, or where transplantation is not available. This paper summarises current intraperitoneal insulin delivery technology, its potential risks and benefits, and an expert position statement. It is intended for use by diabetes specialist healthcare professionals, and as a reference for other healthcare professionals, commissioners, payors, people with diabetes, their carers, and advocates.

Humans↗

PubMed2026

Efficacy of sodium-glucose cotransporter 2 inhibitors after acute myocardial infarction: Are the benefits limited to patients with diabetes? A systematic review and meta-analysis.

BACKGROUND: Acute myocardial infarction remains one of the leading causes of death worldwide. Recently, studies have focused on evaluating the effectiveness of SGLT2 inhibitors in this scenario. Objectives We aimed to perform a meta-analysis comparing the efficacy of SGLT2 inhibitors vs standard care. METHODS: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) and observational studies comparing patients with acute myocardial infarction using iSGLT2 inhibitors and standard care. Statistical analyses were conducted using R software (v 4.3.2) and a random-effects model was employed for all outcomes. RESULTS: A total of 31,378 patients were included, with 10,897 (34.7%) assigned to the SGLT2 inhibitor group. Among these studies, three were randomized controlled trials (RCTs). There was a significant difference in reduction of HF readmissions (OR 0.61; p < 0.01), all-cause mortality (OR 0.62; p < 0.01;) and stroke (OR 0.67; p < 0.01;). However, there was no significant difference in cardiovascular death, rehospitalization for any cause and recurrence of acute MI. Meta regression and subgroup analysis showed a trend toward better outcomes in the diabetic and non-STEMI population. CONCLUSIONS: SGLT2 inhibitors were associated with lower HF rehospitalization, stroke, and all-cause mortality after acute MI, mainly in observational studies. Benefits appeared greater in diabetic and non-STEMI patients. Dedicated RCTs focusing on diabetic, particularly non-STEMI, populations are needed to confirm these findings. KEY POINTS: What is already known on this topic: SGLT2 inhibitors have demonstrated cardiovascular and renal benefits in patients with heart failure and type 2 diabetes mellitus. However, their role in the acute myocardial infarction (AMI) setting remains uncertain, particularly regarding post-AMI outcomes such as heart failure readmissions, mortality, and recurrent ischemic events, with current evidence derived from heterogeneous and predominantly observational studies. WHAT THIS STUDY ADDS: This meta-analysis, including over 31,000 patients, suggests that SGLT2 inhibitors are associated with reductions in heart failure readmissions, all-cause mortality, and stroke following AMI. These associations were more consistently observed in patients with type 2 diabetes and in non-ST-segment elevation myocardial infarction (NSTEMI) populations. However, randomized controlled trials showed neutral results, and the observed benefits were mainly driven by observational studies. Meaning: These findings should be interpreted as hypothesis-generating. While SGLT2 inhibitors may represent a potential therapeutic strategy in selected post-AMI populations, particularly patients with diabetes and NSTEMI, current evidence does not support routine early in-hospital initiation. Dedicated randomized trials specifically enrolling diabetic post-AMI patients are required to clarify optimal timing and clinical benefit.

Humans↗

PubMed2026

Breastfeeding Outcomes After Radiofrequency Ablation and Surgical Excision of Fibroadenomas Compared to Natural History: A Retrospective Cohort Study.

BACKGROUND: Fibroadenomas, common benign breast tumors in women of reproductive age, are increasingly managed with minimally invasive radiofrequency ablation (RFA) or surgical excision. However, their impact on breastfeeding outcomes remains underexplored. We aimed to assess breastfeeding ability and breast tissue changes in women treated with RFA or surgery compared to those with untreated fibroadenomas. METHODS: In this retrospective cohort study, we evaluated 153 women with biopsy-confirmed fibroadenomas across five groups: RFA with prior breastfeeding (RFA-PreBF; n = 26), RFA with posttreatment breastfeeding (RFA-PostBF; n = 22), surgical excision with prior breastfeeding (Surgical-PreBF; n = 30), surgical excision with posttreatment breastfeeding (Surgical-PostBF; n = 20), and noninterventional with breastfeeding (Observation-BF; n = 55). Breastfeeding ability was assessed using a 5-point scale, and breast tissue changes were evaluated via ultrasound at 18 months, and all breastfeeding attempts occurred at a minimum of 12 months postprocedure. Fisher's exact test compared complete lactation failure rates, and a power analysis validated the study design (Fig. 1). FINDINGS: The combined RFA group (n = 48) had a higher complete lactation failure rate (14.6%) than the Observation-BF group (3.6%; Fisher's exact test, p = 0.045). Similarly, the combined surgical group (n = 50) had a higher complete lactation failure rate (16.0%) than the Observation-BF group (p = 0.034). When pooled, the combined intervention group (n = 98) showed a complete lactation failure rate of 15.3% versus 3.6% in the Observation-BF group. Residual tissue correlated with lactation impairment in the RFA group (Spearman's ρ, p < 0.05). Ultrasound showed no tumor recurrence, with cystic changes in some cases not linked to breastfeeding impairment. Power analysis confirmed 80% power to detect a medium effect size (f = 0.25, Fig. 1), supporting the study's robustness.7 RFA-PreBF (n = 26), RFA-PostBF (n = 22), Surgical-PreBF (n = 30), Surgical-PostBF (n = 20), and Observation-BF (n = 55). Breastfeeding ability was assessed using a 5-point scale, and breast tissue changes were evaluated via ultrasound at 18 months. Fisher's exact test compared complete lactation failure rates, and a power analysis validated the study design (Fig. 1).[Figure: see text]Interpretation:RFA and surgical excision are effective for fibroadenoma management but increase the risk of complete lactation failure compared to untreated fibroadenomas. Careful patient selection, precise procedural techniques, and vigilant posttreatment monitoring are essential to optimize breastfeeding outcomes, particularly for women planning future pregnancies.

Humans↗