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PubMed2026

Artificial intelligence-supported double reading in European population breast cancer screening: A systematic review and meta-analysis of prospective programs.

BACKGROUND: Most European population mammography screening programs rely on double reading with arbitration, a model that delivers mortality benefit but is increasingly challenged by radiologist workload, variable specificity, and interval cancers. Artificial intelligence (AI) is being evaluated to support or optimize these established European screening pathways. PURPOSE: To synthesize prospective or program-embedded evaluations of AI conducted within European-style population screening programs and to estimate exploratory program-level absolute risk differences (RDs) per 1000 examinations for cancer detection rate (CDR) and recall. MATERIALS AND METHODS: We performed a prespecified, focused evidence synthesis of three large studies embedded within routine population screening programs operating under European-relevant workflows: MASAI (randomized AI-supported risk triage within a national program), ScreenTrustCAD (prospective paired-reader evaluation with AI as an independent reader in a double-reading framework), and PRAIM (nationwide decision-referral implementation). Outcomes were harmonized as AI-control RDs per 1000 examinations. Random-effects pooling used Hartung-Knapp-Sidik-Jonkman models. For the paired-reader design, sensitivity analyses applied a Kish effective sample-size approach across plausible within-examination correlations (ρ = 0.3-0.8). Positive predictive value (PPV) and workflow/time outcomes were summarized descriptively. RESULTS: Across 597,419 examinations, the pooled CDR RD was +0.9 per 1000 (95% CI -0.0 to +1.8; I2 ≈ 12%), consistent with a modest directional increase with borderline statistical uncertainty. The pooled recall RD was -0.6 per 1000 (95% CI -3.1 to +2.1; I2 ≈ 41-43%), indicating no consistent recall increase across screening programs. Where reported, PPV was higher with AI-supported screening. Efficiency signals included 44.3% fewer total readings in MASAI and shorter reading times for AI-normal examinations in PRAIM; in PRAIM, a program-level safety-net mechanism recovered 204 cancers that would otherwise have been missed. CONCLUSION: In European population screening programs characterized by double reading and arbitration, prospective program-embedded evidence suggests that AI integration may yield a small absolute increase in cancer detection (≈1/1000) without a consistent increase in recall, alongside improved PPV and efficiency signals. These findings suggestAI primarily as a complementary reader within European screening workflows, with implementation requiring explicit quality assurance and monitoring of interval cancers and stage distribution.

Humans↗

PubMed2026

Lifestyle interventions to prevent gestational and type 2 diabetes among migrant women from low- and middle-income countries: a systematic review.

Migrant women from low- and middle-income countries (LMICs) living in high-income settings experience disproportionately high risk of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM). This review aimed to identify and synthesise culturally adapted lifestyle interventions for preventing or managing GDM and T2DM among migrant women from LMICs, focusing on intervention components, cultural adaptation strategies, and behavioural and metabolic outcomes. Five databases (PubMed, Embase, Scopus, CINAHL, Cochrane Central) were searched using Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 guidelines. Eligible studies included experimental designs involving lifestyle interventions delivered to migrant women from LMICs in high-income countries, reporting outcomes related to GDM or T2DM targeting behaviour change. Data were synthesised narratively; study quality was appraised using RoB2 for RCTs and a structured narrative approach for non-randomised designs. Certainty of evidence was evaluated using GRADE. Eight studies met the inclusion criteria. Sample sizes ranged from 28 to 641 participants. Intervention duration varied from 6 weeks to 12 months. Most interventions incorporated atleast one culturally tailored component, such as bilingual delivery, culturally adapted dietary education, or community-based engagement. Improvements were reported across dietary behaviours, physical activity, glycaemic measures, or diabetes-related knowledge; however, effect sizes were modest and inconsistent. Interventions combining dietary modification, physical activity, and culturally adapted delivery demonstrated greater improvements than exercise-only or digital-only programmes. Overall certainty of evidence ranged from low to moderate. Culturally adapted, multi-component lifestyle interventions show promise for improving behavioural and metabolic outcomes among migrant women from LMICs; however, the evidence base remains limited.

Humans↗

PubMed2026

Clinical outcomes of zirconia dental restorations: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the survival and success rates of zirconia dental restorations (ZDRs) and their complications. DATA & SOURCES: Electronic searches of PubMed, Cochrane, Embase and Web of Science were conducted up to January 1, 2026. Clinical studies with at least 1-year follow-up evaluating zirconia dental restorations in natural teeth were included. Survival rates, success rates, and biological and mechanical complications were analyzed. Risk of bias was assessed using RoB 2, Newcastle-Ottawa Scale (NOS), and Joanna Briggs Institute tools (JBI). Certainty of evidence was evaluated using the GRADE approach. STUDY SELECTION & RESULTS: Sixty-six studies published between 2008 and 2025 were included. Pooled survival rates ranged from 92.9% to 98.7% up to 10 years for single crowns (SCs), 77.6% over 10 to 13 years for fixed dental prostheses (FPDs), 97.4% for resin-bonded FPDs (RBFPDs) over 10 to 15 years, from 50.0% to 52.6% over 9 to 13 years for conventional cantilever FPDs (CFPDs) and 89.0% for inlay-retained FPDs (IRFPDs) over 10 years. Pooled success rates were 46.1% for SCs over 10 years, 40.1% for FDPs over 10 to 13 years, 84.3% for RBDPDs over 10 to 15 years, 12.5% to 22.6% for CFPDs over 9 to 13 years and 70.3% for IRFPDs over 10 years. Biological and mechanical complication rates were 12.1% and 53.9% for SCs at 10 years, 19.4% and 46.7% for FPDs over 10 to 13 years, 50.0% and 37.5% for CFPDs at 9 years, 21.4% and 14.3% for IRFPDs at 3 years, and 3.3% and 8.0% for RBFPDs over 10 to 15 years. Restorations treated with airborne-particle abrasion (APA) combined with 10-methacryloyloxydecyl dihydrogen phosphate (MDP) achieved favorable short-term clinical outcomes, with pooled survival and success rates of 98.6% and 97.7% for SCs, and 98.1% and 70.1% for IRFPDs, respectively. The included studies were assessed as having low to moderate risk of bias using RoB 2, NOS, and JBI tools, but GRADE assessment yielded evidence of very low certainty. CONCLUSIONS: ZDRs generally demonstrated acceptable to excellent short- to long-term survival and success outcomes. Mid- to long-term clinical performance was varied according to restoration types. The RBFPDs had relatively low complication rates, followed by the SCs, the FPDs and the IRFPDs. CFPDs exhibited relatively low success rates and high complication rates. The predominant biological complications were secondary caries and pulpitis or apical periodontitis, while chipping and debonding were the most common mechanical complications. APA treatment followed by application of MDP is capable of producing favorable short-term clinical outcomes. CLINICAL SIGNIFICANCE: ZDRs except for CFPDs could achieve favorable mid- to long-term clinical performance. CFPDs should be conducted with caution.

Zirconium↗

PubMed2026

Contrast Heat-Cold Versus Thermoneutral Showering in Trained Combat Sport Athletes: A Randomized Field Trial of Recovery Outcomes.

Contrast heat-cold showering is popular for recovery, but multisystem evidence and persistence after cessation remain unclear. To evaluate whether a 4-week post-training contrast heat-cold shower intervention produces an integrated recovery profile across four domains (autonomic, endocrine, perceptual, and microvascular) rather than testing a single isolated physiological pathway, across baseline (T0), post-intervention (T1), and 2-week wash-out (T2). Sixty combat-sport athletes were randomized to contrast showers (10 min alternating warm 38-40°C and cold 13-15°C) or an active thermoneutral-shower comparator (10 min, 32-34°C) after training for 4 weeks. Primary analyses were per-protocol (≥ 75% compliance; n = 57), with intention-to-treat sensitivity analyses. Outcomes were Total Quality Recovery (TQR), morning salivary cortisol (two mornings averaged), resting HRV, and post-occlusive reactive hyperemia (PORH). From T0 to T1, favorable between-group changes were observed for resting HR (ΔΔ -2.10 bpm, 95% CI -2.24 to -1.96; g -0.65; p < 0.001), lnRMSSD (ΔΔ 0.123 log units, 95% CI 0.108 to 0.137; g 0.74; p < 0.001), with similar T1 effects for RMSSD and SDNN, and TQR (ΔΔ 0.61 points, 95% CI 0.27 to 0.95; g 0.80; p < 0.001). These T1 autonomic and perceptual changes were not maintained at T2 (all T2-T0 ΔΔ p > 0.05). Cortisol and PORH-derived outcomes showed no statistically clear between-group differences at T1 or T2 (all p > 0.05). Compared with thermoneutral showering, 4 weeks of post-training contrast heat-cold showering produced short-term favorable between-group changes in autonomic regulation and perceived recovery, but not in morning cortisol or PORH-derived microvascular reactivity. These effects were not maintained after wash-out; therefore, causal attribution to the shower intervention alone and claims of persistent physiological adaptation should be made cautiously. Trial registration: ISRCTN15418049.

Humans↗

PubMed2026

Costs of surgeries in low- and middle-income countries: a systematic literature review.

BACKGROUND: Surgical care is essential for achieving global health equity, yet low- and middle-income countries (LMICs) face major gaps in access and planning, partly due to limited evidence on the costs and resource requirements of surgical interventions. Understanding these costs is vital for designing efficient and equitable health systems. METHODS: We conducted a systematic literature review (covering MEDLINE, EMBASE, Global Health, EconLit and grey literature) to identify studies reporting the costs of surgeries in LMICs from January 2000 to June 2023. Minor and major surgical procedures were considered, focusing on therapeutic procedures (excluding diagnostic interventions). Studies that clearly identified, quantified and costed hospital resources and services deployed in the provision of surgical care, and included at least two of the surgical production factors (ie, consumables, diagnostics, personnel, infrastructure and overhead) in the costing were included. Costs were standardised to 2023 International dollars (I$) for comparability. RESULTS: A total of 74 studies from 29 countries met the inclusion criteria, with 210 cost estimates across 65 procedure groups. Costs varied widely: from I$1.54 for a caesarean section in Tanzania to I$618 098 for paediatric cataract surgery in Zambia. Full costing studies reported higher estimates than partial costing studies. Most studies (60%) originated from upper-middle-income countries, with limited data (10%) from low-income settings. CONCLUSION: This review provides a reference list of surgical procedure costs across LMICs, highlighting considerable cost variation by procedure, specialty and country. The findings underscore the need for better-quality, standardised cost data-especially from low-income countries-to inform national surgical plans, universal health coverage benefit packages and reimbursement policies.

Developing Countries↗

PubMed2026

Comparison of the clinical efficacy, safety and EEG functional connectivity changes between 18-Hz rTMS and iTBS of accelerated dTMS treatment for major depressive disorder: a randomized controlled trial.

Although the antidepressant efficacy of 18-Hz deep transcranial magnetic stimulation (dTMS) has been validated, its prolonged treatment duration has considerable limitations for treatment capacity and patient adherence. Therefore, novel short-course protocols such as accelerated dTMS and intermittent theta burst stimulation (iTBS) present promising alternative options. Here we addressed the question of whether iTBS of accelerated dTMS achieves comparable therapeutic and electrophysiological effects to accelerated dTMS with the conventional 18-Hz rTMS protocol in patients with major depressive disorder (MDD). In a randomized controlled trial (n = 73), participants received either 18-Hz rTMS of accelerated dTMS (rTMS-dTMS group), iTBS of accelerated dTMS (iTBS-dTMS group), or pharmacotherapy alone (drug group). Both dTMS protocols were administered twice daily for 10 days targeting the left lateral prefrontal cortex including the dorsolateral region. Results showed that Hamilton Depression Rating Scale (HAMD) score of the iTBS-dTMS group decreased significantly from 22.5 ± 3.7 before treatment to 8.2 ± 4.1 after treatment (t = 15.900, p < 0.001). HAMD score of the rTMS-dTMS group decreased significantly from 21.3 ± 2.9 before treatment to 8.0 ± 3.8 after treatment (t = 17.232, p < 0.001). The drug group also exhibited significantly improved patients' mood symptoms, and the HAMD score decreased from 24.7 ± 6.8 to 14.0 ± 5.0 (t = 6.363, p < 0.001). The treatment response rate was 85.7% in the iTBS-dTMS group and 76.9% in the rTMS-dTMS group, which was much higher than that of the drug group (42.1%). The remission rate was 50.0% in the iTBS-dTMS group and 42.3% in the rTMS-dTMS group, which was significantly higher than 10.5% of the drug group. We demonstrate here that both accelerated dTMS protocols significantly reduced HAMD scores, improved the response rates, and remission rates, outperforming pharmacotherapy alone. Resting-state EEG analysis further revealed unique frequency-specific functional connectivity (FC) modulation effects: the rTMS-dTMS group primarily exhibited weakened alpha-band functional connectivity within the fronto-occipital, fronto-temporal and fronto-central networks after treatment, whereas the iTBS-dTMS group predominantly demonstrated reduced theta-band functional connectivity within the fronto-parietal, fronto-occipital and fronto-temporal pathways after treatment. These findings indicate that iTBS of accelerated dTMS demonstrates comparable efficacy and tolerability to 18-Hz rTMS of accelerated dTMS, whilst inducing treatment-specific network-level neurophysiological alterations. In the rTMS-dTMS group, relative changes in FC between the frontal and temporal/precentral regions showed significant negative correlation with HAMD score reduction rates, while relative changes in FC between the frontal lobe and parietal lobe showed a significant positive correlation with the rate of HAMD score reduction for the iTBS-dTMS group. This study revealed novel mechanisms by which accelerated dTMS protocols modulate brain networks, providing evidence for the clinical application of accelerated iTBS-dTMS as an efficient, evidence-based treatment for MDD.

Humans↗

PubMed2026

Transcriptomic insights into temperature regulation of proliferation and differentiation in skeletal muscle cells of Nibea albiflora.

Myogenesis involves sequential stages of muscle satellite cell activation, myoblast proliferation, differentiation, and fusion into multinucleated myotubes. Teleost muscle exhibits indeterminate growth and is highly sensitive to environmental temperature, yet the underlying mechanisms by which temperature regulate proliferation and differentiation remain poorly understood. In this study, we established a primary skeletal muscle cell culture from the yellow drum (Nibea albiflora), an economically important marine fish, and integrated morphological observations with comparative transcriptomics analysis to characterize cellular and molecular responses at 28 °C and 20 °C during both proliferation and differentiation stages. Phenotypic analysis revealed that 28 °C significantly enhanced both myoblast proliferation and myogenic differentiation ability compared with 20 °C. Transcriptomic profiling revealed that at 28 °C, differentiation upregulated extracellular matrix(ECM) organization, calcium signaling, and sarcomere assembly, while proliferation enhanced focal adhesion, growth factor signaling, and lipid metabolism. At 20 °C, differentiation was characterized by glutathione metabolism, and ferroptosis, while proliferation involved cytokine-cytokine receptor interaction and negative regulation of signal transduction. Core myogenic regulatory factors (MRFs), particularly myogenin, were strongly upregulated at 28 °C during the differentiation stage, serving as an internal control. Based on these findings, we propose a testable model that elevated temperature coordinates Ca2+-dependent MRF activation with ECM-integrin signaling to drive sarcomere assembly and muscle growth. Key differentially expressed genes (DEGs) regulating myogenesis in N. albiflora were also identified. This study provides a mechanistic framework for temperature adaptation in teleost skeletal muscle and identifies candidate genes for functional validation and marker-assisted selection, as well as a rationale for temperature management strategies to improve aquaculture yield of N. albiflora.

Animals↗

PubMed2026

Pharmacokinetic and Pharmacodynamic Bio-Similarity of ADL-018 to Innovator Omalizumab: A Randomized Study in Healthy Adults.

Bioequivalence and safety of ADL-018, an omalizumab biosimilar, were compared with United States-licensed omalizumab (US-OMA) and European Union-approved omalizumab (EU-OMA), both approved for allergies. Healthy adults were randomized (1:1:1) to receive a dose of ADL-018, US-OMA, or EU-OMA (150 mg/mL). Pharmacokinetic (PK) parameters, including AUC(0-last), AUC(0-∞), and Cmax, were considered equivalent if 90% CIs of geometric mean ratios (GMRs) were within predefined equivalence margin (0.80-1.25) using ANCOVA model. Other PK parameters, pharmacodynamics (PD) (free/total immunoglobulin E [IgE]), immunogenicity, and safety were compared. Overall, 306 participants (n = 102 per arm) were dosed; 287 completed the study. Equivalence of primary PK parameters was confirmed for pairwise comparisons, with 90% CIs within the predefined margin (GMRs of ADL-018 vs US-OMA: AUC(0-last)-1.08, AUC(0-∞)-1.07, Cmax-1.05; GMRs of ADL-018 vs EU-OMA: AUC(0-last)-1.06, AUC(0-∞)-1.06, Cmax - 1.05; and GMRs of US-OMA vs EU-OMA: AUC(0-last)-0.99, AUC(0-∞)-0.99, Cmax-1.00). PK/PD parameters were comparable across arms. Increase in total IgE (AUEC ∼30,000 to 35,000 h IU/mL) and decrease in free IgE (AUEC ∼29,000 to 35,000 h IU/mL) were comparable across arms. Similar incidence of adverse events across arms (treatment-emergent adverse events: ADL-018, n = 6; US-OMA, n = 5; EU-OMA, n = 4) was observed. ADL-018 demonstrated PK/PD equivalence and comparable safety profile to reference omalizumab.

Humans↗

PubMed2026

ESC quality indicators for post-myocardial infarction care: transition and chronic coronary syndrome phases.

AIMS: We aimed to develop the European Society of Cardiology (ESC) quality indicators (QIs) for myocardial infarction (MI), from 1 year after hospital discharge, corresponding to transition to the chronic coronary syndrome phases. METHODS AND RESULTS: We collaborated with the European Association of Preventive Cardiology (EAPC) and developed QIs for the long-term management of patients following MI. We applied the ESC methodology for QI development by (i) determining key domains of post-MI care; (ii) developing candidate QIs by performing a systematic review of the literature, and (iii) selecting the final set of QIs using a modified Delphi approach. In total, 18 QIs were identified across seven domains of care including (i) structural framework, (ii) risk assessment and follow-up, (iii) pharmacological management, (iv) rehabilitation, behavioural, and preventive interventions, (v) coronary revascularization, (vi) clinical outcomes, and (vii) patient-reported outcomes. CONCLUSION: We present the ESC QIs from 1 year after hospitalization for MI, to standardize and address gaps in care for this high-risk group. These QIs are supported by evidence from contemporary literature, endorsed by expert consensus, and aligned with the 2024 ESC guidelines on the management of chronic coronary syndromes. LAY SUMMARY: Measures to evaluate and improve the long-term management of patients following a heart attack are needed. In this paper, we identified key aspects of care that can help clinicians, decision-makers and patients improve the quality of care, from one year after a heart attack onwards, and help address inequalities and variations in clinical practice.

Humans↗

PubMed2026

Surgical management of jugular foramen meningiomas: a function-prioritized perioperative workflow.

OBJECTIVE: Jugular foramen meningiomas are challenging because of their deep, neurovascularly crowded location and multicompartment extension; hyperostosis and rigid dural attachment further narrow the corridor and increase the risk of lower cranial nerve morbidity, causing dysphagia and airway complications that may rarely require tracheostomy. This study aimed to describe a contemporary function-first workflow integrating compartment-based anatomy, venous sinus status, preoperative embolization, and continuous vagus nerve monitoring and its relation to clinically actionable recovery endpoints. METHODS: The authors retrospectively reviewed 26 consecutive patients who underwent primary surgery for jugular foramen meningiomas (2014-2025). Tumors were classified as intradural + intrajugular (IJ) or intradural + intrajugular + extracranial extension (IJE). Retrosigmoid, suprajugular, or transjugular approaches were selected by tumor extension and sigmoid-jugular venous status. Selective embolization and continuous vagus nerve monitoring were used when feasible. Outcomes included extubation timing, time to oral intake, 1-year swallowing/voice severity, extent of resection, and salvage stereotactic radiosurgery (SRS) for progression/regrowth. RESULTS: Twenty tumors were IJ and 6 were IJE. Selective embolization was performed in 16 patients (62%) without complications. Continuous vagus nerve monitoring was implemented in 16 patients (62%); lower preservation rates showed an exploratory association with worse 1-year swallowing. All patients were extubated immediately after surgery. Oral intake began by postoperative day ≤ 7 in 20 patients (77%); only 1 required > 14 days before resuming oral intake. At 1 year, swallowing and hoarseness remained worse in 54% and 46% of patients, respectively, but almost all cases were mild; the same patient had moderate dysphagia/hoarseness, and none required tracheostomy, gastrostomy, long-term tube feeding, or phonosurgery. Simpson grade IV comprised 69% of cases but predominantly reflected intrajugular/extracranial residual rather than persistent intradural disease. No patient without preoperative facial nerve palsy developed new palsy; serviceable hearing was preserved in 70%, and 38% with preoperative nonserviceable hearing improved to serviceable hearing. During a median 55.6-month follow-up, 3 patients (12%) underwent salvage SRS for regrowth; none required reoperation. CONCLUSIONS: A function-first workflow guided by anatomical compartment extension and intraoperative monitoring can support rapid recovery and durable functional independence in jugular foramen meningiomas. The IJE phenotype identifies a higher-risk subgroup for delayed oral intake and postoperative subjective dysphagia/hoarseness, while continuous vagus nerve monitoring may provide actionable insights to calibrate surgical aggressiveness and support function-prioritized acceptance of intrajugular/extracranial residual with close surveillance and salvage SRS when needed.

Humans↗

PubMed2026

Novel splice site variants in GBA1 are associated with Gaucher disease and genotype-phenotype correlations.

BACKGROUND: Variants in GBA1 are associated with neurodegenerative disease. This study aimed to explore pathogenic GBA1 variants. METHODS: Four patients with progressive myoclonic epilepsy (PME) and extremely low β-glucosidase levels were recruited. Whole-exome sequencing and long-range PCR were performed to identify GBA1 variants. Bioinformatic analyses were used to predict the impact of the identified variants. A literature review was performed to explore the genotype-phenotype correlations. GBA1 expression data across different brain regions and developmental stages were analyzed using the BrainSpan database. RT-PCR was performed to verify the splicing effects. RESULTS: Compound heterozygous GBA1 variants were identified in four patients. Five distinct variants were detected, including two novel splice site variants (c.308-2A>G and c.762-2A>C) and three previously reported variants. All identified variants were rare or absent in gnomAD. Splice site variants c.308-2A>G and c.762-2A>C were predicted to cause aberrant splicing. Minigene-based splicing assays coupled with RT-PCR and Sanger sequencing confirmed that both variants cause complete exon skipping (exon 4 and exon 7, respectively). All patients presented with PME onset in childhood/adolescence, intellectual regression, low β-glucosidase, and diffuse brain atrophy and were subsequently diagnosed with Gaucher disease type 3. GBA1 expression in the brain showed two distinct peaks: one in infancy and another after five years of age. The onset age of PME aligned with the second GBA1 expression peak (after five years of age). CONCLUSION: This study identified compound heterozygous GBA1 variants, including two novel candidate pathogenic splice site variants, in Gaucher disease type 3 patients, expanding the known mutational spectrum.

Humans↗

PubMed2026

Rates, Timing, and Predictors of Retreatment Across Risk-Cohorts in Retinopathy of Prematurity: Intravitreal Bevacizumab Injection Versus Laser.

OBJECTIVE: To characterize rates, timing, and predictors of retinopathy of prematurity (ROP) retreatment among infants treated with primary laser or intravitreal bevacizumab injection. DESIGN: Retrospective consecutive, comparative clinical study. PARTICIPANTS: Infants who underwent initial treatment for treatment-warranted ROP (TW-ROP) with either intravitreal bevacizumab or laser photocoagulation between 2017 and 2023. METHODS: Patients were stratified into two treatment groups: primary laser group vs primary bevacizumab group. MAIN OUTCOME MEASURES: Retreatment within the first 3 months (0-90 days) was assessed and classified as early (≤30 days) or late (31-90 days). RESULTS: Two hundred and thirty eight eyes of 122 infants were treated for ROP; of those, 181 (76.1%) eyes of 93 (76.2%) patients were included. There were 116 (64.1%) eyes in the bevacizumab group, and 65 (35.9%) eyes in the laser group. Thirty-three (18.2%) eyes-all micro- or nano-premature (<27 weeks GA and/or <800 grams)-required retreatment for TW-ROP. Sixteen (8.8%) required early retreatment at a median postmenstrual age (PMA) of 40.4 weeks (IQR, 38.44-43.3). There were differences in the proportion of early retreated infants (21.5% for laser vs 1.7% for injection, P < .001). Seventeen (9.4%) eyes required late retreatment. The median PMA at late retreatment was 45.6 weeks (IQR, 43.7-47.4). Infants in the bevacizumab group had lower odds of retreatment within three months than those with laser (OR, 0.23; 95% CI, 0.06-0.82). Similarly, patients in the bevacizumab group had lower odds of requiring early retreatment compared to those with laser (OR, 0.08; 95% CI, 0.04-0.18). Within eyes with retreatment, infants in the bevacizumab group had a later PMA at retreatment than those in the laser group (B = 6.81; 95% CI: 4.68-8.93). AROP was associated with earlier PMA at retreatment (B = -7.72; 95% CI, -9.36 to -6.10). CONCLUSION: In this study, early retreatment was low (8.8%), with most eyes initially treated with laser (21.5%) rather than bevacizumab (1.7%). Aggressive ROP was associated with earlier retreatment, highlighting its role as a marker of more severe disease. Compared to laser, bevacizumab was associated with lower overall and early retreatment, and delayed need for additional intervention when necessary. All retreatments occurred in micro- or nano-premature infants, suggesting that medium-to-low risk infants may require less strict post-treatment monitoring.

Humans↗

PubMed2026

Divergent trajectories of genome architecture and chromosome evolution in ferns and angiosperms.

Ferns and angiosperms represent the two largest vascular plant lineages but exhibit striking genomic and ecological contrasts. We investigated whether differences in genome size, chromosome architecture, GC content, and stomatal traits reveal divergent evolutionary trajectories between these lineages. We assembled the most comprehensive dataset to date, integrating genome size, chromosome number and size, GC content, and stomatal traits for over 1100 fern species and compared it with an extensive angiosperm dataset. Ferns exhibited markedly lower variability and c. 16-fold slower rates of chromosome size evolution than angiosperms. A persistent positive relationship between genome size and chromosome number in ferns suggests limited cytological post-polyploid diploidization. While ferns generally possess larger stomata, this difference disappears after accounting for genome size, indicating that nucleotypic constraints, rather than lineage-specific physiology, dictate stomatal dimensions. Both groups share a unimodal GC-genome size relationship peaking at c. 14 Gbp. Larger fern chromosomes imply lower genome-wide recombination rates, potentially limiting genetic reshuffling and adaptive potential. Our results highlight fundamentally divergent evolutionary trajectories, likely shaped by meiotic symmetry in ferns and meiotic asymmetry, possibly centromere drive, and post-polyploid diploidization in angiosperms, defining the functional and genomic landscapes of these lineages across deep evolutionary timescales.

Genome, Plant↗

PubMed2026

Adeno-Associated Virus Gene Therapy Translation: Lessons from Early Regulatory Meetings.

The Platform Vector-Gene Therapy (PaVe-GT) program is a National Institutes of Health (NIH) initiative that aims to develop adeno-associated virus (AAV) gene therapies for four monogenic rare diseases, two organic acidemias and two congenital myasthenic syndromes. PaVe-GT's platform-based approach identifies and diminishes redundancies and applies efficiencies in preclinical, clinical, and regulatory activities. The program's hypothesis is that implementing these efficiencies can accelerate clinical trial initiation. Based on its platform-centric experience and public-serving mission, the PaVe-GT program actively shares its scientific and regulatory learnings with the public to benefit the development of similar gene therapy products for rare diseases. PaVe-GT's first investigational AAV gene therapy candidate is AAV serotype 9 human propionyl-CoA carboxylase alpha subunit (AAV9-hPCCA) for propionic acidemia caused by PCCA deficiency, which received initial feedback from the Food and Drug Administration (FDA) in an INitial Targeted Engagement for Regulatory Advice on CBER/Center for Drug Evaluation and Research (CDER) ProducTs (INTERACT) meeting. Upon further product development that took into consideration the FDA's initial advice, the program obtained the Agency's feedback in pre-investigational new drug (IND) (Type B) and Type C meetings. Here, we share our experience from these meetings, including strategy, preparation, pre- and post-meeting feedback from the FDA, and lessons learned during the AAV9-hPCCA regulatory process, which the program plans to apply across the PaVe-GT platform. Topics discussed in the regulatory meetings included animal model and efficacy studies, toxicology study plans, manufacturing of the investigational AAV product, and clinical trial design. The main lessons learned from the pre-IND and Type C meetings for AAV9-hPCCA are: (1) Pharmacology/Toxicology studies in a single rodent species are sufficient for filing an initial IND; (2) FDA feedback guides product quality improvements and early development of a quantitative potency assay; (3) use of biomarkers as potential surrogate endpoints in a future efficacy trial benefits from collection of data in the natural history study and the first-in-human Phase 1/2 study; and (4) evidence from the Phase 1/2 clinical trial could be leveraged to support a license application. Lightly redacted regulatory documents and comprehensive templates developed by the PaVe-GT team are available on the PaVe-GT website.

Dependovirus↗

PubMed2026

Comparison of Adult Tracheostomy Outcomes Before and After Implementation of a Dedicated Tracheostomy Team.

OBJECTIVE: (A) Determine patient and institutional factors associated with increased length of stay (LOS) and complications of tracheostomy, (B) Develop data-driven quality improvement in tracheostomy care. DESIGN: Mixed methods protocol used cross-sectional survey assessing institutional trends in tracheostomy-specific care. Retrospective chart review compared tracheostomy patient outcomes prior to and during implementation of a multidisciplinary tracheostomy care team and standardized guidelines. PARTICIPANTS: Patients undergoing tracheostomy from January 2019 to December 2021 at a tertiary hospital. METHODS: Patient factors, procedure type and indication, tracheostomy tube size, management timeline, insurance, and disease severity using Acute Physiology and Chronic Health Evaluation II (APACHE II) score were analyzed for associations with LOS and adverse events. Multivariate analyses controlled for APACHE II score and payer source. LOS and complications were compared between patients before and during implementation of multidisciplinary tracheostomy care team and standardized guidelines. RESULTS: Three-hundred and eighteen patients met criteria with a 21.7% complication rate, average LOS of 24 days (SD = 28.523), and median LOS post-tracheostomy of 14 days (IQR 7, 29). Departments without standardized protocols had greater LOS (F[1,316] = 28.706, P < .001]) and complication odds (OR = 2.92, P = .015, 95% CI[1.231, 6.930]). Larger tracheostomy tube size was linked to increased LOS (β = .253, t(314) = 4.741, P < .001, 95% CI[4.137, 10.081]). Delays from ventilation discontinuation to cuffless tube exchange and decannulation correlated with increased LOS (β = .406, t(184) = 6.321, P < .001, 95% CI[.928, 1.771]); (β = .554, t(129) = 7.625, P < .001, 95% CI[1.008, 1.715]). When focusing on a single department, comparing 2019 patients to 2021 patients (pre- and post-guideline and care team), overall, LOS decreased from 33.08 to 30.83 days (P = .586). When excluding patients discharged on a ventilator, the 2019 group had average LOS of 37.938 days versus 33.41 days in 2021 (P = .344). CONCLUSIONS: Standardized tracheostomy care guidelines and multidisciplinary care teams are critical to improving institutional outcomes. Data-driven approaches to quality improvement ensure efficient and targeted methods to improving patient care. LEVEL OF EVIDENCE: 4.

Humans↗

PubMed2026

Naltrexone Is Superior to Placebo for Abstinence and Craving Reduction in Alcohol-Associated Cirrhosis: NAL-CI Trial.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) coexisting with cirrhosis carries high morbidity and mortality, with no approved pharmacotherapy for AUD. We evaluated the safety and efficacy of naltrexone, an opioid receptor antagonist, in patients with compensated alcohol-associated cirrhosis (AaC) and AUD. METHODS: One hundred patients with compensated AaC and DSM-5 AUD were randomised 1:1 to naltrexone (50 mg/day) or placebo for 12 weeks. The primary endpoint was point-prevalence abstinence at 12 weeks, defined as no alcohol use in the four preceding weeks. Secondary endpoints included craving (Obsessive Compulsive Drinking Scale [OCDS]-Obsessive and Compulsive subscales), lapses, relapses, and hepatic safety. Standardised psychosocial support was provided to both arms. RESULTS: Baseline characteristics were well matched between groups (mean MELD 12.6 vs. 12.7; CTP score 5.9 vs. 6.2; age 42.9 vs. 44.3 years). AUDIT and OCDS scores were comparable between groups. Abstinence at 12 weeks was significantly higher with naltrexone: 64% (32/50) versus 22% (11/50), p < 0.001; OR 10.86 (95% CI: 1.89-62.2). Naltrexone significantly reduced lapses at 3 months (28% vs. 54%, p = 0.008) and showed a trend toward fewer heavy-drinking relapses (12% vs. 28%, p = 0.07). Maintenance of abstinence at 6 months favoured naltrexone (22% vs. 8%, p = 0.09). No patient developed hepatic decompensation attributable to study medication, and no AST/ALT elevation exceeding 5× ULN was observed in either group. Mean craving scores were lower with naltrexone by week 12 than with placebo: OCDS-O score (6.63 ± 1.16 vs. 9.29 ± 1.78, p < 0.01) and OCDS-C score (6.35 ± 1.23 vs. 9.02 ± 1.86, p < 0.01). Adverse events were comparable between the groups. CONCLUSION: Naltrexone is safe and effective in patients with compensated alcohol-associated cirrhosis, achieving a threefold higher abstinence rate and significantly reducing craving compared with placebo. These findings support the use of naltrexone as a pharmacological option in patients with compensated AaC and AUD. TRIAL REGISTRATION: NCT04391764.

Humans↗

PubMed2026

Aneurysmal subarachnoid hemorrhage care in a middle-income public healthcare system: A real-world neurocritical care cohort.

BACKGROUND AND PURPOSE: Although aneurysm treatment capacity has expanded worldwide, outcomes after aneurysmal subarachnoid hemorrhage (aSAH) remain strongly influenced by neurocritical care (NCC) delivery, referral pathways, and access to specialized treatment. Contemporary data describing real-world aSAH care in resource-limited healthcare systems remain scarce. We aimed to characterize treatment patterns, NCC delivery, complications, and outcomes in a large Brazilian public referral center. METHODS: This retrospective cohort study included consecutive adults with confirmed aSAH admitted between June 2018 and March 2022 to a high-volume Brazilian tertiary referral center. Only patients admitted within five days of symptom onset were included. Demographic, clinical, radiological, treatment, complication, and outcome data were extracted from institutional records. Primary outcomes were in-hospital mortality and 3-month functional outcome assessed by the modified Rankin Scale (mRS). RESULTS: Seventy-four patients were included. Disease severity was high, with 45% presenting WFNS grades 4-5, 73% modified Fisher grade 4 hemorrhage, and 64% hydrocephalus. Endovascular treatment was performed in 73% of cases, and median time from admission to aneurysm treatment was 1 day. Despite early treatment capability, only 28% of patients were admitted to an ICU within 48 h, while 38% never received ICU care. Delayed cerebral ischemia occurred in 43%, radiologic vasospasm in 58%, ventriculitis in 22%, and infectious complications in 57%. External ventricular drainage was required in 42%, and vasoactive drugs were used in 85%. In-hospital mortality was 42%, and 66% had unfavorable 3-month outcomes (mRS 4-6). CONCLUSIONS: This real-world cohort highlights the substantial neurocritical care burden of aSAH in a middle-income public healthcare system. Despite timely access to definitive aneurysm treatment, patients experienced frequent neurological and systemic complications, emphasizing that contemporary aSAH care extends well beyond aneurysm occlusion.

Humans↗

PubMed2026

Effects of hospital planning reforms on access, costs, efficiency, and quality of care in OECD countries: Systematic review and meta-analysis.

BACKGROUND: Many OECD countries have implemented hospital planning reforms to rising healthcare costs, demographic changes, and concerns about access, efficiency, and quality of care. Despite broad implementation, evidence on effectiveness remains fragmented and country-specific. OBJECTIVE: To synthesize evidence on the effects of hospital planning reforms aross four outcome domains: access, costs, efficiency, and quality of care. METHODS: We conducted a systematic review following Cochrane methodology, searching PubMed and Web of Science (January 2000 - September 2025). Studies were categorized into four intervention types - centralization, minimum volume requirements (MVR), performance-based targets, and governance and ownership restructuring. Risk of bias was assessed using Joanna Briggs Institute checklist for quasi-experimental designs. Where data permitted, random-effects meta-analyses pooled standardized mean differences (SMD) for access and efficiency and risk differences (RD) for quality outcomes. RESULTS: 26 studies from 12 countries were included. Centralization increased patient travel distances and reduced length of stay (SMD -0.09, 95% CI -0.17 to -0.01) and complications (RD -14.52 pp, -25.95 to -3.09), and, jointly with performance-based targets, 30-day readmissions (RD -0.43 pp, -0.65 to -0.22). Mortality effects varied by timepoint and intervention: short-term endpoints were largely non-significant, whereas 90-day mortality was reduced under centralization (RD -0.80 pp, -1.25 to -0.35) and 60-day mortality under MVR (RD -2.00 pp, -2.82 to -1.18). Survival was non-significant throughout. No study examined costs. CONCLUSION: The absence of cost evidence is a critical gap. Substantial heterogeneity reflects variation in reform design and context, underscoring the need to interpret findings by intervention and country conditions.

Humans↗