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PubMed2026

Transcriptomic changes in the gut mucosa of fasting northern elephant seal pups reveal immune modulation during early microbiome establishment.

Fasting is an integral component of the life-history of many species. Following abrupt weaning, northern elephant seal pups (Mirounga angustirostris) undergo an extended post-weaning fast of approximately 60 days. During this period, enteric bacterial diversity increases, suggesting that host immune regulation may facilitate the establishment of microbial communities. However, the molecular processes occurring within the intestinal mucosa during this transition remain poorly understood. To investigate these mechanisms, we characterized transcriptional changes in the enteric mucosa of male and female northern elephant seal pups sampled at weaning and after one month of fasting. Total RNA isolated from rectal swabs was sequenced and aligned to the Mirounga angustirostris reference genome. Differential gene expression and gene set enrichment analyses were used to identify genes and pathways associated with fasting and sex-specific responses. Fasting was accompanied primarily by transcriptional downregulation, including genes involved in antimicrobial defense, inflammation, protein turnover, and epithelial remodeling. In contrast, several genes associated with B-cell activity and immune recognition were upregulated. Gene Set Enrichment Analysis revealed coordinated activation of immune-regulatory pathways indicating dynamic modulation of intestinal immunity rather than generalized immune suppression. Pronounced sex-specific differences were also observed. Male pups exhibited transcriptional patterns consistent with enhanced immune tolerance, whereas females showed broader immune-pathway activation, including enrichment of pro-inflammatory and stress-response pathways. Several non-coding RNAs also displayed sex-specific changes in expression. Together, these findings suggest that fasting induces transcriptional remodeling of the gut and may contribute to immune regulation during a critical period of microbiome establishment in northern elephant seal pups.

Animals↗

PubMed2026

Randomized phase-II trial of surufatinib plus FOLFOX/FOLFIRI versus FOLFOXIRI as second-line therapy for metastatic colorectal cancer.

BACKGROUND: Second-line treatment for metastatic colorectal cancer (mCRC) typically involves oxaliplatin- or irinotecan-based doublet chemotherapy with or without anti-angiogenic antibodies. Triplet regimens such as FOLFOXIRI have demonstrated synergy and improved efficacy as first-line therapy. Surufatinib, an oral multi-kinase inhibitor targeting VEGFR1-3, FGFR1, and CSF-1R, may enhance chemotherapy efficacy. We evaluated surufatinib combined with doublet (FOLFOX/FOLFIRI) versus triplet (FOLFOXIRI) chemotherapy as second-line treatment for mCRC. PATIENTS AND METHODS: This multicentre, open-label, randomized phase-II trial used Simon's minimax two-stage design. Eligible patients had mCRC progressing on or within 6 months after first-line doublet chemotherapy. Patients were randomized 1:1 to surufatinib 250 mg once daily plus either mFOLFOX6/FOLFIRI (doublet cohort, selected based on prior regimen) or FOLFOXIRI (triplet cohort). The primary endpoint was objective response rate (ORR). RESULTS: From September 2021 to November 2023, 57 patients were randomized (28 per cohort after one withdrawal). In the doublet cohort, ORR was 35.7% (95% CI: 18.6-55.9), median progression-free survival (PFS) was 5.4 months (95% CI: 3.8-7.0), and median overall survival (OS) was 19.0 months (95% CI: 9.2-28.8). In the triplet cohort, ORR was 39.3% (95% CI: 21.5-59.4), median PFS was 5.8 months (95% CI: 3.3-8.2), and median OS was 10.9 months (95% CI: 6.0-15.8). Grade ≥3 treatment-emergent adverse events occurred more frequently in the triplet (71.4%) versus doublet (57.1%) cohort, with higher rates of treatment delays (89.3% versus 72.0%) and discontinuations (25.0% versus 14.3%). CONCLUSIONS: Surufatinib plus doublet chemotherapy showed encouraging antitumor activity and acceptable tolerability in second-line mCRC, warranting further evaluation in a larger randomized trial. In contrast, surufatinib plus triplet chemotherapy was associated with increased toxicity, more frequent treatment delays or discontinuations, and shorter overall survival; this combination is not recommended for further investigation in this setting.ClinicalTrials.gov: NCT04734249Date of registration: January 31, 2021.

Humans↗

PubMed2026

In Vitro comparison of herbal and conventional antifungals against Candida strains in Oral candidiasis: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to systematically review and meta-analyze the in vitro antifungal activity of herbal and conventional antifungals against Candida strains. DESIGN: In vitro studies were identified through PubMed, Embase, Scopus, and Web of Science up until May 2026. This review is registered with Prospero (CRD420251128404). Eligibility was determined using the Population, Intervention, Comparison, and Outcome (PICO) framework, with specific inclusion and exclusion criteria focused on in vitro antifungal investigations comparing herbal antifungals with conventional antifungals. The risk of bias was assessed using the modified Quality Assessment Tool for In Vitro Studies (QUIN Tool). A meta-analysis was performed, with the primary outcome measure being the ratio of means (RoM). RESULTS: The systematic review included twenty-five articles. Most studies showed different results in inhibition zones or minimum inhibitory concentrations between herbal and conventional agents. The meta-analysis indicates that certain herbal antifungals are equally effective as or more effective than conventional antifungals against Candida dubliniensis, Candida lusitaniae, and Candida tropicalis. While the efficacy of herbal antifungals for Candida albicans and Candida glabrata was modest, Piper betle L. demonstrated significant inhibitory potential. In contrast, conventional antifungals outperformed herbal antifungals against Candida krusei and Candida parapsilosis. CONCLUSIONS: This systematic review and meta-analysis highlight herbal medicine as a potential antifungal therapy for oral candidiasis, emphasizing the need for new strategies due to resistance to conventional antifungals.

Humans↗

PubMed2026

A review into the recent advances in the world of amoebiasis.

PURPOSE OF REVIEW: Amoebiasis is a parasitic infection caused by Entamoeba histolytica , affecting 10% of the global population. It is a well recognized cause of morbidity and mortality in low-middle-income countries where it is endemic. However, with increased migration and global travel, amoebiasis is now more common in high-income countries, although diagnosis is often delayed or even missed due to lack of awareness of the latest epidemiology and optimal diagnostic testing. This review discusses the evolving prevalence, and the current international guidelines for the investigation and treatment of amoebiasis, focusing on recent advances. RECENT FINDINGS: The recent literature shows that the primary investigations for amoebiasis remain the same, though newer modalities such as artificial intelligence-powered microscopy and metagenomics have been developed recently, which aids the accuracy and speed of diagnosis. Treatment remains the same, though current research has found potential new drugs and drug targets which show promise. SUMMARY: This review reinforces the importance of early clinical suspicion, diagnosis and treatment for amoebiasis. What was once a disease only seen in endemic countries or travel-associated imported cases is now more common and must not be missed.

Humans↗

PubMed2026

Artificial intelligence for anticancer drug discovery from natural products of macroalgae and sponges: A systematic review.

Marine natural products (MNPs) from macroalgae and marine sponges have inspired clinically important anticancer agents, including the cytarabine pharmacophore and the eribulin scaffold, while cyanobacterial dolastatin chemistry supplies the auristatin payloads of several marine-inspired antibody-drug conjugates (ADCs) such as brentuximab vedotin. Artificial intelligence (AI) methods, encompassing both classical machine learning (ML) with hand-engineered features and modern deep learning (DL) with many-layered neural networks, are increasingly supporting key decisions in natural-product anticancer drug discovery, including bioactivity prediction, target identification, absorption, distribution, metabolism, excretion and toxicity (ADMET) filtering, generative analogue design, and the selection of preclinical candidates. DL architectures relevant to this field include graph neural networks, transformer-based molecular generators, diffusion models for protein-ligand docking, and convolutional networks for mass spectrometry, while classical ML contributes interpretable fingerprint-based bioactivity models and molecular networking for dereplication. This review follows a systematic literature review methodology to organize the landscape of AI methods now applied to MNP anticancer discovery, distinguishing ML and DL approaches where relevant, situating them within the chemical context of macroalgal and sponge-derived oncology leads, and critically examining published case studies, including validation level (computational, in vitro, in vivo, clinical). The principal bottleneck for medical translation has shifted partly from algorithmic capability toward data infrastructure and experimental validation. Sparse, heterogeneous, and taxonomically biased bioactivity records limit what current models can learn and reduce the reliability of AI-prioritized candidates entering the preclinical pipeline. A roadmap is proposed that prioritizes open MNP-specific benchmarks, symbiont-aware modeling, and active learning loops with synthesizability and ADMET constraints. These AI workflows may accelerate the prioritization of marine-derived anticancer leads and support earlier, more evidence-based translational decisions in oncology drug development.

Biological Products↗

PubMed2026

Outcomes of patients with myelofibrosis treated with ruxolitinib and anemia-supporting medications.

OBJECTIVE: This post hoc analysis of the phase 3b JUMP trial evaluated addition of anemia-supporting medications to ruxolitinib in patients with myelofibrosis and anemia. METHODS: 101 patients with baseline hemoglobin <12.0 g/dL initiated an erythropoiesis-stimulating agent (ESA) or danazol <3 months post-enrollment and maintained ESA/danazol ≥3 months; 97% initiated ESAs. Patients enrolled in JUMP who had hemoglobin <12.0 g/dL but did not initiate ESAs/danazol within 3 months were evaluated as an unmatched comparator. Total JUMP population data were also analyzed for spleen length (≥50% reduction from baseline) and symptom response (≥6.5-point improvement in FACT-Lym score). RESULTS: Baseline characteristics were similar to comparator JUMP patients (no ESAs/danazol within 3 months, n = 1242). Mean total daily ruxolitinib dose remained >25 mg. Week 24 spleen length response was achieved by 37% of patients; 26% achieved symptom response, similar to the comparator population (28% and 26%, respectively) and comparable to the total JUMP population (N = 2233). Outcomes were similar between the hemoglobin <12.0 g/dL analysis population and patients with baseline hemoglobin <10.0 g/dL (n = 52). In all groups, hemoglobin levels increased after Week 4 following an expected initial decrease. DISCUSSION: This analysis suggests that patients treated with ruxolitinib and anemia-supporting care continued to receive optimal ruxolitinib dosing; spleen-length and symptom response rates in these patients were comparable to the overall JUMP population, the majority of whom did not have anemia. CONCLUSION: Results support use of anemia-supporting medications with ruxolitinib and may allow maintenance of ruxolitinib dose intensity in patients with myelofibrosis and anemia.

Humans↗

PubMed2026

Chemical and sensory profiling of fermented, washed, and artificially flavored coffee beans: Insights into flavour quality, authenticity, and food safety implications.

This study establishes an integrated framework combining chemical profiling, sensory analysis, and molecular mechanism evaluation to compare flavour quality and authenticity among fermented, washed, and artificially flavored coffees. GC × GC-TOF-MS and UHPLC-HRMS showed that fermented samples had markedly higher ester and aromatic alcohol levels (total esters 74.5 ± 7.8 mg kg-1; phenylethanol 27.5 ± 3.2 mg kg-1, p < 0.01), enhancing fruity-floral notes. Washed coffees contained the highest organic acid concentrations (45.2 ± 3.8 mg kg-1, p < 0.01), supporting brightness and umami. Artificially flavored coffees exhibited elevated exogenous aromatics (vanillin 21.5 ± 3.1 mg kg-1) but significantly fewer Maillard products (p < 0.05) and reduced flavour retention (55% after 14 days). Molecular docking revealed higher theoretical binding affinities for naturally generated compounds, suggesting a potential molecular basis for their greater sensory persistence. The framework supports constructing coffee quality fingerprints and verifying flavour authenticity.

Flavoring Agents↗

PubMed2026

Efficacy, acceptability, and related outcomes of pharmacological interventions for acute bipolar mania: a systematic review and dose-related network meta-analysis across different age groups.

BACKGROUND: Acute bipolar mania carries negative social and economic consequences. We investigated the comparative efficacy/response/acceptability of pharmacological interventions for acute bipolar mania, considering dose effects across different age groups. METHODS: We conducted a network meta-analysis (NMA) to search for randomized controlled trials (RCTs) comparing pharmacological interventions with one another or placebo in acute bipolar mania patients, indexed in PubMed/MEDLINE, Embase, Web of Science, and Scopus (from inception through 2025.12.24). Co-primary outcomes were change in manic symptoms/response/and acceptability. Tolerability/remission and rate of adverse events were secondary outcomes. Confidence-In-Network-Meta-Analysis was likewise appraised. RESULTS: 113 RCTs, encompassing 49 distinct treatment combinations, included 20,666 participants. Sensitivity analysis retaining only low-risk-of-bias studies and excluding outliers for possible effect modifiers indicated that risperidone 3 mg/day(SMD = -7.57;95%C.I. = -8.25;-5.85); tamoxifen 160 mg/day(SMD = -1.73;95%C.I. = -2.32;-1.13); rivastigmine 3 mg/day(SMD = -1.13;95%C.I. = -1.06;-0.58); haloperidol 30 mg/day(SMD = -0.96;95%C.I. = -1.25;-0.75); valproate 750 mg/day(SMD = -0.76;95%C.I. = -1.48;-0.58); tamoxifen 40 mg/day(SMD = -0.75;95%C.I. = -1.41;-0.59); celecoxib 400 mg/day(SMD = -0.74;95%C.I. = -1.20;-0.38); paliperidone extended-release 12 mg/day(SMD = -0.62; 95%C.I. = -0.91;-0.32); olanzapine 15 mg/day(SMD = -0.59;95%C.I. = -0.60;-0.38); olanzapine 20 mg/day(SMD = -0.52;95%C.I. = -0.66;-0.38); risperidone 4 mg/day(SMD = -0.53;95%C.I. = -0.76;-0.29); allopurinol 600 mg/day(SMD = -0.54;95%C.I. = -0.67;-0.22); cariprazine 12 mg/day(SMD = -0.49;95%C.I. = -0.66;-0.33); risperidone 4.2 mg/day(SMD = -0.46;95%C.I. = -0.75;-0.17); lithium 1500 mg/day(SMD = -0.42;95%C.I. = -0.57;-0.28); ziprasidone 160 mg/day(SMD = -0.49;95%C.I. = -0.68;-0.31); asenapine 20 mg/day(SMD = -0.38;95%C.I. = -0.53;-0.22); haloperidol 8 mg/day(SMD = -0.34;95%C.I. = -0.63;-0.05); aripiprazole 15 mg/day(SMD = -0.33;95%C.I. = -0.61;-0.06) outperformed placebo. Ziprasidone 160 mg/day, celecoxib 200 mg/day, asenapine 20 mg/day, and asenapine 10 mg/day proved more efficacious than placebo in children. No statistically significant differences were reported between treatments and placebo for response/remission/acceptability/tolerability, and manic/hypomanic switch. A meta-regression of efficacy effect sizes against the adapted AMSTAR-Plus content scores showed that larger SMDs were associated with lower AMSTAR scores, indicating lower study quality, warranting further caution for such large efficacy estimates. CONCLUSIONS: Our findings are consistent with previous NMAs and current guidelines, expanding the current knowledge base while concurrently appraising different drugs, doses, and age groups.

Humans↗

PubMed2026

Closed-loop insulin delivery for glycaemic control in hospitalised and perioperative adults: A systematic review and meta-analysis of randomised controlled trials.

We evaluated whether closed-loop insulin delivery improves glycaemic control in hospitalised and perioperative adults. PubMed/MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched from inception to 29 June 2026 for randomised controlled trials comparing closed-loop or automated insulin delivery with usual care or conventional insulin therapy. Random-effects meta-analyses were conducted; risk of bias was assessed using RoB 2 and certainty of evidence using GRADE. Seven trials involving 375 analysed participants were included. Closed-loop insulin delivery increased time in target glucose range by 23.91 percentage points (95% CI 19.40 to 28.43; I2 = 0%) and reduced mean glucose by 1.79 mmol/L (95% CI 1.06 to 2.53 lower; I2 = 36.3%); certainty was moderate for both outcomes. Two trials involving 69 participants reported compatible participant-level data for clinically significant hyperglycaemia, and both estimates favoured closed-loop insulin delivery, although the evidence was exploratory and imprecise. No severe hypoglycaemic events occurred in either group, precluding reliable estimation of comparative safety. Closed-loop insulin delivery may improve glycaemic process measures, but larger pragmatic trials are needed to establish clinical benefits, safety, and implementation feasibility.

Humans↗

PubMed2026

A 12-week, double-blind, quasi-randomized, placebo-controlled study to evaluate the efficacy and safety of Coleus forskohlii (Forcslim) on body weight loss.

BACKGROUND: Overweight and obesity have emerged as a global epidemic, significantly impacting human health. Traditional usage and growing scientific evidence suggest that Coleus forskohlii extract (Forcslim) may aid in reducing excess body weight and fat. This study aimed to evaluate the efficacy and safety of Forcslim supplementation in overweight individuals. METHODS: A quasi-randomized, double-blind, placebo-controlled clinical trial was conducted in 60 overweight subjects aged 20-70 years over a period of 12 weeks. The participants were assigned to receive either Forcslim or placebo. The key outcome measures included body weight, body mass index (BMI), body composition, and anthropometric parameters. Additionally, lipid profile parameters and safety markers (including metabolic, hepatic, and cardiovascular indicators) were assessed throughout the study duration. RESULTS: Compared to the placebo group, the Forcslim group showed significant reductions in waist circumference (-1.83 cm; p < 0.01) and body weight (-1.93 kg; p < 0.001). Significant improvements in anthropometric parameters were observed exclusively in the Forcslim group. Furthermore, triglyceride (TG) levels were significantly reduced (p < 0.01), while high-density lipoprotein (HDL) levels showed a significant increase (p = 0.001). No clinically significant changes were observed in metabolic markers, liver and muscle enzyme levels, heart rate, blood pressure, or reported adverse effects, indicating a favorable safety profile. CONCLUSIONS: Forcslim demonstrated significant anti-obesity effects, including reductions in body weight, waist circumference, and improvements in the lipid profile. These findings suggest that C. forskohlii extract supplementation may serve as a safe and effective alternative to synthetic anti-obesity drugs.

Humans↗

PubMed2026

Efficacy of afoxolaner (NexGard®) for the treatment of myiasis caused by the zoonotic tumbu fly, Cordylobia anthropophaga, in domestic dogs under field conditions.

Cordylobia anthropophaga is a major cause of furuncular myiasis in dogs and humans in sub-Saharan Africa, yet evidence for pharmacological control remains limited. Current management relies mainly on mechanical larval removal, and no controlled studies have assessed the efficacy of modern antiparasitic agents. This study evaluated the curative and preventive efficacy of a single dose of afoxolaner (NexGard®) in dogs with naturally acquired C. anthropophaga infestation under field conditions and explored a possible indirect protective effect in puppies after maternal treatment. A randomized, blinded, negative-controlled field study was conducted in Samburu County, Kenya, and included 104 naturally infested dogs allocated to a treated group (n = 53) or an untreated control group (n = 51). Clinical evaluations were performed on Days 0, 15 (±2), 30 (±2), and 45 (±2). Efficacy was assessed based on the presence of active nodules and clinical scores. Additional observational data were collected from puppies born to or nursing from treated bitches. Compared to the control group, parasiticide efficacy was 94% on Day 15 and 100% on Day 30. The number of parasite-free dogs reached 86.3% on Day 15, 100% on Day 30, and 95.3% on Day 45. Treated dogs showed a significant clinical improvement from the first post-treatment assessment, whereas infestation persisted in controls (nodules: OR = 0.003, 95% CI 0.001-0.017; skin lesions: OR = 0.010, 95% CI 0.002-0.051; lymph node: OR = 0.013, 95% CI 0.002-0.074; body condition: OR = 0.073, 95% CI 0.027-0.195; all p < .001), with large effect sizes at the final visit for all outcomes (r = 0.521-0.793). No C. anthropophaga infestations were detected in examined puppies from treated dams, including puppies exposed during pregnancy or lactation, up to 4 weeks after birth and up to 11 weeks of age, respectively. Afoxolaner appears effective to control canine cordylobiosis and may offer indirect protection to puppies, warranting further investigation.

Animals↗

PubMed2026

Effects of H-coil TMS on suicidality in major depression: A secondary analysis of data from a multisite randomized trial comparing accelerated to once-a-day stimulation.

Suicide is the 10th leading cause of death in US adults. Standard once-daily repetitive transcranial magnetic stimulation (rTMS) can reduce suicidal ideation. Yet, antidepressant and anti-suicidal effects often take several weeks to emerge, while rapid improvement is often required. Accelerated TMS has been proposed as a strategy to hasten therapeutic response. A recent FDA-regulated multicenter trial evaluated accelerated intermittent theta burst Deep TMS with the H1-coil versus standard high-frequency Deep TMS in MDD. Both groups demonstrated high remission and response rates for depression, with the accelerated protocol showing non-inferiority and a shorter time to remission. The goal of this exploratory secondary analysis was to evaluate the impact of these two H-coil TMS dosing paradigms on suicidal ideation. The Scale for Suicide Ideation (SSI), as well as suicidality items of HDRS, MADRS and CUDOS were collected and analyzed. On all scales, both accelerated and standard Deep TMS protocols were associated with meaningful reductions in suicidality. The accelerated protocol achieved a faster onset of improvement. Comparison between the timeline of improvement in suicidality and in overall depressive symptoms found a trend for faster improvement in suicidality, especially with the accelerated protocol. These findings highlight the importance of treatment frequency in determining time to clinical benefit and support the use of scalable accelerated protocols for patients requiring more rapid symptom relief.

Humans↗

PubMed2026

Examining early-phase symptom trajectories in interpersonal psychotherapy versus antidepressant medication for adults with depression: A dynamic time warp network analysis.

BACKGROUND: Depression is characterized by substantial symptom heterogeneity, which is often concealed when examining total severity scores. Analyzing symptom-level change can improve our understanding of treatment effects and recovery processes. This study, therefore, examined dynamic symptom networks during early-phase interpersonal psychotherapy (IPT) and selective serotonin reuptake inhibitor (SSRI) antidepressant treatment, assessing patterns of symptom change across as well as differences between treatments. METHODS: Using weekly item-level Hamilton Depression Rating Scale (HAM-D) data from a randomized clinical trial comparing IPT and SSRIs for adults with depression, this preregistered study examined symptom trajectories in the first six weeks of treatment with Dynamic Time Warping (DTW). RESULTS: Depressive symptom trajectories and DTW-based symptom networks were largely similar for IPT and SSRI. In both conditions, changes in somatic symptoms of anxiety and middle insomnia tended to precede improvements in depressed mood. CONCLUSIONS: Early symptom change may occur outside the core affective domain, underscoring the importance of monitoring symptoms broadly. Symptom-level patterns may reflect patients' stage of recovery and provide clinically relevant information beyond total severity scores. The absence of differences in improvement patterns between IPT and SSRI suggest few indications for treatment selection based on baseline symptom profiles. Future research should replicate and extend these findings to subsequent treatment phases using more frequent assessments and a broader range of interventions.

Humans↗

PubMed2026

Autophagy activation in granulosa cells as a mechanism of astaxanthin action: evidence from a pilot randomised trial in PMOS-associated infertility.

Astaxanthin (AST) has been reported to influence oxidative stress, endoplasmic reticulum stress, and apoptosis in women with polyendocrine metabolic ovarian syndrome (PMOS), formerly referred to as polycystic ovary syndrome (PCOS), but its effects on granulosa-cell (GC) autophagy remain unclear. Given the central role of autophagy in follicular development, this triple-blind, placebo-controlled pilot randomised trial evaluated whether AST modulates autophagy-related signalling in GCs and how these molecular effects relate to ovarian response. Fifty women with PMOS-related anovulatory infertility were enrolled between November 2023 and September 2024 and received AST (12 mg/day) or placebo for six weeks prior to oocyte retrieval; forty-four completed the study (21 AST, 23 placebo). Primary exploratory endpoints were molecular markers of adenosine monophosphate-activated protein kinase (AMPK)-autophagy signalling, and primary clinical outcomes included ovarian response indicators and cleavage stage embryo quality. AST supplementation increased autophagy-related gene 7 (ATG7) expression, enhanced autophagy flux, reduced apoptosis, and showed a trend toward increased AMPK activation. Before adjustment, AST improved oocyte maturity rate (OMR) and increased mature (metaphase II; MII) oocyte yield. After adjusting for age, body mass index, and anti-mullerian hormone level, total oocyte and MII oocyte yields remained significantly higher with AST, while OMR became non-significant. Among embryology outcomes, both the top-ranking embryo rate and the number of embryos suitable for cryopreservation were significantly higher with AST after adjustment. Pregnancy outcomes were numerically higher but not statistically significant. This pilot trial suggests that AST activates autophagy- and apoptosis-related pathways in GCs and may enhance oocyte competence and embryo quality in PMOS. Larger studies are needed to confirm these mechanistic and clinical effects.

Female↗

PubMed2026

Glycemic and safety outcomes of the insulin-only bionic pancreas in older adults and individuals with impaired awareness of Hypoglycemia: a post hoc analysis of a randomized pivotal trial.

AIMS: Evaluate the efficacy and safety of iLet Bionic Pancreas (BP) in older adults and individuals with impaired awareness of hypoglycemia (IAH). METHODS: This post hoc analysis used individual participant-level data from the Insulin-Only Bionic Pancreas Pivotal Trial (n = 440; NCT04200313). Eligible participants (n = 96) with type 1 diabetes, aged ≥ 60 years and/or had IAH (Clarke score ≥ 4), were randomized to BP with aspart/lispro (BP-Asp/Lis; n = 45), BP with fast-acting aspart configuration (BP-Fiasp; n = 31), or standard care (SC; n = 20) for 13 weeks. RESULTS: Compared with SC, time-in-range (70-180 mg/dL) significantly increased by 7.49 % (95 % CI: 2.61 to 12.38; ∼1.8 h/day) with BP-Asp/Lis and by 8.28 % (95 % CI: 3.15 to 13.41; ∼2.0 h/day) with BP-Fiasp, driven by reduced hyperglycemia. No significant differences were observed in hypoglycemia exposure. Severe hypoglycemia occurred in four participants (four events) on BP-Asp/Lis and one participant (two events) on SC. One diabetic ketoacidosis event occurred on BP-Fiasp due to an infusion set failure. CONCLUSIONS: In high-risk, clinically vulnerable populations, the BP system significantly improved glycemic control while maintaining safety parity with respect to hypoglycemia risk, providing a resilient therapeutic alternative for vulnerable cohorts.

Humans↗

PubMed2026

Single-slice Functional Lung MRI During Metronome-Paced Tachypnea Detects Changes in Regional Ventilation Dynamics After a Single Dose of Dual Bronchodilator Treatment in COPD.

Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p < 0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p < 0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.

Humans↗

PubMed2026

Safety of early discharge and abbreviated nimodipine course in patients with good-grade aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating cerebrovascular emergency associated with substantial morbidity and mortality. Current guidelines recommend 14-21 days of inpatient monitoring and a 21-day course of nimodipine following aSAH. This retrospective study evaluates early outcomes early discharge (≤14 days post-ictus) and an abbreviated nimodipine course in highly selected patients with good-grade aSAH managed under a standardized institutional protocol. Consecutive patients enrolled in the Vancouver Ruptured Aneurysm Database (VRAD) at Vancouver General Hospital between 2022 and 2025 were included. Inclusion criteria were good-grade aSAH (WFNS Grade I-III) and discharge home within 14 days of ictus. The primary outcome was re-presentation to emergency care within 30 days of discharge; secondary outcomes included hospital readmission and need for additional treatment. Of 333 total patients in VRAD, 49 patients met inclusion criteria. All patients received ≤ 14 days of nimodipine therapy. Forty-two patients (85.7%) were WFNS Grade I on presentation, 3 (6.1%) were WFNS Grade II, and 4 (8.2%) were WFNS Grade III. Radiographic vasospasm was reported in 18 cases (36.7%). No patients developed DCI or clinical vasospasm. Four patients (8.2%) re-presented to emergency care within 30 days of discharge, and only one patient (2%) required hospital re-admission within 30 days. While radiographic vasospasm was seen in over one third of patients, none developed clinical sequelae, supporting the premise that radiographic vasospasm alone may be insufficient to preclude early discharge in select good-grade patients.

Humans↗

PubMed2026

Skin cell suspension autograft as an evidence-based innovation in burn and wound treatment: A systematic review of global evidence across two decades.

BACKGROUND: Skin cell suspension autograft (SCSA) is a point-of-care approach to wound management facilitating epithelialization while reducing burden associated with conventional autografting. Despite growing clinical use of SCSA across diverse wound etiologies, the global clinical evidence describing its use has not yet been comprehensively synthesized. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines to identify studies between January 2000 and December 2024 reporting clinical use of SCSA for wound closure. Data on patient demographics, wound characteristics, and treatment methods were extracted. Clinical, safety, and health economic outcomes were extracted for comparative studies evaluating SCSA against control treatments. RESULTS: Ninety-nine studies across 13 countries were included. Across the overall dataset, SCSA was used alone or in combination with autografting for burns, surgical wounds, traumatic injuries, inflammatory conditions, and chronic wounds. Among comparative studies (n=27), SCSA consistently reduced donor skin, and healing outcomes favored SCSA in 61%, while 39% reported equivalent outcomes. Pain and esthetic outcomes more frequently favored SCSA, while safety outcomes were generally similar, with some studies favoring comparators. Health-economic outcomes suggested potential reductions in length of stay and resource utilization, although findings were variable across studies. CONCLUSION: The available global evidence supports SCSA as a versatile modality for supporting epidermal coverage across wound types and clinical contexts. However, the findings should be interpreted in the context of the limitations of this review, which include heterogenous study designs, variable outcome reporting, predominance of non-randomized data, and the absence of a formal quantitative analysis. Nevertheless, the demonstrated clinical and economic benefits in comparative studies reinforce the role of SCSA as an evidence-based innovation for burn and wound treatment.

Humans↗