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PubMed2026

Infra-low-frequency neurofeedback alters EEG network efficiency: exploratory evidence from healthy volunteers.

Infra-Low-Frequency Neurofeedback (ILF-NFB) combines classic frequency-band (FB) and infra-low-frequency (ILF) EEG components in implicit training protocols and is increasingly applied in clinical contexts. Yet, the neurophysiological mechanisms underlying ILF-NFB remain to be further elucidated. In this randomized, sham-controlled and double-blind study, we explored the online impact of a one-session ILF-NFB application on EEG correlates in healthy participants (39 analyzed datasets). Continuous 31-channel EEG was recorded during verum and sham feedback in a double-blind, randomized crossover design. In this exploratory analysis approach, functional connectivity was estimated using the debiased weighted phase-lag index (dwPLI) and analyzed with graph-theoretical measures. The results revealed higher global efficiency during verum compared to sham in the Beta1 band (12-15 Hz), reaching significance in the primary comparison but not surviving Bonferroni correction across the five tested bands; block-wise follow-ups showed a significant verum-sham difference in the first half of the neurofeedback session and a directionally consistent pattern in the second half. The Condition × Block interaction was not significant. No consistent differences were observed in other frequency bands, nor for betweenness centrality. While preliminary, these exploratory results point to possible network-level effects during ILF-NFB and motivate further confirmatory work in extended training protocols and clinical populations.

Humans↗

PubMed2026

Plasma proteomics: considerations for preanalytical variability; a systematic review with narrative synthesis.

BACKGROUND: The plasma proteome (PP) is a dynamic system subject to pathology-associated changes and a focus for novel disease biomarker discovery. Disease-related PP research assumes protein concentrations in test specimens accurately reflect the in vivo milieu. However, measures to maintain the physicochemical integrity of the proteome before assay are often rudimentary, poorly described, or lacking standardisation in published studies. Contrastingly, in laboratory medicine, there is an expectation that errors in the so-called "preanalytical phase" (PAP) that impact patient results are understood, monitored, and mitigated against, while also being well described in research publications. There is therefore scope for good practice from laboratory medicine to inform PP research workflows. This review considers factors in the PAP which may impact the validity of PP results. CONTENT: A systematic review was conducted per PRISMA guidelines, limited to English-language peer-reviewed studies (2014-2024). Candidate studies were imported, screened, and managed using Covidence systematic review software. SUMMARY: 15 eligible studies were reviewed, covering many relevant processes. 11 studies reported statistically significant differences in PP due to factors in the PAP. Temperature and time-to-processing were the most commonly reported factors affecting the PP, with significant effects reported in 8 studies. OUTLOOK: PAP variability can significantly affect results in PP studies. Careful consideration of the effect of each stage of the PAP is needed when working with the PP. In multicenter studies, pre-defined and research question-specific sample processing workflows are essential for reducing PAP variability, which helps ensure the validity of PP studies.

Humans↗

PubMed2026

Safety, Pharmacokinetics, and Pharmacodynamics of Single-Dose Programmed Cell Death Protein 1 Inhibitor, Budigalimab, in People With HIV-1 With Antiretroviral Therapy-Suppressed Viral Load.

BACKGROUND: Blockade of inhibitory immune checkpoint receptor programmed cell death protein 1 (PD-1) on target immune cells is associated with improved HIV-specific immune function and activation of latent HIV. This randomized, placebo-controlled, Phase 1b study assessed low doses of investigational anti-PD-1 monoclonal antibody, budigalimab, for safety, tolerability, pharmacokinetics, and pharmacodynamics in people with HIV (PWH) on antiretroviral therapy. METHODS: Participants received single doses of budigalimab 10 mg subcutaneous (SC), 20 mg SC, 10 mg intravenous (IV), or placebo (n = 8 per arm) and were followed for 24 weeks. RESULTS: Of 32 randomized participants, 22 reported adverse event(s) (AE); most (n = 19) were grade ≤2 and no grade ≥4 AE or treatment-related serious AE. Two participants reported a non-treatment-related grade 3 AE (placebo, n = 1 pneumonia; 10 mg IV, n = 1 elevated aspartate aminotransferase). One reversible immune-related AE (grade 2 lichenoid keratosis) was reported (20 mg SC). Geometric mean maximum serum concentrations were 0.37, 1.57, and 3.2 µg/mL with 10 mg SC, 20 mg SC, and 10 mg IV, respectively. Drug exposure with 20 versus 10 mg SC dosing was more than dose proportional and less variable. Subcutaneous bioavailability was approximately 53%-62%. The PD-1 receptor saturation was ≥95% in most participants (median duration: 20 mg SC, 42 days; 10 mg SC, 14 days; 10 mg IV, 35 days). CONCLUSIONS: Findings suggest an acceptable safety profile for single-dose budigalimab in PWH, with a favorable pharmacokinetic profile for 20 mg SC and 10 mg IV. Further evaluation as a potential component of an HIV treatment is underway.

Humans↗

PubMed2026

Descemet Stripping Only in Fuchs Endothelial Corneal Dystrophy: Results of a Randomized Clinical Trial of Topical Ripasudil and Directions for Future Innovation.

PURPOSE: To review history of Descemet stripping only (DSO) in Fuchs endothelial corneal dystrophy, describe the results of a clinical trial of topical ripasudil after DSO (K-321-201 study), and discuss future directions. METHODS: A 1-year, phase 2, randomized, placebo-controlled multicenter clinical trial of two doses of K-321 (ripasudil) administered for 12 weeks after DSO surgery in Fuchs endothelial corneal dystrophy was performed. The primary endpoint, central corneal endothelial cell density (ECD) at 12 weeks after surgery, was determined by an independent reading center that was masked to study group assignment. Duration of corneal edema, need for medical or surgical rescue therapy, corneal thickness, and central ECD throughout the entire study period were also examined. Adverse events and exploratory endpoints were collected. RESULTS: Sixty-five subjects were enrolled (21 in the QID group, 22 in the BID, and in the placebo group). Over 95% of subjects completed the trial. The QID group had a higher central ECD 12 weeks after DSO than the placebo group (531 ± 312 cells/mm2 vs 228 ± 298 cells/mm2, P = .0065). Corneal edema cleared in 17/21 (81.0%) of the QID group at 12 weeks, compared with 2/22 (9.1%) of the placebo group (P < .0001). Rescue was required in 2/21 (9.5%) subjects in the QID group and 6/22 (27.3%) subjects in the placebo group (P = .0092). Adverse events were mild and did not lead to discontinuation of treatment. CONCLUSIONS: Topical K-321 given QID improves DSO outcomes, as demonstrated by a higher ECD, more rapid resolution of corneal edema, and reduced failure rate. The medication was well-tolerated.

Humans↗

PubMed2026

Efficacy and Safety Profile of a Triple Single-Pill Combination of Valsartan/Amlodipine/Chlorthalidone in Patients with Uncontrolled Hypertension.

PURPOSE: This randomized, double-blind, multicenter Phase III study evaluated the efficacy and safety profile of a single-pill triple combination of valsartan/amlodipine/chlorthalidone (KDF1901, Valdipine Plus) compared with a dual combination of valsartan/amlodipine (KDF1901-R) in patients with essential hypertension. METHODS: Patients (n = 294) with inadequately controlled hypertension after a 4-week run-in phase with valsartan/amlodipine (80/5 mg) were randomized to receive KDF1901 (valsartan/amlodipine/chlorthalidone 160/10/25 mg, n = 147) or KDF1901-R (valsartan/amlodipine 160/10 mg, n = 147) for 8 weeks. The primary efficacy endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Secondary endpoints included changes in mean sitting diastolic blood pressure (MSDBP), BP normalization rates, and response rates. Safety profile outcomes assessed treatment-emergent adverse events (TEAEs), laboratory parameters, and serious adverse events. FINDINGS: At week 8, the KDF1901 group exhibited a significantly greater reduction in MSSBP (-22.8 ± 1.0 mmHg) compared with the dual therapy group (-16.7 ± 1.0 mmHg, P < 0.0001). Similarly, the mean MSDBP reduction was significantly greater with KDF1901 (P = 0.0006). BP normalization rates (75.9% vs 54.5%, P < .0001) and response rates (73.8% vs 51.7%, P < 0.0001) were significantly higher in the triple combination group. Overall, the incidence of TEAEs was similar between groups (24.7% vs 21.5%, P = 0.5783), with mild cases of dizziness were most commonly reported. Exploratory ad hoc analyses showed statistically greater changes in sodium, potassium, and uric acid levels with triple therapy, but clinically meaningful extreme electrolyte abnormalities were rare in both groups, and the overall laboratory profile remained acceptable. IMPLICATIONS: This trial reported that the single-pill triple combination KDF1901 significantly improved BP control compared with dual therapy without compromising tolerability. GOV IDENTIFIER: NCT07116863.

Humans↗

PubMed2026

Evaluation of Sexual Function With Adjunctive Lumateperone in Patients With Major Depressive Disorder.

Objective: Lumateperone is an atypical antipsychotic to treat schizophrenia, bipolar I or II depression, and major depressive disorder (MDD). Randomized phase 3 Study 502 (NCT05061706) investigated the impact of adjunctive lumateperone 42 mg/day on sexual functioning, per Changes in Sexual Functioning Questionnaire 14-item version (CSFQ-14). Methods: Adults meeting DSM-5 criteria for MDD with inadequate response to 1-2 antidepressant therapies (ADTs) in the current depressive episode, Montgomery-Åsberg Depression Rating Scale Total score ≥24, Clinical Global Impression Scale-Severity score ≥4, and Quick Inventory of Depressive Symptomatology-Self Report-16-item score ≥14 were randomized to 6-week lumateperone 42 mg+ADT or placebo+ADT. Sexual function was assessed by CSFQ-14 Total and domain scores in the intent-to-treat (ITT) population and subgroups. Results: Of 480 patients in the ITT population, 82.5% had sexual dysfunction at baseline (women=284; men=112). Lumateperone+ADT significantly improved CSFQ-14 Total score at Day 43 vs placebo+ADT (least squares mean difference [LSMD]=2.7; effect size [ES]=0.38; P<.0001). Significantly greater improvements were observed in patients with baseline sexual dysfunction (LSMD=3.1; ES=0.42; P<.0001), with no change in those without. Improvements were observed in women (LSMD=3.5; ES=0.47; P<.0001) and in men (LSMD=1.9; ES=0.33; P=.08). Significant improvements in CSFQ-14 Total score at Day 43 were observed across age groups and CSFQ domain scores, with both sexes having significant improvements in pleasure and arousal/ excitement. Improvements in depressive symptoms may be linked to improvement in sexual functioning. Conclusions: Adjunctive lumateperone 42 mg did not worsen sexual functioning and was not associated with treatment-related sexual dysfunction in patients with MDD with inadequate response to ADT. Trial Registration: ClinicalTrials.gov identifier: NCT05061706.

Humans↗

PubMed2026

Longitudinal Prediction of Retinal Sensitivity Based on Disease Progression Quantified From Optical Coherence Tomography in Geographic Atrophy.

PURPOSE: The purpose of this study was to analyze the association between disease progression of geographic atrophy (GA) from optical coherence tomography (OCT) with retinal sensitivity (RS) in microperimetry (MP) over a 2-year follow-up period. METHODS: This is a longitudinal analysis of the OAKS Phase-III clinical trial. Both study and fellow eyes with GA that underwent imaging with the Spectralis OCT and consecutive MP examination were eligible. Pointwise quantification of ellipsoid zone (EZ) thickness, EZ and retinal pigment epithelium (RPE) loss from OCT volumes was correlated with localized RS. A longitudinal predictive model using a Markov Chain framework was implemented to predict RS change over time based on OCT biomarkers. The modeling of morphological and functional progression was based on the fellow-eye cohort. RESULTS: A total of 39,681 MP points from 406 patients were analyzed. In the fellow eye cohort, baseline (BSL) EZ thickness was positively associated with RS (0.3 decibel [dB]/µm, P < 0.001). Decrease in EZ thickness between visits during follow-up was significantly associated with decrease in RS (0.1 dB / 1 µm change). RS was significantly lower in MP points within EZ loss during follow-up compared with MP points within the retina with measurable EZ (P < 0.001). The largest functional decline was observed within RPE loss, also associated with the highest probability of absolute scotoma (P < 0.001). Morphological progression to EZ and RPE loss was influenced by EZ thickness and the morphology of adjacent MP points (P < 0.001). CONCLUSIONS: Two exploratory endpoints were developed, namely quantification of EZ thickness and loss, and localized RS within high-risk OCT areas. RS decline during follow-up is associated with automatically quantified disease progression in OCT.

Humans↗

PubMed2026

Comparison of immunogenicity, safety, and efficacy of EVA71 vaccine in children: a systematic review and meta-analysis.

INTRODUCTION: Enterovirus 71 (EV-A71) is a principal cause of hand, foot, and mouth disease (HFMD), potentially leading to severe neurological complications in children. Inactivated EV-A71 vaccines have been introduced. This study compares the immunogenicity, safety, and efficacy of EV-A71 vaccines versus placebo in pediatric populations. RESEARCH DESIGN AND METHODS: Following a PROSPERO-registered protocol, RCTs involving EV-A71 in children were identified via PubMed, Scopus, Cochrane, and ClinicalTrials.gov. Two independent reviewers performed screening, extraction, and RoB assessments (RoB 2.0). RESULTS: Five phase III RCTs involving 36,659 children were included. EV-A71 vaccination significantly increased seropositivity across follow-up periods, including early (RR 5.8), medium-term (RR 3.09), and long-term (RR 2.95) response. Seroconversion was significantly higher in the vaccinated group (pooled RR 13.04, 95% CI 2.80-60.61; p < 0.001). Geometric mean titers, analyzed using the ratio of means approach, were significantly higher in the vaccinated group during early and medium-term follow-up. Vaccine efficacy against EV-A71-associated HFMD exceeded 98% (pooled RR 0.02, 95% CI 0.01-0.09; p = 0.0028; I2 = 50%). Solicited local and systemic adverse events were mild and comparable between groups. CONCLUSION: Inactivated EV-A71 vaccines robust immunogenicity, high clinical efficacy, and an acceptable safety profile in children. Future studies should explore long-term protection, booster schedules, and multivalent formulations against non-EV-A71 serotypes.

Humans↗

PubMed2026

Selective monitoring of trace-level catechin and myricetin in herbal and aqueous matrices using magnetic MIP-DSPME: Optimization via design of experiments.

A novel dispersive solid-phase microextraction approach utilizing a magnetic molecularly imprinted polymer (MMIP) integrated with HPLC-UV detection was developed for the concurrent quantification of catechin and myricetin in herbal extracts and aqueous samples. The sorbent was engineered as a core-shell nanocomposite, consisting of a selective polymer layer deposited onto Fe3O4@SiO2-APTMS magnetic nanoparticles. Dual-template imprinting using catechin and myricetin generated complementary binding cavities within the polymer framework. Experimental variables influencing extraction were systematically screened and subsequently optimized. A Plackett-Burman design was first applied to identify the most influential factors, with pH and sorption time identified as the dominant variables. These parameters were subsequently fine-tuned using a central composite design, and the optimization process was completed in only 30 experimental runs. The sorption characteristics of the imprinted sorbent (MMIP) were compared with those of its non-imprinted counterpart (MNIP). The MMIP demonstrated markedly higher maximum binding capacities (Qmax), reaching 119.3 mg g-1 for myricetin and 112.1 mg g-1 for catechin, whereas the corresponding values for the MNIP were 32.55 and 32.08 mg g-1, respectively. Moreover, the affinity constants (KL = 0.760-0.950 L mg-1) were approximately 2.3-fold higher for the MMIP, confirming its stronger and more selective interactions with the target analytes. The selectivity coefficients for the targeted flavonoids relative to structurally related compounds, including ferulic acid, p-coumaric acid, melatonin, and curcumin, exceeded 3.5 for the MMIP, whereas the corresponding values for the MNIP were close to 1.1, demonstrating the high molecular recognition capability of the imprinted sorbent. Method validation demonstrated limits of detection (LODs) of 0.33-0.59 ng mL-1 and limits of quantification (LOQs) of 1.10-1.96 ng mL-1, and excellent linearity over the concentration range of 5.0-5500 ng mL-1 (R2 > 0.998). The method achieved recoveries of 93.96% to 105.69% with RSDs below 5.5%, while the preconcentration factors ranged from 209 to 229. Furthermore, the sorbent retained more than 95% of its extraction efficiency after four consecutive reuse cycles and more than 80% after six cycles, demonstrating excellent stability and reusability. The proposed method was successfully applied to the analysis of six medicinal plant extracts and water samples, showing negligible matrix interference and superior sensitivity, selectivity, and operational simplicity compared with conventional solid-phase extraction methods.

Flavonoids↗

PubMed2026

Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics and the Pharmacokinetics of Balcinrenone When Dosed with a P-gp Inhibitor.

Balcinrenone (AZD9977) is a novel selective non-steroidal mineralocorticoid receptor antagonist with a distinct mode of action being developed as a fixed-dose combination with the sodium-glucose cotransporter-2 inhibitor dapagliflozin for the treatment of heart failure with impaired kidney function, and chronic kidney disease. In this Phase 1 randomized open-label three-way crossover study we investigated the effect of food on balcinrenone/dapagliflozin pharmacokinetics, and the pharmacokinetics of balcinrenone when dosed with a P-glycoprotein (P-gp) inhibitor. Fourteen healthy participants were administered an oral capsule of balcinrenone/dapagliflozin 40 mg/10 mg in three dosing periods: fasted (reference), fed (high-fat, high-calorie meal) and with a P-gp inhibitor (quinidine 300 mg × 2). Balcinrenone exposure was comparable in the fed and fasted states (geometric mean ratios [GMRs] [90% CI]: maximum plasma concentration [Cmax] 1.05 [0.88, 1.25]; area under the plasma concentration-time curve from time 0 to infinity [AUCinf] 1.12 [1.06, 1.19]). In the fed state, dapagliflozin AUCinf was comparable to the fasted state (GMR [90% CI] 1.05 [1.01, 1.09]), whereas Cmax was decreased (GMR [90% CI] 0.59 [0.51, 0.69]), in line with previous dapagliflozin food interaction studies. Co-administration with quinidine increased balcinrenone exposure: GMRs (90% CI) 1.48 (1.24, 1.76) and 1.24 (1.17, 1.31) for Cmax and AUCinf, respectively, but AUC fold increase was <2, the level used for classification of sensitive P-gp substrates. All interventions were well tolerated. In conclusion, this study supports dosing of balcinrenone/dapagliflozin without regard to food. Balcinrenone is not considered a sensitive P-gp substrate. No P-gp based dosing precautions are warranted based on this study.

Adult↗

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

Ablative radiotherapy in castration-resistant prostate cancer.

OBJECTIVE: To prove the oncological benefit of ablative radiotherapy in patients with up to five metastases from castration-resistant prostate cancer (CRPC) a single-centre randomised trial was initiated. PATIENTS AND METHODS: This monocentric, randomised, phase II clinical trial enrolled patients with up to five prostate-specific membrane antigen-positive bone or lymph node metastases developing prostate-specific antigen (PSA) progression during androgen deprivation (ADT) or ADT and androgen-receptor targeted therapy. Participants were randomised (2:1) to receive metastasis-directed therapy (MDT) or observation (OBS) without changing systemic therapy. The primary endpoint was the proportion of patients having PSA progression within 1 year, with statistical analyses conducted using intention-to-treat principles. Here, results of a planned interim analysis of the primary endpoint are reported. RESULTS: A total of 30 patients (12 in the observation arm and 18 in the MDT arm) were enrolled, PSA progression within 1 year occurred in 44% of the MDT group vs 75% in the OBS group (P = 0.14, not significant). The median time to PSA progression was significantly longer in the MDT arm (12.4 months) compared to the OBS arm (2.9 months, P = 0.03). The pre-defined criteria to discontinue the study were not met. Limitations include the single-centre design and small sample size at interim analysis. CONCLUSION: This pre-planned interim analysis of the primary endpoint did not meet the discontinuation criteria of the study protocol, suggesting that MDT in oligometastatic CRPC may extend the time to PSA progression without immediate change of systemic therapy. The continuation of the study in a multicentre setting is planned (Institutional funding by the TU Dresden, ClinicalTrials.gov identifier: NCT04141709).

Humans↗

PubMed2026

Pathogenic properties of myasthenia gravis AChR autoantibodies associate with clinical response to efgartigimod.

BACKGROUND: Efgartigimod, a neonatal Fc receptor (FcRn) blocker, effectively reduces total IgG, including pathogenic acetylcholine receptor (AChR) autoantibodies in myasthenia gravis (MG); however, clinical responses vary. To investigate this variability, we studied how efgartigimod impacts AChR-specific autoantibody profiles and associated pathogenic mechanisms, including complement activation, AChR internalisation and ACh-binding site blockade. METHODS: Serum samples (N=150) were sourced from 50 AChR autoantibody-positive generalised MG patients participating in the phase 3 ADAPT study, randomised to receive efgartigimod (N=40) or placebo (N=10) in cycles of 4-weekly infusions. Samples were collected at baseline, day 29 and day 57 during the first cycle. Live cell-based assays quantified AChR-specific IgG subclasses and isotypes and assessed their capacity to mediate pathomechanisms. RESULTS: Efgartigimod decreased all detectable AChR-specific IgG subclasses. At baseline, AChR autoantibody-mediated C3b deposition, AChR internalisation and ACh-binding site blockade were detected in 42 (84%), 41 (82%) and 10 (20%) patients, respectively. After 4-weekly infusions of efgartigimod, the magnitude of all three pathomechanisms was significantly decreased. However, the extent of this reduction varied across individuals. Double responders on both MG-activities of daily living and quantitative MG scores demonstrated a greater reduction in complement activity and AChR internalisation compared with patients who responded on only one score or were double non-responders. In addition, efgartigimod reduced IgG-dependent IgM binding to AChR. CONCLUSIONS: These findings suggest that clinical efficacy may be more closely associated with functional modulation of the AChR-specific autoantibodies than with their absolute quantity alone. These results support the evaluation of mechanistic pathway monitoring as a potential strategy to predict or guide efgartigimod treatment response.

Humans↗

PubMed2026

Efficacy and Safety of Once-Weekly Semaglutide 2.0 mg as an Add-On to Dose-Reduced Insulin Glargine versus Dose-Titrated Insulin Glargine in People With Type 2 Diabetes and Overweight (SUSTAIN OPTIMIZE).

AIMS: Type 2 diabetes (T2D) management with basal insulin can lead to hypoglycaemia and weight gain. SUSTAIN OPTIMIZE compared once-weekly semaglutide 2.0 mg as add-on to dose-reduced insulin glargine (Sema+IGlarreduced) versus dose-titrated IGlar (IGlartitrated) on glycated haemoglobin (HbA1c), body weight (BW), daily insulin dose, and participant satisfaction. MATERIALS AND METHODS: SUSTAIN OPTIMIZE was a 40-week, phase 3b, open-label, randomised study. Adults with T2D, overweight (body mass index ≥ 25 kg/m2), and treatment with basal insulin ≤ 40 units/day were randomised 1:1 into Sema+IGlarreduced or IGlartitrated. The primary endpoint was change in HbA1c using a non-inferiority approach. Secondary endpoints assessed superiority of Sema+IGlarreduced versus IGlartitrated in reducing HbA1c, BW, daily insulin dose, and improving Diabetes Treatment Satisfaction Questionnaire change version (DTSQc) scores. RESULTS: Overall, 573 participants were randomised. Sema+IGlarreduced achieved both non-inferiority and superiority versus IGlartitrated in HbA1c reduction (estimated treatment difference [ETD]: -0.74%; 95% confidence interval [CI95]: -0.90, -0.59) and superiority in BW change (ETD: -8.5 kg; CI95: -9.5, -7.4), relative daily insulin dose change (ETD: -121.9%; CI95: -143.1, -100.6), and DTSQc scores (ETD: 2.6; CI95: 1.6, 3.5) (p < 0.0001 for all endpoints). No new safety concerns were identified. Severe hypoglycaemia was reduced (rate ratio: 0.45; CI95: 0.23, 0.87; p = 0.02), while gastrointestinal events were higher for Sema+IGlarreduced (310 vs. 32 events). CONCLUSIONS: Once-weekly subcutaneous semaglutide 2.0 mg as add-on to dose-reduced IGlar achieved superior reductions in HbA1c, BW, and daily insulin dose in people with T2D and overweight, while reducing their risk for severe hypoglycaemia compared to dose-titrated IGlar alone.

Adult↗

PubMed2026

Azacitidine-Venetoclax or Induction Chemotherapy for Acute Myeloid Leukemia.

BACKGROUND: Induction chemotherapy has long been a key component of curative therapy for fit patients with acute myeloid leukemia (AML), despite its frequently severe side effects and substantial health care utilization. For patients who are ineligible for induction chemotherapy, hypomethylating therapy plus venetoclax is the standard treatment owing to its efficacy and side-effect profile. METHODS: In this multicenter, phase 2 trial, we randomly assigned, in a 1:1 ratio, previously untreated adults with AML who were eligible for induction chemotherapy to receive either azacitidine plus venetoclax or induction chemotherapy. Patients with core binding factor fusions, mutations in the gene encoding FMS-like tyrosine kinase 3 (FLT3), or mutations in the gene encoding nucleophosmin-1 (NPM1; unless the patient was ≥60 years of age) were excluded. The primary end point was event-free survival. RESULTS: A total of 172 patients underwent randomization, with 86 patients assigned to each group. The median age of the patients was 64 years. A total of 72% of the patients had adverse-risk disease according to the European LeukemiaNet 2022 classification. At a median follow-up of 21.9 months, the median event-free survival was 14.5 months (95% confidence interval [CI], 10.4 to 24.4) in the azacitidine-venetoclax group, as compared with 6.2 months (95% CI, 4.1 to 10.1) in the induction chemotherapy group, corresponding to a hazard ratio for event or death of 0.57 (95% CI, 0.39 to 0.84; P = 0.002 by the stratified log-rank test). Infection of grade 3 or higher occurred in 28% of the patients (95% CI, 19 to 39) receiving azacitidine-venetoclax and in 41% of those (95% CI, 30 to 52) receiving induction chemotherapy; hemorrhage of grade 3 or higher occurred in 2% (95% CI, 0.3 to 8) and 12% (95% CI, 6 to 20), respectively. CONCLUSIONS: In this phase 2, randomized trial, azacitidine-venetoclax therapy led to significantly longer event-free survival than induction chemotherapy among induction-eligible patients with AML. (Funded by AbbVie and others; PARADIGM ClinicalTrials.gov number, NCT04801797.).

Adult↗

PubMed2026

Predictors of Efficacy Maintenance After Vunakizumab Discontinuation in Patients With Moderate-to-Severe Plaque Psoriasis: A Post Hoc Analysis of a Randomized Controlled Trial.

BACKGROUND: Efficacy cannot be maintained in some psoriasis patients after biological discontinuation. This study aimed to explore predictors of efficacy maintenance after vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. METHODS: This post hoc analysis used data from a phase III trial (NCT04839016); 291 patients with moderate-to-severe plaque psoriasis who achieved 100% improvement in Psoriasis Area and Severity Index (PASI) score at Week 52 were enrolled. Efficacy maintenance was defined as patients who maintained PASI 90 or PASI 100 after 20 weeks of vunakizumab discontinuation. RESULTS: There were 44.7% and 72.5% of patients with PASI 100 and PASI 90 maintenance, respectively. In the multivariate logistic regression model, body mass index (BMI) (odds ratio [OR] = 0.922, p = 0.024) and treatment interruption (OR = 0.550, p = 0.020) were independently associated with a lower possibility of PASI 100 maintenance; however, the association of family history of psoriasis and the first time of PASI 100 achievement with PASI 100 maintenance did not achieve statistical significance. Duration of psoriasis (OR = 0.972, p = 0.049) and treatment interruption (OR = 0.257, p < 0.001) were independently associated with a lower possibility of PASI 90 maintenance. Two nomograms for predicting PASI 90 and PASI 100 maintenance were constructed based on the multivariate models, which disclosed good calibration performance. CONCLUSIONS: PASI 90 and PASI 100 maintenance rates are 72.5% and 44.7% after 20 weeks of vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. BMI, treatment interruption, and duration of psoriasis predict a lower possibility of efficacy maintenance after vunakizumab discontinuation.

Humans↗

PubMed2026

Reduced Length of ADT and ARTA With XRT in High-Risk Prostate Cancer (RELAX): A Randomised Controlled Trial.

AIM: To assess the efficacy of a short, intensified regimen of androgen deprivation therapy (ADT) and androgen receptor-targeted agent (ARTA) with curative-intent external beam radiotherapy (XRT) for high-risk prostate cancer (HRPCa) staged with prostate specific membrane antigen (PSMA) imaging. MATERIALS AND METHODS: The RELAX (Reduced Length of ADT and ARTA with XRT in high-risk prostate cancer) trial is a multicentre, phase II randomised non-inferiority trial comparing 9 months of ADT and 6 months of ARTA against the standard 24-month ADT, with definitive dose-escalated hypofractionated pelvic radiotherapy for PSMA-staged non-metastatic HRPCa. The primary endpoint is 5-year disease-free survival (DFS), defined from randomisation to first biochemical or clinico-radiological recurrence or any-cause death. Secondary endpoints include biochemical failure-free survival, metastasis-free survival, overall survival, testosterone recovery, treatment-related adverse effects, and patient-reported outcomes. Participants are monitored with serial serum PSA and testosterone levels, CTCAE and PRO-CTCAE assessments, and PSMA-PETCT at recurrence. The non-inferiority margin is set at 10% absolute difference from an expected 5-year DFS of 85% in the standard arm, with intention-to-treat analysis. The trial is ethics board approved and funded by institutional intramural grant, and registered on clinicaltrials.gov (NCT06818682). RESULTS: The planned accrual of 206 participants commenced in February 2025, with nearly a third of enrolment completed till date. CONCLUSION: The RELAX trial incorporates contemporary standards of PSMA-based staging, dose-escalated hypofractionated radiotherapy, and ARTA for HRPCa. The results are expected to inform the efficacy of a shorter, intensified androgen suppression strategy against the prevailing standard of long-term ADT for these patients.

Humans↗

PubMed2026

Molecular evaluation of residual disease following neoadjuvant chemotherapy in triple-negative breast cancer CALGB 40603 (Alliance).

BACKGROUNDDespite therapeutic advances in early-stage triple-negative breast cancer (TNBC), residual disease (RD) following neoadjuvant therapy remains a key predictor of a worse prognosis and obstacle to improving patient outcomes.METHODSTo better characterize RD and identify survival-associated features, we performed comprehensive transcriptomic profiling of 340 pretreatment stage II/III TNBCs and 70 matched posttreatment RD samples from the randomized CALGB 40603 (Alliance) phase II clinical trial. To explore preclinical treatment strategies for RD, patient-derived xenograft (PDX) mouse models mimicking RD were treated with antibody-drug conjugates (ADCs).RESULTSOur study shows prognostic genomic features measured pretreatment may differ from prognostic features measured posttreatment from RD specimens. Patients with a genomic PAM50 subtype of basal-like in RD specimens had a poor survival outcome, and their matching pretreatment tumors were characterized by elevated chromosomal amplifications of oncogenic drivers and significantly reduced B and T cell expression features. Paired analyses of basal-like RD and matched pretreatment tumors revealed further lymphocyte depletion in RD, along with lower expression of MHC class I and interferon signaling, indicating an immune-cold RD microenvironment. Treatment of a basal-like and conventional chemotherapy-resistant PDX model, resembling basal-like RD, with sacituzumab govitecan or trastuzumab deruxtecan produced a marked antitumor response.CONCLUSIONRD biology differs from pretreatment tumors, with basal-like subtype RD following neoadjuvant chemotherapy being immune cold and associated with poor survival. Preclinical modeling suggests this high-risk group may benefit from adjuvant ADC therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT00861705.FUNDINGNIH NCI U10CA180821 (Alliance for Clinical Trials in Oncology), NCI U24CA176171 (Alliance for Clinical Trials in Oncology), NCI UG1CA233373 (Alliance for Clinical Trials in Oncology), NCI Breast SPORE program P50-CA058223; Susan G. Komen SAC-160074; Breast Cancer Research Foundation BCRF-23-127; NIH NCI R01-CA229409; UNC LCCC Triple Negative Breast Cancer Center.

Humans↗