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PubMed2026

Obesity in obstetric anesthesia: A systematic review.

Maternal obesity presents complex challenges for anesthetic management, with implications spanning neonatal, cardiovascular, airway, neuraxial, and procedural domains. This review synthesizes evidence on how elevated maternal body mass index (BMI) impacts perioperative evaluations, risks, complications, and outcomes, in addition to anesthetic modalities and efficacy in the pregnant population. Given the increasing global prevalence of maternal obesity, anesthesiologists must refine clinical practices, employing tailored, evidence-based strategies to mitigate risks and enhance patient outcomes. This review aims to provide anesthesiologists and obstetricians with key considerations and best practices for managing obstetric anesthesia patients with obesity. Clinical recommendations herein are based on current research and evaluated using Oxford Centre for Evidence-Based Medicine for level of evidence and class of recommendation.

Humans↗

PubMed2026

Potential Links Between Physiological and Perceptual Strain in High Heat Stress.

The physiological strain index (PhSI) is widely used to quantify thermoregulatory and cardiovascular strain during heat stress. However, direct physiological measurements may not always be feasible in occupational or athletic settings. Therefore, this study aimed to examine the relationship and agreement between perceptual strain and integrated physiological strain indices during high heat stress. Ten healthy, physically active, non-heat-acclimated males (29 (7) yr; 1.79 (0.11) m; 77.4 (9.3) kg) completed two randomized crossover exercise trials in hot-dry (HD) and warm-humid (WH) environments with equivalent wet-bulb globe temperatures. Heart rate, rectal temperature, skin temperature, rating of perceived exertion, and thermal sensation were measured at baseline and every 15 minutes during 60 minutes of cycling. Physiological strain index (PhSI), adaptive physiological strain index (aPhSI), and perceptual strain index (PeSI) were calculated using validated equations. Repeated-measures correlation analyses demonstrated very strong associations between PeSI and both PhSI and aPhSI under HD (Rrm = 0.940-0.943) and WH (Rrm = 0.980-0.982; all p < 0.001). Receiver operating characteristic analyses demonstrated good-to-excellent discrimination of physiological strain by PeSI (AUC = 0.895-0.969). Mixed-effects analyses showed that higher PeSI values were associated with increased PhSI (β = 1.325, p < 0.001) and aPhSI (β = 1.459, p < 0.001). However, Bland-Altman analyses demonstrated relatively small mean biases (0.4-0.9 AU) but wide limits of agreement (-2.8 to 4.2 AU), indicating that PeSI and physiological strain indices are not interchangeable. These findings suggest that PeSI may serve as a practical adjunctive or screening indicator of physiological strain when direct physiological measurements are unavailable.

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

Assessing comorbidities and predicting risk: A primer for APRNs.

Today's clinical environments are rife with tools designed to comprehensively account for medical complexity and comorbidities while predicting risk for a host of adverse health-related outcomes. Therefore, it is imperative that advanced practice registered nurses (APRNs) understand the structure and function of these tools, their similarities and differences, their limitations, and strategies for appropriate incorporation into practice. This article offers a practical overview for APRNs, emphasizing clinical implications and guidance for aligning assessment tools with the clinical population of interest to improve care delivery, quality, and patient outcomes.

Humans↗

PubMed2026

Socioeconomic differences in the effectiveness of oral health programs for dental caries prevention in Europe: A systematic review and meta-analysis.

AIM: The meta-analysis systematically summarized evidence on how socioeconomic status (SES), access to dental care, and oral health programs (OHP) affect caries prevalence and severity among children and adults in Europe. METHODS: Four electronic databases (PubMed, Scopus, Cochrane Library and Embase) were systematically screened from 1947-2026, supplemented by cross-referencing and manual searches, without language restrictions. Study selection, data extraction and quality assessment were done in duplicate. Methodological quality was assessed using the NHLBI Study Quality Assessment Tools according to study design. Certainty of evidence was graded using GRADE Profiler 3.6. Mean differences (MD) were calculated for changes in DMFT, and odds ratios (OR) for the presence of dental caries in individuals using fixed-or random-effects models. RESULTS: Electronic searching identified 1800 articles; 23 studies were included in the review (>169,000 participants) and 14 in the meta-analyses (>88,000). Nine studies evaluated the effectiveness of OHP stratified by SES, and ten examined OHP in low-SES populations. Among low-SES individuals, participation in OHP was associated with a significantly lower increase in DMFT (MD[95% CI]=-0.63[-0.94;-0.31];very low certainty) and significantly lower odds of having dental caries (OR[95% CI]=0.61[0.52;0.73];very low) compared with non-participation. Among program participants, individuals with low SES showed a significantly greater increase in DMFT than those with high SES (MD[95% CI]=0.79[0.30;1.21];very low) and had significantly higher odds of having dental caries (OR[95% CI]= 2.88[1.97;4.22];very low). CONCLUSION: Participation in OHP may be associated with reducing dental caries in European populations, but benefits are unequally distributed and increase with higher SES. However, this conclusion is based on a limited number of well-conducted trials.

Humans↗

PubMed2026

Association of the Charlson Comorbidity Index With 1-Year Outcomes in Patients With Macular Edema Secondary to Retinal Vein Occlusion.

OBJECTIVE: To determine the predictive value of the Charlson Comorbidity Index (CCI) for outcomes in patients with macular edema secondary to retinal vein occlusion (RVO). DESIGN: Retrospective clinical cohort study. SUBJECTS: Patients seen between 2013 and 2023 at the Cole Eye Institute, Cleveland Clinic, were included. All patients were >18, diagnosed with RVO (International Classification of Diseases (ICD)-9 and 10 codes), had a complete CCI score, and had at least 1 year of ophthalmic follow-up data after their first intravitreal injection (baseline). Patients with ocular surgery, trauma, or panretinal photocoagulation were excluded. METHODS: Age-adjusted CCI scores were calculated for each patient from chart review. For patients with bilateral RVO, one eye was selected randomly. Patients were stratified into tertiles by CCI distribution: tertile 1 (CCI 0-5; mean 3.4), tertile 2 (age-CCI 4.1-6; mean 4.9), and tertile 3 (CCI ≥ 8; mean 9.6). Multivariable linear regression was performed to determine the predictive value of CCI and other covariates on visual and anatomical outcomes. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) and central subfield thickness (CST) at 1-year follow-up. RESULTS: A total of 972 patients met all criteria, with an average age-adjusted CCI score of 6.2. Each one-point increase in CCI predicted 0.38 fewer letters in BCVA at follow-up (P < .001). Baseline BCVA was a significant predictor of follow-up BCVA in all tertiles (P < .001). In the third tertile, each one-point increase in CCI was associated with a 0.72 letter reduction in follow-up BCVA (P < .001). For CST, baseline CST was strongly predictive of final CST (P < .001), while CCI was only significant in the first tertile, where each point increase in CCI predicted a 13.7 µm increase in CST (P = .02). In RVO subtype interaction models, the age-adjusted CCI × CRVO interaction was not statistically significant for either 1-year BCVA (P = .269) or 1-year CST (P = .695). CONCLUSIONS: Higher CCI scores are significantly associated with worse visual outcomes in patients with RVO, particularly in the combined population and most comorbid patients (tertile 3). CCI was significantly associated with higher (thicker) CST only among the least comorbid patients (tertile 1).

Humans↗

PubMed2026

Evaluation of the effects of domestic tomato processing on biopesticide residue using natural deep eutectic solvents (NADES) extractions.

The present study evaluated the fate of fourteen botanical biopesticides in processed tomato samples. Various processing methods were employed, including washing, dehydration, and the preparation of juice and sauce. The extraction was performed using more sustainable techniques, aimed at minimizing the environmental impact of conventional organic solvents by substituting them with natural deep eutectic solvents (NADES). Solid-liquid extraction (SLE) and dispersive liquid-liquid microextraction with solidification of floating organic drop (DLLME-SFOD) were utilized for solid and liquid tomato samples, respectively. The NADES used was choline chloride:2,3-butanediol (ChClBt) at a 1:4 molar ratio for both techniques, resulting in recovery values ranging from 69.2 to 106.2% for SLE, and extraction efficiencies reaching up to 46.2% for DLLME-SFOD. The impact of these processes was evaluated employing the processing factor (PF), yielding PF values of less than 1 in all cases. Compounds as pyrethrins, azadirachtin, and rotenone persisted after processing, posing a potential consumer risk.

Solanum lycopersicum↗

PubMed2026

Duration and characteristics of hypoglycemia with once-weekly insulin efsitora alfa versus once-daily basal insulins in adults with type 2 diabetes: Exploratory safety analysis of QWINT 2-4.

AIMS: Efsitora is a novel once-weekly basal insulin. Efsitora demonstrated similar efficacy and safety compared with once-daily basal insulin comparators across four phase 3 clinical trials for type 2 diabetes. This exploratory safety analysis further characterizes hypoglycemia events in the efsitora and once-daily treatment groups in three of these trials (QWINT-2, -3, and -4). METHODS: Median duration of hypoglycemia events was assessed with masked continuous glucose monitoring. Incidence of persistent-recurrent (PR) hypoglycemia was assessed by investigators and by a pre-specified algorithm using SMBG e-diary data. Factors contributing to hypoglycemia, characteristics of hypoglycemia, and treatment methods were reported by participants and assessed across groups. RESULTS: Across the three trials, durations of hypoglycemic events for efsitora vs once-daily basal insulin comparators were: Level 1 and 2 [<70 mg/dL]: 40-42.5 vs 40 min; Level 2 [<54 mg/dL]: 35-39.9 vs 35 min. Few incidences of PR hypoglycemia were reported for efsitora or once-daily comparators. No major descriptive differences were observed between hypoglycemia contributing factors, characteristics, or treatment methods in efsitora and once-daily treatment groups. CONCLUSIONS: No clinically relevant differences were observed between the duration or characteristics of hypoglycemic events in efsitora and once-daily treatment groups in the QWINT-2, -3, and -4 trials.

Adult↗

PubMed2026

Durvalumab and tremelimumab, with or without lenvatinib, combined with transarterial chemoembolisation in participants with embolisation-eligible hepatocellular carcinoma (EMERALD-3): a global, randomised, open-label, sponsor-blinded, phase 3 study.

BACKGROUND: Transarterial chemoembolisation (TACE), a standard treatment for embolisation-eligible hepatocellular carcinoma (HCC), induces tumour immune responses. Single tremelimumab regular interval durvalumab (STRIDE) is a standard treatment in advanced HCC. In this phase 3 trial, we assessed the efficacy and safety of STRIDE, with or without lenvatinib, plus TACE, in participants with embolisation-eligible HCC. METHODS: EMERALD-3 is a phase 3, randomised, open-label, sponsor-blinded study, conducted at 177 medical sites in 21 countries. Eligible participants were 18 years or older (aged ≥21 years in Egypt or Singapore) at screening and had confirmed HCC (by imaging or histopathologically from biopsy specimen, surgery, or both) not amenable to curative surgery, curative ablation, or transplantation but amenable to TACE. Participants had Child-Pugh class A liver function, an Eastern Cooperative Oncology Group performance status of 0-1, and at least one measurable target intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours. Participants were randomly allocated in a 1:1:1 ratio to receive STRIDE plus lenvatinib plus TACE, STRIDE plus TACE, or TACE until each group reached its preplanned enrolment target of 175 participants. After the STRIDE plus TACE group reached its enrolment target, randomisation was adjusted to continue in a 1:1 ratio between the STRIDE plus lenvatinib plus TACE group and TACE group until approximately 275 participants were enrolled in each of these two groups. Randomisation used a centrally assigned interactive response technology system, stratified by region, baseline tumour burden, and previous palliative embolisation. In the STRIDE plus lenvatinib plus TACE group, on the first day, participants were given 300 mg tremelimumab intravenously, followed by 1500 mg durvalumab plus oral lenvatinib (8 mg for <60 kg bodyweight or 12 mg for ≥60 kg bodyweight); participants then received 1500 mg durvalumab every 4 weeks plus once-daily lenvatinib for up to 36 cycles. In the STRIDE plus TACE group, participants were given 300 mg tremelimumab and 1500 mg durvalumab intravenously on the first day, followed by 1500 mg durvalumab every 4 weeks. The technique and number of TACE procedures were at the investigators' discretion, with the first procedure administered at least 7 days after the first dose of durvalumab in the two investigation treatment groups and within 7 days of random allocation in the TACE group. The primary endpoint was progression-free survival for STRIDE plus lenvatinib plus TACE versus TACE. Key secondary endpoints were overall survival for STRIDE plus lenvatinib plus TACE versus TACE and progression-free survival and overall survival for STRIDE plus TACE versus TACE. This study was registered with ClinicalTrials.gov (NCT05301842), with enrolment completed. FINDINGS: From March 28, 2022, to Nov 20, 2024, 1124 participants were screened. The full analysis set comprised 760 participants, who were randomly allocated to STRIDE plus lenvatinib plus TACE (n=293), STRIDE plus TACE (n=175), or TACE (n=292). 633 (83%) participants were male and 127 (17%) were female; 548 (72%) were Asian. At the first data cutoff (Sept 2, 2025); the overall median follow-up for progression-free survival was 10·0 months (IQR 4·6-17·2); median follow-up for progression-free survival was 11·0 months (IQR 4·8-18·4) for STRIDE plus lenvatinib plus TACE and 8·3 months (4·1-15·5) for TACE. Median progression-free survival was 13·0 months (95% CI 12·2-16·7) for STRIDE plus lenvatinib plus TACE versus 9·8 months (8·0-11·4) for TACE (HR 0·70 [95% CI 0·57-0·86]; p=0·0007). At the second data cutoff (Feb 23, 2026) and a median follow-up for overall survival of 24·6 months (IQR 16·5-31·5) for STRIDE plus lenvatinib plus TACE and 22·9 months (14·9-30·2) for TACE, median overall survival was 39·5 months (95% CI 34·1-not reached) for STRIDE plus lenvatinib plus TACE and 34·7 months (28·8-not reached) for TACE (HR 0·84 [95% CI 0·65-1·09]; p=0·18). At this data cutoff, median progression-free survival was 12·9 months (95% CI 10·2-15·9) for STRIDE plus TACE and 8·1 months (6·5-10·2) for the first 175 participants randomised to TACE (HR 0·71 [95% CI 0·56-0·91]), with median follow-up of 10·3 months (IQR 4·6-23·7) for STRIDE plus TACE and 7·7 months (3·0-18·5) for the first 175 participants randomly allocated to TACE. The most common adverse events of maximum grade 3 or 4 were hypertension (34 [12%] of 287) for STRIDE plus lenvatinib plus TACE, post-embolisation syndrome and anaemia (ten [6%] of 175 each) for STRIDE plus TACE, and post-embolisation (17 [6%] of 290) for TACE. 184 (64%) participants receiving STRIDE plus lenvatinib plus TACE, 89 (51%) receiving STRIDE plus TACE, and 68 (23%) receiving TACE had serious adverse events. Treatment-related adverse events with an outcome of death during the treatment-emergent period occurred in seven (2%) of 287 participants who received STRIDE plus lenvatinib plus TACE (two for myocarditis; and one each for hepatic failure, haemophagocytic lymphohistiocytosis, septic shock, cardiac failure, and unknown cause), none of 175 participants who received STRIDE plus TACE, and two (1%) of 290 participants who received TACE (one each for acute myocardial infarction and unknown cause). INTERPRETATION: STRIDE plus lenvatinib plus TACE showed a statistically significant progression-free survival improvement versus TACE. These findings support a STRIDE-based regimen as a potential new treatment option for people with embolisation-eligible HCC; additional follow-up is being conducted for final analysis of overall survival across treatment groups. FUNDING: AstraZeneca.

Adult↗

PubMed2026

Photothermal-Activated Platelet-Rich Plasma Versus Conventional Platelet-Rich Plasma for Melasma: A Split-Face, Double-Blind Randomized Controlled Trial.

BACKGROUND: Melasma is a common acquired pigmentary disorder that predominantly affects women with darker skin types and substantially impairs quality of life. Current treatments are limited by variable efficacy, adverse effects, and frequent recurrence. Platelet-rich plasma (PRP) has emerged as a potential regenerative treatment through growth-factor-mediated modulation of melanogenesis. Photothermal activation, which combines photobiomodulation with controlled hypothermic conditioning, has been hypothesized to promote a more sustained growth-factor release than conventional PRP. This study compared the efficacy and safety of photothermal-activated PRP (PT-PRP) and conventional PRP (C-PRP) for melasma treatment. METHODS: This split-face, double-blind, randomized controlled trial included 26 women with epidermal or mixed-type melasma. Each participant received three monthly sessions of intradermal PRP, with PT-PRP and C-PRP injected into opposite facial sides. Outcomes were assessed at weeks 0, 4, 8, and 12 using the modified Melasma Area and Severity Index (mMASI), Mexameter melanin and erythema indices, patient satisfaction, overall improvement, and adverse events. RESULTS: Both treatments significantly reduced mMASI by week 12, with no significant between-group differences at any time point. C-PRP showed significant mMASI improvement from week 4, whereas PT-PRP reached significance from week 8. For the melanin index, PT-PRP produced a significant within-group reduction at week 12, while C-PRP did not. At week 12, PT-PRP showed a significantly lower melanin index than C-PRP. Mild injection-site bruising was the only adverse event. CONCLUSION: PT-PRP and C-PRP produced comparable clinical improvement, but PT-PRP achieved greater objective melanin reduction at week 12. PT-PRP may represent a safe alternative treatment for melasma. TRIAL REGISTRATION: Thai Clinical Trials Registry: TCTR20260318004.

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

Evaluation of Physical and Mental Workload and Transfusion Time in Trauma Resuscitation.

BACKGROUND: Trauma resuscitation is time sensitive and complex. Whole blood (WB) and blood components are standard treatments for trauma related hemorrhage, yet their nursing workload and transfusion time have not been well evaluated. PURPOSE: To assess feasibility of a simulation-based crossover trial and obtain preliminary estimates comparing nursing workload and transfusion completion time between WB and blood component administration. METHODS: A randomized crossover pilot study using in situ simulation was conducted with experienced trauma nurses. Time-motion analysis measured transfusion completion time, and the National Aeronautical and Space Administration Task Load Index assessed workload domains. RESULTS: Strong feasibility was demonstrated across recruitment, retention, adherence, and completion. WB was associated with significantly shorter transfusion time, lower overall workload and mental demand, less effort, and better perceived performance. CONCLUSIONS: These findings support the feasibility and justify a fully powered trial. WB may improve resuscitation efficiency and reduce cognitive burden, with potential implications for patient outcomes and nursing workflow.

Humans↗

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

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

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

From premature adrenarche to adult metabolic risk and hyperandrogenism: a systematic review and meta-analysis.

CONTEXT: Idiopathic premature adrenarche (IPA) has been associated with a higher risk of metabolic and reproductive dysfunction, but long-term/adult outcomes remain incompletely known. OBJECTIVE: To assess the relationship between IPA and metabolic syndrome, as well as polycystic ovarian syndrome, in premenarcheal adolescent and adult women. METHODS: We conducted a systematic review and meta-analysis of observational studies reporting outcomes in females with IPA after menarche. Databases were searched through February 2025. Primary outcomes included body mass index (BMI), insulin resistance markers, and clinical and biochemical markers of hyperandrogenism. Data were pooled using random-effects models. The GRADE approach was applied to assess the certainty of evidence. RESULTS: A total of 21 studies comprising 635 females with IPA and 307 age-matched controls were included. Compared to controls, IPA individuals showed significantly higher BMI (mean difference: 1.4; CI: 1.0-1.9), fasting insulin, and homeostasis model assessment of insulin resistance, indicating persistent insulin resistance. Markers of hyperandrogenism, including Ferriman-Gallwey score, dehydroepiandrosterone sulfate, and Free androgenic index, were also elevated. Secondary analyses revealed higher triglycerides, lower high-density lipoprotein, increased leptin, and greater carotid intima-media thickness, supporting an early pattern of cardiometabolic risk. GRADE assessment rated most outcomes as low certainty. CONCLUSION: Women with a history of IPA are at increased risk of long-term insulin resistance and hyperandrogenism, with early signs of adverse cardiometabolic profiles. These findings support the need for long-term monitoring in this population.

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↗