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PubMed2026

The future of precision oncology and artificial intelligence in Belgium: scenarios and policy responses.

PURPOSE: Precision medicine, also known as personalized medicine, enables the provision of tailored health services to patients. In the prevention, early detection, and treatment of cancers, precision medicine is highly promising, given the increasing use of genomic profiling for diagnosis and adapting therapies in several tumor types. Artificial Intelligence (AI) can support this process by analyzing vast amounts of relevant data. However, high-quality data and financial investments in the health system are essential for the implementation of precision medicine and AI solutions in routine cancer care. DESIGN/METHODOLOGY/APPROACH: Building on the quantitative outcomes of a foresight exercise published in another study, this article collects qualitative data to gain more detailed insights into the future of precision oncology in Belgium and discusses the role of AI in this field. It reports the results of a series of expert workshops, focusing on four hypothetical future scenarios that are centered around technological and economic issues that must be overcome for the widespread use of precision oncology in Belgium. FINDINGS: The study concludes that all four scenarios discussed in the workshops would require supportive policy measures in Belgium, which should go beyond mere technological and economic considerations, such as involving patient associations and the public in policy design or creating multi-disciplinary expert groups for precision medicine. ORIGINALITY/VALUE: To the best of our knowledge, this is the first study to employ foresight methodology to illustrate possible future scenarios, scrutinize feasible approaches for implementing precision oncology in Belgium, and discuss the use of AI in this context.

Belgium↗

PubMed2025

A Systematic Review of Quantitative Studies of Depression and Loneliness in Black Women with Hypertension in the United States.

INTRODUCTION: Hypertension disproportionately affects Black women with subsequent complications that can extend beyond physical health. Notably, there is a significant relationship between hypertension, depression, and loneliness, with hypertensive Black women more likely to exhibit symptoms of depression. Since loneliness and social isolation are predictors of depression, recognizing and addressing these interconnected health concerns could improve patient outcomes and quality of life. This systematic review presents a synthesis of findings on depression screening practices, depression symptoms, and loneliness in quantitative studies of Black women with hypertension in the United States. METHODS: Using the EbscoHost platform, a comprehensive literature search for studies measuring depression and loneliness in Black women with hypertension was conducted. The following databases were selected: Medline Complete, CINAHL Complete, APA PsychArticles, and PsychINFO. RESULTS: Twenty-three articles were included; 16 focused on depression, and these studies highlighted a significant burden of depression in this demographic compared to their counterparts. Five studies reported loneliness and its relation to depression and hypertension. Loneliness and social isolation, as independent risk factors, exacerbated symptoms of depression and contributed to the onset and progression of hypertension. Two prior reviews corroborated these findings. Studies have emphasized the role of trust in clinical interactions and the importance of appropriate therapeutic interventions. DISCUSSION: Black women with hypertension are at a heightened risk for symptoms of depression, compounded by feelings of loneliness. Loneliness and depression are linked to physiological stress, contributing to hypertension. These problems are underrecognized and undertreated across populations, and this lack of recognition and treatment contributes to health inequity.

Humans↗

PubMed2026

Proteomic responses of the oil palm pest Metisa plana (Psychidae) to farnesyl acetate exposure.

Metisa plana Walker (Lepidoptera: Psychidae) is a major defoliator of oil palm in Malaysia, causing substantial economic losses. Farnesyl acetate (FA), a sesquiterpenoid compound, has been proposed as a potential insecticidal agent against M. plana, yet its molecular impact on larval physiology remains poorly understood. Here, we employed label-free quantitative proteomics, functional enrichment analysis, and targeted transcript assessment to characterize the temporal proteomic response of M. plana larvae at 7 and 14 days after treatment (DAT) with FA. Principal component analysis revealed robust separation between treated and control samples at both time points, indicating sustained treatment-driven proteomic restructuring. Early exposure (7 DAT) elicited a heterogeneous response involving stress-associated proteins, redox enzymes, and cytoskeletal regulators, whereas later exposure (14 DAT) produced a consolidated profile characterized by metabolic reprogramming, downregulation of ribosomal proteins, induction of heat shock proteins, and enrichment of RNA surveillance and mitochondrial pathways. Targeted transcript analysis qualitatively supported proteomic trends for HSP83 and aldehyde dehydrogenase X, although limited amplification precluded quantitative inference. Collectively, these findings demonstrate that FA exposure drives a shift from acute proteomic perturbation toward a maintenance-oriented physiological state, prioritizing proteostasis, energy management, and stress adaptation over growth and development. This integrated molecular perspective provides mechanistic insight into the chronic effects of FA, highlighting its potential to suppress larval performance and informing the development of biorational, physiology-based pest management strategies in non-model insects.

Animals↗

PubMed2026

Biomimetic mesoporous silica nanosphere ameliorate experimental autoimmune uveitis by delivering sCD83.

Autoimmune uveitis (AU) is an autoimmune disease that may lead to blindness, but there are currently no precise targeted therapies for its prevention and treatment. Dendritic cell (DC) is key cell involved in the pathogenesis of AU, and specific regulation of their state can help improve AU. In this work, mesoporous silica nanospheres were loaded with the immunomodulator soluble CD83 (sCD83) and subsequently camouflaged with dendritic cell (DC) membranes to fabricate the nanocarrier DCM@MSN/sCD83 for treating experimental autoimmune uveitis (EAU). Research results show that DCM@MSN/sCD83 effectively alleviated the symptoms of uveitis in EAU, reduced the proportion of CD4+CD25-T cell/CD4+CD25+T cell and the percentage of DC in the eyes and cervical lymph nodes. It also decreased the expression of STING in Müller cell. Furthermore, the efficacy of DCM@MSN/sCD83 was found to be primarily targeting DC, and promoted the expression of IL-10 and TGF-β1 in DC by activating the phosphorylated HIF/STAT3 pathway, to induce the production of CD4+CD25+ T. This effect is superior to nanomedicine loaded with dexamethasone. Moreover，DCM enabled the nanocarriers to efficiently cross the blood-eye barrier and reach cervical lymph nodes, thereby regulating peripheral immunity. This research indicate that cell membrane-modified nanoparticles targeting homologous cells can effectively improve treatment efficiency and duration, which is potential therapy strategy for uveitis.

Animals↗

PubMed2026

Comparison of Ketamine and Pregabalin on Postoperative Opioid Usage and Pain Management in Spinal Fusion: Systematic Review and Network Meta-analysis.

BACKGROUND CONTEXT: Spinal fusion is associated with substantial early postoperative pain and opioid exposure. Both ketamine and pregabalin are widely incorporated into Enhanced Recovery After Surgery (ERAS) protocols as opioid-sparing adjuncts. However, their comparative efficacy and safety in this specific setting remain uncertain. Our objective was to compare ketamine and pregabalin indirectly for early postoperative opioid consumption, pain, and adverse events in adults undergoing spinal fusion. METHODS: Pubmed, Embase, and Cochrane Trials were searched from inception through October 2025. Eligible studies were randomized trials enrolling adults undergoing instrumented spinal fusion, randomized to perioperative ketamine, pregabalin, or control, and reported extractable 24-hour opioid consumption or pain outcomes. Continuous outcomes were pooled as mean differences in MME or VAS units, and adverse events were reported descriptively. A connected treatment network was analyzed using random-effects models. Risk of bias (RoB) was assessed with the Cochrane RoB 2 tool. RESULTS: Thirteen trials (n=879) were included: ketamine (n=210), pregabalin (n=271), and control (n=398). Six trials contributed opioid data (3 ketamine, 3 pregabalin). Using pregabalin 150 mg as reference, ketamine was associated with lower 0-24-hour opioid use (MD -56.99 mg MME; 95% CI -99.56 to -14.43). Control (MD +21.31; 95% CI -1.05 to +43.66) and pregabalin 300 mg (MD -13.22; 95% CI -40.41 to +13.96) did not significantly differ from pregabalin 150 mg. Seven trials contributed 24-hour VAS data, with control being associated with higher pain versus pregabalin 150 mg (MD +0.84; 95% CI +0.01 to +1.66), while ketamine and pregabalin 300 mg were not k significantly different. Adverse events were generally infrequent and similar to control. CONCLUSIONS: Both ketamine and pregabalin provide early opioid sparing with comparable 24-hour analgesia. Ketamine showed a larger opioid-sparing point estimate, but indirect comparisons are imprecise. Adequately powered head-to-head trials with standardized protocols and adverse event reporting are needed.

Humans↗

PubMed2026

A systematic review of international/national guidelines for the management of nasopharyngeal carcinoma: Convergence and divergence of recommendations.

Increasing numbers of clinical practice guidelines have been published by international/national groups for nasopharyngeal carcinoma (NPC), providing valuable references for clinicians in making evidence-based decisions on treatment. However, there are substantial discrepancies in various recommendations, leading to uncertainties in choosing the optimal strategies. The authors systematically searched databases and organizational websites for NPC guidelines published between January 2000 and November 2025. All identified guidelines underwent quality appraisal; in total, 26 clinical practice guidelines rated recommended for use were included. The recommendations covering all management aspects (diagnosis, staging, radiotherapy, systemic therapy, follow-up surveillance, biomarkers, and salvage of recurrent/metastatic diseases) were summarized and comparatively analyzed for consistency and disparities. Strong consensus exists for diagnostic workup, staging systems, and induction chemotherapy plus concurrent chemoradiotherapy for advanced disease, whereas marked disparities exist on radiotherapy details, particularly target volume delineation, elective coverage extent, and dose specifications. Although systemic therapy strategies for different stage groups were mostly consistent, substantial disparities exist in alternative options and treatment details. This first comprehensive systematic synthesis of international NPC guidelines provides a practical reference for clinicians to understand all recommendations and select optimal options based on local resources and expertise while identifying current controversies that demand future research for further standardization and harmonization.

Humans↗

PubMed2026

Effects of digital health-based exercise interventions on older adults with sarcopenia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Sarcopenia, the progressive loss of muscle mass and function, impairs independence in older adults. Digital health exercise interventions are scalable solutions for older adults with sarcopenia. This systematic review and meta-analysis aimed to synthesize the evidence on their efficacy in populations with clinically diagnosed sarcopenia and identify influential intervention characteristics associated with treatment outcomes. METHODS: We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library, CINAHL, CNKI, and Wanfang on May 20, 2026, with no date restrictions. We included randomized controlled trials involving adults aged ≥60 with sarcopenia receiving digital exercise interventions. Two reviewers independently screened studies, extracted data, and assessed risk of bias; analyses were performed using R and Review Manager. RESULTS: Fourteen trials (n = 927) were included. Digital interventions showed potential improvements in muscle mass (MD = 0.25, 95%CI:0.03-0.46, 95% PI:-0.36 to 0.85), muscle strength (MD = 2.14, 95% CI:1.18-3.11, P < 0.001), balance ability (SMD = 0.31, 95% CI:0.12-0.51, P = 0.001), walking performance (SMD = 0.55, 95% CI:0.21-0.89, 95% PI:-0.70 to 1.79), and physical function (SMD = 0.89, 95% CI:0.08-1.71, 95% PI:-2.33 to 4.12), but not quality of life (SMD = 0.08, 95% CI:-0.19 to 0.35, P = 0.53). Exploratory subgroup analyses suggested that factors such as supervision, program duration, and measurement tools may influence outcomes; however, formal tests for subgroup differences were generally non-significant, and consistent patterns across all metrics were not observed. CONCLUSION: Digital exercise interventions show potential for managing sarcopenia in older adults, though the very low to moderate certainty of evidence indicates that true effects may differ substantially from observed estimates. This review explores potential roles of intervention design, supervision, and multimodal delivery. Future research should adopt rigorous designs and longer follow-up to validate results and enhance clinical application. TRIAL REGISTRATION: PROSPERO CRD420251135174.

Humans↗

PubMed2026

Preoperative Carbohydrate Supplementation Reduces Thirst and Improves Patient Satisfaction Before Elective Cesarean Delivery: A Randomized Controlled Trial.

BACKGROUND & AIMS: Prolonged preoperative fasting is a major source of patient discomfort, particularly thirst, before elective cesarean delivery. This study aimed to evaluate whether preoperative carbohydrate (CHO) supplementation could alleviate these discomforts and improve patient satisfaction without compromising safety. METHODS: In this single-center randomized controlled trial, 262 women scheduled for elective cesarean delivery under neuraxial anesthesia were randomly allocated to either the CHO group (Group CHO, n = 131), which received 355 mL of an oral carbohydrate solution on the night before and the morning of surgery, or the control group (Group C, n = 131), which followed conventional fasting. The primary outcome was the thirst Numeric Rating Scale (NRS, 0-10) score measured immediately before surgery. Secondary outcomes included hunger NRS, satisfaction NRS, and maternal and neonatal safety parameters. RESULTS: Baseline characteristics were comparable between groups. Despite a longer preoperative fasting duration in Group CHO (9.25 ± 1.05 vs. 8.74 ± 0.97 h, P < 0.001), this group exhibited significantly lower thirst NRS scores (1.69 ± 0.90 vs. 4.02 ± 0.99, P < 0.001) and hunger NRS scores (1.25 ± 0.94 vs. 2.09 ± 0.82, P < 0.001), as well as higher satisfaction NRS scores (7.70 ± 0.69 vs. 5.69 ± 1.17, P < 0.001). Subgroup analyses confirmed consistent benefits of CHO supplementation across most patient characteristics. Further analyses suggested that the maximum effect on thirst reduction occurred at approximately 9.2 h of solid fasting; however, the interaction between fasting duration and treatment group was not statistically significant (P = 0.187). CONCLUSION: Preoperative carbohydrate supplementation effectively reduces thirst and hunger and improves patient satisfaction before elective cesarean delivery without increasing maternal or neonatal risk. The beneficial effects were consistent across varying fasting durations, with exploratory spline analyses suggested a potential peak effect around 9.2 h, though this was not statistically significant and should be interpreted cautiously. These findings support the incorporation of carbohydrate loading into enhanced recovery protocols. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2500097956.

Humans↗

PubMed2026

Primary ACL Repair and Reconstruction in Isolated ACL Ruptures: Forgotten Joint Scores and the Association Between Residual Laxity and Joint Awareness.

BACKGROUND: Primary anterior cruciate ligament (ACL) repair has recently reemerged as a treatment option for carefully selected proximal ACL tears. However, evidence regarding patient-reported joint awareness and the relationship between postoperative laxity and joint awareness remains limited. PURPOSE: To compare joint awareness, clinical outcomes, and postoperative laxity between primary ACL repair and hamstring tendon autograft reconstruction in carefully selected patients with isolated ACL rupture, and to explore the association between residual laxity and postoperative joint awareness. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective cohort study included 85 patients with isolated ACL rupture treated with either primary ACL repair (n = 26) or hamstring autograft reconstruction (n = 59), with a minimum follow-up of 24 months. Clinical outcomes, including visual analog scale score, Lysholm score, International Knee Documentation Committee (IKDC) score, Tegner activity scale score, postoperative knee laxity, return to sport, and rerupture rates, were evaluated. The authors also used the Forgotten Joint Score-12 (FJS-12), a measure of joint awareness, to evaluate patients. A higher score reflects lower joint awareness, suggesting function more similar to a native knee. Multivariable regression analyses were performed to evaluate variables associated with postoperative FJS-12 values. RESULTS: No differences were observed between groups in postoperative Lysholm, IKDC, and Tegner activity scale scores; Lachman- and pivot-shift-assessed postoperative laxity; and return-to-sport rates. However, postoperative FJS-12 values were significantly higher in the repair group compared with the reconstruction group (87.0 ± 15.0 vs 77.5 ± 14.2; mean difference, 9.5 points [95% CI, 2.8-16.3]; P = .006), corresponding to a moderate effect size (Cohen d = 0.66). Secondary exploratory regression analyses demonstrated that residual postoperative laxity was associated with lower postoperative FJS-12 values in both Lachman- and pivot-shift-based models (R2 = 0.649 and 0.680, respectively; P < .001 for both). CONCLUSION: In carefully selected patients with proximal ACL tears and adequate tissue quality, no significant between-group differences were detected in conventional clinical outcomes, postoperative laxity, return-to-sport rates, or rerupture rates between primary ACL repair and reconstruction. Primary ACL repair was associated with higher postoperative FJS-12 values at short- to midterm follow-up, suggesting function more similar to that of a native knee. Residual postoperative laxity was associated with lower FJS-12 values in secondary exploratory analyses.

Humans↗

PubMed2026

An individualized nomogram for predicting progression-free survival in systemic anaplastic large cell lymphoma: a multicenter, retrospective, and internally validated study.

OBJECTIVES: To develop an individualized nomogram for predicting disease progression risk in systemic anaplastic large cell lymphoma (sALCL). METHODS: Independent predictors of progression-free survival (PFS) were identified using Cox regression in a multicenter retrospective cohort of 109 sALCL patients (2010-2022). These were incorporated into a three-factor nomogram, evaluated via bootstrapped internal validation (1000 resamples), ROC analysis, C-index, decision curve analysis (DCA), and clinical impact curve (CIC). RESULTS: A total of 29 PFS events occurred during a median follow-up of 31 months. Multivariable modelling selected serum β2-microglobulin elevation, extranodal disease, and front-line chemotherapy choice (CHOP versus CHOPE or BV+CHP) as autonomous progression drivers. Upon internal bootstrap validation, the nomogram yielded strong prognostic accuracy, achieving AUCs of 0.81, 0.85 and 0.87 for 1-, 3- and 5-year progression-free survival, alongside a corrected C-index of 0.779 (95% CI: 0.699 - 0.861). Calibration plots showed close agreement between predicted and observed outcomes, while DCA confirmed superior net clinical benefit versus conventional IPI or Ann Arbor stratification across multiple decision thresholds. CONCLUSION: This first sALCL-specific nomogram integrates clinical and treatment variables to provide personalized PFS risk estimation. While internally validated, this exploratory, observation-based tool requires external validation and recalibration in prospective cohorts before clinical implementation.

Humans↗

PubMed2026

Comparison between the thoracoabdominal rebalancing (TAR) method and the slow expiratory flow acceleration (SEFA) technique in preterm newborns: protocol for a randomised controlled clinical trial.

INTRODUCTION: Preterm newborns (PTNB) present respiratory immaturity and increased susceptibility to muscle fatigue. The thoracoabdominal rebalancing (TAR) method is a physiotherapeutic intervention developed in Brazil that aims to reorganise the synergy of the thoracoabdominal muscles and reduce the effort of the respiratory muscles, a benefit that is particularly important for PTNB; however, the evidence regarding its effectiveness in this population remains inconclusive. Therefore, this study aims to compare the short-term effects of the TAR method and the slow expiratory flow acceleration (SEFA) technique in improving respiratory distress and peripheral oxygen saturation (SpO2) in PTNB admitted to neonatal intensive care unit (NICU). METHODS AND ANALYSIS: The study will be a randomised, controlled, two-arm, parallel-group, single-blind clinical trial. 68 participants will be randomly assigned to one of the two treatment groups. Group 1 will receive four handling techniques of the TAR method for 10 min, followed by the rhinopharyngeal retrograde clearance with saline instillation (RRC+I) technique. Group 2 will receive the SEFA technique for 10 min, also followed by RRC+I. Primary outcomes are respiratory distress and SpO2. Secondary outcomes are respiratory rate (RR), heart rate (HR), pain, behaviour and diaphragmatic excursion. Assessments will be conducted by a blinded researcher at baseline (T0), immediately after the intervention (T1) and at the 30-minute follow-up (T2). Data will be described using measures of central tendency and dispersion and absolute and relative frequencies. An intention-to-treat analysis will be performed, and intragroup and intergroup comparisons will be assessed using generalised estimating equations (GEE). ETHICS AND DISSEMINATION: The Research Ethics Committee of the Faculty of Health Sciences of Trairi of the Federal University of Rio Grande do Norte approved this study (number 8,055,786). The results will be disseminated through peer-reviewed journal publications, scientific conferences presentations and knowledge translation to the public. TRIAL REGISTRATION NUMBER: This study was registered on Brazilian Registry of Clinical Trials (ReBEC) on 9 January 2026 (RBR-3gbsyc2).

Humans↗

PubMed2026

The global potential of freshwater microbes for plastic degradation.

Plastic pollution is becoming increasingly severe on a global scale, and the potential for biodegradation as a treatment method that is environmentally friendly merits greater attention. A significant number of genes that associated the degradation of plastic (PDAGs) have been identified, however, the distribution of these genes among microorganisms in global inland waters remains to be elucidated. A global-scale meta-analysis was conducted, incorporating approximately 1000 metagenome datasets of inland waters across seven continents. A total of 13,109 metagenome-assembled genomes (MAGs) were obtained by means of metagenomics binning, and 22,621 PDAGs were identified from these. Among these recognized PDAGs, phenylacetaldehyde dehydrogenase (PAD) was the most dominant (n = 16,664), followed by catalase (n = 5931). The predominant hosts for PAD and catalase were identified as Gamma-proteobacteria and Bacteroidia, respectively. The largest number of both PAD and catalase was found in MAGs from North America, while the average gene number in single MAG was highest in MAGs from Oceania. In accordance with the prediction of traits, PDAG-carrying MAGs from Europe demonstrated the fastest growth rate and the lowest optimal growth rate. Furthermore, 25 styrene monooxygenase (StyA) enzymes were identified, which were found to cluster into two distinct groups hosted by Alpha-proteobacteria and Gamma-proteobacteria, respectively. Moreover, 11 MAGs were observed to possess the complete pathway of polystyrene degradation. These results explored the potential of inland water microorganisms as a biological resource for plastic degradation and provided valuable microbial reference information that can be used to develop biological treatment technologies for mitigating plastics.

Plastics↗

PubMed2026

Quantification of appetite-regulating hormones in children with hypothalamic and common obesity.

CONTEXT: The pathophysiology of hypothalamic obesity (HyOb) remains incompletely understood with no effective treatments. OBJECTIVE: We examined differences in appetite-regulating hormone concentrations between patients with HyOb, common obesity, and lean controls. DESIGN: Multiway cross-sectional case-control study of patients aged 2 through 19 years. SETTING: Two tertiary pediatric endocrinology centers. PATIENTS: Cases were obese (body mass index [BMI] > +2 SD score [SDS], "HyOb") and lean ("HyLean") patients with congenital (septo-optic dysplasia) or acquired (suprasellar brain tumor) hypothalamic disorders. Controls had common obesity ("Ob") or nonhypothalamic disorders and normal BMI ("Lean"). MAIN OUTCOME MEASURES: Relationships between the Dykens' Hyperphagia Questionnaire Score (DHQS), plasma or serum concentrations of leptin, insulin, α-melanocyte stimulating hormone (αMSH), brain-derived neurotrophic factor, oxytocin, acylated ghrelin, agouti-related peptide and copeptin, and BMI SDS. RESULTS: Dykens' Hyperphagia Questionnaire Score did not differ between HyOb and Ob patients (24 [17-34] vs 24 [18-31]) but correlated with BMI SDS in patients with hypothalamic disorders (P = 0.02). HyOb and Ob patients exhibited similarly increased anorexigens (insulin, leptin) and decreased orexigens (ghrelin, agouti-related peptide) compared to HyLean and Lean patients. The rate of BMI increase was independently associated with lower αMSH (β = -0.23 [-0.36 to -0.11], P = .0007) and ghrelin (β=-0.004 [-0.01 to 0.00], P = .001) concentrations, suggesting that αMSH replacement may be a therapeutic target for HyOb. HyLean patients demonstrated intermediate insulin responses to glucose compared to other subcohorts. CONCLUSION: In our cohort, patients with HyOb appeared indistinguishable from Ob in terms of their appetite and appetite-regulating neuroendocrine circuitry. Higher αMSH concentrations are associated with reduced weight gain and may be a target for therapeutic intervention.

alpha-MSH↗

PubMed2026

Phentermine/Topiramate in Obese, Diabetic Uric Acid Stone Formers: An Open-Label Randomized Feasibility Trial.

PURPOSE: The purpose of this study was to determine whether medical treatment of obesity, diabetes, and low urine pH with combination phentermine/topiramate affects uric acid (UA) kidney stone burden. MATERIALS AND METHODS: Participants with obesity, diabetes mellitus, normal renal function, urine pH < 5.8, and stone analysis ≥ 80% UA were block randomized (2:1 ratio) to phentermine 18.75 mg/topiramate 100 mg vs pragmatic controls for an 18-month, prospective, open-label feasibility study with dose escalation. The primary outcome was change in CT stone volume. Secondary outcomes included medication adherence; patient safety; and change in anthropometrics, laboratory studies, and body composition. RESULTS: Nineteen participants (age 62.1 ± 9.8 years; 68% male; mean BMI = 36.3 ± 2.9 kg/m2) were randomized, and 15 completed the study with 73% pill adherence and no serious adverse events. Stone volume by intention-to-treat analysis fell by 52% in the intervention group and rose by 8.6% in the control group (P = .10), with per-protocol analysis demonstrating statistically significant stone volume reduction (P = .02). At study end and compared with means of controls, the intervention group had greater weight loss (-10.2 vs +2.9 kg), reduction in hemoglobin A1c levels (-0.2 vs +0.5), lower 24-hour urine citrate (309 ± 81 vs 951 ± 782 mg), and lower UA supersaturation (0.7 ± 1.1 vs 1.8 ± 1.0), along with higher 24-hour urine pH (6.2 ± 0.5 vs 5.5 ± 0.4) and calcium phosphate supersaturation (0.9 ± 0.8 vs 0.2 ± 0.1; all P < .05). CONCLUSIONS: Among obese participants with diabetes mellitus and UA nephrolithiasis, phentermine/topiramate was well tolerated and demonstrated significant stone burden reductions by per-protocol analysis. The intervention group also had greater weight loss, higher urinary pH, and lower hemoglobin A1c and urinary citrate levels. These data provide a framework to study the impact of this novel alternative UA therapy on a wider range of patients with obesity and diabetes.

Aged↗

PubMed2026

High-dose radiotherapy in patients with high-risk prostate cancers treated with long-term androgen deprivation therapy (GETUG AFU 18): a randomised, phase 3 trial.

BACKGROUND: For patients with high-risk prostate cancer, the role of dose-escalated radiotherapy in combination with long-term androgen deprivation treatment (ADT) is controversial, without any demonstrated benefit on cancer-specific or overall survival. We aimed to evaluate the effect of a 10 Gy dose increase, from 70 Gy to 80 Gy, on progression-free survival in men with high-risk prostate cancer. METHODS: In this multicentre, open-label, randomised, phase 3 trial, we enrolled patients with high-risk prostate cancer, defined as prostate-specific antigen of 20 ng/mL or more, Gleason score of at least 8, or clinical stage T3-T4, from 25 centres in France. Participants were randomly assigned (1:1) by minimisation, stratified by centre and previous pelvic lymph node dissection, to receive prostate-targeted dose-escalated external beam radiotherapy (80 Gy; 2 Gy per fraction for 8 weeks) or standard-dose external beam radiotherapy (70 Gy; 2 Gy per fraction for 7 weeks), combined with long-term ADT. Neither the participants nor the investigators were masked to the allocated treatment. The primary endpoint was 5-year progression-free survival defined as the time from randomisation to first biochemical (defined as prostate-specific antigen >nadir plus 2 ng/mL) or clinical (ie, local, regional, or metastatic) disease progression, analysed in the intention-to-treat population, with 197 events required. 5-year progression-free survival was the prespecified endpoint, and 10-year progression-free survival was additionally reported (post hoc) in view of the low number of events at 5 years. The trial is registered at ClinicalTrials.gov, NCT00967863, and is complete. FINDINGS: Between April 6, 2009, and Jan 24, 2013, 505 patients with high-risk prostate cancer were enrolled; 250 were assigned to receive dose-escalated radiotherapy (80 Gy) and 255 to receive standard dose radiotherapy (70 Gy). All participants were male and ethnicity data were not collected. At a median follow-up of 9·5 years (IQR 8·5-10·3), 5-year progression-free survival was 91·4% (95% CI 87·0-94·4) in the dose-escalation group versus 88·1% (83·2-91·6) in the control group, and 10-year progression-free survival was 83·6% (77·8-88·0) versus 72·2% (65·3-78·0; stratified HR 0·56, 95% CI 0·40-0·78, p<0·0001). Grade 3 or worse adverse events assessed at 6 months (acute toxicity) were observed in 60 (24%) of patients in the dose-escalation group and 62 (25%) in the control group. The most frequent grade 3 or worse adverse events were sexual disorders (28 [11%] in the dose-escalation group vs 20 [8%] in the control group) and bladder or urethra disorders (12 [5%] vs 19 [8%]). Adverse events assessed at 5 years (late toxicity) occurred in 118 (70%) of 168 in the dose-escalation group and 122 (73%) of 168 in the control group; grade 3 or worse late toxicities occurred in 19 (8%) participants in the dose-escalated radiotherapy group versus 17 (7%) participants in the control group. The most common late grade 3 adverse event was bladder or urethra disorders (seven [4%] vs three [2%], respectively). Serious adverse events occurred in nine (4%) patients in the dose escalation group and nine (4%) in the control group; none were considered to be treatment related. There were no treatment-related deaths. INTERPRETATION: For patients with high-risk prostate cancer, radiotherapy at a total dose of 80 Gy, in combination with long-term ADT, improved progression-free survival and could be a potential option in this situation. However, given the low number of events, further research is needed to consolidate and confirm the benefit in dose-escalation in prostate cancer-specific survival and overall survival. FUNDING: French National Cancer Institute and AstraZeneca.

Aged↗

PubMed2026

Integrated photoelectrocatalytic reduction and oxidation processes to achieve efficient degradation of fluoxetine in pharmaceutical wastewater.

Fluorinated organic compounds have been frequently detected in aquatic environments, with the widespread use of fluorinated drugs. The existing processes of urban sewage treatment plants are difficult to completely remove these pollutants containing the persistent C-F bonds. In this work, an integrated system of UV-activated sulfite and UV-assisted electrochemical oxidation was innovatively constructed for efficient degradation of fluoxetine. For the UV-activated sulfite unit system, when the sulfite dosage was 0.5 mmol/L and the initial pH was about 10, the defluorination efficiency of 5 mg/L fluoxetine wastewater under nitrogen atmosphere was about 98 %. Subsequently, the UV-assisted electrochemical oxidation unit system was employed to treat the reduced wastewater mentioned above. When the sodium chloride dosage was 25 mmol/L, the initial pH was about 5, and the current density was 30 mA/cm2, the total organic carbon (TOC) removal of the wastewater arrived at 65 %. Active species capture experiments and ESR tests confirmed that hydrated electrons, hydroxyl, and chlorine radicals were the main components for the efficient degradation of fluoxetine. According to the analysis of Fukui function and HPLC-MS, the degradation pathway of pollutants was proposed including defluorination and mineralization. Meanwhile, the toxicity of intermediates was predicted using the ECOSAR program. In addition, the verification test of actual wastewater treatment indicated that the defluorination and TOC removal efficiency of fluorouracil by the integrated system were similar to those for fluoxetine. This work provided a new approach for the efficient degradation of fluorinated organic pollutants in pharmaceutical wastewater.

Fluoxetine↗

PubMed2026

Immune dysregulation in depression and psychosis: summary of current evidence and future perspectives.

Despite compelling epidemiological, genetic and cellular evidence linking immune dysregulation to depression and schizophrenia (and other psychotic disorders), causality remains contested and no immune biomarker has yet demonstrated robust clinical utility. Emerging methodological approaches - from target trial emulation on observational data to functional genomics - offer a potential path towards precision immunopsychiatry and stratified immunomodulatory treatment.

Neuroimmunology↗

PubMed2026

Causal Relationship of Polyunsaturated Fatty Acids With Mental Disorders: A Systematic Review and Meta-analysis.

CONTEXT: Mental disorders (MDs) pose a important global health challenge, with a complex pathogenesis complicating treatment development. Nutritional interventions, particularly polyunsaturated fatty acids (PUFAs), have gained attention as potential therapeutic options. OBJECTIVE: This Mendelian randomization (MR) meta-analysis aimed to evaluate the potential causal relationship between PUFAs and MDs. DATA SOURCES: Genome-wide association study data were utilized to analyze the association between PUFAs (including omega-3, omega-3 percentage [omega-3%], omega-6, omega-6 percentage [omega-6%], and omega-6 to omega-3 ratio) and 12 major MDs. DATA EXTRACTION: Two-sample MR technology was used to assess the role of PUFAs in MDs. DATA ANALYSIS: The MR analysis revealed that genetically predicted omega-3 was causally linked to MDs, such as obsessive-compulsive disorder, bipolar disorder, schizophrenia, and major depressive disorder. Omega-3% exhibited protective effects against emotional personality disorder. Conversely, omega-6 was inversely correlated with attention-deficit/hyperactivity disorder risk, while a high omega-6 to omega-3 ratio was associated with an increased risk of depression and other mood disorders. CONCLUSION: High omega-3 levels and omega-3% may reduce the risk of MDs, whereas a high omega-6:omega-3 ratio may elevate the risk. These findings highlight the potential of PUFAs, particularly omega-3, in MD prevention and treatment, while underscoring the need for further research into the complex interactions between omega-3 and omega-6. The study provides a scientific foundation for future clinical trials and dietary intervention strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42024598472.

Humans↗