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PubMed2026

De-escalation of radiotherapy in HPV-negative non-nasopharyngeal head and neck squamous cell carcinoma: a systematic review.

BACKGROUND: Definitive and postoperative radiotherapy are central components of treatment for head and neck squamous cell carcinoma (HNSCC) but are associated with significant toxicities that can impair long-term function and quality of life. De-escalation strategies, aiming to reduce treatment-related morbidity while maintaining tumor control, have attracted increasing interest. However, most research has focused on HPV-positive oropharyngeal carcinoma. Systematic evidence for HPV-negative disease remains limited. METHODS: PubMed and EMBASE were searched for prospective studies investigating radio(chemo)therapy de-escalation in HPV-negative, HPV-unspecified, or mixed non-nasopharyngeal HNSCC populations. CLINICALTRIALS: gov was searched for ongoing prospective trials. Data extraction and verification were performed independently by three investigators. RESULTS: Screening of 3156 records identified 14 published prospective studies, 10 in the definitive and four in the postoperative setting. Strategies included reduction or omission of elective nodal volumes, dose reduction, and combined approaches. Additionally, 23 ongoing prospective trials were identified. Across studies, elective nodal failure rates were consistently low (0-4.6%), with most recurrences occurring within high-dose volumes rather than de-escalated elective regions. Randomized evidence for elective nodal dose reduction is mixed: two trials maintained regional control and reduced acute toxicity, whereas another was stopped for futility. CONCLUSION: Available evidence on de-escalation in HPV-negative HNSCC is limited, derived primarily from small, heterogeneous phase II studies with mixed HPV populations. Although data are promising in selected settings, notably for elective nodal control, the randomized evidence for elective nodal dose reduction is conflicting, and further adequately designed prospective randomized trials are required.

Humans↗

PubMed2026

Shielding performance and clinical applicability of lead-free materials in computed tomography.

Owing to the high radiation exposure associated with computed tomography (CT) examinations and the image quality degradation caused by conventional radiation shielding materials, this study evaluated the dose reduction performance and image quality maintenance potential of a newly developed lead-free composite shielding material. This material was composed of bismuth, tungsten, tungsten carbide, aluminium, and polyurethane. Phantom-based dose measurements demonstrated that the shielding material achieved dose reduction rates ranging from 17.6% to 37.6%, depending on tube voltage. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and changes in tube current-time product (mAs) under a scout-based automatic exposure control (AEC) protocol were analysed according to the presence or absence of the shielding material across regions. For the clinical evaluation, CT scans were performed on four patients. Furthermore, the images were reviewed to evaluate whether this material affected image quality. The shielding material exhibited radiation reduction levels comparable to those reported in previous studies. SNR and CNR analyses showed minor statistical variations in certain regions; however, most differences were not statistically significant, and even significant differences remained within a range that did not compromise diagnostic image quality. Under the scout-based AEC protocol, the use of the shielding material resulted in less than 1% variation in mAs values. No visually perceptible artefacts or clinically significant image quality degradation were observed. The proposed composite shielding material demonstrated the potential to mitigate some limitations of conventional shielding materials and showed preliminary clinical feasibility as an adjunctive strategy for radiation dose reduction in CT examinations.

Radiation Protection↗

PubMed2026

Timing matters: Impact of covalent BTK inhibitor dose modifications on outcomes in chronic lymphocytic leukemia/small lymphocytic leukemia-A 7-year real-world study.

BACKGROUND: Covalent BTK inhibitors (cBTKis) are the cornerstone of chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) therapy, yet real-world data on dose modifications and their differential impact on long-term outcomes remain incompletely defined. This study investigated the incidence, timing, and the effectiveness of drug switching in a real-world CLL cohort. METHODS: In this 7-year retrospective real-world study, 324 CLL/SLL patients treated at a specialized Shanghai outpatient clinic (April 2018-April 2025; median follow-up, 42 months) were analyzed. Dose modifications were classified as dose interruption (DI) or dose reduction (DR). Their prognostic impact on progression-free (PFS) and overall survival (OS) was assessed by Kaplan-Meier analysis and multivariate Cox regression. RESULTS: The 42-month PFS rate was 70.2%. Of 324 patients, 229 (70.7%) experienced dose reductions or interruptions; infections were the predominant cause (61.9%). The full-dose (FD) group (n = 90) demonstrated superior 4-year PFS (93% vs. 58%, p < .001) and OS (98% vs. 76%, p = .007). Early modifications (0-3 months) were independent predictors of inferior PFS (hazard ratio [HR], 3.93, p = .008) and OS (HR, 3.29, p = .014). Prolonged DI (>14 days) was associated with inferior PFS (HR, 2.64) and OS (HR, 2.15), whereas DR and short DI (≤14 days) had negligible impact. Early (0-3 months) prolonged DI was devastating (3-year PFS, 41.2%; HR, 3.84, p < .001). cBTKi switching (n = 82; 100% nonprogression-driven) shortened DI (median, 6 vs. 14 days) and was independently associated with superior OS (HR, 0.34, p = .018) and PFS (HR, 0.36, p = .022). CONCLUSIONS: Early prolonged DI is the dominant adverse prognostic factor in cBTKi-treated CLL/SLL. Proactive switching minimizes treatment gaps and improves survival, supporting a timing-aware, DI- versus DR-informed approach to dose management.

Humans↗

PubMed2026

Optimizing Initial Dosing for Tacrolimus and Mycophenolate in Living Donor Liver Transplantation: A Systematic Critical Review.

BACKGROUND: The pharmacokinetics (PK) of immunosuppressive agents in living donor liver transplantation (LDLT) recipients are expected to differ from those in deceased donor liver transplantation (DDLT) recipients because of the smaller initial liver volume transplanted and pathophysiological changes during liver regeneration. Consequently, the hepatic metabolism, CYP enzyme activity, and glucuronidation may be reduced. The PK of tacrolimus (metabolized by CYP3A5) and mycophenolate (metabolized through glucuronidation) are expected to be affected early post-LDLT. However, the initial dosing recommendations for post-LDLT remain unclear. PURPOSE: This study aimed to recommend initial dosing approaches for tacrolimus and mycophenolate in LDLT recipients based on available PK data in humans. METHODS: A PubMed search was conducted in March 2025 to identify studies investigating the PK data of immediate-release tacrolimus and mycophenolate in pediatric or adult LDLT recipients. RESULTS: After screening, 8 and 8 articles on tacrolimus and mycophenolates, respectively, met the review criteria. The current literature suggests that LDLT recipients require lower tacrolimus doses than DDLT recipients, particularly in the early post-transplant period. In addition, CYP3A5 polymorphisms in both donors and recipients contribute to interindividual variability in tacrolimus exposure, further complicating tacrolimus management. Studies on mycophenolate use in LDLT recipients are limited, with insufficient evidence to support dose reduction. CONCLUSIONS: Reducing the initial tacrolimus dose in LDLT recipients by 30%-50% compared with that in DDLT recipients would be reasonable while maintaining the same initial dose of mycophenolate between LDLT and DDLT recipients.

Humans↗

PubMed2026

Long-Term Outcomes in Patients With Recurrent Ovarian Cancer and Exceptional Response to PARP Inhibitors.

IMPORTANCE: A subset of patients with platinum-sensitive recurrent ovarian cancer (PS-ROC) treated with maintenance poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have exceptional response. Although licensing recommends continuing PARP inhibitors until progression or unacceptable toxic effects, the optimal duration of PARP inhibitors, and the risks of late progression, myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML) in patients with exceptional response are unknown. OBJECTIVE: To determine the long-term outcomes of patients with PS-ROC who have exceptional response to PARP inhibitors, and to explore genotype-phenotype associations. DESIGN, SETTING, AND PARTICIPANTS: This was an international, multicenter, retrospective cohort study of patients with exceptional response to PARP inhibitors, defined as patients with PS-ROC and progression-free survival (PFS) of 5 years or longer from PARP inhibitor commencement. The study was conducted across 41 sites in 14 countries from January 11, 2023, to November 10, 2025. EXPOSURES: Treatment with PARP inhibitors. MAIN OUTCOMES AND MEASURES: The primary end point was PFS, and secondary end points included overall survival, toxic effects, and dose reductions. RESULTS: A total of 320 patients with exceptional response (mean [SD] age, 56.4 [9.4] years) were included, with a median follow-up of 6.8 years (95% CI, 6.6-7.0 years). The median (IQR) PARP inhibitor duration was 75.0 (64.0-91.0) months. Of patients with exceptional response, 211 (65.9%) received continuous PARP inhibitors, but 109 (34.1%) discontinued: 34 (10.6%) due to physician recommendation, 2 (7.5%) had disease progression beyond 5 years, 22 (6.9%) had toxic effects, 17 (5.3%) for patient preference, and 12 (3.8%) for another reason. The 7.5-year and 10-year PFS rates were 88.8% (95% CI, 84.5%-93.3%) and 78.7% (95% CI, 70.5%-87.9%), respectively. Among the patients, 85 (26.6%) discontinued PARP inhibitors for reasons other than disease progression, with a 10-year PFS of 90.1% (95% CI, 80.6%-100%) vs 72.5% (95% CI, 60.3%-87.2%) for those who continued taking PARP inhibitors. Five patients (1.6%) were diagnosed with late-onset MDS/AML. Patients with exceptional response were enriched for variants in the BRCA1 RING domain and the BRCA2 DNA-binding domain. CONCLUSIONS AND RELEVANCE: In this cohort study, most patients with exceptional response to PARP inhibitors remained progression free, including those who discontinued PARP inhibitors without progression. The risk of late-onset MDS/AML was low. These results can guide counseling on the duration of maintenance PARP inhibitors in patients with exceptional response and suggest that functional cure may be possible in patients with PS-ROC and exceptional response to PARP inhibitors.

Humans↗

PubMed2026

Older adults with resectable gastric cancer undergoing perioperative chemotherapy or preoperative chemoradiotherapy plus perioperative chemotherapy: A secondary analysis of the AGITG TOPGEAR phase III trial.

PURPOSE: To evaluate treatment adherence, adverse events, and survival in older (≥70 years) adults undergoing perioperative treatment for gastric cancer. METHODS: Patients with resectable gastric/gastro-esophageal junction adenocarcinoma (ECOG 0-1) enrolled in the phase III TOPGEAR trial were randomized to perioperative chemotherapy (ECF/ECX or FLOT) alone or perioperative chemotherapy plus preoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent fluoropyrimidine). In this exploratory analysis, treatment completion, grade ≥ 3 adverse events (CTCAE v3.0), surgical outcomes, overall survival (OS) and progression-free survival (PFS) were compared between older and younger adults. RESULTS: Of the 574 patients enrolled, 135 (24%) were ≥ 70 years. Older adults more frequently required preoperative chemotherapy dose reductions, omissions, or delays (chemoradiotherapy: 55% vs 35%, p = 0.004; chemotherapy: 60% vs 48%, p = 0.087). Rates of grade ≥ 3 adverse events were comparable between older and younger patients (chemoradiotherapy: 66% vs 67%, p = 0.874; chemotherapy: 68% vs 59%, p = 0.220), but older adults more often had hematologic toxicity and grade ≥ 3 diarrhea in the chemotherapy group (56% vs 37%, p = 0.006; 21% vs 6%, p < 0.001). Resection rates, grade 3/4 surgical complications, number of removed lymph nodes, and 30-/90-day mortality were similar by age. OS and PFS were comparable across age groups, with numerically favorable outcomes for older adults (OS: HR 0.86, 95% CI 0.58-1.26 [chemoradiotherapy]; HR 0.75, 95% CI 0.51-1.11 [chemotherapy]; PFS: HR 0.78, 95% CI 0.53-1.15 [chemoradiotherapy]; HR 0.70, 95% CI 0.47-1.03 [chemotherapy]). CONCLUSIONS: Older adults with gastric cancer achieved comparable oncologic outcomes to younger patients, despite more frequent treatment modifications and higher hematologic toxicity.

Humans↗

PubMed2026

Identifying biomarkers of accelerated ageing in cancer patients from routine clinical data.

INTRODUCTION: Cancer and ageing have a bidirectional relationship: age is the strongest risk factor for cancer, and cancer and treatments can accelerate ageing. Therefore, biological age can differ from chronological age; biomarkers are needed to stratify interventions to minimise accelerated ageing. METHODS: PhenoAge was calculated from routine blood test results of patients attending a Geriatric Oncology clinic. PhenoAgeAccel was the residual from a regression of PhenoAge against age. RESULTS: Data were available for 173 patients (62% male). Mean PhenoAge was higher than age (84.3 (12.6) vs 76.2 (7.24), p < 0.001), though the two were correlated (r = 0.579, p < 0.001). Unlike age, PhenoAge and PhenoAgeAccel were associated with one-year mortality (PhenoAge OR=1.083, 95% CI: 1.038-1.136; PhenoAgeAccel OR=1.096, 95% CI: 1.047-1.155). PhenoAge correlated with Clinical Frailty Score and Timed Up and Go (CFS: Rs=0.31, p < 0.001; TUG: Rs=0.25, p < 0.005); there were no correlations with age. PhenoAgeAccel correlated with the number of CGA interventions made (Rs=0.17, p < 0.05), unlike age and PhenoAge. Patients with diabetes mellitus had a higher PhenoAgeAccel compared to those without (3.40 vs -1.71, p = 0.002). In patients receiving systemic anti-cancer treatment, patients with PhenoAgeAccel calculated pre-treatment had less age acceleration than those with PhenoAgeAccel calculated post-treatment, both overall (2.18 vs -2.87; p = 0.048) and in matched samples (n = 21, 7.76 vs -2.87, p < 0.001). CONCLUSIONS: PhenoAgeAccel is a greater predictor of risk than chronological age in older people with cancer. This makes it a promising biomarker to stratify patients for holistic geriatric assessment, dose reductions, or future geroprotective measures which could be integrated within electronic healthcare record systems.

Humans↗

PubMed2019

CYP2D6 genotype and adverse events to risperidone in children and adolescents.

BACKGROUND: There are few and conflicting data on the role of cytochrome P450 2D6 (CYP2D6) polymorphisms in relation to risperidone adverse events (AEs) in children. This study assessed the association between CYP2D6 metabolizer status and risk for risperidone AEs in children. METHODS: Children ≤18 years with at least 4 weeks of risperidone exposure were identified using BioVU, a de-identified DNA biobank linked to electronic health record data. The primary outcome of this study was AEs. After DNA sequencing, individuals were classified as CYP2D6 poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers. RESULTS: For analysis, the 257 individuals were grouped as poor/intermediate metabolizers (n = 33, 13%) and normal/ultrarapid metabolizers (n = 224, 87%). AEs were more common in poor/intermediate vs. normal/ultrarapid metabolizers (15/33, 46% vs. 61/224, 27%, P = 0.04). In multivariate analysis adjusting for age, sex, race, and initial dose, poor/intermediate metabolizers had increased AE risk (adjusted odds ratio 2.4, 95% confidence interval 1.1-5.1, P = 0.03). CONCLUSION: Children with CYP2D6 poor or intermediate metabolizer phenotypes are at greater risk for risperidone AEs. Pre-prescription genotyping could identify this high-risk subset for an alternate therapy, risperidone dose reduction, and/or increased monitoring for AEs.

Adolescent↗

PubMed2026

Photon-counting detector computed tomography (PCD-CT) in multiple myeloma: a systematic review and trial sequential meta-analysis on image quality and radiation dose.

OBJECTIVES: To systematically review and perform a meta-analysis comparing the effects of PCD-CT versus EID-CT on image quality (sharpness) and radiation dose (CTDIvol) in patients with bone lesions due to multiple myeloma (MM). METHODS: A comprehensive search of PubMed, Embase, Scopus, and Cochrane Central was conducted from inception to October 2025. Studies comparing PCD-CT and EID-CT in MM patients were included. Methodological quality was assessed using ROBINS-I, and the certainty of evidence was assessed using GRADE. RESULTS: A total of 41 studies were identified that matched our search criteria. After duplicate removal and screening, five studies (n = 170 patients) were included in the systematic review, with four contributing to the meta-analysis. PCD-CT showed a significant pooled mean difference in image sharpness (mean difference, + 0.99 points; 95% CI, 0.62-1.37; p < 0.001). PCD-CT also demonstrated a reduction in radiation dose (mean difference, -4.95 milligrays; 95% CI, -8.39 to -1.50; p = 0.005). Trial sequential analysis (TSA) confirmed stability of pooled estimates, with conclusive evidence for image sharpness improvement, and suggestive yet incomplete evidence for radiation dose reduction. CONCLUSION: Compared to EID-CT in MM, PCD-CT significantly improves subjective image sharpness as supported by trial sequential analysis. Conventional meta-analysis suggested a reduction in radiation dose with PCD-CT; however, trial sequential analysis indicated that the cumulative evidence remains inconclusive. Further large-scale studies are suggested to confirm the magnitude of the radiation dose reduction benefit.

Humans↗

PubMed2026

Spiramycin fermentation residue-derived biochar regulates soil nutrient cycling, microbial communities, and antibiotic resistance gene dynamics.

Spiramycin fermentation residues (SFR) are hazardous wastes enriched with residual antibiotics, yet they can serve as potential feedstocks for resource recovery after appropriate treatment. In this study, SFR-derived biochar (SFR-BC) was produced by pyrolysis and applied to agricultural soil to evaluate its effects on soil properties, microbial communities, potential pathogenic bacteria, antibiotic resistance genes (ARGs), and mobile genetic elements (MGEs). A 60-day soil incubation experiment was conducted with one control and three SFR-BC application rates of 0.5%, 1.0%, and 2.0%. SFR-BC improved soil physicochemical properties, nutrient status, enzyme activities, and microbial alpha diversity. Metagenomic analysis showed that SFR-BC altered the abundance of functional genes associated with carbon and nitrogen cycling, indicating shifts in microbial functional potential. SFR-BC also changed bacterial co-occurrence patterns, with the high-dose treatment showing a more complex and highly connected network structure during incubation. In addition, high-dose SFR-BC reduced several potential pathogenic bacteria, including major plant pathogenic taxa. SFR-BC decreased soil ARG abundance by 9.38%-33.67% and MGE abundance by 6.49%-27.89% relative to the control, showing a dose-dependent reduction in antibiotic resistance-related genetic elements. Network and PLS-PM analyses further indicated that ARG variation was statistically associated with soil physicochemical properties, microbial diversity, potential bacterial hosts, and MGEs. Overall, these results suggest that SFR-BC can improve short-term soil nutrient status and reduce ARGs, MGEs, and several potential pathogenic taxa under controlled incubation conditions, providing useful evidence for the potential valorization of antibiotic fermentation residues through pyrolysis.

Charcoal↗

PubMed2026

CDK4/6 inhibitor dose patterns among older patients with metastatic breast cancer: A multinational survey study.

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CDK4/6 inhibitors↗

PubMed2025

Structural investigation of an RNA device that regulates PD-1 expression in mammalian cells.

Synthetic RNA devices are engineered to control gene expression and offer great potential in both biotechnology and clinical applications. Here, we present multidisciplinary structural and biochemical data for a tetracycline (Tc)-responsive RNA device (D43) in both ligand-free and bound states, providing a structure-dynamical basis for signal transmission. Activation of self-cleavage is achieved via ligand-induced conformational and dynamical changes that stabilize the elongated bridging helix harboring the communication module, which drives proper coordination of the catalytic residues. We then show the utility of CRISPR-integrated D43 in EL4 lymphocytes to regulate programmed cell death protein 1 (PD-1), a key receptor of immune checkpoints. Treatment of these cells with Tc showed a dose-dependent reduction in PD-1 by immunostaining and a decrease in messenger RNA levels by quantitative PCR as compared with wild type. PD-1 expression was recoverable upon removal of Tc. These results provide mechanistic insight into RNA devices with potential for cancer immunotherapy or other applications.

Programmed Cell Death 1 Receptor↗

PubMed2026

Efficacy and Safety of the Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist Mazdutide in Predominantly Chinese Adults With Obesity and/or Type 2 Diabetes: A Systematic Review and Meta-Analysis.

AIM: To assess the effects of mazdutide on body weight, HbA1c, metabolic outcomes, and adverse events in adults with overweight/obesity and/or type 2 diabetes (T2D). METHODS: This systematic review and meta-analysis included randomized controlled trials (RCTs) comparing mazdutide with placebo or active comparators in adults with overweight/obesity and/or T2D, identified through PubMed, Scopus, Web of Science, and ClinicalTrials.gov to 20 February 2026. Co-primary outcomes were percent change in body weight and change in HbA1c. Secondary outcomes included other weight-related and metabolic outcomes, as well as safety. Random-effects models were used to generate pooled mean differences (MDs) or risk ratios with 95% confidence intervals, and the certainty of the evidence (COE) was assessed using GRADE. RESULTS: Nine RCTs (N = 2292; most with low risk of bias) were included. In overweight/obesity without diabetes, mazdutide 3, 4, and 6 mg reduced body weight more than placebo (MDs -6.56%, -9.92%, and -11.1%, respectively; very low COE due to substantial heterogeneity and few trials). In T2D, mazdutide 4 and 6 mg reduced body weight and HbA1c versus placebo (moderate COE) and also outperformed dulaglutide for both outcomes. Mazdutide also improved waist circumference, lipids, liver enzymes, and uric acid levels. Gastrointestinal adverse events were more frequent, but serious adverse events and treatment discontinuation rates were comparable with those of the comparators. CONCLUSIONS: Mazdutide was associated with dose-dependent reductions in body weight and HbA1c, with broader metabolic benefits in predominantly Chinese adults with obesity and/or T2D. Longer-term, multi-ethnic studies are needed to confirm durability, generalizability, and cardiovascular safety.

Humans↗

PubMed2025

Antisense oligonucleotide-mediated MSH3 suppression reduces somatic CAG repeat expansion in Huntington's disease iPSC-derived striatal neurons.

Expanded CAG alleles in the huntingtin (HTT) gene that cause the neurodegenerative disorder Huntington's disease (HD) are genetically unstable and continue to expand somatically throughout life, driving HD onset and progression. MSH3, a DNA mismatch repair protein, modifies HD onset and progression by driving this somatic CAG repeat expansion process. MSH3 is relatively tolerant of loss-of-function variation in humans, making it a potential therapeutic target. Here, we show that an MSH3-targeting antisense oligonucleotide (ASO) effectively engaged with its RNA target in induced pluripotent stem cell (iPSC)-derived striatal neurons obtained from a patient with HD carrying 125 HTT CAG repeats (the 125 CAG iPSC line). ASO treatment led to a dose-dependent reduction of MSH3 and subsequent stalling of CAG repeat expansion in these striatal neurons. Bulk RNA sequencing revealed a safe profile for MSH3 reduction, even when reduced by >95%. Maximal knockdown of MSH3 also effectively slowed CAG repeat expansion in striatal neurons with an otherwise accelerated expansion rate, derived from the 125 CAG iPSC line where FAN1 was knocked out by CRISPR-Cas9 editing. Last, we created a knock-in mouse model expressing the human MSH3 gene and demonstrated effective in vivo reduction in human MSH3 after ASO treatment. Our study shows that ASO-mediated MSH3 reduction can prevent HTT CAG repeat expansion in HD 125 CAG iPSC-derived striatal neurons, highlighting the therapeutic potential of this approach.

Huntington Disease↗

PubMed2026

Assessment of the safety and efficacy of sodium pentaborate pentahydrate in individuals with overweight and obesity: a randomized, double-blind, placebo-controlled, phase 1/2 dose-finding trial.

The present study aimed to examine the short-term safety and tolerability of sodium pentaborate pentahydrate (NaB) and to explore preliminary efficacy and dose selection as secondary objectives in individuals with overweight or obesity. In this randomized, double-blind, placebo-controlled, phase 1/2 trial, conducted from July 2024 to January 2025, 177 adults with overweight or obesity were randomized, of whom 116 completed the 12-week trial. Participants received placebo or NaB at doses of 200, 400, 600, 800, or 1,000 mg for 12 weeks, alongside a standardized diet and exercise programme. The primary safety objective was to investigate short-term safety and tolerability through adverse events, hypoglycaemic episodes, gastrointestinal adverse events, and changes in haematological and biochemical parameters. The primary exploratory efficacy outcome was percentage change in body weight from baseline to week 12. Secondary and exploratory efficacy outcomes included body weight, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, glycaemic markers, lipid parameters, and blood pressure. Baseline characteristics were broadly similar across groups (all p ≥ 0.05), and no major short-term safety signal was observed. Mean body weight decreased in the 400 mg (-2.6 kg), 600 mg (-1.2 kg), and 1,000 mg groups (-3.1 kg). Compared with placebo, the 1,000 mg dose resulted in the largest reductions in body weight (mean difference, -2.30 kg; p = 0.01) and BMI (mean difference, -0.85 kg/m2; p = 0.02). The 1,000 mg dose showed preliminary efficacy for reducing body weight and BMI over 12 weeks compared with placebo, with no major short-term safety signal and no clinically meaningful changes in renal, hepatic, or haematological markers. All reported adverse events were mild. These short-term findings are exploratory and require confirmation in future phase 3 trials with extended follow-up to investigate long-term safety and efficacy.

Humans↗

PubMed2026

Comparative Efficacy of Non-opioid Analgesic Drugs for Chronic Cancer Pain: A Bayesian Network Meta-analysis.

PURPOSE: While opioids remain the primary pharmacological intervention for cancer pain management, their clinical utility is frequently compromised by dose-limiting toxicities. This study aimed to determine the comparative efficacy, opioid-sparing potential, and clinical hierarchy of non-opioid adjuvant drug classes. The study was structured around the PICO framework to evaluate the pharmacological strategies currently utilized in multimodal clinical oncology. METHODS: A systematic search of electronic databases (PubMed, Embase, Cochrane) was conducted for randomized controlled trials (RCTs) published between 2000 and 2025. The primary outcome was global analgesic efficacy (standardized mean difference [SMD]), while secondary outcomes included the opioid-sparing effect, defined as the percentage reduction in morphine equivalent daily dose (MEDD) and the incidence of treatment-emergent adverse events (Harms). A Bayesian network meta-analysis (NMA) was performed to rank treatments using SUCRA values. The methodological quality was assessed using the Cochrane Risk of Bias (RoB 2.0) tool. RESULTS: Twenty-three RCTs (n = 1845) met the inclusion criteria. Nonsteroidal anti-inflammatory drugs (NSAIDs) (-1.10) and anticonvulsants (-1.06) demonstrated the most robust analgesic effects. The SUCRA ranking confirmed a clear hierarchy, with the combination of anticonvulsants and antidepressants showing the highest probability of efficacy. A significant opioid-sparing effect was observed for gabapentinoids and ketamine, facilitating MEDD reduction. While serious adverse events were rare, minor harms (somnolence, dizziness) were more frequent in the most effective classes. CONCLUSION: Our NMA provides a robust evidence base for a "Clinical Tier" system, ranking adjuvants by their balance of efficacy and safety. These findings support the early integration of Tier I agents (anticonvulsants and NSAIDs) to optimize pain control and reduce opioid-related toxicities in chronic cancer pain management.

Humans↗

PubMed2025

Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.

The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n = 6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-β-CoV vaccines.

Animals↗

PubMed2026

Optimal dose and exercise modality to improve HbA1c in older adults with type 2 diabetes mellitus: a systematic review with pairwise, network, and dose-response meta-analyses.

We aimed to compare exercise modalities and evaluate dose-response relationships with glycemic control including continuous aerobic exercise (CAE), resistance training (RT), combined exercise (CE), mind-body exercise (MBE), and high-intensity interval training (HIIT) in older adults with type 2 diabetes mellitus (T2DM). Three databases were searched for randomized controlled trials of exercise interventions in older adults with T2DM reporting glycated hemoglobin (HbA1c). Pairwise, Bayesian network, and dose-response meta-analyses were conducted. Compared with control, HIIT demonstrated the largest estimated reduction (MD = -0.95%; 95% CrI -1.45, -0.49), followed by CE (MD = -0.59%; 95% CrI -0.93, -0.25), CAE (MD = -0.46%; 95% CrI -0.69, -0.24), MBE (MD = -0.42%; 95% CrI -0.76, -0.10), and RT (MD = -0.29%; 95% CrI -0.51, -0.08). Dose-response network meta-analyses suggested a non-linear association between overall exercise dose and HbA1c reduction, with maximal estimated benefits at approximately 704 METs-min/week with the 95% CrI excluding zero between 241 and 920 METs-min/week. HIIT demonstrated the steepest estimated dose-response relationship, but with wider credible intervals. Other exercise modalities showed more gradual dose-response patterns across their estimated effective ranges. Our findings suggest that exercise prescription for older adults with T2DM should be individualized according to exercise modality, dose, and health status.

Humans↗