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Patient selection for triplet therapy with darolutamide in metastatic castration-sensitive prostate cancer and patterns of administration: a Spanish multicenter study

Clin Transl Oncol. 2026 Jan 4. doi: 10.1007/s12094-025-04174-8. Online ahead of print.

ABSTRACT

BACKGROUND: Triplet therapy with androgen deprivation therapy (ADT), docetaxel, and darolutamide is approved for treating patients with metastatic castration-sensitive prostate cancer (mCSPC) based on the results of the ARASENS trial. However, no guideline exists for patient selection beyond patient fitness for chemotherapy, personal preferences, disease volume, and metastases presentation. Evidence on patient selection and treatment administration in clinical practice is scarce.

PATIENTS AND METHODS: Prospective, multicenter study conducted in Spain between November 2023 and June, 2024 in mCSPC patients selected for triplet therapy. Sociodemographic and clinical characteristics of patients at primary diagnosis, disease-related characteristics and symptoms at mCSPC diagnosis, and information on triplet therapy administration were collected. Descriptive statistics were used.

RESULTS: During the study period, 105 patients from 15 Spanish hospitals were included in the study. The median age was 66 years (range 44-85). Ninety-three patients (88.6%) had synchronous disease. Most patients had ECOG-PS 0/1 (90.4%). Ninety-two (87.6%) patients had high-volume disease and 96 (91.4%) high-risk disease. Five (4.5%), 70 (67.3%), and 29 (27.8%) patients had M1a, M1b, and M1c disease, respectively. Bone (77.1%) and pelvic lymph node (70.5%) were the most frequent metastatic locations. Docetaxel and darolutamide were simultaneously initiated in 39 (37.1%) patients.

CONCLUSION: As in the ARASENS trial, most patients offered triplet therapy in this representation of Spanish clinical practice were young and had synchronous disease. However, poorer disease characteristics, such as high-volume, high-risk disease, and involvement of visceral metastases, were more frequent. The rate of simultaneous initiation of darolutamide and docetaxel was low.

PMID:41485187 | DOI:10.1007/s12094-025-04174-8

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Pharmacist-Led Deprescribing Interventions for Older Adults with Polypharmacy: A Retrospective Cohort Study of Community Pharmacy Practice in Japan

Drugs Aging. 2026 Jan 4. doi: 10.1007/s40266-025-01275-5. Online ahead of print.

ABSTRACT

BACKGROUND: Global aging makes polypharmacy in older adults a critical concern. Pharmacist-led deprescribing shows promise, but lacks routine implementation. Japan introduced “the Medication Adjustment Support Fee (the Adjustment Fee)” in 2018 for deprescribing medications in patients with polypharmacy based on pharmacists’ recommendations.

OBJECTIVE: We aimed to investigate: (1) medication distribution among older patients; (2) medications most frequently deprescribed based on pharmacists’ recommendations; and (3) factors associated with successful deprescribing.

METHODS: This retrospective study analysed patients aged ≥ 65 years who had prescriptions dispensed for ≥ 60 days from 2069 community pharmacies (April 2020-September 2023). Eligibility for the adjustment fee required six or more oral medications for ≥ 4 weeks, with pharmacists receiving remuneration when two or more medications were deprescribed and sustained for ≥ 4 weeks. We examined: (1) medication distribution in older patients; (2) most frequently deprescribed medications based on pharmacists’ recommendations; and (3) factors associated with deprescribing using multi-level logistic regression.

RESULTS: Amongst 1,458,323 older patients, 36.9% (537,884) met the eligibility criteria for the adjustment fee, but only 0.08% had medications deprescribed based on pharmacist recommendations. At the pharmacy level, 10% of pharmacies (213/2069) claimed the fee at least once. The most frequently deprescribed medications were rebamipide (0.05%), mecobalamin (0.06%) and magnesium oxide (0.02%). Older age, higher number of medications taken, presence of a family pharmacist, and longer evaluation periods were significantly associated with claiming for the adjustment fee (p < 0.001 for all).

CONCLUSIONS: Pharmacist-led deprescribing is infrequently implemented. Future studies could investigate the potential of strengthened incentives, enhanced collaboration, and robust protocols to optimize medication management in older adults.

PMID:41485177 | DOI:10.1007/s40266-025-01275-5

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The dietary index for gut microbiota and risk of advanced cardio-kidney-metabolic syndrome

Clin Exp Med. 2026 Jan 4. doi: 10.1007/s10238-025-02013-2. Online ahead of print.

ABSTRACT

As a novel dietary assessment tool, the dietary index for gut microbiota (DI-GM) measured food intake patterns that influenced GM balance. The association of DI-GM with advanced cardiovascular-kidney-metabolic syndrome (CKM) remained unclear. We aimed to explore the relationship between DI-GM and the advanced CKM risk. Participants from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018 were included. The DI-GM was defined based on intake levels of 10 beneficial and 4 unfavorable foods. To assess the association of DI-GM with advanced CKM risk, we employed multivariate logistic regression, receiver operating characteristic (ROC) analysis, and weighted quantile sum (WQS) regression. About 13,226 eligible participants were enrolled. Multivariable logistic regression showed that each 1-point increment in the DI-GM and beneficial food scores were associated with a 6% (95% CI: 0.92-0.97) and 7% (95% CI: 0.90-0.97) reduction in advanced CKM risk, respectively. Unfavorable food scores showed no significant association with advanced CKM risk. ROC analysis indicated that compared with the baseline model, the addition of the DI-GM (AUC: 0.743 vs. 0.741; P = 0.013) and the beneficial food scores (AUC: 0.743 vs. 0.741; P = 0.005) significantly improved the discriminatory ability of the baseline model for advanced CKM. WQS regression further identified broccoli, soybeans, fermented dairy products, and dietary fiber as the key dietary components strongly associated with advanced CKM. The DI-GM can function as a promising tool for assessing advanced CKM risk. For the general population, especially individuals with metabolic risk factors, increasing the intake of broccoli, soybeans, fermented dairy products, and dietary fiber may help reduce advanced CKM risk.

PMID:41485164 | DOI:10.1007/s10238-025-02013-2

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Long-term mechanical circulatory support in childhood in Hungary

Orv Hetil. 2026 Jan 4;167(1):30-36. doi: 10.1556/650.2026.33440. Print 2026 Jan 4.

ABSTRACT

INTRODUCTION: Mechanical circulatory support devices play a key role in stabilizing patients with end-stage heart failure and preparing them for heart transplantation. These devices significantly reduce waitlist mortality, especially in the pediatric population, where donor shortage and treatment challenges pose major difficulties.

OBJECTIVE: The aim of our study was to summarize domestic experiences with long-term mechanical circulatory support in pediatric patients and compare our outcomes with international data.

METHOD: We retrospectively analyzed data from 27 pediatric patients implanted with ventricular assist devices between 2008 and 2025. The patients were categorized into pulsatile and continuous-flow device groups. Anthropometric data, clinical status (INTERMACS profiles), organ perfusion, perioperative parameters, and long-term outcomes were evaluated.

RESULTS: The mean age of the 27 children was 9.14 years, with an average weight of 36.6 kg and an average height of 130 cm. The average duration of mechanical support was 217 days, significantly shorter in the pulsatile group compared to the continuous-flow group (141 vs. 312 days, p = 0.009). The pulsatile group consisted of younger and smaller patients (5.3 vs. 13.9 years, p<0,001; 21 vs. 56 kg, p<0.001). More than 70% of the patients were successfully bridged to transplantation, with rates of 66% in the pulsatile and 83% in the continuous-flow groups. Continuous-flow devices were associated with fewer complications (33% vs. 60%), and less need for intensive care ventilatory support (6 vs. 20 days). No significant differences were found in organ perfusion and immunological sensitization between the groups. Post-transplant rejection rates were low and similar in both groups.

DISCUSSION: Mechanical circulatory support represents a significant advancement in the care for advanced heart failure children. Continuous-flow devices show a more favorable complication profile. However, significant risks remain in lower-weight patients (e.g., under 1 year of age), reflecting current technological and protocol limitations.

CONCLUSION: The domestic use of mechanical circulatory support in pediatric patients is effective and enables successful transplantation. Continuous-flow devices offer advantages due to lower complication rates and feasibility of outpatient care. Larger prospective studies are needed to further improve outcomes. Orv Hetil. 2026; 167(1): 30-36.

PMID:41485160 | DOI:10.1556/650.2026.33440

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Effects of blood flow restriction training on the function of chronic ankle instability: a systematic review and network meta-analysis

Physiother Theory Pract. 2026 Jan 4:1-15. doi: 10.1080/09593985.2025.2608879. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic ankle instability (CAI) is often treated with strength and balance training, but pain and fear of re-injury can limit tolerance to high-intensity exercise. Blood flow restriction training (BFRT) allows strength gains under low loads and may serve as an alternative for these patients. However, current research lacks a systematic evaluation of BFRT in individuals with CAI, particularly comparing different training modalities.

OBJECTIVE: To systematically evaluate the effects of BFRT on individuals with CAI through meta-analysis.

METHODS: Relevant randomized controlled trials were identified by searching eight databases (CNKI, VIP, Wanfang, PubMed, Embase, Web of Science, Cochrane Library, and PEDro) from their inception to October 17, 2025. Methodological quality was evaluated using the Cochrane Risk of Bias tool. Publication bias was assessed with Egger’s test.

RESULTS: A total of 3206 records were identified, and 11 studies were included. Compared with control groups, BFRT improved anterior Y balance score [MD = 2.08, 95%CI (0.37 to 3.79), p < .05], posterolateral Y balance score [MD = 2.88, 95%CI (0.64 to 5.11), p < .05], and CAIT score [MD = 2.39, 95%CI (1.28 to 3.51), p < .05]. There was no statistical difference between the BFRT and control groups in overall Y balance score [MD = 1.48, 95%CI (-0.18 to 3.13), p > .05] and posteromedial balance score [MD = 0.30, 95%CI (-1.85 to 2.44), p > .05]. Subgroup analysis was conducted based on pressure type. BFRT of relative pressure improved CAIT scores and most balance measures except posteromedial. BFRT of absolute pressure significantly improved CAIT scores but showed no effects on Y-balance in any direction or overall score. The probability ranking indicated that relative pressure BFRT was superior to absolute pressure BFRT.

CONCLUSION: Training under blood flow restriction can improve ankle balance and stability in individuals with CAI through neuromuscular adaptations. Relative pressure is more effective than absolute pressure, emphasizing the need for individualized training. Further high-quality studies are required to confirm long-term effects and refine protocols.

PMID:41485135 | DOI:10.1080/09593985.2025.2608879

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Individual and neighborhood socioeconomic inequality and the risk of dementia: A 14-year follow-up study

Alzheimers Dement. 2026 Jan;22(1):e71060. doi: 10.1002/alz.71060.

ABSTRACT

INTRODUCTION: Socioeconomic inequality is a non-negligible risk factor for dementia. However, complex associations of individual socioeconomic status (ISES) and neighborhood socioeconomic status (NSES) with dementia risk have not been determined.

METHODS: In 327,641 adults aged 40-69 years from the UK Biobank, we estimated the separate, interactive, and joint associations of ISES and NSES with the risk of dementia and explored the role of inflammatory markers and metabolites.

RESULTS: Low ISES and low NSES were associated with higher risks of all-cause dementia and its subtypes. A stronger association between ISES and dementia was observed in those with low NSES. The subpopulation with disadvantages in both ISES and NSES showed the highest risk of dementia. Inflammatory markers (e.g., lymphocyte percentage) and metabolites (e.g., valine) mediated the associations of socioeconomic status (SES) profiles with all-cause dementia.

DISCUSSION: These findings underscore the importance of eliminating socioeconomic inequality at both individual and neighborhood levels for preventing dementia.

HIGHLIGHTS: Disadvantages in both individual socioeconomic status (ISES) and neighborhood socioeconomic status (NSES) are associated with higher risks of dementia. There are significant interactions between ISES and NSES on dementia risk. The low SES subpopulation with disadvantages in both ISES and NSES has the highest risk of dementia. Inflammatory markers and metabolites partially mediate the associations of socioeconomic status (SES) profiles with all-cause dementia. Narrowing socioeconomic inequality at both the individual and neighborhood levels may help prevent dementia.

PMID:41485131 | DOI:10.1002/alz.71060

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Physeal Allograft Transfer for Physeal Bars: A Safety and Feasibility Study in a Domestic Swine Model

J Orthop Res. 2026 Jan;44(1):na. doi: 10.1002/jor.70133.

ABSTRACT

Premature physeal closure occurs following trauma, cancer, or infection. Current treatments have poor success rates. With recent pediatric donor tissue availability, physeal allograft transfer (PAT) can now be considered. The purpose of this study was to study the safety and feasibility of PAT in a large animal model. The aim of this study is to gather foundational data to inform future studies into the efficacy of PAT. Physeal defects were created in the distal femur of nine female domestic swine and treated with PAT from two male donor pigs, cementation, or bone autograft. Viability was assessed. After 3 months, physes were visualized using CT and MRI. Integration, tissue composition, donor DNA presence, and microscopic appearance were evaluated. Physeal allografts demonstrated 93% viability after procurement and preservation. All animals reached the 3-months study endpoint without gross deformations. No physeal bars formed in any group. Cystic changes were seen in experimental and control femurs. All groups showed disorganized tissue architecture without growth plate recapitulation. High allografts viability and structural integrity after procurement support the potential of this treatment. Although no gross deformities were found, transferred physes demonstrate poor integration and incomplete repair. The lack of physeal bar formation in the control group limits the reliability of the animal model for studying physeal allograft transfer. Lastly, this study was designed as a feasibility study and lacks power to compare treatment effects statistically. The efficacy of PAT for preventing growth arrest remains undetermined.

PMID:41485130 | DOI:10.1002/jor.70133

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Robot-Assisted Ileal Ureter Replacement: Comparisons Between Totally Intracorporeal and Extracorporeal Ileal Segment Preparation

Int J Med Robot. 2026 Feb;22(1):e70131. doi: 10.1002/rcs.70131.

ABSTRACT

BACKGROUND: The comparative perioperative outcomes of totally intracorporeal robot-assisted ileal ureteral replacement (TI-RAIUR) versus that of RAIUR with extracorporeal ileal segment preparation (RAIUR-EI) remain undefined. This study pioneers a comparative analysis between these approaches to guide clinical individualised therapy.

METHODS: Thirty-four patients who underwent RAIUR (22 via RAIUR-EI and 12 via TI-RAIUR) were included. Baseline characteristics, perioperative outcomes, and follow-up data were systematically compared.

RESULTS: There were no between-group differences in baseline characteristics. The RAIUR-EI approach significantly reduced the reoperation time for initial failed procedures. Both groups achieved 100% 1-year subjective success and stable long-term renal function. The complication rates were statistically similar, although one Clavien-Dindo III incisional hernia occurred in the RAIUR-EI group. In addition, the TI-RAIUR approach demonstrated better aesthetic outcomes.

CONCLUSIONS: Both techniques achieve reliable outcomes for long-segment ureteral reconstruction. The RAIUR-EI approach may optimise efficiency in more complex cases, whereas the TI-RAIUR technique results in better aesthetic outcomes.

PMID:41485112 | DOI:10.1002/rcs.70131

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Anti-mitochondrial M2 antibody links to cardiac involvement and immune-mediated inflammatory myopathy-like pathology in myositis

Rheumatology (Oxford). 2026 Jan 2:keaf670. doi: 10.1093/rheumatology/keaf670. Online ahead of print.

ABSTRACT

OBJECTIVES: Cardiac involvements in idiopathic inflammatory myopathies (IIM) is rare but potentially severe. Anti-mitochondrial M2 antibody (AMA-M2) has been implicated in cardiac involvements, but the association remains under-explored. This study aims to evaluate the clinical, pathological, and prognostic features of AMA-M2 IIM.

METHODS: This historic prospective cohort included IIM patients hospitalized at Peking Union Medical College Hospital between 2008 and 2020. Outcomes were prospectively collected through the PROMIS registry. Cox regression models were employed to identify risk factors of cardiac involvements and mortality.

RESULTS: Among 987 IIM patients, 55 (6%) were AMA-M2 positive. These patients exhibited higher rates of polymyositis (56% vs 23.5%, p< 0.001), and elevated baseline gamma-glutamyl transferase (GGT) (78.0 vs 35.0, p< 0.001) and alkaline phosphatase (ALP) (85.0 vs 64.0, p< 0.001). Throughout disease courses, AMA-M2 positive patients had significantly higher rates of cardiac involvements (60% vs 12.9%, p< 0.001), including arrhythmias (56%), heart failure (44%), and pulmonary hypertension (31%). Some of the muscle biopsies showed features consistent with immune-mediated necrotizing myopathy (IMNM), cardiac biopsies demonstrating structural degeneration with minimal inflammation, and liver biopsies confirming early-stage primary biliary cholangitis (PBC). Multivariate COX analysis identified AMA-M2 positivity as an independent risk factor for cardiac involvements (HR 3.156, p< 0.001). Despite frequent cardiac manifestations, long-term survival did not differ between AMA-M2 positive and negative patients (mean survival: 103.9 months vs 98.0 months, p= 0.86).

CONCLUSION: AMA-M2 positivity defines an IIM subgroup with significant cardiac involvements, an immune-mediated inflammatory muscle histology, but not necessarily worse long-term survival. These findings highlight the need for early recognition and tailored management of AMA-M2 IIM.

PMID:41485097 | DOI:10.1093/rheumatology/keaf670

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Clinical and radiographic outcomes of double-triangle locking compression plate (DT-LCP) versus T-shaped locking compression plate (T-LCP) in medial open-wedge high tibial osteotomy: a follow-up study of over 5 years

J Orthop Surg Res. 2026 Jan 3;21(1):1. doi: 10.1186/s13018-025-06507-3.

ABSTRACT

OBJECTIVE: The purpose of this retrospective study was to investigate the differences in clinical efficacy and radiographic outcomes of the double-triangle locking compression plate (DT-LCP) and the T-shaped locking compression plate (T-LCP) fixation systems in open-wedge high tibial osteotomy (OWHTO).

METHODS: A retrospective analysis was conducted on the clinical data of 127 patients who underwent OWHTO at the Affiliated Hospital of Qingdao University between January 2019 and May 2020. Patients were divided into two groups based on the different steel plate fixation systems used: the DT-LCP group with 65 patients and the T-LCP group with 62 patients. Both groups underwent clinical and radiographic assessments preoperatively and at 5 years postoperatively. Clinical assessments were performed using the Visual Analog Scale (VAS), the Lysholm score, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Radiographic evaluations included measurements of the hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), weight-bearing line ratio (WBLR), joint line convergence angle (JLCA), and tibial posterior slope (PTS) to assess lower limb alignment correction postoperatively. The compensatory changes in adjacent joints were evaluated by measuring the hip abduction angle (HAA), talar tilt angle (TIA), and Carton-Deschamps index (CDI) in both groups. Complications were also analyzed for both groups.

RESULTS: At the 5-year follow-up, the complication rate was 20% in the DT-LCP group and 24.19% in the T-LCP group (χ2 = 0.324, p = 0.569). All radiographic measures of coronal alignment (HKA, MPTA, WBLR and JLCA) improved significantly from baseline in both groups (p < 0.001). After adjustment for pre-operative values, ANCOVA showed no between-group difference in HKA or JLCA (p = 0.319 and p = 0.287, respectively). MPTA and WBLR reached statistical significance, but with small effect sizes (MPTA: 0.89°, 95% CI 0.28-1.51; WBLR: 0.06, 95% CI 0.03-0.08). PTS increased similarly in both groups (effect – 0.80°, 95% CI – 1.95 to 0.34, p = 0.114). Compensatory changes in adjacent-joint parameters (HAA, TIA and CDI) did not differ between groups: HAA 0.21° (95% CI – 0.13 to 0.55, p = 0.226), TIA – 0.50° (95% CI – 1.43 to 0.42, p = 0.151), and CDI 0.08 (95% CI – 0.01 to 0.17, p = 0.225). Peri-operatively, the DT-LCP group outperformed the T-LCP group, with smaller incision, shorter operative time, less intra-operative blood loss (all p < 0.001) and lower hospitalization cost (p = 0.014). Clinical scores (VAS, WOMAC and Lysholm) improved markedly in both cohorts (p < 0.001), with no significant between-group differences in the magnitude of improvement (all p > 0.05).

CONCLUSION: This study demonstrates that both DT-LCP and T-LCP achieve favorable clinical outcomes after OWHTO, as evidenced by significant reductions in mean VAS scores and improvements in WOMAC and Lysholm ratings. The two fixation systems provide reliable correction in both the coronal and sagittal planes, with good alignment of lower-limb parameters such as HKA and MPTA, showing excellent durability and safety. Satisfactory functional results were obtained with either implant. However, the DT-LCP group demonstrated superior peri-operative performance, with a significantly lower incidence of implant-related irritation, thereby reducing the need for secondary hardware removal and resulting in a lighter economic burden.

PMID:41485088 | DOI:10.1186/s13018-025-06507-3