PURPOSE: Inavolisib plus palbociclib and fulvestrant has been approved for treating PIK3CA-mutated, hormone receptor-positive human epidermal growth factor receptor 2-negative (HR + HER2-), advanced breast cancer in the USA. This study evaluated the cost-effectiveness of inavolisib plus palbociclib and fulvestrant compared with palbociclib plus fulvestrant from the US payer perspective. METHODS: We developed a partitioned survival model at a 28-day cycle length over 15-year time horizons to predict total costs, life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and incremental cost-utility ratio (ICUR) at willingness-to-pay (WTP) threshold of $150,000 per QALY. Survival data were extracted from the INAVO120 clinical trial, costs and utilities were obtained from the department of Veterans Affairs, published literature and quality-of-life studies using the EQ-5D-5L scale. Uncertainty was addressed via scenario, one-way and probabilistic sensitivity analyses. RESULTS: In the base-case, inavolisib plus palbociclib and fulvestrant resulted in 1.99 life-years and 1.43 QALYs at an incremental cost of $211,639.64 with an ICER of $106,595.61 per life-year and an ICUR of $148,417.37 per QALY. The utility value of progression-free survival was the most influential parameter on the base-case results. Alterations in each model parameter did not significantly impact on the conclusions. The probability of inavolisib plus palbociclib and fulvestrant was cost-effective at the WTP threshold of $150,000 was 54.59%. CONCLUSION: Inavolisib plus palbociclib and fulvestrant may be a high-value treatment option for patients with PIK3CA-mutated, HR + HER2-, advanced breast cancer in the USA.

ALKBH5, as an m6A demethylase, plays a crucial regulatory role in various kidney diseases such as acute kidney injury, chronic kidney disease, renal fibrosis and renal cell carcinoma. However, its function often exhibits contradictory effects: In renal fibrosis, ALKBH5 has been reported to both promote and suppress fibrogenesis, whereas in renal cell carcinoma most studies support an oncogenic role, but some clinical observations link ALKBH5 downregulation to poor prognosis. These contradictions may stem from differences in cell types, disease stages, and microenvironments. This manuscript systematically reviews the complex function of ALKBH5 in kidney diseases and its underlying mechanisms, explores its potential as a therapeutic target, evaluates its therapeutic potential, and highlights the need for cell- and pathology-specific strategies to enable precise intervention. Future research should focus on its cell and pathological background specificity to achieve precise intervention.

Tyrosine kinase inhibitors are recommended as maintenance therapy following allogeneic stem cell transplantation (HSCT) for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), but optimal medication, dose, and duration remain a subject of ongoing study. We provide the final analysis of a prospective randomized trial comparing prophylactic and minimal residual disease (MRD)-triggered imatinib maintenance. The two patient cohorts did not differ significantly in terms of cumulative incidence of relapse (CIR; 14% vs. 18%), non-relapse mortality (NRM; 12% vs. 11%), leukemia-free survival (LFS) 64% vs. 69%, and overall survival (OS) at 10 years (68% vs. 71%). Endpoints were assessed every 6 weeks within the trial from 4 weeks after SCT until EOS at week 55 and after that according to local standards. In summary, this provides a framework for MRD-based treatment of patients for maintenance after HSCT with excellent long-term outcome after 10 years in both groups.

INTRODUCTION: Moderate-to-severe postoperative pain is common after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Evidence that liposomal bupivacaine provides clinically important advantages over conventional local anesthetics is inconsistent, and evidence in CRS + HIPEC remains limited. This trial evaluated the incremental efficacy and safety of liposomal bupivacaine incisional infiltration added to patient-controlled intravenous analgesia (PCIA) compared with saline infiltration plus PCIA. METHODS: In this single-center, randomized, participant- and assessor-blinded, placebo-controlled trial, adults aged 18-65 years scheduled for elective CRS + HIPEC were assigned 1:1 to standardized PCIA plus liposomal bupivacaine incisional infiltration (PCIA-LB) or PCIA plus normal saline infiltration (PCIA-NS). The primary endpoint was the incidence of moderate-to-severe movement-evoked incisional pain (numeric rating scale >  = 4) within 72 h. The prespecified primary efficacy analysis used the per-protocol set (PPS), with a conservative intention-to-treat (ITT) sensitivity analysis. PCIA followed an institutional standard operating procedure. Monitoring was continuous in the intensive care unit (ICU); after transfer to the ward, pulse oximetry was continued through postoperative day 3, with intermittent electrocardiography and noninvasive blood pressure monitoring. RESULTS: The PPS included 94 patients (PCIA-NS, n = 48; PCIA-LB, n = 46). Moderate-to-severe movement-evoked pain within 72 h was less frequent with PCIA-LB than with PCIA-NS (19.6% versus 70.8%, P < 0.001). The conservative ITT sensitivity analysis supported the same conclusion (26.0% versus 68.0%, P < 0.001). PCIA-LB also produced a modest reduction in cumulative 72-h study-recorded oral morphine milligram equivalents (556.8 [473.4, 600.0] versus 600.0 [557.4, 630.0] mg, P = 0.002) and reduced rescue analgesia (30.4% versus 54.2%, P = 0.020). QoR-15 scores did not differ significantly. Overall analgesia-related adverse events occurred in 23.9% and 10.4% of the PCIA-LB and PCIA-NS groups, respectively (P = 0.143). No participant required naloxone, emergency airway intervention, or ventilatory support for a clinically recognized opioid-related respiratory event, and no local anesthetic systemic toxicity, incisional infection, or fat liquefaction was observed. CONCLUSIONS: Compared with saline infiltration, liposomal bupivacaine incisional infiltration reduced early movement-evoked incisional pain and rescue analgesia and produced a statistically significant but quantitatively modest reduction in 72-h opioid consumption captured by the study records after CRS + HIPEC. It did not improve QoR-15. These findings do not establish superiority over plain bupivacaine, ropivacaine, or catheter-based regional techniques, and the study was not powered to establish safety. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2500100826. Registered at 00:00 on 15 April 2025, before enrollment of the first participant later the same day.

BACKGROUND: FGF/FGFR alterations are recurrent but heterogeneous in head and neck cancer, and which types predict benefit from selective fibroblast growth factor receptor (FGFR) inhibition is unknown. OBJECTIVE: We examined whether response to gunagratinib, a pan-FGFR1-4 inhibitor, differs by FGF/FGFR alteration type in recurrent or metastatic head and neck cancer. METHODS: Patients with recurrent or metastatic head and neck cancer and fibroblast growth factor(FGF)/FGFR alterations treated with gunagratinib in two prospective trials were combined (phase I ICP-CL-00301, n = 10; phase IIa ICP-CL-00304 at the recommended phase II dose [RP2D] of 20 mg once daily, n = 27). Confirmed objective response rate (Response Evaluation Criteria in Solid Tumours [RECIST] Version 1.1, investigator assessed) was the primary endpoint. Exploratory analyses examined efficacy by alteration type, with an RP2D sensitivity analysis and post-hoc CCND1 outcomes. RESULTS: Among 37 patients (23 head and neck squamous cell carcinoma, 9 nasopharyngeal carcinoma, 5 other; 78.4% with three or more prior therapy lines), confirmed the objective response rate at the RP2D (n = 27) was 7.4% (95% confidence interval 0.9-24.3) and disease control rate 55.6%, with no responses among FGFR-mutant patients (0/6) and single responses among fusions (1/2) and amplifications (1/6). In the pooled cohort (N = 37, including ten treated at sub-RP2D doses), objective response rate was 13.5% (95% confidence interval 4.5-28.8), disease control rate 56.8%, median progression-free survival 4.1 months, median duration of response 11.0 months and median overall survival 7.4 months. Four of five responses arose in receptor-level FGFR alterations rather than FGF3/4/19 amplification alone; because both mutation responses occurred at sub-RP2D doses, this pattern is hypothesis generating. Grade ≥3 treatment-related adverse events occurred in 35.1%, most commonly hyperphosphataemia; no treatment-related deaths occurred. CONCLUSIONS: At the RP2D, gunagratinib monotherapy had limited activity (0/6 among FGFR-mutant tumours). In the pooled cohort, confirmed responses concentrated among FGFR receptor-level alterations rather than the FGF3/4/19-amplified majority; because part of this signal came from sub-RP2D dosing, alteration type is a candidate enrichment criterion requiring prospective RP2D testing. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03758664 (registered 29 November, 2018) and NCT05372120 (registered 12 May, 2022, retrospectively).

BACKGROUND: Lung adenocarcinoma (LUAD) is marked by significant tumor heterogeneity and immune interactions that influence therapeutic response, while radiation-induced fibrosis poses a critical clinical challenge by compromising pulmonary function and complicating post-treatment surveillance. METHODS: A prognostic risk signature for lung adenocarcinoma was established by integrating transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repositories. The methodology involved initial screening for differentially expressed radiotherapy-related fibrosis genes, followed by least absolute shrinkage and selection operator (LASSO) regression coupled with multivariate Cox analysis to derive a compact risk model. Rigorous validation-encompassing survival analysis, receiver operating characteristic (ROS) evaluation, and external cohort testing-confirmed its predictive accuracy. Subsequent analyses delved into functional enrichment pathways, the tumor immune microenvironment, mutational characteristics, and potential chemotherapeutic responsiveness. RESULTS: Following construction and validation, a model based on six genes demonstrated high accuracy in predicting patient outcomes. Low-risk patients exhibited "hot" immune phenotypes with favorable immunotherapy responses, while high-risk patients showed elevated tumor mutational burden (TMB) and differential drug sensitivity. Three molecular subtypes were identified, with Group 3 representing a "cold" tumor phenotype associated with poorest prognosis. CONCLUSION: This study developed and validated a six-gene-fibrosis-based prognostic model for LUAD. The model stratifies survival risk and correlates with immune features and drug sensitivity, but provides a preliminary framework requiring prospective clinical validation.

The isatin scaffold has emerged as a promising platform for the development of anticancer agents, as evidenced by several clinically relevant isatin-based compounds. In this study, 85 novel isatin derivatives were designed based on literature reports and evaluated using drug-likeness prediction, ADME profiling, molecular docking, and molecular dynamics simulations. The compounds were screened against VEGFR-2, EGFR, and caspase-6 to identify potential multi-target lead candidates. Based on their binding affinity and pharmacokinetic properties, 41 compounds were shortlisted for further evaluation. Among them, compound 4 exhibited the most favorable binding profile and stable interactions with the selected targets. These findings suggest that compound 4 represents a promising lead for further investigation. However, experimental studies, including enzyme inhibition, cell-based assays, and evaluation, are required to validate its therapeutic potential. Overall, this study highlights the usefulness of computational approaches in the discovery of novel isatin-based multi-target lead candidates for cancer therapy.

Skeletal muscle aging is associated with increased lipid accumulation, or myosteatosis, leading to lipotoxicity and loss of muscle function. Here, we report that loss of the lactate receptor GPR81 in cellular and progeroid models of muscle aging is associated with impaired lipid oxidation and enhanced lipid accumulation. Knockdown of GPR81 in young healthy myoblasts led to an increase in senescence hallmarks such as DNA damage, accumulation of reactive oxygen species (ROS), impaired mitochondrial activity, and autophagy. Conversely, treatment of senescent myoblasts with GPR81 agonists enhanced lipid oxidation, leading to a decrease in lipid accumulation, ultimately resulting in decreased DNA damage, ROS accumulation, and enhanced ability to form myotubes. In agreement with our in vitro findings, we observed significant improvement in muscle regeneration and overall health of progeric mice that were treated with GPR81 agonists. Our findings suggest that GPR81 plays a key role in skeletal muscle lipid metabolism, and agonists of GPR81 might play a promising role in reversing age-associated lipid accumulation and loss of muscle function.

BACKGROUND: Hot flashes are common and often debilitating side effects of castration therapy; a cornerstone in the treatment of metastatic prostate cancer (PCa) as well as in localized or locally advanced PCa when combined with radiotherapy. The evidence for relieving vasomotor symptoms is limited. This systematic review presents both pharmacological and non-pharmacological interventions for treating hot flashes in men with PCa undergoing castration therapy, primarily androgen deprivation therapy (ADT). METHODS: a systematic literature search was conducted in PubMed using ("hot flash*" OR "hot flush*" OR "vasomotor*") AND ("prostate") as keywords. Studies with intervention for hot flashes due to castration therapy, estimation of treatment response (e.g., reduction in frequency or impact on quality of life) and patients with PCa (any stage) were eligible. RESULTS: Of 469 papers, 35 were included in the review. The included studies evaluated cyproterone acetate, estrogen or estrogen derivatives, progesterone derivatives, selective serotonin reuptake inhibitors (SSRIs), gabapentin, oxybutynin, and clonidine, as well as non-pharmacological interventions such as acupuncture, cognitive behavioral therapy (CBT), and dietary supplements (e.g., Dong Quai/Angelica Sinensis, Serelys Homme, soy protein, and Salvia officinalis). Across all blinded pharmacological interventions, the relative reduction in hot flash frequency ranged from -21% to -84%, and the placebo effect was between -19% and -30%. CONCLUSION: Hormonal agents such as cyproterone acetate and estrogen appear to be the most effective treatments, although they are associated with side effects. Non-pharmacological options like acupuncture and CBT may offer some benefit, while dietary supplements seem to be ineffective. Future studies are needed also to evaluate newer treatments, such as fezolinetant, in this patient population.

OBJECTIVE: Incidental prostate cancer (PCa) patients are currently stratified to either cT1a vs. cT1b stage, depending on tumor volume (< 5% vs. > 5%) in the resected tissue. We tested for other models that could improve cancer-specific survival (CSS) predictions. METHODS: Incidental (cT1a/cT1b) PCa patients were retrospectively identified within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). Kaplan-Meier plots illustrated CSS at 5 years of follow-up. Combination of variables resulted in three distinct stratification models based on cT1a vs. cT1b and Gleason score sum (GS). Multivariable Cox regression models that predicted CSS were used for area under the curve (AUC) quantification after 20-fold cross validation. RESULTS: We identified a total of 5155 incidental PCa patients. CSS at 5 years was 98% for cT1a vs. 90% for cT1b (p < 0.0001). CSS at 5 years for combination of cT1a and GS 6 patients was 99% vs. 92% for patients with either cT1b or GS ≥ 7 (p < 0.0001). Finally, for patients with GS < 8, CSS at 5 years was 98% vs. 72% for patients with GS ≥ 8 (p < 0.0001). The multivariable adjusted AUC was 0.83 vs. 0.82 vs. 0.88, for each model, respectively. CONCLUSION: Of all tested stratification models, the consideration of GS stratified between < 8 and ≥ 8 resulted in the best survival discrimination, as well as highest accuracy after cross-validation. In consequence, the use of this model (GS < 8 vs. ≥ 8) appears better suited than the standard cT1a vs. cT1b substaging, when CSS represents the endpoint of interest.

BACKGROUND: Upfront treatment intensification with androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor has become a standard approach for metastatic hormone-sensitive prostate cancer (mHSPC). However, prognosis remains poor for some patients despite second-generation androgen receptor antagonist-based doublet therapy. Although triplet therapy with darolutamide and docetaxel is available, its added clinical value over apalutamide- or enzalutamide-based doublet therapy in real-world practice remains unclear. Gleason pattern 5 (GP5) reflects aggressive tumor biology and may be relevant for treatment selection. We evaluated whether triplet therapy was associated with longer castration-resistant prostate cancer-free survival (CRPC-FS) than apalutamide- or enzalutamide-based doublet therapy in systemic treatment-naïve mHSPC, with a particular focus on effect modification by GP5 status. METHODS: This retrospective multicenter cohort study used the ULTRA-J multicenter collaborative database in Japan. We included systemic treatment-naïve patients with mHSPC who received either doublet therapy with ADT plus apalutamide or enzalutamide, or triplet therapy with ADT, darolutamide, and docetaxel, between February 2018 and October 2024. The final analytic cohort consisted of 294 patients. Overlap weighting was used to reduce treatment-selection bias. The primary endpoint was CRPC-FS, and overall survival (OS) was assessed as a supportive endpoint. Progression-free survival 2 (PFS2) and post-CRPC docetaxel use were evaluated as exploratory post-progression outcomes. RESULTS: The median follow-up duration estimated using the reverse Kaplan-Meier method was 18.0 months in the doublet group and 11.0 months in the triplet group. In the overlap weighting-adjusted overall cohort, triplet therapy was associated with longer CRPC-FS than doublet therapy (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.13-0.64; p = 0.002). A significant interaction was observed for GP5 status (p for interaction = 0.037). In the GP5-positive subgroup, triplet therapy was associated with longer CRPC-FS than doublet therapy (HR, 0.16; 95% CI, 0.06-0.42; p < 0.001), whereas no clear advantage of triplet therapy was observed in the GP5-negative subgroup (HR, 1.85; 95% CI, 0.29-11.94; p = 0.52). No clear difference in OS was observed at the current follow-up. CONCLUSIONS: Triplet therapy was associated with longer CRPC-FS than apalutamide- or enzalutamide-based doublet therapy in systemic treatment-naïve mHSPC. This association appeared more evident in patients with GP5-positive disease. Given the shorter follow-up in the triplet group, limited event numbers in subgroup and PFS2 analyses, and the nonrandomized nature of post-CRPC treatment sequencing, these findings should be interpreted as hypothesis-generating.

BACKGROUND: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) is reshaping nodal staging in prostate cancer by detecting regional lymph node metastases with greater accuracy than conventional imaging. This has created a new cohort of patients with N1M0 disease detectable only on advanced imaging, raising important questions regarding prognosis, treatment intensification and the applicability of historical management paradigms derived from conventional imaging. The aim of this review is to consider de novo N1M0 management on PSMA-PET and current evidence. METHODS: A comprehensive review of the literature was performed using Medline, PubMed and Web of Science. Search terms included combinations of "N1M0", "prostate cancer", "PSMA", "PET", "lymph node" and "metastasis". English-language studies and relevant reference lists were reviewed, with interpretation focused on diagnostic performance, stage migration and management implications of PSMA-PET-detected nodal disease. RESULTS: PSMA-PET outperforms conventional imaging for nodal staging, improving diagnostic confidence and frequently altering management. However, sensitivity for small-volume nodal disease remains imperfect, limiting exclusion of microscopic metastases. Emerging data suggest PSMA-PET drives stage migration whilst influencing use of surgery, radiotherapy and systemic therapy to better tailor treatment fields. However, high-level prospective evidence demonstrating improved long-term oncological outcomes remains limited. CONCLUSIONS: PSMA-PET is a practice-changing staging modality in N1M0 prostate cancer, but whether earlier detection and treatment escalation translate into meaningful survival benefit remains uncertain.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute leukemia; however, the first year after transplantation is associated with an increased risk of morbidity and mortality. This study aimed to evaluate changes in nutritional intake and body composition during the first 100 days following allo-HSCT and to examine their associations with one-year all-cause mortality. In this single-center prospective study, 152 adults scheduled to undergo allo-HSCT were assessed at baseline and on days +30 and +100 after transplantation. Assessments included anthropometric and body-composition measurements, dietary intake evaluation, and nutritional risk screening using the Nutritional Risk Screening 2002 (NRS-2002) tool. The prevalence of nutritional risk increased from 8.6% at baseline to 69.1% on day +30. In the primary analysis, a greater decline in fat-free mass (FFM) was associated with an increased risk of death within one year after transplantation (adjusted HR = 1.04 per 1-kg loss). However, this association was no longer observed in the landmark sensitivity analysis. During the first 100 days following allo-HSCT, nutritional status and body composition deteriorated markedly. A greater decline in FFM was associated with higher one-year mortality in the primary analysis; however, this association was attenuated and was no longer statistically significant in the landmark sensitivity analysis.

PURPOSE OF REVIEW: During infectious and noninfectious inflammatory diseases, disruption of the immune-hemostatic balance increases both thrombotic and hemorrhagic risk. We propose that this bidirectional dysregulation reflects the integrated contribution of megakaryocyte reprogramming during thrombopoiesis and direct remodeling of circulating platelets by inflammatory mediators, two interconnected regulatory levels that together shape the prothrombotic and hemorrhagic platelet phenotypes observed across inflammatory conditions. RECENT FINDINGS: Current evidence supports a two-level framework through which inflammation remodels platelet responses. Upstream, recent studies demonstrate that inflammation remodels thrombopoiesis, megakaryocyte transcriptional programs, and immunometabolism, generating platelets with altered immunothrombotic, thromboinflammatory, and prothrombotic properties. Converging evidence from aging, sepsis, myeloproliferative neoplasms, and rheumatoid arthritis identifies autophagy as a central target of inflammatory signaling linking megakaryocyte and platelet reprogramming to mitochondrial dysfunction and impaired clot contraction. Downstream, inflammatory mediators directly remodel platelet receptor signaling and promote receptor transfer, generating context-dependent platelet functional states that contribute to both thrombotic and hemorrhagic complications. SUMMARY: The platelet phenotype observed across inflammatory diseases reflects the integrated contribution of megakaryocyte reprogramming during thrombopoiesis and direct remodeling of circulating platelets by inflammatory mediators. These two levels of regulation likely operate simultaneously and may amplify each other, yet how they interact to determine platelet functional outcomes in specific inflammatory contexts remains to be determined. Defining these interactions will inform the development of mechanism-based therapeutic strategies that target inflammation-driven platelet dysfunction to reduce thrombotic and hemorrhagic complications across inflammatory diseases.

PURPOSE OF REVIEW: Immune reconstitution after adult allogeneic haematopoietic stem cell transplantation (allo-HSCT) shapes infection risk, vaccine responsiveness, relapse and nonrelapse mortality. Advances in graft-vs.-host disease (GvHD) prophylaxis, serotherapy exposure management, cytomegalovirus (CMV) control, functional immune monitoring and adoptive cellular therapy have changed which aspects of recovery can be modified and which augmentors are realistic in current practice. This review sets out what has evolved in adult practice and where intervention can now improve it. RECENT FINDINGS: GvHD prophylaxis, serotherapy dosing and CMV prophylaxis can increasingly be tuned to individual risk rather than applied uniformly, and exposure-guided and function-based measures are beginning to supplement simple subset counts. Adoptive approaches such as virus-specific T-cells offer targeted immune replacement in refractory viral disease, while thymic regeneration and cytokine-based strategies remain investigational. Updated vaccination guidance and recent immunogenicity data are sharpening humoral monitoring. SUMMARY: Taken together, these developments point towards a move from numerical subset counts to function- and exposure-guided assessment of immune reconstitution. Several determinants, including serotherapy exposure, GvHD prophylaxis, CMV control, microbiome preservation and selective adoptive immune replacement, now support individualised decisions, although prospectively validated intervention thresholds remain few.

Intercalary reconstruction following diaphyseal tumor resection is advantageous in that they preserve the joint above and below. Recently, intramedullary devices such as intramedullary nails (IMN), photodynamic bone stabilizing system (PBSS), and intercalary endoprosthetic reconstruction (EPR) have become increasingly used. Understanding the tradeoffs associated with each construct as well as characterizing their mechanical stability is essential for making a patient-specific decision for reconstruction. The mechanical properties of four different constructs used in the reconstruction of segmental defects in a femur model were compared: Double plate (DP) allograft secured by 90-90 plating, allograft secured by IMN and plate fixation, allograft secured by PBSS and plate fixation, as well as an intercalary prosthesis (EPR). Samples were tested in axial, bending and torsional loading, and mechanical properties were compared. The EPR during anterior-posterior bending had 51.63% of the displacement compared to the DP (p = 0.0007), and 55% of the creep over 100 cycles (p = 0.0126) with a rigidity of 201.3% (p = 0.0067). This difference also exists for cyclic torsion where the EPR rotates 52.32% the amount of the DP (p = 0.0044) and has 4.44% of the creep (p < 0.0001). The PBSS and IMN constructs had comparable results across all tests (p > 0.05). Overall, the EPR has comparable or superior mechanical stability to the DP, while the PBSS and IMN have similar mechanical properties. Together, these results can be used as a guide for surgeons to choose different implants depending on individual patient needs.

Introduction In recent years, artificial intelligence (AI)-generated prostate whole-gland segmentation has shown promise for clinical use. This study compares AI- and human-derived prostate segmentation on magnetic resonance imaging (MRI) and evaluates its practical application. Methods A retrospective study from December 2020 to December 2022 evaluated 31 randomly selected patients who had previously undergone MRI-ultrasound (US)-guided fusion biopsies. AI-generated auto-contours of the whole-gland prostate, seminal vesicle, and urethra were produced using the ProtégéAI feature of the MIM Software from MRIs obtained on GE Signa HDxt 3.0T and Siemens Altea Magnetom 1.5T scanners. The same MRIs were independently contoured manually by a board-certified urologist (U) and a board-certified radiologist (R) using MIM Software contouring tools. Volumetric conformity among the three contour sets was assessed using the Dice similarity coefficient, Hausdorff distance (HD), and mean distance to agreement (MDA). Contouring time was recorded for each method, with AI timed from command execution to file generation and physicians timed from file opening to save. Pairwise Wilcoxon signed-rank tests (JMP Pro 15) compared contouring times and similarities across AI to urologist (AI-U), AI to radiologist (AI-R), and urologist to radiologist (U-R) contours. Results The average volumetric Dice similarity, HD, and MDA for the AI-U contours were 0.875±0.039, 9.186±4.004 mm, and 1.410±0.511 mm for the whole-gland prostate, 0.283±0.185, 18.117±13.265 mm, and 4.907±4.992 mm for the urethra, and 0.377±0.244, 14.708±9.489 mm, and 4.260±4.092 mm for the seminal vesicle. For the AI-R contours, the values were 0.757±0.072, 17.562±7.240 mm, and 3.050±1.339 mm for the prostate, 0.162±0.105, 19.956±11.962 mm, and 4.798±3.879 mm for the urethra, and 0.451±0.219, 16.069±9.245 mm, and 4.075±3.734 mm for the seminal vesicle. For the U-R contours, the values were 0.769±0.070, 15.109±6.177 mm, and 2.733±1.265 mm for the prostate, 0.144±0.091, 13.560±7.087 mm, and 3.406±1.985 mm for the urethra, and 0.471±0.216, 12.981±6.756 mm, and 3.264±2.308 mm for the seminal vesicle. Using the Wilcoxon signed-rank test with statistical significance defined as p<0.01, the AI-U Dice similarity for the prostate differed significantly from both the AI-R and U-R comparisons. Similarly, AI-U demonstrated significantly different HD values than both AI-R and U-R, whereas the AI-R and U-R HD comparison was statistically insignificant. All pairwise MDA comparisons for the prostate were statistically significant. For the urethra, the AI-U Dice similarity differed from the other two comparisons, while for HD, the AI-R and U-R comparisons differed significantly from each other. No significant differences were observed among the three comparisons for the seminal vesicle across any metric. The average times to produce contours for the AI, urologist, and radiologist were 96.5 seconds, 285.8 seconds, and 217.9 seconds, respectively (p<0.01 for each time comparison). Conclusion This study suggests that AI may be a useful tool for prostate segmentation workflows in streamlining MRI-US prostate cancer diagnostics by producing similar contouring results in less time. Additional investigation should be conducted regarding the differences between the pathological outcomes of AI and non-AI contours, and the accuracy, cost analysis, and efficiency of AI technology should be elucidated.

Inflammatory myofibroblastoma tumor (IMT) is a rare mesenchymal neoplasm that develops in the lungs, retroperitoneum, or abdominopelvic region, and is most common in children and adolescents; although IMT usually has a good prognosis, some cases still show local invasion, recurrence, and even distant metastasis. Effective standard treatment for locally advanced or metastatic IMT is limited, but therapy with anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) improves the prognosis in some patients with ALK protein expression or ALK gene fusions. This case reports a 39-year-old woman with recurrent fever, cough, sputum, chest tightness, and shortness of breath for more than 2 weeks. Contrast-enhanced computed tomography (CT) revealed a mass in the upper lobe of the right lung with ill-defined borders involving the mediastinum, pleura, and right hilum. Multiple pleural nodules and right-sided pleural effusion were also observed. IMT was diagnosed by lung biopsy, and ALK positive was confirmed by immunohistochemistry. The patient's lung CT was reviewed after 3 weeks of treatment with brigatinib, and the right lung lesion and multiple metastases in the right pleura, hilar region, and mediastinum were significantly smaller than before. Additionally, the right pleural effusion was reduced, and the clinical symptoms were significantly improved compared to prior evaluations. Unlike most IMT cases, this patient's tumor showed highly malignant biology, with pleural metastasis at the initial diagnosis, as well as rapid progression and a favorable response to ALK TKI. Brigatinib represents a potential therapeutic option for the treatment of IMT.

Cancer remains a leading cause of mortality worldwide, highlighting the need for therapeutic strategies that reduce systemic toxicity and drug resistance. Resveratrol (RES), a natural polyphenolic stilbenoid, possesses antioxidant, anti-inflammatory, pro-apoptotic, anti-metastatic, and chemosensitizing activities. However, its clinical translation is limited by poor aqueous solubility, chemical instability, rapid metabolic clearance, and consequently low systemic bioavailability. Nanotechnology-based drug delivery systems provide a promising strategy to address these limitations. This review summarizes recent advances in RES-loaded nanoformulations, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, micelles, inorganic nanocarriers, protein-based systems, and biomimetic vesicles. Their therapeutic performance is evaluated across prostate, lung, colorectal, breast, and other cancers, with attention to tumor targeting, controlled release, combination therapy, multidrug-resistance reversal, and modulation of cancer-relevant pathways such as NF-κB, p53, and PI3K/Akt/mTOR. Current oncology-related clinical evidence for RES is still largely based on conventional oral or micronized formulations. Translation of engineered RES nanocarriers therefore requires stronger evidence on scalable manufacturing, carrier-specific safety, heterogeneous tumor delivery, and biomarker-guided trial design. This review also introduces a semi-quantitative prioritization framework based on model-readiness, translational priority, and safety-alert scoring for future PBPK, PK-PD, nano-QSAR, and machine-learning analyses.

BACKGROUND: Opioid-induced constipation is a practical bowel-management issue when opioids are started for cancer pain, but real-world naldemedine timing and subsequent laxative needs remain variable. OBJECTIVE: To describe naldemedine initiation timing/context after oxycodone start and early additional laxative adjustment among adults with cancer. DESIGN: Single-center retrospective cohort study using routine clinical records. SETTING/SUBJECTS: Adults with cancer pain in a single-center Japanese cancer-care setting who started oxycodone between June 1, 2017, and December 31, 2018, and subsequently received naldemedine. MEASUREMENTS: Concurrent initiation was naldemedine prescribed as part of the same oxycodone-start prescribing decision; reactive initiation was naldemedine added as a separate prescribing decision after physician-recognized constipation during ongoing oxycodone therapy. The primary outcome was prescription-record-based additional laxative initiation or dose escalation of existing laxatives within 7 days after naldemedine initiation. Secondary outcomes were oxycodone-to-naldemedine interval and diarrhea-related discontinuation within 28 days. RESULTS: Among 101 patients, the primary outcome occurred in 6/31 (19.4%) concurrent and 2/70 (2.9%) reactive cases ( = 0.010). The reactive group had a median oxycodone-to-naldemedine interval of 15 days (interquartile range, 5-83); diarrhea-related discontinuation occurred in 2/31 (6.5%) versus 6/70 (8.6%). CONCLUSIONS: Concurrent naldemedine at oxycodone start did not eliminate early additional laxative initiation or escalation. Naldemedine timing should be understood within individualized bowel-management planning, with conventional or rescue laxatives considered when clinically appropriate.

BACKGROUND: Oral lichen planus (OLP) is a chronic autoimmune disease that negatively affects patients' quality of life through symptoms such as pain, irritation, bleeding, and ulceration. Despite numerous therapeutic approaches, there is no definitive cure, and conventional corticosteroid therapy is often associated with prolonged use and adverse effects. Photobiomodulation therapy (PBMT) has emerged as a promising non-invasive alternative with no reported side effects. This systematic review aimed to evaluate the efficacy of PBMT in the treatment of OLP. MATERIALS AND METHODS: Electronic searches were conducted in PubMed, LILACS, Livivo, Scopus, Embase, Web of Science, and EBSCO up to March 1, 2025. Randomized and non-randomized clinical trials involving human participants were included, comparing PBMT with conventional pharmacological therapy. Risk of bias was assessed using the Cochrane tools, and the certainty of the evidence was evaluated using the GRADE approach. RESULTS: A total of 4,118 studies were identified, and 15 met the inclusion criteria after screening. Meta-analysis showed that PBMT slightly reduced pain levels compared with conventional therapy but did not significantly affect disease severity or anxiety scores. However, PBMT was associated with higher rates of complete mucosal healing and lower recurrence rates in patients with erosive OLP. CONCLUSIONS: PBMT appears to be a safe and effective therapeutic alternative for the management of OLP, particularly by reducing pain, promoting mucosal healing, and decreasing lesion recurrence. These findings support its potential role in clinical practice, although further high-quality randomized clinical trials are warranted to strengthen the current evidence.

BACKGROUND: Children and young people (CYP) with life-limiting conditions (LLCs) comprise a clinically heterogeneous population with diverse disease trajectories and survival patterns. However, studies evaluating long-term survival according to disease group and sociodemographic characteristics remain limited. OBJECTIVES: We assessed long-term survival patterns among CYP with LLCs and evaluated differences in mortality outcomes according to disease group and selected sociodemographic characteristics. DESIGN: Cohort study. METHODS: Using the Korean National Health Insurance database, we identified individuals aged 0-24 years who were newly diagnosed with LLCs between 2011 and 2013. Patients were followed from the date of diagnosis until death or December 31, 2020. Kaplan-Meier survival analyses and Cox proportional hazards models were used to evaluate long-term mortality outcomes according to disease groups and sociodemographic indicators, including insurance premium-based income categories and residential area. RESULTS: In total, 175,813 CYP with LLCs were included. Survival patterns differed significantly across disease groups, age groups, and income levels. Disease group distribution varied by age, with premature and neonatal conditions predominating in infancy. Survival probabilities were lowest among children aged < 1 year and among medical aid beneficiaries. Premature and neonatal disorders and cardiovascular diseases were associated with the shortest observed survival durations. Male patients demonstrated a higher hazard of death from cancer (hazard ratio [HR] 1.83), metabolic diseases (HR 1.61), and neurologic and neuromuscular diseases (HR 1.33) compared to female patients. Higher hazard ratios among medical aid beneficiaries were observed primarily in patients with metabolic, neurologic and neuromuscular diseases, whereas residence-related differences in survival were observed among patients with cardiovascular diseases. CONCLUSION: Distinct survival trajectories exist across disease groups among CYP with LLCs. Early mortality predominates in premature and neonatal disorders and cardiovascular diseases, whereas more prolonged survival patterns are observed in cancer and neurologic disorders. These findings may inform the development of disease-specific integrated treatment strategies, long-term care planning, and supportive care policies for CYP with LLCs and their families.

OBJECTIVE: This study aims to systematically evaluate the impact of exercise interventions on reproductive endocrine profiles in adult patients with polycystic ovary syndrome (PCOS) using a three-level meta-analytical approach. METHODS: We performed a systematic search of PubMed, Web of Science, The Cochrane Library, and Embase for randomized controlled trials (RCTs) investigating the effects of exercise on reproductive endocrine profiles in PCOS patients, spanning from database inception through April 7, 2026. A three-level meta-analysis was conducted in R using a random-effects model fitted restricted maximum likelihood (REML). Effect sizes were quantified as Hedges' g with 95% confidence intervals (CIs). Global heterogeneity was assessed using the Cochran's Q test, and the robustness of results was verified through leave-one-out sensitivity analyses. Model fit was compared using likelihood ratio tests (LRT). Publication bias was scrutinized Egger's test, with the trim-and-fill method employed as a corrective measure where necessary. Methodological quality was appraised using the PEDro scale, and the certainty of evidence was graded the GRADE profiler. RESULTS: Nineteen studies involving 1,018 participants were synthesized. Exercise interventions significantly lowered testosterone levels (g = -0.34; 95% CI [-0.61 to -0.07]; = 0.0146). Subgroup analysis revealed that the "aerobic exercise" group was statistically significant (k = 14, g = -0.5120, 95% CI [-0.8230 to -0.2010], = 0.0027). The mean body mass index (BMI) "25 to 29.9" group was also statistically significant (k = 17, g = -0.4859, 95% CI [-0.7775 to -0.1943], = 0.0025), as was the mean age group of "26 to 30 years old" (k = 13, g = -0.4878, 95% CI [-0.8465 to -0.1290], = 0.0105). CONCLUSIONS: In conclusion, exercise interventions exert a favorable impact on serum testosterone (T) levels in adult patients with polycystic ovary syndrome (PCOS). OTHER: PROSPERO (registration no. CRD420251108464; https://www.crd.york.ac.uk/prospero/).

BACKGROUND: Patients with hepatocellular carcinoma (HCC) presenting with both portal vein tumor thrombus (PVTT) and pulmonary metastasis (PM) have a particularly poor prognosis and limited treatment options. Hepatic arterial infusion chemotherapy (HAIC)-based combination therapy has shown promising activity in advanced HCC, but evidence in this high-risk population remains limited. OBJECTIVES: To evaluate the efficacy and safety of HAIC combined with lenvatinib and tislelizumab (HLP) in patients with HCC with concurrent PVTT and PM. DESIGN: Multicenter retrospective cohort study with propensity score matching (PSM). METHODS: Treatment-naïve patients with HCC with concurrent PVTT and PM who received lenvatinib plus tislelizumab (LP), with or without HAIC, between June 2018 and June 2024 were included. PSM was performed to balance baseline characteristics between treatment groups. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). RESULTS: A total of 262 patients were enrolled, including 114 patients in the HLP group and 148 patients in the LP group. After 1:1 PSM, 96 matched pairs were analyzed. The HLP group achieved significantly longer median OS than the LP group (15.1 vs 7.0 months; hazard ratio (HR), 0.55; 95% confidence interval (CI), 0.40-0.76;  < 0.001) and longer median PFS (7.3 vs 3.7 months; HR, 0.77; 95% CI, 0.56-0.94;  = 0.033). The ORR (47.7% vs 19.8%;  < 0.001) and DCR (86.1% vs 49.0%;  < 0.001) were also significantly higher in the HLP group. Although both all-grade and grade 3/4 treatment-related AEs were more frequent in the HLP group, toxicities were manageable, and no grade 5 AEs were observed. CONCLUSION: In patients with HCC with concurrent PVTT and PM, HLP was associated with improved survival outcomes and tumor response compared with lenvatinib plus tislelizumab alone, with a manageable safety profile.

BACKGROUND: Well-differentiated Grade 3 neuroendocrine tumors (G3 NETs) represent a heterogeneous entity with limited therapeutic standards. Surufatinib, a small-molecule inhibitor, has shown efficacy in G1/G2 NETs, but its specific role in the G3 subpopulation and optimal patient selection strategies remain to be elucidated. OBJECTIVES: This study aimed to evaluate the real-world efficacy of surufatinib in G3 NETs and identify the factors that influenced progression-free survival (PFS). DESIGN: A national, multicenter, retrospective observational study. METHODS: We analyzed data from 77 patients with unresectable or metastatic G3 NETs (Ki-67 > 20%) treated with surufatinib across 15 centers in China between January 2021 and April 2024. The reporting of this study conforms to the STROBE statement. The primary endpoint was PFS. A multivariable Cox proportional hazards model was used to explore prognostic factors. RESULTS: The median Ki-67 index was 30% (range: 22%-70%), and 49 patients were of pancreatic origin. A total of 11 patients were treatment-naïve, and 27 patients received surufatinib-based combination therapy. The overall median PFS was 9.4 months (95% confidence interval: 8.5-13.0), and the objective response rate (ORR) was 22.1%. Patients with a Ki-67 index ⩽ 30% had longer PFS than the Ki-67 > 30% group (12.6 vs 9.0 months, hazard ratio = 0.270,  = 0.003). Combined treatment showed a numerical trend toward improved ORR (33.3% vs 16.0%,  = 0.08), but did not significantly prolong PFS compared to surufatinib monotherapy (9.7 vs 9.4 months,  = 0.64). CONCLUSION: Surufatinib was a promising therapeutic option for G3 NETs. Prospective, larger-scale cohorts are warranted to confirm the efficacy and address the predictive markers for better patient selection.