Background : Creatine is one of the most widely used dietary supplements worldwide and is increasingly consumed by non-athletic populations, including older adults and individuals with chronic metabolic, neurological, and musculoskeletal conditions. Given the high prevalence of prescription drug use in these populations, concomitant use of creatine and medications is common. Several biological pathways suggest potential creatine-drug interactions, particularly related to renal handling and biomarker interpretation; however, the clinical relevance of such interactions remains unclear. Methods : A PRISMA-aligned narrative and evidence-mapping review was conducted. PubMed (MEDLINE), Scopus, and the Cochrane Library (CENTRAL) were searched without date restrictions for human studies evaluating oral creatine supplementation in the context of concomitant prescription drug use, pharmacokinetics, or interaction-related safety outcomes. Title and abstract screening was performed using predefined eligibility criteria. In parallel, major drug-drug interaction databases (UpToDate, DDInter, Medscape, DrugBank, Drugs.com, the Merck Manual, and the FDA Drug Development and Drug Interactions resource) were queried to contextualize potential interaction signals. Results : Database searches identified 270 records, of which 132 unique articles remained after deduplication; none met inclusion criteria for full-text evaluation as human studies directly assessing creatine-drug interactions. Across drug-drug interaction databases, no clinically established creatine-drug interactions of moderate or high severity were identified. Reported interaction signals were uniformly classified as minor or theoretical and were primarily attributed to renal excretion–based mechanisms, without evidence of confirmed adverse clinical outcomes. Conclusions : Despite widespread real-world co-use of creatine supplements and prescription medications, no controlled human studies have directly evaluated creatine-drug interactions. Available evidence from creatine-drug interaction resources suggests predominantly low-severity, theoretical interaction signals rather than clinically confirmed interaction risk. However, the absence of documented clinical evidence should not be interpreted as evidence that interactions cannot occur, particularly in high-risk populations. These findings highlight a substantial evidence gap and underscore the need for targeted human studies to inform clinical guidance.
Background/Purpose Definitive chemoradiotherapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) has limitations in advanced disease. Paclitaxel, carboplatin, and cetuximab (PCE) offers a potentially safer induction chemotherapy alternative. This study evaluated the feasibility and outcomes of PCE induction followed by CRT compared with CRT alone among patients with Stage IV HNSCC who received definitive CRT. Materials and Methods This retrospective study included 128 patients with Stage IV HNSCC without distant metastases treated at a single institution (PCE group, n=52; CRT group, n=76). Survival analyses were restricted to the 127 patients who initiated definitive CRT, with time measured from CRT initiation to reduce immortal time bias; CRT completion was analyzed as an outcome, not an eligibility criterion. An adjusted Cox model accounted for baseline imbalances in T classification and Stage. Results Median follow-up was 17.0 months (PCE) and 65.0 months (CRT). The PCE group had more advanced disease (T3-4: 90.4% vs. 65.8%; Stage IVB: 34.6% vs. 15.8%). PCE achieved an 82.7% response rate, CRT completion in 51 of 52 patients (98.1%), and significantly higher cisplatin ≥200 mg/m² achievement (86.5% vs. 59.2%, p=0.002). PFS was longer with PCE in both unadjusted (HR: 0.515, 95% CI:0.271–0.980, p=0.043) and adjusted analysis (adjusted HR: 0.477, 95% CI:0.247–0.924, p=0.028). OS did not differ significantly (adjusted HR: 0.553, p=0.147), and its interpretation is limited by the shorter follow-up in the PCE group. Exploratory inflammatory and nutritional markers showed no reliable prognostic association. Conclusions PCE induction was feasible, with a high rate of CRT completion and acceptable tolerability. PFS was longer in the PCE group after limited adjustment, whereas OS did not differ significantly. Given the retrospective, nonrandomized design, residual confounding, and shorter follow-up in the PCE group, these findings are hypothesis-generating and require confirmation in larger, prospective studies.
Background Urothelial carcinoma (UC) is regarded as the third most common cancer in adults, with a high incidence and mortality rate, and lacks specific tumor markers. With the advancement of technology, DNA ploidy analysis technology has become more convenient and efficient. Through meta-analysis of the correlation between DNA aneuploidy rate and UC prognosis, a more efficient UC prognosis indicator was discovered. Methods Through searching PubMed, Web of Science, Embase and Cochrane Library database, we were able to identify the studies evaluating the prognostic value of DNA aneuploidy in UC. Results In all, 15 citations were included in this meta-analysis. Pooled results showed that DNA aneuploidy was significantly corrected with poor OS (HR = 4.32, 95% CI = 2.39-7.81, P < 0.001), poor DFS (HR = 1.84, 95% CI = 1.36-2.50, P < 0.001) and poor PFS (HR = 1.97, 95% CI = 1.37-2.83, P < 0.001) in UC patients. However, subgroup analysis revealed that DNA aneuploidy was associated with poor OS in Asian and American, but not in European. Correlation analysis of clinical pathological features suggested that DNA aneuploidy was related to the TNM stage, tumor grade, lymph node metastasis, tumor type and recurrence of UC. Conclusion Our meta-analysis showed the clinical value of DNA aneuploidy and its prognostic value in UC.
Background:Leptin plays a key role in regulating energy balance and lipid reserves. Leptin has a broad spectrum of regulatory actions. Adiponectin, an adipokine released by adipocytes, is recognized as an important factor in maintaining balance of blood glucose levels, lipid metabolism and insulin sensitivity. Recent studies have investigated the role of Ascorbic acid (AA) in the management of metabolic syndrome or the effect of high dose AA supplementation on serum AA, leptin and cortisol parameters. Purpose:The purpose of the current systematic review was to identify associations between AA supplementation and plasma leptin and adiponectin level in vivo and in vitro setting. Methods:Comprehensive systematic search was performed in the PubMed/Medline, SCOPUS, and Web of Science databases up to 14 May 2026. A total of 948 studies were initially searched, 187 from PubMed, 204 from the Web of Science, and 557 from Scopus databases. After excluding the duplicates, the remaining 435 articles were screened by reviewing the title and abstract, and 411 unrelated articles were excluded. Of the remaining 24 articles, 9 articles met our inclusion/exclusion. Results:The results obtained from the in vivo studies show that AA supplementation positively influences the secretion of adiponectin hormone from adipose tissue cells. Moreover, in vivo studies reveal an inverse relationship between AA concentration and leptin secretion, suggesting that AA supplementation may reduce leptin levels. However, human studies present conflicting evidence regarding the effect of AA on leptin levels. Conclusion:This systematic review demonstrates a positive relationship between AA and adiponectin and inverse relationship with leptin.
Background:Treatments for Hemophilia A include prophylaxis with factor VIII (FVIII) replacement therapy. With standard and extended half-life therapies, patients still experience bleeds, and administration 2-4 times a week is needed, which affects adherence. Efanesoctocog alfa is a once-weekly FVIII replacement therapy approved to treat and prevent bleeding in patients with hemophilia A for all age groups. Objectives:To analyze patient treatment preferences and satisfaction comparing once-weekly efanesoctocog alfa with pre-study prophylaxis in adults and adolescents with severe hemophilia A in the pivotal Phase 3 XTEND-1 study (NCT04161495). Methods:Exploratory post-hoc patient-reported outcomes were assessed by treatment preference at Week 52 (via a treatment preference survey) and patient satisfaction at baseline and up to Week 52 (via the 9-item Treatment Satisfaction Questionnaire for Medication [TSQM-9], covering: global satisfaction, effectiveness and convenience domains). Relationships between treatment satisfaction and preference versus bleeding and region were also explored. Results:Of 130 patients who completed the preference survey, 90.0% preferred efanesoctocog alfa versus their previous prophylaxis regimen. Similar trends were observed by region. The most common reasons were 'less frequent treatment', 'bleeds and bleed-related complications reduction', and 'feel better protected'. Of 115 patients who completed the TSQM-9 at Week 52, there was a statistically significant improvement from baseline in all three domains. By study end, an increase in the proportion of patients selecting the "best response" for all TSQM-9 items was observed. There were no strong correlations with treatment satisfaction improvements at Week 52 and improvement in quality of life or bleeding episodes. Conclusions:Prophylactic efanesoctocog alfa was preferred to prior prophylactic regimens by most patients and improved patient satisfaction at 52 weeks.
Renal transplant recipients (RTRs) have a 2-4 fold increased risk of malignancy due to long-term immunosuppression. We report a diagnostically challenging case of a 36-year-old man with a 16-year history of renal transplantation who presented with perineal pain, fever, and rising prostate-specific antigen (PSA), initially diagnosed as prostatic abscess. Ultrasound-guided aspiration yielded bloody rather than purulent fluid, prompting immediate biopsy that revealed poorly differentiated, PSA-negative prostate adenocarcinoma with BRCA2, ATM, and TP53 mutations. He underwent 3D laparoscopic radical prostatectomy with a modified surgical approach to avoid the transplant kidney. Postoperative genomics revealed multiple DNA damage repair gene mutations, raising therapeutic dilemmas regarding PARP inhibitor use in transplant recipients due to drug interactions with tacrolimus and potential nephrotoxicity. At 1-year follow-up, PSA was undetectable and graft function stable. This case highlights that in RTRs with pelvic symptoms, bloody aspirate from a presumed abscess should prompt immediate tissue biopsy, and rising PSA trajectory warrants investigation even in the "gray zone."
Background Despite the health benefits of vitamin B12, the potential association between vitamin B12 and all-cause mortality in populations with obesity remains understudied. Objective: To dissect this intrinsic association in adults with obesity and identify potential threshold effects. Methods: Data from 1999 to 2006 and 2011 to 2014 were retrieved from the National Health and Nutrition Examination Survey database. Three models were developed by adjusting for demographic characteristics, clinical factors, and comorbidities, and the relationship between vitamin B12 and all-cause mortality was further analyzed using Cox proportional hazards modelling, restricted cubic spline, survival curve analysis, and threshold effect analysis. Results Among 8301 participants with 1347 all-cause mortality over median follow-up of 9.08 years, the lowest groups Q1, Q2 and the highest group Q5 showed significantly increased all-cause mortality risk, although the P for trend was nonsignificant. The unweighted threshold effect analysis showed an inflection point of 354 pmol/L for serum vitamin B12 levels. Below this point, lower B12 levels were associated with lower all-cause mortality, whereas above the threshold, higher vitamin B12 levels were associated with high all-cause mortality. Conclusions All-cause mortality in the population with obesity showed an approximately U-shaped association with serum vitamin B12 levels. Maintaining serum B12 levels within 300 to 500 pmol/L is associated with a lower mortality risk. Owing to its observational design, causality cannot be inferred. Dynamic monitoring of vitamin B12 levels may help identify individuals at increased risk; however, further studies are needed to establish causality.
BACKGROUND:Risankizumab (RZB) is an anti-interleukin 23 (anti-IL-23) approved for the treatment of Crohn disease (CD). STUDY QUESTION:We aimed to evaluate the effectiveness and safety of RZB in the treatment of CD in real-world settings. STUDY DESIGN:We performed a retrospective review of a multicentre consortium of patients with CD treated with RZB. MEASURES AND OUTCOMES:Coprimary outcomes were clinical remission at week 12, 24, and 52 (Harvey-Bradshaw Index score of ≤4), and safety. Secondary outcomes included steroid-free clinical remission, clinical response, and endoscopic remission at 52 weeks. RESULTS:A total of 487 patients were included. The median follow-up was 24 (interquartile range: 16-38) weeks. A total of 372 (76.4%) patients achieved clinical remission at maximal follow-up. According to the treatment line in which RZB was administered, clinical remission occurred in 115/134 (85.8%) patients on second-line therapy, 112/153 (73.2%) on third-line therapy, and 145/200 (72.5%) on fourth-line therapy, with a significant difference ( P = 0.010). Adverse events occurred in 60 patients (12.6%) during follow-up; most of them were mild (50/60, 83.3%). Regarding the secondary outcomes: steroid-free clinical remission was achieved in 342 (71.8%) patients, and clinical response was observed in 443 (91.0%) patients. Six (1.2%) patients underwent surgery during follow-up. Mucosal healing was achieved in 34/67 (50.7%) patients. CONCLUSIONS:In this extensive, real-world study, RZB was effective and well tolerated in an advanced-therapy-exposed population of patients with CD and associated with favorable clinical and endoscopic outcomes.
