Tag: pubmed

Am J Cancer Res. 2025 Jun 15;15(6):2618-2630. doi: 10.62347/RLWT8295. eCollection 2025.

ABSTRACT

Osteosarcoma is a prevalent primary malignant bone tumor in young adults and adolescents, characterized by a high recurrence rate despite advancements in chemotherapy and surgical methods. This study investigated the effects of integrating high-dose methotrexate with cisplatin and paclitaxel on survival outcomes in osteosarcoma patients, and to identify prognostic factors influencing these outcomes. A retrospective analysis was conducted on 208 osteosarcoma patients treated between January 2013 and December 2018. Patients were divided into two groups: standard chemotherapy group (SC, n = 104) and cisplatin + paclitaxel + high-dose methotrexate (CPM, n = 104). The primary endpoints were progression-free survival (PFS) and overall survival (OS), while secondary endpoints included efficacy assessments. Kaplan-Meier survival curves were used to assess survival distributions, and statistical analyses were performed using SPSS 29.0. The CPM group demonstrated significantly longer PFS (16.85 ± 3.40 months vs. 15.72 ± 3.21 months, P = 0.015) and higher 5-year OS rates (54.81% vs. 40.38%, P = 0.037) compared to the SC group. Completion of chemotherapy and a response rate greater than 90% were identified as strong positive prognostic indicators. In contrast, pathologic fractures at diagnosis, lung metastases, and elevated lactate dehydrogenase levels were associated with poorer outcomes. Multivariate analysis underscored chemotherapy response and treatment adherence as independent survival predictors. The combination of cisplatin and paclitaxel with high-dose methotrexate significantly improves PFS and OS compared to standard chemotherapy. Moreover, treatment completion and achieving a chemotherapy response greater than 90% are critical factors for favorable prognosis.

PMID:40667547 | PMC:PMC12256419 | DOI:10.62347/RLWT8295

Ann Appl Stat. 2025 Jun;19(2):1314-1331. doi: 10.1214/25-aoas2013. Epub 2025 May 28.

ABSTRACT

Semi-continuous data frequently arise in clinical practice. For example, while many surgical patients still suffer from varying degrees of acute postoperative pain (POP) sometime after surgery (i.e., POP score > 0), others experience none (i.e., POP score = 0), indicating the existence of two distinct data processes at play. Existing parametric or semi-parametric two-part modeling methods for this type of semi-continuous data can fail to appropriately model the two underlying data processes as such methods rely heavily on (generalized) linear additive assumptions. However, many factors may interact to jointly influence the experience of POP non-additively and non-linearly. Motivated by this challenge and inspired by the flexibility of deep neural networks (DNN) to accurately approximate complex functions universally, we derive a DNN-based two-part model by adapting the conventional DNN methods with two additional components: a bootstrapping procedure along with a filtering algorithm to boost the stability of the conventional DNN, an approach we denote as sDNN. To improve the interpretability and transparency of sDNN, we further derive a feature importance testing procedure to identify important features associated with the outcome measurements of the two data processes, denoting this approach fsDNN. We show that fsDNN not only offers a statistical inference procedure for each feature under complex association but also that using the identified features can further improve the predictive performance of sDNN. The proposed sDNN- and fsDNN-based two-part models are applied to the analysis of real data from a POP study, in which application they clearly demonstrate advantages over the existing parametric and semi-parametric two-part models. Further, we conduct extensive numerical studies and draw comparisons with other machine learning methods to demonstrate that sDNN and fsDNN consistently outperform the existing two-part models and frequently used machine learning methods regardless of the data complexity. An R package implementing the proposed methods has been developed and is available in the Supplementary Material (Zou et al, 2025) and is also deposited on GitHub (https://github.com/BZou-lab/fsDNN).

PMID:40667518 | PMC:PMC12263096 | DOI:10.1214/25-aoas2013

Front Pharmacol. 2025 Jul 1;16:1608657. doi: 10.3389/fphar.2025.1608657. eCollection 2025.

ABSTRACT

BACKGROUND: With the increasing clinical use of tirzepatide, its safety profile has garnered significant attention. This article systematically reviews case reports of tirzepatide-associated adverse drug reactions (ADRs) to summarize their characteristics.

METHOD: We searched PubMed, Web of Science, ScienceDirect, Wiley Online, and Embase databases for case reports on tirzepatide adverse events using the keywords: “tirzepatide”, “adverse reaction”, “adverse event”, “side effect”, “safety”, “case report”, “induced”, “associated”, and “related”. Statistical analysis was performed on the identified cases.

RESULTS: A total of 43 cases of tirzepatide ADR were identified from 37 articles. Among these patients (24 female, 19 male; mean age 50.23 ± 17.24 years), 19 involved concomitant medications affecting multiple systems. ADR was reported in each dosage of tirzepatide, with the most occurring at 2.5-5 mg (16 cases), and primarily occurred within 1-6 months of initiation. Regarding rechallenge, 15 patients discontinued tirzepatide, three continued use, and one reduced the dose. ADR involved seven gastrointestinal tract and endocrine systems, including liver and gallbladder, circulation, nerve, skin, and urinary. Notable manifestations included ketoacidosis, liver injury, hypotension, intestinal obstruction, and allergic reactions. Among them, ketoacidosis and common peroneal neuropathy causing foot sagging, acute appendicitis, lower limb venous thrombosis, gastric outlet obstruction, gastric emptying delay, and acute liver injury were not mentioned in the drug instructions. ADR correlation assessment was performed for 8 patients:4 cases of cardiovascular events and ketoacidosis were all evaluated as “probable” using the Naranjo scale, 3 cases of liver injury were assessed by RUCAM (2 case as “possible”, 1 cases as “probable”), 1 case did not specify the evaluation method, with the result being “highly probable”. All 43 patients underwent ADR correlation re-evaluation:32 cases (74.42%) were assessed as “probable”,11 cases (25.58%) were assessed as “possible”.

CONCLUSION: Tirzepatide-associated ADRs most commonly occur within the first 6 months of treatment, primarily affecting the digestive, endocrine, liver, and gallbladder systems. Enhanced monitoring of liver and kidney function is warranted, especially in patients concurrently taking other potentially hepatotoxic or nephrotoxic medications. Additionally, intensified therapeutic drug monitoring is recommended for patients with cardiovascular disease, those requiring weight-based dosing adjustments, and those experiencing rapid weight loss.

PMID:40667509 | PMC:PMC12259682 | DOI:10.3389/fphar.2025.1608657

Front Pharmacol. 2025 Jul 1;16:1587440. doi: 10.3389/fphar.2025.1587440. eCollection 2025.

ABSTRACT

PURPOSE: Glaucoma, characterized by progressive retinal ganglion cell (RGC) degeneration and optic nerve atrophy, remains a leading global cause of irreversible blindness, despite advancements in clinical management. While current therapies predominantly focus on lowering intraocular pressure (IOP), neuroprotective strategies to preserve visual function remain an unmet clinical need. Stem cells exhibit high proliferative capacity and multilineage differentiation potential, demonstrating notable efficacy in glaucoma treatment. Emerging preclinical evidence further highlights dual neuroprotective mechanisms (i.e., paracrine neurotrophic support and cellular replacement) of stem cell-based interventions. Accordingly, this systematic review and meta-analysis evaluated the therapeutic efficacy and safety of stem cell transplantation in experimental glaucoma models, with a focus on functional outcomes (IOP modulation), structural preservation (RGC survival, and nerve fiber layer integrity), and neuroprotective efficacy.

METHODS: A systematic literature retrieval from multiple online databases (e.g., PubMed, Web of Science, Embase, Cochrane Library, Scopus, CNKI, WFSD, VIP, and CBM) was conducted through 3 January 2025, to identify relevant animal experimental studies. After the assessment of the risk of bias in the listed articles, this study further computed effect sizes of stem cell transplantation on indices such as IOP, RGC count. Statistical analyses were completed using RevMan 5.3.

RESULTS: In the meta-analysis involving 19 studies, the stem cell transplantation group had significantly lower IOP (MD = -1.55,95% CI = -2.62 to -0.47) at weeks 3 and 4, higher RGC count at weeks 2, 3, and 4 (MD = 23.06,95%CI = 18.22-27.89), and greater nerve fiber layer thickness (MD = 10.69, 95%CI = 9.44-11.94) compared to the control group. Meanwhile, the stem cell transplantation group also had higher retinal BDNF expression at weeks 2 and 4 (MD = 0.75,95%CI = 0.67-0.83), GDNF expression at weeks 1, 2, 3, and 4, and IGF-1 expression (MD = 0.49,95%CI = 0.39-0.58). None of these studies reported any adverse systemic events.

CONCLUSION: This meta-analysis provides preclinical evidence supporting stem cell transplantation as a multimodal therapeutic strategy for glaucoma, demonstrating significant efficacy in IOP modulation, neurostructural preservation, and neurotrophic factor expression. Given the severity of glaucoma-induced ocular structural damage, it underscores the significance of stem cell transplantation as a secure and promising therapeutic option with notable neuroprotective potential, despite existing translational challenges regarding optimal cell sources, delivery routes, and long-term safety profiles.

SYSTEMATIC REVIEW REGISTRATION: www.inplasy.com, identifier 202520023.

PMID:40667506 | PMC:PMC12259681 | DOI:10.3389/fphar.2025.1587440

Ther Adv Musculoskelet Dis. 2025 Jul 14;17:1759720X251354898. doi: 10.1177/1759720X251354898. eCollection 2025.

ABSTRACT

BACKGROUND: Hormonal changes in menopause might interact with the presentation of underlying autoimmune diseases, such as systemic sclerosis (SSc).

OBJECTIVES: Our study aimed to evaluate the association of (1) current menopausal status, (2) early menopause, and (3) disease onset during fertile or post-menopausal age on SSc clinical phenotype in a large SSc cohort from the Italian Systemic sclerosis Progression INvestiGation (SPRING-SIR) registry.

DESIGN: Female SSc patients from the SPRING-SIR registry, fulfilling the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2013 classification criteria, with data on SSc disease onset, menopausal status, and menopausal age, were eligible. SSc onset was categorized as pre-menopausal if SSc onset happened >1 year before menopause or as post-menopausal onset if it occurred >1 year after menopause. An early menopause was defined by a menopausal age <45 years.

METHODS: Descriptive statistics and regression models were built to test the association between current menopausal status, pre-menopausal disease onset, and early menopause with SSc-related features.

RESULTS: At baseline, 1157/1538 (75%) patients were in menopause, 632 (50.4%) had a pre-menopausal SSc onset, and 130 (14.4%) reported an early menopause. Post-menopausal patients had more frequent limited cutaneous SSc, anti-centromere antibody positivity, interstitial lung disease, and gastrointestinal manifestations. Pre-menopausal onset cases showed more frequent diffuse cutaneous involvement and peripheral vasculopathy. Patients with early menopause had more frequent peripheral vasculopathy and interstitial lung disease, being early menopause an independent risk factor for digital ulcers and lower diffusing capacity of the lung for carbon monoxide.

CONCLUSION: Current post-menopausal status and early menopause may impact SSc presentation, being associated with vascular and gastrointestinal manifestations. Menopausal status and age should therefore be thoroughly addressed, aiming at better disease management.

PMID:40667478 | PMC:PMC12260299 | DOI:10.1177/1759720X251354898

Front Neurol. 2025 Jul 1;16:1542833. doi: 10.3389/fneur.2025.1542833. eCollection 2025.

ABSTRACT

OBJECTIVE: To evaluate the efficacy of remote ischemic conditioning (RIC) in improving neurological function and short-term prognosis in patients with acute ischemic stroke (AIS).

METHODS: This randomized, controlled, single-blind study aimed to evaluate the short-term (7-day) effects of RIC on neurological function in patients with AIS. 264 AIS patients (median age 65 years, 63.3% male) with ischemic symptoms <72 h post-onset were randomly assigned to either the RIC group (n = 65) or the control group (n = 199). RIC was administered manually using a cuff sphygmomanometer, while the control group received a sham RIC treatment. Patients with cardioembolic sources or a history of prior stroke were excluded from the study. Primary outcomes were the proportion of patients with an mRS score of ≤2 at 7 days, as well as changes in the National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Activities of Daily Living (ADL), and Rancho Los Amigos (RLA) scores. Data were collected at baseline and 7 days post-enrollment, with in-person follow-up visits conducted by blinded clinicians.

RESULTS: At 7 days, the RIC group showed a significantly higher proportion of patients with an mRS score of ≤2 compared to the control group (41.5% vs. 28.1%, p = 0.043). Significant improvements were observed in the RIC group compared to the control group in NIHSS (p = 0.004) and ADL scores (p = 0.005), but not in RLA scores (p > 0.05). Binary Logistic Regression Analysis indicated that, after adjusting for baseline factors, the treatment effect of RIC remained statistically significant.

CONCLUSION: RIC treatment enhances neurological function and improves short-term prognosis in AIS patients. These findings support the potential clinical application of RIC in AIS management.

PMID:40667471 | PMC:PMC12259425 | DOI:10.3389/fneur.2025.1542833

Front Neurol. 2025 Jul 1;16:1539407. doi: 10.3389/fneur.2025.1539407. eCollection 2025.

ABSTRACT

BACKGROUND AND PURPOSE: Serum ferritin, a well-established biomarker of iron status, has been inconsistently linked to stroke risk in previous studies. This meta-analysis aims to systematically evaluate the association between serum ferritin levels and the risk of stroke.

METHODS: We conducted a systematic literature search across the PubMed and Embase databases to identify relevant studies. Studies meeting predefined eligibility criteria were selected, and relevant data were extracted. Statistical analysis was performed using Stata 12.0.

RESULTS: Ten studies, including eight longitudinal and three cross-sectional, were included in our meta-analysis. Cross-sectional studies showed that stroke patients had significantly higher serum ferritin levels than controls. Longitudinal studies suggested a 22% increase in stroke risk in individuals with higher serum ferritin. Subgroup analysis indicated that further high-quality population-based cohort studies are warranted to validate these findings. Dose-response meta-analysis confirmed a positive association between serum ferritin levels and stroke risk.

CONCLUSION: This meta-analysis provides evidence of a positive association between increased serum ferritin levels and stroke incidence. While these results are promising, definitive conclusions cannot be drawn at this time. Therefore, additional robust, prospective cohort studies are imperative to substantiate this relationship.

PMID:40667468 | PMC:PMC12259440 | DOI:10.3389/fneur.2025.1539407

HIV AIDS (Auckl). 2025 Jul 11;17:185-194. doi: 10.2147/HIV.S527111. eCollection 2025.

ABSTRACT

PURPOSE: Men who have sex with men are at high risk of Human immunodeficiency virus (HIV) infection and bear the highest burden of the disease in Tanzania. Although pre-exposure prophylaxis (PrEP) has demonstrated high efficacy in the prevention of HIV infection in clinical trials, challenges with retention threaten its effectiveness. Therefore, we assessed the extent and predictors of retention in PrEP care among men who have sex with men in Tanga, Tanzania.

METHODS: This study included 369 men who have sex with men who were recruited using respondent-driven sampling. Baseline data were collected using structured questionnaires that captured socio-demographic and behavioral characteristics. The primary outcome was one-month retention in PrEP care. A statistical analysis using modified Poisson regression was conducted to identify independent factors associated with 1-month retention.

RESULTS: A total of 369 men (mean age, 24.7 (± 5.5 years)) participated in the study. After one month, 87 participants (23.6%) were retained in PrEP care. Independent factors associated with retention included assuming a receptive position in anal sex (aPR 1.6, 95 CI: 1.0-2.6, p = 0.030), having initiated sexual activity with anal, oral, or thigh sex (aPR 2.1, 95% CI: 1.2-3.8, p = 0.011), and having adequate social support (aPR: 1.6, 95% CI: 1.0-2.6, p = 0.030).

CONCLUSION: Tailored interventions that improve social support and address the varying needs of men who have sex with men with diverse sexual behavior patterns are essential for improving retention and maximizing the effectiveness of PrEP in HIV prevention. Practically, this highlights the need to strengthen supportive environments within communities and healthcare systems to enhance retention in PrEP, reduce HIV transmission, and advance progress toward ending HIV as a public health threat by 2030.

PMID:40667454 | PMC:PMC12262076 | DOI:10.2147/HIV.S527111

Front Child Adolesc Psychiatry. 2025 Jul 1;4:1544344. doi: 10.3389/frcha.2025.1544344. eCollection 2025.

ABSTRACT

INTRODUCTION: This Clinical Experimental Study aimed to evaluate the effectiveness of Cooperative Parent Mediated therapy (CPMT), a targeted parent-coaching program for Autism Spectrum Disorder (ASD), in Community Healthcare Service in Italy.

METHODS: Forty children with ASD and their parents were randomly assigned to treatment conditions: the Control group received Individual Treatment As Usual (TAU Control group); while CPMT group received weekly parent-child sessions in addition to Individual TAU. Primary blinded outcomes were 6-months post-intervention change in parent-child interaction scores. Secondary outcomes included ASD symptom severity, adaptive functioning and parental stress levels. Baseline and post-treatment evaluations, at 6 months of follow up, were performed by an independent team.

RESULTS: CPMT group showed significant add-on benefits on parent-child interactions, severity of autism symptoms, adaptive skills and parental stress level.

DISCUSSION: This study provides preliminary evidence for the effectiveness of the CPMT model also in community services, representing a further step forward in research on the implementation of therapy for ASD in community healthcare service.

PMID:40667447 | PMC:PMC12259642 | DOI:10.3389/frcha.2025.1544344

Front Nutr. 2025 Jul 1;12:1583556. doi: 10.3389/fnut.2025.1583556. eCollection 2025.

ABSTRACT

PURPOSE: This study aimed to assess the effect of acupoint catgut embedding therapy (ACET) on anthropometric parameters and endocrine function in obese women through a systematic review and meta-analysis.

METHODS: A comprehensive search was conducted across international and Chinese databases [CNKI, Wanfang, Weipu, Sinomed, PubMed, Embase, Cochrane Library, Web of Science (WOS), and Scopus]. The search terms included “female,” “women,” “catgut implantation at acupoint,” “catgut embedding,” “acupoint embedding therapy,” “obesity,” “adiposity,” and “body weight,” etc. Studies included in this analysis were randomized controlled trials (RCTs) assessing the effects of ACET on obesity indicators such as body mass index (BMI), waist-to-hip ratio (WHR), lipid profiles such as triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), and hormone levels such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and estradiol (E2). We used ROB 2.0 to assess the risk of bias. Data was analyzed using weighted mean differences (WMD) and risk ratios (RR) to measure effect sizes, and heterogeneity was assessed using I ² statistics. Conduct sensitivity analysis, publication bias testing, and subgroup analysis on indicators with high heterogeneity to explore the sources of heterogeneity.

RESULTS: Twenty-three studies involving over 2,000 obese women were included. Risk of bias assessment revealed generally low bias in randomization and measurement domains, though selective reporting and missing data handling raised concerns in some studies. ACET significantly reduced BMI [-1.72 (95% CI: -2.13, -1.31)] and WHR [WMD -0.016 (95% CI: -0.034, 0.001)], with high heterogeneity in BMI analysis (I ² = 92.3%). Subgroup analyses suggested that heterogeneity decreased in different control groups and different treatment courses, such as diet guidance (I ² = 0.0%) and 12-week treatment duration (I ² = 32.9%). Publication bias assessments (Begg’s and Egger’s tests) indicated no significant bias for most indicators. However, the clinical efficacy rate showed potential publication bias upon trim-and-fill adjustment, though the effect remained significant. ACET significantly reduced TG and TC but not HDL, LDL, or insulin resistance. Hormonal changes included decreased LH and FSH and increased E2.

CONCLUSION: Our meta-analysis demonstrates that ACET significantly improves anthropometric parameters and endocrine function in obese women, though it does not significantly impact lipid metabolism or insulin resistance. The therapy’s influence on female hormones may contribute to its efficacy in obesity treatment, highlighting the need for further studies to explore long-term effects and mechanisms.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier: CRD42025640157.

PMID:40667439 | PMC:PMC12259452 | DOI:10.3389/fnut.2025.1583556