Pemigatinib is a selective inhibitor of fibroblast growth factor receptors (FGFR) 1-3 with demonstrated activity in tumors harboring FGFR2 fusions or amplifications. This phase Ib/II trial assessed the efficacy and safety of pemigatinib in combination with paclitaxel in patients with recurrent or advanced gastric cancer exhibiting FGFs/FGFRs alterations.

Patients with gastric cancer harboring FGFs/FGFRs aberrations who experienced progression following first-line therapy were enrolled. The phase Ib component established the recommended phase II dose (RP2D); the phase II component evaluated clinical efficacy.

Twelve patients were enrolled. The RP2D was determined as pemigatinib 13.5 mg/day (days 1-21) plus paclitaxel 80 mg/m² (days 1, 8, 15) every 4 weeks. Median progression-free and overall survival were 4.4 and 10.5 months, respectively. Patients with FGFR2 amplification (n=6) exhibited prolonged progression-free survival (6.5 vs. 3.5 months, p=0.049), while overall survival did not differ significantly. The objective response and disease control rates were 33.3% and 91.7%, respectively. The most frequent treatment-related adverse events were neutropenia (83.3%, grade ≥3: 58.3%) and hyperphosphatemia (83.3%, grade ≥3: 33.3%).

Pemigatinib plus paclitaxel demonstrated antitumor activity with an acceptable safety profile in FGFR2-amplified gastric cancer. Further investigation is warranted to elucidate resistance mechanisms and validate these findings in larger cohorts.

Breast cancer remains a leading cause of cancer-related mortality worldwide, with obesity markedly increasing the risk in affected individuals. Liquid biopsy-based extracellular vesicles (EVs) offer a minimally invasive platform for molecular profiling of tumor-derived markers. Plasma small-EVs from obese, chemotherapy-naïve breast cancer patients (n = 76; stages I-III) and age-matched obese controls (n = 36) were enriched and characterized by high-resolution transmission electron microscopy, dynamic light scattering (DLS) and specific EV markers. Proteomic profile of the enriched small-EVs using nanoLC-MS/MS identified Fibronectin 1 (FN1) and von Willebrand Factor (VWF) as candidate markers. Bioinformatics and STRING networks revealed interactions with Syndecan-2 (SDC2) and Galectin-3 (Gal-3). As an independent validation, western blot confirmed that FN1, VWF, and SDC2 were higher enriched in the small-EVs of breast cancer with different stages than in those of normal and that high content of small-EVs FN1 and SDC2 was primarily associated with the aggressive triple-negative breast cancer (TNBC) subtype. Interestingly, Gal-3 was reduced in small-EVs but elevated in breast carcinoma tissues and microvesicle (MV)-enriched EVs. Functionally, treatment with TNBC-derived plasma small-EVs not only downregulated expression of epithelial marker CDH1, and upregulated expression of the mesenchymal markers ZEB2 and FN1 in low-invasive MCF-7 breast cancer cells, but also elevated expression of inflammatory and matrix-remodeling mediators (Il-6, Tnf-α, and Mmp-9) in BNL CL.2 normal liver cells. ROC-Plotter and drug-gene interaction analyses indicated associations with therapy response, with approved compounds targeting FN1 and VWF. Overall, these findings reveal proteomic signatures of minimally invasive plasma small-EVs as promising markers associated with diagnosis, molecular subtyping, disease progression, and guiding therapeutic strategies in obese breast cancer patients.

In this study, we systematically investigated bladder cancer-related gene signatures using a toxicogenomics-informed framework, with particular attention to genes associated with lactylation-related pathways. Multi-omics data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were integrated, and Weighted Gene Co-expression Network Analysis (WGCNA), a toxicology database, and lactylation-related gene sets were combined for intersection screening. Machine learning algorithms, including LASSO, SVM, and random forest, were then applied to identify key genes. Four prioritized BPA-lactylation-associated candidate genes-ENO1, WBP11, GTF2F1, and SPR-were ultimately identified and showed consistent associations with metabolic, immune, and transcription-related features. Multi-level validation, including immune infiltration analysis, single-cell transcriptome localization, proteomic validation, and molecular docking and kinetic simulation, supported the structural plausibility of BPA-protein interactions at the molecular level. This study proposes a toxicogenomics-informed, hypothesis-generating framework that prioritizes candidate genes and pathways potentially linking BPA-related signatures with lactylation-associated processes in bladder cancer.

To evaluate whether non-tobacco nicotine dependence (NTND) in adolescents and young adults is associated with an increased risk of new-onset fractures over a medium and long term follow up.

Design: retrospective cohort query of TriNetX network.

Multi-center study conducted using de-identified electronic health records from the TriNetX network of participating healthcare organizations.

Adolescents and young adults (≤21 years) were included if they had a diagnosis of NTND between June 1, 2005, and June 1, 2020. Exclusions: any prior tobacco use, environmental tobacco exposure, tobacco use disorder, pre-existing bone/joint pathology (e.g., osteoporosis, osteoarthritis, osteogenesis imperfecta, malignant neoplasms of bone/cartilage), or prior fracture. NTND patients were propensity score matched 1:1 with controls without any documented nicotine or tobacco use.

The primary outcome was incident fracture after the most recent eligible clinical encounter documented between June 1, 2005, and June 1, 2020. Fracture risk was assessed over a fixed 5-year period following the index date and across the longest available follow-up in TriNetX. Risk ratios (RR) and 95% confidence intervals (CI) were calculated. Kaplan-Meier survival analysis was used to estimate hazard ratios (HR) for time-to-event comparison.

The matched cohort was comprised of 10,576 patients per group with an average age at index of 19.4 + 1.7 years. The NTND group was comprised of 44.9% males and 54.7% females while the control group was comprised of 44.7% males and 55.0% females. At 5 years, fracture incidence was 1.1% in the NTND group and 0.5% in controls (RR, 2.1; 95% CI, 1.5 - 2.9; p < 0.001). Over the extended follow-up, fracture incidence was observed to be 2.0% in NTND group and 1.0% in the control group (RR, 1.9; 95% CI, 1.5-2.4; p < 0.001). Over the extended follow-up, the elevated fracture risk in NTND group when compared to controls was confirmed time-to-event analysis (HR, 1.9; 95% CI, 1.5-2.4).

Non-tobacco nicotine dependence was associated with a two-fold increased risk of fracture among adolescents and young adults (RR, 2.1; 95% CI, 1.5-2.9 at 5 years; RR, 1.9; 1.5-2.4 over an extended follow up period). It is suggested by these findings that skeletal health consequences should be considered when evaluating the long-term impact of nicotine use in youth.

Level III.

Cuproptosis represents a promising therapeutic strategy for cancer; however, its clinical application remains limited. We observed elevated copper levels and increased expression of DLAT, a key procuproptosis gene, in colorectal cancer (CRC) tissues, suggesting inherent susceptibility to cuproptosis. Furthermore, NAT10 enhances DLAT mRNA stability by mediating its N⁴-acetylcytidine (ac4C) modification, thereby promoting cuproptosis. We also discovered that lactylation of NAT10 at lysine 426 (K426) enhances NAT10 catalytic activity. Conversely, SIRT1 mediates the delactylation of NAT10-K426, leading to the inhibition of cuproptosis. The combination of elesclomol (a cuproptosis inducer) and selisistat (a SIRT1 inhibitor) effectively induced cuproptosis in CRC. Notably, the reduction of soluble DLAT induced by elesclomol treatment was found to enhance NAT10-K426 lactylation. Moreover, DLAT supplementation establishes a positive feedback loop that amplifies cuproptosis. These results underscore the critical role of nonhistone NAT10 lactylation in tumor cuproptosis and highlight the therapeutic potential of targeting this pathway for CRC treatment.

Solitary fibrous tumors are mesenchymal neoplasms that make up 2% of soft tissue tumors. Doege-Potter syndrome (DPS) occurs between 5-10% of patients with solitary fibrous tumor of the pleura (SFTP). Little is mentioned about DPS in the relapse setting, where malignant transformation should always be ruled out (until 12% of cases) according to tumor size, histopathologic aspects (including mitotic index) and immunohistochemical markers. This is the first case of Doege-Potter syndrome in the setting of a fibrous tumor relapse of the pleura without malignant transformation described in Colombia.

This systematic review study method to investigate the effects of yoga therapy in oncological nursing care for children undergoing cancer treatment. Between 2009 and 2024, searches were conducted in Science Direct, Web of Science, PubMed, and Google Scholar databases using the keywords "pediatric oncology, cancer, child, adolescent, yoga, nursing care, stress, fatigue, sleep quality," yielding a total of 502 studies, 45 of which were classified as articles. Twelve of the reviewed articles met the inclusion criteria. In this systematic review, the question "What is the effectiveness of yoga therapy on stress, fatigue, and sleep quality in pediatric oncology care?" was addressed. The reviewed articles found that yoga therapy improved stress, fatigue, physical activity, psychological well-being, sleep quality, and pain levels in pediatric oncology. While reviewing the articles, the identities of the authors, the publishing journals, the research method, the country in which the study was conducted, the number of patients, the age range of the intervention, the type of intervention, and the parameters determined to be effective on yoga were all examined, and it was concluded that yoga can be used as an alternative nursing care for children with cancer.

BackgroundLimited research evidence exists on the experiences of adolescents living with HIV about their access to antiretroviral therapy during the COVID-19 pandemic in Tanzania.ObjectiveTo explore the lived experiences of adolescents living with HIV during the COVID-19 pandemic, including COVID-19-related anxiety, facilitators and barriers to accessing HIV care and treatment, and the coping strategies employed to remain healthy and resilient and if differences existed based on levels of anxiety.MethodsWe adopted a case study design to understand both normative and individual lived experiences of purposefully sampled adolescents receiving HIV care during the COVID-19 pandemic with higher and lower anxiety levels. A total of 32 participants took part in the study, including 24 in focus group discussions and 8 in in-depth interviews. Data were analyzed using thematic analysis.ResultsAdolescents living with HIV faced heightened anxiety and notable barriers to accessing HIV services during the COVID-19 pandemic. Their anxiety was driven by fear of infection, uncertainty about prevention measures, concerns about receiving care outside HIV clinics, and a perceived increased vulnerability. Many reported difficulty attending clinic appointments, largely due to government- and parent-imposed restrictions such as stay-at-home directives, mandatory mask use, and limited public transport capacity, but no difference based on anxiety level.To cope, adolescents relied on treatment adherence knowledge, self-efficacy, and family support. Both low- and high-anxiety groups encountered similar barriers to care and treatment adherence; however, those with higher anxiety reported greater fear of infection, less confidence in coping, and less helpful coping skills. No differences were observed by sex or age.ConclusionThe findings highlight that self-efficacy, risk-reduction knowledge, problem-solving skills, and family support helped reduce anxiety and support treatment adherence among adolescents living with HIV, underscoring the need for targeted support programs during public health crises.

Post-transplant deep vein thrombosis (DVT) is common after lung transplantation and may contribute to pulmonary embolism and other complications. Whether DVT adversely affects contemporary outcomes and how venovenous ECMO (VV-ECMO) bridging influences early DVT patterns remain unclear. We performed a retrospective single-center study of adult lung transplant recipients (2018-2025). DVT and clinical outcomes were ascertained. Primary analyses compared outcomes and overall survival between recipients with and without DVT in the overall cohort. Secondary analyses assessed DVT-free survival and early anatomic distribution among recipients bridged with preoperative VV-ECMO. Comparisons used Fisher's exact/Mann-Whitney U tests; survival used Kaplan-Meier/log-rank tests. Among 502 recipients, 240 developed DVT. Compared with those without DVT, recipients with DVT had higher rates of pulmonary embolism (22.5% vs. 5.0%, p < 0.0001), acute kidney injury (52.9% vs. 41.2%, p = 0.009), PGD grade 3 (18.3% vs. 10.7%, p = 0.016), longer hospitalization (21 vs. 14 days, p < 0.001), and worse overall survival (HR 2.19, 95% CI 1.49-3.23; log-rank p < 0.001). Of 240 DVT cases, 31 (12.9%) were bridged with VV-ECMO. Within 14 days, upper-extremity DVT was more frequent with VV-ECMO (53.3% vs. 23.5%, p = 0.03), whereas lower-extremity and neck distributions were similar. In multivariable models, operative time was independently associated with DVT (OR 1.18 per hour, 95% CI 1.07-1.31, p < 0.001). Post-transplant DVT is frequent and portends worse outcomes. VV-ECMO bridging is associated with an upper-extremity-predominant DVT pattern but is not an independent DVT predictor after adjustment. Vigilant surveillance is warranted in this high-risk population.

Although coronavirus disease 2019 (COVID-19) usually exhibits a mild clinical course in children, concerns remain regarding persistent airway dysfunction after recovery. This study aimed to evaluate pulmonary function tests (PFTs) in children following mild COVID-19 infection and to compare the findings with those of healthy controls.

In this prospective cross-sectional study, children aged 6-18 years with polymerase chain reaction-confirmed COVID-19 infection were identified retrospectively from February 2022 and evaluated prospectively between June and December 2022. Fifty-eight post-COVID-19 patients and 56 age- and sex-matched healthy controls were included, and their demographic and clinical characteristics were recorded. PFTs were assessed using impulse oscillometry (IOS) followed by spirometry.

There were no significant differences in demographic and anthropometric measurements between the post-COVID-19 group and the healthy controls. In terms of IOS measurements, zR5 and R5-20 (reflecting airway resistance) were higher and zX5 and zX20 (reflecting airway reactance) were lower in the post-COVID-19 group (p = .006, p = .002, p < .001, and p = .001, respectively). No significant differences were observed in spirometric parameters, including zFEV1, zFVC, zFEV1/FVC, and zFEF25-75. Notably, three patients exhibited persistent cough and dyspnea after COVID-19, had FEV1 values <90% predicted, positive bronchodilator reversibility, and inhalant allergen sensitization despite having no prior history of asthma or allergic rhinitis.

Children recovering from mild COVID-19 infection may exhibit persistent airway dysfunction detectable by IOS despite normal spirometric findings. IOS appears to be a sensitive tool for identifying subclinical airway involvement in children following COVID-19.