ASXL1 mutations (ASXL1^MUT) are common in acute myeloid leukemia (AML) and have historically conferred an adverse prognosis with intensive chemotherapy. Given the increasing use of venetoclax (VEN)-based lower intensity therapy (LIT), the European LeukemiaNet introduced a four-gene genetic risk classifier in 2024 that categorizes ASXL1 ^MUT as favorable risk in the absence of FLT3-ITD, RAS, and TP53 mutations. However, the prognostic significance of ASXL1^MUT across different contemporary LIT+VEN backbones remains controversial.

A retrospective analysis in 554 adults with newly diagnosed AML treated with LIT was conducted, stratified by ASXL1 mutation status and treatment backbone.

Within the European LeukemiaNet 2024 favorable-risk strata, ASXL1^MUT were associated with lower response rates and inferior overall survival, with outcomes more closely resembling those of intermediate-risk disease. Survival differences were most pronounced in patients treated with cladribine plus low-dose cytarabine and VEN, but inferior outcomes were also observed with hypomethylating agent + VEN-based regimens. On multivariable analyses accounting for age, cytogenetics, co-mutations, treatment backbone, and stem cell transplantation, ASXL1^MUT remained independently associated with inferior overall survival.

Collectively, these findings suggest that ASXL1^MUT AML may be more appropriately classified as intermediate risk in the context of LIT+VEN-based therapy, with the depth of impact influenced by the specific LIT backbone.

Stereotactic radiation therapy (SRT) requires extreme precision due to its high dose per treatment, high total dose, and very small error margins. Even small positioning errors may result in serious normal tissue toxicity or underdosing the tumor. Respiratory motion (resulting in tumor motion) represents a significant challenge to the delivery of SRT in some tumor types. A retrospective study of pet dogs receiving a rocuronium-sugammadex combination (ROC-SUG) as a means of inducing apnea was performed. The study included 14 pet dogs (43 treatments; 1-5 treatments per patient) undergoing SRT. A bolus of ROC was effective in preventing spontaneous breathing during treatment in 3/11 (27%) treatments and in 28/32 (88%) treatments when an ROC constant rate infusion (CRI) was given throughout treatment delivery, following the initial bolus. The median duration of apnea per treatment session was 6 min (range 4-7 min). The longest period of apnea during any treatment without interruption was 7 min. Adverse effects encountered during treatment include hypercapnia, bradycardia, and hypotension. Hypercapnia was observed in 34/43 treatments (79%). However, only 1/43 treatments (2%) resulted in bradycardia and hypotension, which were rapidly reversed. All dogs recovered rapidly following SUG with complete neuromuscular blockade reversal in a median of 1 min (range: 1-2 min), and there was no evidence of recurarization in any patient. The ROC-SUG combination, particularly when used with an ROC CRI, facilitated the induction of apnea without significant adverse effects. Future studies should use a uniform treatment protocol to confirm efficacy and patient safety.

Nutritional status is an independent factor that affects clinical outcomes in patients with liver cirrhosis (LC). This study aimed to investigate the prognosis of patients with LC according to their nutritional risk.

From January 2020 to April 2021, the medical records of patients with LC with/without hepatocellular carcinoma (HCC) who underwent abdominal computed tomography and nutritional risk evaluation using the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) were retrospectively reviewed.

In total, 243 patients were analyzed, 92: LC without HCC and 151: LC with HCC. Nutritional risk analysis using RFH-NPT revealed that 121 (49.8%) patients were low-risk, 35 (14.4%) moderate-risk, and 87 (35.8%) high-risk. Child-Pugh class (P < 0.001), albumin-bilirubin score (P < 0.001), and psoas muscle index (P < 0.001) significantly correlated with nutritional risk in all patients. Serum sodium levels were significantly different based on the nutritional risk in LC without HCC (P = 0.008) and with HCC (P = 0.001). Total cholesterol levels were significantly correlated with nutritional risk in all patients (P < 0.001) and in patients with LC with HCC (P < 0.001). Survival rates differed significantly according to nutritional risk in all patients (P < 0.001), patients with LC without HCC (P = 0.017), and patients with LC with HCC (P < 0.001). RFH-NPT high risk (hazard ratio [HR], 3.115; 95% confidence interval [CI], 1.396-6.950; P = 0.006), Child-Pugh C (HR, 12.802; 95% CI, 5.062-32.372; P < 0.001) and HCC (HR, 9.078; 95% CI, 3.657-22.535; P < 0.001) were significant factors affecting the survival rate of all patients.

RFH-NPT is a useful method for evaluating nutritional risk and predicting the survival rate of patients with LC with/without HCC.

Despite expanding therapeutic options, the prognosis of lung squamous cell carcinoma (LUSC) remains poor. Immune checkpoint inhibitors benefit only a subset of patients, and epithelial-mesenchymal transition (EMT) has been implicated in invasion, metastasis, treatment resistance, and immune heterogeneity. Therefore, EMT-related biomarkers may offer improved risk stratification.

To identify differentially expressed EMT-related genes (DEEMTGs) in LUSC, construct an EMT-based prognostic signature, and evaluate its associations with the tumor microenvironment (TME), tumor mutational burden (TMB), and tissue-level expression patterns.

The Cancer Genome Atlas (TCGA) RNA-seq and clinical data were analyzed to obtain DEEMTGs. A prognostic model was built using LASSO and multivariable Cox regression. Survival performance was assessed via Kaplan-Meier, ROC, and Cox analyses. Immune infiltration (CIBERSORT), stromal/immune scores (ESTIMATE), and TMB were compared between risk groups. Exploratory immunohistochemistry (IHC; n = 8) provided orthogonal expression validation.

A total of 1,651 DEEMTGs were identified, and a six-gene signature (GAB2, ALDOA, PCDHA3, TMEM92, ERH, IRS4) was established. The risk score independently predicted overall survival and corresponded to distinct TME patterns: low-risk tumors showed higher CD8⁺ T cells, activated CD4⁺ memory T cells, and naïve B cells, whereas high-risk tumors had more resting CD4⁺ memory T cells and M0 macrophages. TMB differences were nonsignificant. IHC provided directional protein-level support while acknowledging transcript-protein variability.

We developed a biologically interpretable EMT-based prognostic model that stratifies survival and reflects immune-microenvironment heterogeneity in LUSC. Larger, stage-balanced and immunotherapy-treated cohorts are needed to further validate its clinical utility.

Background Knee joint disorders are a major cause of musculoskeletal morbidity and functional disability worldwide, involving a broad spectrum of traumatic, degenerative, cystic, and neoplastic pathologies. Accurate evaluation of these conditions is essential for appropriate clinical assessment. MRI provides detailed visualization of intra-articular and periarticular structures due to its superior soft tissue contrast and multiplanar capability. However, there remains a need for region-specific observational data describing the spectrum of MRI findings in routine clinical practice. Materials and methods This retrospective observational study was conducted in the Department of Radiodiagnosis at Hi-Tech Medical College and Hospital, Rourkela, India, following institutional ethics approval. A total of 236 patients who underwent MRI of the knee between August 2024 and July 2025 were included. Patients referred with clinical suspicion of knee joint pathology were evaluated. MRI findings were analyzed to determine the distribution of knee joint pathologies and their association with demographic variables. Results Of the 236 patients, 149 (63.13%) were males, and 87 (36.87%) were females. Ligamentous and meniscal injuries were the most common findings, observed in 134 patients (56.78%), with a predominance among younger male patients. Anterior cruciate ligament tears were the most frequent ligamentous injury, followed by medial meniscus tears. Osteoarthritis was identified in 47 cases (19.92%) and was more frequently observed in older female patients. Baker's cysts were observed in 25 cases (10.59%), fractures in 20 cases (8.47%), and malignant neoplasms in 10 cases (4.24%). Among fractures, patellar fractures were the most common pattern. Among malignant lesions, synovial sarcoma was the most frequently identified tumor. Conclusions Knee joint pathologies demonstrated a distinct distribution pattern, with ligamentous and meniscal injuries predominating in younger males and degenerative changes more frequent in older females. Within the framework of this observational study, MRI facilitated detailed characterization of a wide spectrum of knee abnormalities; however, in the absence of comparative or outcome-based data, conclusions regarding diagnostic accuracy or clinical impact cannot be established. These findings provide context-specific insights into the epidemiological and imaging profile of knee joint pathologies and may serve as a foundation for future prospective and comparative studies.

This study analyzed the epidemiological characteristics and distribution patterns of gynecological diseases among hospitalized patients in a tertiary hospital serving China's northeastern mining region, compared disease profiles with national averages, and discussed implications for targeted nursing interventions.

A retrospective cross-sectional study was conducted using electronic medical records from 4,935 gynecological inpatients at Jixi Jikuang Hospital, Heilongjiang Province (January 2021-December 2025). Data collected included age, primary diagnosis (ICD-10 classification), residential district, insurance type, and length of stay. Regional hospitalization rates were calculated using Seventh National Census population data. Chi-square tests compared disease proportions with published national averages.

Analysis of 4,935 patients revealed distinct epidemiological patterns. The majority (60.7%) were aged 40-59 years, with peak prevalence observed in the 40-49 age group (33.8%; mean age 47.2 ± 12.8 years). Uterine pathologies dominated disease composition (57.6%), primarily endometrial polyps (18.9%) and uterine fibroids (18.6%), followed by ovarian diseases (15.9%) and cervical pathologies (13.5%). Geospatial analysis identified that hospitalization rates in mining-intensive districts (518.9-914.3 per 100,000) were higher compared with non-mining areas (178.2-207.8 per 100,000). Most hospitalizations lasted 3-8 days (66.2% of cases). Compared with national averages, significantly higher proportions were observed for endometrial polyps (18.9% vs. 14.5%, P < 0.001), uterine fibroids (18.6% vs. 15.2%, P < 0.001), and cervical neoplasms (10.2% vs. 7.8%, P < 0.001).

Gynecological hospitalizations in this northeastern mining region exhibit clustering in perimenopausal women, elevated uterine pathology prevalence, and geographic disparities favoring mining-intensive districts. These findings suggest potential environmental or healthcare access factors, warranting further investigation, and support the development of region-specific, age-stratified nursing care models.

Immune-based combination therapies have become the standard first-line treatment for metastatic renal cell carcinoma (mRCC) and have positively impacted survival outcomes in phase III clinical trials. However, these trials are conducted in highly selected populations and controlled settings, which may limit the generalizability of toxicity profiles to routine clinical practice. Real-world data are therefore essential to better characterize the incidence and determinants of severe adverse events (AEs) associated with immune-based combinations.

We conducted a multinational, retrospective analysis of the ARON-1 registry, of patients with mRCC who received first-line immune-based combination therapy across 17 countries. The primary endpoint was to evaluate the real-world incidence of grade 3-4 (G3-G4) AEs. Logistic regression analyses were performed to identify clinical factors associated with toxicity. Overall survival (OS) was assessed using Kaplan-Meier methods, with landmark analyses to explore the association between G3-G4 AEs and survival outcomes.

Among 2, 401 patients receiving immune-based combinations, 1, 921 (80%) had complete data on grade 3-4 AEs and were included in the analysis. G3-G4 AEs occurred in 34% (n=653). Pembrolizumab plus lenvatinib was associated with the highest incidence of high-grade AEs, whereas nivolumab plus ipilimumab showed the lowest. Older age and female sex were independently associated with an increased risk of G3-G4 toxicity. Although the occurrence of severe AEs was associated with improved OS in unadjusted analyses, this association was non-significant in the 6-month landmark analyses.

In this large, multinational real-world cohort, the incidence of G3-G4 adverse events in patients with mRCC treated with immune-based combinations was lower than that reported in pivotal clinical trials, underscoring meaningful differences between trial and routine practice settings. Patient- and regimen-specific factors significantly influenced toxicity risk. These findings highlight the complementary role of real-world evidence in informing toxicity management and support individualized treatment strategies to optimize outcomes in everyday clinical practice.

This review examines the evolving first-line immunotherapy landscape in metastatic renal cell carcinoma (mRCC), with emphasis on the comparative clinical logic of dual immune checkpoint blockade (ICI-ICI) and immune checkpoint inhibitor-tyrosine kinase inhibitor combinations (ICI-TKI), the persistent efficacy-effectiveness gap, biomarker development, and translational resistance biology. Pivotal phase III trials have established superior survival for contemporary ICI-based regimens over sunitinib; however, cross-trial heterogeneity, differences in IMDC risk distribution, varying toxicity profiles, and selection of fitter trial populations complicate simple regimen ranking. Real-world studies confirm that outcomes in routine practice are frequently less favorable than those reported in registration studies, but these differences are partly explained by confounding related to performance status, comorbidity burden, access to care, toxicity management, and treatment sequencing. Renal cell carcinoma remains a biomarker-challenged disease in which PD-L1 and tumor mutational burden have limited predictive value, while PBRM1 status, VHL-driven pseudohypoxia, and spatial immune architecture are biologically informative but not yet clinically validated as stand-alone selection tools. Resistance arises through tumor-intrinsic metabolic reprogramming, impaired antigen presentation, compensatory checkpoint signaling, and stromal-myeloid exclusion within the tumor microenvironment. Taken together, the field is moving from empirical regimen selection toward a model that integrates disease tempo, patient fitness, translational biomarkers, and mechanism-based sequencing. Future progress will depend on composite biomarker validation, biomarker-enriched trials, rational resistance-directed combinations, and structural measures that improve external validity and equitable access.

Human papillomavirus (HPV) is the leading cause of cervical cancer in the United States (U.S.), yet HPV vaccination coverage remains suboptimal and uneven across states. Policy approaches to improve HPV vaccine uptake vary widely across states in terms of health financing, provider authority, school requirements, and consent requirements.

A comprehensive review of state-level HPV vaccination policies was conducted. Information was identified through peer-reviewed literature (PubMed, Scopus, Google Scholar) and authoritative policy and legislative sources, including the Centers for Disease Control and Prevention, National Alliance of State Pharmacy Associations, National Academy for State Health Policy, and state statutes. Policies were categorized into macro-level health policies (Medicaid expansion, pharmacy and pharmacist authority, and state vaccine purchase programs) and HPV-specific policies (school-entry requirements, classroom sex education mandates, parental education mandates, minor consent laws, and exemption frameworks). Evidence on policy implementation and effectiveness was narratively synthesized.

Substantial heterogeneity in HPV vaccination policy adoption and implementation across U.S. states was documented. Medicaid expansion, pharmacist vaccination authority, and well-enforced school-entry requirements were consistently associated with higher HPV vaccine initiation or completion, while policies with permissive exemptions or weak enforcement demonstrated limited impact. Financing mechanisms such as universal and selective vaccine purchase programs reduced cost barriers but showed inconsistent effects on uptake when implemented in isolation. Evidence suggests that no single policy is sufficient; multi-level, coordinated policy environments yield the greatest improvements in vaccination coverage.

HPV vaccination uptake in the U.S. is shaped by complex and interacting policy mechanisms rather than individual interventions. Integrated policy approaches that combine financing, access expansion, school-based strategies, provider engagement, and enforcement structures are most likely to achieve sustained and equitable improvements in HPV vaccine uptake.

Perioperative treatment of gastric and gastroesophageal junction (G/GEJ) cancer is evolving towards multimodal strategies incorporating HER2-targeted therapy, immunotherapy and chemotherapy. Disitamab vedotin (RC48), an HER2-targeted antibody-drug conjugate, shows promising antitumour activity and potential synergy with immune checkpoint inhibitors. This study evaluated neoadjuvant RC48 combined with camrelizumab and S-1 in resectable HER2-overexpressing locally advanced G/GEJ adenocarcinoma.

Patients with histologically confirmed HER2-overexpressing (IHC 3+ or 2+) resectable G/GEJ cancer staged as cT3-4aN1-3M0 were enrolled in this prospective single-arm phase II study. Patients received three 3-weekly cycles of RC48, camrelizumab and S-1 before surgery. Pathological complete response (pCR) was defined as the primary endpoint, whereas major pathological response (MPR), objective response rate (ORR), tumour downstaging, disease-free survival (DFS), overall survival (OS) and safety were evaluated as secondary endpoints. Exploratory circulating tumour DNA (ctDNA) methylation profiling (PredicineEPIC) assessed molecular response dynamics and ERBB2 copy number variation.

From 18 September 2022 to 12 December 2024, 32 patients were enrolled; 24 proceeded to D2 resection. The ORR after neoadjuvant therapy was 80.0% (24/30). In the surgical cohort, pCR and MPR were achieved in 25.0% (6/24) and 45.8% (11/24) of patients, respectively, with an R0 resection rate of 100%. The median DFS and OS were not reached at the time of analysis. In the ctDNA substudy (n = 14), methylation-derived tumour fraction declined during therapy and ERBB2 plasma copy number gain aligned with tissue HER2 status. Treatment-related adverse events of grade ≥3 were reported in 31.3% of patients.

Neoadjuvant RC48 combined with camrelizumab and S-1 showed potential antitumour activity with an acceptable safety profile in HER2-overexpressing locally advanced resectable G/GEJ adenocarcinoma.

Neoadjuvant RC48 plus camrelizumab and S-1 showed encouraging pathological responses in HER2-overexpressing gastric cancer. The regimen achieved a pCR rate of 25% and an MPR rate of 45.8%. The combination therapy demonstrated a manageable safety profile. Exploratory ctDNA methylation analysis suggested potential for dynamic response monitoring.