Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health problem. Measuring the burden of cirrhosis and its complications in people with MASLD is important to inform health care delivery.

We aimed to quantify the changes in the burden of MASLD-related cirrhosis and hepatocellular carcinoma (HCC) in a nationwide U.S. healthcare system. We used data from the Veterans Health Administration to examine temporal trends between 2010 and 2021 in the annual incidence and prevalence of cirrhosis and HCC in a large cohort of patients with MASLD, and to compare them to those in patients with hepatitis C virus infection (HCV) and alcohol-associated liver disease (ALD).

The MASLD cohort grew from 78,082 in 2010 to 621,400 patients in 2021. The annual age-standardized incidence rates of MASLD-related cirrhosis rose from 1.39 (95% CI, 1.13, 1.65) to 1.91 (95% CI, 1.80, 2.02) per 1000 patients (37.4% increase). HCC incidence increased from 0.08 (95% CI, 0.02, 0.14) to 0.22 (0.18, 0.26) per 1000 patients (175% increase). Cirrhosis and HCC prevalence also increased, particularly among adults older than age 65, Whites, Hispanics, and individuals with diabetes. Temporal trends in the incidence and prevalence of cirrhosis and HCC among patients with ALD were similar to those in MASLD. In contrast, patients with HCV experienced a sharp decline in the incidence of cirrhosis and HCC in this time frame.

The burden of MASLD-related cirrhosis and HCC is growing. While the burden of liver complications is similar between MASLD and ALD, the substantially larger size of the MASLD population means that the modest increases in incidence of cirrhosis and HCC could translate into a large absolute burden.

The improvement of childhood cancer outcomes has relied on clinical trials, primarily from high-income countries (HICs). Inconsistent access to clinical trials, especially in low-income countries (LICs) and middle-income countries, contributes to disparate care and limits the generalizability of conclusions from trials conducted in HICs.

To describe the global availability of clinical trials for children and adolescents with cancer in different economic settings.

In this cross-sectional study, the World Health Organization's International Clinical Trials Registry Platform was used to search for clinical trials on May 8, 2024. Trials were included if they were interventional studies for pediatric patients (<18 years old) with an active cancer diagnosis.

Clinical trials were analyzed based on geographic location, World Bank country income classification, and trial characteristics, including study phase, sponsor type, intervention type, and inclusion criteria. The main outcome was differences between HICs and low- and middle-income countries in the availability, design, and results of clinical trials for children and adolescents with cancer.

Of 138 595 oncology trials, 5645 met the inclusion criteria. Of these, 3149 (55.8%) were pediatrics-only trials. Most pediatrics-only trials (2558 of 3149 [81.2%]) were conducted by sponsors in HICs. Among identified trials, 12.5% (394 of 3149) were open for accrual in upper-middle-income countries (UMICs), 8.9% (281 of 3149) in lower-middle-income countries (LMICs), and 0.2% (7 of 3149) in LICs. Compared with HICs, LMICs or LICs registered fewer early-phase trials (28.8% [42 of 146] vs 81.4% [1709 of 2100]; P < .001), trials with cancer-directed treatments (17.6% [46 of 262] vs 76.8% [1964 of 2558]; P < .001), and multi-institutional trials (6.5% [17 of 262] vs 54.2% [1386 of 2558]; P < .001). LMICs or LICs registered more supportive care-based trials (81.7% [214 of 262] vs 19.9% [509 or 2558]; P < .001). Supportive care trials, later-phase trials, and trials from UMICs, LMICs, and LICs were more likely to publish clinical trial results within 10 years.

In this cross-sectional study of global pediatric oncology clinical trials, low- and middle-income countries were underrepresented. These data illustrate the need to improve the clinical research infrastructure in low- and middle-income countries and foster inclusive collaborations to promote equity in global pediatric cancer clinical trials.

Tagraxofusp (TAG), a first-in-class CD123-targeted therapy, is a recombinant fusion protein of human interleukin-3 conjugated to a truncated diphtheria toxin payload. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive orphan hematologic cancer with a poor prognosis, and is derived from plasmacytoid dendritic cells that overexpress interleukin-3 receptor subunit alpha (IL3RA or CD123). This open-label phase I/II study evaluated the efficacy and safety of TAG in 11 Japanese BPDCN patients, of whom seven were treatment-naïve (TN) and four had relapsed/refractory (R/R) disease. In the phase I portion, seven patients (five TN, two R/R) were treated, and no dose-limiting toxicity was observed, with 12 μg/kg/day tolerated. In the phase II portion, four patients (two TN, two R/R) were treated. Among the seven TN BPDCN patients, the rate of complete response (CR) + clinical CR (CRc: CR with minimal residual skin abnormality) was 57.1% (90% confidence interval [CI], 22.5-87.1), and the lower limit of the 90% CI (22.5%) exceeded the pre-specified threshold of 10%. Common adverse events included increased alanine aminotransferase (81.8%) and aspartate aminotransferase (72.7%), hypoalbuminemia, hypokalemia, and capillary leak syndrome (54.5%). The results indicate that TAG was effective and had a manageable safety profile in Japanese BPDCN patients.

Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related mortality worldwide. A significant proportion of patients present as emergencies with obstruction, perforation, or bleeding, necessitating emergency colorectal surgery (EMCRS). This study aimed to compare the outcomes of patients undergoing EMCRS with those undergoing elective colorectal surgery (ELCRS).

This retrospective-prospective cohort study included patients undergoing curative CRC resections at a tertiary center in Southern India between January 2010 and June 2022. Patients with metastatic disease or palliative procedures were excluded. Propensity score matching (PSM) was performed (1:1) based on age, sex, tumor location, and stage. Outcomes assessed included postoperative complications, inpatient mortality, disease-free survival (DFS), and overall survival (OS).

Among 558 patients (106 EMCRS, 305 ELCRS), 106 matched pairs were analysed. Before PSM, EMCRS had significantly higher morbidity (71.4% vs. 40.7%, p < 0.001) and mortality (17.9% vs. 2.3%, p < 0.001). After PSM, EMCRS continued to show increased severe complications (Clavien-Dindo IV/V), sepsis, pulmonary and cardiac complications, and higher inpatient mortality (17.9% vs. 0.9%, p < 0.001). However, long-term outcomes were not significantly different (DFS: 58 ± 3 vs. 55.5 ± 4.7 months, p = 0.19; OS: 67.5 ± 2.9 vs. 69.7 ± 4.9 months, p = 0.391).

EMCRS is linked to significantly worse short-term outcomes. The difference in long-term survival appears to stem from advanced disease at presentation rather than the emergency nature of surgery. Enhanced screening and preoperative optimization strategies may help improve patient outcomes.

The CHEK2 gene confers a moderate risk for breast cancer, but existing knowledge is largely based on the European founder variant, 1100delC. This study aimed to characterize the distinct phenotypes associated with unique CHEK2 variants in Brazilian families. In this cross-sectional study, 1055 patients meeting criteria for Hereditary Breast and Ovarian Cancer syndrome underwent germline multigene panel testing. Pathogenic/likely pathogenic variants (PVs) were found in 141 patients (13.4%), of whom 13 (9.2%) had a CHEK2 PVs. Subsequent family cascade testing brought the total number of individuals studied to 57. Three distinct CHEK2 PVs were identified: c.846 + 1G > C, c.349 A > G, and c.593-1G > T. While breast cancer was the most frequent tumor, specific PVs correlated with different cancer spectra. The c.349 A > G variant showed an enrichment for papillary thyroid cancer. In contrast, the c.846 + 1G > C variant was associated with melanoma, prostate, and testicular cancer, in addition to breast, colon, and kidney cancers. These findings suggest that different CHEK2 PVs may confer distinct cancer risks. Investigating these variants across diverse populations is crucial for refining phenotype characterization and improving genetic counseling as access to genetic testing expands.

To investigate the prognosis and endocrine therapy (ET) efficacy in patients with estrogen receptor (ER)-low breast cancer.

This retrospective cohort study included patients diagnosed with early-stage breast cancer at a single institution in China from January 2010 to December 2020. Clinicopathological features, survival outcomes, and the effect of ET were compared among patients with ER-low, ER-high, and ER-negative breast cancer. Analyses were stratified by human epidermal growth factor receptor 2 (HER2) status (positive or negative).

A total of 2951 patients were included, consisting of 131 (4.4%) ER-low, 2040 (69.1%) ER-high, and 780 (26.4%) ER-negative patients. In the HER2-negative subgroup, ER-low patients had significantly worse breast cancer-free survival (BCFS) (P = 0.016) and a higher risk of locoregional recurrence (P < 0.001) compared to ER-high patients, while no significant differences were observed in prognosis between ER-low and ER-negative patients. In the HER2-positive subgroup, there were no significant differences in prognosis among patients with different ER expression levels. ET could significantly reduce the risk of locoregional recurrence and distant metastasis and significantly improve BCFS for ER-low patients, especially in the HER2-negative subgroup. However, in the HER2-positive subgroup, ET did not improve BCFS or overall survival for ER-low patients.

HER2-negative/ER-low breast cancer has a similar clinical behavior to triple-negative breast cancer, and ET could significantly reduce the risk of recurrence and metastasis for this subgroup. However, in HER2-positive patients, ER-low breast cancer lacks a predictive role in prognosis and derives no clear benefit from ET.

Glycosylation is a crucial post-translational modification, and numerous studies have reported its significant role in cancer progression. Nevertheless, no study has comprehensively analyzed the causal effect of glycosylation on the risk of cancer till now. Herein, we identified 32 SNPs of glycosylation-related genes (GRGs) that correlated with the risk of 8 kinds of cancer by summary-statistics-based mendelian randomization (SMR) analysis for genome-wide association study (GWAS) data. Next, the heterogeneity in dependent instrument (HEIDI) test and colocalisation analysis were utilized to verify the heterogeneity and consistency of SMR results. Further fine-mapping of causal gene set (FOCUS) analysis based on transcriptome-wide association study (TWAS) data showed that rs9810189 of ST6GAL1 and rs223489 of MANBA were negatively correlated with the risk of breast cancer and squamous cell carcinoma, respectively. Moreover, the MANBA protein in blood plasma also exhibited a probably negative causal effect on squamous cell carcinoma according to two-sample MR analyses for protein quantitative trait locus (pQTLs). In addition, single-cell RNA sequencing analysis and Kaplan-Meier plot analysis were performed to evaluate the potential role of GRGs in corresponding cancer prioritized by the above MR analysis. Finally, we attempted to illustrate the function of glycosyltransferases and investigate the druggable status of GRGs. Together, our study comprehensively analyzed the causal effect of glycosylation on cancer risk and identified potential strategies for cancer treatment.

Managing cardiovascular risk is key for breast cancer survivors, many of whom have pre-existing conditions like hypertension and hyperlipidaemia. Research suggests compliance with cardiovascular medication declines after a breast cancer diagnosis. However, these studies rely on population-level averages, which mask patient heterogeneity and longitudinal variations in compliance. This study aimed to identify compliance trajectories with cardiovascular medication around a breast cancer diagnosis and describe associated characteristics.

Using the French National Health Data System, we constructed a cohort of women diagnosed with incident breast cancer (2016-2020) who received at least 2 cardiovascular drug classes before diagnosis for primary prevention, defined as treatment of cardiovascular risk factors in the absence of established cardiovascular disease. Compliance trajectories were analysed over 3 years using group-based trajectory modelling.

Among 35,399 women, 6 trajectories were identified: stable high compliance (49.9%), moderate stable (21.2%), low stable (12.8%), sharp decline post-diagnosis (9.8%), treatment discontinuation post-diagnosis (3.4%), and very low and declining (2.9%). Declining trajectories were associated with higher rates of metastases and chemotherapy.

This study revealed substantial heterogeneity in compliance responses post-diagnosis. While most women maintained stable compliance, a significant subset experienced sharp declines, likely linked to cancer severity. Early interventions post-diagnosis could reduce cardiovascular risk and improve outcomes.

This prospective study evaluated the impact of computer-aided design/manufacturing (CAD/CAM) palatal augmentation prostheses (PAPs) rehabilitation on maximum tongue pressure in tongue cancer patients underwent glossectomy.

Twelve patients (7 men, 5 women; mean age 53.2 years) with T1N0M0 or T2N0M0 tongue cancer that had undergone a type IIIa glossectomy without radiotherapy or chemotherapy were enrolled. All the participants had intact palates for good retention of PAP. Six weeks postoperatively, maxillary arches were scanned with an intraoral scanner; PAPs were digitally designed to lower the palatal vault utilizing CAD and then were fabricated from biocompatible PMMA via 3D printing and delivered. Patients wore the PAP daily and performed tongue-PAP contact exercises for at least four hours per day over six months. Maximum tongue pressure was measured using the Iowa Oral Performance Instrument before PAP delivery and after six months of rehabilitation. Statistical analysis was conducted using ANOVA with p < 0.05 considered significant.

Mean maximum tongue pressure increased from 16.93 ± 13.16 kPa pre-rehabilitation to 26.93 ± 15.60 kPa post-rehabilitation (median: 11.9 to 21.9 kPa). ANOVA showed a significant improvement (F = 5.31, p = 0.0038).

CAD/CAM PAP rehabilitation significantly improved the maximum tongue pressure in glossectomy patients, suggesting potential benefits for oral-phase swallowing efficiency. Early postoperative delivery through a digital workflow minimized tongue-palate distance, enabling prompt exercises, and accelerating functional recovery. This approach represents an innovative rehabilitation strategy. Integration of pressure sensors into PAPs could enable real-time monitoring of tongue activity, expanding their role as dynamic training devices.

Lung cancer treatment options have advanced, chemotherapy continues to play a central role in its management. However, the prognostic impact of individualized chemotherapy dose modifications remains uncertain. To examine the association between intravenous chemotherapy dose variations and disease-free survival (DFS) in lung cancer patients, and to identify factors influencing dose adjustment.

Lung cancer patients who received chemotherapy at Xiangya Hospital, Central South University from 2016 to 2021. Patients were classified into three groups based on deviation from the standard dose: dose reduction group, standard dose group, and dose increase group. Multivariable Cox proportional hazards models and inverse probability weighting (IPW) were used to evaluate the relationship between dose changes and DFS. Multivariate logistic regression was performed to identify factors associated with dose modification.

Among 23,231 patients, 7673 received standard doses, 13,655 reduced doses and 1903 increased doses. After adjustment by multivariable Cox regression and IPW, dose reduction (HR 1.06, 95% CI 1.01-1.11; P = 0.015) and dose increase (HR 1.11, 95% CI 1.02-1.22; P = 0.022) were associated with shorter DFS; in the platinum-doublet subgroup, only dose reduction remained significant (HR 1.08, 95% CI 1.02-1.15; P = 0.007). Logistic regression identified age, sex, height, weight, pathology, TNM stage and use of targeted/immunotherapy as associated factors.

Dose reduction was associated with significantly shorter DFS. Individualized dosing strategies should be based on comprehensive clinical evaluation to improve outcomes. These findings provide evidence to support rational chemotherapy planning in lung cancer care.