Background KMT2A-altered acute myeloid leukemia (AML) is a rare, aggressive high-risk subtype. The prognostic value of flow-cytometric phenotypic MRD versus KMT2A gene-specific molecular MRD, and the role of allogeneic hematopoietic stem cell transplantation (Allo-HSCT), remain poorly defined.Methods This single-center retrospective cohort enrolled 155 newly diagnosed adolescent and adult patients with KMT2A-altered AML. Treatment response, MRD status, and survival were analyzed by Kaplan–Meier and multivariate Cox regression; time-dependent Cox regression was used as a sensitivity analysis to account for guarantee-time bias.Results Among 153 evaluable patients, the complete remission rate was 70.7% and overall response rate 78.9%, with median RFS of 12.4 months and OS of 16.4 months. After excluding transplanted patients, the three non-transplant regimens yielded similar survival, indicating no inherent advantage of induction regimens. Flow-MRD-negative patients had superior OS, and concurrent KMT2A molecular MRD negativity conferred the best outcomes. Allo-HSCT was associated with a markedly higher rate of sustained molecular MRD negativity (74.6% vs. 14.4%, p < 0.0001). On multivariate analysis, persistent molecular MRD positivity and absence of Allo-HSCT independently predicted inferior RFS and OS; after time-dependent adjustment, Allo-HSCT showed only a non-significant trend, while molecular MRD positivity remained the dominant adverse prognostic factor.Conclusion In KMT2A-altered AML, sustained KMT2A molecular MRD negativity is the key determinant of favorable long-term survival. Allo-HSCT promotes molecular MRD clearance and may serve as a consolidation strategy to achieve deep molecular remission.
Background Intrahepatic cholestasis of pregnancy (ICP) tends to be more severe in twin pregnancies and is associated with adverse maternal and neonatal outcomes. However, data on the specific effects of ICP in twin gestations remain limited. This study aimed to investigate comprehensively the maternal and neonatal consequences of twin pregnancies complicated by ICP.Methods This retrospective cohort study enrolled 3,109 twin pregnancies delivered at Northwest Women’s and Children’s Hospital in China from January 2018 through December 2022. Pregnancy and delivery data were extracted from the medical records of women with twin pregnancies who delivered at the hospital. Women were allocated into two groups: ICP (n = 244) and non-ICP (n = 2,865). ICP was diagnosed based on the presence of pruritus together with serum total bile acid (TBA) concentrations ≥10μmol/L. Propensity score matching (PSM) was used to balance baseline characteristics between the two groups. Multivariable logistic regression and generalized estimating equations (GEE) were applied to evaluate the associations between ICP and adverse maternal and neonatal outcomes.Results After matching, ICP increased the risk of maternal outcomes, including preterm labor (early preterm birth: OR = 2.87, 95% CI 1.95–4.23; preterm birth: OR = 4.30, 95% CI 2.11–8.77; very preterm birth: OR = 2.97, 95% CI 1.50–5.87) and hypoproteinemia (OR = 2.83, 95% CI 1.12–7.14), as well as adverse neonatal outcomes, including low birth weight (OR = 2.66, 95% CI 1.99–3.55), small vulnerable newborns (OR = 5.30, 95% CI 2.34–12.00), respiratory distress syndrome (OR = 2.43, 95% CI 1.61–3.67), and necrotizing enterocolitis (OR = 5.71, 95% CI 2.34–13.92).Conclusion Twin pregnancies complicated by ICP were associated with increased risks of adverse perinatal outcomes, including preterm birth, low birth weight, and neonatal morbidity. These findings highlight the importance of heightened clinical awareness and individualized risk assessment in this high-risk population.
Background Gallbladder and biliary diseases are assessed across all ages, obscuring their burden before age 40. We assessed burden, trends, disparities, attributable risks, and projections to 2040 among adolescents and young adults.Methods We conducted a repeated cross-sectional analysis using the Global Burden of Disease (GBD) Study 2021. Age-standardized prevalence, incidence, and disability-adjusted life-year (DALY) rates were estimated for ages 15–39 years during 1990–2021. Trends were quantified using estimated annual percentage changes (EAPCs) and examined by sex, Socio-demographic Index (SDI) quintiles and geographic regions. Age-specific patterns, associations with SDI, attributable DALY fractions, and projections to 2040 were assessed.Results From 1990 to 2021, global age-standardized prevalence, incidence, and DALY rates decreased by 13.0%, 12.1%, and 16.9%, respectively. However, absolute burdens increased: prevalent cases by 24.9%, incident cases by 26.3%, and DALYs by 19.2%. Prevalence increased in high- and high-middle-SDI quintiles and most rapidly in East Asia, and incidence increased in higher-SDI settings. Females and individuals aged 35–39 years had higher rates. The fraction of DALYs attributable to high body-mass index increased from 21.2% to 31.7%, whereas the smoking-attributable fraction declined from 4.4% to 3.3%. By 2040, age-standardized prevalence and incidence rates were projected to remain near 2021 levels, but prevalent and incident cases were projected to increase by 7.6% and 11.1%, respectively.Conclusions Global age-standardized rates declined, but these trends concealed sex, age, socioeconomic, and geographical disparities. The increasing contribution of high body-mass index and projected growth in absolute case numbers support prevention and service planning before mid-adulthood.
Introduction Fibromyalgia combines widespread pain, nonrestorative sleep, fatigue, cognitive symptoms, and functional impairment. Sublingual cyclobenzaprine received US approval for fibromyalgia in August 2025. This narrative review evaluates its development, rationale, pharmacokinetics, efficacy, safety, and therapeutic positioning.Discussion The search covered PubMed/MEDLINE, trial registries, regulatory sources, and reference lists through 20 August 2026, with an update on 28 September 2026; primary reports and regulatory documents were prioritized. Two of three 5.6-mg phase 3 trials met the pain endpoint; earlier 2.8-mg trials did not. Mean placebo-adjusted pain reductions were 0.4–0.66 points in positive trials. One additional participant achieved ≥30% pain reduction per 6–9 treated; pooled safety data suggested one additional oral mucosal reaction per three treated. These estimates derive from different evidence sets and are not a formal benefit–harm ratio. Frequent oral sensory reactions may cause functional unblinding. Threshold-matched indirect responder benchmarks do not establish superiority over established therapies; altered pharmacokinetics do not establish less next-day impairment than low-dose oral cyclobenzaprine. Positive studies lasted 14 weeks; responder estimates were exploratory. Controlled long-term and comparative-effectiveness data remain limited. Sponsor involvement, the negative RALLY trial, limited geriatric evidence, and absence of active-comparator trials constrain interpretation.Conclusions A monitored trial may be reasonable in selected adults with persistent, sleep-prominent symptoms despite multimodal care and low treatment risk, although this phenotype is unvalidated. Continuation should require net improvement in symptoms and daytime function. Independent active-comparator trials, particularly against low-dose bedtime oral cyclobenzaprine, assessing morning alertness, tolerability, and masking would most change the assessment.
Background Brain templates are pivotal tools for standardized image analysis and interpretation in neuroimaging studies. However, matching data and reference remains essential. With growing awareness of sex as a relevant biological variable and male-centric biases in past medical investigations, the continuous limited use and availability of female-specific brain templates, particularly in preclinical research are alarming.Methods To address this gap in preclinical neuroimaging, we created a high-resolution, in vivo structural MRI brain template for female C57Bl/6N mice, a population-average derived from 153 axial and coronal scans of 80 female mice. We further analyzed the template’s characteristics regarding the achieved effective resolution and compared it to currently available standard brains. Validation was performed by spatially normalizing external data to established templates and the novel reference, contrasting the degree of deformation.Results We present a readily applicable and accessible set of files (structural images, tissue probability maps, anatomical annotations, and transformation matrices) as reference for female-centric neuroimaging research questions. The novel template brain exhibits high nominal and effective resolution, differs significantly in spatial and cohort characteristics from previous references and shows improved performance with external data of female mice.Conclusion We propose that integrating sex-specific tools into preclinical neuroimaging studies is essential for reducing sex bias, enhancing data reproducibility and strengthening the translational validity of neuroscientific findings. Research further disentangling (sub-)strain- and sex-differences is warranted.
