β-thalassemia major is an inherited hemoglobinopathy that requires lifelong red blood cell transfusions and iron chelation therapy to prevent complications due to iron overload. Traditionally, β-thalassemia has been more common in certain regions of the world such as the Mediterranean, Middle East, and Southeast Asia. However, the prevalence of β-thalassemia is increasing in other regions, including Northern Europe and North America, primarily due to migration. This review summarizes the available data on the changing incidence and prevalence of β-thalassemia as well as factors influencing disease frequency. https://www.selleckchem.com/products/blu9931.html The data suggest that the epidemiology of β-thalassemia is changing Migration has increased the prevalence of the disease in regions traditionally believed to have a low prevalence, while, at the same time, prevention and screening programs in endemic regions have reduced the number of affected individuals. Various approaches to prevention and screening have been used. Region-specific prevention and treatment programs, customized to align with local healthcare resources and cultural values, have been effective in identifying patients and carriers and providing information and care. Significant challenges remain in universally implementing these programs. This study investigated the co-occurrence of borderline personality disorder (BPD), attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD) features in elementary-aged youth. Latent profile analysis characterized subgroups of youth based on the presence of BPD, ADHD, and ODD features, and subgroups were compared on academic, social, and emotional impairment. Seven subgroups were identified, including subgroups with slight, subclinical, clinical, and severe levels of co-occurring BPD, ADHD, and ODD features, and a subgroup of youth with no elevations in these symptom domains. Subgroups of youth with only clinical elevations in ADHD and only clinical levels in BPD features were also identified. Groups differed on level and type of impairment. Youth with ADHD and ODD represent a high-risk group likely to also show early prodromal clinical elevations in BPD. Future work is needed to examine the longitudinal outcomes of these subgroups to inform prevention and treatment.Youth with ADHD and ODD represent a high-risk group likely to also show early prodromal clinical elevations in BPD. Future work is needed to examine the longitudinal outcomes of these subgroups to inform prevention and treatment.Melanoma can be classified based on the detection of relevant oncogenic driver mutations. These mutations partially determine a patient's treatment options. MEK inhibitors have demonstrated little efficacy in patients with NRAS-mutated melanoma owing to primary and secondary resistance. We report two patients with NRAS-mutant metastatic melanoma with long-term response to intermittent MEK-inhibitor binimetinib therapy. Intermittent dosing schedules could play a key role in preventing resistance to targeted therapy. This article highlights the efficacy of an intermittent dosing schedule, toxicities associated with binimetinib, and possible mechanisms preventing resistance in targeted therapy. Intermittent MEK-inhibitor therapy may be considered in patients with NRAS-mutated melanoma that have failed all standard therapies. KEY POINTS Melanomas harbor NRAS mutations in 10%-30% of the cases. These mutations promote hyperactivation of the MAPK pathway, leading to proliferation and prolonged survival of tumor cells. Currently, drugs directly targeting NRAS are not available. Downstream inhibition of the MAPK pathway can be considered as a therapeutic option after immunotherapeutic failure. Intermittent administration of kinase inhibitors might be the way to partially overcome the development of drug resistance by (a) inducing a fitness deficit for drug-resistant cells on treatment break, (b) increasing the immunogenicity, and (c) inducing apoptosis and cell cycle arrest. It also enhances expression of numerous immunomodulating molecules, and reduction of immunosuppressive factors, which suggests better access of the immune system to the tumor. Our study describes the feasibility and efficacy of a first-line FOLFIRINOX (5-fluorouracil [5FU], folinic acid, irinotecan, and oxaliplatin) induction chemotherapy (CT) followed by de-escalation as a maintenance strategy for advanced pancreatic cancer. This multicenter retrospective study was conducted from January 2011 to December 2018. FOLFIRINOX de-escalation was defined as stopping oxaliplatin and/or irinotecan after at least four cycles of FOLFIRINOX, without evidence of disease progression. Maintenance schedules were fluoropyrimidine monotherapy (intravenous or oral [capecitabine]), FOLFOX (5FU, oxaliplatin), or FOLFIRI (5FU, irinotecan). Primary endpoint was overall survival (OS). Secondary endpoints were first progression-free survival (PFS1), second progression-free survival (PFS2), and toxicity. Among 321 patients treated with FOLFIRINOX, 147 (45.8%) were included. Median OS was 16.1 months (95% confidence interval [CI], 13.7-20.3) and median PFS1 was 9.4 months (95% CI, 8.5-10.4). The preferlly meaningful. Fluoropyrimidine monotherapy maintenance seems to be as efficient as FOLFIRI and should be a reference arm in future pancreatic cancer maintenance trials.FOLFIRINOX de-escalation and maintenance is a feasible strategy in advanced pancreatic cancer that decreases chemotherapy toxicity to improve both survival and quality of life. Survivals in patients with maintenance therapy are clinically meaningful. Fluoropyrimidine monotherapy maintenance seems to be as efficient as FOLFIRI and should be a reference arm in future pancreatic cancer maintenance trials. Proton pump inhibitor (PPI)-induced hypochondria can change the composition of the gut microbiota, inducing overgrowth of small bowel bacteria, which has been suggested to promote the development of fatty liver disease through the gut-liver axis. In this study, we aimed to investigate the association between PPI use and the risk of fatty liver disease. A retrospective cohort study was conducted using the Korean National Health Insurance Service-National Sample Cohort, a nationwide population-based representative sample, from January 1, 2002, to December 31, 2015. PPI use was identified from treatment claims and considered as a time-varying variable. During 1463556 person-years of follow-up, 75727 patients had at least one PPI prescription, and 3735 patients developed fatty liver disease. The hazard ratio for fatty liver disease comparing PPI users with non-PPI users was 1.68 (95% confidence interval, 1.61-1.75). When adjusted for multiple confounders, including age, sex, body mass index, smoking, alcohol intake, exercise, income level, and comorbidities, the association was still significant (hazard ratio, 1.