Icahn School of Medicine at Mount Sinai

About: Icahn School of Medicine at Mount Sinai is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 37488 authors who have published 76057 publications receiving 3704104 citations. The organization is also known as: Mount Sinai School of Medicine.

3-Year Follow-up of the NIMH MTA Study

Abstract: Objective: In the intent-to-treat analysis of the Multimodal Treatment Study of Children With ADHD (MTA), the effects of medication management (MedMgt), behavior therapy (Beh), their combination (Comb), and usual community care (CC) differed at 14 and 24 months due to superiority of treatments that used the MTA medication algorithm (Comb+MedMgt) over those that did not (Beh+CC). This report examines 36-month outcomes, 2 years after treatment by the study ended. Method: For primary outcome measures (attention-deficit/hyperactivity disorder [ADHD] and oppositional defiant disorder [ODD] symptoms, social skills, reading scores, impairment, and diagnostic status), mixed-effects regression models and orthogonal contrasts examined 36-month outcomes. Results: At 3 years, 485 of the original 579 subjects (83.8%) participated in the follow-up, now at ages 10 to 13 years, (mean 11.9 years). In contrast to the significant advantage of MedMgt+Comb over Beh+CC for ADHD symptoms at 14 and 24 months, treatment groups did not differ significantly on any measure at 36 months. The percentage of children taking medication >50% of the time changed between 14 and 36 months across the initial treatment groups: Beh significantly increased (14% to 45%), MedMed+Comb significantly decreased (91% to 71%), and CC remained constant (60%-62%). Regardless of their treatment use changes, all of the groups showed symptom improvement over baseline. Notably, initial symptom severity, sex (male), comorbidity, public assistance, and parental psychopathology (ADHD) did not moderate children's 36-month treatment responses, but these factors predicted worse outcomes over 36 months, regardless of original treatment assignment. Conclusions: By 36 months, the earlier advantage of having had 14 months of the medication algorithm was no longer apparent, possibly due to age-related decline in ADHD symptoms, changes in medication management intensity, starting or stopping medications altogether, or other factors not yet evaluated.

An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans

Abstract: To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects) We identified 13 novel T2D-associated loci (P < 5 × 10-8), including variants near the GLP2R, GIP, and HLA-DQA1 genes Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology

A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments.

Abstract: Intratumoral stimulatory dendritic cells (SDCs) play an important role in stimulating cytotoxic T cells and driving immune responses against cancer. Understanding the mechanisms that regulate their abundance in the tumor microenvironment (TME) could unveil new therapeutic opportunities. We find that in human melanoma, SDC abundance is associated with intratumoral expression of the gene encoding the cytokine FLT3LG. FLT3LG is predominantly produced by lymphocytes, notably natural killer (NK) cells in mouse and human tumors. NK cells stably form conjugates with SDCs in the mouse TME, and genetic and cellular ablation of NK cells in mice demonstrates their importance in positively regulating SDC abundance in tumor through production of FLT3L. Although anti-PD-1 ‘checkpoint’ immunotherapy for cancer largely targets T cells, we find that NK cell frequency correlates with protective SDCs in human cancers, with patient responsiveness to anti-PD-1 immunotherapy, and with increased overall survival. Our studies reveal that innate immune SDCs and NK cells cluster together as an excellent prognostic tool for T cell–directed immunotherapy and that these innate cells are necessary for enhanced T cell tumor responses, suggesting this axis as a target for new therapies.

Management of the Child Born Small for Gestational Age through to Adulthood: A Consensus Statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society

Abstract: Objective: Low birth weight remains a major cause of morbidity and mortality in early infancy and childhood. It is associated with an increased risk of health problems later in life, particularly coronary heart disease and stroke. A meeting was convened to identify the key health issues facing a child born small for gestational age (SGA) and to propose management strategies.

The safety of vedolizumab for ulcerative colitis and Crohn's disease

Abstract: Objective Vedolizumab is a gut-selective antibody to α 4 β 7 integrin for the treatment of ulcerative colitis (UC) and Crohn9s disease (CD). We report an integrated summary of the safety of vedolizumab. Design Safety data (May 2009–June 2013) from six trials of vedolizumab were integrated. Adverse events were evaluated in patients who received ≥1 dose of vedolizumab or placebo and were reported as exposure-adjusted incidence rates as the number of patients experiencing the event per 100 person-years (PYs) of exposure. Predictors of serious infection were assessed using a Cox proportional hazards model. Results In total, 2830 patients had 4811 PYs of vedolizumab exposure (median exposure range, 1–1977 days). No increased risk of any infection or serious infection was associated with vedolizumab exposure. Serious clostridial infections, sepsis and tuberculosis were reported infrequently (≤0.6% of patients). No cases of progressive multifocal leucoencephalopathy were observed. Independent risk factors for serious infection in UC were prior failure of a tumour necrosis factor α antagonist (HR, 1.99; 95% CIs 1.16 to 3.42; p=0.0122) and narcotic analgesic use (HR, 2.68; 95% CI 1.57 to 4.58; p=0.0003), and in CD were younger age (HR, 0.97; 95% CI 0.95 to 0.98; p Conclusions Vedolizumab has a favourable safety profile with low incidence rates of serious infections, infusion-related reactions and malignancies over an extended treatment period. Trial registration number NCT01177228, NCT00619489, NCT00783718, NCT00783692, NCT01224171, NCT00790933.