Project description:BackgroundMultifood oral immunotherapy (mOIT) with adjunctive anti-IgE (omalizumab, XOLAIR® ) treatment affords safe, effective, and rapid desensitization to multiple foods, although the specific immune mechanisms mediating this desensitization remain to be fully elucidated.MethodsParticipants in our phase 2 mOIT trial (NCT02643862) received omalizumab from baseline to week 16 and mOIT from week 8 to week 36. We compared the immune profile of PBMCs and plasma taken at baseline, week 8, and week 36 using high-dimensional mass cytometry, component-resolved diagnostics, the indirect basophil activation test, and Luminex.ResultsWe found (i) decreased frequency of IL-4+ peanut-reactive CD4+ T cells and a marked downregulation of GPR15 expression and CXCR3 frequency among γδ and CD8+ T-cell subsets at week 8 during the initial, omalizumab-alone induction phase; (ii) significant upregulation of the skin-homing receptor CCR4 in peanut-reactive CD4+ T and Th2 effector memory (EM) cells and of cutaneous lymphocyte-associated antigen (CLA) in peanut-reactive CD8+ T and CD8+ EM cells; (iii) downregulation of CD86 expression among antigen-presenting cell subsets; and (iv) reduction in pro-inflammatory cytokines, notably IL-17, at week 36 post-OIT. We also observed significant attenuation of the Th2 phenotype post-OIT, defined by downregulation of IL-4 peanut-reactive T cells and OX40 in Th2EM cells, increased allergen component-specific IgG4/IgE ratio, and decreased allergen-driven activation of indirectly sensitized basophils.ConclusionsThis exploratory study provides novel comprehensive insight into the immune underpinnings of desensitization through omalizumab-facilitated mOIT. Moreover, this study provides encouraging results to support the complex immune changes that can be induced by OIT.
Project description:Schizophrenia patients have significantly lower life expectancy than the general population. Clozapine is the most effective antipsychotic to reduce the mortality rate in these patients. Here, we report a schizophrenic patient with clozapine-induced myocarditis and successful retrial. In the first trial, clozapine was discontinued due to myocarditis. In the second trial, the titration rate was slower, and sodium valproate was not coadministered with clozapine. The patient has not developed myocarditis over 3.5 years of observation. It may be possible to take clozapine for a long time even after clozapine-induced myocarditis, and thus improve the life expectancy of schizophrenia patients.
Project description:IntroductionThe American College of Obstetricians and Gynecologists recommends prompt postpartum follow-up. However, 40% of women do not attend postpartum visits. These rates are lower in populations with limited resources. In response, the Department of Obstetrics, Gynecology, and Reproductive Science in the Mount Sinai Health System created a postpartum follow-up phone call project that utilized medical students and was conducted at three health system hospitals from April 6 to May 30, 2020.MethodsThe number of patients contacted by medical students within 72 hours of hospital discharge was recorded. Students at two of the three sites also recorded the number of patients who needed (1) urgent evaluation and subsequent hospital readmission, (2) medications prescribed, and (3) referral for social work services. Students completed questionnaires at the project beginning and end regarding confidence in rendering of postpartum care. Confidence level was based on a 5-point Likert scale (1 = not confident at all, 5 = very confident).ResultsNine students participated. Overall, confidence on providing postpartum care significantly increased from 2.2 to 3.7 (p < .001). Three hundred eighty-seven patients were contacted. Four patients were advised to return to the hospital emergently; two were readmitted. Forty-seven patients needed medication prescribed. Two patients were referred for social work services.DiscussionOur medical student-driven postpartum follow-up phone call project was associated with a high number of patients called and management of significant postpartum issues. Students' confidence in managing postpartum issues was significantly higher after versus before project participation.
Project description:Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with 5-year survival of ~50%. Genomic profiling studies have identified important somatic mutations in this disease which presents an opportunity for precision medicine. We demonstrate that KMT2D, a histone methyltransferase harbors somatic mutations in ~17% of HNSCC and is associated with 2-year recurrence in TCGA data. Consistent with algorithmic prediction of bring a driver tumor-suppressor event, its loss results in larger oral tumors in immune-proficient orthotopic models. Mechanistically, we find that KMT2D knockdown or KMT2D mutation causes loss of H3K4me1-marked enhancers harboring IRF7/9 binding sites, which is known to regulate interferon signaling. Indeed, KMT2D loss in human and murine cell lines deregulated transcriptional levels of cytokine expression and impacted numerous immune signaling pathways, including interferon signaling. Consistently, Kmt2d knockdown in murine tumors exhibited decrease in IFN-producing effector T cells and an increase in T-cells with an exhausted phenotype. Epistasis experiments showed that exogenous treatment with IFNabrogated the increased tumor growth in Kmt2d-deficient oral tumors. Together, these results support the role of KMT2D as a tumor suppressor in HNSCC that regulates the tumor microenvironment by modulating H3K4me1-marked enhancers controlling interferon signaling.