Deletion of ΔdblGata motif leads to increased predisposition and severity of IgE-mediated food-induced anaphylaxis response.

BackgroundPrevious studies have revealed an important role for the transcription factor GATA-1 in mast cell maturation and degranulation. However, there have been conflicting reports with respect to the requirement of GATA-1 function in mast cell dependent inflammatory processes. Herein, we examine the requirement of GATA-1 signaling in mast cell effector function and IgE-mast cell-dependent anaphylaxis.ObjectiveTo study the requirement of GATA-1 dependent signaling in the development and severity of IgE-mast cell-dependent anaphylaxis in mice.MethodsWild type (Balb/c) and mutant ΔdblGata (Balb/c) mice were employed to study the role of GATA-1 signaling in in vitro IgE-mediated activation of bone marrow derived mast cells (BMMCs). Murine models of passive IgE-mediated and oral antigen-induced IgE-mediated anaphylaxis were employed in mice. Frequency of steady state mast cells in various tissues (duodenum, ear, and tongue), peritoneal cavity, and clinical symptoms (diarrhea, shock, and mast cell activation) and intestinal Type 2 immune cell analysis including CD4+ Th2 cells, type 2 innate lymphoid cells (ILC2), and IL-9 secreting mucosal mast cells (MMC9) were assessed.ResultsIn vitro analysis revealed that ΔdblGata BMMCs exhibit a reduced maturation rate, decreased expression of FcεRIα, and degranulation capacity when compared to their wildtype (WT) counterparts. These in vitro differences did not impact tissue resident mast cell numbers, total IgE, and susceptibility to or severity of IgE-mediated passive anaphylaxis. Surprisingly, ΔdblGata mice were more susceptible to IgE-mast cell-mediated oral antigen induced anaphylaxis. The increased allergic response was associated with increased Type 2 immunity (antigen-specific IgE, and CD4+ TH2 cells), MMC9 cells and small intestine (SI) mast cell load.ConclusionDiminished GATA-1 activity results in reduced in vitro mast cell FcεRIα expression, proliferation, and degranulation activity. However, in vivo, diminished GATA-1 activity results in normal homeostatic tissue mast cell levels and increased antigen-induced CD4+ Th2 and iMMC9 cell levels and heightened IgE-mast cell mediated reactions

Trends in Utilization and Patient Demographics for Shoulder Instability Procedures from 2010 to 2019

INTRODUCTION: Improved technique and increased surgeon experience has optimized surgical care in patients with recurrent shoulder instability. Several techniques are used for surgical repair of shoulder instability, yet there is limited data on how utilization has changed over the past decade. The aim of this study was to assess trends in the utilization rate and patient demographics (age and gender) from 2010-2019 for four shoulder instability procedures: coracoid transfer/Latarjet procedure (LP), anterior bone block (ABB), open Bankart repair (OBR), and arthroscopic Bankart repair (ABR). METHODS: We identified over 87,00 patients using an all-payer claims database. The utilization rate was defined as the number of cases for a procedure divided by the total number surgical cases for shoulder instability for any given year. Age was divided into three groups: \u3c25, 25-35, \u3e35-years-old. Trends were reported in terms of compounded annual growth rates (CAGR). RESULTS: While ABR was the most common shoulder instability procedure overall (91% utilization rate), LP had the greatest increase in utilization from 2010-2019 (2.0% to 4.5%; CAGR: +9.8%). In comparison, the utilization for ABB increased +4.3% annually while OBR declined -6.9% annually. The utilization of ABR showed minimal change. Notably, LP was performed more frequently on younger patients over time. The percentage of patients \u3c25-years-old who underwent LP increased from 30% to 41% from 2010-2019 (+3.4%). There was a trend toward performing more LP on men versus women (+1.2% vs. -3.5%, P \u3c 0.05), although most cases (68%) were still performed on men. CONCLUSION: ABR continues to account for most shoulder instability procedures. LP had the greatest increase in utilization rate from 2010-2019 and has now surpassed OBR in utilization rate. ABB is also being more frequently performed but only represents a minority of stabilization cases. During the course of the study period, a greater percentage of patients undergoing shoulder instability procedure were male and \u3c25-years-old

Social Determinants of Health Disparities Impact Postoperative Complications in Patients Undergoing Total Shoulder Arthroplasty

BACKGROUND: Understanding the role of social determinants of health disparities (SDHD) in surgical outcomes can better prepare providers to improve postoperative care. In this study, we utilize International Classification of Diseases (ICD) codes to identify SDHD and investigate the risk of postoperative complication rates among patients undergoing total shoulder arthroplasty (TSA). METHODS: A retrospective cohort analysis was conducted using a national insurance claims database. Using ICD and Current Procedural Terminology (CPT) codes patients who underwent primary TSA with at least two years of follow-up in the database were identified. Patients with a history of SDHD were identified using appropriate ICD-9 and ICD-10 codes. Patients were grouped in one of two cohorts: (1) patients with no history of SDHD (Control) and (2) patients with a history of SDHD (SDHD group) prior to TSA. The SDHD and control groups were matched 1:1 for comorbidities and demographics prior to conducting multivariable analysis for 90-day medical complications and 2-year surgical complications. RESULTS: After matching, there were 8,023 patients in the SDHD group and 8,023 patients in the control group. The SDHD group had significantly higher odds for 90-day medical complications including heart failure, cerebrovascular accident, renal failure, deep vein thrombosis, pneumonia, sepsis, and urinary tract infection. Additionally, the SDHD group had significantly higher odds for revision surgery within 2-years following TSA. Patients in the SDHD group also had a significantly longer length of hospital stay following TSA. DISCUSSION: This study highlights the association between SDHD and postoperative complications following TSA. Quantifying the risk of complications and differences in length of stay for TSA patients with a history of SDHD is important in determining value-based payment models and risk stratifying to optimize patient care