Kanade Shinkai’s research while affiliated with University of California, San Francisco and other places

This retrospective cohort study analyzes the presentation, diagnosis, and treatment outcomes of patients who developed drug rash with eosinophilia and systemic symptoms (DRESS) to tuberculosis (TB) therapy in a TB non‐endemic region. Anti‐TB agents represented 7.5% of all antimicrobial‐induced DRESS cases, and rifampin was the most commonly implicated agent among drugs used to treat TB.

Study objectives: Risk of obstructive sleep apnea appears to be increased among patients with polycystic ovary syndrome (PCOS), but the underlying physiology is unclear. We sought to identify predictors of OSA risk among patients with PCOS. Methods: A cross-sectional analysis of patients evaluated for PCOS at a single tertiary center from 2017 to 2022 was completed. Inclusion criteria included: age 18-44, Rotterdam criteria for PCOS, and had completed a Berlin Questionnaire (BQ) for OSA risk assessment. All patients underwent standardized anthropometric, ultrasound, endocrine, and metabolic phenotyping. Results: Of the 572 patients screened during the study period, 309 patients with PCOS met inclusion criteria, and 104 (33.7%) had a high risk BQ. Those with high-risk BQ, compared to those without, had significantly (p<0.05) higher waist:hip ratio, LDL-C, triglycerides, fasting insulin, 2-hour insulin, fasting glucose, 2-hour glucose, HOMA-IR, HbA1c, CRP, free testosterone, free androgen index, and lower HDL-C and SHBG. In multivariable modeling controlling for all significantly differing variables in univariate analyses, HbA1c (β (S.E.) 1.05 (0.45), p=0.02), CRP (0.09 (0.04), p=0.01), and SHBG (-0.02 (0.01), p=0.02)) associated with high risk BQ. Conclusions: Dysglycemia, inflammation, and androgen status independently associate with predicted OSA risk by BQ. Future studies are needed to comprehensively assess the impact of treatment of OSA on these outcomes among patients with PCOS to better clarify the directionality and clinical implications of these associations.

Importance Pyoderma gangrenosum (PG) is a rare ulcerative skin condition with no current standardized outcomes or outcome measures. With a rich investigational therapeutic pipeline, standardization of outcomes and improvement of data quality and interpretability will promote the appropriate and consistent evaluation of potential new therapies. Core Outcome Sets (COS) are agreed standardized sets of outcomes that represent the minimum that should be measured and reported in all clinical trials of a specific condition. Objective To identify and reach consensus on which domains (what to be measured) should be included in the Understanding Pyoderma Gangrenosum: Review and Analysis of Disease Effects (UPGRADE) Core Domain Set for PG clinical trials. Design Collaborative discussions between patients and PG experts, and a systematic review of the literature identified items and prospective domains. A three-round international eDelphi exercise was performed to prioritize the domains and refine the provisional items (consensus: ≥70% of participants rating a domain as ‘extremely important’ and <15% of participants voting ‘not important’, followed by an international meeting to reach consensus on the core domain set (consensus: <30% disagreement). Setting Item generation discussions and consensus meetings were hosted via online video conferences. Delphi exercise and consensus voting were performed using Qualtrics electronic survey software. Participants Adults with PG, healthcare professionals, researchers, and industry representatives. Findings Collaborative discussions and systematic review yielded 115 items, which were distilled into 15 prospective domains. The eDelphi exercise removed three lowest priority domains (Laboratory Tests, Treatment Costs, and Disease Impact on Family) and ranked Pain, Quality of Life, and Physical Symptoms as the highest priority prospective domains. Consensus was reached on the domains of Pain, Quality of Life, and Clinical Signs. The domain of disease course/disease progression narrowly failed to reach consensus for inclusion in the core set (32.2% of participants voted no). Refinement of this domain definition will be required and presented for consideration at future consensus meetings. Conclusions and Relevance The UPGRADE Core Domain Set for PG clinical trials has been agreed by international multi-stakeholder consensus. Future work will develop and/or select outcome measurement instruments for these domains to establish a core outcome set.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15–20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1–5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28–29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper.

Disclosure: J.P. Christ: None. K. Shinkai: None. J. Corley: None. L. Pasch: None. M.I. Cedars: None. H. Huddleston: None. Background: The 2018 international guidelines for the assessment and management of PCOS exclude ovarian morphology from the diagnosis of PCOS in adolescents due to limited data regarding normative values in this population. Adolescents with oligo-amenorrhea (OA) or hyperandrogenism (HA) alone are thus excluded from diagnosis and ultrasonography has been removed from clinical use without an assessment of its utility in this population. Objective: To characterize ovarian morphology among adolescents with PCOS and evaluate the relevance of PCOM among those currently excluded from diagnosis. Methods: A cross-sectional analysis of patients that underwent a standardized evaluation for PCOS at a single tertiary center from 2006 to 2022 was completed. Participants were included if they were within 8 years of menarche or were <20 years of age at screening and had data on ovarian morphology. Follicle number per ovary (FNPO) and ovarian volume (OV) were assessed by transvaginal ultrasound, or if not tolerated, transabdominal (in which case FNPO was omitted) or transrectal approach. PCOM was defined as a FNPO of >20 follicles or an OV >10cc in either ovary. Maximum FNPO and OV in either ovary was used for analyses. Age based criteria were used to define irregular menstrual cycles and were characterized among those >1 year post menarche. Patients were grouped into those with OA and HA (PCOS-NIH), with OA or HA as well as PCOM (PCOS-Rotterdam), and with one or no features (non-PCOS). Results: Of the 133 subjects included, 95 met PCOS-NIH criteria, 22 met PCOS-Rotterdam criteria and 16 met non-PCOS criteria. Prevalence of PCOM among PCOS-NIH was 82.1%. Significant differences were seen between Non-PCOS, PCOS-Rotterdam, and PCOS-NIH for FNPO (15.5±8.7 vs 30.9±12.5 vs 31.8±14.6), OV (6.1±4 vs 10.8±4.5 vs 11.4±6.4), waist:hip ratio (WHR) (0.7±0.1 vs 0.8±0.1 vs 0.8±0.1), 2-hour glucose (99.5±17.1 vs 84.8±18.9 vs 105.6±41 uIU/mL), QUICKI (0.4±0 vs 0.4±0.1 vs 0.3±0.1), and HOMA-IR (1.9±1.2 vs 2.4±2.1 vs 4.7±5.7) (p<0.05 for overall comparisons between groups). Among PCOS-Rotterdam and Non-PCOS, in multivariable models controlling for WHR, systolic blood pressure (β=0.5, p=0.09) and free testosterone (β=0.03, p=0.03) associated with FNPO and QUICKI (β=69.1, p=0.003) associated with OV. Conclusion: Adolescents meeting NIH criteria appear to be at greatest metabolic risk. Ovarian morphology, however, may reflect degree of hyperandrogenism and metabolic dysfunction among adolescents currently excluded from diagnosis of PCOS (i.e. PCOS-Rotterdam and non-PCOS groups). The inclusion of ultrasound assessment may thus be able to aid in risk stratification and phenotyping among those without a definitive PCOS diagnosis. Presentation Date: Saturday, June 17, 2023