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  1. Article ; Online: Standardized indolent systemic mastocytosis evaluations across a healthcare system: implications for screening accuracy.

    McMurray, Jeremy C / Pacheco, Curtis S / Schornack, Brandon J / Sun, Xiaoping / Brunader, Janet A / Scott, Alexis Erica / Ariza, Juan S / Kou, Chung-Ting J / Costantino, Ryan C / Pittman, Luke M / Adams, Karla E / Waters, Aubri M / Pryor, Eric M / Lyons, Jonathan J / Metcalfe, Dean / Maric, Irina / Boggs, Nathan A

    Blood

    2024  

    Abstract: Timely diagnosis of systemic mastocytosis (SM) remains challenging due to care heterogeneity. We implemented a standardized approach for SM screening and diagnosis utilizing a novel healthcare system-wide international screening registry. A retrospective ...

    Abstract Timely diagnosis of systemic mastocytosis (SM) remains challenging due to care heterogeneity. We implemented a standardized approach for SM screening and diagnosis utilizing a novel healthcare system-wide international screening registry. A retrospective analysis assessed rates of SM, cutaneous mastocytosis (CM), and molecular diagnoses before and two years after care standardization. Accuracy of individual and combined SM screening tests - basal serum tryptase (BST) ≥11.5 and ≥20.0 ng/mL, REMA ≥2, monomorphic maculopapular CM, and elevated BST based upon tryptase genotype - was analyzed. Tryptase genotyping and high-sensitivity KIT p.D816V testing increased substantially two years following care standardization. SM diagnoses doubled from 47 to 94 and KIT p.D816V molecular diagnoses increased from 24 to 79. Mean BST and KIT p.D816V variant allele frequency (VAF) values were significantly lower in patients diagnosed after standardization. Hereditary-alpha tryptasemia prevalence was increased in SM prior to care standardization at 4/30 (13.3%) but reflected the general population prevalence two years later at 5/76 (6.6%). Elevated BST based upon genotype and BST ≥11.5 ng/mL had the highest sensitivities at 84.2% and 88.3%, respectively. Presence of monomorphic MPCM, elevated BST based upon tryptase genotype, and the combination of REMA ≥2 with elevated BST based upon tryptase genotype had specificities >90%. BST >20.0 ng/mL had low sensitivity and specificity and was not required to establish any indolent SM diagnosis. Care standardization increased SM diagnosis rates, particularly in patients with low BSTs. Stratifying BST based upon genotype had the best overall sensitivity and specificity of any indolent SM screening test and improved the REMA score specificity.
    Language English
    Publishing date 2024-04-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2023023347
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Myocarditis and pericarditis recovery following smallpox vaccine 2002-2016: A comparative observational cohort study in the military health system.

    Engler, Renata J M / Montgomery, Jay R / Spooner, Christina E / Nelson, Michael R / Collins, Limone C / Ryan, Margaret A / Chu, Clara S / Atwood, John E / Hulten, Edward A / Rutt, Ahlea A / Parish, Dacia O / McClenathan, Bruce M / Hrncir, David E / Duran, Laurie / Skerrett, Catherine / Housel, Laurie A / Brunader, Janet A / Ryder, Stephanie L / Lohsl, Connie L /
    Hemann, Brian A / Cooper, Leslie T

    PloS one

    2023  Volume 18, Issue 5, Page(s) e0283988

    Abstract: Objectives: (1) Characterize the initial clinical characteristics and long-term outcomes of smallpox vaccine-associated hypersensitivity myocarditis and pericarditis (MP) in United States service members. (2) Describe the process of case identification ... ...

    Abstract Objectives: (1) Characterize the initial clinical characteristics and long-term outcomes of smallpox vaccine-associated hypersensitivity myocarditis and pericarditis (MP) in United States service members. (2) Describe the process of case identification and adjudication using the 2003 CDC nationally defined myocarditis/pericarditis epidemiologic case definitions to include consideration of case-specific diversity and evolving evidence.
    Background: Between 2002 and 2016, 2.546 million service members received a smallpox Vaccinia vaccine. Acute MP is associated with vaccinia, but the long-term outcomes have not been studied.
    Methods: Records of vaccinia-associated MP reported to the Vaccine Adverse Event Reporting System by vaccination date were adjudicated using the 2003 MP epidemiologic case definitions for inclusion in a retrospective observational cohort study. Descriptive statistics of clinical characteristics, presentation, cardiac complications, and time course of clinical and cardiac recovery were calculated with comparisons by gender, diagnosis and time to recovery.
    Results: Out of over 5000 adverse event reports, 348 MP cases who survived the acute illness, including 276 myocarditis (99.6% probable/confirmed) and 72 pericarditis (29.2% probable/confirmed), were adjudicated for inclusion in the long-term follow-up. Demographics included a median age of 24 years (IQR 21,30) and male predominance (96%). Compared to background military population, the myocarditis and pericarditis cohort had a higher percentage of white males by 8.2% (95% CI: 5.6, 10.0) and age <40 years by 4.2% (95% CI: 1.7,5.8). Long-term follow-up documented full recovery in 267/306 (87.3%) with 74.9% recovered in less than a year (median ~3 months). Among patients with myocarditis, the percentage who had a delayed time to recovery at time of last follow-up was 12.8% (95% CI: 2.1,24.7) higher in those with an acute left ventricular ejection fraction (EF) of ≤50% and 13.5% (95% CI: 2.4,25.7) higher in those with hypokinesis. Patient complications included 6 ventricular arrhythmias (2 received implanted defibrillators) and 14 with atrial arrhythmias (2 received radiofrequency ablation). Three of 6 patients (50%) diagnosed with cardiomyopathy had clinical recovery at their last follow-up date.
    Conclusions: Hypersensitivity myocarditis/pericarditis following the smallpox vaccine is associated with full clinical and functional ventricular recovery in over 87% of cases (74.9% <1 year). A minority of MP cases experienced prolonged or incomplete recovery beyond 1 year.
    MeSH term(s) Humans ; Male ; United States ; Adult ; Female ; Smallpox Vaccine/adverse effects ; Myocarditis/epidemiology ; Myocarditis/etiology ; Myocarditis/diagnosis ; Vaccinia/prevention & control ; Retrospective Studies ; Military Health Services ; Stroke Volume ; Ventricular Function, Left ; Vaccination ; Pericarditis/epidemiology ; Pericarditis/etiology ; Pericarditis/diagnosis ; Smallpox/prevention & control ; Vaccinia virus
    Chemical Substances Smallpox Vaccine
    Language English
    Publishing date 2023-05-08
    Publishing country United States
    Document type Observational Study ; Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0283988
    Database MEDical Literature Analysis and Retrieval System OnLINE

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