HLA binding-groove motifs are associated with myocarditis induction after Pfizer-BioNTech BNT162b2 vaccination.

BACKGROUND AND AIMS: We found a higher incidence of myocarditis in young males who had received at least two Pfizer-BioNTech BNT162b2 vaccinations. The human leukocyte antigens (HLA) are known to play an important role in infectious and autoinflammatory diseases. We hypothesized that certain HLA alleles might be associated with vaccination-induced myocarditis. METHODS: HLA typing was performed using next-generation sequencing technology with the Illumina Iseq100 platform. HLA class I and II loci were genotyped in 29 patients with post-vaccination myocarditis and compared with HLA data from 300 healthy controls. RESULTS: We demonstrate that the DRB1*14:01, DRB1*15:03 alleles and the motifs in HLA-A - Leu62 and Gln63, which are part of binding pocket B and HLA-DR Tyr47, His60, Arg70 and Glu74, which are part of binding pockets P4, P7 and P9, were significantly associated with disease susceptibility. CONCLUSIONS: Our findings suggest that immunogenetic fingerprints in HLA peptide-binding grooves may affect the presentation of peptides derived from the Pfizer-BioNTech BNT162b2 vaccination to T cells and induce an inflammatory process that results in myocarditis.

Glucose-6-Phosphate Dehydrogenase Deficiency and COVID-19 Mortality, ICU Admission, and Length of Hospitalization.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has severe consequences in terms of mortality and morbidity. Knowledge of factors that impact COVID-19 may be useful in the search for treatments. OBJECTIVES: To determine the effect of glucose-6-phosphate dehydrogenase (G6PD) deficiency on morbidly and mortality associated with COVID-19. METHODS: All patients admitted to Hadassah Hebrew University Medical Center between 01 March 2020 and 03 May 2021 with a diagnosis of COVID-19 were included. We retrospectively retrieved demographic, clinical, and laboratory data from the hospital's electronic medical records. The main outcomes were mortality, intensive care unit (ICU) admission, and severity of COVID-19. RESULTS: The presence of G6PD deficiency emerged as an independent protective predictor for ICU admission (odds ratio [OR] 0.258, 95% confidence interval [95%CI] 0.077-0.619, P = 0.003) and the development of critical illness (OR 0.121, 95%CI 0.005-0.545, P = 0.006). Moreover, patients with G6PD deficiency had a trend toward lower mortality rates that did not reach statistical significance (OR 0.541, 95%CI 0.225-1.088, P = 0.10). CONCLUSIONS: Patients with G6PD deficiency were less likely to have a severe disease, had lower rates of ICU admission, and trended toward lower mortality rates.

Desensitization protocol to lenalidomide: An effective and safe treatment modality for delayed hypersensitivity-induced rash in patients with multiple myeloma.

INTRODUCTION AND OBJECTIVES: Lenalidomide is considered a standard of care in multiple myeloma (MM) Some MM patients will develop delayed hypersensitivity to lenalidomide, which can lead to treatment discontinuation. Desensitization to lenalidomide can help these patients to complete treatment courses. Here, we aimed to review lenalidomide-treated MM patients who developed delayed hypersensitivity-induced rash and were treated with desensitization. METHODS: A retrospective analysis of medical files of MM patients, who were desensitized to lenalidomide due to delayed hypersensitivity rash. Patients were treated between 2018 and 2022 at Hadassah Medical Center, Jerusalem, Israel. RESULTS: Search of patients yielded 16 patients that underwent desensitization to lenalidomide within the study period. The desensitization protocol consisted of a slow, 3-week-long protocol with lenalidomide's target doses of 10, 15, and 25 mg/day. Of the 16 patients, 10 (62.5%) succeeded to complete the protocol and thus were able to complete lenalidomide treatment cycles. One patient with unsuccessful desensitization was subsequently treated with first-generation IMiD thalidomide, with no rash appearing. None of the patients that were treated with desensitization had severe immune-mediated or non-dermatological adverse reactions. CONCLUSIONS: Desensitization to lenalidomide is safe and effective. Discontinuation of lenalidomide in MM patients with delayed hypersensitivity and no contraindication to desensitization should be discouraged. Collaboration between hematologists and allergists is needed.

[FROM OPTIC NERVE EDEMA TO POLYSOMNOGRAPHY - ANOTHER WAY TO DIAGNOSE OBSTRUCTIVE SLEEP APNEA].

INTRODUCTION: Some systemic diseases have ophthalmic manifestations. Findings on examination of the fundus can assist in the diagnosis and treatment of these diseases. In this manuscript, we present two ophthalmic conditions that cause optic disc edema and are highly associated with obstructive sleep apnea (OSA). The conditions are non-arteritic anterior ischemic optic neuropathy (NAION), and Papilledema associated with the Pickwickian syndrome. When these conditions are suspected, the patient should be referred for a polysomnography examination.