HHV-6 Encephalitis After Chimeric Antigen Receptor T-cell Therapy (CAR-T): 2 Case Reports and a Brief Review of the Literature.

Human herpesvirus 6 (HHV-6) reactivation can occur in patients who are highly immunosuppressed, including those who have undergone hematopoietic stem cell transplantation (HSCT). HHV-6 encephalitis is a severe manifestation that is well described in the HSCT population. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel cancer-directed immunotherapy that results in severe immunosuppression. Patients undergoing CAR-T therapy may be at risk for HHV-6 encephalitis, which can be difficult to distinguish from a common adverse effect of CAR-T therapy, neurotoxicity. Herein, we describe 2 patients diagnosed with HHV-6 encephalitis after CAR-T therapy and discuss the diagnostic approach and differential diagnosis for altered mental status after CAR-T therapy. Diagnosing HHV-6 encephalitis can be difficult in this patient population as altered mental status is common after CAR-T therapy and may be attributed to CAR-T-associated neurotoxicity.

Streptococcus pyogenes Infective Endocarditis-Association With Injection Drug Use: Case Series and Review of the Literature.

BACKGROUND: Streptococcus pyogenes, or Group A Streptococcus (GAS), is not considered a typical cause of infective endocarditis (IE), but has anecdotally been observed in unexpectedly high rates in people who inject drugs (PWID) at our institution. METHODS: All cases of possible or definite GAS IE per Modified Duke Criteria in adults at an academic hospital between 11/15/2015 and 11/15/2020 were identified. Medical records were reviewed for demographics, comorbidities, treatment, and outcomes related to GAS IE. The literature on cases of GAS IE was reviewed. RESULTS: Eighteen cases of probable (11) or definite (7) GAS IE were identified; the mean age was 38 years, and the population was predominantly female (56%) and Caucasian (67%), which is inconsistent with local population demographics. Sixteen cases were in people who inject drugs (PWID; 89%); 14 were also homeless, 6 also had HIV (33%), and 2 were also pregnant. Antibiotic regimens were variable due to polymicrobial bacteremia (39%). One patient underwent surgical valve replacement. Four patients (22%) died due to complications of infection. The literature review revealed 42 adult cases of GAS IE, only 17 of which were in PWID (24%). CONCLUSIONS: The 16 cases of possible and definite GAS IE in PWID over a 5-year period in a single institution reported nearly doubles the number of cases in PWID from all previous reports. This suggests a potential increase in GAS IE particularly in PWID and PWH, which warrants further epidemiologic investigation.

Genomic instability is a principle pathologic feature of FLT3 ITD kinase activity in acute myeloid leukemia leading to clonal evolution and disease progression.

Acute Myeloid Leukemia with FLT3 ITD mutations are associated with a poor prognosis characterized by a higher relapse rate, shorter relapse free survival, and decreased likelihood of response to therapy at relapse. FLT3 ITD signaling drives cell proliferation and survival. FLT3 ITD AML disease progression is associated with cytogenetic evolution and acquired tyrosine kinase inhibitor (TKI) resistance suggesting a potential role of genomic instability. There is growing evidence demonstrating a relationship between FLT3 signaling and increased DNA damage, specifically through increased reactive oxygen species (ROS) resulting in double-strand breaks (DSB), as well as impaired DNA repair, involving deficiencies in the non-homologous end joining (NHEJ), alternative non-homologous end joining (ALT NHEJ) and homologous recombination (HR) pathways. The role of genomic instability in the pathogenesis of FLT3 ITD AML warrants further examination as it offers potential therapeutic targets.