Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill.

Hematopoietic stem cell transplantation (HSCT) remains a cornerstone in the management of patients with hematological malignancies. Endothelial injury syndromes, such as HSCT-associated thrombotic microangiopathy (HSCT-TMA), veno-occlusive disease/sinusoidal obstruction syndrome (SOS/VOD), and capillary leak syndrome (CLS), constitute complications after HSCT. Moreover, endothelial damage is prevalent after immunotherapy with chimeric antigen receptor-T (CAR-T) and can be manifested with cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Our literature review aims to investigate the genetic susceptibility in endothelial injury syndromes after HSCT and CAR-T cell therapy. Variations in complement pathway- and endothelial function-related genes have been associated with the development of HSCT-TMA. In these genes, CFHR5, CFHR1, CFHR3, CFI, ADAMTS13, CFB, C3, C4, C5, and MASP1 are included. Thus, patients with these variations might have a predisposition to complement activation, which is also exaggerated by other factors (such as acute graft-versus-host disease, infections, and calcineurin inhibitors). Few studies have examined the genetic susceptibility to SOS/VOD syndrome, and the implicated genes include CFH, methylenetetrahydrofolate reductase, and heparinase. Finally, specific mutations have been associated with the onset of CRS (PFKFB4, CX3CR1) and ICANS (PPM1D, DNMT3A, TE2, ASXL1). More research is essential in this field to achieve better outcomes for our patients.

ADAMTS13 in the New Era of TTP.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening, often immune-mediated disease that affects 2-13 persons per million per year. Hemolytic anemia, thrombocytopenia, and end-organ damage due to the formation of microthrombi are characteristic of TTP. ADAMTS13 is a disintegrin, metalloproteinase, cleaving protein of von Willebrand factor (VWF) that processes the VWF multimers to prevent them from interacting with platelets and, in turn, to microvascular thrombosis. Prompt diagnosis of TTP is critical yet challenging. Thrombotic microangiopathies have similar clinical presentation. Measurement of ADAMTS13 activity helps in the differential diagnosis. Less than 10% ADAMTS13 activity is indicative of TTP. Laboratory ADAMTS13 activity assays include incubating the test plasma with the substrate (full-length VWM multimers) and detection with direct or indirect measurement of the cleavage product. The purpose of this study is to examine the diagnostic potential, advantages, and weaknesses of the ADAMTS13 potency in TTP.

Pneumocephalus; a rare cause of coma.

We report the case of an 84-years old female patient who developed cerebral air embolism in association with the indwelling hemodialysis central venous catheter. Pneumocephalus, even though rare, should be included in the differential diagnosis of acute manifestation of neurologic deficits, especially in association with central venous access, surgical interventions or trauma, and requests prompt management. Brain computed tomography scanning remains the investigation of choice.

Anaerobic Spondylodiscitis caused by Parvimonas Micra in a Rheumatoid Arthritis Patient: Case Report and Review of the Literature.

We report the rare case of Parvimonas micra bacteraemia and secondary spondylodiscitis probably triggered by tooth injury in a rheumatoid arthritis patient. Anaerobic bacteria associated spondylodiscitis may evade diagnosis due to atypical clinical presentation usually lacking fever, and the difficulties related to microbiological characterisation of the pathogen. Even though anaerobic spinal infections may constitute <3% of the total, clinical suspicion should remain high, especially in the case of positive history for pre-existing oral cavity or gastrointestinal/gynaecological tract infections.

Casivirimab/Imdevimab Effect on COVID-19 Outcome and Reinfection in a Real-World SARS-COV-2 Variant Transition Period Setting.

Monoclonal antibodies targeted against SARS-COV-2 have been recruited in the challenging treatment of COVID-19 with few clinically significant side effects. Casivirimab/imdevimab, a combination of monoclonal antibodies targeted against SARS-COV-2 spike protein, was shown to effectively prevent recently infected high-risk COVID-19 patients from developing severe disease. Its efficacy waned with the emergence of the resistant omicron variant in late 2021. We recorded the real-world effect of casivirimab/imdevimab on 116 high-risk COVID-19 patients. Cumulative need for hospitalization, mortality, new-onset disease, and reinfections was monitored. Casivirimab/imdevimab effect was independent from previous immunization. The cohort was further divided into two subgroups: patients infected during a delta variant prevalent period were more likely to become admitted but as likely to die than patients infected with the omicron variant, in support of its protective effect from clinical studies. Cumulative reinfection incidence in treated patients, interestingly, was lower than in the general population.