T cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL/LBL) is a precursor T cell leukemia/lymphoma that represents approximately 15% of all childhood and 25% of adult acute lymphoblastic leukemia. Although a high cure rate is observed in children, therapy resistance is often observed in adults and mechanisms leading to this resistance remain elusive. Utilizing public gene expression datasets, a fibrotic signature was detected in T-LBL but not T-ALL biopsies. Further, using a T-ALL cell line, CCRF-CEM (CEM) cells, we show that CEM cells induce pulmonary remodeling in immunocompromised mice, suggesting potential interaction between these cells and lung fibroblasts. Co-culture studies suggested that fibroblasts-induced phenotypic and genotypic divergence in co-cultured CEM cells leading to diminished therapeutic responses in vitro. Senescent rather than proliferating stromal cells induced these effects in CEM cells, due, in part, to the enhanced production of oxidative radicals and exosomes containing miRNAs targeting BRCA1 and components of the Mismatch Repair pathway (MMR). Collectively, our studies demonstrate that there may be bidirectional interaction between leukemic cells and stroma, where leukemic cells induce stromal development in vivo and senescent stromal cells generates genomic alterations in the leukemic cells rendering them therapeutic resistant. Thus, targeting senescent stroma might prove beneficial in T-ALL/LBL patients.

Purpose of ReviewThe present review discusses in-depth about neurological complications following acute venous thromboembolism (VTE). Recent Findings Intracranial hemorrhage, acute ischemic cerebrovascular events, and VTE in brain tumors are described as central nervous system (CNS) complications of PE, while peripheral neuropathy and neuropathic pain are reported as peripheral nervous system (PNS) sequelae of PE. Syncope and seizure are illustrated as atypical neurological presentations of PE. Summary Mounting evidence suggests higher risk of venous thromboembolism (VTE) in patients with neurological diseases, but data on reverse, i.e., neurological sequelae following VTE, is underexplored. The present review is an attempt to explore some of the latter issues categorized into CNS, PNS, and atypical complications following VTE.

Introduction While the global dissemination of vaccines targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a decline in the incidence of infections, the case fatality rates have remained relative stable. A major objective of managing hospitalized patients with documented or suspected COVID-19 infection is the rapid identification of features associated with severe illness using readily available laboratory tests and clinical tools. The sequential organ failure assessment (SOFA) score is a validated tool to facilitate the identification of patients at risk of dying from sepsis. Purpose The aim of this study was to assess the discriminatory accuracy of the SOFA score in predicting clinical decompensation in patients hospitalized with COVID-19 infection. Methods We conducted a retrospective analysis at a three-hospital health system, comprised of one tertiary and two community hospitals, located in the Chicago metropolitan area. All patients had positive SARS-CoV-2 testing and were hospitalized for COVID-19 infection. The primary outcome was clinical decompensation, defined as the composite endpoint of death, ICU admission, or need for intubation. We utilized the most abnormal laboratory values observed during the admission to calculate the SOFA score. Receiver Operating Curves (ROC) were then constructed to determine the sensitivity and specificity of SOFA scores. Results Between March 1st and May 31st 2020, 1029 patients were included in our analysis with 367 patients meeting the study endpoint. The median SOFA score was 2.0 IQR (Q1, Q3 1,4) for the entire cohort. Patients who had in-hospital mortality had a median SOFA score of 4.0 (Q1,Q3 3,7). In patients that met the primary composite endpoint, the median SOFA score was 3.0, IQR (Q1, Q3 2,6). The ROC was 0.776 (95% CI 0.746–0.806, p<0.01). Conclusion The SOFA score demonstrates strong discriminatory accuracy for prediction of clinical decompensation in patients presenting with COVID-19 at our urban hospital system. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Loyola University Medical Center

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