Mira A. Kohorst

Bio: Mira A. Kohorst is an academic researcher from Mayo Clinic. The author has contributed to research in topics: Medicine & Transplantation. The author has an hindex of 4, co-authored 14 publications receiving 41 citations. Previous affiliations of Mira A. Kohorst include University of Texas MD Anderson Cancer Center.

Obesity, sedentary lifestyle, and video games: The new thrombophilia cocktail in adolescents

Abstract: Rates of venous thromboembolism have increased in the adolescent population over the last two decades, likely due to advanced diagnostics, increased use of central venous catheters, chronic medical conditions, obesity, and oral contraceptive use. Of these factors, a modifiable risk factor for adolescents is obesity. Sedentary lifestyle and prolonged immobilization are additional prothrombotic risk factors that are often associated with obesity. With ever-increasing screen time, sedentary behavior has risen accordingly, especially among gamers. We present four cases of adolescents who developed life-threatening venous thromboembolic events in the setting of obesity, sedentary lifestyle and/or immobilization, and prolonged video game use.

Immune Effector Cell Associated Neurotoxicity (ICANS) in Pediatric and Young Adult Patients Following Chimeric Antigen Receptor (CAR) T-Cell Therapy: Can We Optimize Early Diagnosis?

Abstract: The Cornell Assessment for Pediatric Delirium (CAPD) was first proposed by the Pediatric Acute Lung Injury and Sepsis Investigators Network-Stem Cell Transplantation and Cancer Immunotherapy Subgroup and MD Anderson CARTOX joint working committees, for detection of immune effector cell associated neurotoxicity (ICANS) in pediatric patients receiving chimeric antigen receptor (CAR) T-cell therapy. It was subsequently adopted by the American Society for Transplantation and Cellular Therapy. The utility of CAPD as a screening tool for early diagnosis of ICANS has not been fully characterized. We conducted a retrospective study of pediatric and young adult patients (n=15) receiving standard-of-care CAR T-cell products. Cytokine release syndrome (CRS) and ICANS occurred in 87% and 40% of patients, respectively. ICANS was associated with significantly higher peaks of serum ferritin. A change in CAPD from a prior baseline was noted in 60% of patients with ICANS, 24-72 h prior to diagnosis of ICANS. The median change from baseline to maximum CAPD score of patients who developed ICANS versus those who did not was 13 versus 3, respectively (p=0.0004). Changes in CAPD score from baseline may be the earliest indicator of ICANS among pediatric and young adult patients which may warrant closer monitoring, with more frequent CAPD assessments.

Effect of CHK1 Inhibition on CPX-351 Cytotoxicity in vitro and ex vivo

Abstract: CPX-351 is a liposomally encapsulated 5:1 molar ratio of cytarabine and daunorubicin that recently received regulatory approval for the treatment of therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes based on improved overall survival compared to standard cytarabine/daunorubicin therapy. Checkpoint kinase 1 (CHK1), which is activated by DNA damage and replication stress, diminishes sensitivity to cytarabine and anthracyclines as single agents, suggesting that CHK1 inhibitors might increase the effectiveness of CPX-351. The present studies show that CPX-351 activates CHK1 as well as the S and G2/M cell cycle checkpoints. Conversely, CHK1 inhibition diminishes the cell cycle effects of CPX-351. Moreover, CHK1 knockdown or addition of a CHK1 inhibitor such as MK-8776, rabusertib or prexasertib enhances CPX-351-induced apoptosis in multiple TP53-null and TP53-wildtype AML cell lines. Likewise, CHK1 inhibition increases the antiproliferative effect of CPX-351 on primary AML specimens ex vivo, offering the possibility that CPX-351 may be well suited to combine with CHK1-targeted agents.

Spectrum of hematological malignancies, clonal evolution and outcomes in 144 Mayo Clinic patients with germline predisposition syndromes.

Abstract: Germline predisposition syndromes (GPS) result from constitutional aberrations in tumor suppressive and homeostatic genes, increasing risk for neoplasia in affected kindred. In this study, we present clinical and genomic data on 144 Mayo Clinic patients with GPS; 59 evaluated prospectively using an algorithm-based diagnostic approach in the setting of a dedicated GPS/ inherited bone marrow failure syndrome (IBMFS) clinic. Seventy-two (50%) patients had IBMFS (telomere biology disorders-32,Fanconi anemia-18, Diamon Blackfan Anemia - 11, congenital neutropenia-5, Schwachman-Diamond Syndrome-5 and Bloom Syndrome-1), 27 (19%) had GPS with antecedent thrombocytopenia (RUNX1-FPD-15, ANKRD26-6, ETV6-2, GATA1-1, MPL-3), 28 (19%) had GPS without antecedent thrombocytopenia (GATA2 haploinsufficiency-16, DDX41-10, CBL-1 and CEBPA-1) and 17 (12%) had general cancer predisposition syndromes (ataxia telangiectasia-7, heterozygous ATM variants-3, CHEK2-2, TP53-2, CDK2NA-1, NF1-1 and Nijmegen Breakage Syndrome-1). Homozygous and heterozygous ATM pathogenic variants were exclusively associated with lymphoproliferative disorders (LPD), while DDX41 GPS was associated with LPD and myeloid neoplasms. The use of somatic NGS-testing identified clonal evolution in GPS patients, with ASXL1, RAS pathway genes, SRSF2 and TET2 being most frequently mutated. Fifty-two (91%) of 59 prospectively identified GPS patients had a change in their management approach, including additional GPS-related screening in 42 (71%), referral for allogenic HSCT workup and screening of related donors in 16 (27%), medication initiation and selection of specific conditioning regimens in 14 (24%), and genetic counseling with specific intent of fertility preservation and preconceptual counselling in 10 (17%) patients; highlighting the importance of dedicated GPS screening, detection and management programs for patients with hematological neoplasms. This article is protected by copyright. All rights reserved.

Membranous nephropathy associated with angiomatoid fibrous histiocytoma in a pediatric patient.

Abstract: Though membranous nephropathy is a much more common cause of nephrotic syndrome in the adult population, it accounts for only a small fraction of cases in pediatrics We report a case of a 16-year-old boy with nephrotic syndrome due to membranous nephropathy in the setting of a rare tumor, angiomatoid fibrous histiocytoma This patient’s nephrotic-range proteinuria completely resolved following resection of this tumor Angiomatoid fibrous histiocytoma, while known to cause other paraneoplastic syndromes such as anemia, has never been reported to cause membranous nephropathy This case highlights a novel and treatable secondary cause of membranous nephropathy Because secondary causes are more common in children than in adults, a high index of suspicion for other underlying pathology including malignancy should be considered It also suggests that urinalysis may be a helpful screening tool in cases of angiomatoid fibrous histiocytoma

Tumors of the liver in children

Abstract: This paper is a concise review of tumors of the liver, which represent 2 to 5% of all tumors in children. Both benign and malignant forms are reviewed. The relationship between hepatitis virus B and carcinoma, cirrhosis, toxic agents and cancer is discussed.

Gamer's Health Guide: Optimizing Performance, Recognizing Hazards, and Promoting Wellness in Esports.

Abstract: Electronic sports (esports), or competitive video gaming, is a rapidly growing industry and phenomenon. While around 90% of American children play video games recreationally, the average professional esports athlete spends 5.5 to 10 h gaming daily. These times and efforts parallel those of traditional sports activities where individuals can participate at the casual to the professional level with the respective time commitments. Given the rapid growth in esports, greater emphasis has been placed on identification, management, and prevention of common health hazards that are associated with esports participation while also focusing on the importance of health promotion for this group of athletes. This review outlines a three-point framework for sports medicine providers, trainers, and coaches to provide a holistic approach for the care of the esports athlete. This esports framework includes awareness and management of common musculoskeletal and health hazards, opportunities for health promotion, and recommendations for performance optimization.