Coagulopathy, Bleeding Events, and Outcome According to Rotational Thromboelastometry in Patients With Acute Liver Injury/Failure.

BACKGROUND AND AIMS: Patients with acute liver injury or failure (ALI/ALF) experience bleeding complications uncommonly despite an abnormal hemostatic profile. Rotational thromboelastometry (ROTEM), which assesses clot formation in whole blood, was used to determine the nature of abnormal hemostasis and whether it contributes to bleeding events, illness severity, or survival. APPROACH AND RESULTS: A total of 200 patients were recruited from sites of the ALF Study Group. Blood collected daily for up to 5 days was analyzed using ROTEM delta devices. Consistent with standard laboratory evidence of hypocoagulability (median international normalized ratio = 2.9 and platelet count = 144 × 109 /L), patients frequently exhibited ROTEM parameters outside the normal range (73% and 62% had abnormalities in clot formation from extrinsic and intrinsic clotting cascades, respectively); however, measures of clot stability were generally normal. Eighteen patients (9%) experienced bleeding events, in whom clot initiation, assembly, and firmness were more severely deranged than patients without bleeding. Abnormal ROTEM parameters were more frequently observed in patients with non-acetaminophen ALI/ALF than those with acetaminophen ALI/ALF (clot initiation [P < 0.001], assembly [P = 0.02], firmness at 10 minutes [P = 0.05], and maximal firmness [P = 0.06]). Patients with more severe systemic complications (high-grade hepatic encephalopathy and need for renal replacement therapy) also had a higher incidence of abnormal ROTEM parameters. Finally, more hypocoagulable ROTEM parameters (clot initiation (P = 0.005), stiffness at 10 minutes (P = 0.05), and maximal stiffness by fibrin assembly (P = 0.004)) were observed in patients who died or underwent liver transplantation than those who survived with their native liver. CONCLUSIONS: In patients with ALI/ALF, abnormal ROTEM parameters are frequent and proportional to disease severity. Whether the increased bleeding risk associated with abnormal ROTEM indicates hemostatic failure or is a proxy for disease severity requires additional study.

Knowledge and perceptions about Pre-diabetes amongst doctors, medical students, and patients in a tertiary care hospital of Islamabad.

OBJECTIVE: To explore the knowledge and perceptions about pre-diabetes screening and management amongst physicians, final year medical students, and patients. METHODS: The cross-sectional observational study was conducted at Shifa International Hospital, Shifa Foundation Clinic and Shifa College of Medicine, Islamabad, Pakistan, from November 2017 to February 2018. A structured questionnaire was used to assess doctors' and final year medical students' knowledge about screening and management of pre-diabetes. A group of patients were also interviewed about pre-diabetes awareness and their primary resources for health-related information. Data was analysed using SPSS 23. RESULTS: Of the 267 participants, there were 85(32%) doctors, 82(31%) medical students and 100(37%) patients. Only 61(71.8%), 44(51.7%) and 34(39.8%) physicians and 53(64.6%), 30(36.5%) and 26(31.6%) students could accurately identify impaired fasting blood glucose, glycated haemoglobin and impaired glucose tolerance criteria for pre-diabetes, respectively. Regarding risk factors for pre-diabetes screening, ethnicity, cardiovascular diseases and gestational diabetes were identified by 8(9.4%), 6(7.1%) and 9(10.6%) physicians and 10(12.2%), 6(7.3%) and 15(18.3%) students, respectively. There was no statistically significant relation of correct identification of pre-diabetes criteria with specialties, designations and years of experience post-qualification (p>0.5). Only 3(3%) patients were aware of pre-diabetes or borderline diabetes. CONCLUSIONS: Knowledge and perception of doctors, medical students and patients about pre-diabetes was found to be deficient. Efforts are required to reinforce its identification and management at all levels..

Molecular Cytogenetic Characterization of a Structural Abnormal Chromosome 16 in a Patient with Acute Myeloid Leukemia Leading to Inversion Chromosome 16 with Concomitant 3'CBFB Deletion.

OBJECTIVES: Acute myeloid leukemia (AML) presents as a heterogeneous blood cancer characterized by the proliferation of immature myeloid cells. We present the case of an 18-year-old female with AML whose symptoms include marked leukocytosis, anemia, as well as thrombocytopenia with spontaneous cerebellar and intracerebral bleeds. The bone marrow biopsy is hypercellular and is expunged by sheets of blast cells with dispersed chromatin, prominent nucleoli, highly irregular nuclei, and moderate cytoplasm. Chromosome analysis reveals an abnormal karyotype with a derivative trisomy 8 and a derivative chromosome 16. The karyotype is described as 47,XX,+der(8)add(8)(q24.3),der(16) inv(16)(p13.1q22)del(16)(q22)[21]/46,XX[1]. DNA FISH analysis reveals abnormalities for RUNX1T1 (8q21.3) and CBFB (16q22) genes. These findings align with that of conventional cytogenetics. The National Comprehensive Cancer Network guidelines for AML state that CBFB gene rearrangements indicate that the patient falls under the favorable risk category. However, AML with core binding factor molecular aberrations is a heterogeneous group and thus the interaction with further cytogenetic abnormalities may result in further pathogenesis. Clinical correlation was suggested.

CRLF2 Gene in B-cell Acute Lymphoblastic Leukemia.

OBJECTIVES: B-cell acute lymphoblastic leukemia (B-ALL) is a subset of ALL that comprises 75% of ALL cases. There are a variety of chromosome aneuploidy or chromosomal rearrangements implicated in B-ALL. Deregulation of CRLF2 expression is seen in 5-15% of B-ALL patients and occurs primarily via a reciprocal translocation with immunoglobulin heavy chain (IGH), rearrangements of CRLF2, deletion within the PAR1 region of the X and Y chromosomes, and CRLF2 mutations as well as mutations of the CRLF2-involved pathways and are seen in Ph-like B-ALL. They are associated with a poor prognosis. Blinatumomab is an available immunotherapy, and there are currently a few ongoing clinical trials to treat CRLF2 B-ALL. This review focuses on the role of CRLF2 in B-ALL and summarizes the literature regarding its molecular pathways, clinical significance, incidence rates across demographics, therapies, and areas of further research.