Knockout of the Carbohydrate Responsive Element Binding Protein Enhances Proliferation and Tumorigenesis in Renal Tubules of Mice.

Glycogen-storing so-called clear cell kidney tubules (CCTs), precursor lesions of renal cell carcinoma, have been described in diabetic rats and in humans. The lesions show upregulation of the Akt/mTOR-pathway and the related transcription factor carbohydrate responsive element binding protein (ChREBP), which is supposedly pro-oncogenic. We investigated the effect of ChREBP-knockout on nephrocarcinogenesis in streptozotocin-induced diabetic and normoglycemic mice.

Ablation Strategies for Repeat Procedures in Atrial Fibrillation Recurrences Despite Durable Pulmonary Vein Isolation: The Prospective Randomized ASTRO AF Multicenter Trial.

Background: Ablation strategies for patients with symptomatic atrial fibrillation and isolated pulmonary veins vary and their effects on arrhythmia recurrence remain unclear. A prospective randomized German multicenter trial sought to compare 2 ablation strategies in this patient cohort.

Methods: Patients with atrial fibrillation despite durable pulmonary vein isolation were randomly assigned at 7 centers to undergo low-voltage area ablation using 3-dimensional mapping and irrigated radiofrequency current ablation (group A) or empirical left atrial appendage isolation (LAAI) using the cryoballoon followed by staged interventional left atrial appendage closure (group B).

Hepatocellular Ballooning is Due to Highly Pronounced Glycogenosis Potentially Associated with Steatosis and Metabolic Reprogramming.

Background And Aims: Hepatocellular ballooning is a common finding in chronic liver disease, mainly characterized by rarefied cytoplasm that often contains Mallory-Denk bodies (MDB). Ballooning has mostly been attributed to degeneration but its striking resemblance to glycogenotic/steatotic changes characterizing preneoplastic hepatocellular lesions in animal models and chronic human liver diseases prompts the question whether ballooned hepatocytes (BH) are damaged cells on the path to death or rather viable cells, possibly involved in neoplastic development.

Methods: Using specimens from 96 cirrhotic human livers, BH characteristics were assessed for their glycogen/lipid stores, enzyme activities, and proto-oncogenic signaling cascades by enzyme- and immunohistochemical approaches with serial paraffin and cryostat sections.

Cervical spine fracture detection in computed tomography using convolutional neural networks.

In the context of primary in-hospital trauma management timely reading of computed tomography (CT) images is critical. However, assessment of the spine is time consuming, fractures can be very subtle, and the potential for under-diagnosis or delayed diagnosis is relevant. Artificial intelligence is increasingly employed to assist radiologists with the detection of spinal fractures and prioritization of cases.

Early Subcellular Hepatocellular Alterations in Mice Post Hydrodynamic Transfection: An Explorative Study.

Hydrodynamic transfection (HT) or hydrodynamic tail vein injection (HTVi) is among the leading technique that is used to deliver plasmid genes mainly into the liver of live mice or rats. The DNA constructs are composed of coupled plasmids, while one contains the gene of interest that stably integrate into the hepatocyte genome with help of the other consisting sleeping beauty transposase system. The rapid injection of a large volume of DNA-solution through the tail vein induces an acute cardiac congestion that refluxed into the liver, mainly in acinus zone 3, also found through our EM study.

IKAROS and MENIN coordinate therapeutically actionable leukemogenic gene expression in MLL-r acute myeloid leukemia.

Acute myeloid leukemia (AML) remains difficult to treat and requires new therapeutic approaches. Potent inhibitors of the chromatin-associated protein MENIN have recently entered human clinical trials, opening new therapeutic opportunities for some genetic subtypes of this disease. Using genome-scale functional genetic screens, we identified IKAROS (encoded by IKZF1) as an essential transcription factor in KMT2A (MLL1)-rearranged (MLL-r) AML that maintains leukemogenic gene expression while also repressing pathways for tumor suppression, immune regulation and cellular differentiation.

Hormonally Induced Hepatocellular Carcinoma in Diabetic Wild Type and Carbohydrate Responsive Element Binding Protein Knockout Mice.

Objective: In the rat, the pancreatic islet transplantation model is an established method to induce hepatocellular carcinomas (HCC), due to insulin-mediated metabolic and molecular alterations like increased glycolysis and de novo lipogenesis and the oncogenic AKT/mTOR pathway including upregulation of the transcription factor Carbohydrate-response element-binding protein (ChREBP). ChREBP could therefore represent an essential oncogenic co-factor during hormonally induced hepatocarcinogenesis.

Methods: Pancreatic islet transplantation was implemented in diabetic C57Bl/6J (wild type, WT) and ChREBP-knockout (KO) mice for 6 and 12 months.

Multicentre evaluation of 5B9, a monoclonal anti-PF4/heparin IgG mimicking human HIT antibodies, as an internal quality control in HIT functional assays: Communication from the ISTH SSC Subcommittee on Platelet Immunology.

Background: Functional tests for the diagnosis of heparin-induced thrombocytopenia (HIT) exhibit variable performance.

Objectives: We evaluated in a multicenter study whether 5B9, a monoclonal anti-PF4/heparin IgG mimicking human HIT antibodies, could be used as an internal quality control.

Methods: 5B9 was sent to 11 laboratories in seven countries, and six initial concentrations ranging from 10 to 400 μg/mL were tested by heparin-induced platelet activation assay (HIPA), serotonin release assay (SRA), platelet aggregation test (PAT), flow cytometry (FC), or heparin-induced multiple-electrode aggregometry (HIMEA).

Prognostic Impact of Membranous/Nuclear Epidermal Growth Factor Receptor Localization in Clear Cell Renal Cell Carcinoma.

EGFR is overexpressed in the majority of clear cell renal cell carcinomas (CCRCCs). Although EGFR deregulation was found to be of great significance in CCRCC biology, the EGFR overexpression is not associated with EGFR-targeted therapy responsiveness. Moreover, the prognostic role of EGFR expression remains controversial.

Pancreatoblastoma in children: EXPeRT/PARTNER diagnostic and therapeutic recommendations.

Pancreatoblastoma (PBL) is a rare malignant epithelial neoplasm that affects typically young children. Signs related to advanced upper-abdominal tumor accompanied by elevated serum α-fetoprotein levels in a young child suggest PBL, however histopathological confirmation is mandatory. The mainstay of the treatment is a complete surgical resection.

Unexpected low-grade infections in revision hip arthroplasty for aseptic loosening : a single-institution experience of 274 hips.

Aims: The purpose of this study was to evaluate unexpected positive cultures in total hip arthroplasty (THA) revisions for presumed aseptic loosening, to assess the prevalence of low-grade infection using two definition criteria, and to analyze its impact on implant survival after revision.

Methods: A total of 274 THA revisions performed for presumed aseptic loosening from 2012 to 2016 were reviewed. In addition to obtaining intraoperative tissue cultures from all patients, synovial and sonication fluid samples of the removed implant were obtained in 215 cases (79%) and 101 cases (37%), respectively.

Heparin-induced thrombocytopenia: Construction of a pretest diagnostic score derived from the analysis of a prospective multinational database, with internal validation.

Background: Diagnosis of heparin-induced thrombocytopenia (HIT) requires pretest probability assessment and dedicated laboratory assays.

Objective: To develop a pretest score for HIT.

Design: Observational; analysis of prospectively collected data of hospitalized patients suspected with HIT (ClinicalTrials.

Transcriptomic and Proteomic Analysis of Clear Cell Foci (CCF) in the Human Non-Cirrhotic Liver Identifies Several Differentially Expressed Genes and Proteins with Functions in Cancer Cell Biology and Glycogen Metabolism.

Clear cell foci (CCF) of the liver are considered to be pre-neoplastic lesions of hepatocellular adenomas and carcinomas. They are hallmarked by glycogen overload and activation of AKT (v-akt murine thymoma viral oncogene homolog)/mTOR (mammalian target of rapamycin)-signaling. Here, we report the transcriptome and proteome of CCF extracted from human liver biopsies by laser capture microdissection.

Ibrutinib as a salvage therapy after allogeneic HCT for chronic lymphocytic leukemia.

The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males; median age at transplantation was 48 years (range: 35-64) and the median number of treatment lines prior to transplantation was 3 (1-10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1-140).

Hepatocellular glycogenotic foci after combined intraportal pancreatic islet transplantation and knockout of the carbohydrate responsive element binding protein in diabetic mice.

Aims: The intraportal pancreatic islet transplantation (IPIT) model of diabetic rats is an insulin mediated model of hepatocarcinogenesis characterized by the induction of clear cell foci (CCF) of altered hepatocytes, which are pre-neoplastic lesions excessively storing glycogen (glycogenosis) and exhibiting activation of the AKT/mTOR protooncogenic pathway. In this study, we transferred the IPIT model to the mouse and combined it with the knockout of the transcription factor carbohydrate responsive element binding protein (chREBP).

Methods: C57BL/6J Wild-type (WT) and chREBP-knockout (chREBP-KO) mice (n = 297) were matched to 16 groups (WT/ chREBP-KO, experimental/control, streptozotocine-induced diabetic/not diabetic, one/four weeks).

Clowns in Paediatric Surgery: Less Anxiety and More Oxytocin? A Pilot Study.

Hospital stays and medical interventions are accompanied by worries and anxiety in children and parents. Recent studies show that hospital clowns may reduce anxiety and enhance well-being. However, so far studies are based solely on subjective measures and clowns are usually not integrated in medical routine.

Sepsis Caused by Extended-Spectrum Beta-Lactamase (ESBL)-Positive K. pneumoniae and E. coli: Comparison of Severity of Sepsis, Delay of Anti-Infective Therapy and ESBL Genotype.

Infections with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are associated with increased mortality. Outcome differences due to various species of ESBL-E or ESBL genotypes are not well investigated. We conducted a cohort study to assess risk factors for mortality in cases of ESBL-E bacteremia (K.

MR microscopy of the human finger and correlation with histology--a proof-of-principle study.

Magnetic resonance imaging (MRI) with small surface coils is a well established method for the diagnostic evaluation of finger masses. Until now, histological examination has been required to reliably assess tumor extent and infiltration of surrounding structures. Ultra-high-field MR microscopy (MRM) allows evaluation of anatomical structures and pathologies with submillimeter resolution.