Evaluation of direct oral anticoagulants versus low molecular weight heparins for venous thromboembolism treatment in patients with gastrointestinal malignancies.

BACKGROUND: Direct oral anticoagulant (DOAC) use in cancer-associated venous thromboembolism (CA-VTE) has increased due to updates in recent guidelines and literature. However, select guidelines caution against DOAC use in patients with gastrointestinal (GI) malignancies due to reported increased bleeding events. The objective of this study was to compare the safety and effectiveness of DOACs versus low-molecular-weight heparins (LMWHs) for CA-VTE treatment in patients with GI malignancies. PATIENTS AND METHODS: This multicenter, retrospective cohort study included patients with primary GI malignancies who received therapeutic anticoagulation with a DOAC or LMWH for CA-VTE between January 1, 2018, and December 31, 2019. The primary outcome was the incidence rate of bleeding events (major, clinically relevant non-major, or minor bleeding events) within a 12-month period following the initiation of therapeutic anticoagulation. The secondary endpoint was the incidence rate of recurrent VTE events within a 12-month period following the start of therapeutic anticoagulation. RESULTS: After screening, 141 patients met inclusion criteria. The incidence rate of all bleeding events significantly differed between DOAC (4.98 events/100 person-months) and LWMH (10.2 events/100 person-months) recipients. The corresponding incidence rate ratio (IRR) with the DOAC group serving as the reference was 2.05 (p = 0.01), with the majority of bleeds in both groups presenting as minor bleeds. No difference was found between the incidence rate of recurrent VTE within a 12-month period of starting therapeutic anticoagulation between groups (IRR 3.08, p = 0.06). CONCLUSION: Our results suggest that DOACs do not pose an additional bleeding risk compared to LMWH in patients with certain GI malignancies. Careful selection of DOAC therapy with respect to bleeding risk is still warranted.

Complete response following treatment of plasma cell leukemia with venetoclax and dexamethasone: A case report.

INTRODUCTION: Plasma cell leukemia (PCL) is a rare but aggressive variant of multiple myeloma (MM) with a poor prognosis. Due to the limited number of prospective clinical trials studying PCL, treatment options are often extrapolated from data available for the treatment of MM. Venetoclax has recently demonstrated antimyeloma activity in patients with relapsed/refractory MM carrying the t(11;14) translocation. However, few cases have reported the analogous efficacy of venetoclax in PCL. CASE REPORT: A 64-year-old Caucasian male developed relapsed PCL despite treatment with hyperCD (hyperfractionated cyclophosphamide and dexamethasone) and Dara-KRd (daratumumab, carfilzomib, lenalidomide, dexamethasone). Due to the refractory nature of his disease and the presence of a t(11:14) translocation, the patient was subsequently initiated on venetoclax 400 mg daily and dexamethasone 4 mg once weekly. MANAGEMENT AND OUTCOME: The patient achieved a complete response by International Myeloma Working Group criteria three months after initiating venetoclax-dexamethasone, including a repeat bone marrow biopsy that showed no abnormal plasma cells. He successfully underwent consolidation with melphalan-based autologous stem cell transplantation. He remains disease-free 9 months after venetoclax initiation. DISCUSSION: Combination all-oral therapy with venetoclax and dexamethasone can induce deep hematologic responses in patients with relapsed/refractory PCL carrying the t(11;14) translocation.

Pseudotemporal Ordering of Single Cells Reveals Metabolic Control of Postnatal ß Cell Proliferation.

Pancreatic ß cell mass for appropriate blood glucose control is established during early postnatal life. ß cell proliferative capacity declines postnatally, but the extrinsic cues and intracellular signals that cause this decline remain unknown. To obtain a high-resolution map of ß cell transcriptome dynamics after birth, we generated single-cell RNA-seq data of ß cells from multiple postnatal time points and ordered cells based on transcriptional similarity using a new analytical tool. This analysis captured signatures of immature, proliferative ß cells and established high expression of amino acid metabolic, mitochondrial, and Srf/Jun/Fos transcription factor genes as their hallmark feature. Experimental validation revealed high metabolic activity in immature ß cells and a role for reactive oxygen species and Srf/Jun/Fos transcription factors in driving postnatal ß cell proliferation and mass expansion. Our work provides the first high-resolution molecular characterization of state changes in postnatal ß cells and paves the way for the identification of novel therapeutic targets to stimulate ß cell regeneration.

Survival of pathogenic bacteria in pesticide solutions and on treated tomato plants.

The ability of Salmonella, Escherichia coli O157:H7, Listeria monocytogenes, and Shigella to survive or grow in pesticide solutions (Ambush 240EC, Benlate T-N-G, Bravo 500, Botran 75WP, Captan 80WDG, Parasol, and Vendex 50W) used by the horticultural industry was examined. In the laboratory, individual cultures were inoculated at 4 log CFU/ml in pesticides diluted with sterile saline to the lowest recommended spray concentrations. During 21 degrees C incubation for < or =96 h, bacterial survivors in the samples and a control consisting of saline were enumerated either by agar surface plating or hydrophobic grid membrane filtration. Most formulations tested were somewhat inhibitory to the pathogenic bacteria. All inoculated bacteria survived or grew in Bravo 500. Among bacteria tested, Salmonella spp. were best able to survive and Listeria spp. were least able to survive in pesticide solutions. When the incubation temperature or pesticide concentration was increased, survival of Salmonella varied depending on the type of formulation. In the field, when a bacterial cocktail containing E. coli O157:H7 and Salmonella Enteritidis was added to Bravo 500 at 6 log CFU/ml, both organisms were recovered from leaves and fruit skins of sprayed tomato plants after the recommended 1 day-to-harvest interval. E. coli and Salmonella survived longer on tomato leaves when sprayed in saline (at least 26 and 56 days, respectively) than when sprayed in Bravo 500 (>45 h and <15 days, respectively). While Salmonella serovars Typhimurium and Heidelberg grew in the fungicide Bravo, and Enteritidis grew in the insecticide Vendex within 96 h at 21 degrees C in the laboratory, pathogen growth in other pesticide formulations did not occur. Higher temperature (< or =30 degrees C) or doubling pesticide concentrations had either no or a negative effect on Salmonella Heidelberg survival. Use of unexpired pesticide formulations may have contributed to the reduced bacterial survival and growth found in the laboratory and during the field trials with Bravo.