Cancer-associated venous thromboembolism in Israel: Incidence, risk factors, treatment, and health care utilization in a population based cohort study.

Background: Recent international guidelines recommend thromboprophylaxis in patients with cancer at intermediate-high venous thromboembolism (VTE) risk. Objectives: We aimed to assess the current incidence, risk factors and management of cancer-associated VTE and associated health care resource utilization in a 2.5-million-member state-mandated health service in Israel. Methods: Patients aged ≥18 years with newly diagnosed cancer, initiating systemic anticancer treatment from 2010 through 2018 were identified from the Israel National Cancer Registry. The index date was fixed as the first day of systemic anticancer treatment. The cumulative VTE incidence from the first day of systemic anticancer treatment and the respective hazard ratios for VTE risk factors were calculated at 12 months of follow-up. Health care resource utilization (primary care physician, emergency room, and hospital visits) during the study period was compared between patients with and without VTE. Results: A total of 15 388 patients were included, and 338 had VTE with a 12-month cumulative incidence of 2.2% (95% confidence interval, 1.96%-2.43%). In a multivariable model, older age, higher comorbidity index, intermediate-high-risk Khorana score, certain malignancy types, and chemotherapy were significantly associated with an increased VTE risk in the year after initiating anticancer treatment. Compared with matched controls, the VTE subcohort were more likely to be hospitalized (81.4% vs 35.2%), have longer hospital stays (20.1 days vs 13.1 days), have an emergency room visit (41.5% vs 19.3%), and have a larger number of primary care physician visits (17.6 vs 12.5). Conclusion: Several risk factors, including the Khorana score, were associated with VTE incidence. VTE was associated with long-term use of anticoagulation. Health care utilization was higher in patients with VTE.

Redifferentiation of expanded human islet ß cells by inhibition of ARX.

Ex-vivo expansion of adult human islet ß cells has been evaluated for generation of abundant insulin-producing cells for transplantation; however, lineage-tracing has demonstrated that this process results in ß-cell dedifferentiation. Redifferentiation of ß-cell-derived (BCD) cells can be achieved using a combination of soluble factors termed Redifferentiation Cocktail (RC); however, this treatment leads to redifferentiation of only a fraction of BCD cells. This study aimed at improving redifferentiation efficiency by affecting the balance of islet progenitor-cell transcription factors activated by RC treatment. Specifically, RC treatment induces the transcription factors PAX4 and ARX, which play key roles in directing pancreas endocrine progenitor cells into the ß/δ or α/PP developmental pathways, respectively. Misactivation of ARX in RC-treated BCD cells may inhibit their redifferentiation into ß cells. Blocking ARX expression by shRNA elevated insulin mRNA levels 12.8-fold, and more than doubled the number of insulin-positive BCD cells. ARX inhibition in expanded α-cell-derived cells treated with RC did not cause their transdifferentiation into insulin-producing cells. The combination of RC and ARX shRNA treatment may facilitate the generation of abundant insulin-producing cells for transplantation into patients with type 1 diabetes.