Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial

The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We ran a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as a risk factor for bleeding or recurrence in patients treated with dalteparin or apixaban for cancer-associated VTE. RI was graded as moderate (creatinine clearance between 30-59 mL/minute; 275 patients) and mild (between 60-89 mL/minute; 444 patients). In the 1142 patients included in this analysis, the incidence of major bleeding was similar in patients with moderate vs. no or mild RI (HR 1.06-95% CI: 0.53-2.11), with no difference in the relative safety of apixaban and dalteparin. Recurrent VTE was not different in moderate vs. no or mild RI (HR=0.67, 95% CI: 0.38-1.20); in moderate RI, apixaban reduced recurrent VTE compared to dalteparin (HR=0.27, 95% CI: 0.08-0.96; P for interaction 0.1085). At multivariate analysis, no association was found between variation of renal function over time and major bleeding or recurrent VTE. Advanced or metastatic cancer was the only independent predictor of major bleeding (HR=2.84, 95% CI: 1.20-6.71), with no effect of treatment with apixaban or dalteparin. In our study, in cancer patients treated with apixaban or dalteparin, moderate RI was not associated with major bleeding or recurrent VTE. In patients with moderate renal failure, the safety profile of apixaban was confirmed with the potential for improved efficacy in comparison to dalteparin. ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03045406","term_id":"NCT03045406"}}NCT03045406.     

Evolução e Estado Atual das Práticas de Implante Transcateter de Válvula Aórtica na América Latina – Estudo WRITTEN LATAM

Background:Transcatheter aortic valve replacement (TAVR) is a worldwide adopted procedure with rapidly evolving practices. Regional and temporal variations are expected to be found.Objective:To compare TAVR practice in Latin America with that around the world and to assess its changes in Latin America from 2015 to 2020.Methods:A survey was applied to global TAVR centers between March and September 2015, and again to Latin-American centers between July 2019 and January 2020. The survey consisted of questions addressing: i) center’s general information; ii) pre-TAVR evaluation; iii) procedural techniques; iv) post-TAVR management; v) follow-up. Answers from the 2015 survey of Latin-American centers (LATAM15) were compared with those of other centers around the world (WORLD15) and with the 2020 updated Latin-American survey (LATAM20). A 5% level of significance was adopted for statistical analysis.Results:250 centers participated in the 2015 survey (LATAM15=29; WORLD15=221) and 46 in the LATAM20. Combined centers experience accounted for 73 707 procedures, with WORLD15 centers performing, on average, 6- and 3-times more procedures than LATAM15 and LATAM20 centers, respectively. LATAM centers performed less minimalistic TAVR than WORLD15 centers, but there was a significant increase in less invasive procedures after 5 years in Latin-American centers. For postprocedural care, a lower period of telemetry and maintenance of temporary pacing wire, along with less utilization of dual antiplatelet therapy was observed in LATAM20 centers.Conclusion:Despite still having a much lower number of procedures, many aspects of TAVR practice in Latin-American centers have evolved in recent years, followingthe trend observed in developed country centers.     

Applicability of 3D-printed models in hepatobiliary surgey: results from “LIV3DPRINT” multicenter study

BackgroundHepatobiliary resections are challenging due to the complex liver anatomy. Three-dimensional printing (3DP) has gained popularity due to its ability to produce anatomical models based on the characteristics of each patient.MethodsA multicenter study was conducted on complex hepatobiliary tumours. The endpoint was to validate 3DP model accuracy from original image sources for application in the teaching, patient-communication, and planning of hepatobiliary surgery.ResultsThirty-five patients from eight centers were included. Process testing between 3DP and CT/MRI presented a considerable degree of similarity in vascular calibers (0.22 ± 1.8 mm), and distances between the tumour and vessel (0.31 ± 0.24 mm). The Dice Similarity Coefficient was 0.92, with a variation of 2%. Bland–Altman plots also demonstrated an agreement between 3DP and the surgical specimen with the distance of the resection margin (1.15 ± 1.52 mm). Professionals considered 3DP at a positive rate of 0.89 (95%CI; 0.73–0.95). According to student's distribution a higher success rate was reached with 3DP (median:0.9, IQR: 0.8–1) compared with CT/MRI or 3D digital imaging (P = 0.01).Conclusion3DP hepatic models present a good correlation compared with CT/MRI and surgical pathology and they are useful for education, understanding, and surgical planning, but does not necessarily affect the surgical outcome.     

Quaking and miR-155 interactions in inflammation and leukemogenesis

Quaking (QKI) is a tumor-suppressor gene encoding a conserved RNA-binding protein, whose expression is downregulated in several solid tumors. Here we report that QKI plays an important role in the immune response and suppression of leukemogenesis. We show that the expression of Qki is reduced in lipopolysaccharide (LPS)-challenged macrophages, suggesting that Qki is a key regulator of LPS signaling pathway. Furthermore, LPS-induced downregulation of Qki expression is miR-155-dependent. Qki overexpression impairs LPS-induced phosphorylation of JNK and particularly p38 MAPKs, in addition to increasing the production of anti-inflammatory cytokine IL-10. In contrast, Qki ablation decreases Fas expression and the rate of Caspase3/7 activity, while increasing the levels of IL-1α, IL-1β and IL-6, and p38 phosphorylation. Similarly, the p38 pathway is also a target of QKI activity in chronic lymphocytic leukemia (CLL)-derived MEC2 cells. Finally, B-CLL patients show lower levels of QKI expression compared with B cells from healthy donor, and Qki is similarily downregulated with the progression of leukemia in Eμ-miR-155 transgenic mice. Altogether, these data implicate QKI in the pathophysiology of inflammation and oncogenesis where miR-155 is involved.     

Real-time clinical note monitoring to detect conditions for rapid follow-up: A case study of clinical trial enrollment in drug-induced torsades de pointes and Stevens-Johnson syndrome

Identifying acute events as they occur is challenging in large hospital systems. Here, we describe an automated method to detect 2 rare adverse drug events (ADEs), drug-induced torsades de pointes and Stevens-Johnson syndrome and toxic epidermal necrolysis, in near real time for participant recruitment into prospective clinical studies. A text processing system searched clinical notes from the electronic health record (EHR) for relevant keywords and alerted study personnel via email of potential patients for chart review or in-person evaluation. Between 2016 and 2018, the automated recruitment system resulted in capture of 138 true cases of drug-induced rare events, improving recall from 43% to 93%. Our focused electronic alert system maintained 2-year enrollment, including across an EHR migration from a bespoke system to Epic. Real-time monitoring of EHR notes may accelerate research for certain conditions less amenable to conventional study recruitment paradigms.     

A decomposition approach for the combined master surgical schedule and surgical case assignment problems

This research aims at supporting hospital management in making prompt Operating Room (OR) planning decisions, when either unpredicted events occur or alternative scenarios or configurations need to be rapidly evaluated. We design and test a planning tool enabling managers to efficiently analyse several alternatives to the current OR planning and scheduling. To this aim, we propose a decomposition approach. More specifically, we first focus on determining the Master Surgical Schedule (MSS) on a weekly basis, by assigning the different surgical disciplines to the available sessions. Next, we allocate surgeries to each session, focusing on elective patients only. Patients are selected from the waiting lists according to several parameters, including surgery duration, waiting time and priority class of the operations. We performed computational experiments to compare the performance of our decomposition approach with an (exact) integrated approach. The case study selected for our simulations is based on the characteristics of the operating theatre (OT) of a medium-size public Italian hospital. Scalability of the method is tested for different OT sizes. A pilot example is also proposed to highlight the usefulness of our approach for decision support. The proposed decomposition approach finds satisfactory solutions with significant savings in computation time.