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Evidence regarding the effectiveness of covid-19 vaccine in patients with impaired immunity, is limited. Initial observations suggest a lower humoral response in these patients. We evaluated the relative effectiveness of the mRNA BNT162b2 vaccine in patients with hematological neoplasms compared to matched controls. Data on patients with hematological neoplasms after two vaccine doses were extracted and matched 1:1 with vaccinated controls. Subpopulation analyses focused on patients receiving therapy for the hematological neoplasm, patients without treatment who are only followed, and recipients of specific treatments. The analysis focused on covid-19 outcomes from day 7 through 43 following the second vaccine dose: Documented covid-19 infection by PCR; Symptomatic infection; Hospitalizations; Severe covid-19 disease and covid-19-related death. Of a population of 4.7 million insured people, 32,516 patients with hematological neoplasms were identified, of whom 5,017 were receiving therapy for an active disease. Vaccinated patients with hematological neoplasms, compared with vaccinated matched controls, had an increased risk of documented infections (RR 1.60, 95% confidence interval [CI] 1.12-2.37), symptomatic covid-19 (RR 1.72, 95% CI 1.05-2.85), covid-19 related hospitalizations (RR 3.13, 95% CI 1.68-7.08), severe covid-19 (RR 2.27, 95% CI 1.18-5.19) and covid-19 related death (RR 1.66, 95% CI 0.72-4.47). Limiting the analysis to patients on hematological treatments showed a higher increased risk. This analysis shows that vaccinated patients with hematological neoplasms, in particular patients on treatment, suffer from covid-19 outcomes more than vaccinated individuals with intact immune system. Ways to enhance covid-19 immunity in this patient population, such as additional doses, should be explored.

Tyrosine kinase inhibitors (TKIs) have revolutionized the management and outcomes of chronic myeloid leukemia (CML) patients. Improved disease control and prolonged life expectancy now mandate focus on improving TKIs' safety profile. Recently, vascular adverse events (VAEs) have emerged as a serious consequence of some of the newer TKIs. In this review, we describe the clinical spectrum of TKI-associated VAE, and examine the unique vascular safety profile of the main TKIs currently used in the treatment of CML: imatinib, nilotinib, dasatinib, bosutinib and ponatinib. The issue of TKI-related platelet dysfunction is discussed as well. We describe the contemporary research findings regarding the possible pathogenesis of the VAE. Finally, the different aspects of TKI-associated VAE management are addressed, including prevention methods, monitoring strategies and treatment options.

Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.

Tyrosine kinase inhibitors (TKIs) have revolutionized the prognosis of chronic myeloid leukemia. With the advent of highly efficacious therapy, the focus has shifted toward managing TKI adverse effects, such as vascular adverse events (VAEs). We used an in vitro angiogenesis model to investigate the TKI-associated VAEs. Our data show that imatinib, nilotinib, and ponatinib reduce human umbilical vein endothelial cells (HUVECs) viability. Pharmacological concentrations of ponatinib induced apoptosis, reduced migration, inhibited tube formation of HUVECs, and had a negative effect on endothelial progenitor cell (EPC) function. Furthermore, in HUVECs transfected with VEGF receptor 2 (VEGFR2), the effect of ponatinib on tube formation and on all parameters representing normal endothelial cell function was less prominent than in control cells. This is the first report regarding the pathogenesis of ponatinib-associated VAEs. The antiangiogenic effect of ponatinib, possibly mediated by VEGFR2 inhibition, as shown in our study, is another piece in the intricate puzzle of TKI-associated VAEs.

Nonadherence to medical recommendations is a widespread problem well documented in a multitude of clinical settings. Nonadherence may adversely affect clinical outcomes such as survival and quality of life and increase health-care-related costs. An understanding of the factors driving nonadherence is key to developing effective adherence-enhancing interventions (AEIs). There are ongoing attempts in contemporary adherence research to better define the various components of adherence, to find optimal measures of adherence and correlations with clinical outcomes, and to create a classification system for AEIs. Nonadherence is also widely prevalent among adolescents and young adults (AYAs) with chronic hematological diseases, affecting up to 50% of patients and increasing with age. Combined use of objective (i.e. electronic monitoring, EM) and subjective (i.e. self-report) measures of adherence may be the preferred approach to assess adherence. The unique physical, social and emotional aspects of the AYA life stage are closely related to intricate causes of nonadherence in AYAs such as problems in transition to adult care. Until proven otherwise, the empirical target in AYAs with hematological disorders should be perfect adherence. Multilevel AEIs, EM feedback and behavioral interventions are among the most effective types of AEIs. Despite the magnitude of the problem, only a handful of AEIs have been evaluated among AYAs with hematological disorders. Thus, this is a field with unmet needs warranting high-quality trials using standardized and well-specified assessment methods and interventions. This review discusses the prevalence, definition, causes and clinical implications of nonadherence among AYAs with hematological disorders, along with strategies to measure and improve adherence.

Background: There are scarce data on venous thromboembolism (VTE) rates among non-small cell lung cancer (NSCLC) patients treated with immune-checkpoint inhibitors (ICI). The Khorana Score (KS), used to guide thromboprophylaxis in cancer patients, was validated in patients receiving chemotherapy.Objective: To assess VTE rates and KS performance among NSCLC patients treated with ICI or chemotherapy. Methods:We performed a retrospective cohort study of NSCLC patients starting either ICI or platinum-based chemotherapy. The 6-month cumulative incidence of VTE in the ICI and chemotherapy cohorts and hazard ratios (HR) with 95% confidence intervals (CI) were calculated, using death as a competing risk. Subgroup analysis of low (0-1) and high (≥2) KS risk groups was performed. Results:The study included 345 NSCLC patients receiving single agent ICI (n = 176) or chemotherapy (n = 169). The 6-month cumulative incidence of VTE was 7.1% in the chemotherapy cohort and 4.5% in the ICI cohort (HR for chemotherapy = 1.6, 95% CI 0.66-3.9). Among chemotherapy treated patients, the high-risk KS group had a trend toward a higher VTE incidence, compared with patients with a low-risk KS (HR 3.04, 95% CI 0.82-11.22). Among ICI-treated patients, the high-risk KS group had a trend toward a lower VTE incidence compared with the low-risk group (HR 0.17, 95% CI 0.02-1.36). Conclusions: VTE rates were higher among NSCLC patients treated with platinumbased chemotherapy than those treated with ICI alone, though the precision of the relative estimate is low. The KS did not identify high-risk ICI-treated patients, suggesting that an ICI-specific risk model is warranted.

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