Xarelto plus Acetylsalicylic acid: Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA): Rationale and design of a prospective registry study to assess rivaroxaban 2.5 mg twice daily plus aspirin for prevention of atherothrombotic events in coronary artery disease, peripheral artery disease, or both

International audienceAims: The role and selection of antithrombotic therapy to improve limb outcomes in chronic lower extremity artery disease (LEAD) is still debated. We conducted a meta-analysis to examine the efficacy and safety of antithrombotic and more intense antithrombotic therapy on limb outcomes and limb salvage in patients with chronic LEAD.Methods and results: Study inclusion criteria were: enrolment of patients with LEAD, randomized allocation to more vs. less intense antithrombotic therapy [more vs. less intense single-antiplatelet therapy (SAPT); dual-antiplatelet therapy vs. SAPT; dual antithrombotic therapy vs. SAPT or oral anticoagulant]; enrolment of ≥200 patients; reporting of at least one of following outcomes: limb amputation or revascularization. Seven randomized studies enrolling 30 447 patients were included. Over a median follow-up of 24 months, more vs. less intense antithrombotic therapy or placebo significantly reduced the risk of limb revascularization [relative risk (RR) 0.89, 95% confidence interval (CI) 0.83-0.94] and limb amputation (RR 0.63, 95% CI 0.46-0.86), as well as stroke (RR 0.82, 95% CI 0.70-0.97). There was no statistically significant effect on the risk of myocardial infarction (RR 0.98, 95% CI 0.87-1.11), all-cause (RR 0.93, 95% CI 0.86-1.01), and cardiovascular death (RR 0.97, 95% CI 0.86-1.08). Risk of major bleeding increased (RR 1.23, 95% CI 1.04-1.44).Conclusion: In patients with LEAD, more intense antithrombotic therapy reduces the risk of limb amputation and revascularization as well as stroke with an increase in the risk of bleeding events

Maximizing the Clinical Benefit of Radiotherapy in Solitary Plasmacytoma: An International Multicenter Analysis

Objective: Although local definitive radiotherapy (RT) is considered the standard of care for solitary plasmacytoma (SP), the optimal RT parameters for SP patients have not been defined. The aim of this retrospective study is to analyze the effectiveness of various RT doses, volumes, and techniques, as well as to define the relevant prognostic factors in SP. Methods: Between 2000 and 2019, 84 patients, including 54 with solitary bone plasmacytoma (SBP) and 30 with extramedullary plasmacytoma (EMP), underwent RT at six institutions. Results: The overall RT median dose was 42 Gy (range, 36.0–59.4). The median follow-up period was 46 months. Overall, the local control (LC) rate was 96%, while the complete remission (CR) rate was 46%. The 5-year local relapse-free survival (LRFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS), and overall survival (OS) rates were 89%, 71%, 55%, and 93%, respectively. Using an RT dose above 40 Gy was associated with a higher complete remission (CR) rate and a lower rate of local relapse. Modern irradiation techniques were associated with a trend toward a higher LC rate (98% vs. 87% for conventional, p = 0.09) and a significantly lower local relapse rate (6% vs. 25% for conventional, p = 0.04). However, RT dose escalation and technique did not lead to a significant effect on MMFS, PFS, and OS. Univariate analyses identified several patient characteristics as potentially relevant prognostic factors. In SBP patients, systemic therapy administration was associated significantly with MMFS and PFS rates. Conclusion: Using an RT dose >40 Gy and modern RT techniques may improve the local control and reduce the rate of relapse, without a significant impact on survival rates. The addition of systemic therapies may improve the MMFS and PFS rates of SBP patients

Expanding the clinical and molecular spectrum of thiamine pyrophosphokinase deficiency: A treatable neurological disorder caused by TPK1 mutations.

Thiamine pyrophosphokinase (TPK) produces thiamine pyrophosphate, a cofactor for a number of enzymes, including pyruvate dehydrogenase and 2-ketoglutarate dehydrogenase. Episodic encephalopathy type thiamine metabolism dysfunction (OMIM 614458) due to TPK1 mutations is a recently described rare disorder. The mechanism of the disease, its phenotype and treatment are not entirely clear.We present two patients with novel homozygous TPK1 mutations (Patient 1 with p.Ser160Leu and Patient 2 with p.Asp222His). Unlike the previously described phenotype, Patient 2 presented with a Leigh syndrome like non-episodic early-onset global developmental delay, thus extending the phenotypic spectrum of the disorder. We, therefore, propose that TPK deficiency may be a better name for the condition. The two cases help to further refine the neuroradiological features of TPK deficiency and show that MRI changes can be either fleeting or progressive and can affect either white or gray matter. We also show that in some cases lactic acidosis can be absent and 2-ketoglutaric aciduria may be the only biochemical marker. Furthermore, we have established the assays for TPK enzyme activity measurement and thiamine pyrophosphate quantification in frozen muscle and blood. These tests will help to diagnose or confirm the diagnosis of TPK deficiency in a clinical setting.Early thiamine supplementation prevented encephalopathic episodes and improved developmental progression of Patient 1, emphasizing the importance of early diagnosis and treatment of TPK deficiency. We present evidence suggesting that thiamine supplementation may rescue TPK enzyme activity.Lastly, in silico protein structural analysis shows that the p.Ser160Leu mutation is predicted to interfere with TPK dimerization, which may be a novel mechanism for the disease