Background: Data regarding long‐term outcome of patients with thromboangiitis obliterans are lacking and most series come from India and Japan. In this study, we assess long‐term outcome and prognostic factors in a large cohort of thromboangiitis obliterans. Methods and Results: Retrospective multicenter study of characteristics and outcomes of 224 thromboangiitis obliterans patients fulfilling Papa's criteria were analyzed. Factors associated with vascular events and amputations were identified. The median age at diagnosis was 38.5 (32–46) years, 51 (23.8%) patients were female, and 81.7% were whites. After a mean follow‐up of 5.7 years, vascular events were observed in 58.9%, amputations in 21.4%, and death in 1.4%. The 5‐, 10‐, and 15‐year vascular event‐free survival and amputation‐free survival were 41% and 85%, 23% and 74%, and 19% and 66%, respectively. Ethnic group (nonwhite) (hazard ratio 2.35 [1.30–4.27] P =0.005) and limb infection at diagnosis (hazard ratio 3.29 [1.02–10.6] P =0.045) were independent factors of vascular event‐free survival. Factor associated with amputation was limb infection (hazard ratio 12.1 [3.5–42.1], P <0.001). Patients who stopped their tobacco consumption had lower risk of amputation ( P =0.001) than those who continued. Conclusions: This nationwide study shows that 34% of thromboangiitis obliterans patients will experience an amputation within 15 years from diagnosis. We identified high‐risk patients for vascular complications and amputations.

Background Unprovoked pulmonary embolism (uPE) is a severe and frequent condition. Identification of new risk factors is mandatory to identify patients that would benefit from a long-term treatment. Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the acquisition of somatic mutations that drive clonal expansion in the absence of cytopenia. Its prevalence is estimated of 5% in the population above 65 years. Since inflammation and endothelial dysfunction may share a pathophysiological pathway(1), we hypothesized that CHIP, may be a risk factor for uPE. Methods We conducted a pilot retrospective observational study. Patients with iPE between 18 to 65 years old were included. PE was considered as unprovoked, when no transient nor persistant risk factor was present and when thrombophilia testing was negative. We excluded documented atherosclerosis, personal or familial history of VTE and presence of cytopenias. CHIP proportion in uPE patients were analyzed using next generation sequencing of the coding sequence of a custom panel composed by DNMT3A, ASXL1, SF3B1, TET2 and TP 53. Results Upon 61 patients with uPE consecutively included, a total of 19 somatic mutations were found in 12 patients (20%) IC95% [10 - 20]. 15 mutations were found in DNMT3A gene, 3 in ASXL1 and one in TET2. There was no diference in terms of age, PE location, DVT presence and risk stratification in CHIP carriers and non carriers. Conclusion We report for the first time, the presence of high rates of CHIP in patients presenting with uPE. Thus, CHIP may be a new risk factor for VTE. These results need to be confirmed in an ongoing prospective case-control study including more patients and using a more diverse gene panel to better determine CHIP incidence in uPE. None. SS contribute to the conception of the research and wrote the manuscript. SS, GJ and EO performed genetic analyses. LG, JPM and MAS contributed to the conception of the research and revised the manuscript. ^* Equally contributors. Received: 11 February 2021 Accepted: 01 July 2021 Article published online: 17 August 2021 © 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Background: Hemostatic complications, ranging from thromboembolism to bleeding, are a significant source of morbidity and mortality in cancer patients. The tumor coagulome represents the multiple genes and proteins that locally contribute to the equilibrium between coagulation and fibrinolysis. We aimed to study the coagulome of Oral Squamous Cell Carcinoma (OSCC) and examine its link to the tumor microenvironment (TME). Methods: We used data from bulk tumor DNA/RNA-seq (The Cancer Genome Atlas), single-cell RNA-seq data and OSCC cells in culture. Results: Among all tumor types, OSCC was identified as the tumor with the highest mRNA expression levels of F3 (Tissue Factor, TF) and PLAU (urokinase type-plasminogen activator, uPA). Great inter- and intra-tumor heterogeneity were observed. Single-cell analyses showed the coexistence of subpopulations of pro-coagulant and pro-fibrinolytic cancer cells within individual tumors. Interestingly, OSCC with high F3 expressed higher levels of the key immune checkpoint molecules CD274/PD-L1, PDCD1LG2/PD-L2 and CD80, especially in tumor dendritic cells. In vitro studies confirmed the particularity of the OSCC coagulome and suggested that thrombin exerts indirect effects on OSCC cells. Conclusions: OSCC presents a specific coagulome. Further studies examining a possible negative modulation of the tumor’s adaptive immune response by the coagulation process are warranted.

Thromboangiitis obliterans (TAO) is an inflammatory disease that usually affects small and medium-sized arteries in the upper and lower limbs of young smokers. Previous studies showed that the spectrum TAO has changed in the 80s: the male-to-female ratio decreased, older patients were diagnosed, and upper limb involvement was more common. The aim of our study was to assess the changing clinical spectrum of TAO in France during the past 40 years. All consecutive patients fulfilling TAO’s criteria between January 1967 and January 2016 were retrospectively included in 3 departments of internal medicine. We compared TAO features in patients diagnosed before and after 2002; 141 (77.5%) men and 41 (22.5%) women were included. Patients diagnosed after 2002 were older (37 [31-39] vs 34 [29-35] years P = .03), had a more frequent isolated upper limb involvement (34.3% vs 7.8% P = .001), and less frequent isolated lower limb involvement (55.7% vs 74.5%, P < .001). The clinical spectrum of TAO has changed in France since the beginning of the 21st century.

Long-term indwelling central venous catheters (CVC) are frequently used to secure vascular access to deliver injectable treatment. Catheter-related thrombosis (CRT) occurs in approximately 2–6% of cancer patients. We conducted a single-center retrospective study to assess the rate of venous thromboembolism (VTE) recurrence in cancer patients; 200 patients were included. Mean age was 56 ± 15.15 years, median follow-up duration was 16.5 [range: 10–36] months. The incidence of recurrence was estimated using Gray’s method for competing risk with death as the competing event of VTE. Recurrent VTE occurred in 25.5% of patients with a median occurrence time of 6.5 [range: 5–11.25] months. In case of recurrence, 94.6% of patients were treated for cancer and 80.4% of them received anticoagulants; 4 major bleeds and 17 non-major bleeds occurred during follow-up. In multivariate analysis, previous VTE (Hazard Ratio (HR) 2.48 (95% CI 1.42–4.32) and presence of CVC (HR 5.56 (95% CI 1.96–15.75) were significant recurrence risk factors. After a first episode of CRT, 25.5% of patients experienced VTE recurrence as UEDVT in 30 cases (55.5%), PE in 17 cases (31.5%), and DVT in 7 cases (13%), mostly during anticoagulation therapy. Anticoagulation therapy does not avoid CRT in case of cancer and must be balanced with hemorrhagic risk.