Critical limb ischaemia and the response to bone marrow-derived cell therapy according to tcPO2 measurement.

BACKGROUND: Cell therapy is an emerging potential biotherapy for critical limb ischaemia (CLI) patients who are not eligible for revascularization. However, the findings on this technique's efficacy are inconsistent. Trials investigating this topic focused on the more severe CLI patients who were often beyond any therapy. Therefore, identifying those who may truly benefit from cell transplantation is now warranted. To this end, we studied the prognostic value of tcPO2 for major amputation after 1 year in patients treated with bone marrow-derived cells. PATIENTS AND METHODS: CLI patients ineligible for revascularization were included in a cell-therapy pilot study. On inclusion, patients underwent tcPO2 measurement in supine and sitting positions. For a tcPO2 < 10 mmHg in the supine position, the vascular reserve was defined by tcPO2 > 30 mmHg in the sitting position. Patients were administered intramuscular injections of mononuclear cells derived from aspirated bone marrow. RESULTS: In total, 25 patients (a lower limbs) were included for analysis. At inclusion, 11 lower limbs had tcPO2 at rest > 10 mmHg, and 16 lower limbs had a tcPO2 < 10 mmHg. The success probability for cell therapy was 0.79 (95 % CI 0.38-0.94) and 0.44 (95 % CI 0.18-0.67), respectively (p = 0.1). Of the 16 limbs with tcPO2 < 10 mmHg, the success rate was considerably higher in patients demonstrating a tcPO2 increase in a sitting position of over 30 mmHg (6/8, success probability 0.71, 95 % CI 0.26-0.92) compared to those without (2/8, success probability 0.15, 95 % CI 0.01-0.48, p = 0.03). CONCLUSIONS: For patients with chronic CLI for whom cellular therapy is a therapeutic option, a tcPO2 < 10 mmHg at rest, without vascular reserve (i. e. < 30 mmHg when sitting), is a prognostic indicator for poor outcome.
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Postthrombotic syndrome and quality of life after deep vein thrombosis in patients treated with edoxaban versus warfarin.

Background: Postthrombotic syndrome (PTS) is a long-term complication after deep vein thrombosis (DVT) and can affect quality of life (QoL). Pathogenesis is not fully understood but inadequate anticoagulant therapy with vitamin K antagonists is a known risk factor for the development of PTS. Objectives: To compare the prevalence of PTS after acute DVT and the long-term QoL following DVT between patients treated with edoxaban or warfarin. Methods: We performed a long-term follow-up study in a subset of patients with DVT who participated in the Hokusai-VTE trial between 2010 and 2012 (NCT00986154). Primary outcome was the prevalence of PTS, defined by the Villalta score. The secondary outcome was QoL, assessed by validated disease-specific (VEINES-QOL) and generic health-related (SF-36) questionnaires. Results: Between 2017 and 2020, 316 patients were enrolled in 26 centers in eight countries, of which 168 (53%) patients had been assigned to edoxaban and 148 (47%) to warfarin during the Hokusai-VTE trial. Clinical, demographic, and thrombus-specific characteristics were comparable for both groups. Mean (SD) time since randomization in the Hokusai-VTE trial was 7.0 (1.0) years. PTS was diagnosed in 85 (51%) patients treated with edoxaban and 62 (42%) patients treated with warfarin (adjusted odds ratio 1.6, 95% CI 1.0-2.6). Mean differences in QoL scores between treatment groups were not clinically relevant. Conclusion: Contrary to our hypothesis, the prevalence of PTS tended to be higher in patients treated with edoxaban compared with warfarin. No differences in QoL were observed. Further research is warranted to unravel the role of anticoagulant therapy on development of PTS.

Quality of life in patients with pulmonary embolism treated with edoxaban versus warfarin.

BACKGROUND: Long-term sequelae of acute pulmonary embolism (PE) include decreased quality of life (QoL). Evidence suggests that adequacy of initial anticoagulant treatment in the acute phase of venous thrombosis has a key impact on late postthrombotic complications. We hypothesize that patients with acute PE treated with edoxaban for acute PE experience have improved QoL compared to those treated with warfarin. METHODS: Patients with PE who participated in the Hokusai-VTE trial were contacted between June 2017 and September 2020 for a single long-term follow-up visit. Main outcomes were the generic and disease-specific QoL measured by the 36-Item Short Form Health Survey (SF-36) and Pulmonary Embolism Quality of Life questionnaire. RESULTS: We included 251 patients from 26 centers in eight countries, of which 129 (51%) had been assigned to edoxaban and 122 (49%) to warfarin. Patient- and thrombus-specific characteristics were similar in both groups. Mean time since randomization in the Hokusai-VTE trial was 7.0 years (standard deviation, 1.0). No relevant or statistical differences were observed in the QoL for patients treated with edoxaban compared to patients treated with warfarin. The mean difference between patients treated with edoxaban and patients with PE treated with warfarin was 0.8 (95% confidence interval [CI]. -1.6 to 3.2) for the SF-36 summary mental score and 1.6 (95% CI, -0.9 to 4.1) for summary physical score. CONCLUSION: Our findings indicate that patients with an index PE treated with edoxaban or warfarin have a similar long-term QoL. Since our study was a follow-up study from a well-controlled clinical trial setting, future studies should be designed in a daily clinical practice setting. We suggest a longitudinal design for investigation of changes in QoL over time.

Comparative study on risk factors and early outcome of symptomatic distal versus proximal deep vein thrombosis: results from the OPTIMEV study.

There is a lack of consensus on the value of detecting and treating symptomatic isolated distal deep-vein thrombosis (DVT) of the lower limbs. In our study, we compared the risk factors and outcomes in patients with isolated symptomatic distal DVT with those with proximal symptomatic DVT. We analysed the data of patients with objectively confirmed symptomatic isolated DVT enrolled in the national (France), multicenter, prospective OPTIMEV study. This sub-study outcomes were recurrent venous thromboembolism, major bleeding and death at three months. Among the 6141 patients with suspicion of isolated DVT included between November 2004 and January 2006, DVT was confirmed in 1643 patients (26.8%). Isolated distal DVT was more frequent than proximal DVT (56.8% vs. 43.2%, respectively; p = 0.01). Isolated distal DVT was significantly more often associated with transient risk factors (recent surgery, recent plaster immobilisation, recent travel), whereas proximal DVT was significantly more associated with more chronic states (active cancer, congestive heart failure or respiratory insufficiency, age >75 years). Most patients (96.8%) with isolated distal DVT received anticoagulant therapies. There was no difference in the percentage of recurrent venous thromboembolism and major bleeding in patients with proximal DVT and isolated distal DVT. However, the mortality rate was significantly higher (p < 0.01) in patients with proximal DVT (8.0%) than in those with isolated distal DVT (4.4%). Symptomatic isolated distal DVT differs from symptomatic proximal DVT both in terms of risk factors and clinical outcome. Whether these differences should influence the clinical management of these two events remains to be determined.

Screening of unrecognized peripheral arterial disease (PAD) using ankle-brachial index in high cardiovascular risk patients free from symptomatic PAD.

OBJECTIVE: To determine the utility of ankle-brachial index (ABI) in screening for unrecognized peripheral arterial disease (PAD). Although PAD is a consistent predictor of cardiovascular morbidity and mortality, it is often under-diagnosed and under-treated. METHODS: In this prospective, observational, real-life, epidemiologic study (ELLIPSE) the prevalence of PAD (ABI < 0.9) was calculated in 2146 asymptomatic patients > or =55 years of age who were at high cardiovascular risk and who were hospitalized in departments of cardiology, diabetology, geriatrics, internal medicine, or neurology in metropolitan France. Univariate and multivariate analyses were performed to identify PAD risk factors. The discriminatory power of the model was evaluated by calculating the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: The ABI was <0.9 in 41.1% of patients. In the multivariate analysis, absence of > or =1 pulse (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.81 to 2.63; P < .0001), arterial bruit (OR, 1.92; 95%CI, 1.34 to 2.75; P < .0004), previous non-Q-wave myocardial infarction (OR, 1.50; 95%CI, 1.08 to 2.08; P = .02), regular smoking (OR, 1.49; 95%CI, 1.22 to 1.80; P < .0001), age > or =81 years (OR, 1.45; 95%CI, 1.15 to 1.82; P = .001), creatinine clearance <60 mL/min (OR, 1.33; 95%CI, 1.08 to 1.63; P = .008), and treated hypertension (OR, 1.28; 95%CI, 1.03 to 1.59; P = .03) were significantly associated with PAD. Although risk increased with the number of variables, the model, based on clinical symptoms and on medical history parameters, was not discriminatory (AUC = 0.66). On average, physicians took 15 minutes to perform the ABI test. CONCLUSIONS: The high prevalence of asymptomatic PAD in this patient population suggests that ABI should systematically be performed in high-risk hospitalized patients to ensure that appropriate secondary prevention programs are initiated.

A clinical prediction score for upper extremity deep venous thrombosis.

It was the objective of this study to design a clinical prediction score for the diagnosis of upper extremity deep venous thrombosis (UEDVT). A score was built by multivariate logistic regression in a sample of patients hospitalized for suspicion of UEDVT (derivation sample). It was validated in a second sample in the same university hospital, then in a sample from the multicenter OPTIMEV study that included both outpatients and inpatients. In these three samples, UEDVT diagnosis was objectively confirmed by ultrasound. The derivation sample included 140 patients among whom 50 had confirmed UEDVT, the validation sample included 103 patients among whom 46 had UEDVT, and the OPTIMEV sample included 214 patients among whom 65 had UEDVT. The clinical score identified a combination of four items (venous material, localized pain, unilateral pitting edema and other diagnosis as plausible). One point was attributed to each item (positive for the first 3 and negative for the other diagnosis). A score of -1 or 0 characterized low probability patients, a score of 1 identified intermediate probability patients, and a score of 2 or 3 identified patients with high probability. Low probability score identified a prevalence of UEDVT of 12, 9 and 13%, respectively, in the derivation, validation and OPTIMEV samples. High probability score identified a prevalence of UEDVT of 70, 64 and 69% respectively. In conclusion we propose a simple score to calculate clinical probability of UEDVT. This score might be a useful test in clinical trials as well as in clinical practice.