Safety and feasibility of a diagnostic algorithm combining clinical probability, d-dimer testing, and ultrasonography for suspected upper extremity deep venous thrombosis: a prospective management study.

BACKGROUND: Although well-established for suspected lower limb deep venous thrombosis, an algorithm combining a clinical decision score, d-dimer testing, and ultrasonography has not been evaluated for suspected upper extremity deep venous thrombosis (UEDVT). OBJECTIVE: To assess the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT. DESIGN: Diagnostic management study. (ClinicalTrials.gov: NCT01324037) SETTING: 16 hospitals in Europe and the United States. PATIENTS: 406 inpatients and outpatients with suspected UEDVT. MEASUREMENTS: The algorithm consisted of the sequential application of a clinical decision score, d-dimer testing, and ultrasonography. Patients were first categorized as likely or unlikely to have UEDVT; in those with an unlikely score and normal d-dimer levels, UEDVT was excluded. All other patients had (repeated) compression ultrasonography. The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a normal diagnostic work-up. RESULTS: The algorithm was feasible and completed in 390 of the 406 patients (96%). In 87 patients (21%), an unlikely score combined with normal d-dimer levels excluded UEDVT. Superficial venous thrombosis and UEDVT were diagnosed in 54 (13%) and 103 (25%) patients, respectively. All 249 patients with a normal diagnostic work-up, including those with protocol violations (n = 16), were followed for 3 months. One patient developed UEDVT during follow-up, for an overall failure rate of 0.4% (95% CI, 0.0% to 2.2%). LIMITATIONS: This study was not powered to show the safety of the substrategies. d-Dimer testing was done locally. CONCLUSION: The combination of a clinical decision score, d-dimer testing, and ultrasonography can safely and effectively exclude UEDVT. If confirmed by other studies, this algorithm has potential as a standard approach to suspected UEDVT. PRIMARY FUNDING SOURCE: None.

Corrigendum: Diagnostic and therapeutic management of the thoracic outlet syndrome. Review of the literature and report of an Italian experience.

[This corrects the article DOI: 10.3389/fcvm.2022.802183.].

Wound Care During the COVID-19 Emergency in Padua Hospital, Italy.

Chronic vascular wounds have a significant economic and social impact on our society, calling for the allocation of a great deal of attention and resources. The coronavirus disease (COVID-19) outbreak has represented a difficult challenge to face for health care providers and fragile patients, such as for outpatients and Day-Hospital patients needing continuous care at the Angiology Unit of the University Hospital of Padova in Italy, one of the most crucial areas worldwide. The project consisted of a critical revision of all the procedures from the patients' arrivals to their discharge after completing the entire course of treatment. The previous standard of practice was modified according to the current evidence-based guidelines and the national and local government's indications. The new standard of practice allowed our unit to protect every patient and staff member from the coronavirus infection, providing the same high standard of care as before the COVID-19 outbreak.

Safety and Efficacy of Rivaroxaban as Extended-Phase Anticoagulation in Patients with Cancer and Venous Thromboembolism: A Preliminary Data Analysis from the Mac Project.

Extended-phase anticoagulation with direct oral Xa inhibitors (OAXI) is suggested in patients with cancer-associated venous thromboembolism (CAT). We report on patients enrolled in the MAC (Monitoring AntiCoagulants) Project, given rivaroxaban as extended-phase anticoagulation after CAT. The primary efficacy outcome was the incidence of symptomatic recurrent VTE; the primary safety outcomes were incidence of major and non-major clinically relevant bleeding, adverse events, and all-cause mortality. The mean patients' follow-up was 19 months (SD 16); 64/604 (11%) had CAT. Recurrent VTE occurred in 9.3% and in 8.1% of patients with and without CAT (OR 1.2, 95% CI 0.5 to 2.9; p = 0.6). Major bleeding occurred in 4.7% and in 2.6%, respectively (OR = 1.8, 95% CI 0.5 to 6.6, p = 0.4), and non-major clinically-relevant bleeding in 4.7% and in 4.1% (OR = 1.2, 95% CI 0.3 to 3.9, p = 0.7). The relative figures for fatal haemorrhage and all-cause death were 1.6% versus 0%, and 1.6% versus 0.4%. Rivaroxaban appears to be effective and safe as extended-phase anticoagulation in patients with CAT. The mean treatment period was 3-times the standard 6-month course.

Safety and Efficacy of Rivaroxaban for Extended-Phase Anticoagulation of Patients with Unprovoked or Recurrent Venous Thromboembolism: Real-Life Data from the MAC Project.

Venous thromboembolism (VTE) is a major cause of death in the world. After the acute-phase treatment, the optimal duration of anticoagulation is still debatable. The latest guidelines suggest maintaining long-term anticoagulation in patients with cancer-associated thrombosis (CAT) or with unprovoked VTE and a low bleeding risk. Methods: The MAC Project is an ongoing prospective-cohort, multi-center, observational study in Italy. The project aims to collect real-life clinical information in unselected patients given oral anticoagulants for VTE over a 5-year follow-up period. There were no exclusion criteria, except for life expectancy <6 months and refusal to sign the informed consent form or to attend the planned follow-up visit. All patients were followed-up prospectively with clinical controls scheduled at 3, 6, and 12 months after the index event, and then annually for up to 5 years. The primary efficacy and safety outcomes were symptomatic recurrent VTE and major bleeding. Results: We analyzed 450 consecutive patients treated with rivaroxaban and referred them to the MAC Project database for unprovoked or recurrent VTE. Of these, 267 (55%) were unprovoked VTE, and 377 (87%) were symptomatic. We followed up with the patients for a mean of 22 months (Q1 10.7; Q3 37.4 months). Recurrent VTE occurred in 12 patients on rivaroxaban treatment (IR 1.7 per 100 person-years). Males had more recurrence than women. During the follow-up period, we recorded 13 (2.9%) major bleeding, 12 (2.7%) clinically relevant non-major bleeding, 8 minor bleeding, and no fatal bleeding events. Overall, bleeding events occurred in 33 (7.3%) patients, most occurring within the first 2 years of treatment. In addition, we observed a statistically significant higher incidence of bleeding in patients with a baseline HAS-BLED score of 3 to 4 compared with those with a score of 0 to 2, with most events occurring during the first 3 months of treatment (RR 5.9). Discussion: Rivaroxaban appears to be safe and effective for the long-term treatment of patients with recurrent or unprovoked VTE. Our results match previously published data, and we are confident that the continuation of the follow-up for up to 5 years will confirm these outcomes.

Diagnostic and Therapeutic Management of the Thoracic Outlet Syndrome. Review of the Literature and Report of an Italian Experience.

The Thoracic Outlet Syndrome is a clinical potentially disabling condition characterized by a group of upper extremity signs and symptoms due to the compression of the neurovascular bundle passing through the thoracic outlet region. Because of the non-specific nature of signs and symptoms, to the lack of a consensus for the objective diagnosis, and to the wide range of etiologies, the actual figure is still a matter of debate among experts. We aimed to summarize the current evidence about the pathophysiology, the diagnosis and the treatment of the thoracic outlet syndrome, and to report a retrospective analysis on 324 patients followed for 5 years at the Padua University Hospital and at the Naples Fatebenefratelli Hospital in Italy, to verify the effectiveness of a specific rehabilitation program for the syndrome and to evaluate if physical therapy could relieve symptoms in these patients.

MAC Project-Monitoring Anticoagulant Therapy Observational Study: Rationale and Protocol.

Real-life studies complement data from registrative trials. Because of the delayed registration of direct oral anticoagulants in Italy, scarce real-life data on such treatments is available for the Italian population. The aim of the MAC project is to collect real-life clinical information in unselected patients given oral anticoagulants for venous thromboembolism, during a 5-year follow-up period. This is a prospective-cohort, multi-center, observational study performed in four Italian centers. The estimated samples size is 4,000 patients. The efficacy outcomes are: incidence of symptomatic recurrent venous thromboembolism and of post-thrombotic syndrome. The safety outcomes are: incidence of major bleeding, clinically relevant non-major bleeding, minor bleeding, serious adverse events, and mortality. The MAC project has the potential to improve our understanding of the epidemiology and of the therapeutic strategies adopted in Italian patients with venous thromboembolism. Clinical Trial Registration: WWW.ClinicalTrials.Gov, identifier: NCT0432939.

Carotid atherosclerosis and risk for ischemic stroke in patients with atrial fibrillation on oral anticoagulant treatment.

BACKGROUND AND AIMS: Whether carotid atherosclerosis is associated with an increased risk for ischemic stroke in patients with atrial fibrillation (AF) on anticoagulant treatment is undefined. To explore this association, patients with AF on treatment with vitamin K antagonists were included in a multicenter, prospective study. METHODS: At inclusion in the study, patients underwent Doppler-ultrasonography for the assessment of carotid atherosclerosis and then were prospectively followed. Ischemic stroke or transient ischemic attack (TIA) were the primary study outcomes; death and its causes were reported. RESULTS: Overall, 587 patients were included in the study. At ultrasonography, 380 patients had carotid atherosclerosis (64.7%) and 45 internal carotid (ICA) stenosis ≥50% (7.7%). During a mean follow-up of 41 ±â€¯15 months, 30 patients had an ischemic stroke or TIA (1.49% per patient-year, 95% CI 0.96-2.03) and 81 patients died (4.01% per patient-year, 95% CI 3.16-4.86). Carotid atherosclerosis was associated with a significant increase in the risk for the composite of ischemic stroke or TIA or death after adjusting for CHA2DS2VASc (6.0% vs. 3.1% patient-year; HR 1.60, 95% CI 0.99-2.59; p = 0.05). ICA ≥50% was associated with a not significant increase in the risk of ischemic stroke or TIA (2.05% vs. 1.45% patient-year; HR 1.39, 95% CI 0.42-4.58) or all-cause death (6.1% vs. 3.8% patient-year; HR 1.66, 95% CI 0.83-3.32). CONCLUSIONS: In patients with AF, carotid atherosclerosis is a predictor for the composite of cerebrovascular events or death while on anticoagulant therapy. In patients with AF and carotid atherosclerosis, the clinical benefit of a more intense antithrombotic treatment should be evaluated.

The management of patients with venous thromboembolism in Italy: insights from the PREFER in VTE registry.

Venous thromboembolism (VTE) is the third most common cardiovascular disease. Real-life data on the clinical presentation, risk factors, diagnosis, and treatment of VTE in Italy and Europe are required to optimize the management of this disease. The PREFER in VTE registry, a prospective non-interventional real-life study, was designed to assess clinical characteristics and management of patients with VTE, use of health care resources, and on-treatment patient quality of life. Eligible consecutive patients with objectively diagnosed VTE were enrolled in the registry and followed up for 12 months. Between January and December 2013, 816 Italian and 1027 patients from 6 European countries other than Italy (European patients) were enrolled in the registry, and followed up until December 2014. Italian patients were the oldest (mean age 65.7 years) among the European patients. The Italian patients with a history of cancer were 24.6 % of whom 63.2 % had an active cancer (18.2 and 57.0 %, respectively, in Europe). Parenteral heparin was given, as initial treatment, in 73.8 % of Italian patients (66.4 % in Europe); VKA in combination with other treatments in 45.8 % (34.7 % in Europe); and VKA as the only anticoagulant treatment in 24.4 % (17.2 % in Europe). Of the Italian patients, 43.2 and 90.6 % of patients were hospitalized for deep vein thrombosis and pulmonary embolism, respectively; 65.4 % were admitted to the hospital through the emergency department. Following a real world approach, PREFER in VTE shows that the Italian patients, among and compared to the European patients, are the oldest, have a history of cancer more commonly, receive an initial treatment with heparin more commonly, and are more commonly hospitalized, particularly if affected by PE.

Efficacy of Rivaroxaban for thromboprophylaxis after Knee Arthroscopy (ERIKA). A phase II, multicentre, double-blind, placebo-controlled randomised study.

Without thromboprophylaxis, knee arthroscopy (KA) carries a low to moderate risk of venous thromboembolism. Over 5 million arthroscopies are performed worldwide yearly. It was our study objective to assess the efficacy and safety of rivaroxaban for thromboprophylaxis after therapeutic KA. Patients undergoing KA in nine Italian teaching or community hospitals were allocated to once-daily rivaroxaban (10 mg) or placebo for seven days in a phase II, multicentre, double-blind, placebo-controlled randomised trial. The primary efficacy outcome was a composite of all-cause death, symptomatic thromboembolism and asymptomatic proximal DVT at three months; major bleeding represented the primary safety outcome. All patients underwent whole-leg ultrasonography at day 7(+1), or earlier if symptomatic. A total of 241 patients were randomised (122 rivaroxaban, 119 placebo), and 234 completed the study. The primary efficacy outcome occurred in 1/120 of the rivaroxaban group and in 7/114 of the placebo group (0.8 % vs 6.1 %, respectively, p=0.03; absolute risk difference, -5.3 %, 95 % CI, -11.4 to -0.8; crude relative risk 0.14, 95 % CI, 0.02 to 0.83; number-needed-to-treat=19). No major bleedings were observed. We found no association between different arthroscopic procedures and thrombotic events. Small sample size, high exclusion rate, and low number of anterior cruciate ligament reconstruction procedures are the main limitations of our study. In conclusion, a seven-day course of 10-mg rivaroxaban may be safely employed for thromboprophylaxis after KA. Whether prophylaxis after KA should be given to all patients, or to selected "high-risk" subjects, remains to be determined. A larger trial to verify our preliminary results is warranted.

Analysis of an algorithm incorporating limited and whole-leg assessment of the deep venous system in symptomatic outpatients with suspected deep-vein thrombosis (PALLADIO): a prospective, multicentre, cohort study.

BACKGROUND: Compression ultrasonography is the mainstay of diagnosis of deep-vein thrombosis (DVT) of the legs. Compression ultrasonography can be extended to the entire deep venous system (whole-leg) or restricted to the proximal veins only (limited), and the two approaches are clinically equivalent. We aimed to assess the diagnostic value of an algorithm combining whole-leg and limited compression ultrasonography. METHODS: We did a prospective, multicentre, cohort study at eight centres in five countries. Consecutive outpatients aged 18 years or older with suspected DVT underwent D-dimer measurement and pretest clinical probability assessment. DVT was ruled out without further testing if pretest probability was unlikely and D-dimer was negative (group 1). Patients in whom either pretest probability was likely or who were positive for D-dimer underwent limited compression ultrasonography only (group 2). Finally, patients in whom pretest probability was likely and who had a positive measurement for D-dimer underwent extended whole-leg compression ultrasonography (group 3). All patients in whom DVT was ruled out were followed up for 3 months. The primary outcome was the incidence of objectively recorded venous thromboembolism. The primary analysis included all patients managed according to the study protocol. This study is registered with ClinicalTrials.gov, number NCT01412242. The final results are reported here. FINDINGS: Between March 1, 2011, and July 31, 2014, 1348 consecutive outpatients were referred for this study, of whom 1162 were eligible to participate. After pretest probability assessment and D-dimer testing, 351 were in group 1, 401 in group 2, and 410 in group 3. Limited compression ultrasonography was positive in 12 (3%) patients in group 2 and extended whole-leg compression ultrasonography was positive in 200 (49%) patients in group 3. 82 (39%) of all DVT diagnosed at baseline were isolated distal thromboses. 26 protocol violations were reported. Thus, 351 patients from group 1, 371 patients in group 2, and 202 patients in group 3 who had been excluded for DVT by the algorithm were included in the primary analysis at 3 months. One, four, and three DVTs were reported, respectively. Thus, the 3-month incidence of venous thromboembolism in untreated patients after a negative diagnostic strategy was 0·87% (95% CI 0·44-1·70). INTERPRETATION: An algorithm combining limited and whole-leg compression ultrasonography could be a reliable, safe, and convenient method for diagnostic management of outpatients with clinically suspected DVT. FUNDING: None.