Peripheral arterial disease and systematic detection of circulating tumor cells: rationale and design of the DETECTOR prospective cohort study.

BACKGROUND: Smoking is a strong risk factor for cancer and atherosclerosis. Cancer mortality, especially from lung cancer, overtakes cardiovascular (CV) death rate in patients with peripheral arterial disease (PAD). Only a few patients with lung cancer after PAD management may benefit from surgical excision. Circulating tumor cells (CTC) associated with low-dose chest CT (LDCT) may improve early cancer detection. This study focuses on a screening strategy that can address not only lung cancer but all tobacco-related cancers in this high-risk population. METHODS: DETECTOR Project is a prospective cohort study in two French University hospitals. Participants are smokers or former smokers (≥30 pack-years, quitted ≤15 years), aged ≥55 to 80 years, with atherosclerotic PAD or abdominal aortic aneurysm. After the first screening round combining LDCT and CTC search on a blood sample, two other screening rounds will be performed at one-year interval. Incidental lung nodule volume, volume doubling time and presence of CTC will be taken into consideration for adapted diagnostic management. In case of negative LDCT and presence of CTC, a contrast enhanced whole-body PET/CT will be performed for extra-pulmonary malignancy screening. Psychological impact of this screening strategy will be evaluated in population study using a qualitative methodology. Assuming 10% prevalence of smoking-associated cancer in the studied population, a total of at least 300 participants will be enrolled. DISCUSSION: Epidemiological data underline an increase incidence in cancer and related death in the follow-up of patients with PAD, compared with the general population, particularly for tobacco-related cancers. The clinical benefit of a special workup for neoplasms in patients with PAD and a history of cigarette smoking has never been investigated. By considering CTCs detection in this very high-risk selected PAD population for tobacco-induced cancer, we expect to detect earlier pulmonary and extra-pulmonary malignancies, at a potentially curable stage. TRIAL REGISTRATION: The study was registered in the French National Agency for Medicines and Health Products Safety (No N° EUDRACT_ID RCB: 2016-A00657-44) and was approved by the ethics Committee for Persons Protection (IRB number 1072 and n° initial agreement 2016-08-02; ClinicalTrials.gov identifier NCT02849041).

Osteitis in Systemic Sclerosis: A Nationwide Case-Control Retrospective Study.

OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by skin fibrosis, vasculopathy, and dysimmunity. Data regarding osteitis in SSc are scarce. METHODS: We performed a nationwide multicenter, retrospective, case-control study including patients with SSc, according to the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification, with a diagnosis of osteitis. The objectives of the study were to describe, to characterize, and to identify associated factors for osteitis in patients with SSc. RESULTS: Forty-eight patients were included. Twenty-six patients (54.1%) had osteitis beneath digital tip ulcers. Physical symptoms included pain (36 of 48, 75%), erythema (35 of 48, 73%), and local warmth (35 of 48, 73%). Thirty-one (65%) patients had median (interquartile range) C-reactive protein levels >2 mg/liter of 8 (2.7-44.3) mg/liter. On radiography, computed tomography, or magnetic resonance imaging, osteitis was characterized by swelling or abscess of soft tissues, with acro-osteolysis or lysis in 28 patients (58%). Microbiological sampling was performed in 45 (94%) patients. Most pathogens were Staphylococcus aureus (43.8%), anaerobes and Enterobacteriaceae (29.1%), and Pseudomonas aeruginosa (10.4%). Management comprised antibiotics in 37 (77.1%) patients and/or surgery in 26 (54.2%). Fluoroquinolones were used in 22 (45.8%) patients, and amoxicillin plus ß-lactamase inhibitor in 7 (14.6%). Six (12.6%) patients relapsed, 6 (12.6%) patients had osteitis recurrence, 15 (32%) sequelae, and 2 patients had septic shock and died. CONCLUSION: This study confirmed digital tip ulcers as an associated factor for osteitis and revealed a high rate of functional sequelae. Antimicrobial therapy with oral fluoroquinolone or intravenous amoxicillin and ß-lactamase inhibitor are used as first-line antibiotic therapy in SSc patients with osteitis.

Low admission blood pressure as a marker of poor 1-year survival in patients with revascularized critical limb ischemia.

OBJECTIVE: To contrast the association between blood pressure (BP) level and antihypertensive medications at hospital admission with 1-year mortality in patients undergoing revascularization for critical limb ischemia (CLI). METHODS: From November 2013 to May 2019, 315 consecutive patients were retrospectively included. A median of seven (IQR 3-13) separate readings were recorded for each patient before revascularization procedure and the average represented patient's mean BP. BP-lowering medications, clinical and biological parameters were recorded at baseline. The main outcome was total 1-year mortality. RESULTS: The cohort included 172 men (55%) and 143 women (45%), with a mean age of 77.9 ±â€Š11.9 years. Treated hypertension was present in 245 (78%) patients; 288 (91%) patients had BP-lowering drug prescriptions (2.1 ±â€Š1.3 medications at baseline). Mean SBP, DBP, mean BP (MBP) and pulse pressure (PP) were 132 ±â€Š18, 70 ±â€Š8, 90 ±â€Š10 and 62 ±â€Š16mmHg. During 1-year follow-up, 80 (25.4%) patients died. In single-pressure multivariate analysis, SBP (hazard ratio 0.97; 95% CI 0.96-0.99; P = 0.005), MBP (hazard ratio 0.96; 95% CI 0.92-0.99; P = 0.01), PP (hazard ratio 0.97; 95% CI 0.95-0.99; P = 0.009), but not DBP, were inversely correlated with 1-year mortality, independently of age, coronary heart disease, left ventricular ejection fraction, brain natriuretic peptide, serum albumin, institutionalized status and antihypertensive drugs. Association between SBP, MBP and PP with 1-year mortality had a quite linear reverse pattern. CONCLUSION: Among patients undergoing revascularization for CLI, there is an inverse correlation between admission SBP, MBP and PP with 1-year mortality. BP may represent a modifiable therapeutic target to prevent poor outcome in CLI patients.

A reappraisal of the presence of small or large fiber neuropathy in patients with erythromelalgia.

OBJECTIVE: To assess the contribution of large and small nerve fiber alteration in erythromelalgia (EM). METHODS: Thirty-three EM patients were included and underwent clinical evaluation based on EM severity score, DN4, and Utah Early Neuropathy Scale (UENS) score. Neurophysiological evaluation consisted in nerve conduction studies (NCS) for large nerve fibers and specific tests for small nerve fibers: electrochemical skin conductance, cold and warm detection thresholds, and laser evoked potentials. Finally, the evaluation of vascular changes was based on the presence of clinical feature of microvascular disorders and the measurement of the Toe Pressure Index (TPI). RESULTS: While 28 patients (85%) had vascular alteration on TPI or clinical features, 23 patients (70%) had small-fiber neuropathy on neurophysiological tests, and only 10 patients (30%) had large fiber neuropathy on NCS. Regarding clinical scores, there was no difference between groups (presence or absence of large- or small-fiber neuropathy or microvascular disorder) except for a higher UENS score in patients with large fiber neuropathy. CONCLUSION: Peripheral neuropathy, mostly involving small nerve fibers, is almost as common as microvascular changes in EM, but remains inconstant and not related to a specific neuropathic pattern or higher clinical severity. SIGNIFICANCE: The association of neuropathic and vascular factors is not systematic in EM, this syndrome being characterized by different pathophysiological mechanisms leading to a common clinical phenotype.

Prevalence and characteristics of pulmonary embolism in 1042 COVID-19 patients with respiratory symptoms: A nested case-control study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders. Previous studies reported pulmonary embolism (PE) in severe COVID-19 patients. Aim of the study was to estimate the prevalence of symptomatic PE in COVID-19 patients and to identify the clinical, radiological or biological characteristics associated with PE. PATIENTS/METHODS: We conducted a retrospective nested case-control study in 2 French hospitals. Controls were matched in a 1:2 ratio on the basis of age, sex and center. PE patients with COVID-19 were compared to patients in whom PE was ruled out (CTPA controls) and in whom PE has not been investigated (CT controls). RESULTS: PE was suspected in 269 patients among 1042 COVID-19 patients, and confirmed in 59 patients (5.6%). Half of PE was diagnosed at COVID-19 diagnosis. PE patients did not differ from CT and CTPA controls for thrombosis risk factors. PE patients more often required invasive ventilation compared to CTPA controls (odds ratio (OR) 2.79; 95% confidence interval (CI) 1.33-5.84) and to CT controls (OR 8.07; 95% CI 2.70-23.82). PE patients exhibited more extensive parenchymal lesions (>50%) than CT controls (OR 3.90; 95% CI 1.54-9.94). D-dimer levels were 5.1 (95% CI 1.90-13.76) times higher in PE patients than CTPA controls. CONCLUSIONS: Our results suggest a PE prevalence in COVID-19 patients close to 5% in the whole population and to 20% of the clinically suspected population. PE seems to be associated with more extensive lung damage and to require more frequently invasive ventilation.

Predictive value of admission blood pressure for 3-month mortality in patients undergoing revascularization for critical limb ischemia.

OBJECTIVE: In patients with critical limb ischemia (CLI), blood pressure (BP) impact on mortality is unknown. We analyzed the predictive value of SBP, DBP and pulse pressure (PP) at hospital admission on 3-month mortality in patients with CLI undergoing revascularization procedure. METHODS: From November 2013 to December 2018, 297 consecutive patients were retrospectively included. Admission BP was recorded using automated brachial sphygmomanometer, before revascularization procedure. A median of seven (IQR3-13) separate readings were recorded for each patient and the average represented patient's mean BP (mBP). Clinical and biological parameters were recorded at baseline. RESULTS: The cohort included 163 men (55%) and 134 women (45%) with a mean age of 77.7 ±â€Š11.9 years. Treated hypertension and diabetes were present in, respectively, 62 and 48% of patients. Mean SBP, DBP and PP were 132 ±â€Š18, 70 ±â€Š8 and 62 ±â€Š16 mmHg. Thirty-four patients (11.4%) died during 3-month follow-up, mostly from cardiovascular causes. In univariate analysis, age, female sex, brain natriuretic peptide and C-reactive protein were positively correlated with mortality. BMI, mSBP, mDBP, mPP, hemoglobin, serum albumin and statin treatment were negatively correlated with mortality. In single-pressure multivariate analyses, mSBP (P = 0.024) and mPP (P = 0.030) were negatively correlated with mortality. Association between mSBP and mortality had an asymptotic curve pattern and SBP level 135 mmHg or less was significantly correlated with mortality. CONCLUSION: In patients undergoing revascularization for CLI, admission SBP is an independent predictor for short-term mortality with a negative relationship. SBP level 135 mmHg or less represents a warning sign to explore and correct associated comorbidities.

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.

Loss of chromosomes 9 and 11 may be recurrent chromosome imbalances in juxtaglomerular cell tumors.

Juxtaglomerular cell tumor (JGCT), first described in 1967, is a rare tumor of the kidney that derived from specialized smooth muscle cells of the wall of the glomerular afferent arteriole. Less than 100 cases have been published, mainly as isolated case reports or small series. JGCTs are considered benign, but the clinical follow-up is short in most reported cases. Only 1 metastatic case has been reported to date, raising the question of tumors of uncertain malignant potential rather than clearly benign neoplasms. Genomic features have been studied in only 2 cases that showed gain of chromosome 10 as well as loss of chromosomes 9, 11q, and X. The present work studied the genomic characteristics of 2 additional cases of JGCT by comparative genomic hybridization. Similarly to the 2 previously reported cases, these 2 tumors showed loss of chromosomes 9 and 11, suggesting recurrent chromosomal imbalances. In addition, 1 case showed gain and loss of entire chromosomes, similar to a previous case studied by karyotyping. Such an aneuploid karyotype may reflect a potential for malignancy as previously reported. Thus, JGCT might be better considered as a tumor of uncertain malignant potential and then necessitates a prolonged follow-up. Future clinicopathologic and genomic studies of large retrospective and prospective series may help to better understand the biology of this fascinating entity.

Femoral vein thrombosis after right-sided electrophysiological procedures.

PURPOSE: Electrophysiological studies and radiofrequency catheter ablations require single or multiple sheath placements through femoral vein cannulation. The objective of this study was to determine the incidence, predictors, and outcomes of deep vein thrombosis (DVT) following such procedures. METHODS AND RESULTS: We prospectively enrolled 220 consecutive patients with a median age of 70 [60-79] years. The median duration of the procedures from insertion to removal of sheaths was 45 [30-75] min. At least two sheaths were inserted in 158 (72%) of the cases. Duplex ultrasonography evaluation of the lower leg veins was performed 6 h after the procedure and revealed common femoral vein thrombosis in 11 (5%) patients. All thrombi were partial and none was complete. Thrombi were mobile in four patients and extended to the external iliac vein in three patients. None of the patients presented with clinical signs of DVT or pulmonary embolism. Anticoagulation was prescribed for 2-4 weeks and a follow-up duplex ultrasonography obtained in the first seven patients revealed complete resolution of thrombi in all cases. On multivariate analysis, two predictors of thrombosis occurrence were identified: a greater sum of sheath diameters (odds ratio, 1.41 [95% confidence interval, 1.25-1.60] per 1-French increase; p < 0.001) and a longer procedural duration (odds ratio, 1.02 [95% confidence interval, 1.00-1.04] per 1-min increase; p = 0.04). CONCLUSIONS: Asymptomatic femoral DVT occur in 5% of electrophysiological studies and right-heart radiofrequency catheter ablations, particularly when large sheaths are inserted for a longer period. The role of anticoagulation in this clinical setting warrants further evaluation.

Prevalence of unknown peripheral arterial disease in patients with coronary artery disease: data in primary care from the IPSILON study.

BACKGROUND: Peripheral arterial disease (PAD) is a marker of increased risk of cardiovascular events and of poor prognosis in patients with coronary artery disease (CAD). The prevalence of unknown PAD among patients with CAD varies between studies according to the mode of diagnosis. AIMS: To evaluate the prevalence of unknown PAD, diagnosed using the ankle-brachial index (ABI), in patients from the IPSILON study with a CAD diagnosis; to assess the profile of these patients; and to determine predictors of PAD. METHODS: IPSILON was an observational, cross-sectional study. General practitioners measured ABI in 5679 consecutive adults aged 55 years or over with signs or symptoms suggestive of PAD (21.3%), a history of an atherothrombotic event (42.1%) or two or more cardiovascular risk factors (36.6%). This analysis focuses on the subgroup of patients with CAD and no other known overt atherothrombotic disease. RESULTS: A total of 1340 patients presented with isolated CAD. PAD (ABI<0.90) was diagnosed in 26.6% of these patients; 16.2% were asymptomatic. Older age, symptoms suggestive of PAD and cardiovascular risk factors were found to be independent predictors of PAD in multivariable analysis. CONCLUSION: Over 26% of patients with CAD present with unknown PAD, as diagnosed using ABI measurement. More than half of these patients are asymptomatic. Screening for PAD in patients with CAD will allow detection of a subpopulation at particularly high cardiovascular risk. An aggressive medical treatment strategy could help to improve their outcome.

Peripheral arterial disease versus other localizations of vascular disease: the ATTEST study.

OBJECTIVE: Despite the increased cardiovascular morbidity and mortality risk of patients with peripheral arterial disease, previous worldwide studies have documented undertreatment of cardiovascular risk factors in such patients. METHOD: The ATTEST study was an observational cross-sectional epidemiologic study. Patients (n = 8475) were selected by 3020 general practitioners in France who were asked to include the first three patients with at least one site of proven atherothrombotic disease (peripheral arterial disease of the lower limbs for two patients and coronary artery disease or ischemic stroke for the third patient). We designed the ATTEST study to compare medical management of patients with peripheral arterial disease, including pharmacologic treatment, cardiovascular tests, and physician's assessment of future cardiovascular and amputation risks, with patients with coronary artery disease or ischemic stroke. RESULTS: Only 13% of the patients with peripheral arterial disease (n = 3811) received angiotensin converting enzyme inhibitors, statins, and antiplatelet agents vs 30% of the patients with coronary artery disease or ischemic stroke (n = 4664). This undertreatment of the population with peripheral arterial disease was associated with a too-optimistic physician's assessment of future cardiovascular risk: only 27% of the general practitioners predicted a 5-year cardiovascular risk >20%. Conversely, amputation risk prediction was greatly overestimated: only 44% of the practitioners predicted a 5-year amputation risk <5%. CONCLUSIONS: Patients with atherothrombotic disease recruited from primary care practices were not adequately tested and treated, especially the patients with peripheral arterial disease. To improve the medical management of patients with peripheral arterial disease, there is a need for epidemiologic and clinical education of physicians.