Treatment of cancer-associated venous thromboembolism: A focus on special populations.

Current evidence-based clinical practice guidelines recommend the use of both low-molecular-weight heparin (LMWH) and direct factor Xa inhibitors (apixapan, edoxaban and rivaroxaban) as first-line options for the treatment of venous thromboembolism (VTE) in patients with cancer. However, most of these guidelines refer to the general cancer patient population and provide limited guidance for specific subgroups of patients at particularly high risk of bleeding, such as those with gastrointestinal cancers, primary or metastatic brain tumors, thrombocytopenia, or renal impairment. In these complex populations, the management of cancer-associated thrombosis (CAT) poses unique challenges and requires a nuanced approach based on the primum non nocere principle. This comprehensive review critically examines the relevant literature and discusses the therapeutic options currently available for the management of CAT in these special situations.

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.

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.

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.

Body Mass Index as a Major Risk Factor for Severe Breast Cancer-Related Lymphedema.

Background: A few studies have examined the characteristics of severe breast cancer-related lymphedema (BCRL). This study aims at analyzing the factors associated with severe lymphedema (LE) across a specific population of patients with BCRL. Methods and Results: Seventy-four patients with BCRL were included and cared for in the Lymphology Unit of Toulouse University Hospital between 2015 and 2016. Characteristics of patients and factors related to severe BCRL were retrospectively assessed. The median age at time of LE was 56 years (30-82). Thirty-five patients (47.3%) had a mastectomy and 72 (97.3%) an axillary lymphadenectomy. Among patients treated with radiation therapy (n = 72), 76.3% received lymphatic nodes irradiation. Fifty-five patients (74.3%) received chemotherapy and 52 (70.3%) a hormonal suppression therapy. A high proportion of patients had severe (>400 mL, 64.9%) and premature LE, with a median time of 13 months since onset of surgery (0.1-400.2). Weight gain between surgery and LE management was more prevalent in obese patients (p = 0.0164). Body mass index (BMI) at BCRL diagnosis was the only risk factor associated with severe LE (p = 0.0132). There was no significant association between LE severity and treatments received for breast cancer. Conclusions: Our study did not show any influence of tumor characteristics and cancer-related treatments on the severity of BCRL. Only BMI at BCRL diagnosis appears as a factor related to severe LE. These results highlight the importance of an education care unit promoting personalized nutritional lifestyle and encouraging physical activity early in the management of breast cancer.

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).

Endermology treatment for breast cancer related lymphedema (ELOCS): Protocol for a phase II randomized controlled trial.

OBJECTIVES: Secondary lymphedema is a serious and debilitating condition, which may cause a range of cutaneous, infectious and joint complications with major psychological and social consequences. There is no curative treatment available. Initial symptomatic treatment includes Intensive Decongestive Treatment (IDT), which involves the use of multi-layered compression bandages, along with manual lymph drainage, physical exercise and skin care. IDT leads to an average decrease in limb volume of 20-40%, when compared to the contralateral limb. A better reduction may be obtained through the use of new adjuvant techniques, of which endermology is an example. The aim of this phase II study is to validate an IDT protocol combining endermology with standard of care in breast cancer related lymphedema. STUDY DESIGN: A standardised care protocol was proposed by the University Hospital of Toulouse's Lymphology team for the treatment of upper limb lymphedema after breast cancer surgery using Cellu M6 (LPG) Endermologie over 30 min. Every patient benefitted from IDT over 5 consecutive days, within the multidisciplinary Lymphology unit. Patients were randomised into three arms as follows: Arm 1: IDT for 5 days with bandages + manual lymphatic drainage. Arm 2: IDT with bandages + manual lymphatic drainage + Cellu M6 for 5 days. Arm 3: bandages + Cellu M6 for 5 days. During the study, patients will be followed-up for a period of 6 months. Use of LPG's Cellu M6 in combination with IDT may improve upper limb volume reduction compared with standard of care. By improving breast cancer related lymphedema, we expect to minimise further fluid build-up and to improve skin care, thus reducing the number of consultations and hospital admissions caused by this condition. The results of the present research protocol are expected to promote evidence supporting the use of endermology in the field of lymphology.

Determinants of pulse pressure amplification in hypertensive and diabetic patients.

Hypertensive diabetic patients remain at high cardiovascular risk despite adequate blood pressure and glycemic control. Pulse pressure amplification (PPA) is expressed as the peripheral-to-central PP ratio and provides complementary information for use in assessing cardiovascular risk. The aim of our study was to determine the clinical and biological determinants of PPA in hypertensive and diabetic patients. A cross-sectional study was conducted in 624 patients. Applanation tonometry was used to determine hemodynamic parameters. Age, gender, and the association between hypertension and diabetes were the independent factors of PPA in our population (N = 624). A threshold of 55 years of age was chosen because of its link with menopause in our analysis. Multivariate regression analyses were performed to evaluate the independent determinants of PPA for hypertensive diabetic and hypertensive nondiabetic male and female patients. HbA1c level is the main factor of increased PPA regardless of age and gender (P < 0.05). Mean BP negatively regulates PPA in the overall study: men > 55 years (P = 0.0001) and women > 55 years (P = 0.03). The threshold calculated glomerular filtration rate (cGFR) < 60 mL/min/1.73 m2 was an independent and negative factor of PPA in hypertensive diabetic men regardless of age (P < 0.05) and in women > 55 years (P = 0.04). Mean BP negatively regulates PPA in hypertensive nondiabetic patients (P < 0.04) regardless of age and gender, except in women > 55 years, where cGFR < 60 (P = 0.04) negatively regulates the modulation of PPA. HbA1c and threshold cGFR < 60 have highly significant impacts on PPA in hypertensive diabetic patients, whereas mean BP appears as the main factor of PPA in hypertensive nondiabetic patients.

Determinants of the aortic pulse wave velocity index in hypertensive and diabetic patients: predictive and therapeutic implications.

OBJECTIVE: Aortic stiffness may provide information to classical risk factors information regarding cardiovascular risk. Aortic pulse wave velocity (PWV) can be measured by applanation tonometry but also theoretical PWV was calculated according to age, blood pressure, heart rate and sex. We aim to highlight biological and hemodynamic determinants of the aortic PWV index, that is the individually calculated [(measured PWV - theoretical PWV)/theoretical PWV] difference, in hypertensive diabetic patients. METHODS: A cross-sectional study was conducted in 514 patients, involving normotensive and hypertensive patients and people with and without diabetes. Biological parameters were measured during day-hospital for cardiovascular screening. Hemodynamic parameters were determined by applanation tonometry. Multivariate regression analyses evaluated the PWV index determinants. RESULTS: Hypertensive and/or diabetic population presents higher PWV index in correlation with the presence of proteinuria (P = 0.0428) and previous cardiovascular events (P = 0.0227). Hypertensive diabetic patients present a higher PWV index than the other patients (P < 0.05). Presence of insulin therapy (P = 0.0101) and the type 1 diabetes (P = 0.0065) were positively and independently modulating PWV index in hypertensive diabetic patients. HDL cholesterol levels (P = 0.0245) and absence of carotid (P = 0.0468) plaques were independently modulating PWV index with a negative correlation in hypertensive without diabetes patients. C reactive protein levels were significantly associated with increased PWV index in hypertensive patients (P = 0.0074) and in hypertensive and/or diabetic population (P = 0.0184). CONCLUSION: PWV index was correlated with numerous cardiovascular risk factors, in addition of being a marker of age and hypertension. Therefore, this index appears as a cardiovascular risk integrator. Its use could be interesting in cardiovascular risk assessment and reduction strategies.

Giant Pilomatricoma Arising as a Rapidly Growing Vascularized Tumor in a Child.

In this observation, we report an unusual presentation of a pilomatricoma in an 8-year-old girl who was initially referred to the department of vascular medicine for diagnosis and care of a suspected mixed lymphatic venous malformation. The lesion on her left shoulder presented as a giant bluish-purple red solitary mass, painful and rapidly growing, measuring 7 cm in anteroposterior diameter. This mass did not present the typical characteristics of a lymphatic venous malformation but exhibited warning signs of malignancy on clinical examination and imaging. The diagnosis of pilomatricoma was reached by fine-needle aspiration biopsy of the mass, showing mummified "ghost" squamous cells and a granulomatous inflammatory reaction stroma with scattered multinucleated giant cells and no sign of malignancy. Complete surgical excision associated with plastic surgery was curative. Diagnostic and management approach to skin lesion in childhood is subject of great concern for health care professionals, including dermatologists and vascular medicine specialists who may be confronted with this atypical presentation of one of the most common causes of superficial neck masses in children.

[Arterial hemodynamic parameters and cardiovascular risk in HIV patients with controlled infection]. / Paramètres hémodynamiques artériels et risque cardiovasculaire chez les patients vivant avec le VIH et en succès immuno-virologique.

Although viral replication is apparently controlled with highly active antiretroviral therapy, cardiovascular risk of patients living with HIV remains a concern in clinical practice with population ageing. Cardiovascular risk profile in patients living with HIV is changing with the emergence of new parameters related to the persistence of residual viral replication, the antecedent and severity of immunodepression, the resulting chronic inflammation, as well as prolonged exposure to antiretroviral drugs and "classical" cardiovascular risk factors. Estimating risk models in patients living with HIV are not sufficient to integrate duration of exposure and control quality of all cardiovascular risk factors at the individual level. Aortic stiffness is a marker of the alteration of structural and functional properties of the wall of the large arterial trunks. This marker has an independent predictive value for total and cardiovascular mortality in the general population but also in the presence of risk factors and may offer clinical information about accelerated vascular ageing in people living with HIV. Aortic stiffness can be estimated non-invasively by applanation tonometry with carotid-femoral pulse wave velocity. This measure may be useful in clinical practice for early identification of at risk patients. Study of the determinants of aortic stiffening process in this population may optimize cardiovascular prevention.

Clinical relevance of aortic stiffness in end-stage renal disease and diabetes: implication for hypertension management.

: Evidence suggests that aortic stiffness may antedate and contribute initially to the development of hypertension and cardiovascular risk (CVR). In treated hypertensive patients, both diabetes and end-stage renal disease (ESRD) are comorbid conditions associated with increased aortic stiffness and high CVR. Thus, the pathophysiological relationship between aortic stiffness, blood pressure (BP) and CVR may have clinical implication in the management of hypertension. In patients with diabetes or ESRD, aortic stiffness is a significant predictor of CVR, independently of BP control. The hallmark of accelerated aortic stiffening in these patients associates the presence of vascular calcification, which is considered as a time-dependent process. Aortic stiffness represents a marker of structural but also functional arterial damage associated with increased pressure pulsatility. Carotid-femoral pulse wave velocity (cf-PWV), as a marker of aortic stiffness, may provide a readily available information for the effectiveness of risk reduction strategies. SBP, hyperglycemia and progressive alteration of renal function are considered as determinants of accelerated aortic stiffening. These findings suggest that earlier and intensive treatment of glycemia and BP could be important to limit or even reverse stiffening process. In patients with ESRD, more specific and potentially modifiable kidney disease-related parameters such as phosphocalcic disorders and vitamin K deficiency, appear correlated with aortic calcification and cf-PWV. An important and recent finding is that the magnitude of longitudinal increase in cf-PWV may represent a clinically pertinent surrogate for cardiovascular events. Aortic stiffness may be, thus, considered as an intermediate marker to monitor effectiveness of preventive strategies in these high-risk patients.

Aortic stiffness improves the prediction of both diagnosis and severity of coronary artery disease.

Elective coronography has low diagnostic yield for obstructive coronary artery disease (CAD). We aim to determine whether non-invasive aortic stiffness assessment improves diagnostic accuracy of CAD screening by reducing the number of false-positive results from the cardiac stress test. A cross-sectional study was conducted from January 2013 to September 2014 in our medical center. Electrocardiogram (ECG) stress test coupled with nuclear imaging was performed in 367 consecutive patients routinely followed for myocardial ischemia screening. Aortic pulse wave velocity (PWV) was assessed by applanation tonometry in the overall population. Forty-two patients underwent elective coronography because of ischemia. Theoretical PWV was calculated according to age, blood pressure and gender. The results were expressed as an index ((measured PWV-theoretical PWV)/theoretical PWV) for each patient. Ten patients presented with obstructive CAD, 16 patients had non-obstructive CAD and 16 patients had normal coronary angiography. PWV index and severity of CAD were positively correlated (P=0.001). All patients with obstructive CAD had a positive PWV index. When considering the PWV index retrospectively, the false positive results of cardiac stress test were significantly reduced (P<0.001). Twenty-three procedures may have been avoided in the present study cohort. The salient finding of this study was that in patients with known or suspected CAD, routinely followed aortic PWV index may be considered clinically useful for reducing the rate of unnecessary invasive angiographies. The clinical relevance of this individualized decision approach should be confirmed in a large-scale study. Prospective studies have the potential to evaluate the PWV index as a marker of CAD.

Longitudinal Study of Hypertensive Subjects With Type 2 Diabetes Mellitus: Overall and Cardiovascular Risk.

Despite adequate glycemic and blood pressure control, treated type 2 diabetic hypertensive subjects have a significantly elevated overall/cardiovascular risk. We studied 244 816 normotensive and 99 720 hypertensive subjects (including 7480 type 2 diabetics) attending medical checkups between 1992 and 2011. We sought to identify significant differences in overall/cardiovascular risk between hypertension with and without diabetes mellitus. Mean follow-up was 12.7 years; 14 050 all-cause deaths were reported. From normotensive to hypertensive populations, a significant progression in overall/cardiovascular mortality was observed. Mortality was significantly greater among diabetic than nondiabetic hypertensive subjects (all-cause mortality, 14.05% versus 7.43%; and cardiovascular mortality, 1.28% versus 0.7%). No interaction was observed between hemodynamic measurements and overall/cardiovascular risk, suggesting that blood pressure factors, even during drug therapy, could not explain the differences in mortality rates between diabetic and nondiabetic hypertensive patients. Using cross-sectional regression models, a significant association was observed between higher education levels, lower levels of anxiety and depression, and reduced overall mortality in diabetic hypertensive subjects, while impaired renal function, a history of stroke and myocardial infarction, and increased alcohol and tobacco consumption were significantly associated with increased mortality. Blood pressure and glycemic control alone cannot reverse overall/cardiovascular risk in diabetics with hypertension. Together with cardiovascular measures, overall prevention should include recommendations to reduce alcohol and tobacco consumption and improve stress, education levels, and physical activity.