Treating Femoral Artery Pseudoaneurysm by Tumescence Anesthesia and Echo-Guided Compression Technique (TACT): Clinical Outcome in 82 Consecutive Patients.

PURPOSE: Pseudoaneurysm (PA) of the access artery is a common and potentially severe complication after percutaneous endovascular interventions. Most PA require interventional therapy, including thrombin injection, covered stent implantation, or surgical repair, which are costly and associated with other complications. Treating PA by external compression is uncomfortable and time consuming, with a low success rate. By injecting local tumescence anesthesia around the PA and close to its neck, the tumescence anesthesia and echo-guided compression technique (TACT) aims to improve efficacy and patient's comfort. MATERIALS AND METHODS: We retrospectively reviewed all consecutive patients treated for femoral PA in our center from May 2009 to July 2019 and estimated efficacy and safety. Vascular specialists performed TACT according to a standardized protocol including ultrasound-guided injection of tumescence solution (45 ml of 0.9% saline, 15 ml of lidocaine 1%/epinephrine 5 µg/ml) in the soft tissue around the PA and its neck, local compression with the sonography probe until PA closure, and external compression by elastic belt for 3 hours. RESULTS: Among a total of 125 patients with femoral artery PA, 82 (65.6%) were treated by TACT (including 3 patients with haemorrhagic shock), 14 (11.2%) by thrombin injection; 12 (9.6%) by endovascular interventions; 8 (6.4%) by open surgery; and 9 (7.2%) conservatively. In patients treated by TACT, PA neck was short (<1 cm) in 51.8% and mean cavity diameter 30 ± 23 mm. After injection of 58 ± 8 ml of tumescence solution, mean time of echo-guided compression was 12 ± 8 minutes. Pseudoaneurysm was successfully closed in 92.7% after the first attempt and in 96.3% after the second attempt. The intervention was well tolerated, without any adverse event. CONCLUSION: Tumescence anesthesia and echo-guided compression technique (TACT) is an effective and safe treatment for PA. Compared to other therapies, TACT is minimally invasive and widely available for minimal costs, even for large PA and in unstable patients. CLINICAL IMPACT: Tumescence anesthesia and echo-guided compression technique seems to be an efficient, safe, and a fair economical choice in comparison with alternative techniques. The implementation of this procedure is simple with low risk of complications. Based on the results of this study, we believe that TACT should be considered as the first-line treatment of most iatrogenic PA.

Arterial Preparation by Longitudinal Micro-Incisions Before Balloon Angioplasty of the Superficial Femoral and Popliteal Artery: Acute and 12-Month Results.

PURPOSE: Percutaneous transluminal angioplasty (PTA) with conventional plain old balloon (POBA) and/or drug-coated balloon (DCB) is the primary intervention to treat peripheral artery stenoses. However, acute dissections during the procedure and potential for future target lesion revascularization remain procedural complications. The purpose of this study was to assess the acute and 12-month outcomes in patients who underwent novel vessel preparation with longitudinal, controlled-depth micro-incisions prior to PTA. MATERIALS AND METHODS: Patients with symptomatic lower extremity peripheral arterial disease with a Rutherford class of 2 to 6 and >70% de novo stenosis of the superficial femoral or popliteal arteries were included in this retrospective study. Patients with thrombotic or embolic lesions, restenosis, or in-stent restenosis were excluded. The FLEX Vessel Prep System (FLEX VP) was used to prepare the vessel prior to PTA by creating micro-incisions at the target lesion. The FLEX VP was followed by POBA or paclitaxel DCB. RESULTS: The study included 65 patients. Lesion characteristics were 90% median stenosis (range = 70%-100%), 75.4% mild-to-severe calcifications, and 33.8% occlusion rate, and median lesion length was 196 (range = 10-480) mm. Following vessel preparation, 82.1% of the patients had low severity dissection or no flow-limiting dissection. The provisional stent rate postprocedure was 16.9%, with a median stent length of 60 mm. The freedom from target lesion revascularization (FFTLR) in 63 evaluable patients at 6 and 12 months was 98.4% and 93.7%, respectively. Freedom from amputation was 100%. CONCLUSION: In this real-world/all-comers patient population with long, stenotic lesions across the calcification spectrum, vessel preparation with longitudinal micro-incisions prior to PTA was associated with low dissection rate, low dissection severity, low stent implantation, and high FFTLR with the absence of amputation at 12 months relative to published reports in long-lesion cohorts. These results support vessel preparation via micro-incisions.

Impact of concomitant popliteal vein thrombosis in patients with acute iliofemoral deep vein thrombosis treated with endovascular early thrombus removal.

Background: Catheter-based thrombus removal (CBTR) reduces the risk of moderate to severe post-thrombotic syndrome (PTS) in patients with acute iliofemoral deep vein thrombosis (IF-DVT). However, the impact of concomitant popliteal DVT on clinical and duplex sonographic outcomes is unknown. Patients and methods: In this post-hoc analysis including the entire cohort of the randomized controlled BERNUTIFUL trial (48 patients), we compared clinical (incidence/severity of PTS assessed by Villalta score and revised venous clinical severity scores, rVCSS), disease-specific quality-of-life (QOL, CIVIQ-20 survey) and duplex sonographic outcomes (patency, reflux, post-thrombotic lesions) at 12 months follow-up between patients with IF-DVT with and without concomitant popliteal DVT treated by CBTR. Results: Overall, 48 IF-DVT patients were included (48% men, median age of 50 years), of whom 17 (35%) presented with popliteal DVT. At baseline, patients with popliteal DVT were older, had a higher body mass index and more important leg swelling. At 12 months, freedom from PTS (93% vs 87%, P=0.17), median total Villalta score (1 vs 1.5; P=0.46), rVCSS (2 vs 1.5, P=0.5) and disease-specific QOL (24 points vs 24 points, P=0.72) were similar between patient with and without popliteal DVT, respectively. Duplex sonographic outcomes were similar, except for more frequent popliteal post-thrombotic lesions and reflux (P=0.02) in patients with popliteal DVT. Conclusions: Relevant clinical outcomes 1 year after successful CBTR were favorable, regardless of the presence or absence of concomitant popliteal DVT. However, post-thrombotic popliteal vein lesions and reflux are more frequent in IF-DVT patients with popliteal involvement. Their impact on long-term outcomes remains to be investigated.

Pulmonary Embolism and Deep Vein Thrombosis in COVID-19: A Systematic Review and Meta-Analysis.

Background The association of pulmonary embolism (PE) with deep vein thrombosis (DVT) in patients with coronavirus disease 2019 (COVID-19) remains unclear, and the diagnostic accuracy of D-dimer tests for PE is unknown. Purpose To conduct meta-analysis of the study-level incidence of PE and DVT and to evaluate the diagnostic accuracy of D-dimer tests for PE from multicenter individual patient data. Materials and Methods A systematic literature search identified studies evaluating the incidence of PE or DVT in patients with COVID-19 from January 1, 2020, to June 15, 2020. These outcomes were pooled using a random-effects model and were further evaluated using metaregression analysis. The diagnostic accuracy of D-dimer tests for PE was estimated on the basis of individual patient data using the summary receiver operating characteristic curve. Results Twenty-seven studies with 3342 patients with COVID-19 were included in the analysis. The pooled incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9; I2 = 0.93) and 14.8% (95% CI: 8.5, 24.5; I2 = 0.94), respectively. PE was more frequently found in patients who were admitted to the intensive care unit (ICU) (24.7% [95% CI: 18.6, 32.1] vs 10.5% [95% CI: 5.1, 20.2] in those not admitted to the ICU) and in studies with universal screening using CT pulmonary angiography. DVT was present in 42.4% of patients with PE. D-dimer tests had an area under the receiver operating characteristic curve of 0.737 for PE, and D-dimer levels of 500 and 1000 µg/L showed high sensitivity (96% and 91%, respectively) but low specificity (10% and 24%, respectively). Conclusion Pulmonary embolism (PE) and deep vein thrombosis (DVT) occurred in 16.5% and 14.8% of patients with coronavirus disease 2019 (COVID-19), respectively, and more than half of patients with PE lacked DVT. The cutoffs of D-dimer levels used to exclude PE in preexisting guidelines seem applicable to patients with COVID-19. © RSNA, 2020 Supplemental material is available for this article. See also the editorial by Woodard in this issue.

Incidence of gestational diabetes and birth complications in Switzerland: screening in 1042 pregnancies.

To evaluate the incidence of gestational diabetes mellitus (GDM), gestational glucose intolerance (GGI), and birth major complications, a population of 1042 pregnant women was screened after the end of the second trimester with a two-step screening method. Patients with a positive 50-g screening test (plasma glucose ≥ 7.8 mmol/l at 1 h) underwent a 3-h standard 100-g oral glucose tolerance test. Clinical records of patients and newborns were analysed and compared to normotolerant patients group. GDM was found in 4.8% and GGI in 2.6% of all screened women of this study population. The patient group with GDM significantly differed from control, with a higher proportion of Asiatic women (32.0% versus 2.9%, p = 0.001) and high prevalence of previous GDM (26.0% versus 0.0%, p < 0.001). Major neonatal complications occurred more frequently in the dysmetabolic groups compared to normotolerant group. Macrosomia was not noted in our population. Asiatic origin and previous GDM were strongly associated with an increased incidence of GDM in multivariate analysis. This study represents the first epidemiological evaluation of GDM/GGI in Switzerland, with a two-step screening method. Incidence of GDM and GGI as well as birth complications resulted significant in our country.

Severe acute kidney injury in a patient with renal artery stenosis of a single-functioning kidney: A case report of rapid normalisation of the renal function after percutaneous transluminal angioplasty with stent placement.

Revascularisation of renal arterial stenosis in acute settings, such as uncontrolled arterial hypertension, flash pulmonary oedema and/or acute renal failure, has shown controversial results in observational and prospective studies. Current guidelines do not recommend revascularisation in the occurrence of renal failure as revascularisation and best medical treatment have shown similar long-term outcomes on renal function. We describe a case of acute degradation of the renal function (with oligo-anuria and a peak creatinine of 462 µmol/L) after the re-introduction of an angiotensin-II receptor blocker (irbesartan) in a 66-year-old Caucasian diabetic male patient with bilateral renal stenosis and a right-sided single-functioning kidney, with a rapid improvement of the renal function which normalized 5 days after percutaneous angioplasty and stenting of the right renal artery.

[Folie à deux - Thrombosis and Infections]. / Folie à deux ­ Thrombose und Infektionen.

Folie à deux - Thrombosis and Infections Abstract: Although infections are not represented in the Revised Geneva or Wells score, they increase the risk of venous thromboembolism (VTE) similarly to the known risk factors (immobilization, major surgery, active neoplasia). This increased risk of VTE can persist for six to twelve months after infection; moreover, the more severe the infection, the higher the risk of VTE may be. In addition to VTEs, infections can promote arterial thromboembolism. For example, 20% of pneumonias are accompanied by an acute cardiovascular event (acute coronary syndrome, heart failure, atrial fibrillation). In the case of infection-associated atrial fibrillation, the CHA2DS2 VASc score remains an appropriate guide for the indication of anticoagulation.

The effect of valsartan versus non-RAAS treatment on autoregulation of cerebral blood flow.

BACKGROUND: Cerebral autoregulation (CA) is a protective mechanism which maintains the steadiness of the cerebral blood flow (CBF) through a broad range of systemic blood pressure (BP). Acute hypertension has been shown to reduce the cerebrovascular adaptation to BP variations. However, it is still unknown whether CA is impaired in chronic hypertension. This study evaluated whether a strict control of BP affects the CA in patients with chronic hypertension, and compared a valsartan-based regimen to a regimen not inhibiting the renin-angiotensin-aldosterone system (non-RAAS). METHODS: Eighty untreated patients with isolated systolic hypertension were randomized to valsartan 320 mg or to a non-RAAS regimen during 6 months. The medication was upgraded to obtain BP <140/90 mm Hg. Continuous recordings of arterial BP and CBF velocity (transcranial Doppler) were performed during periods of 5 minutes, at rest, and at different levels of alveolar CO(2) pressure provided by respiratory maneuvers. The dominant frequency of CBF oscillations was determined for each patient. Dynamic CA was measured as the mean phase shift between BP and CBF by cross-spectral analysis in the medium frequency and in the dominant CBF frequency. RESULTS: Mean ambulatory 24-hour BP fell from 144/87 to 127/79 mm Hg in the valsartan group and from 144/87 to 134/81 mm Hg in the non-RAAS group (p = 0.13). Both groups had a similar reduction in the central BP and in the carotido-femoral pulse wave velocity. The average phase shift between BP fluctuations and CBF response at rest was normal at randomization (1.82 ± 0.08 s), which is considered a preserved autoregulation and increased to 1.91 ± 0.12 s at the end of study (p = 0.45). The comparison of both treatments showed no significant difference (-0.01 ± 0.17 s vs. 0.16 ± 0.16 s, p = 0.45) for valsartan versus non-RAAS groups. The plasmatic level of glycosylated hemoglobin decreased in the valsartan arm compared to the non-RAAS arm (-0.23 ± 0.06 vs. -0.08 ± 0.07%, p = 0.07). CONCLUSIONS: In elderly hypertensive men with isolated chronic systolic hypertension, CA seems efficient at baseline and is not significantly affected by 6 months of BP-lowering treatment. This suggests that the preventive effects of BP medication against stroke are not mediated through a restoration of the CA.

Reduction of small infrarenal abdominal aortic aneurysm expansion rate by statins.

BACKGROUND: To evaluate the effect of statins on the annual expansion rate (ER) of small infrarenal abdominal aortic aneurysms (AAA). PATIENTS AND METHODS: All patients under regular surveillance for small AAA between January 2000 and September 2007, in the Department of Angiology, Lausanne University Hospital, were included. Inclusion criteria were baseline abdominal aortic diameter between 25 and 55 mm, at least two measurements of AAA diameter and a minimum follow up of 6 months. Patients with Marfan disease, infectious or inflammatory AAA, and patients with prior AAA repair were excluded. The influence of statin use and other factors on ER were examined by bivariate and multivariate analysis. RESULTS: Among 589 patients who underwent an abdominal aorta evaluation, 94 patients (89 % men, mean age 69.1 years) were finally included in the analysis. Baseline AAA size was 39.9 ± 7.7 mm (mean±SE) and 48.7 ± 8.4 mm at end of follow-up. Patients had a regular aneurysm size assessment during 38.5 ± 27.7 months. Mean ER was 3.59 mm/y (± 2.81). The 50 patients who were treated with statin during the study period had a lower ER compared to the 44 controls (2.91 vs 4.37 mm/year, p = 0.01). CONCLUSIONS: This study confirms the considerable individual variations in the AAA expansion rate, and emphasizes the need for regular aortic diameter assessments. In this study, patients treated with statin demonstrate a significant decrease in the ER compared to controls. This finding need to be evaluated in prospective interventional studies powered to demonstrate the potential benefit of statin treatment.

Major adverse limb events in patients with femoro-popliteal and below-the-knee peripheral arterial disease treated with either sirolimus-coated balloon or standard uncoated balloon angioplasty: a structured protocol summary of the "SirPAD" randomized controlled trial.

BACKGROUND: Peripheral arterial disease is a progressive atherosclerotic disease with symptoms ranging from an intermittent claudication to acute critical limb ischemia and amputations. Drug-coated balloons and stents were developed to prevent neo-intimal proliferation and restenosis after percutaneous transluminal angioplasty. Randomized controlled trials showed that drug-coated, notably paclitaxel-coated, devices reduce restenosis, late lumen loss, and the need for target lesion re-vascularization compared with uncoated ones. However, the size of these trials was too small to prove superiority for "hard" clinical outcomes. Moreover, available studies were characterized by too restrictive eligibility criteria. Finally, it remains unclear whether paclitaxel-coated balloons may impair long-term survival. Alternative drug-coated balloons, the so-called limus-based analogs, have been approved for clinical use in patients with peripheral arterial disease. By encapsulating sirolimus in phospholipid drug nanocarriers, they optimize adhesion properties of sirolimus and provide better bioavailability. METHODS: In this investigator-initiated all-comer open-label phase III randomized controlled trial, we will evaluate whether sirolimus-coated balloon angioplasty is non-inferior and eventually superior, according to a predefined hierarchical analysis, to uncoated balloon angioplasty in adults with infra-inguinal peripheral arterial disease requiring endovascular angioplasty. Key exclusion criteria are pregnancy or breastfeeding, known intolerance or allergy to sirolimus, and participation in a clinical trial during the previous 3 months. The primary efficacy outcome is the composite of two clinically relevant non-subjective "hard" outcomes: unplanned major amputation of the target limb and endovascular or surgical target lesion re-vascularization for critical limb ischemia occurring within 1 year of randomization. The primary safety outcome includes death from all causes. DISCUSSION: By focusing on clinically relevant outcomes, this study will provide useful information on the efficacy and safety of sirolimus-coated balloon catheters for infra-inguinal peripheral arterial disease in a representative ("all-comer") population of unselected patients. As regulatory agencies had raised safety concerns in patients exposed to paclitaxel-coated devices (versus uncoated ones), collect mortality data up to 5 years after randomization will be collected. TRIAL REGISTRATION: ClinicalTrials.gov NCT04238546.

[Aortic calcification and the risk of osteoporotic fractures]. / Calcification des grandes artères et risque de fracture ostéoporotique.

Osteoporosis and atherosclerosis seem to be epidemiologically correlated. Several medical conditions are risk factors for both osteoporosis and atheromatosis (i.e. age, diabetes, end stage renal disease, sedentarity, smoking), but a common pathogenic link may be present beyond this. The burden of cardiovascular events and of osteoporotic fracture is considerable for the health care system in term of costs and resources. However, both diseases are rarely managed together. This article is a review of the recent studies in this new field.

Lower limb high arterial flow induced by tenofovir and emtricitabine treatment.

Here, we describe a case of an HIV-infected patient with right lower limb oedema that appeared after initiation of tenofovir and emtricitabine treatment. The patient was fully investigated by serial heart and vessel echo-Doppler examination. Oedema of the lower limb was attributed to a transient drug-induced fivefold increase in peripheral artery flow, which was induced by a reduction in peripheral arterial resistance. The possible mechanisms of disease are discussed.

[Cardiovascular markers]. / Marqueurs cardiovasculaires.

Despite enormous progress made in cardiovascular prevention and treatment, sudden death remains the first manifestation of ischemic heart disease for too many subjects. A better individual cardiovascular risk assessment would definitely help select the most efficacious interventions allowing to prevent the development of atherosclerosis and its complications. Risk scores, although not used as frequently as expected in everyday practice are a first step towards helping decision making to reduce cardiovascular diseases. The use of vascular markers for early atherosclerosis detection should be even more profitable to reduce CV diseases. Pulse wave velocity, intima-media thickness and ankle brachial index measurements are among the most simple and promising markers of early vascular disease are discussed briefly in this paper.

[Medical therapy in peripheral arterial occlusive disease]. / Traitement médicamenteux de l'artériopathie périphérique.

Atherosclerotic peripheral arterial disease (PAD) is often asymptomatic. If symptomatic, patients present intermittent claudication, ischemic rest pain or tissue necrosis. The prevalence of PAD increases with age and affects about 2% of patients at 60 years. Patients with PAD have an increased risk of coronary or cerebro-vascular events. Measure of the ankle-brachial index (ABI) allows early detection of asymptomatic patients, and allows early preventive interventions, in order to reduce their cardio-vascular risk. The most important interventions are smoking cessation, normalisation of blood pressure and lipid levels, and introduction of an antiplatelet agent, such as aspirin 75 to 160 mg/d.

Enhanced Thrombolysis by Ultrasound-Assisted Catheter-Directed Thrombolysis and Microbubbles in an In Vitro Model of Iliofemoral Deep Vein Thrombosis.

There is a need to improve the efficacy and safety of catheter-directed thrombolysis (CDT) for thrombo-occlusive diseases, and ultrasound-assisted CDT (USAT) is a promising approach. We tested if thrombolysis efficacy of USAT can be improved by adding gaseous microbubbles (MB). We developed an in vitro dynamic overflow model for iliofemoral deep vein thrombosis, and added MB to an USAT system with ultrasound energy and dose of tissue plasminogen activator according to clinical practice. A total of 64 clots (mean baseline weight of 8.23 ± 1.12 g, generated from citrated human whole blood from 7 healthy male volunteers) were randomly assigned to 1 of 4 study protocols of 30 minutes' duration: negative control, CDT, USAT, and USAT + MB.Thrombolysis efficacy was assessed by measuring the change in D-dimer levels in the overflow liquid and the percentage of clot weight reduction. Compared to negative control, change in D-dimer increased by 62% (p = 0.017), 128% (p = 0.002), and 177% (p < 0.001) in the CDT, USAT, and USAT + MB groups, respectively. D-dimer increase was greater in the USAT than in the CDT group (p = 0.014), and greater in the USAT + MB than in the USAT group (p = 0.033). Compared to negative control, percentage of clot weight reduction increased by 123% (p = 0.016), 154% (p = 0.002), and 233% (p < 0.001) in the CDT, USAT, and USAT + MB groups, respectively. Percentage of clot weight reduction was greatest in the USAT + MB group (p < 0.05 compared with all other groups). In conclusion, our in vitro study suggests that the thrombolytic efficacy of USAT in human whole blood clots can be improved by local administration of MB.

High prevalence of peripheral arterial disease in HIV-infected persons.

BACKGROUND: Atherosclerosis has been assessed in human immunodeficiency virus (HIV)-infected persons by using various methods. Peripheral arterial disease (PAD) has not been evaluated, however. We studied the cross-sectional prevalence of lower limb PAD in an HIV-infected population. METHODS: PAD was assessed using the Edinburgh Claudication Questionnaire and by measuring the systolic ankle-brachial blood pressure index (ABI) at rest and after exercise. Patients with PAD were further evaluated by duplex scan of lower limb arteries. RESULTS: Ninety-two consecutive HIV-infected patients were evaluated (23.9% women; mean age, 49.5 years; 61.9% current smokers). Claudication was reported by 15.2% of the patients. PAD was found in 20.7% of the patients: 9.8% had an abnormal ABI (<0.90) at rest, and 10.9% had normal ABI at rest but a >25% decrease after exercise. Of the patients with PAD, 84.2% were investigated with duplex scan, all of whom had atherosclerotic occlusions or stenoses of the iliac or femoral arteries. Age, diabetes, smoking, and low CD4+ T lymphocyte counts were identified as independent predictors of PAD. CONCLUSIONS: The prevalence of symptomatic and asymptomatic PAD is high in the HIV-infected population and is much higher than expected (prevalence in the general population, approximately 3% at 60 years). This study suggests the presence of an epidemic of PAD approximately 20 years earlier in the HIV-infected than in the general population. Larger epidemiological studies are needed to better define risk factors and to evaluate whether PAD is associated with increased mortality, as it is in the general population.

Rivaroxaban or vitamin-K antagonists following early endovascular thrombus removal and stent placement for acute iliofemoral deep vein thrombosis.

BACKGROUND: The optimal anticoagulant following catheter-based therapy of acute iliofemoral deep vein thrombosis (IFDVT) is unknown. METHODS: From the Swiss Venous Stent registry, an ongoing prospective cohort study, we performed a subgroup analysis of patients with acute IFDVT who underwent catheter-based early thrombus removal followed by nitinol stent placement. Duplex ultrasound and Villalta scores were used to determine patency rates and incidence of the post-thrombotic syndrome (PTS) in patients treated with either rivaroxaban (n = 73) or a vitamin K-antagonist (VKA; n = 38) for a minimum duration of 3 months. RESULTS: Mean follow-up duration was 24 ±â€¯19 months (range 3 to 77 months). Anticoagulation therapy was time-limited (3 to 12 months) in 56% of patients (47% in the rivaroxaban group and 58% in the VKA group, p = 0.26), with shorter mean duration of anticoagulation in the rivaroxaban group (180 ±â€¯98 days versus 284 ±â€¯199 days, p = 0.01). Overall, primary and secondary patency rates at 24 months were 82% (95%CI, 71-89%) and 95% (95%CI, 87-98%), respectively, with no difference between the rivaroxaban (87% [95%CI, 76-94%] and 95% [95%CI, 85-98%]) and the VKA group (72% [95%CI, 52-86%] and 94% [95%CI, 78-99%]; p > 0.10 for both). Overall, 86 (86%) patients were free from PTS at latest follow-up, with no difference between the rivaroxaban and the VKA groups (57 [85%] versus 29 [88%]; p = 0.76). Two major bleeding complications (1 in each group) occurred in the peri-interventional period, without any major bleeding thereafter. CONCLUSIONS: In patients with acute IFDVT treated with catheter-based early thrombus removal and venous stent placement, the effectiveness and safety of rivaroxaban and VKA appear to be similar. CLINICAL TRIAL REGISTRATION: The study is registered on the National Institutes of Health website (ClinicalTrials.gov; identifier NCT02433054).

Are circulating endothelial-derived and platelet-derived microparticles a pathogenic factor in the cisplatin-induced stroke?

BACKGROUND AND PURPOSE: To evaluate whether cisplatin-induced stroke is mediated by vascular toxicity with release of prothrombotic endothelial and platelet-derived microparticles (MPs). METHODS: Endothelial (CD31(+)CD41(-)), platelets (CD31(+)CD41(+)) and prothrombotic (Annexin V(+)) circulating MPs were quantified by flow cytometry in 18 patients with cancer, before and 3 days after administration of cisplatin, and compared with 18 healthy controls. Thrombin-antithrombin complex and prothrombin fragments (F(1+2)) were measured as markers of the activation of the coagulation. RESULTS: In patients with cancer, baseline levels of circulating prothrombotic, endothelial and platelet-derived MPs were similar to healthy controls and decreased significantly after administration of cisplatin. High-baseline MPs levels were observed in 5 patients who received cisplatin for a second or third cycle. A high-baseline activation of the coagulation was observed in all patients without further increase after cisplatin infusion. CONCLUSIONS: Cisplatin treatment is immediately followed by a decrease in circulating levels of endothelial and platelet-derived MPs. However, a transient increase in MPs is observed at the second and third infusion, and this may contribute to the cisplatin-induced stroke.

Associations of baroreflex sensitivity, heart rate variability, and initial orthostatic hypotension with prenatal and recent postnatal methylmercury exposure in the Seychelles Child Development Study at age 19 years.

BACKGROUND: A few studies have suggested an association between prenatal exposure to methylmercury and decreased heart rate variability (HRV) related to autonomic heart function, but no study has examined this association using baroreflex sensitivity (BRS). In this study we assessed the distribution of BRS and immediate orthostatic hypotension (IOH) in young Seychellois adults and their associations with exposure to prenatal and recent postnatal methylmercury. METHODS: Subjects in the Seychelles Child Development Study (SCDS) main cohort were evaluated at age 19 years. Non-invasive beat-to-beat blood pressure (BP) monitoring (Finapres, Ohmeda) was performed at rest and during active standing in 95 consecutive subjects. Recent postnatal mercury exposure was measured in subjects' hair at the age of 19 years and prenatal exposure in maternal hair grown during pregnancy. BRS was estimated by sequence analysis to identify spontaneous ascending and descending BP ramps. HRV was estimated by the following markers: PNN50 (relative numbers of normal-to-normal intervals which are shorter by more than 50 ms than the immediately following normal-to-normal intervals); rMSSD (root mean of the squared sum of successive interval differences); LF/HF (low frequency/high frequency component ratio); ratio of the mean expiratory/inspiratory RR intervals (EI ratio); and the ratio between the longest RR interval 30 s after active standing and the shortest RR interval at 15 s (Max30/Min15). IOH was estimated by the deepest BP fall within the first 15 s after active standing up. RESULTS: Prenatal MeHg exposures were similar in boys and girls (6.7±4.3, 6.7±3.8 ng/g) but recent postnatal mercury levels were higher in males than females (11.2±5.8 vs 7.9±4.3 ng/g, p=0.003). Markers of autonomic heart rate control were within the normal range (BRS: 24.8±7 ms/mm Hg, PNN50: 24.9±6.8%, rMSSD: 68±22, LF/HF: 0.61±0.28) in both sexes. After standing, 51.4% of subjects had a transient systolic BP drop>40 mm Hg, but only 5.3% reported dizziness or had syncope. Prenatal and recent postnatal MeHg levels, overall, were not associated with BRS, E/I ratio, PNN50, rMSSD, LF/HF ratio, Max30/Min15 ratio, and IOH. CONCLUSIONS: This study provides no support for the hypothesis that prenatal or recent postnatal MeHg exposure from fish consumption is associated with impaired autonomic heart rate control.