[Early identification of a clustered epidemic of typhoid fever through pathogen molecular subtyping monitoring].

Objective: To identify a suspected clustered Typhoid fever by whole genome sequencing(WGS) and pulsed field gel electrophoresis (PFGE) subtyping. Methods: The nature of the epidemic was determined by combination of subtyping results of isolates and epidemiological information. Results: Five S. typhimurium isolates showed identical PFGE patterns and almost the same whole genome sequence. Epidemiological survey showed that five cases had dined in the same restaurant on the same day. Conclusion: Combined with the longest incubation period of typhoid fever, molecular subtyping of pathogenic bacteria and the field epidemiological survey, it can be preliminarily determined that the five cases have common infection sources.

Training to Perform Ankle-Brachial Index: Systematic Review and Perspectives to Improve Teaching and Learning.

OBJECTIVE: To conduct a systematic review focusing on the impact of training programs on ankle-brachial index (ABI) performance by medical students, doctors and primary care providers. Lower extremity peripheral artery disease (PAD) is a highly prevalent disease affecting ∼202 million people worldwide. ABI is an essential component of medical education because of its ability to diagnose PAD, and as it is a powerful prognostic marker for overall and cardiovascular related mortality. METHODS: A systematic search was conducted (up to May 2015) using Medline, Embase, and Web of Science databases. RESULTS: Five studies have addressed the impact of a training program on ABI performance by either medical students, doctors or primary care providers. All were assigned a low GRADE system quality. The components of the training vary greatly either in substance (what was taught) or in form (duration of the training, and type of support which was used). No consistency was found in the outcome measures. CONCLUSION: According to this systematic review, only few studies, with a low quality rating, have addressed which training program should be performed to provide the best way of teaching how to perform ABI. Future high quality researches are required to define objectively the best training program to facilitate ABI teaching and learning.

Clinical Interest of Ambulatory Assessment of Physical Activity and Walking Capacity in Peripheral Artery Disease.

The purpose of the present review was to provide, for the first time, a comprehensive analysis and synthesis of the available studies that highlighted the clinical interest of the ambulatory assessment of either physical activity (PA) or walking capacity in patients with lower extremity peripheral artery disease (PAD). We identified 96 related articles published up to March 2015 through a computer-assisted search of the MEDLINE, EMBASE, and Web of Science databases. Ambulatory-measured PA or related energy expenditure (EE) in PAD patients was performed in 87 of the 96 included studies. The main clinical interests of these measurements were (a) the assessment of PA/EE pattern; (b) the characterization of walking pattern; and (c) the control of training load during home-based walking programs. Ambulatory-measured walking capacity was performed in the remaining studies, using either Global Positioning System receivers or the Peripheral Arterial Disease Holter Control device. Highlighted clinical interests were (a) the assessment of community-based walking capacity; (b) the use of new outcomes to characterize walking capacity, besides the conventional absolute claudication distance; and (c) the association with the patient's self-perception of walking capacity. This review also provides for the clinicians step-by-step recommendations to specifically assess PA or walking capacity in PAD patients.

Evidence for a vasomotor cyclo-oxygenase dependent mechanism of sensitization at the cutaneous level.

AIMS: Current-induced vasodilation (CIV) is an axon-reflex response observed during monopolar current application such as iontophoresis. Cyclo-oxygenase derivates (COD) participate in CIV and act as sensitizing agents at the anodal level. Mechanisms involved during cathodal current application (CCA) are partially unknown. In a randomized double-blind crossover trial, we tested in 16 healthy subjects (i) the influence of the inter-stimulation interval (I-I) by comparing CIV following all-at-once 10 s CCA against 2 × 5 s CCA with intervals ranging from15 s-16 min and (ii) the participation of COD in CIV using 1 g aspirin or placebo intake. METHODS: Measurements were repeated 2 h and 14 days after treatment. Laser Doppler flowmetry assessed cutaneous blood flow, reported in multiples of baseline. RESULTS: Before treatment, peak vasodilation 10 min after the last current application (CVCstim2 ) increased compared with baseline whatever the I-I. Increase in CVCstim2 from baseline was greater for the 4 min (9.4 (5.3, 10.9) times; median (1(st) percentile, 3(rd) percentile)) and higher I-Is compared with all-at-once delivery (3.0 (2.1, 4.3) times, P < 0.05). The response was similar after placebo but aspirin abolished this vasodilation (increase by 1.2 (1.1, 1.3) times for all-at-once delivery and by 1.5 (1.3, 1.7) ± 0.3 times for 4 min interval, 2 h after aspirin intake) that recovered after 14 days. CONCLUSIONS: This confirms the participation of COD in CIV with CCA and their sensitizing action. This model can represent an attractive way to study the axon-reflex and sensitizing function of COD in humans.

Safety and accuracy of endovascular aneurysm repair without pre-operative and intra-operative contrast agent.

BACKGROUND: Severe chronic kidney disease is a major limitation for endovascular aortic aneurysm repair (EVAR). The aim of this study is to assess the safety and accuracy of fusion imaging, when performing EVAR in the absence of pre- and intra-operative contrast agents. METHODS: From October 2013 to February 2014, every patient requiring EVAR and presenting with severe chronic renal impairment underwent a specific pre-operative imaging assessment, based on a non-enhanced CT scan. Centrelines were manually extracted and key points were placed at the landing zones. In house software makes it possible to artificially enhance the contrast between vascular structures and the surrounding tissue, by increasing the values attributed to the vascular structure voxels (500 Hounsfield units). EVAR was performed in a hybrid room (Zeego, Siemens), and the artificially enhanced CT scan was used for the construction of fusion imaging. The 3D vascular volume, together with the centrelines and key points, was overlaid onto the 2D live fluoroscopic image. RESULTS: Six patients (mean age 77.1 years) were treated by EVAR (5 abdominal aneurysms and 1 thoracic aneurysm), using fusion imaging without a contrast agent. The median pre-operative estimated glomerular filtration rate (eGFR) was 17.5 mL/min/1.73 m2. No contrast was used during the procedure. No intra-operative endoleak was observed on the duplex scan. No deterioration was observed in the eGFR at 1 week (eGFR = 21.7, p = .49), nor at 1 month follow up (eGFR = 21, p = .28). The stent graft positioning error was assessed in terms of the difference between the effective and planned landing zones, measured on pre- and post-operative CT scans. The mean error was 1.3 mm at the proximal landing zone, and 6.5 mm at the distal landing zone. CONCLUSION: EVAR without the use of pre-operative and intra-operative contrast agents appears to be safe and accurate for patients with severe chronic kidney disease.

In-silico trial emulation to predict the cardiovascular protection of new lipid-lowering drugs: an illustration through the design of the SIRIUS programme.

INTRODUCTION: Inclisiran, an siRNA targeting hepatic PCSK9 mRNA, administered twice-yearly (after initial and 3-month doses), substantially and sustainably reduced LDL-cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a reduced risk of major adverse cardiovascular events (MACE) is not yet established. In-silico trials applying a disease computational model to virtual patients receiving new treatments allow to emulate large scale long term clinical trials. The SIRIUS in-silico trial programme aims to predict the efficacy of inclisiran on CV events in individuals with established atherosclerotic cardiovascular disease (ASCVD). METHODS: A knowledge-based mechanistic model of ASCVD was built, calibrated, and validated to conduct the SIRIUS programme (NCT05974345) aiming to predict the effect of inclisiran on CV outcomes.The SIRIUS Virtual Population included patients with established ASCVD (previous myocardial infarction (MI), previous ischemic stroke (IS), previous symptomatic lower limb peripheral arterial disease (PAD) defined as either intermittent claudication with ankle-brachial index <0.85, prior peripheral arterial revascularization procedure, or vascular amputation) and fasting LDL-C ≥ 70 mg/dL, despite stable (≥ 4 weeks) well-tolerated lipid lowering therapies.SIRIUS is an in-silico multi-arm trial programme. It follows an idealized crossover design where each virtual patient is its own control, comparing inclisiran to 1) placebo as adjunct to high-intensity statin therapy with or without ezetimibe, 2) ezetimibe as adjunct to high-intensity statin therapy, 3) evolocumab as adjunct to high-intensity statin therapy and ezetimibe.The co-primary efficacy outcomes are based on time to the first occurrence of any component of 3P-MACE (composite of CV death, nonfatal MI or nonfatal IS) and time to occurrence of CV death over 5 years. PERSPECTIVES/CONCLUSION: The SIRIUS in-silico trial programme will provide early insights regarding a potential effect of inclisiran on MACE in ASCVD patients, several years before the availability of the results from ongoing CV outcomes trials (ORION-4 and VICTORION-2-P).

The SIRIUS in-silico trial programme is a knowledge-based computer model built to simulate the biological and clinical long-term effects of inclisiran, an siRNA targeting hepatic PCSK9 mRNA, on virtual patients with cardiovascular disease. Key Findings: The model accurately replicates the biological processes of cardiovascular disease and the impact of lipid-lowering therapies, allowing for the prediction of randomized clinical trials.Simulating clinical trials with virtual patients can provide insights into the efficacy and safety of new treatments before the results of randomized clinical trials, potentially speeding up the drug development process.

Cutaneous microvascular functional assessment during exercise: a novel approach using laser speckle contrast imaging.

Cardiovascular diseases are often revealed during exercise and are associated with cutaneous blood flow (CBF) dysfunction. Studies of CBF during exercise are consequently of interest. Laser speckle contrast imaging (LSCI) allows for non-contact and real-time recording of CBF at rest. We tested whether LSCI could allow the study of CBF during a cycling exercise using a specific signal treatment procedure that removes movement-induced artefacts from the LSCI raw signal. We recorded the baseline CBF and peak post-occlusive reactive hyperaemia (PORH) from the cutaneous forearm using LSCI and the mean blood pressure before and during cycling (80 W at 70 rpm) in nine healthy subjects. We determined the cross-correlation coefficient r between LSCI traces obtained before and during cycling and before and after a specifically designed signal processing technique. The results are presented as the median (25th-75th centile) and expressed as the cutaneous vascular conductance (laser speckle perfusion units (LSPU) per millimetre of mercury). Cross-correlation r increased from 0.226 ± 0.140 before to 0.683 ± 0.170 after post-processing. After signal processing, the peak PORH during exercise was reduced [0.38 (0.30-0.52) LSPU/mmHg] compared with the peak PORH during the non-exercise phase [0.69 (0.63-0.74) LSPU/mmHg, p < 0.01], whereas no difference was found between the baseline values. With adequate signal processing, LSCI appears valuable for investigating CBF during exercise. During constant-load lower limb cycling exercise, the upper limb peak PORH is reduced compared with the peak PORH during non-exercise. The underlying mechanisms warrant further investigations in both healthy (trained) subjects and diseased (e.g., coronary heart disease) patients.

Exercise treadmill testing in patients with claudication, with and without diabetes.

AIM: To compare symptoms and walking capacities of patients with and without diabetes reporting vascular-type claudication. METHODS: We recorded self-reported maximal walking distance, maximal walking distance on treadmill test (3.2 km h(-1) , 10% slope), exercise transcutaneous oxygen pressure DROP index [limb transcutaneous oxygen pressure (TcpO2) changes from rest minus chest TcpO2 changes from rest] and symptoms on treadmill in 230 patients with diabetes and 982 patients without diabetes. Exercise-induced proximal and distal symptoms were analysed in the perspective of underlying proximal and distal ischaemia (DROP value < negative 15 mmHg). RESULTS: Self-reported maximal walking distance did not differ between groups, whereas maximal walking distance on treadmill test was lower in patients with diabetes vs. patients without diabetes (261 ± 257 and 339 ± 326 m, respectively; P < 0.05 when adjusted for potential confounders). In patients with ischaemia, the number of ischaemic areas (proximal and/or distal on right and/or left) was comparable between the two groups. Patients with diabetes had more distal ischaemia than patients without diabetes (38 vs. 29%, respectively; P < 0.01), whereas proximal ischaemia was similar between groups. The prevalence of lower-limb exercise-related symptoms without ischaemia was comparable between groups. There were more symptoms other than lower-limb pain in patients with diabetes than patients without diabetes (29.6 vs. 18.3%, respectively; P < 0.01). CONCLUSIONS: Patients with diabetes show more severe limitation on the treadmill and more non-limb symptoms than patients without diabetes, although self-reported walking capacity is comparable between the two groups. Using TcpO2, we confirm that patients with diabetes reporting claudication show more distal ischaemia than patients without diabetes, with no difference at the buttock level. Treadmill testing is of interest in patients with peripheral artery disease and diabetes.

Patency of direct revascularisation of the hypogastric arteries in patients with aortoiliac occlusive disease.

OBJECTIVES: Various indications for internal iliac artery (IIA) revascularisation have been reported. Revascularisations for gluteal ischaemia and buttock claudication remain controversial and uncommon. The objective of the study was to assess the patency of direct conventional revascularisations (CRs) of the IIA in patients with aortoiliac occlusive disease because few studies have focussed on this specific topic. MATERIALS AND METHODS: The charts of all patients who underwent CR of the IIA, between August 2000 and January 2009, were retrospectively reviewed. We recorded for each patient preoperative vascular work-up. All patients were tested for patency on January 2009. A computed tomography (CT) scan was requested if the duplex scan casts any doubt with regard to patency. If non-patent, the last date for confirmed patency was kept for the analysis. Functional outcomes at the proximal level were also collected. RESULTS: We studied 40 patients with occlusive disease. Buttock claudication was observed in 27 patients (66%), including eight (20%) in whom these symptoms were isolated. The 13 other patients had distal claudication or rest pain and documented proximal ischaemia, justifying the IIA revascularisations. We performed 44 conventional direct revascularisations of the IIA concomitant to aorto- or iliofemoral bypasses in these patients. The overall postoperative patency rate was 89%. Five early occlusions of the IIA remained asymptomatic. The median duration of follow-up was 39 months (3-86 months). The survival rate was 95% at 1 year and 86% at 5 years. The primary patency rate of the IIA was 89% at 1 year and 72.5% at 5 years. Buttock claudication disappeared in 23 of the 27 patients (85%), who were symptomatic at the proximal level prior to surgery. CONCLUSION: Direct IIA concomitant revascularisation has an acceptable patency rate in patients undergoing aorto- or iliofemoral bypasses for occlusive disease. When feasible, this technique appears to be safe for the treatment and prevention of buttock claudication.

Limitations of self-reported estimates of functional capacity using the Walking Impairment Questionnaire.

OBJECTIVE: A potential issue with the Walking Impairment Questionnaire (WIQ) is that it is relatively complex. We estimated the number of errors made by patients when self-completing the WIQ, and assessed the benefit of correcting missing, duplicate or paradoxical (i.e., reported lower difficulty for a higher-intensity task) answers. DESIGN: Prospective non-interventional study. MATERIALS: All consecutive new patients with claudication over a 3-month period. METHODS: The WIQ was self-completed before patients performed a constant-load treadmill walking test (maximised to 750 m). MAIN OUTCOME MEASURE: We analysed the coefficient of determination of the linear relationship between overall WIQ score (mean of the available subscales when at least two subscales are available) and treadmill maximal walking distance (MWD), before and after correction of errors. RESULTS: We studied 73 patients. Thirty-seven questionnaires had to be corrected for one or more errors. The coefficient of determination between the overall WIQ score and MWD was R(2) = 0.391 (n = 56) and R(2) = 0.426 (n = 73) before and after correction, respectively. CONCLUSION: Supervision of self-completed WIQs detects errors in almost half of the questionnaires, resulting in a missing overall WIQ score in 23% of cases among uncorrected questionnaires. The overall WIQ score correlates only moderately with MWD, even after correction. CLINICAL TRIAL REGISTRATION: NIH database: NCT01114178.

Functional outcome of hypogastric revascularisation for prevention of buttock claudication in patients with peripheral artery occlusive disease.

We have defined proximal lower limb ischaemia as a decrease in Exercise-transcutaneous oxygen pressure (TcPO(2)) lower than minus 15mmHg at the buttock level in patients with peripheral artery occlusive disease. The purpose of this study was to objectively evaluate the benefits of direct versus indirect revascularisation of internal iliac arteries (IIAs) for prevention of buttock claudication in this population. We retrospectively reviewed the charts of proximal ischaemia patients who underwent revascularisation and both preoperative and postoperative stress TcPO(2) testing. Revascularisation procedures were classified as either direct revascularisation, including percutaneous transluminal angioplasty and internal iliac artery bypass, resulting in a direct inflow in a patent IIA (group 1) or indirect revascularisation, including aortobifemoral bypass and recanalisation of the femoral junction on the ischaemic side, resulting in indirect inflow from collateral arteries in the hypogastric territory (group 2). Patency was checked 3 months after revascularisation in all cases. Treadmill exercise stress tests were performed before and after revascularisation using the same protocol designed to assess pain, determine maximum walking distance (MWD) and measure TcPO(2) during exercise. In addition, ankle-brachial indices (ABIs) were calculated. Between May 2001 and March 2008, a total of 93 patients with objectively documented proximal ischaemia underwent 145 proximal revascularisation procedures using conventional open techniques in 109 cases and endovascular techniques in 36. Direct revascularisation was performed on 50 limbs (35%) (group 1) and indirect revascularisation on 95 limbs (65%) (group 2). The mean interval between revascularisation and stress testing was 60+/-74 days preoperatively and 149+/-142 days postoperatively. No postoperative thrombosis was observed. Buttock claudication following revascularisation was more common in group 2 (p<0.001). No difference was observed between the two groups with regard to improvement in MWD (365 / 294 m) and ABI (0.20/0.22). Disappearance of proximal ischaemia was more common after direct revascularisation (p<0.01). The extent of lesions graded according to the TASC II classification appeared not to be predictive of improvement in assessment criteria following revascularisation. Conversely, patency of the superficial femoral artery was correlated with improvement (p<0.01). This study indicates that direct revascularisation, if feasible, provides the best functional outcome for prevention of buttock claudication.

Discordance of peripheral artery disease diagnosis using exercise transcutaneous oxygen pressure measurement and post-exercise ankle-brachial index.

In patients with exertional limb symptoms and normal ankle-brachial index (ABI) at rest, exercise testing can be used to diagnose lower extremity arterial disease (LEAD). Post-exercise ABI decrease or Exercise transcutaneous oxygen pressure measurement (Exercise-TcPO2) can be used to diagnose LEAD. Objectives were (i) to assess the agreement between both methods (ii) to define the variables associated with the discordance, and (iii) to present results of healthy subjects. In this prospective cross-sectional study, patients with exertional limb symptoms and normal rest ABI were consecutively included. ABI was measured at rest and after standardized exercise protocol as well as Exercise-TcPO2. A kappa coefficient with a 95% confidence interval was used to assess the agreement between the two methods. Logistic regression analysis was performed to outline variables potentially responsible for discordance. Ninety-six patients were included. The agreement between the tests was weak with a k value of 0.23 [0.04-0.41]. Logistic regression analysis found that a medical history of lower extremity arterial stenting (odds ratio 5.85[1.68-20.44]) and age (odds ratio 1.06[1.01-1.11]) were the main cause of discordance. This study suggests that post-exercise ABI and Exercise-TcPO2 cannot be used interchangeably for the diagnosis of LEAD in patients with exertional symptoms and normal rest ABI.

Impact of multidisciplinary team meetings on the management of venous thromboembolism. A clinical study of 142 cases.

OBJECTIVE: Numerous guidelines have been published on the management of venous thromboembolism (VTE). However, therapeutic decision-making may prove challenging in routine clinical practice. With this in mind, multidisciplinary team (MDT) meetings have been set up in Rennes University Hospital, France. This study sought to describe the situations discussed during MDT meetings and to assess whether the meetings bring about changes in the management of these patients. MATERIALS AND METHODS: A retrospective single-center study conducted at the Rennes University Hospital included cases presented from the beginning of the MDT meetings (February 2015) up to May 2017. RESULTS: In total, 142 cases were presented in 15 MDT meetings, corresponding to a mean of 10±4 cases per meeting. Of these, 129 related to VTE patients: 33 provoked VTEs, 22 unprovoked VTEs, 49 cancer-related VTEs, and 25 unspecified VTEs. MDT meetings led to significant changes in the anticoagulation type (therapeutic, prophylactic, or discontinuation) and duration, but not in the anticoagulant choice (direct oral anticoagulants, vitamin K antagonists, heparins, etc.). CONCLUSION: Requests for MDT meetings are made for all VTE types, and these meetings have an impact on VTE management.

Update of the SFMV (French society of vascular medicine) guidelines on the conditions and safety measures necessary for thermal ablation of the saphenous veins and proposals for unresolved issues.

Venous insufficiency is a very common disease affecting about 25% of the French population (if we combine all stages of its progression). It is a complex disease and its aetiology has not yet been fully elucidated. Some of its causes are well known, such as valvular dysfunction, vein wall defect, and the suctioning effect common to all varicose veins. These factors are generally associated and together lead to dysfunction of one or more of the saphenous veins. Saphenous vein dysfunction is revealed by ultrasound scan, a reflux lasting more than 0.5 seconds indicating venous incompetence. The potential consequences of saphenous vein dysfunction over time include: symptoms (heaviness, swellings, restlessness, cramps, itching of the lower limbs), acute complications (superficial venous thrombosis, varicose bleeding), chronic complications (changes in skin texture and colour, stasis dermatitis, eczema, vein atresia, leg ulcer), and appearance of unaesthetic varicose veins. It is not possible to repair an incompetent saphenous vein. The only therapeutic options at present are ultrasound-guided foam sclerotherapy, physical removal of the vein (saphenous stripping), or its thermal ablation (by laser or radiofrequency treatment), the latter strategy having now become the gold standard as recommended by international guidelines. Recommendations concerning thermal ablation of saphenous veins were published in 2014 by the Société française de médecine vasculaire. Our society has now decided to update these recommendations, taking this opportunity to discuss unresolved issues and issues not addressed in the original guidelines. Thermal ablation of an incompetent saphenous vein consists in destroying this by means of a heating element introduced via ultrasound-guided venous puncture. The heating element comprises either a laser fibre or a radiofrequency catheter. The practitioner must provide the patient with full information about the procedure and obtain his/her consent prior to its implementation. The checklist concerning the interventional procedure issued by the HAS should be validated for each patient (see the appended document).

Transcutaneous oxygen pressure measurements in diabetic and non-diabetic patients clinically suspected of severe limb ischemia: a matched paired retrospective analysis.

AIM: It was recently suggested that a 6 mmHg difference exists in both chest and foot transcutaneous oxygen pressure (TcPo2) between diabetic and non-diabetic volunteers apparently free from vascular disease. If a difference can also be found in diabetic and non-diabetic patients with clinically suspected critical limb ischemia (CLI), this may question the use of the same 30 mmHg threshold proposed by the "TASC" in the definition of CLI. We analyse whether a difference can be found for chest and foot TcPo2 respectively between diabetic and non-diabetic patients referred for clinically suspected CLI. METHODS: A retrospective matched paired study was performed among 60 diabetic and 60 non-diabetic subjects with peripheral artery disease and suspected critical limb ischemia. Results are presented as median [25-75 centiles]. RESULTS: Groups were comparable in terms of gender, age, height, systolic blood pressure and treatments (except for renin-angiotensin inhibitors). Chest-TcPo2 was 53 [43-57] mmHg in diabetic and 60[49-65] mmHg in non-diabetic patients (P<0.01). Foot-TcPo2 was 12[3-34] mmHg in diabetic and 15[3-36] mmHg in non-diabetic patients (Non significant). A multi-parametric step by step regression analysis showed that chest-TcPo2 was inversely associated with weight, then with diabetes and gender. CONCLUSIONS: TcPo2 is lower at the chest but not at the foot level in diabetic than in non-diabetic patients with suspected CLI. Then, the "30 mmHg threshold" proposed in the definition of lower-limb CLI is likely applicable in both diabetic and non-diabetic patients.