Effects of iloprost in patients with critical limb ischemia: Results of a cohort study from the COPART registry.

BACKGROUND: Iloprost has been proposed as an alternative to amputation in Critical Limb Ischemia (CLI) patients when revascularization was unsuccessful or not possible. Nonetheless, there is limited evidence of its benefit. The main objective was to evaluate the effectiveness of iloprost and the secondary objective was to evaluate its safety. METHODS: In this cohort study including CLI patients from the COPART registry from 2006/10 to 2021/01, patients exposed to iloprost were matched with up to three unexposed patients according to age, sex, and Propensity Score (PS) for exposure to iloprost. The main outcome combined the occurrence of all-cause death and major amputations; survival was assessed over one-year using Kaplan-Meier estimates and Cox model analyses. Major Adverse Cardiovascular Events (MACE) were chosen as the safety outcome; the association with iloprost was estimated using a logistic regression model. RESULTS: Among 1850 CLI patients, 201 were exposed to iloprost (71.6% men; median age: 72 years vs. 72.1%; 75 years for unexposed). In 134 exposed patients matched to 375 unexposed patients, 14 major amputations and 24 deaths occurred in exposed patients (28.4%) vs. 33 and 46 respectively in the unexposed patients (20.9%). The hazard ratio (HR) was of 1.49 (95% Confidence Interval: 1.01-2.20). The association remained in the subgroup of "no option" patients (HR: 1.74; [1.01-2.20]). Regarding safety, 21/201 (10.7%) exposed patients experienced MACE vs. 146/1649 (9.41%) unexposed patients (unadjusted Odds Ratio [OR]: 1.17 [0.72-1.90]; adjusted OR: 1.23 [0.72-2.11]). CONCLUSION: The study did not find any benefit of iloprost in CLI patients and even suggested a deleterious effect.

Pharmacological characterization of GLPG1972/S201086, a potent and selective small-molecule inhibitor of ADAMTS5.

OBJECTIVE: A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) is a key enzyme in degradation of cartilage in osteoarthritis (OA). We report the pharmacological characterization of GLPG1972/S201086, a new, potent and selective small-molecule ADAMTS5 inhibitor. METHODS: Potency and selectivity of GLPG1972/S201086 for ADAMTS5 were determined using fluorescently labeled peptide substrates. Inhibitory effects of GLPG1972/S201086 on interleukin-1α-stimulated glycosaminoglycan release in mouse femoral head cartilage explants and on interleukin-1ß-stimulated release of an ADAMTS5-derived aggrecan neoepitope (quantified with ELISA) in human articular cartilage explants were determined. In the destabilization of the medial meniscus (DMM) mouse and menisectomized (MNX) rat models, effects of oral GLPG1972/S201086 on relevant OA histological and histomorphometric parameters were evaluated. RESULTS: GLPG1972/S201086 inhibited human and rat ADAMTS5 (IC50 ± SD: 19 ± 2 nM and <23 ± 1 nM, respectively), with 8-fold selectivity over ADAMTS4, and 60->5,000-fold selectivity over other related proteases in humans. GLPG1972/S201086 dose-dependently inhibited cytokine-stimulated aggrenolysis in mouse and human cartilage explants (100% at 20 µM and 10 µM, respectively). In DMM mice, GLPG1972/S201086 (30-120 mg/kg b.i.d) vs vehicle reduced femorotibial cartilage proteoglycan loss (23-37%), cartilage structural damage (23-39%) and subchondral bone sclerosis (21-36%). In MNX rats, GLPG1972/S201086 (10-50 mg/kg b.i.d) vs vehicle reduced cartilage damage (OARSI score reduction, 6-23%), and decreased proteoglycan loss (∼27%) and subchondral bone sclerosis (77-110%). CONCLUSIONS: GLPG1972/S201086 is a potent, selective and orally available ADAMTS5 inhibitor, demonstrating significant protective efficacy on both cartilage and subchondral bone in two relevant in vivo preclinical OA models.

[Social representations of cardiovascular disease in the Tanvè Health Study (TAHES) cohort in Benin]. / Représentations sociales des maladies cardio-vasculaires dans la cohorte Tanvè Health Study (TAHES) au Bénin.

OBJECTIVE: To describe the social representations associated with cardiovascular diseases (CVD) in the village of Tanvè in Benin. METHODS: Focus groups discussions and semi-structured interviews were conducted among participants of Tanvè Health Study (TAHES) cohort. Audio recordings were made during the interviews, as well as some note-taking. Data were organized by themes and analyzed to identify key representations that underlie attitudes and health care practices. RESULTS: A total of 19 subjects (including 11 women) participated in 2 focus groups and 17 (including 5 women) in individual interviews. Etymologies of CVD's names evoke either clinical signs (example: ''tesisi glô mɛ'' [can't stand up]), guessed etiology (example: ''kuvitɔ zɔn'' [ghosts' disease]) or a local adaptation of a biomedical name (example: ''a'tension'' [from hypertension]), to cite the example of stroke. According to beliefs about etiology, diseases were classed as ''simple'' or "organic" diseases ("azɔn yaya") and ''supernatural'' or ''induced'' diseases linked to "azé" [immaterial witchcraft] or "bô" [material bewitchment]. Chronic or recurrent diseases usually end up in the ''supranatural'' category and induce the consultation of "bokɔnɔ᷉" (diviner) or other religious for diagnosis. Health care seeking refer to modern medicine, "amanɔn" (leaf-based care), "bokɔnɔ᷉" or traditional religious (various rites) and Christians (prayers). CONCLUSION: Social representations of CVD in this community are based on ancestral beliefs, but are also influenced by modern knowledge. Taking them into account could improve quality of health to fulfill communities' care needs.

A massive rock and ice avalanche caused the 2021 disaster at Chamoli, Indian Himalaya.

On 7 February 2021, a catastrophic mass flow descended the Ronti Gad, Rishiganga, and Dhauliganga valleys in Chamoli, Uttarakhand, India, causing widespread devastation and severely damaging two hydropower projects. More than 200 people were killed or are missing. Our analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27 × 106 cubic meters of rock and glacier ice collapsed from the steep north face of Ronti Peak. The rock and ice avalanche rapidly transformed into an extraordinarily large and mobile debris flow that transported boulders greater than 20 meters in diameter and scoured the valley walls up to 220 meters above the valley floor. The intersection of the hazard cascade with downvalley infrastructure resulted in a disaster, which highlights key questions about adequate monitoring and sustainable development in the Himalaya as well as other remote, high-mountain environments.

Evolution of Major Amputation Risk in Patients Hospitalized in France for Critical Limb Ischemia: The COPART Registry.

Over the past decade, improvements in medical treatment and revascularization techniques have been beneficial for patients with peripheral artery disease in the late stage of critical limb ischemia (CLI). We evaluated the putative reduction in the number of major amputees in the Cohorte des Patients ARTeriopathes (COPART) cohort over time. Patients were selected from this multicenter cohort, from 2006 to 2016, for CLI according to Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease II criteria. Patients included before and after 2011 were compared. Patients were followed for 1 year. Primary outcome was the rate of major amputations. Secondary outcomes were minor amputations, deaths from all causes, cardiovascular deaths; 989 patients were included, 489 before 2011 and 450 after 2011. There was a significant decrease in rates of major amputation after 2011 (17% vs 25%), confirmed in multivariate analysis (odds ratio [OR]: 1.5 [1.1-2.2]), an increase in revascularization, particularly distal angioplasty (OR: 2.7 [1.7-4.4]) and increased statin intake (OR: 1.6 [1.1-2.1]). For secondary outcomes, there was no significant difference. Limb prognosis of CLI patients has improved over the past decade, possibly due to more revascularizations, particularly distal ones, and increased statin use.

Prevalence of stroke survivors in Parakou in northern Benin: A door-to-door community survey.

INTRODUCTION: Stroke is a major public health problem with a high burden in Sub-Saharan Africa. We aimed to determine the prevalence of stroke in Titirou in Parakou. METHODS: It was a cross-sectional study using a door-to-door survey in Titirou (Parakou) from 15 march to 15 October 2016 and included 4671 adults. We did a two stages survey. In the first stage the World Health Organization (WHO) tool for the diagnosis of stroke in community was used. In the second phase all suspected cases underwent neurological exam and sometimes brain CT-scan. The WHO definition was used for the diagnosis of stroke. We recorded the socio-demographic data and the vascular risk factors. The prevalence was standardized on age according to the WHO type population. Multiple logistic regression was done to identify associated factors and estimate the adjusted prevalence ratio (aPR) and their 95% confidence interval (CI). RESULTS: The mean age of the subjects was 27.7±12.9 years with a sex ratio of 0.97. After screening 161 were suspected and 54 confirmed cases, the overall prevalence of stroke in Titirou was 1.156 per 100,000 inhabitants [95% CI: 0.850 to 1.426]. The age-standardized prevalence of stroke was 3223 cases per 100,000 inhabitants. The associated factors were age (aPR 1.7 [1.5-1.9] for 10 years), history of hypertension (aPR: 64.8 [46.1-108.9]), diabetes mellitus (aPR: 4.5 [1.6-12.3]), low consumption of fruits and vegetables (aPR: 2.3 [1.2-4.4]), history of heart disease (aPR: 6.0 [2.6-13.7]), family history of stroke (PR: 4.6 [2.1-10.0]). Among the 54 subjects who had a stroke 10 were able to perform the brain CT-Scan: 40% were hemorrhagic and 60% ischemic stroke. CONCLUSION: Our study showed a high prevalence of stroke in Titirou and suggested urgent action for prevention.

[Ejaculation disorders in multiple sclerosis: Prospective study of 44 patients]. / Troubles de l'éjaculation et sclérose en plaques : étude prospective de 44 patients.

INTRODUCTION: To analyze in a descriptive way the ejaculation disorders during MS and to study the correlations between dysejaculations, other sexual, urinary and anorectal disorders. MATERIAL: Prospective, monocentric, non-interventional study. Ejaculation disorders were assessed by Premature Ejaculation Profile (PEP) scores, intravaginal latency, and the Male Sexual Health Questionnaire - Ejaculation (MSHQ-Ej). The sexual disorders were evaluated by the International Index of Erectile Function (IIEF15) and the Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ). RESULTS: Forty-four men of mean age 46.8 (±10.3) years, with an average EDSS of 5.0 (±1.5) were included. According to the MSHQ-Ej score, ejaculation disorders were present in 28 out of 44 patients included (64%); 26/44 (59%) had an orgasm disorder, 23/44 (52%) a delay in ejaculation, 26/44 (59%) a decrease in ejaculation flow, 24/44 (55%) decreased ejaculated volume, 18/44 (41%) decreased ejaculation frequency, 15/44 (33%) ejaculatory pain and 11 34 (25%) showed systematic non ejaculation. The PEP score showed premature ejaculation in 14 patients (32%). The intra-vaginal latency time was less than 1minute in 6 patients (13.6%). There was a statistically significant correlation between ejaculation disorders and erectile dysfunction (P<0.05, correlation coefficient at 0.53) but no statistically significant correlation between ejaculation disorders and urinary or ano-rectal disorders. CONCLUSIONS: Dysejaculation was present in 64% of MS. These disorders were mainly characterized by a decrease in the volume of the ejaculation, the strength of ejaculation and the delay in ejaculation. LEVEL OF EVIDENCE: 4.

[Aneurysm of the portal venous system: A rare and unknown pathology]. / Anévrisme du tronc porte : une pathologie rare et méconnue.

INTRODUCTION: Portal vein aneurysms are rare, representing 3% of venous aneurysms, with about 200 cases described in the literature, probably underestimated. CASE REPORT: A 66-year-old man, suspect of splenomegaly, underwent an abdominal ultrasound and a thoraco-abdomino-pelvic CT scan showing a 40mm portal vein aneurysm. Final diagnosis was T-cell hemopathy. Five and six months later, abdominal imaging was stable, suggesting congenital origin due to lack of obliteration of the vitelline vein. CONCLUSION: Portal vein aneurysms are often asymptomatic and an incidental finding. Monitoring is recommended because of their potential complications (thrombosis, rupture of aneurysm, portal hypertension, adjacent organs compression), annually if asymptomatic or more frequently with sometimes a surgical management in case of clinical manifestations.

[College of the French Vascular Medicine Teachers (CEMV) statement: Arterial Doppler waveforms analysis (simplified Saint-Bonnet classification)]. / Recommandations du Collège des enseignants de médecine vasculaire (CEMV) : analyse des flux artériels Doppler (classification de Saint-Bonnet simplifiée).

Lower extremity peripheral artery disease is a frequent disease. Arterial Doppler waveforms analysis is a key element in vascular medicine, especially to diagnose lower peripheral artery disease. Although Doppler waveforms are often used, descriptions are highly heterogeneous. This review presents the simplified Saint-Bonnet classification that is tought to vascular medicine residents in order to homogenize arterial flow description.

The Visible Human Project male CAD based computational phantom and its use in bioelectromagnetic simulations.

Use of numerical simulation tools to provide qualitative estimates on electromagnetic safety, characterize antenna performance for WBAN applications and facilitate ground breaking research on diagnostic and therapeutic bioelectrical solutions has steadily grown over the past twenty years. However, the accuracy and applicability of such tools are directly proportional to the fidelity of the model used during the simulation. This paper describes the construction of a new CAD based male computational phantom, the Visible Human Project (VHP)-Male model, suitable for use in major commercial electromagnetics simulation packages.

Renal Artery Stenosis in Patients with Peripheral Artery Disease: Prevalence, Risk Factors and Long-term Prognosis.

OBJECTIVE/BACKGROUND: The objective was to determine the prevalence and clinical determinants of renal artery stenosis (RAS) in patients undergoing digital subtraction angiography (DSA) for the assessment of peripheral artery disease (PAD), and to evaluate its prognostic significance. METHODS: All DSAs performed from January 2000 to January 2006 were retrospectively reviewed for assessment of PAD in patients naive for any prior revascularisation of lower-limb arteries. All DSA studies were read by two senior physicians blinded to outcome, and consensus was reached in cases of disagreement. RAS was defined as the presence of ≥50% stenosis in either renal artery. Patients' electronic medical files were systematically reviewed and follow-up was completed by contact with family physicians until January 2014. The primary outcome was composite, including death, peripheral revascularisation, or any limb amputation. Secondary outcomes were all-cause mortality, and another composite, including death and non-fatal myocardial infarction or stroke or coronary or carotid revascularisation. RESULTS: In total, 400 consecutive patients having a first DSA of lower extremities, two thirds of whom were for critical limb ischaemia, were studied. Thirteen patients were excluded owing to poor renal artery imaging. RAS was detected in 57 patients (14%). Only two factors were independently and significantly associated with RAS in multivariate analysis: diffuse PAD (involving both proximal and distal segments [odds ratio {OR} 3.50, 95% confidence interval {CI} 1.16-10.54; p = .026]) and decreased glomerular filtration rate (OR 0.55 per 30 mL/minute/1.73 m2, 95% CI 0.41-0.75; p < .001). During follow-up (mean ± SD 62 ± 47 months), 25% experienced limb amputation and 54% died. In multivariate analysis, no significant association was found between RAS and primary outcome (hazard ratio 0.80; 95% CI 0.57-1.10). No significant association was found with secondary outcomes. CONCLUSION: Incidental RAS is frequent (14%) among patients with PAD undergoing lower extremity imaging. No difference in outcome in patients with RAS versus those without RAS was seen. Larger studies are necessary to draw definite conclusions.

[Prevalence and prognosis of aspirin resistance in critical limb ischemia patients]. / Prévalence et valeur pronostique de la résistance à l'aspirine chez les patients en ischémie critique chronique des membres inférieurs.

OBJECTIVES: To assess the prevalence and the association between aspirin resistance in critical limb ischemia patients using the VerifyNow® bed-side platelet test, and occurrence of cardiovascular morbidity and/or death at one year. MATERIALS AND METHODS: National multicenter prospective observational study related to COPART II centers. From 2010 through 2014, 64 subjects hospitalized for critical limb ischemia and already treated by aspirin before the VerifyNow® test were included. A VerifyNow® test>550 ARU was defined as aspirin resistance. Critical limb ischemia was defined according to the TASC I criteria. The primary outcome was a composite including death, acute coronary syndrome, stroke and major amputation during the one-year follow-up period. RESULTS: In all, 9/64 patients were aspirin resistant, the status was confirmed in one case. The prevalence of aspirin resistance was 14.06%. There was no significant difference between aspirin resistant and aspirin non-resistant groups in terms of cardiovascular history and glycemia status. Neither was there significant difference between the two groups in terms of survival. CONCLUSION: Aspirin resistance was not predictive of poorer survival in critical limb ischemia patients. However, our population was limited. Considering that a clear definition of aspirin resistance and standardized diagnostic tests are lacking, complementary studies might be useful.

[Calcified bullet thrombus of the inferior vena cava and left renal vein in an adult]. / Une calcification de la veine cave inférieure et de la veine rénale gauche chez l'adulte.

Calcifications are rarely located within the inferior vena cava and the renal veins. The etiology is poorly understood and the prognosis is uncertain. We report a case in a 55-year-old man.

Anemia, an independent predictive factor for amputation and mortality in patients hospitalized for peripheral artery disease.

OBJECTIVES: Anemia is associated with poorer outcome in coronary artery disease (CAD) and heart failure (HF), but data on patients with peripheral artery disease (PAD) are scarce, especially regarding the local (limb) prognosis. It was hypothesized that anemia is associated with poorer prognosis in patients hospitalized for PAD, and this relationship would be proportional to the severity of the anemia. DESIGN: Prospective cohort study. MATERIALS: The Cohorte des Patients Artéritiques (COPART) is a multicenter registry of patients hospitalized for PAD in three university hospitals in southwestern France. METHODS: Clinical and biological data were collected at entry. Patients were followed up to 1 year. Anemia was defined by Hb < 8.2 mmol/L in men and <7.6 mmol/L in women. The primary outcome was 1-year survival free from major amputation. The secondary outcome was 1-year major amputation. RESULTS: Data of 925 consecutive patients (70.7 ± 12.8 years, 29.2% females) were analyzed. Patients were hospitalized either for revascularization or medical therapy, with Rutherford categories 3 (25%), 4 (9.1%), 5 or 6 (55.1%) as well as acute limb ischemia (10.8%). Anemia was present in 471 patients (50.9%). These patients were significantly older, with higher rates of hypertension, diabetes, clinical CAD, HF, chronic kidney disease, and cancer, and with lower rates of smoking and dyslipidemia than their counterparts (p < .05 for all). In multivariate models, anemia was significantly and independently associated (p < 0.001) with death and amputation (HR 1.44; 95% CI 1.15-1.80) with similar findings for secondary outcomes. A lower level of hemoglobin is associated with a higher risk of mortality and amputation (HR 1.20; 95% CI 1.09-1.32). CONCLUSION: Anemia and its severity are independent predictors of mortality and limb loss in patients hospitalized for PAD.

[Clinical and electrophysiological study of sensory penile alterations. A prospective study of 44 cases]. / Analyse clinique et neurophysiologique des troubles de la sensibilité pénienne. Étude prospective de 44 cas.

OBJECTIVE: To precise clinical presentations, pathophysiology and etiologies of penile sensory alteration. METHODS: Forty-four patients with penile sensory dysfunction underwent clinical and electrophysiological testing with electromyography of bulbocavernosus muscles, study of sacral reflex latencies, somatosensory cortical responses following stimulation of the dorsal nerve of the penis, sensory velocity of the dorsal nerve and pudendal nerve terminal sensory latencies. RESULTS: Penile anesthesia was observed in six (13%) patients, loss of sensibility in 34 (77%), paresthesia in four (9%). Erectile dysfunction was noted in 19 (43%) patients, hypo-orgasmia in seven (16%), cold glans penis sensation in four and loss of spatial sensation during intercourse in three (7%). Abnormalities of electrophysiological perineal testing were observed in 17 (38%) patients. In 27 (62%) cases, no alteration of electrophysiological testing was observed. In 17 (38%) patients, a specific aetiology was founded by means nerve palsy during orthopedic surgery in five cases, entrapment neuropathy following byking in nine cases, two La Peyronie diseases and one diabetes mellitus. CONCLUSION: In the current series, the prevalence of neuropathy of the dorsal nerve of the penis (that can determine a loss of sensibility) was 40%.

Prophylaxis of catheter-related deep vein thrombosis in cancer patients with low-dose warfarin, low molecular weight heparin, or control: a randomized, controlled, phase III study.

PURPOSE: Whether an anticoagulant prophylaxis is needed for patients with cancer with a central venous catheter is a highly controversial subject. We designed a study to compare different prophylactic strategies over 3 months of treatment. METHODS: We performed a phase III prospective, open-label randomized trial. After the insertion of a central venous access device, consecutive patients with planned chemotherapy for cancer were randomized to no anticoagulant prophylaxis, low molecular weight heparin [low molecular weight heparin (LMWH); with isocoagulation doses], or warfarin 1 mg/day. Treatments were given over the first 3 months. Doppler ultrasound and venographies were performed on days 1 and 90, respectively, or sooner in case of clinical presumption of thrombosis. RESULTS: A total of 420 patients were randomized, and 407 were evaluable. Forty-two catheter-related deep vein thrombosis (DVT) occurred (10.3 %), 20 in those with no anticoagulation, 8 in those receiving warfarin, and 14 in those receiving LMWH. Nine additional non-related catheter deep vein thrombosis (CDVT) occurred. Anticoagulation significantly reduced the incidence of catheter-related DVT (p = 0.035) and catheter non-related DVT (p = 0.007), with no difference between warfarin and LMWH. Safety was good (3.4 % of attributable events) but compliance with randomized prophylaxis was lower than expected. CONCLUSIONS: Prophylaxis showed a benefit regarding catheter-related and non-catheter-related DVT with no increase in serious side effects.

A hospital discharge risk score for 1-year all-cause mortality or non-fatal cardiovascular events in patients with lower-extremity peripheral artery disease, with and without revascularisation.

OBJECTIVES: This study aims to determine a hospital discharge prognostic risk score for patients with lower-extremity peripheral artery disease (PAD) with and without revascularisation. DESIGN, MATERIALS AND METHODS: A prognostic score on mortality or non-fatal cardiovascular events was determined using the database of a multicentre prospective study enrolling consecutive patients hospitalised for PAD (COhorte de Patients ARTeriopathes, COPART). RESULTS: We analysed the data of 640 patients in the derivation cohort and 517 in the validation cohort. The risk score (and corresponding points) included the following factors: age 75-84 years (+2), ≥ 85 years (+3); previous myocardial infarction (+1); creatinine clearance: ≤ 30 ml min(-1) 1.73 m⁻² (+1.5), 0.30-0.59 (+1), ankle-brachial index: <0.3 (+2), 0.3-0.49 (+1.5) and >1.3 (+2); C-reactive protein (CRP) ≥ 70 mg l⁻¹ (+2); and association of statins, anti-platelet agents and renin-angiotensin system inhibitors (-1.5). The frequency of the composite outcome increased significantly with the predicted risk: low risk (≤ 0 point), 2%; medium (0.5-2 points), 12.8%; high (2.5-4 points), 23%; very high (≥ 4.5 points): 42.2%. The model had a good performance in terms of discrimination (C-statistic 0.74 and 0.76) and calibration (Hosmer-Lemeshow 0.65). CONCLUSIONS: We propose the validated COPART risk score for hospitalised severe PAD. This prognostic risk score is based on six variables easily identifiable in clinical practice. Our study highlights the favourable prognostic impact of the prescription at discharge of combined drug therapies.