[Assessing post-hospitalization therapeutic ranges in elderly patients treated for atrial fibrillation with vitamin k antagonists]. / Évaluation de l'équilibre des AVK après hospitalisation, chez des sujets âgés, traités pour une fibrillation atriale.

BACKGROUND: In France, anticoagulants are among the most recommended treatments for serious accidents, particularly among the elderly. OBJECTIVES: The purpose of this study was to evaluate the impact of practical and validated tools designed to reduce the negative effects of vitamin K antagonist (VKA) treatments by assessing patients before and after the tools were implemented. METHODS: An exhaustive before and after multi-centric cohort study was performed in the Agen territory. The follow-up period corresponded to the six-month period post-hospitalization. The principal criterion was the time in the therapeutic range (TTR) at values of 2 to 3 according to the Rosendaal method. RESULTS: The overall time spent in the follow-up period before and after the implementation of the tools in 65- and 74-year-old patients was 58% and 64%, respectively (P=0.584). After the treatments, the TTR in the 85- to 90-year-old patients was 71.1%. An increase was observed in the number of subjects with a TTR≥70% after the implementation of the tools according to age, particularly in the 85- to 90-year-old patients (8 vs. 41; [P=0.01]). Prescription help software revealed a tendency of improvement in TTR values from 61% to 68% (P=0.472). In addition, longer therapeutic periods corresponded to longer patient lifespans (r=0.86). CONCLUSION: This study demonstrates the feasibility and advantages of implementing tools to improve the efficacy of VKA treatment in primary care, particularly for patients from 85 to 90 years old. The results should promote the implementation of this type of treatment method at the national level.

Perfusion magnetic resonance imaging in pediatric brain tumors.

PURPOSE: The use of DSC-MR imaging in pediatric neuroradiology is gradually growing. However, the number of studies listed in the literature remains limited. We propose to assess the perfusion and permeability parameters in pediatric brain tumor grading. METHODS: Thirty children with a brain tumor having benefited from a DSC-MR perfusion sequence have been retrospectively explored. Relative CBF and CBV were computed on the ROI with the largest lesion coverage. Assessment of the lesion's permeability was also performed through the semi-quantitative PSR parameter and the K2 model-based parameter on the whole-lesion ROI and a reduced ROI drawn on the permeability maps. A statistical comparison of high- and low-grade groups (HG, LG) as well as a ROC analysis was performed on the histogram-based parameters. RESULTS: Our results showed a statistically significant difference between LG and HG groups for mean rCBV (p < 10-3), rCBF (p < 10-3), and for PSR (p = 0.03) but not for the K2 factor (p = 0.5). However, the ratio K2/PSR was shown to be a strong discriminating factor between the two groups of lesions (p < 10-3). For rCBV and rCBF indicators, high values of ROC AUC were obtained (> 0.9) and mean value thresholds were observed at 1.07 and 1.03, respectively. For K2/PSR in the reduced area, AUC was also superior to 0.9. CONCLUSIONS: The implementation of a dynamic T2* perfusion sequence provided reliable results using an objective whole-lesion ROI. Perfusion parameters as well as a new permeability indicator could efficiently discriminate high-grade from low-grade lesions in the pediatric population.

Pigmented skin patches without scleroderma as a predominant clinical symptom revealing systemic sclerosis.

Skin induration remains the major clinical symptom of systemic sclerosis (SSc), an autoimmune disease with potentially life-threatening visceral involvement. However, skin induration can be absent in some patients, making the diagnosis difficult to confirm and leading to delay in management. Skin pigmentation abnormalities have been reported in patients with SSc, and can be important to recognize for diagnosis. We report two patients who developed hyperpigmented skin patches without any sign of scleroderma, as a major clinical skin symptom of incipient SSc.

Hippocampal modifications in transient global amnesia.

Transient global amnesia (TGA) is an acute and transient syndrome with a remarkably stereotypical set of signs and symptoms. It is characterized by the abrupt onset (no forewarning) of massive episodic memory impairment, both anterograde and retrograde. Ever since it was first described, TGA has fascinated neurologists and other memory experts, and in recent years, there has been a surge of neuroimaging studies seeking to pin down the brain dysfunction responsible for it. Several pathophysiological hypotheses have been put forward, including the short-lived suggestion of an epileptic mechanism. All the available data indicate that the brain modifications are reversible, and that the mechanism behind TGA is of a functional nature. However, while diffusion-weighted imaging studies have clearly identified the hippocampus and, more specifically, the CA1 area, as the locus of brain modifications associated with TGA, researchers have yet to determine whether the origin of the mechanism is vascular or neurochemical. Spectroscopy may provide a means of settling this issue once and for all.

REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours.

BACKGROUND: Brain metastases (BMs) are associated with a poor prognosis. Standard treatment comprises whole-brain radiation therapy (WBRT). As neo-angiogenesis is crucial in BM growth, combining angiogenesis inhibitors such as bevacizumab with radiotherapy is of interest. We aimed to identify the optimal regimen of bevacizumab combined with WBRT for BM for phase II evaluation and provide preliminary efficacy data. PATIENTS AND METHODS: In this multicentre single-arm phase I study with a 3 + 3 dose-escalation design, patients with unresectable BM from solid tumours received three cycles of bevacizumab at escalating doses [5, 10 and 15 mg/kg every 2 weeks at dose levels (DL) 0, 1 and 2, respectively] and WBRT (30 Gy/15 fractions/3 weeks) administered from day 15. DL3 consisted of bevacizumab 15 mg/kg with WBRT from day 15 in 30 Gy/10 fractions/2 weeks. Safety was evaluated using NCI-CTCAE version 3. BM response (RECIST 1.1) was assessed by magnetic resonance imaging at 6 weeks and 3 months after WBRT. RESULTS: Nineteen patients were treated, of whom 13 had breast cancer. There were no DLTs. Grade 1-2 in-field and out-field toxicities occurred for five and nine patients across all DLs, respectively, including three and six patients (including one patient with both, so eight patients overall) of nine patients in DL3. One patient experienced BM progression during treatment (DL0). At the 3-month post-treatment assessment, 10 patients showed a BM response: one of three treated at DL0, one of three at DL1, two of three at DL2 and six of seven at DL3, including one complete response. BM progression occurred in five patients, resulting in two deaths. The remaining patient died from extracranial disease progression. CONCLUSION: Bevacizumab combined with WBRT appears to be a tolerable treatment of BM. DL3 warrants further efficacy evaluation based on the favourable safety/efficacy balance. ClinicalTrials.gov Identifier: NCT01332929.

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.

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.

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.

Descriptive study of pneumococcal vaccination in cases of inflammatory disease: Analysis of practices.

INTRODUCTION: Pneumococcal infections are frequent and potentially serious in patients with inflammatory diseases treated with immunosuppressants and/or biotherapies. This patient population considered to be at very high risk of infection is subject to national vaccination recommendations. The main objective of this study was to assess pneumococcal vaccine coverage in a day hospital (internal medicine and vascular disease) in patients treated with immunosuppressants. METHODS: An observational, descriptive, retrospective, and single-center study. We included 150 consecutive patients for 3 months (February to April 2018). We studied pneumococcal vaccination coverage and the time elapsed between the date of vaccination with the 13-valent polysaccharide conjugate vaccine (PCV13) and the start of immunosuppressive therapy. RESULTS: Among the 150 patients included in the study, vaccination coverage with PCV13 was 85% (127/150) and decreased to 46.7% (70/150) for the recommended vaccination schedule. Taking into account vaccine efficacy according to the date of initiation of the treatment, only 28.7% (43/150) of the patients in the study were able to benefit from an optimal complete vaccination schedule, i.e. 33.8% (43/127) among patients vaccinated with PCV13. CONCLUSION: Despite official recommendations, vaccination coverage against pneumococcus remains insufficient in patients under immunosuppressants and/or biotherapies. In addition to the continued training of doctors, optimizing computer prescription of vaccines in view of facilitating vaccination tracing and having vaccination carried out at the site of consultation are avenues for improvement to be considered.

The human parahippocampal region: I. Temporal pole cytoarchitectonic and MRI correlation.

The temporal pole (TP) is the rostralmost portion of the human temporal lobe. Characteristically, it is only present in human and nonhuman primates. TP has been implicated in different cognitive functions such as emotion, attention, behavior, and memory, based on functional studies performed in healthy controls and patients with neurodegenerative diseases through its anatomical connections (amygdala, pulvinar, orbitofrontal cortex). TP was originally described as a single uniform area by Brodmann area 38, and von Economo (area TG of von Economo and Koskinas), and little information on its cytoarchitectonics is known in humans. We hypothesize that 1) TP is not a homogenous area and we aim first at fixating the precise extent and limits of temporopolar cortex (TPC) with adjacent fields and 2) its structure can be correlated with structural magnetic resonance images. We describe here the macroscopic characteristics and cytoarchitecture as two subfields, a medial and a lateral area, that constitute TPC also noticeable in 2D and 3D reconstructions. Our findings suggest that the human TP is a heterogeneous region formed exclusively by TPC for about 7 mm of the temporal tip, and that becomes progressively restricted to the medial and ventral sides of the TP. This cortical area presents topographical and structural features in common with nonhuman primates, which suggests an evolutionary development in human species.

Long-term outcome of patients with polymyositis/ dermatomyositis and anti-PM-Scl antibody.

BACKGROUND: To date, no series has analysed long-term outcome in patients with polymyositis/dermatomyositis (PM/DM) with anti-PM-Scl antibody. OBJECTIVES: The aims of the present study were: (i) to assess clinical features and long-term outcome, including organ complications, functional course and mortality rate, in patients with isolated PM/DM with anti-PM-Scl antibody; and (ii) to evaluate prevalence, characteristics and long-term outcome of interstitial lung disease (ILD) in patients with isolated PM/DM with anti-PM-Scl antibody. METHODS: The medical records of 20 consecutive patients with isolated PM/DM with anti-PM-Scl antibody were reviewed. RESULTS: Two patients (10%) achieved remission of PM/DM, whereas 14 (70%) improved and four (20%) had a worsened clinical status. Short-term recurrences (during tapering of therapy) occurred in nine patients and long-term recurrences (after discontinuation of therapy) in three patients. Moreover, patients with PM/DM with anti-PM-Scl antibody exhibited severe complications, as follows: oesophageal involvement (n = 4) requiring enteral feeding in three cases, ventilatory insufficiency (n = 3) requiring mechanical ventilation in two cases; three other patients had cancer. Interestingly, patients with PM/DM with anti-PM-Scl antibody often presented symptoms that are usually found in antisynthetase syndrome, i.e. hyperkeratotic rhagadiform hand symptoms (n = 2; 10%), Raynaud's phenomenon (n = 8; 40%), arthralgia/arthritis (n = 7; 35%) and ILD (n = 12; 60%). In our cohort, the associated ILD often required combined therapy of steroids and immunosuppressive agents. CONCLUSIONS: Our series suggests that the presence of anti-PM-Scl antibody is not a good prognostic factor in patients with PM/DM, as there appears to be an association with lung and oesophageal involvement; in addition, anti-PM-Scl antibody may coexist with malignancy in patients with PM/DM. Furthermore, anti-PM-Scl antibody-positive patients with PM/DM often exhibit 'mechanic's hands', Raynaud's phenomenon and joint involvement. Our latter findings raise the possibility that the immunogenetic background influences the autoantibody status of these patients; HLA-DR3 has, in fact, been found in association with antisynthetase syndrome antibodies and with anti-PM-Scl antibodies.

Characteristics and outcome of patients hospitalised for lower extremity peripheral artery disease in France: the COPART Registry.

OBJECTIVES: To assess the current 'real-world' management of hospitalised patients with lower-extremity peripheral artery disease (LE-PAD) and to assess the 1-year outcome. DESIGN, MATERIALS AND METHODS: The prospective and multicentre registry COhorte des Patients ARTériopathes (COPART) recruited consecutive patients from the departments of vascular medicine of three academic hospitals in Southwestern France. RESULTS: Among the 940 patients, 27.4% had intermittent claudication (IC), 9.3% ischaemic rest pain, 54.3% ulceration or gangrene and 9.3% acute limb ischaemia (ALI). Patients with IC were younger and more likely to be men, with a history of smoking (89.5%) and chronic obstructive pulmonary disease (17%). Among those with IC, 8.9% had bypass surgery and 41.5% were treated with percutaneous angioplasty. Those with tissue loss had higher rates of cardiovascular disease (CVD) risk factors and co-morbidities. At entry to the study, the level of control of the CVD risk factors was poor. The 1-year mortality rate was of 5.7% in patients with IC, 23.1% in patients with ischaemic rest pain, 28.7% in patients with tissue loss and 23% in those with ALI. Compliance with evidence-based medicine and pharmacological treatment was sub-optimal. CONCLUSION: This registry underscores the differences in patient profiles in the daily clinical setting, compared to those enrolled in several trials.

Role of flow magnetic resonance imaging in the monitoring of facial allotransplantations: preliminary results on graft vasculopathy.

Chronic vascular rejection characterized by the myointimal proliferation of smooth muscle cells that progressively obstruct the arterial graft lumen may become the main cause of long-term graft loss in vascularized composite allotransplantation (VCA), as observed in solid organ transplantation. As such, new diagnostic tools are required. The objective of this study was to evaluate the usefulness of flow magnetic resonance imaging (MRI) in the qualitative and quantitative monitoring of VCA in three patients transplanted between 2005 and 2012. Seven flow MRI acquisitions were performed concurrently with standardized clinical and histological monitoring between 2015 and 2017. A progressive reduction in the average flow rate and intraluminal diameter of the arterial pedicle of the grafts was demonstrated. During follow-up, two patients developed chronic vascular rejection requiring partial resection of the graft. For these patients, flow MRI acquisitions were characterized by a significant reduction in vascular signal, with a reduction in intravascular flow prior to anatomical injury. The results of this study confirm the feasibility of reproducible, non-invasive, and non-operator-dependent morphometric and haemodynamic radiological analysis, providing clinicians with new information on the vascular status of VCA over time and offering the prospect of an imaging technique specific to vascular outflow.

COVID-19 Neurologic Complication with CNS Vasculitis-Like Pattern.

Coronavirus disease 2019 (COVID-19) is a viral infection caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), which spreads rapidly from person to person and manifests in most symptomatic patients as a respiratory illness, similar to prior SARS viruses. Neurologic manifestations of COVID-19 are uncommon; those so far reported include encephalopathy, stroke from large-vessel occlusion, and polyneuropathy. We report a unique neurologic complication of COVID-19 in a patient who had extensive cerebral small-vessel ischemic lesions resembling cerebral vasculitis in a characteristic combined imaging pattern of ischemia, hemorrhage, and punctuate postcontrast enhancement. Also, a characteristic lower extremity skin rash was present in our patient. Our observation lends support to the increasingly suspected mechanism of "endotheliitis" associated with this novel coronavirus.

Group-specific component: evidence for two subtypes of the Gc1 gene.

A new method based on isofocusing electrophoresis in the study of the Gc (group-specific component) polymorphism, revealed differing electrophoretic patterns. These patterns can be explained by the existence of two codominant Gc1 subtypes. This hypothesis is in accordance with several family studies. These subtypes are called Gc1F and Gc1S. Eight hundred samples were analyzed, including three different populations: Caucasoid (a western Pyrenean valley), African (Pygmy Bi-Aka), and AMerindian (Quechua-Aymara, from Bolivia). These two subtype phenotypes cannot be explored with the usual technique. They were present in each population sample studied.

[Educational assessment of the first computerized national ranking exam in France in 2016: Opportunities for improvement]. / Analyse docimologique des premières Épreuves classantes nationales informatisées (ECNi) de 2016 : propositions d'amélioration.

In June 2016, 8124 medical students in their sixth year of graduation passed the first computerized national ranking exam (CNRE) in France after which they will have to choose what medical specialty they will be practicing all their life. We conducted the first educational assessment of this CNRE according to two criteria: the relevance of the questions and the cognitive domain mainly required to answer these questions. We propose two improvements for the future CNRE: promote student reasoning in the multiple choices questions, reduce to 10 the number of multiple choice questions in the progressive clinical cases and increase by 9 their total number (from 18 to 27), and use a majority of mini-clinical cases for isolated multiple choice questions in order to focus students on reasoning instead of simple knowledge restitution.

Contribution of flow MRI in the therapeutic management of middle face high flow arteriovenous malformation: A case report.

BACKROUND: The radiosurgical management of high flow arteriovenous malformations (HFAVM) in the "destructive" stage requires a precise hemodynamic and anatomical assessment. PATIENT AND METHODS/CASE REPORT: We report the case of a 32 years-old patient with a large ulcerated face HFAVM, on which Doppler ultrasound was impossible to perform. We show that, by combining 3D PCA and 2D CINE PC-MRI sequences, magnetic resonance imaging is capable to provide a complete morphometric and velocimetric mapping of the nidus and feeding arteries of the HFAVM. CONCLUSION: Although Doppler ultrasound is the reference examination in the HFAVM, Flow MRI without contrast agent provides an advantageous alternative to assess vascular pathologies and choose the therapeutic strategy.