French National Diagnostic and Care Protocol for antiphospholipid syndrome in adults and children.

Antiphospholipid syndrome (APS) is a chronic autoimmune disease involving vascular thrombosis and/or obstetric morbidity and persistent antibodies to phospholipids or certain phospholipid-associated proteins. It is a rare condition in adults and even rarer in children. The diagnosis of APS can be facilitated by the use of classification criteria based on a combination of clinical and biological features. APS may be rapidly progressive with multiple, often synchronous thromboses, resulting in life-threatening multiple organ failure. This form is known as "catastrophic antiphospholipid syndrome" (CAPS). It may be primary or associated with systemic lupus erythematosus (associated APS) and in very rare cases with other systemic autoimmune diseases. General practitioners and paediatricians may encounter APS in patients with one or more vascular thromboses. Because APS is so rare and difficult to diagnosis (risk of overdiagnosis) any suspected case should be confirmed rapidly and sometimes urgently by an APS specialist. First-line treatment of thrombotic events in APS includes heparin followed by long-term anticoagulation with a VKA, usually warfarin. Except in the specific case of stroke, anticoagulants should be started as early as possible. Any temporary discontinuation of anticoagulants is associated with a high risk of thrombosis in APS. A reference/competence centre specialised in autoimmune diseases must be urgently consulted for the therapeutic management of CAPS.

Fetal biometry in ultrasound: A new approach to assess the long-term impact of simulation on learning patterns.

CONTEXT: Simulation-based education (SBE) has demonstrated its acceptability and effectiveness in improving ultrasound training. Because of the high cost of its implementation (investment in equipment and supervision), a pragmatic assessment of the transfer of skills learned in SBE to clinical practice and the identification of its optimal scheduling conditions have been requested to optimize its input. OBJECTIVES: To quantify the long-term impact of simulation-based education (SBE) on the adequate performance of ultrasound fetal biometry measurements (I). The secondary objective was to identify the temporal patterns that enhanced SBE input in learning (II). METHODS: Trainees were arbitrarily assigned to a 6-month course in obstetric ultrasound with or without an SBE workshop. In the SBE group, the workshop was implemented 'before' or at an 'early' or a 'late-stage' of the course. Those who did not receive SBE were the control group. The ultrasound skills of all trainees were prospectively collected, evaluated by calculating the delta between OSAUS (Objective Structured Assessment of Ultrasound Skills) scores before and after the course (I). Concomitantly, the accuracy of trainees' measurements was assessed throughout the course by verifying their correlation with the corresponding measurements by their supervisors. The percentage of trainees able to perform five consecutive sets of correct measurements in the control group and in each SBE subgroup were compared (II). RESULTS: The study included 61 trainees (39 SBE and 22 controls). Comparisons between groups showed no significant difference in the quantitative assessment of skill enhancement (difference in the pre- and post-internship OSAUS score: 1.09 ± 0.87 in the SBE group and 0.72 ± 0.98 in the control group) (I). Conversely, the predefined acceptable skill level was reached by a significantly higher proportion of trainees in the 'early' SBE subgroup (74%, compared with 30% in the control group, P<0.01)(II). CONCLUSIONS: The quantitative assessment does not support the existence of long-term benefits from SBE training, although the qualitative assessment confirmed SBE helped to raise the minimal level within a group when embedded in an 'early' stage of a practical course.

Pseudoxanthoma elasticum overlaps hereditary spastic paraplegia type 56.

PURPOSE: Pseudoxanthoma elasticum (PXE) is a recessive disorder involving skin, eyes and arteries, mainly caused by ABCC6 pathogenic variants. However, almost one fifth of patients remain genetically unsolved despite extensive genetic screening of ABCC6, as illustrated in a large French PXE series of 220 cases. We searched for new PXE gene(s) to solve the ABCC6-negative patients. METHODS: First, family-based exome sequencing was performed, in one ABCC6-negative PXE patient with additional neurological features, and her relatives. CYP2U1, involved in hereditary spastic paraplegia type 56 (SPG56), was selected based on this complex phenotype, and the presence of two candidate variants. Second, CYP2U1 sequencing was performed in a retrospective series of 46 additional ABCC6-negative PXE probands. Third, six additional SPG56 patients were evaluated for PXE skin and eye phenotype. Additionally, plasma pyrophosphate dosage and functional analyses were performed in some of these patients. RESULTS: 6.4% of ABCC6-negative PXE patients (n = 3) harboured biallelic pathogenic variants in CYP2U1. PXE skin lesions with histological confirmation, eye lesions including maculopathy or angioid streaks, and various neurological symptoms were present. CYP2U1 missense variants were confirmed to impair protein function. Plasma pyrophosphate levels were normal. Two SPG56 patients (33%) presented some phenotypic overlap with PXE. CONCLUSION: CYP2U1 pathogenic variants are found in unsolved PXE patients with neurological findings, including spastic paraplegia, expanding the SPG56 phenotype and highlighting its overlap with PXE. The pathophysiology of ABCC6 and CYP2U1 should be explored to explain their respective role and potential interaction in ectopic mineralization.

[Training in fetal ultrasound biometry: Prospective assesment of Objective Structured Assessment of Ultrasound Skills (OSAUS) efficiency]. / Apprentissage de la biométrie échographique fœtale : évaluation prospective de la performance de l'Objective Structured Assessment of Ultrasound Skills (OSAUS).

BACKGROUND: Fetal biometry quality directly influences obstetrical care relevance. However, obstetrician proficiencies are heterogeneous in particular during initial training. OBJECTIVES: To assess the predictive value of OSAUS scale to identify operators with enough command to perform a valid estimation of fetal weight (EFW) (I). This study also assesses OSAUS intra-operator inter-exams variability (II) and pass/fail score relevancy (III). METHODS: Lecturers in Nancy University Hospital assessed trainees' proficiency for EWF systematically and prospectively through OSAUS scale. The trainee assessment was performed right after the one of the senior operator (reference EFW) on three consecutive patients during standard care ultrasounds. To ensure variability in proficiency within the sample, previous practice was taken into account during enrollment ("novices" and "intermediates" for<20 and 20 past exams, respectively). Correlation between mean OSAUS and validity of EFW (a valid EFW was defined by a difference with the reference EWF<0.8 Z-score) and variability between consecutive assessments were assessed. RESULTS: The study population was constituted of 8 "novice" and 8 "intermediate" trainees. Association between OSAUS and EFW validity was significant (P<0.03) (I). Intra-operator inter-exams variability was majored in the "novice" group (coefficients of variation were 25% vs. 10% in "novice" and "intermediate" group respectively) (II). Within the sample, specificity and positive predictive value of a pass/fail score OSAUS>3.5 to predict EFW validity were 77% and 71%, respectively (III). CONCLUSION: A 3.5 OSAUS pass/fail score could provide a relevant threshold to estimate operator proficiency in assessing fetal biometry in an autonomous and secure way.

[Epidemiologic and etiologic patterns of uveitis in a University Hospital]. / Caractéristiques épidémiologiques et étiologiques des uvéites dans un centre hospitalier universitaire.

INTRODUCTION: The purpose of this study was to describe the epidemiologic characteristics of adult uveitis evaluated at the regional center of excellence specializing in systemic and autoimmune disease in the Nancy university medical center. The secondary objectives were to describe the progression over time of the various etiologies and to identify local specificities. MATERIALS AND METHODS: We performed a retrospective epidemiological study of patients diagnosed with uveitis. All patients were referred to the regional center of excellence of the Nancy university medical center between January 1, 2005 and December 31, 2016. Patients under 18 years of age, patients with a first episode of acute anterior uveitis, as well as patients for whom the etiological diagnosis was made by the ophthalmologist with no need of internal medicine referral, were excluded. Age, gender, laterality, site of inflammation, clinical signs, etiology (infectious, non-infectious or idiopathic, as well as diagnosis), and date of first consultation were recorded. RESULTS: Six hundred and ninetypatients were included, with 59 % women and a mean age of 49 years. The uveitis was unilateral in 53 % of cases. Panuveitis was the most common form (52 %, N=358), followed by recurrent anterior uveitis (30 %, N=205), posterior uveitis (16 %, N=107), and intermediate uveitis (3 %, N=20). Non-infectious etiologies accounted for 35 % of all uveitis (the most common being HLA-B27 uveitis, sarcoidosis, ankylosing spondylitis and Behçet's disease) and infectious etiologies for 13 % (tuberculosis, toxoplasmosis and Lyme disease were the most frequent). The uveitis was idiopathic in 52 %. A trend toward improvement in diagnostic yield was observed : 53 % of uveitides were considered idiopathic prior to 2011 compared to 50 % after 2011 (P<0,01). CONCLUSION: We identified a majority of panuveitis, which is explained by our inclusion criteria. Fifty-two percent of our series remained idiopathic, with an improvement in the diagnostic yield over time. This could be related to both repeated etiological assessments and better diagnostic performance. The study of this large cohort of patients improved our knowledge of the characteristics of uveitis in our center.

Hydroxychloroquine in the primary thrombosis prophylaxis of antiphospholipid antibody positive patients without systemic autoimmune disease.

Objective The objective of this study was to determine the efficacy of hydroxychloroquine (HCQ) in the primary thrombosis prevention of antiphospholipid antibody (aPL)-positive patients with no other systemic autoimmune diseases. Methods Under the auspices of Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking, a multicenter, international, randomized controlled trial (RCT) was initiated, in which persistently aPL-positive but thrombosis-free patients without systemic autoimmune diseases were randomized to receive HCQ or no treatment in addition to their standard regimen. The primary objective was the efficacy of HCQ in preventing the first thrombosis. The secondary objectives were the thrombosis incidence rate, and the effects of HCQ on aPL profile and mortality rate. Patients were risk-stratified based on antiplatelet agent use. The goal was to follow patients every 6 months for 5 years. Results We recruited 20 persistently aPL-positive patients (female: 19, mean age: 46.6 ± 9.9 years, and baseline antiplatelet medication: 14); 9/20 were randomized to HCQ. During the mean follow-up of 1.7 years, no patients developed thrombosis or a serious adverse event. The study was terminated early due to the low recruitment rate, exacerbated by the prolonged manufacturing shortage and significant price increase of HCQ in the United States. Conclusion Given that a small number of patients with a relatively short follow-up were enrolled in our RCT, and no patients developed thrombosis, we cannot accurately assess the effectiveness of HCQ for primary thrombosis prevention in persistently aPL-positive patients with no other systemic autoimmune diseases. Our experience suggests that conducting an international RCT, especially without pharmaceutical support, is an extremely challenging undertaking.

Reversible drug-induced antiphospholipid syndrome.

We report an original case of reversible antiphospholipid syndrome (APS) due to minocycline in a young male patient who experienced recurrent strokes while taking minocycline. He started minocycline therapy (50 mg twice daily) at 15 years old for acne. After three years of treatment, the patient experienced a lateral medullary syndrome. He was treated with aspirin while minocycline was continued. Eighteen months later, the patient complained about horizontal binocular diplopia. MRI revealed an infarct of the oculomotor nerve nucleus. Laboratory investigations revealed high titers of anti-beta 2 glycoprotein 1 (antiß2GP1) antibodies of 470 U/ml (normal range <15 U/ml) and antiphosphatidylethanolamine antibodies of 137.4 U/ml (normal range <18 U/ml). Other laboratory tests were normal. Six weeks after discontinuation of minocycline, anti-ß2GP1 antibodies decreased to 335 U/ml and to 36 U/ml at six months and then remained negative for six years. Many drugs have been considered as possibly causing APS but only in a limited number of patients. To our knowledge this is the first case of drug-induced APS with complete disappearance of high titers of anti-ß2GP1 antibodies after minocycline withdrawal. This case also illustrates the need to monitor the levels of antiphospholipid antibodies, even though initial values are high and confirmed after 12 weeks.

[Development of an objective structured clinical examination (OSCE) for evaluating clinical competence in vascular medicine]. / Développement d'un examen clinique objectif structuré (ECOS) pour évaluer les compétences des étudiants en médecine vasculaire.

OBJECTIVES: Vascular medicine is now a clinical specialty in France. During their studies, students will acquire clinical reasoning in addition to technical skills. An Objective Structured Clinical Examination (OSCE) is considered as the gold standard for evaluating clinical competence. Our main objective was to evaluate the feasibility and acceptability of OSCE for the evaluation of students, secondarily their performance. METHODS: Three representative clinical cases of the specialty were developed. The OSCE consisted of a sequence of clinical situations presented in three stations of 7minutes each. The role of the simulated patient was played by medical students. At the end of the OSCE, observers and students completed the evaluation form. We compared the performances between junior and senior vascular medicine students. Written questionnaires were used to measure OSCE satisfaction. RESULTS: We were able to develop and organize this examination without difficulties. Fifteen students were evaluated. All participants agreed that the clinical situations were representative of vascular medicine practice, the cases were realistic and standardized patients were convincing. The performance of senior students was statistically higher than junior students in one case. DISCUSSION: Our study demonstrates the feasibility and acceptability of the OSCE in students in vascular medicine. The small number of stations and candidates requires further studies on a larger scale to evaluate their performance.

Extensive lymph node dissection during pancreaticoduodenectomy: a risk factor for hepatic steatosis?

PURPOSE: The first reports of hepatic steatosis following pancreaticoduodenectomy (PD) were published several years ago; however, clear risk factors remain to be identified. Therefore, the aim of this study was to identify the risk factors for hepatic steatosis post-PD. METHODS: We studied 90 patients who had undergone PD between September 2005 and January 2015. The inclusion criteria were as follows: available unenhanced CT within one month before PD and at least one unenhanced CT acquisition between PD and chemotherapy initiation. Using scanners, we studied the liver and spleen density as well as the surface areas of visceral (VF) and subcutaneous fat (SCF). These variables were previously identified by univariate and multivariate analyses. RESULTS: Hepatic steatosis occurred in 25.6% of patients at 45.2 days, on average, post-PD. Among the patients with hepatic steatosis, the average liver density was 52 HU before PD and 15.1 HU post-PD (p < 0.001). The Patients with hepatic steatosis lost more VF (mean, 28 vs. 11 cm2) and SCF (28.8 vs. 13.7 cm2) (p < 0.01 and p = 0.01, respectively). Portal vein resection and extensive lymph node dissection were independent risk factors in the multivariate analysis (odds ratio [OR] 5.29, p = 0.009; OR 3.38, p = 0.04, respectively). CONCLUSION: Portal vein resection and extensive lymph node dissection are independent risk factors for post-PD hepatic steatosis.

Impairment of quality of life in patients with antiphospholipid syndrome.

OBJECTIVES: Health-related quality of life (HRQoL) has not been fully explored in antiphospholipid syndrome (APS); therefore, we compared HRQoL between APS patients and the general population and assessed the impact of thromboembolic history. METHODS: HRQoL was measured in a multicentre cohort study by the Medical Outcomes Study Short-Form 36 (MOS-SF-36) questionnaire. HRQoL scores were compared to the French general population norms. Factors significantly associated with an impaired HRQoL were identified. RESULTS: A total of 115 patients with aPL and/or systemic lupus erythematosus (SLE) were included (mean age 42.7 ± 14.1 years old, 86 women). In 53 patients APS was diagnosed. Compared to general population norms, patients with APS had an impaired HRQoL. SLE-associated APS patients had the worst HRQoL scores (physical component summary (PCS)=40.8 ± 10.6; mental component summary (MCS)=40.6 ± 16.5) in comparison with SLE or aPL patients without thromboembolic history. In APS patients, history of arterial thrombosis significantly impaired HRQoL (PCS score: 42.2 ± 9.4 vs 49.2 ± 8.5; MCS score: 33.9 ± 13.7 vs 44.6 ± 10.3). CONCLUSION: Compared to the general population, APS patients experienced a lower HRQoL. In these patients, a history of arterial thrombosis significantly impaired HRQoL. Therefore, measurements of HRQoL should be included in APS patient management to assess the burden of the disease from a patient's perspective and to provide patients with the support they need.

[Impact of training conferences on medical student's performance for the French National Ranking Examination in Lorraine University. The ETIMCEL experimental study]. / ÉTude de l'IMpact de Conférences sur la réussite aux ECN en Lorraine. Étude interventionnelle ETIMCEL.

PURPOSE: To describe factors associated with a better rank, and to assess the impact of training conferences on medical student's performance for the French National Ranking Examination (FNRE) in Lorraine University, France in 2012. METHODS: Between October 2011 and May 2012, assistant professors of the faculty of medicine of Nancy, France, organized a cycle of 15 conferences combining clinical cases theoretical training and student peer assessment. Data were recorded with a self-administered questionnaire in January 2012 to collect potential confounders. RESULTS: Among 287 students enrolled in the last year of medical school in 2011-2012 in Lorraine University, 195 (67.9%) of them registered to the cycle of conferences. Among the potential prognostic factors assessed, not repeating the first year of medical curriculum (P=0.013), the number of courses validated at the first session during the second part of the medical curriculum (P=0.002), absence of difficulties experienced in the fifth and sixth year (P=0.032) and a desired ranking among the best (P=0.011) were independently associated with a better rank at the FNRE. Regular participation in conferences was significantly and independently associated with a higher ranking (mean gain for the participation in 13 or more conferences: 873; mean gain by conference: 63). CONCLUSION: Regular participation in conferences provided by assistant professors and based on clinical cases theoretical training and student peer assessment was significantly associated with a higher ranking to the FNRE in Lorraine University in 2012.