Centre Hospitalier Régional de Metz-Thionville

Biped robots form a subclass of legged or walking robots. The study of mechanical legged motion has been motivated by its potential use as a means of locomotion in rough terrain, as well as its potential benefits to prothesis development and testing. The paper concentrates on issues related to the automatic control of biped robots. More precisely, its primary goal is to contribute a means to prove asymptotically-stable walking in planar, underactuated biped robot models. Since normal walking can be viewed as a periodic solution of the robot model, the method of Poincare sections is the natural means to study asymptotic stability of a walking cycle. However, due to the complexity of the associated dynamic models, this approach has had limited success. The principal contribution of the present work is to show that the control strategy can be designed in a way that greatly simplifies the application of the method of Poincare to a class of biped models, and, in fact, to reduce the stability assessment problem to the calculation of a continuous map from a subinterval of R to itself. The mapping in question is directly computable from a simulation model. The stability analysis is based on a careful formulation of the robot model as a system with impulse effects and the extension of the method of Poincare sections to this class of models.

OBJECTIVE: Earlier studies of eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), with limited patient numbers and followup durations, demonstrated that clinical presentation at diagnosis, but not outcome, differed according to antineutrophil cytoplasmic antibody (ANCA) status. This study was undertaken to describe the main characteristics of a larger patient cohort and their long-term outcomes. METHODS: A retrospective study of EGPA patients in the French Vasculitis Study Group cohort who satisfied the American College of Rheumatology criteria and/or Chapel Hill definitions was conducted. Patient characteristics and outcomes were compared according to ANCA status and year of diagnosis. RESULTS: We identified 383 patients diagnosed between 1957 and June 2009 (128 [33.4%] before 1997 or earlier) and followed up for a mean±SD of 66.8±62.5 months. At diagnosis, their mean±SD age was 50.3±15.7 years, and 91.1% had asthma (duration 9.3±10.8 years). Main manifestations included peripheral neuropathy (51.4%); ear, nose, and throat (ENT) signs (48.0%); skin lesions (39.7%); lung infiltrates (38.6%); and cardiomyopathy (16.4%). Among the 348 patients tested at diagnosis for ANCA, the 108 ANCA-positive patients (31.0%) had significantly more frequent ENT manifestations, peripheral neuropathy, and/or renal involvement, but less frequent cardiac manifestations, than the ANCA-negative patients. Vasculitis relapses occurred in 35.2% of the ANCA-positive versus 22.5% of the ANCA-negative patients (P=0.01), and 5.6% versus 12.5%, respectively, died (P<0.05). The 5-year relapse-free survival rate was 58.1% (95% confidence interval [95% CI] 45.6-68.6) for ANCA-positive and 67.8% (95% CI 59.8-74.5) for ANCA-negative patients (P=0.35). Multivariable analysis identified cardiomyopathy, older age, and diagnosis during or prior to 1996 as independent risk factors for death and lower eosinophil count at diagnosis as predictive of relapse. CONCLUSION: The characteristics and long-term outcomes of EGPA patients differ according to their ANCA status. Although EGPA relapses remain frequent, mortality has declined, at least since 1996.

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI) management has evolved considerably over the past 2 decades. Little information on mortality trends in the most recent years is available. We assessed trends in characteristics, treatments, and outcomes for acute myocardial infarction in France between 1995 and 2015. METHODS: We used data from 5 one-month registries, conducted 5 years apart, from 1995 to 2015, including 14 423 patients with acute myocardial infarction (59% STEMI) admitted to cardiac intensive care units in metropolitan France. RESULTS: From 1995 to 2015, mean age decreased from 66±14 to 63±14 years in patients with STEMI; it remained stable (68±14 years) in patients with NSTEMI, whereas diabetes mellitus, obesity, and hypertension increased. At the acute stage, intended primary percutaneous coronary intervention increased from 12% (1995) to 76% (2015) in patients with STEMI. In patients with NSTEMI, percutaneous coronary intervention ≤72 hours from admission increased from 9% (1995) to 60% (2015). Six-month mortality consistently decreased in patients with STEMI from 17.2% in 1995 to 6.9% in 2010 and 5.3% in 2015; it decreased from 17.2% to 6.9% in 2010 and 6.3% in 2015 in patients with NSTEMI. Mortality still decreased after 2010 in patients with STEMI without reperfusion therapy, whereas no further mortality gain was found in patients with STEMI with reperfusion therapy or in patients with NSTEMI, whether or not they were treated with percutaneous coronary intervention. CONCLUSIONS: Over the past 20 years, 6-month mortality after acute myocardial infarction has decreased considerably for patients with STEMI and NSTEMI. Mortality figures continued to decline in patients with STEMI until 2015, whereas mortality in patients with NSTEMI appears stable since 2010.

BACKGROUND: Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. METHODS: In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. RESULTS: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. CONCLUSIONS: Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

BACKGROUND: Drug patch tests (PTs) can reproduce delayed hypersensitivity to drugs and entail a moderate re-exposure of patients to offending drugs. OBJECTIVES: To determine the value of PTs for identifying the responsible drug in severe cutaneous adverse drug reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: In a multicentre study, PTs were conducted on patients referred for DRESS, AGEP or SJS/TEN within 1 year of their SCAR. All drugs administered in the 2 months prior to and the week following the onset of the SCAR were tested. RESULTS: Among the 134 patients included (48 male, 86 female; mean age 51·7 years), positive drug PTs were obtained for 24 different drugs. These included positive tests for 64% (46/72) of patients with DRESS, 58% (26/45) of those with AGEP and 24% (4/17) of those with SJS/TEN, with only one relapse of AGEP. The value of PTs depended on the type of drug and the type of SCAR (e.g. carbamazepine was positive in 11/13 DRESS cases but none of the five SJS/TEN cases). PTs were frequently positive for beta lactams (22 cases), pristinamycin (11 cases) and in DRESS with pump proton inhibitors (five cases), but were usually negative for allopurinol and salazopyrin. Of 18 patients with DRESS, eight had virus reactivation and positive PTs. In DRESS, multiple drug reactivity was frequent (18% of cases), with patients remaining sensitized many years later. CONCLUSIONS: PTs are useful and safe for identifying agents inducing SCAR.

Prognostic factors for response and survival in higher-risk myelodysplastic syndrome patients treated with azacitidine (AZA) remain largely unknown. Two hundred eighty-two consecutive high or intermediate-2 risk myelodysplastic syndrome patients received AZA in a compassionate, patient-named program. Diagnosis was RA/RARS/RCMD in 4%, RAEB-1 in 20%, RAEB-2 in 54%, and RAEB-t (AML with 21%-30% marrow blasts) in 22%. Cytogenetic risk was good in 31%, intermediate in 17%, and poor in 47%. Patients received AZA for a median of 6 cycles (1-52). Previous low-dose cytosine arabinoside treatment (P = .009), bone marrow blasts > 15% (P = .004), and abnormal karyotype (P = .03) independently predicted lower response rates. Complex karyotype predicted shorter responses (P = .0003). Performance status ≥ 2, intermediate- and poor-risk cytogenetics, presence of circulating blasts, and red blood cell transfusion dependency ≥ 4 units/8 weeks (all P < 10(-4)) independently predicted poorer overall survival (OS). A prognostic score based on those factors discriminated 3 risk groups with median OS not reached, 15.0 and 6.1 months, respectively (P < 10(-4)). This prognostic score was validated in an independent set of patients receiving AZA in the AZA-001 trial (P = .003). Achievement of hematological improvement in patients who did not obtain complete or partial remission was associated with improved OS (P < 10(-4)). In conclusion, routine tests can identify subgroups of patients with distinct prognosis with AZA treatment.

This review focuses on the radiosensitization strategies that use high-Z nanoparticles. It does not establish an exhaustive list of the works in this field but rather propose constructive criticisms pointing out critical factors that could improve the nano-radiation therapy. Whereas most reviews show the chemists and/or biologists points of view, the present analysis is also seen through the prism of the medical physicist. In particular, we described and evaluated the influence of X-rays energy spectra using a numerical analysis. We observed a lack of standardization in preclinical studies that could partially explain the low number of translation to clinical applications for this innovative therapeutic strategy. Pointing out the critical parameters of high-Z nanoparticles radiosensitization, this review is expected to contribute to a larger preclinical and clinical development.

Importance: High-flow nasal oxygen therapy is increasingly used for acute hypoxemic respiratory failure (AHRF). Objective: To determine whether high-flow oxygen therapy decreases mortality among immunocompromised patients with AHRF compared with standard oxygen therapy. Design, Setting, and Participants: The HIGH randomized clinical trial enrolled 776 adult immunocompromised patients with AHRF (Pao2 <60 mm Hg or Spo2 <90% on room air, or tachypnea >30/min or labored breathing or respiratory distress, and need for oxygen ≥6 L/min) at 32 intensive care units (ICUs) in France between May 19, 2016, and December 31, 2017. Interventions: Patients were randomized 1:1 to continuous high-flow oxygen therapy (n = 388) or to standard oxygen therapy (n = 388). Main Outcomes and Measures: The primary outcome was day-28 mortality. Secondary outcomes included intubation and mechanical ventilation by day 28, Pao2:Fio2 ratio over the 3 days after intubation, respiratory rate, ICU and hospital lengths of stay, ICU-acquired infections, and patient comfort and dyspnea. Results: Of 778 randomized patients (median age, 64 [IQR, 54-71] years; 259 [33.3%] women), 776 (99.7%) completed the trial. At randomization, median respiratory rate was 33/min (IQR, 28-39) vs 32 (IQR, 27-38) and Pao2:Fio2 was 136 (IQR, 96-187) vs 128 (IQR, 92-164) in the intervention and control groups, respectively. Median SOFA score was 6 (IQR, 4-8) in both groups. Mortality on day 28 was not significantly different between groups (35.6% vs 36.1%; difference, -0.5% [95% CI, -7.3% to +6.3%]; hazard ratio, 0.98 [95% CI, 0.77 to 1.24]; P = .94). Intubation rate was not significantly different between groups (38.7% vs 43.8%; difference, -5.1% [95% CI, -12.3% to +2.0%]). Compared with controls, patients randomized to high-flow oxygen therapy had a higher Pao2:Fio2 (150 vs 119; difference, 19.5 [95% CI, 4.4 to 34.6]) and lower respiratory rate after 6 hours (25/min vs 26/min; difference, -1.8/min [95% CI, -3.2 to -0.2]). No significant difference was observed in ICU length of stay (8 vs 6 days; difference, 0.6 [95% CI, -1.0 to +2.2]), ICU-acquired infections (10.0% vs 10.6%; difference, -0.6% [95% CI, -4.6 to +4.1]), hospital length of stay (24 vs 27 days; difference, -2 days [95% CI, -7.3 to +3.3]), or patient comfort and dyspnea scores. Conclusions and Relevance: Among critically ill immunocompromised patients with acute respiratory failure, high-flow oxygen therapy did not significantly decrease day-28 mortality compared with standard oxygen therapy. Trial Registration: clinicaltrials.gov Identifier: NCT02739451.

BACKGROUND: It is speculated that opioid-free anesthesia may provide adequate pain control while reducing postoperative opioid consumption. However, there is currently no evidence to support the speculation. The authors hypothesized that opioid-free balanced anesthetic with dexmedetomidine reduces postoperative opioid-related adverse events compared with balanced anesthetic with remifentanil. METHODS: Patients were randomized to receive a standard balanced anesthetic with either intraoperative remifentanil plus morphine (remifentanil group) or dexmedetomidine (opioid-free group). All patients received intraoperative propofol, desflurane, dexamethasone, lidocaine infusion, ketamine infusion, neuromuscular blockade, and postoperative lidocaine infusion, paracetamol, nefopam, and patient-controlled morphine. The primary outcome was a composite of postoperative opioid-related adverse events (hypoxemia, ileus, or cognitive dysfunction) within the first 48 h after extubation. The main secondary outcomes were episodes of postoperative pain, opioid consumption, and postoperative nausea and vomiting. RESULTS: The study was stopped prematurely because of five cases of severe bradycardia in the dexmedetomidine group. The primary composite outcome occurred in 122 of 156 (78%) dexmedetomidine group patients compared with 105 of 156 (67%) in the remifentanil group (relative risk, 1.16; 95% CI, 1.01 to 1.33; P = 0.031). Hypoxemia occurred 110 of 152 (72%) of dexmedetomidine group and 94 of 155 (61%) of remifentanil group patients (relative risk, 1.19; 95% CI, 1.02 to 1.40; P = 0.030). There were no differences in ileus or cognitive dysfunction. Cumulative 0 to 48 h postoperative morphine consumption (11 mg [5 to 21] versus 6 mg [0 to 17]) and postoperative nausea and vomiting (58 of 157 [37%] versus 37 of 157 [24%]; relative risk, 0.64; 95% CI, 0.45 to 0.90) were both less in the dexmedetomidine group, whereas measures of analgesia were similar in both groups. Dexmedetomidine patients had more delayed extubation and prolonged postanesthesia care unit stay. CONCLUSIONS: This trial refuted the hypothesis that balanced opioid-free anesthesia with dexmedetomidine, compared with remifentanil, would result in fewer postoperative opioid-related adverse events. Conversely, it did result in a greater incidence of serious adverse events, especially hypoxemia and bradycardia.

PURPOSE The PRIMA study (ClinicalTrials.gov identifier: NCT00140582 ) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety. METHODS Patients (&gt; 18 years of age) with previously untreated high–tumor-burden follicular lymphoma were nonrandomly assigned to receive one of three immunochemotherapy induction regimens. Responding patients were randomly assigned (stratified by induction regimen, response to induction treatment, treatment center, and geographic region) 1:1 to receive 2 years of rituximab maintenance (375 mg/m 2 , once every 8 weeks), starting 8 weeks after the last induction treatment, or observation (no additional treatment). All patients in the extended follow-up provided their written informed consent (data cutoff: December 31, 2016). RESULTS In total, 1,018 patients completed induction treatment and were randomly assigned to rituximab maintenance (n = 505) or observation (n = 513). Consent for the extended follow-up was provided by 607 patients (59.6%) of 1,018 (rituximab maintenance, n = 309; observation, n = 298). After data cutoff, median PFS was 10.5 years in the rituximab maintenance arm compared with 4.1 years in the observation arm (hazard ratio, 0.61; 95% CI, 0.52 to 0.73; P &lt; .001). No OS difference was seen in patients randomly assigned to rituximab maintenance or observation (hazard ratio, 1.04; 95% CI, 0.77 to 1.40; P = .7948); 10-year OS estimates were approximately 80% in both study arms. No new safety signals were observed. CONCLUSION Rituximab maintenance after induction immunochemotherapy provides a significant long-term PFS, but not OS, benefit over observation.

Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical dysgenesis disorder associated with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder, which mainly affects females, can be inherited in a single pedigree with lissencephaly, a more severe disease which affects the male individuals. This clinical entity has been described as X-SCLH/LIS syndrome. Recently we have demonstrated that the doublecortin gene, which is localized on the X chromosome, is implicated in this disorder. We have now performed a systematic mutation analysis of doublecortin in 11 unrelated females with SCLH (one familial and 10 sporadic cases) and have identified mutations in 10/11 cases. The sequence differences include nonsense, splice site and missense mutations and these were found throughout the gene. These results provide strong evidence that loss of function of doublecortin is the major cause of SCLH. The absence of phenotype-genotype correlations suggests that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females.

BACKGROUND: Serum thyroglobulin (Tg) is the marker of differentiated thyroid cancer after initial treatment and TSH stimulation increases its sensitivity for the diagnosis of recurrent disease. AIM: The goal of the study is to compare the diagnostic values of seven methods for serum Tg measurement for detecting recurrent disease both during L-T4 treatment and after TSH stimulation. METHODS: Thyroid cancer patients who had no evidence of persistent disease after initial treatment (total thyroidectomy and radioiodine ablation) were studied at 3 months on L-T4 treatment (Tg1) and then at 9-12 months after withdrawal or recombinant human TSH stimulation (Tg2). Sera with anti-Tg antibodies or with an abnormal recovery test result were excluded from Tg analysis with the corresponding assay. The results of serum Tg determination were compared to the clinical status of the patient at the end of follow-up. RESULTS: Thirty recurrences were detected among 944 patients. A control 131I total body scan had a low sensitivity, a low specificity, and a low clinical impact. Assuming a common cutoff for all Tg assays at 0.9 ng/ml, sensitivity ranged from 19-40% and 68-76% and specificity ranged from 92-97% and 81-91% for Tg 1 and Tg2, respectively. Using assays with a functional sensitivity at 0.2-0.3 ng/ml, sensitivity was 54-63% and specificity was 89% for Tg1. Using the two methods with a lowest functional sensitivity at 0.02 and 0.11 ng/ml resulted in a higher sensitivity for Tg1 (81% and 78%), but at the expense of a loss of specificity (42% and 63%); finally, for these two methods, using an optimized functional sensitivity according to receiver operating characteristic curves at 0.22 and 0.27 ng/ml resulted in a sensitivity at 65% and specificity at 85-87% for Tg1. CONCLUSION: Using an assay with a lower functional sensitivity may give an earlier indication of the presence of Tg in the serum on L-T4 treatment and may be used to study the trend in serum Tg without performing any TSH stimulation. Serum Tg determination obtained after TSH stimulation still permits a more reliable assessment of cure and patient's reassurance.

AIM OF FAST-MI 2010: To gather data on characteristics, management and outcomes of patients hospitalised for acute myocardial infarction (AMI) at the end of 2010 in France. INTERVENTIONS: To provide cardiologists and health authorities national and regional data on AMI management every 5 years. SETTING: Metropolitan France. 213 academic (n=38), community (n=110), army hospitals (n=2), private clinics (n=63), representing 76% of centres treating AMI patients. Inclusion from 1 October 2010. POPULATION: Consecutive patients included during 1 month, with a possible extension of recruitment up to one additional month (132 centres); 4169 patients included over the entire recruitment period, 3079 during the first 31 days; 249 additional patients declining participation (5.6%). STARTPOINTS: Consecutive adults with ST-elevation and non-ST-elevation AMI with symptom onset ≤48 h. Patients with AMI following cardiovascular procedures excluded. DATA CAPTURE: Web-based collection of 385 items (demographic, medical, biologic, management data) recorded online from source files by external research technicians; case-record forms with automatic quality checks. Centralised biology in voluntary centres to collect DNA samples and serum. Long-term follow-up organised centrally with interrogation of municipal registry offices, patients' physicians, and direct contact with the patients. DATA QUALITY: Data management in Toulouse University. STATISTICAL ANALYSES: Université Paris Descartes, Université de Toulouse, Université Pierre et Marie Curie-Paris 06, Paris. ENDPOINTS AND LINKAGES TO OTHER DATA: In-hospital events; cardiovascular events, hospital admissions and mortality during follow-up. Linkage with Institute for National Statistics. ACCESS TO DATA: Available for research to any participating clinician upon request to executive committee (fastmi2010@yahoo.fr).

BACKGROUND: Anaphylaxis hospitalizations are increasing in many countries, in particular for medication and food triggers in young children. Food-related anaphylaxis remains an uncommon cause of death, but a significant proportion of these are preventable. AIM: To review published epidemiological data relating to food-induced anaphylaxis and potential risk factors of fatal and/or near-fatal anaphylaxis cases, in order to provide strategies to reduce the risk of severe adverse outcomes in food anaphylaxis. METHODS: We identified 32 published studies available in MEDLINE (1966-2017), EMBASE (1980-2017), CINAHL (1982-2017), using known terms and synonyms suggested by librarians and allergy specialists. RESULTS: Young adults with a history of asthma, previously known food allergy particularly to peanut/tree nuts are at higher risk of fatal anaphylaxis reactions. In some countries, cow's milk and seafood/fish are also becoming common triggers of fatal reactions. Delayed adrenaline injection is associated with fatal outcomes, but timely adrenaline alone may be insufficient. There is still a lack of evidence regarding the real impact of these risk factors and co-factors (medications and/or alcohol consumption, physical activities, and mast cell disorders). CONCLUSIONS: General strategies should include optimization of the classification and coding for anaphylaxis (new ICD 11 anaphylaxis codes), dissemination of international recommendations on the treatment of anaphylaxis, improvement of the prevention in food and catering areas, and dissemination of specific policies for allergic children in schools. Implementation of these strategies will involve national and international support for ongoing local efforts in relationship with networks of centres of excellence to provide personalized management (which might include immunotherapy) for the most at-risk patients.

BACKGROUND: Taking into account radiation doses, safety, and protection, we highlighted the features in which cone-beam computed tomography (CBCT) can offer an advantage compared to the conventional two-dimensional imaging in paediatric dentistry before orthodontic treatment. OBJECTIVE: The aim of this article was to conduct a systematic review to assess the diagnostic efficacy of CBCT in the paediatric population at a pre-orthodontic phase. SEARCH METHODS: MEDLINE via PubMed was searched to identify all peer-reviewed articles potentially relevant to the review until 1 July 2018. Relevant publications were selected by two reviewers independently. SELECTION CRITERIA: The literature selection for this systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was based on predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Data were collected on overall study characteristics and examination characteristics of the selected studies. Methodological quality of the selected studies was evaluated. Original studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Thereafter, levels of evidence were obtained according to Grading of Recommendations Assessment, Development and Evaluation criteria. RESULTS: As a result of the QUADAS assessment, a total of 37 articles were included in the protocol. Following a proper protocol, CBCT was regarded as a reliable tool for assessment and management of impacted canine and root fracture. It provided a better evaluation of normal and pathological condylar shape and volume. CBCT was a superior choice for pre-surgical diagnostic applications in cleft lip and/or palate over a medical computed tomography based on its lower radiation exposure, shorter investigation time, and low purchase costs. CONCLUSIONS: CBCT is justified only in those cases where conventional radiography fails to provide a correct diagnosis of pathology. Therefore, it cannot be regarded as a standard method of diagnosis. CBCT imaging may also be justified when it positively affects treatment options or provides treatment optimization. REGISTRATION: None. CONFLICT OF INTEREST: None to declare.

A previous randomized trial found that sunscreen use could extend intentional sun exposure, thereby possibly increasing the risk of cutaneous melanoma. In a similarly designed trial, we examined the effect of the use of sunscreens having different sun protection factor (SPF) on actual exposure to ultraviolet B (UVB) and ultraviolet A (UVA) radiation. In June 1998, 58 European participants 18-24 years old were randomized to receive a SPF 10 or 30 sunscreens and were asked to complete daily records of their sun exposure during their summer holidays of whom 44 utilized a personal UVA and UVB dosimeter in a standard way during their sunbathing sessions. The median daily sunbathing duration was 2.4 hours in the SPF 10 group and 3.0 hours in the SPF 30 group (P = 0.054). The increase in daily sunbathing duration was paralleled by an increase in daily UVB exposure, but not by changes in UVA or UVB accumulated over all sunbathing sessions, or in daily UVA exposure. Of all participants, those who used the SPF 30 sunscreen and had no sunburn spent the highest number of hours in sunbathing activities. Differences between the two SPF groups in total number of sunbathing hours, daily sunbathing duration, and daily UVB exposure were largest among participants without sunburn during holidays. Among those with sunburn, the differences between the two groups tended to reduce. In conclusion, sunscreens used during sunbathing tended to increase the duration of exposures to doses of ultraviolet radiation below the sunburn threshold.

OBJECTIVE: The aim of this study was to describe the presentation and outcomes of patients with granulomatosis with polyangiitis (GPA) presenting with CNS involvement. METHODS: Patients were included in this nationwide retrospective study if they had GPA according to ACR criteria and/or the European Medicines Agency algorithm and CNS involvement. RESULTS: Thirty-five patients were included in the study. CNS involvement was observed in 51% of patients at GPA diagnosis. Headache (66%) was the main symptom, followed by sensory (43%) and motor impairment (31%). CNS involvement was characterized by pachymeningitis in 20, cerebral ischaemic lesions in 15 and haemorrhagic lesions in 2, with hypophyseal involvement in 2 patients. According to the clinical-radiological presentation, we distinguished granulomatous (G-CNS) and vasculitic (V-CNS) phenotypes. G-CNS patients more frequently had headaches, while V-CNS patients more frequently had motor impairment and renal involvement. Induction therapy produced clinical responses in 86% of patients. Baseline modified Rankin scale was higher for V-CNS than G-CNS patients (3 vs 2, P = 0.002). Initial spinal cord pachymeningitis was significantly associated with the need for a new induction regimen for relapsing/refractory disease (P = 0.01). Long-term neurological sequelae were noted in 51% of patients, including 35% with G-CNS and 69% with V-CNS (P = 0.08). Neurological sequelae were mainly noted in cases of spinal cord pachymeningitis (100%) and ischaemic or haemorrhagic lesions (73%). CONCLUSION: The clinical-radiological phenotype distinguished different long-term outcomes in patients with GPA and CNS involvement. Long-term neurological sequelae persisted in half of patients, mainly those with spinal cord pachymeningitis and vasculitic lesions.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)-like, acute lymphoid leukemia (ALL)-like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])-like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.

To compensate for poor acute pain detection in elderly inpatients with inability to communicate verbally (ICV), the Doloplus Collective team devised the 5-item Algoplus behavior-assessment scale specifically aimed at quickly detecting acute pain in these individuals. Algoplus was developed in three successive phases, including expert opinions, caregivers interviews, patient video recordings and statistical procedures. Among the 1500 recorded primary pain behaviors, 48 were selected and clustered into a 5-item scale. This version was validated based on 349 old inpatients (204 with acute pain and 145 without) from different care settings and hospitals. Comparators were objective acute pain clinical situations, experts' clinical judgment on acute pain presence, and self-rating scales (Visual Analog Scale, Numeric Rating Scale and Verbal Descriptor Scale) for a communicative subsample (n=134). Algoplus showed good discriminant validity with adequate internal consistency (Kuder-Richardson-20, 0.712), excellent interrater reliability (intraclass coefficient, 0.812) and high sensitivity to change during specific pain situations and after starting pain management. Excellent correlations were observed between Algoplus and experts' clinical judgment, acute pain clinical situations or each comparator self-rating-pain score. For patients with acute pain conditions, a score ⩾2 out of 5 on the Algoplus scale was retained as the threshold for the presence of acute pain in elderly ICV inpatients, with 87% sensitivity and 80% specificity. In addition, the very brief rating time of ∼1min is particularly relevant in acute-care settings, where repetitive pain-monitoring is required.

Membranous Nephropathy (MN) is an autoimmune disease associated with antibodies against podocyte proteins: M-type phospholipase A2 receptor (PLA2R1) or thrombospondin type-1 domain-containing 7A (THSD7A) in 70% and 3% of patients, respectively. Antibody titer is correlated with disease activity. Therefore, decreasing PLA2R1-Antibodies titer has become an important goal of therapy. Rituximab a chimeric monoclonal antibody induces remission in 60-80% of MN patients. All monoclonal antibodies such as rituximab can elicit antidrug antibodies, which may interfere with therapeutic response. We aim to analyze the relevance of anti-rituximab antibodies on the outcome of MN after a first course of rituximab. Forty-four MN patients were included and treated with two 1g infusions of rituximab at 2-week interval. Anti-rituximab antibodies, CD19 count, and clinical response were analyzed. Then, we (i) analyzed the association of anti-rituximab antibodies at month-6 with response to treatment: remission, relapse and the need for another rituximab course; (ii) confirmed if anti-rituximab antibodies could neutralize rituximab B-cells depletion and (iii) tested whether anti-rituximab antibodies could cross-inhibit new humanized anti-CD20 therapies. Anti-rituximab antibodies were detected in 10 patients (23%). Seventeen patients received a second rituximab course after a median time of 12 months [7-12], following nine cases of resistance and eight relapses. Anti-rituximab antibodies were significantly associated with faster B-cell reconstitution at month-6 (75 [57-89] vs 2 [0-41] cells/μl, p=0.006), higher proteinuria 12 months after rituximab infusion (1.7 [0.7; 5.8] vs 0.6 [0.2; 3.4], p=0.03) and before treatment modification (3.5 [1.6; 7.1] vs 1.7 [0.2; 1.7] p=0.0004). Remission rate 6 months after rituximab was not different according to anti-rituximab status (p>0.99) but the rate of relapse was significantly higher for patients with anti-rituximab antibodies (p<0.001). These patients required more frequently a second course of rituximab infusions (7/10 vs 10/34, p=0.03). Anti-rituximab antibodies neutralized rituximab activity in 8/10 patients and cross-reacted with other humanized monoclonal antibodies in only two patients. Three patients with anti-rituximab antibodies were successfully treated with ofatumumab. Anti-rituximab antibodies could neutralize rituximab B cells cytotoxicity and impact clinical outcome of MN patients. Humanized anti-CD20 seems to be a satisfying therapeutic alternative for patients with anti-rituximab antibodies and resistant or relapsing MN.