Elodie Drumez

Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphoma

Allogeneic hematopoietic cell transplantation (allo-HCT) is indicated for patients with relapsed or refractory Hodgkin lymphoma (HL). Although long-term disease control can be achieved, relapse is still frequent. The programmed cell death protein 1 (PD-1) pathway-blocking antibody nivolumab has shown substantial therapeutic activity and an acceptable safety profile in patients with relapsed or refractory HL who did not receive allo-HCT. However, PD-1 blocking strategy can increase the risk of graft-versus-host disease (GVHD) in murine models. We retrospectively assessed the efficacy and toxicity of nivolumab as a single agent in 20 HL patients relapsing after allo-HCT. GVHD occurred in 6 patients (30%) after nivolumab initiation. All 6 patients had prior history of acute GVHD. The patients with nivolumab-induced GVHD were managed by standard treatment for acute GVHD. Two patients died as a result of GVHD, 1 of progressive disease and 1 of complications related to a second allo-HCT. Overall response rate was 95%. At a median follow-up of 370 days, the 1-year progression-free survival rate was 58.2% (95% CI, 33.1%-76.7%) and the overall survival rate was 78.7% (95% CI, 52.4%-91.5%). Among 13 patients still in response, 6 received a single dose of nivolumab and 7 remain on nivolumab. Compared with standard options for this indication, our results show that nivolumab is effective with an acceptable safety profile.

Predictors of the Aspiration Component Success of a Direct Aspiration First Pass Technique (ADAPT) for the Endovascular Treatment of Stroke Reperfusion Strategy in Anterior Circulation Acute Stroke.

Background and Purpose— A direct aspiration first pass technique (ADAPT) has been reported to be fast, safe, and effective for the treatment of acute ischemic stroke. The aim of this study is to determine the preoperative factors that affect success of the aspiration component of the technique in ischemic stroke patients with large vessel occlusion in the anterior circulation. Methods— We enrolled all 347 consecutive patients with anterior circulation acute ischemic stroke admitted for mechanical thrombectomy at our institution from August 2013 to October 2015 and treated by ADAPT for the endovascular treatment of stroke. Baseline and procedural characteristics, modified thrombolysis in cerebral infarction scores, and 3-month modified Rankin Scale were captured and analyzed. Results— Among the 347 patients (occlusion sites: middle cerebral artery=200, 58%; internal carotid artery Siphon=89, 25%; Tandem=58, 17%), aspiration component led to successful reperfusion (modified thrombolysis in cerebral infarction 2b/3 scores) in 55.6% (193/347 patients), stent retrievers were required in 40%, and a total successful final reperfusion rate of 83% (288/347) was achieved. Overall, procedural complications occurred in 13.3% of patients (48/347). Modified Rankin Scale score of 0 to 2 at 90 days was reported in 45% (144/323). Only 2 factors positively influenced the success of the aspiration component: an isolated middle cerebral artery occlusion (P<0.001) and a shorter time from stroke onset to clot contact (P=0.018). Conclusions— In this large retrospective study, ADAPT was shown to be safe and effective for anterior circulation acute ischemic stroke with a final successful reperfusion achieved in 83%. The site of arterial occlusion and delay of the procedure were predictors for reperfusion. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02523261, NCT02678169, and NCT02466893.

Reproducibility of digital measurements of lower-limb deformity on plain radiographs and agreement with CT measurements

INTRODUCTIONnFive angles (HKA, HKS, alpha, beta, tibial slope) are used for goniometry in total knee arthroplasty. The reproducibility of the measurement of these angles has been assessed on plain and digitized x-rays, but to our knowledge, this has not been confirmed on x-rays taken on the PACS system and they have not been compared to computed tomography (CT) measurements, the reference for angle measurement. This prospective study aimed to: (1) evaluate the inter- and intrarater reliability of the measurement of these angles on digital x-rays taken on a PACS; (2) determine the agreement of these measurements with those obtained using a CT protocol.nnnHYPOTHESISnThe measurements of these five angles on digitized radiographs are reproducible and in agreement with CT values.nnnMATERIAL AND METHODSnForty-two patients suffering from knee osteoarthritis and scheduled for total knee arthroplasty were included in the study. Each patient had a PACS digitized x-ray and a CT intended to produce patient-specific instrumentation (Symbios, Yverdon, Switzerland) including measurements of the angles evaluated. Four senior orthopaedic surgeon-raters measured all the angles twice. Inter- and intrarater reliability was then calculated as well as the agreement between the second measurement of each rater and the CT measurement using interclass correlation and kappa coefficients (data provided as means and 95% confidence intervals).nnnRESULTSnThe inter- and intrarater reliability values were excellent for the HKA, alpha, and beta angles (with, respectively, a coefficient of 0.99 [0.97-0.99], 0.84 [0.76-0.9], and 0.94 [0.86-0.96] interrater reliability and 0.98 [0.96-0.99], 0.86 [0.75-0.92], and 0.65 [0.44-0.8] intrarater reliability). Interrater reliability was low for HKS and tibial slope angles (coefficients all<0.4 for interrater reliability and <0.7 for intrarater reliability). The x-ray/CT agreement was very good for the HKA, alpha, and beta angles (0.81 [0.67-0.99], 0.74 [0.56-0.91], and 0.74 [0.45-0.92], respectively) and low for the HKS and tibial slope angles (all<0.45).nnnDISCUSSION/CONCLUSIONnThe HKA, alpha, and beta angles were reproducible for digital radiographs and showed good agreement with CT measurements. HKS and tibial slope angles should be used with greater caution, and other navigation methods or patient-specific instrumentation should be explored.nnnLEVEL OF EVIDENCEnLevelxa0III, prospective, comparative diagnostic case-control study.

Long-term outcome of implantable cardioverter-defibrillator implantation in secondary prevention of sudden cardiac death.

BACKGROUNDnLittle is known about the long-term outcomes of patients who receive an implantable cardioverter-defibrillator (ICD) for purely secondary prevention indications.nnnAIMSnTo assess the rates and predictors of appropriate therapies over a very long-term follow-up period in this population.nnnMETHODSnBetween June 2003 and August 2006, 239 consecutive patients with structural left ventricular disease and a secondary prophylaxis indication for ICD therapy (survivors of life-threatening ventricular tachyarrhythmias) were prospectively enrolled. An extended follow-up of these patients was carried out. The primary endpoint was the occurrence of appropriate device therapy. Secondary endpoints were all-cause death, electrical storm and inappropriate therapy.nnnRESULTSnThe study population consisted of 239 patients (90% men; mean age 64±12 years; 72% ischaemic cardiomyopathy; left ventricular ejection fraction 37±12%). During a median follow-up of 7.8 (3.5-9.3) years, appropriate device therapy occurred in 139 (58.2%) patients. Death occurred in 141 patients (59%), electrical storm in 73 (30.5%) and inappropriate therapy in 42 (17.6%). Multivariable analysis identified patients whose presenting arrhythmia was ventricular fibrillation as being less likely to require appropriate device therapy than those whose presenting arrhythmia was ventricular tachycardia (sub-hazard ratio 0.62, 95% confidence interval 0.40-0.97; P=0.04). Independent predictors of all-cause death were age at implantation (P<0.0001), wide QRS complexes (P=0.024), creatinine concentration (P=0.0002) and B-type natriuretic peptide at implantation (P=0.0001).nnnCONCLUSIONnSecondary prevention ICD recipients exhibit a high risk of appropriate device therapy and death over prolonged follow-up. Patients who presented initially with ventricular fibrillation were less likely to require the delivery of appropriate device therapy.

Low HDL levels in sepsis versus trauma patients in intensive care unit

BackgroundThe protective cardiovascular effect of high-density lipoproteins (HDLs) is considered to chiefly rely on reverse cholesterol transport from peripheral tissues back to the liver. However, HDL particles display pleiotropic properties, including anti-inflammatory, anti-apoptotic or antioxidant functions. Some studies suggest that HDL concentration decreases during sepsis, and an association was reported between low HDL levels and a poor outcome. Like sepsis, trauma is also associated with a systemic inflammatory response syndrome. However, no study has yet explored changes in lipid profiles during trauma. We sought to compare lipid profiles between sepsis and trauma patients in intensive care unit (ICU). In septic patients, we analyzed the association between lipid profile, severity and prognosis.MethodsA prospective, observational, single-centered study was conducted in a surgical ICU. For each patient, total cholesterol, HDL, triglyceride and low-density lipoprotein cholesterol levels were assessed at admission. Short-term prognosis outcome was prospectively assessed.ResultsSeventy-five consecutive patients were admitted (50 sepsis and 25 trauma). There was no difference in SOFA and SAPSII scores between the two groups. Patients with sepsis had lower total cholesterol levels than patients with trauma. Regarding the lipoprotein profile, only HDLs differed significantly between the two groups (median [IQR]xa0=xa00.33xa0mmol/l [0.17–0.78] in sepsis patients versus median [IQR]xa0=xa00.99xa0mmol/l [0.74–1.28] in trauma patients; Pxa0<xa00.0001). Whereas ICU mortality was not associated with lipid levels in the sepsis group, a significant negative correlation was found between HDL concentration and the length of ICU stay (rxa0=xa0−0.35; Pxa0=xa00.03) in the group of survivor septic patients at ICU discharge. In addition, poor outcome defined as death or a SOFA score >6 at day 3 was associated with lower HDL levels (median [IQR]xa0=xa00.20xa0mmol/l [0.11–0.41] vs. 0.35xa0mmol/l [0.19–0.86] in patients with poor outcome versus others; Pxa0=xa00.03).ConclusionsLipid profile was totally different between sepsis and trauma in ICU patients: HDL levels were low in septic patients, whereas their concentration was not altered in trauma patients. This major difference reinforces the necessity to explore the therapeutic potential of HDL in sepsis.

Physical Fitness Reference Standards in French Youth: The BOUGE Program

Abstract Vanhelst, J, Julien, JL, Beghin, L, Drumez, E, Fardy, PS, Chapelot, D, Mikulovic, J, and Ulmer, Z. Physical fitness reference standards in French youth: The BOUGE program. J Strength Cond Res 31(6): 1709–1718, 2017—The aim of this study was to establish sex- and age-specific physical fitness percentiles in French youth. A sample of 11,186 children and adolescents (5,546 boys and 5,640 girls), aged between 10 and 15 years, was assessed in the French national BOUGE study. Participants were tested for their cardiorespiratory fitness, muscular endurance, speed, flexibility, and agility using the following tests: 20-m shuttle run tests, curl-ups test, 50-m sprint test, back-saver sit and reach test, and 10 × 5-m shuttle run test. Percentile values were estimated for French youth as a function of age stratified by sex using the generalized additive model for location, scale, and shape (GAMLSS). In general, physical fitness was better in boys than in girls, except for the back-saver sit and reach test, in which girls performed better. Except for the back-saver sit and reach test and 10 × 5-m shuttle run test, physical fitness performance was significantly associated with age. Sex- and age-specific normative values for physical fitness tests in French youth expressed as percentiles from the fifth to the 95th are provided. Reference values provide normative data for French youth. The data are useful in identifying special needs for appropriate intervention programs.

Does medial collateral ligament pie-crusting induce residual laxity in arthroscopic management of medial meniscus tears? A prospective study of 40 cases

INTRODUCTIONnArthroscopic meniscectomy and medial meniscal repair are frequent procedures, liable to be complicated by iatrogenic cartilage lesions, especially in tight knee. Medial collateral ligament pie-crusting was developed to counter this, but, although the technique is employed, its impact on medial laxity has not been precisely determined. We therefore conducted a prospective observational study to compare radiographic laxity preoperatively versus 6 weeks following pie-crusting.nnnHYPOTHESISnMedial collateral ligament pie-crusting alters radiographic laxity at 6 weeks.nnnMATERIAL AND METHODSnBetween December 2015 and February 2017, 40 patients (33 male, 7 female) underwent surgery with pie-crusting for isolated medial meniscal lesion. Mean age was 39 years (range, 20-54 years). Meniscectomy was performed in 33 cases (82.5%) and repair in 7 (17.5%). Pie-crusting used an intramuscular needle under arthroscopic control, adjacent to the medial meniscus at the posterior two-thirds junction of the compartment, until opening was deemed satisfactory. Laxity was compared on preoperative versus 6 weeks stress valgus views (Telos ™), by 2 independent observers, on 2 measurements: opening angle, and medial tibiofemoral joint space height. Each measurement was taken twice at a 2-week interval by each observer.nnnRESULTSnInter- and intra-observer concordance was excellent on both measurements: intraclass correlation coefficient was 0.82 (95% CI, 0.73-0.89) and 0.91 (95% CI, 0.86-0.94) pre- and post-operatively for opening angle, and 0.87 (95% CI, 0.79-0.92) and 0.88 (95% CI, 0.82-0.92) for joint space height. Tibiofemoral joint space opening was significantly greater at 6 weeks on both measurements: 0.9±1° [range, -1° to 4°] (p<0.0001) and 1.1±1mm [range, -0.6 to 3.2mm] (p<0.0001).nnnDISCUSSIONnMedial collateral ligament pie-crusting led to a moderate but significant increase in medial laxity at 6 weeks. A longer-term study is needed to assess progression.nnnLEVEL OF EVIDENCEnIV, prospective study without control group.

Conséquences dentosquelettiques du port d’orthèse d’avancée mandibulaire dans le cadre d’un SAHOS

Resume Les ortheses d’avancee mandibulaire (OAM) sont recommandees dans certains cas pour le traitement du syndrome d’apnees hypopnees obstructives du sommeil (SAHOS). L’objectif de cette etude est de comparer de facon retrospective les effets dentaires et squelettiques chez des patients atteints d’un SAHOS, apres port d’une OAM puis en fonction de son typexa0: semi-rigide ou rigide. Des criteres cephalometriques sur des teleradiographies de profil avant et apres au moins 6xa0mois de traitement ont ete analyses. Vingt-deux patients ont ete inclus. Nous avons retrouve une vestibuloversion moyenne des incisives mandibulaires (+4,1xa0±xa05,6 [ p xa0=xa00,0023]) et une diminution moyenne de l’ overbite (−1,6xa0±xa02,0xa0mm [ p xa0=xa00,0026]) et de l’ overjet (−1,4xa0±xa02,3xa0mm [ p xa0=xa00,0114]). La vestibuloversion des incisives mandibulaires a ete plus importante avec les OAM semi-rigides, de meme la diminution de l’ overbite et de l’ overjet a ete plus importante avec les OAM semi-rigides. Le port d’OAM a moyen terme entraine des modifications occlusales d’origine dentaire qui ne pourront etre corrigees que de facon orthodontique.

Dentoskeletal sequellae after wearing of a mandibular advancement device in an OSAHS setting

Mandibular advancement devices (MAD) are recommended in certain cases for the treatment of obstructive sleep apnea and hypopnea syndrome (OSAHS). The aim of this study was to make a retrospective investigation into the dental and skeletal effects in patients suffering from OSAHS after wearing an MAD, and according to the type of device, rigid or semi-rigid. Cephalometric criteria on lateral cephalograms before and after at least 6xa0months of treatment were analyzed. Twenty-two patients were included. We observed average labial tipping of the lower incisors (+4.1±5.6 [P=0.0023]) and reduced overbite (-1.6±2.0mm [P=0.0026]) and overjet (-1.4±2.3mm [P=0.0114]). Labial tipping of the mandibular incisors was more pronounced with semi-rigid MAD. Similarly, the decrease in overbite and overjet was more marked with the semi-rigid MAD. Medium-term wearing of MAD gives rise to dentally related occlusal changes, which can only be corrected by orthodontic treatment.