Efficacy and safety of turoctocog alfa in patients with hemophilia A requiring surgical procedures: A multicentre retrospective study.

BACKGROUND: Turoctocog alfa is a recombinant Factor VIII used in patients with hemophilia A. The aim is to assess the real-life evidence of turoctocog alfa in surgery. STUDY DESIGN AND METHODS: Data were extracted from a national database. RESULTS: Turoctocog alfa was used for 86 surgeries (49 major and 37 minor) in 56 patients. The results are expressed as medians (interquartile range). Six (10.7%) patients had severe hemophilia A, four (7.1%) moderate, and 46 (82.2%) mild. For patients who underwent major surgeries, basal plasma FVIII coagulant activity (FVIII:C) levels were 15 IU.dL-1 (8-22). Eight (5-14) infusions were given, at a preoperative loading dose of 40.0 (35.0-45.5) IU.kg-1 and a total dose of 253.3 (125.0-507.0) IU.kg-1 . In patients who underwent minor surgeries, basal FVIII:C levels were 18 IU.dL-1 (9-31). Two (1-3) infusions were required, at a preoperative loading dose of 34.0 (28.8-38.5) IU.kg-1 and a total dose of 73.7 (37.6-122.1) IU.kg-1 . The overall clinical efficacy was judged excellent/good in 77 procedures (89.5%) and fair/poor in nine (10.5%). The fair/poor efficacy concerned seven patients (six mild hemophilia and one severe), for four urological surgeries, two dermatological procedures, one heart surgery, one ear-nose-throat procedure, and one dental avulsion in the patient with severe hemophilia. Three out of those seven patients received antiplatelet therapy. No thromboembolic events, anti-FVIII antibodies, or adverse events were reported. DISCUSSION: The efficacy and safety of turoctocog alfa were confirmed for the management of surgery in patients with hemophilia A. No adverse events were observed and overall efficacy was good.

Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: Kappa free light chains (KFLC) seem to efficiently diagnose MS. However, extensive cohort studies are lacking to establish consensus cut-offs, notably to rule out non-MS autoimmune CNS disorders. Our objectives were to (1) determine diagnostic performances of CSF KFLC, KFLC index, and KFLC intrathecal fraction (IF) threshold values that allow us to separate MS from different CNS disorder control populations and compare them with oligoclonal bands' (OCB) performances and (2) to identify independent factors associated with KFLC quantification in MS. METHODS: We conducted a retrospective multicenter study involving 13 French MS centers. Patients were included if they had a noninfectious and nontumoral CNS disorder, eligible data concerning CSF and serum KFLC, albumin, and OCB. Patients were classified into 4 groups according to their diagnosis: MS, clinically isolated syndrome (CIS), other inflammatory CNS disorders (OIND), and noninflammatory CNS disorder controls (NINDC). RESULTS: One thousand six hundred twenty-one patients were analyzed (675 MS, 90 CIS, 297 OIND, and 559 NINDC). KFLC index and KFLC IF had similar performances in diagnosing MS from nonselected controls and OIND (p = 0.123 and p = 0.991 for area under the curve [AUC] comparisons) and performed better than CSF KFLC (p < 0.001 for all AUC comparisons). A KFLC index of 8.92 best separated MS/CIS from the entire nonselected control population, with better performances than OCB (p < 0.001 for AUC comparison). A KFLC index of 11.56 best separated MS from OIND, with similar performances than OCB (p = 0.065). In the multivariate analysis model, female gender (p = 0.003), young age (p = 0.013), and evidence of disease activity (p < 0.001) were independent factors associated with high KFLC index values in patients with MS, whereas MS phenotype, immune-modifying treatment use at sampling, and the FLC analyzer type did not influence KFLC index. DISCUSSION: KFLC biomarkers are efficient tools to separate patients with MS from controls, even when compared with other patients with CNS autoimmune disorder. Given these results, we suggest using KFLC index or KFLC IF as a criterion to diagnose MS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that KFLC index or IF can be used to differentiate patients with MS from nonselected controls and from patients with other autoimmune CNS disorders.

Risk factors for dislocation after revision total hip arthroplasty with a dual-mobility cup. Matched case-control study (16 cases vs. 48 controls).

BACKGROUND: Reports of high dislocation rates after revision total hip arthroplasty (THA) have encouraged the widespread use of dual-mobility cups. Dislocation has been less common but not fully abolished with dual-mobility cups, and its causes have remained unidentified. The objectives of this retrospective matched case-control study were: 1) to identify risk factors for dislocation, 2) and to assess dislocation outcomes. HYPOTHESIS: The causes of dislocation after revision THA with a dual-mobility cup can be identified. MATERIAL AND METHOD: Among 653 consecutive patients identified retrospectively as having undergone revision THA with a dual-mobility cup (Medial Cup, Aston, Saint-Étienne, France) between January 2007 and December 2017, 16 (2.45%) subsequently experienced dislocation, after a mean of 3.6 months (range, 0.9-19 months). For each of these 16 patients, we collected the main patient characteristics (age, sex, body mass index [BMI], ASA score, and reason for the initial arthroplasty procedure), local history (number of previous surgical procedures, reason for revision, femoral and acetabular bony defects classified according to Paprosky, and status of the abductor apparatus), and characteristics of the revision (approach, diameters of the cup and femoral head, cup inclination, femoral offset, lower limb length, and implant anteversion). Controls were patients without dislocation after revision dual-mobility THA. Each of the 16 patients was matched to 3 controls on age (±10 years), sex, year of revision, and whether revision was only acetabular or bipolar. Univariate and multivariate analyses were done to compare the cases and controls, and dislocation outcomes in the cases were evaluated. RESULTS: By univariate analyses, factors associated with dislocation were BMI>30 (cases, 37.5%; controls, 10.4%; p=0.02), larger number of previous surgical procedures on the same hip (cases, 2.8; controls, 1.8; p=0.004), larger number of arthroplasties (cases, 2.3; controls, 1.5; p=0.004), history of instability (cases, 31% with chronic dislocation and 13% with recurrent dislocation; controls, 6.25% and 2.1%, respectively; p=0.004), and compromised abductor apparatus (cases, 56.25%; controls, 14.6%; p=0.002). Independent risk factors for dislocation identified by multivariate analysis were instability (odds ratio [OR], 14.5; 95% confidence interval [95%CI], 1.5-149.9) and, most importantly, abductor apparatus compromise (OR, 43.1; 95%CI, 3.18-586.3). Of the 16 cases, 1 was lost to follow-up, 1 had contra-indications to anaesthesia, 1 died after several dislocation episodes, and 1 died 3 months after surgical reduction. In 5 cases, there was a single dislocation episode. Further surgery was performed in 8 cases (surgical reduction, n=1; constrained cup, n=3; trochanteric internal fixation, n=1; exchange of the dual-mobility cup, n=2, including 1 with subsequent dislocation episodes; and femoral component exchange followed by a retentive cup due to further dislocation episodes, n=1). CONCLUSION: Risk factors for dislocation consisted of a history of instability and, most importantly, abductor apparatus compromise. A constrained cup should be considererd in patients with impaired abductor apparatus. No further dislocations occurred after reduction of the first episode in 31.25% of cases. Recurrent dislocation should prompt measures to correct impaired abductor apparatus whenever possible, as well as correction of any component malposition. Whether a retentive cup should be implanted routinely remains unclear. LEVEL OF EVIDENCE: III, matched case-control study.

Treatment of large deep osteochondritis lesions of the knee by autologous matrix-induced chondrogenesis (AMIC): Preliminary results in 13 patients.

BACKGROUND: Osteochondral defects due to advanced osteochondritis of the knee eventually cause osteoarthritis. Autologous matrix-induced chondrogenesis (AMIC) may hold potential for overcoming the treatment challenges raised by defects larger than 2cm2. The primary objective of this study was to assess medium-term functional outcomes of AMIC. The secondary objective was to confirm the absence of adverse events. HYPOTHESIS: AMIC significantly improves knee function in patients with osteochondritis responsible for osteochondral defects grade III or IV in the International Cartilage Repair Society (ICRS) classification. MATERIAL AND METHODS: A total of 13 consecutive patients managed using AMIC between September 2011 and November 2016 were included in a prospective, single-centre, single-surgeon study. There were 8 males and 5 females with a mean age of 29 years (range, 15-51 years). Among them, 9 had had previous surgery. The ICRS grade was IV in 12 patients and III in 1 patient. The defects had a mean surface area of 3.7cm2 (range, 2.2-6.9cm2) and mean depth of 0.5mm (range, 0.4-0.8). In each patient, knee function was assessed by an independent examiner based on validated instruments (Knee injury and Osteoarthritis Outcome Score [KOOS], subjective International Knee Documentation Committee [IKDC] score, and visual analogue scale [VAS] pain score). RESULTS: After a median follow-up of 24 months (range, 12-42 months; minimum, 1 year), 11 patients had significant improvements, with mean increases in the IKDC score and KOOS of 27 and 28 points, respectively. The scores remained stable after the first year. Of the 2 patients with poorer outcomes, 1 had a history of multiple surgical procedures and the other was a 51-year-old female with a defect surface area of 6.9cm2. No post-operative complications were recorded. CONCLUSION: AMIC is a reliable single-stage method that is both reproducible and widely available. AMIC significantly improves knee function scores in patients with large osteochondral defects due to advanced osteochondritis of the knee. LEVEL OF EVIDENCE: IV, prospective cohort study.