Search

Different types of ground hot-melt extrudates loaded with 10, 20 or 30 % of the poorly water-soluble drug tadalafil were prepared and characterized in vitro and in vivo (in rats). Soluplus was used as an amorphous carrier material, whereas mannitol and lactitol were studied as crystalline matrix formers. The systems were characterized using X-ray powder diffraction, thermogravimetric analysis coupled with quadruple mass spectrometry, differential scanning calorimetry, X-ray computed microtomography, in vitro drug release measurements and monitoring of drug plasma levels upon oral administration to rats. The pure drug substance and physical mixtures of tadalafil with the carrier materials were used as references. Importantly, the bioavailability of this poorly water-soluble drug could be substantially increased with the proposed formulations, and the in vitro and in vivo release rates could be effectively adjusted by choosing the appropriate type of carrier material: Whereas mannitol-based ground hot-melt extrudates rapidly released the drug and led to an early rise in drug plasma concentrations, Soluplus-based systems released tadalafil more slowly, resulting in delayed plasma peaks. These behaviors could be explained by the rapid disintegration/dissolution of the porous mannitol-based formulations, whereas Soluplus significantly swelled and the dissolved drug had to diffuse through the polymeric network prior to release. Blending these formulations can be expected to allow providing elevated drug concentrations in vivo during prolonged periods of time upon one single administration with a rapid onset of drug action., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Increasing the femoral offset when performing total hip arthroplasty (THA) theoretically increases the stresses and risks of the stem not integrating itself into bone. But this concept has not been validated for cementless stems; this led us to conduct a retrospective study to determine: (1) the risk factors for the occurrence of symptomatic femoral radiological abnormalities, (2) the incidence of these abnormal radiological findings, (3) the revision rate for aseptic non-integration of a cementless lateralized stem., Hypothesis: Young patients with significant femoral canal flare and a small cementless lateralized stem have a higher risk of abnormal osseointegration., Material and Methods: We analyzed retrospectively 172 consecutive lateralized stems (KHO, Corail™ product line) implanted during primary THA between 2006 and 2012 in 157 patients (mean age 68years±12.6 (20-95), 89% men). Radiographs were used to evaluate osseointegration scores, offset restoration and the Noble index. Kaplan-Meier survival analysis was performed using "symptomatic femoral radiological abnormalities" and "revision for aseptic stem non-integration" as endpoints., Results: The mean follow-up was 5.9years±2.7 (range, 2-12.4years). Being more than 70years of age (HR=0.7, 95% CI: [0.3-0.9], P=0.004) and having a larger stem (HR=0.6, 95% CI: [0.4-0.9], P=0.03) were protective against symptomatic femoral radiological abnormalities, while increasing the postoperative femoral offset (HR=1.1, 95% CI: [1.01-1.2], P=0.02) was deleterious. The survival free of "symptomatic femoral radiological abnormalities" was 93% (95% CI: 89-97) at 5years and 84% (95% CI: 75-95) at 8years. The survival free of "revision for aseptic stem non-integration" was 98% (95% CI: 96.8-100) at 5years and 97% (95% CI: 95.2-100) at 8years., Discussion: In this study, the risk factors for symptomatic radiological abnormalities were being less than 70years of age, having a small lateralized stem and restoring a large femoral offset. Lateralized stems used in this study had a 10% rate of symptomatic radiological abnormalities and a 4% rate of revision for aseptic non-integration., Level of Evidence: IV, retrospective study., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: In cases of chronic anterior laxity, reconstruction of the anterior cruciate ligament (ACL) can slow the development of osteoarthritis. This study was conducted to determine the overall prevalence of osteoarthritis and to identify the risk factors after ACL reconstruction., Hypothesis: Meniscus tears, time from injury to surgery, body mass index (BMI), residual laxity, and cartilage lesions influence the progression towards osteoarthritis., Materials and Methods: This multicenter, retrospective study on the outcome of cruciate ligaments at 12 years of follow-up was conducted within the 2014 SOFCOT Symposium. The cohort included 675 arthroscopic reconstructions of the ACL from January 2002 to December 2003. The clinical evaluation included the objective and subjective IKDC score. Osteoarthritis was analyzed on 589 knee X-rays according to the IKDC classification. The predictive factors of osteoarthritis development studied were age, gender, BMI, time from injury to surgery, activity level, medial or lateral meniscectomy, type of graft, medial or lateral chondropathy, tunnel positioning, and residual laxity. Univariate and multivariate analyses with logistic regression were performed., Results: The mean follow-up was 11.9±0.8 years. The subjective IKDC score was 83.7±13. At 12 years, the rate of moderate to severe osteoarthritis l (IKDCC or D) was 19% (16% medial tibiofemoral osteoarthritis, 4% lateral tibiofemoral osteoarthritis, and 2% patellofemoral osteoarthritis). The prognostic factors were age at surgery greater than 34 years (P<0.05), cartilage lesions at surgery (P<0.05), medial or lateral meniscectomy (P<0.05), and residual laxity (P<0.05)., Conclusions: This large-scale study identified risk factors for osteoarthritis that should improve the information provided to patients on long-term progression after ACL reconstruction., Level of Evidence: Retrospective cohort study, level IV., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Restoring the native hip anatomy increases hip prosthesis survival, whereas increased femoral lateralisation creates high torque stresses that may alter prosthesis fixation. After finding lucent lines around cementless lateralised stems (Corail™, DePuy Synthes, St Priest, France) in several patients, we evaluated the effects of lateralisation in a large case-series. The objective of our study was to compare lateralised vs standard stems of identical design in terms of radiological osteo-integration and survival., Hypothesis: Lateralised stems, despite being used only when indicated by the anatomical parameters, carry a higher risk of impaired osteo-integration., Materials and Methods: A retrospective study was conducted in 807 primary total hip arthroplasties (THAs) performed between 2006 and 2010 in 798 patients with a mean age of 65 ± 14.2 years. Lateralised stems were used in 280 cases (Corail High Offset KHO, n = 169; and Corail coxa vara KLA, n = 111 cases) and standard stems in 527 cases (Corail KA). Mean follow-up was 2.3 years (range, 1-7 years). The clinical evaluation included determination of the Postel-Merle d'Aubigné (PMA) score. Bone fixation and stability of the implants were assessed by determining the Engh and Massin score and the ARA score on the radiographs at last follow-up. Femoral, acetabular and global offset values were determined before and after THA. Nobles's Canal Flare Index was computed. Survival was estimated using the Kaplan-Meier method with surgical revision for aseptic loosening as the end-point., Results: The PMA score improved from 12 (10-15) pre-operatively to 17.7 (14-18) (P < 0.05). After THA, in the lateralised stem group, femoral offset was restored in 217 (77%) hips and the mean change vs the pre-operative offset value was -2 mm; in the standard stem group, femoral offset was restored in 440 (83.5%) hips and the mean change was +1 mm. The Engh and Massin score values were similar in the standard stem and lateralised stem groups (24.4 ± 2.2 and 22.6 ± 2.4, respectively, NS). Revision for aseptic loosening was required in 5 patients with lateralised stems (3 KHO and 2 KLA) versus none of the patients with standard stems. There were no cases of excessive femoral offset and the mean change in offset was -2.3mm (-5.3 to -1.1). Noble's index was increased (4.27 ± 0.5 for the loosened lateralised stems, 3.65 ± 0.8 for the well-fixed lateralised stems and 3.82 ± 0.6 for the standard stems), with no significant difference across groups. Overall survival after 3.5 years of follow-up was 94.6% (95% confidence interval, 88.4-100%) with lateralised stems and 100% with standard stems (P < 0.05)., Discussion: The risk of aseptic loosening was significantly higher with the lateralised stem (5/280, 1.8%) than with the standard stem (n = 0). Our findings indicate a need for careful preparation to obtain primary fixation of lateralised stems., Level of Evidence: III, retrospective case-control study., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Purpose: The purpose of this study is to review the indications for and outcomes of high tibial osteotomy in the treatment of patients with chronic knee laxity., Methods: A comprehensive literature review was performed to identify surgical indications and results of high tibial osteotomy for the treatment of chronic knee laxity., Results: Four distinct situations were identified in which a high tibial osteotomy may be advantageous: (1) anterior laxity with varus osteoarthritis, (2) chronic anterior laxity in the setting of varus with lateral ligamentous laxity, (3) chronic anterior laxity in the setting of a high tibial slope, and (4) chronic posterior laxity or posterolateral corner injury. A total of 24 studies were included in this report, including reports of the treatment of 410 knees as well as several review articles. The most frequently reported indication for that addition of HTO was anterior laxity in the setting of varus OA, which was noted to have good results, minimizing anterior knee laxity and allowing return to sports, while reducing the progression of osteoarthritis. More advanced cases in which lateral structures have also become stretched and incompetent are an excellent indication for HTO, with the need for subsequent lateral procedures dependent on the degree of varus laxity and especially hyperextension that is present. Excessive tibial slope has been identified as a cause of ACL reconstruction failure, and some authors have recommended addressing very high slope in revision cases. In knees with chronic posterior or posterolateral instability, correction of alignment first is generally recommended, with subsequent ligamentous procedures performed when instability persists., Conclusions: Knees with chronic instability pose a difficult treatment challenge. In all cases, the contribution of coronal plane alignment to varus-valgus knee stability must be carefully considered and addressed prior to ligament surgery. Sagittal plane alignment is also key and must not be overlooked. Such considerations drive the indication for osteotomy as well as the type of osteotomy that is chosen. Level of evidence IV.

Isolated congenital elbow contracture is a rare upper-extremity disorder and there are few data about management of this condition. Authors report their experience after aggressive management of children with isolated congenital elbow contracture in flexion. Because of total absence of range of motion (ROM) improvement despites physical therapy (ROM 90-120°) and bone deformity, an anterior surgical release of the elbow was performed through an extensive lateral approach, at sixteen months of age. After surgery, this child was treated by three casts at maximal gained extension followed by sequential Turnbuckles splints. After five years of follow-up, the result was excellent with ROM 5-135°, normal function and absence of growth disturbance. The limiting factor of this protocol was excessive traction in elbow extension on the neurovascular structures, especially the radial nerve. This treatment represents an aggressive management with multiple general anaesthesia, but was found to be a valid option., (Copyright © 2012. Published by Elsevier Masson SAS.)

We developed an automated pipeline for the detection of single nucleotide polymorphisms (SNPs) in expressed sequence tag (EST) data sets, by combining three DNA sequence analysis programs: Phred, Phrap and PolyBayes. This application requires access to the individual electrophoregram traces. First, a reference set of 65 SNPs was obtained from the sequencing of 30 gametes in 13 maritime pine (Pinus pinaster Ait.) gene fragments (6671 bp), resulting in a frequency of 1 SNP every 102.6 bp. Second, parameters of the three programs were optimized in order to retrieve as many true SNPs, while keeping the rate of false positive as low as possible. Overall, the efficiency of detection of true SNPs was 83.1%. However, this rate varied largely as a function of the rare SNP allele frequency: down to 41% for rare SNP alleles (frequency < 10%), up to 98% for allele frequencies above 10%. Third, the detection method was applied to the 18498 assembled maritime pine (Pinus pinaster Ait.) ESTs, allowing to identify a total of 1400 candidate SNPs, in contigs containing between 4 and 20 sequence reads. These genetic resources, described for the first time in a forest tree species, were made available at http://www.pierroton.inra/genetics/Pinesnps. We also derived an analytical expression for the SNP detection probability as a function of the SNP allele frequency, the number of haploid genomes used to generate the EST sequence database, and the sample size of the contigs considered for SNP detection. The frequency of the SNP allele was shown to be the main factor influencing the probability of SNP detection.