Double-bundle transtibial posterior cruciate ligament reconstruction with a tendon-patellar bone-semitendinosus tendon autograft: clinical results with a minimum of 2 years' follow-up.

PURPOSE: The purpose of this study was to evaluate the clinical and subjective outcomes after arthroscopic-assisted double-bundle posterior cruciate ligament (PCL) reconstruction. METHODS: A series of 15 patients with grade III isolated chronic PCL tears underwent double-bundle PCL reconstruction. Of these patients, 8 (53%) had simultaneous fractures. The mean time from accident to surgery was 10.8 months (range, 8 to 15 months). The mean age at the time of surgery was 28.2 years (range, 17 to 43 years). All of the patients reported knee insecurity during activities of daily living or light sporting activities, with associated anterior knee pain in 5 patients. Preoperatively, posterolateral or posteromedial corner injuries were ruled out through accurate clinical examination. The knees were assessed before surgery and at a mean follow-up of 3.2 years (range, 2 to 5 years) with a physical examination, 4 different rating scales, and stress radiographs obtained with a Telos device (Telos, Marburg, Germany). RESULTS: Postoperative physical examination revealed a reduction of the posterior drawer and tibial step-off in all cases, although the posterior laxity was not completely normalized. Nevertheless, the patients were subjectively better after surgery. The subjective International Knee Documentation Committee score was significantly ameliorated. With regard to the objective International Knee Documentation Committee score, 6 knees (40%) were graded as abnormal because of posterior displacement of 6 mm or greater on follow-up stress radiographs with the Telos device. On the Lysholm knee scoring scale, the score was excellent in 13% of patients and good in 87%. The mean score on the Hospital for Special Surgery knee ligament rating scale was 85.8. The Tegner activity score showed an amelioration after surgery, but no patient resumed his or her preinjury level of activities. The postoperative stress radiographs revealed an improvement in posterior instability of 50% or more in all but 3 knees (20%). CONCLUSIONS: Our technique of double-bundle PCL reconstruction produced a significant reduction in knee symptoms and allowed the patients to return to moderate or strenuous activity, although the posterior tibial translation was not completely normalized and our results appear to be no better than the results of single-bundle PCL reconstruction. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Measurement of multi-segment foot joint angles during gait using a wearable system.

Usually the measurement of multi-segment foot and ankle complex kinematics is done with stationary motion capture devices which are limited to use in a gait laboratory. This study aimed to propose and validate a wearable system to measure the foot and ankle complex joint angles during gait in daily conditions, and then to investigate its suitability for clinical evaluations. The foot and ankle complex consisted of four segments (shank, hindfoot, forefoot, and toes), with an inertial measurement unit (3D gyroscopes and 3D accelerometers) attached to each segment. The angles between the four segments were calculated in the sagittal, coronal, and transverse planes using a new algorithm combining strap-down integration and detection of low-acceleration instants. To validate the joint angles measured by the wearable system, three subjects walked on a treadmill for five minutes at three different speeds. A camera-based stationary system that used a cluster of markers on each segment was used as a reference. To test the suitability of the system for clinical evaluation, the joint angle ranges were compared between a group of 10 healthy subjects and a group of 12 patients with ankle osteoarthritis, during two 50-m walking trials where the wearable system was attached to each subject. On average, over all joints and walking speeds, the RMS differences and correlation coefficients between the angular curves obtained using the wearable system and the stationary system were 1 deg and 0.93, respectively. Moreover, this system was able to detect significant alteration of foot and ankle function between the group of patients with ankle osteoarthritis and the group of healthy subjects. In conclusion, this wearable system was accurate and suitable for clinical evaluation when used to measure the multi-segment foot and ankle complex kinematics during long-distance walks in daily life conditions.

Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial.

BACKGROUND: Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses. Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis. METHODS: In this double-blind, randomised, placebo-controlled, parallel group phase III study, 623 patients with moderate to severe active rheumatoid arthritis were randomly assigned with an interactive voice response system, stratified by site with a randomisation list provided by the study sponsor, to receive tocilizumab 8 mg/kg (n=205), tocilizumab 4 mg/kg (214), or placebo (204) intravenously every 4 weeks, with methotrexate at stable pre-study doses (10-25 mg/week). Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20% improvement in both swollen and tender joint counts. The primary endpoint was the proportion of patients with 20% improvement in signs and symptoms of rheumatoid arthritis according to American College of Rheumatology criteria (ACR20 response) at week 24. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00106548. FINDINGS: The intention-to-treat analysis population consisted of 622 patients: one patient in the 4 mg/kg group did not receive study treatment and was thus excluded. At 24 weeks, ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo (120 [59%] patients in the 8 mg/kg group, 102 [48%] in the 4 mg/kg group, 54 [26%] in the placebo group; odds ratio 4.0 [95% CI 2.6-6.1], p<0.0001 for 8 mg/kg vs placebo; and 2.6 [1.7-3.9], p<0.0001 for 4 mg/kg vs placebo). More people receiving tocilizumab than those receiving placebo had at least one adverse event (143 [69%] in the 8 mg/kg group; 151 [71%] in the 4 mg/kg group; 129 [63%] in the placebo group). The most common serious adverse events were serious infections or infestations, reported by six patients in the 8 mg/kg group, three in the 4 mg/kg group, and two in the placebo group. INTERPRETATION: Tocilizumab could be an effective therapeutic approach in patients with moderate to severe active rheumatoid arthritis. FUNDING: F Hoffmann-La Roche, Chugai Pharmaceutical.

The joint influence of gender and amount of smoking on weight gain one year after smoking cessation.

Weight gain is often associated with smoking cessation and may discourage smokers from quitting. This study estimated the weight gained one year after smoking cessation and examined the risk factors associated with weight gain in order to identify socio-demographic groups at higher risk of increased weight after quitting. We analyzed data from 750 adults in two randomized controlled studies that included smokers motivated to quit and found a gradient in weight gain according to the actual duration of abstinence during follow-up. Subjects who were abstinent for at least 40 weeks gained 4.6 kg (SD = 3.8) on average, compared to 1.2 kg (SD = 2.6) for those who were abstinent less than 20 weeks during the 1-year follow-up. Considering the duration of abstinence as an exposure variable, we found an age effect and a significant interaction between sex and the amount of smoking before quitting: younger subjects gained more weight than older subjects; among light smokers, men gained more weight on average than women one year after quitting, while the opposite was observed among heavy smokers. Young women smoking heavily at baseline had the highest risk of weight gain after quitting.

Visualisation of human rad52 protein and its complexes with hRad51 and DNA.

The human Rad52 protein stimulates joint molecule formation by hRad51, a homologue of Escherichia coli RecA protein. Electron microscopic analysis of hRad52 shows that it self-associates to form ring structures with a diameter of approximately 10 nm. Each ring contains a hole at its centre. hRad52 binds to single and double-stranded DNA. In the ssDNA-hRad52 complexes, hRad52 was distributed along the length of the DNA, which exhibited a characteristic "beads on a string" appearance. At higher concentrations of hRad52, "super-rings" (approximately 30 nm) were observed and the ssDNA was collapsed upon itself. In contrast, in dsDNA-hRad52 complexes, some regions of the DNA remained protein-free while others, containing hRad52, interacted to form large protein-DNA networks. Saturating concentrations of hRad51 displaced hRad52 from ssDNA, whereas dsDNA-Rad52 complexes (networks) were more resistant to hRad51 invasion and nucleoprotein filament formation. When Rad52-Rad51-DNA complexes were probed with gold-conjugated hRad52 antibodies, the presence of globular hRad52 structures within the Rad51 nucleoprotein filament was observed. These data provide the first direct visualisation of protein-DNA complexes formed by the human Rad51 and Rad52 recombination/repair proteins.

A double-blind, randomized study comparing pure chromated glycerin with chromated glycerin with 1% lidocaine and epinephrine for sclerotherapy of telangiectasias and reticular veins.

BACKGROUND Chromated glycerin (CG) is an effective, although painful, sclerosing agent for telangiectasias and reticular leg veins treatment. OBJECTIVE To determine pain level and relative efficacy of pure or one-third lidocaine-epinephrine 1% mixed chromated glycerin in a prospective randomized double-blind trial. METHOD Patients presenting with telangiectasias and reticular leg veins on the lateral aspect of the thigh (C(1A) or (S) E(P) A(S) P(N1) ) were randomized to receive pure CG or CG mixed with one-third lidocaine-epinephrine 1% (CGX) treatment. Lower limb photographs were taken before and after treatment and analyzed by blinded expert reviewers for efficacy assessment (visual vein disappearance). Patients' pain and satisfaction were assessed using visual analogue scales. RESULTS Data from 102 of 110 randomized patients could be evaluated. Patient pain scores were significantly higher when pure CG was used than with CGX (p<.001). Patient satisfaction with treatment outcome was similar in the two groups. Objective visual assessment of vessel disappearance revealed no significant difference between the two agents (p=.07). CONCLUSION Addition of lidocaine-epinephrine 1% to CG, in a ratio of one-third, significantly reduces sclerotherapy pain without affecting efficacy when treating telangiectasias and reticular leg veins. The authors have indicated no significant interest with commercial supporters.

Chondrodysplasia and Abnormal Joint Development Associated with Mutations in IMPAD1, Encoding the Golgi-Resident Nucleotide Phosphatase, gPAPP.

We used whole-exome sequencing to study three individuals with a distinct condition characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, cleft palate, and facial dysmorphism. Affected individuals carried homozygous missense mutations in IMPAD1, the gene coding for gPAPP, a Golgi-resident nucleotide phosphatase that hydrolyzes phosphoadenosine phosphate (PAP), the byproduct of sulfotransferase reactions, to AMP. The mutations affected residues in or adjacent to the phosphatase active site and are predicted to impair enzyme activity. A fourth unrelated patient was subsequently found to be homozygous for a premature termination codon in IMPAD1. Impad1 inactivation in mice has previously been shown to produce chondrodysplasia with abnormal joint formation and impaired proteoglycan sulfation. The human chondrodysplasia associated with gPAPP deficiency joins a growing number of skeletoarticular conditions associated with defective synthesis of sulfated proteoglycans, highlighting the importance of proteoglycans in the development of skeletal elements and joints.

Efficacy of vitamin D3 as add-on therapy in patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon β-1a: a Phase II, multicenter, double-blind, randomized, placebo-controlled trial.

Recent studies have demonstrated the immunomodulatory properties of vitamin D, and vitamin D deficiency may be a risk factor for the development of MS. The risk of developing MS has, in fact, been associated with rising latitudes, past exposure to sun and serum vitamin D status. Serum 25-hydroxyvitamin D [25(OH)D] levels have also been associated with relapses and disability progression. The identification of risk factors, such as vitamin D deficiency, in MS may provide an opportunity to improve current treatment strategies, through combination therapy with established MS treatments. Accordingly, vitamin D may play a role in MS therapy. Small clinical studies of vitamin D supplementation in patients with MS have reported positive immunomodulatory effects, reduced relapse rates and a reduction in the number of gadolinium-enhancing lesions. However, large randomized clinical trials of vitamin D supplementation in patients with MS are lacking. SOLAR (Supplementation of VigantOL(®) oil versus placebo as Add-on in patients with relapsing-remitting multiple sclerosis receiving Rebif(®) treatment) is a 96-week, three-arm, multicenter, double-blind, randomized, placebo-controlled, Phase II trial (NCT01285401). SOLAR will evaluate the efficacy of vitamin D(3) as add-on therapy to subcutaneous interferon beta-1a in patients with RRMS. Recruitment began in February 2011 and is aimed to take place over 1 calendar year due to the potential influence of seasonal differences in 25(OH)D levels.