Faculty Bibliography
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372
Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
BACKGROUND:modulator, on disability progression in patients with SPMS. METHODS:This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18-60 years) with SPMS and an Expanded Disability Status Scale score of 3·0-6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. FINDINGS:1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65-0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. INTERPRETATION:Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. FUNDING:Novartis Pharma AG.
PMID: 29576505
ISSN: 1474-547x
CID: 5348122
I Am What I Am Because of Who We All Are: The 2017 American-British-Canadian Traveling Fellowship
PMID: 29509624
ISSN: 1535-1386
CID: 2974752
Medial meniscus grafting restores normal tibiofemoral contact pressures
BACKGROUND:Tissue excision in the setting of a meniscal tear has been shown to dramatically increase peak contact stresses in the affected tibiofemoral joint compartment, leading to the development of degenerative changes and osteoarthritis. PURPOSE/HYPOTHESIS/UNASSIGNED:The current in vitro study utilized a porcine model to evaluate the effectiveness of segmental medial meniscal grafting following partial meniscectomy. The study hypothesis was that the procedure would normalize medial tibofemoral joint compartment pressure magnitudes, areas, and locations relative to an intact meniscus. STUDY DESIGN/METHODS:Controlled laboratory study. METHODS:Using pressure film, medial tibiofemoral joint compartment peak, and mean pressure magnitudes, peak pressure location and peak pressure area were determined using 12 potted, fresh frozen, porcine knee specimens. Data were collected at three different knee flexion angles (90°, 45°, and 0°) for three conditions: intact medial meniscus, following resection of the central third of the medial meniscus, and following segmental medial meniscal grafting. For each condition, the potted femur was positioned horizontally in a bench vise clamp, while a 20 pound (88.96 N) axial compression force was manually applied for a 60 s duration by the primary investigator through the base of the potted tibia using a digital force gauge. RESULTS:Loss of the central 1/3 of the medial meniscus resulted in significant increases in the mean and peak pressures of the medial tibiofemoral joint compartment and decreased peak pressure area. Segmental meniscal grafting of the central third defect closely recreated the contact pressures and loading areas of the native, intact medial meniscus. CONCLUSION/CONCLUSIONS:From a static, time zero biomechanical perspective, segmental medial meniscus grafting of a partially meniscectomized knee restored mean pressure, peak pressure, and mean peak contact pressure areas of the medial tibiofemoral joint compartment back to levels observed in the intact medial meniscus at different knee flexion angles. In-vivo analysis under dynamic conditions is necessary to verify the healing efficacy and ability of the healed segmental medial meniscal allograft to provide long-term knee joint homeostasis when confronted with dynamic shear, rotatory, and combined, higher magnitude physiologic loading forces.
PMID: 29198047
ISSN: 1434-3916
CID: 2965132
Meniscal Root Tears Evaluation and Management
The management of meniscal root injuries has changed as biomechanical studies have demonstrated the importance of meniscal integrity in load distribution across the knee joint. Meniscal injury causes altered joint mechanics, which is postulated to be related to the onset of arthrosis. Arthroscopic meniscal root repair has been shown to restore more normal joint mechanics and is considered a treatment option in the appropriately indicated patient. Short- and midterm clinical results of meniscal root repair are promising, but long-term results are yet to be established. Herein, we review meniscal root injuries and repairs with respect to their anatomy, biomechanics, clinical diagnosis, treatment indications, operative techniques, potential complications, postoperative management, and clinical outcomes.
PMID: 29537952
ISSN: 2328-5273
CID: 3005472
Ulnar Collateral Ligament Reconstruction Past, Present, and Future Past, Present, and Future
Shoulder and elbow injuries have been described in baseball players as early as the 1940s. Ulnar collateral ligament (UCL) tears have been recognized as a significant source of disability for baseball players and have been seen in increasing frequency as training regimens and level of play have become more intense and rigorous. Our understanding and treatment of these injuries have also evolved over time. This article summarizes the evolution of the treatment of UCL tears and discusses future directions for the treatment and prevention of these injuries.
PMID: 29537953
ISSN: 2328-5273
CID: 3005482
Management of Biceps Tendon Pathology: From the Glenoid to the Radial Tuberosity
Management of proximal and distal biceps tendon pathology is evolving. The long head of the biceps tendon, if inflamed, may be a pain-producing structure. In appropriately indicated patients, a symptomatic long head of the biceps tendon can be surgically managed via tenotomy, tenodesis, and/or superior labrum anterior to posterior repair. In some patients, primary superior labrum anterior to posterior pathology can be managed via biceps tenodesis. Determining which procedure is most appropriate for and which technique and implant are preferred in a given patient with biceps tendon pathology is controversial. Less debate exists with regard to the timing of distal biceps tendon repair; however, considerable controversy exists with regard to selection of an appropriate surgical technique and implant. In addition, the treatment of patients with a chronic and/or retracted distal biceps tendon tear and patients in whom distal biceps tendon repair fails is extremely challenging. Orthopaedic surgeons should understand the anatomy of, nonsurgical and surgical treatment options for, and outcomes of patients with proximal or distal biceps tendon pathology.
PMID: 31411431
ISSN: 0065-6895
CID: 4042412
Management of Meniscal Pathology: From Partial Meniscectomy to Transplantation
Meniscal tears are common injuries that may result in functionally limiting pain, swelling, and mechanical symptoms. The management of meniscal pathology has evolved as surgeons' understanding of the important role the menisci play in normal knee kinematics increases. Recent emphasis on partial meniscectomy, expanding indications for meniscal repair, and the increased use of meniscal allograft transplantation have helped improve the outcomes of patients with a meniscal tear who undergo treatment. Orthopaedic surgeons should understand meniscal function, pathology, and treatment approaches.
PMID: 31411434
ISSN: 0065-6895
CID: 4042422
Journal of the American Academy of Orthopaedic Surgeons. 2018:26(4):e77-e89.DOI: 10.5435/JAAOS-D-17-00085
Management of Biceps Tendon Pathology: From the Glenoid to the Radial Tuberosity
Management of proximal and distal biceps tendon pathology is evolving. The long head of the biceps tendon, if inflamed, may be a pain-producing structure. In appropriately indicated patients, a symptomatic long head of the biceps tendon can be surgically managed via tenotomy, tenodesis, and/or superior labrum anterior to posterior repair. In some patients, primary superior labrum anterior to posterior pathology can be managed via biceps tenodesis. Determining which procedure is most appropriate and which technique and implant are preferred for a given patient with biceps tendon pathology is controversial. Less debate exists with regard to the timing of distal biceps tendon repair; however, considerable controversy exists with regard to selection of an appropriate surgical technique and implant. In addition, the treatment of patients with a chronic and/or retracted distal biceps tendon tear and patients in whom distal biceps tendon repair fails is extremely challenging. Orthopaedic surgeons should understand the anatomy of, nonsurgical and surgical treatment options for, and outcomes of patients with proximal or distal biceps tendon pathology.
PMID: 29337716
ISSN: 1940-5480
CID: 2916142
Journal of the American Academy of Orthopaedic Surgeons. 2018:26(1):e11-e25.DOI: 10.5435/JAAOS-D-17-00087
The Utility of Biologics, Osteotomy, and Cartilage Restoration in the Knee
The management of complex cartilage and meniscal pathology in young, athletic patients is extremely challenging. Joint preservation surgery is most difficult in patients with concomitant knee pathologies, including cartilage defects, meniscal deficiency, malalignment, and/or ligamentous insufficiency. Clinical decision making for these patients is further complicated by articular cartilage lesions, which often are incidental findings; therefore, treatment decisions must be based on the confirmed contribution of articular cartilage lesions to symptomatology. Surgical management of any of the aforementioned knee pathologies that is performed in isolation typically results in acceptable patient outcomes; however, concomitant procedures for the management of concomitant knee pathologies often are essential to the success of any single procedure. The use of biologic therapy as an alternative to or to augment more conventional surgical management has increased in popularity in the past decade, and indications for biologic therapy continue to evolve. Orthopaedic surgeons should understand knee joint preservation techniques, including biologic and reconstructive approaches in young, high-demand patients.
PMID: 29261554
ISSN: 1940-5480
CID: 2892472
A Biomechanical Study of Two Distinct Methods of Anterior Cruciate Ligament Rupture, and a Novel Surgical Reconstruction Technique, in a Small Animal Model of Posttraumatic Osteoarthritis
Small animal models are critical for studies of sports-related knee injury and disease such as posttraumatic osteoarthritis (PTOA) following anterior cruciate ligament (ACL) rupture. In such models, ACL damage can be achieved by surgical transection or, using a more recent innovation, by noninvasive biomechanical means. Whether these approaches differentially alter normal mechanics is unknown. Furthermore, while surgical reconstruction of ruptured ACL can greatly improve joint stability, its effect on PTOA development is also unclear. Our primary purpose was to characterize rodent knee joint mechanics in two models of ACL rupture using a novel quantitative laxity mechanical test. Our secondary aim was to characterize a new reconstruction technique using autograft tail tendon, and to assess its effect on joint mechanics. Our hypothesis was that surgical ACL transection would have a greater effect on joint mechanics. A total of 24 rat knee specimens underwent surgical or biomechanical ACL rupture and were stabilized using a new reconstruction technique using autograft tail tendon. Joint mechanics were assessed three times; preinjury, postinjury, and again after reconstruction, using quantitative joint laxity testing. Primary test readouts were maximum anteroposterior (AP) laxity, loading curve slope, and energy absorption. Student's t-tests were performed to identify intragroup differences. All surgical transections were completed successfully; maximum load in the biomechanical model was 67 +/- 7.7 N, with a coefficient of variation of 11.43%. Surgical transection caused increased AP laxity, while biomechanical injury nonsignificantly increased this parameter. In both cases, these changes recovered to baseline by reconstruction. Loading curve slope was reduced in both models and was also returned to baseline by repair. Energy absorption followed the same pattern except it remained significantly different from baseline postreconstruction in the surgical group. This study supports our hypothesis knee joint mechanics is differentially affected by injury mechanism in a small animal model. We also report a novel reconstruction technique in this model, using autograft tail tendon.
PMID: 28355681
ISSN: 1938-2480
CID: 2508932
