Research Spotlight

Fox, R. J., R. Gold, J. T. Phillips, M. Okwuokenye, A. Zhang and J. L. Marantz (2017). “Efficacy and tolerability of delayed-release dimethyl fumarate in black, hispanic, and asian patients with relapsing-remitting multiple sclerosis: Post hoc integrated analysis of define and confirm.” Neurol Ther 6(2): 175-187.

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INTRODUCTION: Clinical course and treatment response may vary according to race/ethnicity in multiple sclerosis (MS) patients. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) demonstrated significant efficacy and a favorable benefit-risk profile in relapsing-remitting MS (RRMS) patients in the 2-year phase III DEFINE/CONFIRM studies. METHODS: In this post hoc analysis of integrated data from DEFINE/CONFIRM, we assessed clinical efficacy and safety/tolerability in black, Hispanic, and Asian patients treated with DMF 240 mg twice daily (approved dosage) or placebo. Eligible patients were 18-55 years of age with an Expanded Disability Status Scale score of 0-5.0. In the integrated intention-to-treat population, 769 and 771 patients were treated with DMF or placebo, respectively, of whom 10 and 19 were black, 31 and 23 were Hispanic, and 66 and 70 were Asian. RESULTS: In the black, Hispanic, and Asian subgroups, DMF was associated with lower annualized relapse rates at 2 years compared with placebo [rate ratio (95% confidence interval (CI)), 0.05 (0.00-1.07); 0.31 (0.10-0.95); and 0.64 (0.30-1.34), respectively]. The percentage of black, Hispanic, and Asian patients with 12-week confirmed disability progression was lower with DMF (43%, 8%, and 20%, respectively) compared with placebo [57%, 30%, and 25%, respectively; hazard ratio (95% CI), 0.53 (0.02-1.39); 0.17 (0.00-0.60); and 0.71 (0.32-1.58), respectively]. The safety/tolerability profile of DMF was generally consistent with that in the overall population of DEFINE/CONFIRM. The incidence of adverse events leading to treatment discontinuation in black, Hispanic, and Asian patients was 2/10, 2/31, and 3/66, respectively, with DMF, and 2/19, 1/23, and 8/70, respectively, with placebo. CONCLUSION: DMF may be an efficacious treatment with a favorable benefit-risk profile in black, Hispanic, and Asian patients with RRMS. Further clinical studies are needed to characterize differences in MS presentation and treatment outcomes across ethnic and racial groups.

Gomes, L. R., L. H. Cevidanes, M. R. Gomes, A. C. Ruellas, D. P. Ryan, B. Paniagua, L. M. Wolford and J. R. Goncalves (2017). “Counterclockwise maxillomandibular advancement surgery and disc repositioning: Can condylar remodeling in the long-term follow-up be predicted?” Int J Oral Maxillofac Surg 46(12): 1569-1578.

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This study investigated predictive risk factors of condylar remodeling changes after counterclockwise maxillomandibular advancement (CCW-MMA) and disc repositioning surgery. Forty-one female patients (75 condyles) treated with CCW-MMA and disc repositioning had cone beam computed tomography (CBCT) scans taken pre-surgery, immediately after surgery, and at an average 16 months post-surgery. Pre- and post-surgical three-dimensional models were superimposed using automated voxel-based registration on the cranial base to evaluate condylar displacements after surgery. Regional registration was performed to assess condylar remodeling in the follow-up period. Three-dimensional cephalometrics, shape correspondence (SPHARM-PDM), and volume measurements were applied to quantify changes. Pearson product-moment correlations and multiple regression analysis were performed. Highly statistically significant correlation showed that older patients were more susceptible to overall condylar volume reduction following CCW-MMA and disc repositioning (P

Jaffe, D., D. Vier, J. Kane, M. Kozanek and C. Royer (2017). “Rate of neurologic injury following lateralizing calcaneal osteotomy performed through a medial approach.” Foot Ankle Int 38(12): 1367-1373.

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BACKGROUND: Calcaneal osteotomies are commonly used to correct varus hindfoot alignment in patients with symptomatic cavovarus deformity. Translational, closing wedge, and Malerba-type osteotomies have been implicated in the development of tarsal tunnel syndrome and neurologic injury to branches of the tibial nerve. The authors hypothesized that there would be minimal clinically important injury to the tibial nerve by performing a translational calcaneal osteotomy from a medial approach. METHODS: All patients undergoing a cavovarus reconstruction by a single surgeon were identified. Patients were included if they underwent a lateralizing calcaneal osteotomy via medial approach. Demographics, operative reports, and clinic notes were reviewed to identify concomitant procedures performed, incidence of postoperative tarsal tunnel syndrome, complications, and preoperative and postoperative nerve examinations. Postoperative radiographs were reviewed for location of the osteotomy relative to the posterior tubercle. RESULTS: Twenty-four patients underwent lateralizing calcaneal osteotomy via a medial approach. Of the osteotomies, 83.3% (20/24) were in the middle third of the calcaneus, with a mean of 11.6-mm translation. No patients developed postoperative tarsal tunnel syndrome or tibial nerve palsy. CONCLUSION: Lateralizing calcaneal osteotomy performed via a medial approach had a clinically negligible incidence of neurologic injury. Adequate translation was achieved to obtain correction of varus hindfoot deformity. The authors believe that there is less direct and less percussive injury to branches of the tibial nerve when performing the osteotomy from medial to lateral. This technique may represent an operative strategy to minimize risk to the tibial nerve and reduce neurologic deficit following cavovarus reconstruction.

Kasiske, B. L., S. K. Asrani, M. A. Dew, M. L. Henderson, C. Henrich, A. Humar, A. K. Israni, K. L. Lentine, A. J. Matas, K. A. Newell, D. LaPointe Rudow, A. B. Massie, J. J. Snyder, S. J. Taler, J. F. Trotter and A. D. Waterman (2017). “The living donor collective: A scientific registry for living donors.” Am J Transplant 17(12): 3040-3048.

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In the setting of an overall decline in living organ donation and new questions about long-term safety, a better understanding of outcomes after living donation has become imperative. Adequate information on outcomes important to donors may take many years to ascertain and may be evident only by comparing large numbers of donors with suitable controls. Previous studies have been unable to fully answer critical questions, primarily due to lack of appropriate controls, inadequate sample size, and/or follow-up duration that is too short to allow detection of important risks attributable to donation. The Organ Procurement and Transplantation Network does not follow donors long term and has no prospective control group with which to compare postdonation outcomes. There is a need to establish a national living donor registry and to prospectively follow donors over their lifetimes. In addition, there is a need to better understand the reasons many potential donors who volunteer to donate do not donate and whether the reasons are justified. Therefore, the US Health Resources and Services Administration asked the Scientific Registry of Transplant Recipients to establish a national registry to address these important questions. Here, we discuss the efforts, challenges, and opportunities inherent in establishing the Living Donor Collective.

Kay, J., D. de Sa, L. Morrison, E. Fejtek, N. Simunovic, H. D. Martin and O. R. Ayeni (2017). “Surgical management of deep gluteal syndrome causing sciatic nerve entrapment: A systematic review.” Arthroscopy 33(12): 2263-2278.e2261.

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PURPOSE: To assess the causes, surgical indications, patient-reported clinical outcomes, and complications in patients with deep gluteal syndrome causing sciatic nerve entrapment. METHODS: Three databases (PubMed, Ovid [MEDLINE], and Embase) were searched by 2 reviewers independently from database inception until September 7, 2016. The inclusion criteria were studies reporting on both arthroscopic and open surgery and those with Level I to IV evidence. Systematic reviews, conference abstracts, book chapters, and technical reports with no outcome data were excluded. The methodologic quality of the studies was assessed with the MINORS (Methodological Index for Non-randomized Studies) tool. RESULTS: The search identified 1,539 studies, of which 28 (481 patients; mean age, 48 years) were included for assessment. Of the studies, 24 were graded as Level IV, 3 as Level III, and 1 as Level II. The most commonly identified causes were iatrogenic (30%), piriformis syndrome (26%), trauma (15%), and non-piriformis (hamstring, obturator internus) muscle pathology (14%). The decision to pursue surgical management was made based on clinical findings and diagnostic investigations alone in 50% of studies, whereas surgical release was attempted only after failed conservative management in the other 50%. Outcomes were positive, with an improvement in pain at final follow-up (mean, 23 months) reported in all 28 studies. The incidence of complications from these procedures was low: Fewer than 1% and 8% of open surgical procedures and 0% and fewer than 1% of endoscopic procedures resulted in major (deep wound infection) and minor complications, respectively. CONCLUSIONS: Although most of the studies identified were case series and reports, the results consistently showed improvement in pain and a low incidence of complications, particularly for endoscopic procedures. These findings lend credence to surgical management as a viable option for buttock pain caused by deep gluteal syndrome and warrant further investigation.