Recent genome-wide association scans (GWAS) and meta-analysis studies on European populations have identified many genes previously implicated in lipid regulation. Validation of these loci on different global populations is important in determining their clinical relevance, particularly for development of novel drug targets for treating and preventing diabetic dyslipidemia and coronary artery disease (CAD). In an attempt to replicate GWAS findings on a non-European sample, we examined the role of six of these loci (CELSR2-PSRC1-SORT1 rs599839; CDKN2A-2B rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4-C2 rs4420638) in our Asian Indian cohort from the Sikh Diabetes Study (SDS) comprising 3,781 individuals (2,902 from Punjab and 879 from the US). Two of the six SNPs examined showed convincing replication in these populations of Asian Indian origin. Our study confirmed a strong association of CETP rs3764261 with high-density lipoprotein cholesterol (HDL-C) (p = 2.03×10−26). Our results also showed significant associations of two GWAS SNPs (rs964184 and rs12286037) from BUD13-ZNF259 near the APOA5-A4-C3-A1 genes with triglyceride (TG) levels in this Asian Indian cohort (rs964184: p = 1.74×10−17; rs12286037: p = 1.58×10−2). We further explored 45 SNPs in a ∼195 kb region within the chromosomal region 11q23.3 (encompassing the BUD13-ZNF259, APOA5-A4-C3-A1, and SIK3 genes) in 8,530 Asian Indians from the London Life Sciences Population (LOLIPOP) (UK) and SDS cohorts. Five more SNPs revealed significant associations with TG in both cohorts individually as well as in a joint meta-analysis. However, the strongest signal for TG remained with BUD13-ZNF259 (rs964184: p = 1.06×10−39). Future targeted deep sequencing and functional studies should enhance our understanding of the clinical relevance of these genes in dyslipidemia and hypertriglyceridemia (HTG) and, consequently, diabetes and CAD.

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Background: Loss of motion (LOM) remains a common complication after anterior cruciate ligament (ACL) reconstruction and can be detrimental to patient outcomes after surgery. LOM is multifactorial, but nonsurgical and surgical solutions to this complex problem are available. A paucity of quality data exists evaluating clinical outcomes after the surgical treatment of patients with LOM after ACL reconstruction. Hypothesis: Patients undergoing surgical lysis of adhesions and manipulation under anesthesia for LOM after ACL reconstruction will exhibit decreased function, lower outcome scores, and delayed time of release to play when compared with matched controls without LOM. Study Design: Cohort study; Level of evidence, 3 Methods: A database of 1572 patients undergoing ACL reconstruction was sampled from 2013 to 2017 to identify a total of 58 patients (LOM group [n = 29] vs matched control group [n = 29]). Group comparisons were examined for patients requiring a second surgical procedure for LOM versus matched controls after ACL reconstruction for differences in surgical timing, self-reported International Knee Disability Committee scores, objective function at release to play, and subjective knee function at 2 years with the Single Assessment Numeric Evaluation. The risk of a type I error was set at α = .05 for all statistical analyses. Results: Patients who underwent lysis of adhesions and manipulation under anesthesia for LOM after ACL reconstruction exhibited no differences in Single Assessment Numeric Evaluation knee function at 2 years when compared with matched controls (85.8 ± 14.9 vs 88.0 ± 10.8, P = .606). All patients met release-to-play criteria. Only International Knee Disability Committee scores ( P = .046) and single-legged hop testing ( P = .050) reached statistically significant differences, with higher scores in the control group. There was no difference in the time to release to play ( P = .034) or level of participation ( P = .180) between the control and surgical groups. Subjective function scores at 2 years were not significantly different between groups. Tourniquet time during the index ACL reconstruction was shorter in the control group ( P = .034). Conclusion: The findings of this study suggest that patients who undergo surgical treatment for LOM after ACL reconstruction can release to play at similar times but display relative deficits in single-legged-hop symmetry and lower self-reported function when compared with matched controls. Longer surgical times may increase the risk for LOM after ACL reconstruction. Registration: NCT03704376 (ClinicalTrials.gov identifier)

This study reviewed pain and outcome scores of patients undergoing revision surgery with heterotopic ossification (HO) excision following previous hip arthroscopy. The aim was to determine if performing the excision arthroscopically improved clinical outcomes. Data were prospectively collected and retrospectively reviewed in patients who had HO removed arthroscopically between February 2008 and 2014. Four patient-reported outcome (PRO) measures were collected: Modified Harris Hip Score (mHHS), Non-Arthritis Hip Score (NAHS), Hip Outcome Score-Activity of Daily Living (HOS-ADL) and Sport-Specific (HOS-SS) subscales. Minimum 1.5 year follow-up from index procedure was available for 23 patients (mean age = 38.6 years). Of the 23 patients who had revision surgery and HO removal, 19 (83%) were available for follow-up. Prior to revision, the average mHHS was 53.4, HOS-ADL 51.4, HOS-SS 24.5, NAHS 50.3 and VAS 6.7. Following revision with HO excision, each score had improved with an average mHHS of 73.62, HOS-ADL of 68.88, HOS SS of 58.51, NAHS of 70.83 and VAS of 4.33. Overall, mHHS increased by 20.26 points (P < 0.001), HOS-ADL increased by 17.48 points (P = 0.023), HOS-SS increased by 34.03 points (P < 0.001), NAHS increased by 20.55 points (P = 0.001) and VAS decreased by 2.38 points (P < 0.001). Patients undergoing revision hip surgery with HO excision demonstrated improved outcome scores and pain resolution; however, few patients achieved a good or excellent result. Revision hip surgery with HO excision should be approached cautiously because of the modest results in this patient group.