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Whether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 SNPs corresponding to one of four independent associations at the locus in European ancestry individuals but with an elevated odds ratio for Crohn disease in African Americans. A rare variant aggregate analysis implicates Ca2+-binding neuro-immunomodulator CALB2 in ulcerative colitis. Highly significant overall overlap of common variant risk for inflammatory bowel disease susceptibility between individuals with African and European ancestries was observed, with 41 of 241 previously known lead variants replicated and overall correlations in effect sizes of 0.68 for combined inflammatory bowel disease. Nevertheless, subtle differences influence the performance of polygenic risk scores, and we show that ancestry-appropriate weights significantly improve polygenic prediction in the highest percentiles of risk. The median amount of variance explained per locus remains the same in African and European cohorts, providing evidence for compensation of effect sizes as allele frequencies diverge, as expected under a highly polygenic model of disease.

The article provides a contemporary review of tendon lacerations in the foot and ankle, focusing on their detection, treatment, and management strategies. Topics discussed include the importance of timely intervention, initial management principles such as wound care and imaging, and an overview of tendon-specific injuries including those to the Achilles, extensor, flexor, and peroneal tendons.

Background: Ankle fracture treatment is predicated on minimal displacement, leading to abnormal joint contact area. The purpose of this investigation is to determine whether computed tomography (CT) detects subtle mortise malalignment undetectable by x-ray in supination-external rotation–II (SER-II) injuries. Methods: A total of 24 patients with SER-II injuries, as demonstrated by negative gravity stress radiography, were included. Medial clear space (MCS) measurements were performed on bilateral ankle x-rays (injured and contralateral, uninjured side) at several time points as well as bilateral non-weight-bearing CT performed once clinical and radiographic healing was demonstrated (mean = 66 days post injury, range = 61-105 days). Statistical analyses examined differences in measurements between both sides. Results: Final x-rays demonstrated no differences between normal and injured ankle MCS (P =.441). However, CT coronal/axial MCS measurements were different (P <.05). CT coronal MCS measured wider by a mean difference of 0.67 mm (P <.001). Conclusion: There is a high incidence of subtle mortise malalignment in SER-II ankle fractures, as demonstrated by CT, which is undetectable when assessed by plain radiographs. Although clinical outcomes are yet unknown, there are important implications of the finding of confirmed, subtle mortise malalignment in SER-II injuries and the limitations of x-ray to detect it. Level of Evidence: Level III [ABSTRACT FROM AUTHOR]

Background: Total talus replacement (TTR) implants are designed to replace the diseased talar anatomy, reduce pain, maintain ankle range of motion, and restore ankle function after conservative treatments have failed. Currently TTR implants are produced by 3D printing a patient-specific implant designed from the patient's preoperative anatomy. TTR surgery using patient-specific implants is a relatively new technique that remains understudied in the literature. Therefore, the purpose of this investigation was to determine the early safety and potential benefit of the TTR implant in patients with talar avascular necrosis. Methods: This retrospective, multicenter, cohort study evaluates the safety and potential benefits of TTR using 3D-printed patient-specific implants across 4 US centers. The primary outcome was the occurrence of early adverse events after TTR surgery. Secondary outcomes including, pain, and physical function were assessed using the pain visual analog scale (VAS), and Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF), respectively. Results: The study team analyzed 15 patients with more than 1 year of follow-up. The mean duration of follow-up was 25.9 months (range: 18.3-41 months). Although 33.3% (5 of 15) of patients experienced adverse events, primarily occurring within the initial 6 months postoperatively, 93% (14 of 15) of patients reported implant survivorship. Of the 5 cases (33.3%) resulting in an adverse event, 3 (60.0%) were determined to be unrelated to the subject device, 2 (40.0%) were determined to be possibly procedure-related, and none (0%) were determined to be device-related. Conclusion: Although further studies are needed to compare TTR with the standard of care, the results of this study demonstrate the relative early safety of TTR surgery using a 3D-printed implant for the treatment of challenging talar pathologies. A larger and longer clinical study is required to see if the efficacy of this approach will be statistically and clinically meaningful. [ABSTRACT FROM AUTHOR]

Background: Etiology of osteochondral lesions of the talus (OLT) is multifactorial and may develop from trauma, genetics, or hypovascularity. The talar dome is supplied by the posterior tibial artery (PTA) and, to a lesser degree, the sinus tarsi artery (STA). The role of talar dome hypovascularity on OLT remains poorly studied. We aimed to determine any relationship between the diameter of PTA (dPTA) and STA (dSTA) and the incidence and characteristics of talus OLT. Methods: This retrospective study included 77 patients with OLT and 77 subjects as a matched control group (age range: 30-40 years). Using magnetic resonance imaging, the dPTA was measured 1 cm above the tibial plafond, at the plafond, and at the level of medial malleolar tip. Likewise, dSTA was measured at the level of the talar neck. The area, volume, depth, localization, and surgical intervention for OLT were recorded as well. Results: The study group had significantly smaller dPTA at all 3 levels (1.05 ± 0.22 mm, 0.99 ± 0.18 mm, 0.98 ± 0.31 mm, proximal to distal, respectively) compared with controls (1.25 ± 0.23 mm, 1.20 ± 0.22 mm, 1.14 ± 0.18 mm, respectively) (P <.001). The dSTA was also significantly smaller in the study group compared with the control group (0.5 ± 0.11 mm vs 0.57 ± 0.08 mm, respectively; P =.001). The mean dPTA (of all 3 levels) cutoff value for predicting the occurrence of OLT was 1.1 mm with 74% sensitivity and 75% specificity. A significant inverse correlation was observed between OLT area and arterial diameters (P <.001). Conclusion: Smaller luminal dPTA and dSTA appear to be associated with higher incidence of OLT, with defect size inversely correlated to arterial diameter. [ABSTRACT FROM AUTHOR]

BACKGROUND & AIMS: The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohns disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. METHODS: We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P

Background & aimsInflammatory bowel disease (IBD) has familial aggregation in African Americans (AAs), but little is known about the molecular genetic susceptibility. Mapping studies using the Immunochip genotyping array expand the number of susceptibility loci for IBD in Caucasians to 163, but the contribution of the 163 loci and European admixture to IBD risk in AAs is unclear. We performed a genetic mapping study using the Immunochip to determine whether IBD susceptibility loci in Caucasians also affect risk in AAs and identify new associated loci.MethodsWe recruited AAs with IBD and without IBD (controls) from 34 IBD centers in the United States; additional controls were collected from 4 other Immunochip studies. Association and admixture loci were mapped for 1088 patients with Crohn's disease, 361 with ulcerative colitis, 62 with IBD type unknown, and 1797 controls; 130,241 autosomal single-nucleotide polymorphisms (SNPs) were analyzed.ResultsThe strongest associations were observed between ulcerative colitis and HLA rs9271366 (P = 7.5 × 10(-6)), Crohn's disease and 5p13.1 rs4286721 (P = 3.5 × 10(-6)), and IBD and KAT2A rs730086 (P = 2.3 × 10(-6)). Additional suggestive associations (P < 4.2 × 10(-5)) were observed between Crohn's disease and IBD and African-specific SNPs in STAT5A and STAT3; between IBD and SNPs in IL23R, IL12B, and C2orf43; and between ulcerative colitis and SNPs near HDAC11 and near LINC00994. The latter 3 loci have not been previously associated with IBD, but require replication. Established Caucasian associations were replicated in AAs (P < 3.1 × 10(-4)) at NOD2, IL23R, 5p15.3, and IKZF3. Significant admixture (P < 3.9 × 10(-4)) was observed for 17q12-17q21.31 (IZKF3 through STAT3), 10q11.23-10q21.2, 15q22.2-15q23, and 16p12.2-16p12.1. Network analyses showed significant enrichment (false discovery rate