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  1. Park KS, Chan CK, Kim SK, Li QS, Im CJ, Yoon TR
    J Orthop Sci, 2019 May;24(3):452-457.
    PMID: 30415823 DOI: 10.1016/j.jos.2018.10.016
    BACKGROUND: Due to concern of potential metallosis caused by residual microscopic ceramic particles, metal-on-metal (MoM) bearing is deemed undesirable in revision total hip arthroplasty (THA) for ceramic bearing fracture. We determined whether MoM bearing is suitable to be used in revision THA for ceramic fractures and also evaluated whether this treatment increases serum iron levels compared with MoM bearing revision THA for polyethylene failure.

    METHODS: Between 2006 and 2012, 22 patients underwent revision surgery using MoM bearing (28 mm femoral head in 18 hips and 32 mm in 4 hips) for ceramic bearing fracture and followed average 52.1 months. We assessed radiological parameter and functional outcome using Harris hip score (HHS) and WOMAC score. Also, serum cobalt (Co) and chromium (Cr) blood tests were performed and compared with the result obtained from age, sex- and follow-up duration-matched patients with MoM revision THA for failed polyethylene bearing.

    RESULTS: The mean HHS improved from 60.6 preoperatively to 90.3 at final follow-up. There were no changes in cup position, progression of osteolytic lesions, and measurable wear of MoM bearing articulation at final follow-up radiographs. There was one case of recurrent dislocation after surgery, which was treated with greater trochanter distal advancement and one case of deep infection, which underwent two-stage revision. Mean serum Co level (1.7 vs. 1.4 μg/dl; p = 0.211) and Cr level (0.70 vs. 1.01 μg/dl; p = 0.327) showed no significant difference.

    CONCLUSIONS: MoM articulation with liner cementation into the acetabular cup along with total synovectomy can be chosen in revision surgery for ceramic fracture with good midterm follow-up. However, the use of MoM bearing is indicated when the stem and metal shell can be retained and ceramic on ceramic or ceramic on polyethylene bearing cannot be selected. Also long-term outcome needs to be further evaluated.

  2. Pain O, Hodgson K, Trubetskoy V, Ripke S, Marshe VS, Adams MJ, et al.
    Biol Psychiatry Glob Open Sci, 2022 Apr;2(2):115-126.
    PMID: 35712048 DOI: 10.1016/j.bpsgos.2021.07.008
    BACKGROUND: Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction.

    METHODS: Genome-wide analysis of remission (n remit = 1852, n nonremit = 3299) and percentage improvement (n = 5218) was performed. Single nucleotide polymorphism-based heritability was estimated using genome-wide complex trait analysis. Genetic covariance with eight mental health phenotypes was estimated using polygenic scores/AVENGEME. Out-of-sample prediction of antidepressant response polygenic scores was assessed. Gene-level association analysis was performed using MAGMA and transcriptome-wide association study. Tissue, pathway, and drug binding enrichment were estimated using MAGMA.

    RESULTS: Neither genome-wide association study identified genome-wide significant associations. Single nucleotide polymorphism-based heritability was significantly different from zero for remission (h 2 = 0.132, SE = 0.056) but not for percentage improvement (h 2 = -0.018, SE = 0.032). Better antidepressant response was negatively associated with genetic risk for schizophrenia and positively associated with genetic propensity for educational attainment. Leave-one-out validation of antidepressant response polygenic scores demonstrated significant evidence of out-of-sample prediction, though results varied in external cohorts. Gene-based analyses identified ETV4 and DHX8 as significantly associated with antidepressant response.

    CONCLUSIONS: This study demonstrates that antidepressant response is influenced by common genetic variation, has a genetic overlap schizophrenia and educational attainment, and provides a useful resource for future research. Larger sample sizes are required to attain the potential of genetics for understanding and predicting antidepressant response.

  3. Mullins N, Kang J, Campos AI, Coleman JRI, Edwards AC, Galfalvy H, et al.
    Biol Psychiatry, 2022 Feb 01;91(3):313-327.
    PMID: 34861974 DOI: 10.1016/j.biopsych.2021.05.029
    BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.

    METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.

    RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.

    CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

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