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Background Perioperative hyperglycemia is a risk factor for postoperative complications after total joint arthroplasty (TJA). However, the variability of fasting blood glucose (FBG) after TJA remains unknown. We aimed to assess the fluctuation and extent of elevation of FBG following primary or revision TJA. Methods We retrospectively evaluated the medical records of 1788 patients who underwent primary or revision TJA between 2013 and 2018. We examined FBG values collected during 6 days of the perioperative period. The findings for each time point were evaluated with descriptive statistics. Postoperative glycemic variability was assessed by the coefficient of variation (CV). Results The final cohort included the medical records of 1480 patients (1417 primary and 63 revision). FBG was highest on postoperative day 1 in the primary and revision groups (P < 0.001), which had the highest number of hyperglycemic patients (FBG > 100 mg/dL), with 66.4% and 75.5% in the primary and revision groups, respectively. The CV of diabetics in the primary group, and diabetics and non-diabetics in the revision group, was higher than that of non-diabetics in the primary group. Conclusion Postoperative day 1 showed the highest FBG levels and proportion of patients with hyperglycemia in the perioperative period. Primary group diabetics, and revision group diabetics and non-diabetics, had higher postoperative fluctuation of FBG than primary group non-diabetics. Frequent FBG monitoring may therefore be warranted in diabetic patients undergoing TJA, and all patients undergoing revision TJA.

BackgroundEarly-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening.MethodsIn this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited.ResultsAfter ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis.ConclusionES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES.

Study Design A prospective cohort study. Objectives To report a new index, the realigned K-line, for predicting surgical outcomes after laminoplasty in patients with degenerative cervical myelopathy (DCM). Methods One hundred twenty-eight patients with DCM undergoing laminoplasty were enrolled from January 2018 to April 2021 in our department. A realigned K-line was defined as the line connecting the midpoints of the spinal cord between C2 and C7 on realigned T1-weighted magnetic resonance imaging. The minimum interval between the anterior compression factors of the spinal cord and the realigned K-line (INTrea), and the modified K-line (INTmod) were measured. A logistic regression analysis was performed to identify factors associated with unsatisfactory surgical outcomes. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) was applied to evaluate the reliability of the multivariate logistic regression model. Results Univariate analysis showed that the score for the bladder function section of the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire, numeric rating scale scores for arm pain, and INTrea might be related to the Japanese Orthopaedic Association (JOA) recovery rate (RR) not achieving the minimal clinically important difference (MCID) (P < .05). Only INTrea (odds ratio = .744, P < .05) was an independent preoperative factor related to the JOA RR not achieving the MCID (area under the curve, .743). A cutoff of 5.0 mm for INTrea had an accuracy of 71.9% and specificity of 80.3% for predicting the JOA RR not achieving the MCID. Conclusions INTrea is an independent preoperative risk factor related to the JOA RR not achieving the MCID in patients with DCM. A cutoff point of 5.0 mm is most appropriate for alerting spine surgeons to a high likelihood of the JOA RR not achieving the MCID.

Congenital scoliosis (CS) is a form of scoliosis caused by congenital vertebral malformations. Genetic predisposition has been demonstrated in CS. We previously reported that TBX6 loss-of-function causes CS in a compound heterozygous model; however, this model can explain only 10% of CS. Many monogenic and polygenic CS genes remain to be elucidated. In this study, we analyzed exome sequencing (ES) data of 615 Chinese CS from the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) project. Cosegregation studies for 103 familial CS identified a novel heterozygous nonsense variant, c.2649G>A (p.Trp883Ter) in FBN1. The association between FBN1 and CS was then analyzed by extracting FBN1 variants from ES data of 574 sporadic CS and 828 controls; 30 novel variants were identified and prioritized for further analyses. A mutational burden test showed that the deleterious FBN1 variants were significantly enriched in CS subjects (OR = 3.9, P = 0.03 by Fisher’s exact test). One missense variant, c.2613A>C (p.Leu871Phe) was recurrent in two unrelated CS subjects, and in vitro functional experiments for the variant suggest that FBN1 may contribute to CS by upregulating the transforming growth factor beta (TGF-β) signaling. Our study expanded the phenotypic spectrum of FBN1, and provided nove insights into the genetic etiology of CS.

Aseptic loosening caused by peri-implant osteolysis (PIO) is a common complication after joint replacement, and there is still no better treatment than revision surgery. The wear particle-induced inflammation response, especially subsequent osteoclastic bone resorption, is responsible for PIO. As the importance of wear particles in inducing autophagy in cells around the prosthesis in PIO has been discovered, this might be a central process underlying aseptic loosening. However, the role of autophagy induced by wear particles in osteoclastogenesis during PIO remains unclear. In this study, we investigated the role of autophagy in osteoclastogenesis and verified it in a mouse calvarial osteolysis model. We found that osteoclasts were increased in the interface membranes of patients with aseptic loosening. In vitro, knocking down the Atg5 gene or using autophagy inhibitors (3-MA, LY294002) to inhibit autophagy was found to repress osteoclastogenesis and decrease expression of the osteoclast-related genes TRAP, cathepsin K, and matrix metalloprotein 9 (MMP-9) with or without titanium (Ti) particles. In vivo, 3-MA and LY294002 repressed Ti particle-stimulated osteolysis and osteoclastogenesis and reduced expression of the pro-inflammatory factors TNF-α, IL-1β, and IL-6. Our results suggest that 3-MA and LY294002 might be the potential medicines to prevent and treat PIO and aseptic loosening.

Introduction PAX1 has been identified to be associated with adolescent idiopathic scoliosis (AIS). However, data are unavailable for northern Chinese populations, and it is important to determine the exact clinical phenotypes of the associated genetic polymorphisms. Methods Five PAX1 single nucleotide polymorphism (SNP) loci were genotyped in 480 northern Chinese Han AIS patients and 841 controls. A stratified genotype-phenotype correlation analysis was conducted based on positive SNP loci and the Peking Union Medical College (PUMC) classification system. Luciferase assays were performed to determine the regulation of PAX1 transcriptional activity. Results The A allele of rs17861031 and the G allele of rs6137473 were significantly associated with AIS [p = 0.05 and 3.12 × 10−3, odds ratio (OR) = 0.78 and 1.30, respectively]. Moreover, rs17861031 may regulate the PAX1 gene. The A allele of rs17861031 was identified as a risk allele for PUMC type I AIS (p = 0.03), and the G allele of rs6137473 was identified as a risk allele for PUMC type II AIS (p = 1.90 × 10−3). Conclusions Both rs17861031 and rs6137473 were significantly associated with AIS and different PUMC classifications of AIS in a northern Chinese Han population.

Background Diagnosing chronic periprosthetic joint infection (PJI) is challenging. No single biomarker can accurately recognize PJI preoperatively in a timely manner. Therefore, the aim of the present study was to investigate the usefulness of the serum neutrophil-to-lymphocyte ratio (NLR) in aiding the diagnosis of chronic PJI. Materials and methods We retrospectively evaluated the medical records of 158 patients who had undergone revision arthroplasty (104 with aseptic mechanic failure and 54 with chronic PJI) from July 2011 to July 2020. Univariate analysis followed by multivariate logistic regression was applied to compare NLR, C-reactive protein (CRP), and erythrocyte sedimentation ratio (ESR) between the two groups. The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of NLR alone and in combination with CRP and ESR. Results NLR, CRP, and ESR were significantly higher in patients with chronic PJI than in the aseptic revision group (p Conclusion Compared with traditional inflammatory biomarkers (ESR and CRP), the value of serum NLR alone or combined with CRP and ESR for diagnosing chronic PJI is limited. Level of evidence Level 3.

Background Periprosthetic joint infection (PJI) has been increasingly documented; however, its preoperative accurate diagnosis remains challenging. Furthermore, there is a dire need to identify appropriate and effective biomarkers. We aimed to evaluate the relationship between globulin, albumin to globulin (A/G) ratio, and development of PJI in patients undergoing revision total joint arthroplasty (TJA). Methods A retrospective study was conducted on patients who had undergone revision TJA between 2011 and 2018 (89 with aseptic mechanic failure and 38 with PJI). The serum proteins were explored using univariate analysis followed by multivariate logistic regression. The diagnostic performance of these proteins was assessed by the receiver operating characteristic (ROC) curve. Results Higher globulin levels (odds ratio [OR], 1.239; P < 0.001) and lower A/G ratio (OR, 0.007; P < 0.001) were strongly associated with the risk of PJI. ROC curve analysis demonstrated reasonable diagnostic performance for globulin (area under the curve [AUC], 0.77; sensitivity, 78.95%; and specificity, 69.66%) and A/G ratio (AUC, 0.779; sensitivity, 65.79%; and specificity, 78.65%). Conclusions Both globulin and A/G ratio were associated with PJI and may serve as potential adjuvant biomarkers in the diagnosis of PJI.

Background Congenital scoliosis (CS) is a spinal deformity due to vertebral malformations. Although insufficiency of TBX6 dosage contributes to a substantial proportion of CS, the molecular etiology for the majority of CS remains largely unknown. TBX6‐mediated genes involved in the process of somitogenesis represent promising candidates. Methods Individuals affected with CS and without a positive genetic finding were referred to this study. Proband‐only exome sequencing (ES) were performed on the recruited individuals, followed by analysis of TBX6‐mediated candidate genes, namely MEOX1, MEOX2, MESP2, MYOD1, MYF5, RIPPLY1, and RIPPLY2. Results A total of 584 patients with CS of unknown molecular etiology were recruited. After ES analysis, protein‐truncating variants in RIPPLY1 and MYF5 were identified from two individuals, respectively. In addition, we identified five deleterious missense variants (MYOD1, n = 4; RIPPLY2, n = 1) in TBX6‐mediated genes. We observed a significant mutational burden of MYOD1 in CS (p = 0.032) compared with the in‐house controls (n = 1854). Moreover, a potential oligogenic disease‐causing mode was proposed based on the observed mutational co‐existence of MYOD1/MEOX1 and MYOD1/RIPPLY1. Conclusion Our study characterized the mutational spectrum of TBX6‐mediated genes, prioritized core candidate genes/variants, and provided insight into a potential oligogenic disease‐causing mode in CS., Our study characterized the mutational spectrum of TBX6‐mediated genes, prioritized core candidate genes/variants, and provided insight into a potential oligogenic disease‐causing mode in CS.

Background: Diagnosing a periprosthetic joint infection (PJI) is challenging. No single biomarker can accurately recognize PJI preoperatively in a timely manner. Therefore, the aim of the present study was to investigate the usefulness of the neutrophil-lymphocyte ratio (NLR) in aiding the diagnosis of PJI.Methods: We retrospectively evaluated the medical records of 109 patients who had undergone revision arthroplasty (77 with aseptic mechanic failure and 32 with PJI) from July 2011 to November 2018. Bivariate analysis followed by multivariate logistic regression was applied to compare NLR between two groups. The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of NLR alone and in combination with C-reactive protein (CRP) and the erythrocyte sedimentation ratio (ESR).Results: NLR was significantly higher in patients with PJI than in patients of the aseptic revision group (3.12 ± 2.45 vs. 2.10 ± 1.03, p 0.05).Conclusions: NLR is associated with PJI and could be regarded as a complementary marker, which in combination with CRP could improve the diagnostic performance for PJI.

To investigate abnormally methylated-differentially expressed genes (DEGs) and their related pathways in osteoarthritis (OA) by comprehensive bioinformatic analysis.Gene expression profiles of GSE51588 and GSE114007, and a gene methylation microarray data GSE63695 were downloaded from the Gene Expression Omnibus (GEO) repository. Abnormally methylated DEGs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of these genes were subsequently performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The protein-protein interaction (PPI) network was built from STRING. Module analysis and hub gene identification were performed by using Cytoscape. Co-expression analysis was also constructed using the CEMiTool package.In total, 133 abnormally methylated DEGs were identified, including 85 hypomethylation high-expression genes and 48 hypermethylation low-expression genes. Among biological processes and KEGG pathways of abnormally methylated DEGs, collagen fibril organization was enriched most frequently, and pathways of oxidative stress and aging were enriched, including HIF-1 signaling pathway, AMPK signaling pathway, and FoxO signaling pathway. In PPI networks, the hub genes of hypomethylation high-expression genes were COL1A1, COL3A1, COL1A2, COL5A2, LUM, MMP2, SPARC, COL2A1, COL6A2, and COL7A1, and the hub genes of hypermethylation low-expression genes were VEGFA, SLC2A1, LDHA, PDK1, and BNIP3. Combined with co-expression analysis, COL3A1, LUM, and MMP2 were the critical hypomethylation high-expression hub genes in medial tibia subchondral bone.Our study implied abnormally methylated DEGs and dysregulated pathways in OA. Common methylation biomarkers included COL3A1, LUM, and MMP2, and we also found that THBS2 may serve as a novel biomarker in end-stage OA. Key Points • Abnormally methylated differentially expressed genes regulate osteoarthritis. • Hypomethylation high-expression genes were related to the extracellular matrix. • Hypermethylation low-expression genes were related to oxidative stress and aging. • COL3A1, LUM, and MMP2 were potential methylation biomarkers for osteoarthritis.

Background Perioperative hyperglycemia is a risk factor for postoperative complications after total joint arthroplasty (TJA). However, the most optimal timing to detect blood glucose and the extent of elevation of postoperative glucose remain unknown. Our study investigated differences in perioperative blood glucose fluctuations between primary and revision groups to determine optimal timing for glycemic control. Methods We retrospectively evaluated medical records of 1,788 TJA patients from October 2013 to November 2018. We examined blood glucose values collected within 6 days perioperatively. Each time point’s findings were evaluated with descriptive statistics. Glucose variability was assessed by coefficient of variation (CV). Differences in glucose levels were compared between primary and revision groups. Results The final cohort included medical records of 1,480 patients (1,417 primary, 63 revision). Mean glucose values were highest on postoperative day 1 (117±35 and 132±50 mg/dL) in primary and revision groups, respectively ( P 100 mg/dL) with 66.4% and 75.5% in primary and revision groups, respectively. The CV of primary and revision group nondiabetic and diabetic patients was 6.85% and 9.02% and 12.83% and 15.31%, respectively. Conclusions Postoperative day 1 was the most sensitive time for glucose control. Hyperglycemia occurred on postoperative day 1 in most patients who underwent TJA in both groups. Primary group diabetics and revision group had higher postoperative glycemic fluctuations than primary group nondiabetics. Our results reveal the need for specialized protocols for clinicians to detect and monitor hyperglycemia in patients under different situations.

Congenital scoliosis (CS) is a birth defect with variable clinical and anatomical manifestations due to a spinal malformation. The genetic etiology underlying about 10% of CS cases in the Chinese population is compound inheritance by which the gene dosage is reduced below that of haploinsufficiency. In this genetic model, the trait manifests as a result of the combined effect of a rare variant and common pathogenic variant allele at a locus. From exome sequencing data of 523 patients in Asia and two patients in Texas, USA, we identified six TBX6 gene-disruptive variants from 11 unrelated CS patients via exome sequencing and in vitro functional testing. The in trans mild hypomorphic allele was identified in 10 out of the 11 subjects; as anticipated these 10 shared a similar spinal deformity of hemivertebrae. The remaining case has a homozygous variant in TBX6 (c.418C>T) and presents with a more severe spinal deformity phenotype. We found decreased transcriptional activity and abnormal cellular localization as molecular mechanisms for TBX6 missense loss-of-function alleles. Expanding the mutational spectrum of TBX6 pathogenic alleles enabled an increased molecular diagnostic detection rate, provided further evidence for the gene dosage-dependent genetic model underlying CS, and refined clinical classification.