Association between genetically plasma proteins and osteonecrosis: a proteome-wide Mendelian randomization analysis.

Background: Previous studies have explored the role of plasma proteins on osteonecrosis. This Mendelian randomization (MR) study further assessed plasma proteins on osteonecrosis whether a causal relationship exists and provides some evidence of causality. Methods: Summary-level data of 4,907 circulating protein levels were extracted from a large-scale protein quantitative trait loci study including 35,559 individuals by the deCODE Genetics Consortium. The outcome data for osteonecrosis were sourced from the FinnGen study, comprising 1,543 cases and 391,037 controls. MR analysis was conducted to estimate the associations between protein and osteonecrosis risk. Additionally, Phenome-wide MR analysis, and candidate drug prediction were employed to identify potential causal circulating proteins and novel drug targets. Results: We totally assessed the effect of 1,676 plasma proteins on osteonecrosis risk, of which 71 plasma proteins had a suggestive association with outcome risk (P < 0.05). Notably, Heme-binding protein 1 (HEBP1) was significant positively associated with osteonecrosis risk with convening evidence (OR, 1.40, 95% CI, 1.19 to 1.65, P = 3.96 × 10-5, P FDR = 0.044). This association was further confirmed in other MR analysis methods and did not detect heterogeneity and pleiotropy (all P > 0.05). To comprehensively explore the health effect of HEBP1, the phenome-wide MR analysis found it was associated with 136 phenotypes excluding osteonecrosis (P < 0.05). However, no significant association was observed after the false discovery rate adjustment. Conclusion: This comprehensive MR study identifies 71 plasma proteins associated with osteonecrosis, with HEBP1, ITIH1, SMOC1, and CREG1 showing potential as biomarkers of osteonecrosis. Nonetheless, further studies are needed to validate this candidate plasma protein.

Identification of a novel cellular senescence-related lncRNA signature for prognosis and immune response in osteosarcoma.

Background: Cellular senescence, a novel hallmark of cancer, is associated with patient outcomes and tumor immunotherapy. However, at present, there is no systematic study on the use of cellular senescence-related long non-coding RNAs (CSR-lncRNAs) to predict survival in patients with osteosarcoma. In this study, we aimed to identify a CSR-lncRNAs signature and to evaluate its potential use as a survival prognostic marker and predictive tool for immune response of osteosarcoma. Methods: We downloaded a cohort of patients with osteosarcoma from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We performed differential expression and co-expression analyses to identify CSR-lncRNAs. We performed univariate and multivariate Cox regression analyses along with the random forest algorithm to identify lncRNAs significantly correlated with senescence. Subsequently, we assessed the predictive models using survival curves, receiver operating characteristic curves, nomograms, C-index, and decision curve analysis. Based on this model, patients with osteosarcoma were divided into two groups according to their risk scores. Then, using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, we compared their clinical characteristics to uncover functional differences. We further conducted immune infiltration analyses using estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE), cell-type identification by estimating relative subsets of rna transcripts (CIBERSORT), and single-sample gene set enrichment analysis for the two groups. We also evaluated the expression of the target genes of immune checkpoint inhibitors (ICIs). Results: We identified six lncRNAs that were significantly correlated with senescence and accordingly established a novel cellular senescence-related lncRNA prognostic signature incorporating these lncRNAs. The nomogram indicated that the risk model was an independent prognostic factor that could predict the survival of patients with osteosarcoma. This model demonstrated high accuracy upon validation. Further analysis revealed that patients with osteosarcoma in the low-risk group exhibited better clinical outcomes and enhanced immune infiltration. Conclusions: The six-CSR-lncRNA prognostic signature effectively predicted survival outcomes and patients in the low-risk group might have improved immune infiltration.

Intravascular papillary endothelial hyperplasia as a rare cause of cervicothoracic spinal cord compression: A case report.

BACKGROUND: Intravascular papillary endothelial hyperplasia (IPEH) is a rare benign reactive vascular lesion that grows into an expansile compressing mass. It most commonly involves the skin and subcutaneous tissue. Spinal involvement is rare, with only 11 reported cases in the literature. We report, to our knowledge, the first case of IPEH in the cervicothoracic spinal canal and present a literature review. CASE SUMMARY: A 27-year-old man presented with acute-onset neck pain, numbness, and weakness in his extremities. Magnetic resonance imaging showed an epidural mass in the cervicothoracic (C6-T1) spinal canal and vertebral hemangioma (VH) involving the C7 vertebral body. C6-T1 Laminectomy and radical excision of the mass were performed. Histopathological examinations revealed papillary proliferation of vascular endothelial cells with thrombus formation, and an IPEH diagnosis was made. By his 6-mo follow-up appointment, his symptoms were relieved without recurrence. The possible pathogenesis, clinical and imaging features, differential diagnosis, and management of IPEH were reviewed. CONCLUSION: We report, to our knowledge, the first case of IPEH in the cervicothoracic spinal canal, treated via complete resection, and showing a favorable outcome. We found a causal relationship between spinal IPEH and VH; this partly explains the mechanism of IPEH.

Management of late-onset deep surgical site infection after instrumented spinal surgery.

BACKGROUND: There are no universally accepted protocols for the treatment of late-onset deep surgical site infection. This study retrospectively evaluates the methods of aggressive debridement with instrumentation retention, high vacuum closed-suction drain without irrigation, primary wound closure, and antibiotic therapy for the treatment of late-onset deep surgical site infection after instrumented spinal surgery. METHODS: A total of 4057 patients who underwent instrumented spinal surgeries were surveyed from January 2010 to June 2014. Surgical debridement was performed immediately after late-onset deep surgical site infection was identified. In addition to extended resection of the devitalized and necrotic tissue, the biofilms adhered to the surface of implants were removed meticulously and thoroughly. Primary wound closure was performed on each patient, and closed suction drains were maintained for about 7-10 days without irrigation. Antibiotic therapy was administered for 3 months according to the results of the pathogenic culture. RESULTS: Forty-two patients were identified as having late-onset deep surgical site infection. Staphylococcus aureus was the most common pathogen in this group. Seven patients with late-onset deep surgical site infection had negative bacterial culture results. Infections resolved in all patients. Forty-one patients retained their instrumentation, whereas 1 patient had the implants removed because of Staphylococcus aureus infection, which was found the implants loosening during debridement. Primary wound healing was found in all patients with no recurrence of infection during the follow-up periods. CONCLUSIONS: A timely diagnosis, aggressive and meticulous debridement, high vacuum closed-suction drain, routine and adequate use of antibacterial agents are the keys to successfully resolving infection and keeping implants retention in the treatment of late-onset deep surgical site infection after instrumented spinal surgery.

Wallis Interspinous Spacer for Treatment of Primary Lumbar Disc Herniation: Three-Year Results of a Randomized Controlled Trial.

BACKGROUND: Limited data have been reported showing whether the second-generation Wallis interspinous spacer improves function after lumbar spine decompression or discectomy. METHODS: We evaluated Wallis interspinous spacer placement in patients with low back pain or sciatica secondary to a confirmed diagnosis of primary lumbar disc herniation. The patients were treated from July 2008 to July 2011 at 1 institution. Of the 77 patients, 40 allocated to undergo posterior lumbar discectomy with Wallis implantation and 37 without Wallis implantation. The primary outcomes were the visual analog scale score, Japanese Orthopedics Association score, and Oswestry Disability Index. The secondary outcomes were the intervertebral disc height, range of motion of the operated segments, complications, and operating time. RESULTS: At 3 years, the improvements in the primary outcomes were not different between the 2 groups (P > 0.05). The disc height was significantly greater in the Wallis group than in the control group (P < 0.001). Two patients in the Wallis group and three patients in the control group underwent further surgery to treat repeated prolapse of the index segment or an adjacent segment. No significant difference was found in the complication rate between the 2 groups (P > 0.05). CONCLUSIONS: We found that discectomy combined with Wallis implantation was not beneficial for pain relief or lumbar function improvement compared with lumbar discectomy alone. Although the Wallis implant was associated with maintenance of the intervertebral disc height and limited range of motion of the spine, it is probably incapable of preventing recurrent herniation or adjacent segment degeneration.

Efficacy of the Wallis interspinous implant for primary lumbar disc herniation : a prospective randomised controlled trial.

PURPOSE: To investigate the efficacy of the Wallis implant after lumbar discectomy compared with discectomy alone for primary lumbar disc herniation. Seventy-seven patients with primary lumbar disc herniation were randomly assigned to undergo either posterior lumbar discectomy with (n=40, Wallis group) or without (n=37, control group) Wallis implantation. The primary outcomes were visual analogue scale score, Japanese Orthopedics Association score, and Oswestry Disability Index. The secondary outcomes were intervertebral disc height, range of motion of the operated segments, complications, and operating time. The primary outcomes at 1 week after treatment (P> 0.05) were not different between groups. The Wallis group had better scores at 12 months (P< 0.05) and the last follow-up visit (P< 0.05), higher disc height (P< 0.001), and significantly longer operating time (P =0.006) than the control group. Combined treatment appears beneficial for pain relief and lumbar function improvement by maintaining intervertebral disc height and limiting the range of motion of the spine compared with lumbar discectomy alone. However, its actual clinical benefit remains controversial because of the longer operating time and the relatively small difference in the visual analogue scale score and Oswestry Disability Index between the groups.

Multidisciplinary treatment based on surgery leading to long-term survival of a patient with multiple asynchronous rare primary malignant neoplasms: A case report and literature review.

Patients that present with multiple primary malignant neoplasms are increasingly encountered, but the treatment of such patients presents specific challenges and long-term survival is rare. The present study reports the case of a 45-year-old female diagnosed with three rare, distinct primary malignant neoplasms, including epithelioid hemangioendothelioma (EHE) of the brain, Ewing's sarcoma of the lumbar 2 vertebra and a malignant solitary fibrous tumour (SFT) of the liver, at different time points. The patient underwent multidisciplinary treatment according to the diagnoses, including radial resection of all primary lesions, chemotherapy (consisting of vincristine, dactinomycin, cyclophosphamide and adriamycin) and radiotherapy, to treat Ewing's sarcoma and metastases of EHE and malignant SFT. Following these treatments, the patient survived for >14 years. Multidisciplinary treatment regimens based on surgery can lead to long-term survival of patients with multiple asynchronous rare primary malignant neoplasms. The present study reported that multidisciplinary treatment regimens based on surgery can lead to the long-term survival of patients with multiple asynchronous rare primary malignant neoplasms.

Transarterial chemoembolization vs. conservative treatment for unresectable infiltrating hepatocellular carcinoma: A retrospective comparative study.

This study was conducted to compare long-term survival between patients with unresectable infiltrating hepatocellular carcinoma (HCC) who were treated with transarterial chemoembolization (TACE) and those who received conservative treatment (best supportive care). Between January, 2007 and January, 2012, a total of 131 consecutive patients with unresectable infiltrating HCC underwent TACE in a cancer center (TACE group), while 156 similar consecutive HCC patients received conservative treatment in another cancer center (conservative treatment group). The diagnosis of unresectable infiltrating HCC was established by agreement between two radiologists coming from the two centers, who performed an independent review of all the cross-sectional imagings of the patients. The two groups were comparable regarding patient characteristics, preoperative liver function, tumor burden and general condition. In the TACE group, 52 patients received one session and 79 patients received more than one session of TACE (mean, 1.5 and range, 1-4 sessions). There was no reported TACE-related mortality. The 1-month mortality rate was 0.8 and 3.8% in the TACE and the conservative groups, respectively (P=0.134). The median survival for the TACE and conservative treatment groups was 7.0 and 3.0 months, respectively. The 6-, 12- and 24-month overall survival rates for the TACE and conservative treatment groups were 61.7, 18.5 and 2.3% vs. 22.7, 12.1 and 0%, respectively (P<0.001). On multivariate analysis, treatment allocation [odds ratio (OR)=1.777; 95% confidence interval (CI): 1.499-2.107; P<0.001] and portal vein tumor thrombosis (OR=1.721; 95% CI: 1.504-1.907; P<0.001) were independent predictors of overall survival. In conclusion, TACE was found to be a safe and feasible treatment option for patients with unresectable infiltrating HCC and it conferred survival benefit over conservative treatment.

Efficacy of autologous bone marrow buffy coat grafting combined with core decompression in patients with avascular necrosis of femoral head: a prospective, double-blinded, randomized, controlled study.

INTRODUCTION: Avascular necrosis of femoral head (ANFH) is a progressive disease that often leads to hip joint dysfunction and even disability in young patients. Although the standard treatment, which is core decompression, has the advantage of minimal invasion, the efficacy is variable. Recent studies have shown that implantation of bone marrow containing osteogenic precursors into necrotic lesion of ANFH may be promising for the treatment of ANFH. METHODS: A prospective, double-blinded, randomized controlled trial was conducted to examine the effect of bone-marrow buffy coat (BBC) grafting combined with core decompression for the treatment of ANFH. Forty-five patients (53 hips) with Ficat stage I to III ANFH were recruited. The hips were allocated to the control group (core decompression + autologous bone graft) or treatment group (core decompression + autologous bone graft with BBC). Both patients and assessors were blinded to the treatment options. The clinical symptoms and disease progression were assessed as the primary and secondary outcomes. RESULTS: At the final follow-up (24 months), there was a significant relief in pain (P <0.05) and clinical joint symptoms as measured by the Lequesne index (P <0.05) and Western Ontario and McMaster Universities Arthritis Index (P <0.05) in the treatment group. In addition, 33.3% of the hips in the control group have deteriorated to the next stage after 24 months post-procedure, whereas only 8% in the treatment group had further deterioration (P <0.05). More importantly, the non-progression rates for stage I/II hips were 100% in the treatment group and 66.7% in the control group. CONCLUSION: Implantation of the autologous BBC grafting combined with core decompression is effective to prevent further progression for the early stages of ANFH. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01613612. Registered 13 December 2011.