Expression profiling of cultured podocytes exposed to nephrotic plasma reveals intrinsic molecular signatures of nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) is a common renal disorder in children attributed to podocyte injury. However, children with the same diagnosis have markedly variable treatment responses, clinical courses, and outcomes, suggesting molecular heterogeneity. PURPOSE: This study aimed to explore the molecular responses of podocytes to nephrotic plasma to identify specific genes and signaling pathways differentiating various clinical NS groups as well as biological processes that drive injury in normal podocytes. METHODS: Transcriptome profiles from immortalized human podocyte cell line exposed to the plasma of 8 subjects (steroidsensitive nephrotic syndrome [SSNS], n=4; steroid-resistant nephrotic syndrome [SRNS], n=2; and healthy adult individuals [control], n=2) were generated using microarray analysis. RESULTS: Unsupervised hierarchical clustering of global gene expression data was broadly correlated with the clinical classification of NS. Differential gene expression (DGE) analysis of diseased groups (SSNS or SRNS) versus healthy controls identified 105 genes (58 up-regulated, 47 down-regulated) in SSNS and 139 genes (78 up-regulated, 61 down-regulated) in SRNS with 55 common to SSNS and SRNS, while the rest were unique (50 in SSNS, 84 genes in SRNS). Pathway analysis of the significant (P≤0.05, -1≤ log2 FC ≥1) differentially expressed genes identified the transforming growth factor-ß and Janus kinase-signal transducer and activator of transcription pathways to be involved in both SSNS and SRNS. DGE analysis of SSNS versus SRNS identified 2,350 genes with values of P≤0.05, and a heatmap of corresponding expression values of these genes in each subject showed clear differences in SSNS and SRNS. CONCLUSION: Our study observations indicate that, although podocyte injury follows similar pathways in different clinical subgroups, the pathways are modulated differently as evidenced by the heatmap. Such transcriptome profiling with a larger cohort can stratify patients into intrinsic subtypes and provide insight into the molecular mechanisms of podocyte injury.

Survivorship of autologous structural bone graft at a minimum of 2 years when used to address significant glenoid bone loss in primary and revision shoulder arthroplasty: a computed tomographic and clinical review.

BACKGROUND: Severe glenoid bone loss remains a challenge in patients requiring shoulder arthroplasty and often requires autogenous bone grafting. The purpose of this study was to assess the integrity of the bone graft at 2 years in a series of primary and revision shoulder replacements where glenoid bone loss was managed using a structural autograft (humeral head or iliac crest bone graft) in combination with a trabecular titanium (TT) implant. METHODS: Ethical approval was sought, and the study has a portfolio study status by the NIHR (17/YH/0318). We contacted patients who had primary and revision shoulder arthroplasty with Lima Axioma TT metal-back glenoid with autologous bone graft and were more than 2 years since their operation. All eligible patients underwent computed tomographic evaluation, clinical review, and scoring. Early failures of composite fixation and patients who had revision procedures were excluded (2 patients). RESULTS: Forty-one patients (43 shoulders) with a mean age of 65 years (range 33-85 years) were reviewed. There were 24 women and 17 men. The average follow-up period was 40 months (range 24-59 months). Primary arthroplasty was performed in 24 shoulders, whereas 19 shoulders had revision arthroplasty. Twenty-five shoulders had reverse shoulder replacement and 18 had anatomic shoulder replacement. Twenty-four shoulders had graft taken from the humeral head, and 19 had iliac crest bone graft, reflecting the number of revisions. We used Wrightington classification for porous metal implant and bone graft incorporation. Satisfactory bone graft incorporation (>50%) was seen in 40 shoulders, and only 3 patients had <50% graft incorporation. The scans at 2 years or later showed no significant deterioration in the bone graft from the early postoperative scans. Average forward elevation improved from 50° (preoperative) to 98° (range 35°-150°). The mean improvement in mean Oxford Shoulder Score was 16 (preoperative, 15; postoperative, 31) and the mean improvement in Constant score improvement was 36 (preoperative, 12; postoperative, 48). The mean postoperative American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score was 64 (range 30-85). CONCLUSION: The use of TT in conjunction with autologous bone graft provides a reliable method of addressing glenoid bone defects in primary and revision shoulder arthroplasty. This graft-trabecular metal composite has been shown to integrate well and remain largely unchanged over a 2-year period. A stable baseplate is essential in difficult primary and revision arthroplasty situations. The stability of this construct in our series is reflected in the satisfactory outcomes.

Disseminated synovial chondromatosis of the knee treated by open radical synovectomy using combined anterior and posterior approaches.

Synovial chondromatosis of the knee is a rare benign neoplasm of the synovium. Likewise, uncertainty on management still prevails. Though rare, it nevertheless warrants greater emphasis than it receives in the literature to allow correct diagnosis and accurate early surgical intervention. It predominantly involves the anterior compartment of the knee and disseminated disease is extremely rare. The optimal approach for surgical treatment of such an extensive synovial chondromatosis of knee remains unclear. Herein, we describe a case of extensive generalized synovial chondromatosis of the knee extending into the Baker's cyst in a 30 years old female. A diagnosis of synovial chondromatosis was made by clinical evaluation and MR imaging and confirmed by histopathological examination. Patient was successfully treated by open radical synovectomy of knee using both anterior and posterior approaches in a single step procedure.