Cemented Endoprosthetic Reconstruction of the Proximal Tibia: How Long Do They Last?

The few available studies documenting the long-term survival of cemented proximal tibial endoprostheses for musculoskeletal tumors do not differentiate between stem designs or patient diagnosis. There is wide variation in survival rates reported, possibly a result of this heterogeneity in patient population and implant design. We therefore asked: (1) How long do proximal tibial endoprostheses last? (2) What is the typical long-term functional result after proximal tibial replacement? And (3) what are the short- and long-term complications associated with endoprosthetic reconstruction of the proximal tibia, particularly with respect to the soft tissue reconstruction? We retrospectively reviewed 52 patients with 52 proximal tibial endoprosthetic reconstructions for a tumor-related diagnosis. Kaplan-Meier survivorship analysis was performed using revision of the stemmed components for any reason as an endpoint for implants, and death due to disease progression for patients. Function was assessed using the MSTS scoring system. The minimum followup was 1 month (mean, 96 months: range, 1–284 months; median, 69 months). Using revision of the stemmed components for any reason as an end point, overall prosthesis survival at 5, 10, 15, and 20 years was 94%, 86%, 66%, and 37%, respectively. The 29 modular implants demonstrated a trend toward improved survival compared to the 23 custom-designed components, with a 15-year survivorship of 88% versus 63%. The mean postoperative Musculoskeletal Tumor Society score at most recent followup was 82% of normal function (mean raw score, 24.6; range, 4–29). Cemented endoprosthetic reconstruction of the proximal tibia provides a reliable method of reconstruction following tumor resection. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence

How Long Do Endoprosthetic Reconstructions for Proximal Femoral Tumors Last?

As the life expectancy of patients with musculoskeletal tumors improves, long-term studies of endoprosthetic reconstructions are necessary to establish realistic expectations for the implants and compare them to other reconstruction approaches. (1) What is the long-term survival of cemented bipolar proximal femoral replacements? (2) How does prosthesis survival compare to patient survival among patients with Stage I, II, and III disease? (3) Do modular implants outperform custom-built prostheses? (4) Do some proximal femoral replacements require conversion to THA? We retrospectively reviewed all 86 proximal femoral replacements used for tumor reconstruction from 1982 to 2008. Primary diagnoses were 43 high-grade tumors (IIA/IIB), 20 low-grade tumors (IA/IB or benign), and 23 with metastatic disease. We reviewed prosthesis survival, patient survival, complication rates, functional outcomes, and rates of conversion to THA. Five of 86 patients (5.8%) required revision of the femoral component. Five-, 10-and 20-year implant survivorships were 93%, 84%, and 56%, respectively. All patients with low-grade disease survived; the 5-year survival rate for patients with metastatic disease was 16%; the 5-, 10-, and 20-year survival for IIA/IIB patients was 54%, 50%, and 44%, respectively. Five of 86 patients (5.8%) underwent conversion to THA for groin pain. Cemented bipolar proximal femoral replacements after tumor resection proved a durable reconstruction technique. The implants outlived patients with metastatic disease and high-grade localized disease while patients with low-grade disease outlived their implants. The survival of modular prostheses was comparable to that of older, one-piece custom designs. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence

FDG-PET/CT Imaging Predicts Histopathologic Treatment Responses after Neoadjuvant Therapy in Adult Primary Bone Sarcomas

Purpose. The aim of this study was to prospectively evaluate whether FDG-PET allows an accurate assessment of histopathologic response to neoadjuvant treatment in adult patients with primary bone sarcomas. Methods. Twelve consecutive patients with resectable, primary high grade bone sarcomas were enrolled prospectively. FDG-PET/CT imaging was performed prior to the initiation and after completion of neoadjuvant treatment. Imaging findings were correlated with histopathologic response. Results. Histopathologic responders showed significantly more pronounced decreases in tumor FDG-SUVmax from baseline to late follow up than non-responders (64 ± 19% versus 29 ± 30 %, resp.; P = .03). Using a 60% decrease in tumor FDG-uptake as a threshold for metabolic response correctly classified 3 of 4 histopathologic responders and 7 of 8 histopathologic non-responders as metabolic responders and non-responders, respectively (sensitivity, 75%; specificity, 88%). Conclusion. These results suggest that changes in FDG-SUVmax at the end of neoadjuvant treatment can identify histopathologic responders and non-responders in adult primary bone sarcoma patients

System size and centrality dependence of the balance function in A+A collisions at sqrt[sNN]=17.2 GeV

Electric charge correlations were studied for p+p, C+C, Si+Si, and centrality selected Pb+Pb collisions at sqrt[sNN]=17.2 GeV with the NA49 large acceptance detector at the CERN SPS. In particular, long-range pseudorapidity correlations of oppositely charged particles were measured using the balance function method. The width of the balance function decreases with increasing system size and centrality of the reactions. This decrease could be related to an increasing delay of hadronization in central Pb+Pb collisions

In-Orbit Performance of the GRACE Follow-on Laser Ranging Interferometer

The Laser Ranging Interferometer (LRI) instrument on the Gravity Recovery and Climate Experiment (GRACE) Follow-On mission has provided the first laser interferometric range measurements between remote spacecraft, separated by approximately 220 km. Autonomous controls that lock the laser frequency to a cavity reference and establish the 5 degrees of freedom two-way laser link between remote spacecraft succeeded on the first attempt. Active beam pointing based on differential wave front sensing compensates spacecraft attitude fluctuations. The LRI has operated continuously without breaks in phase tracking for more than 50 days, and has shown biased range measurements similar to the primary ranging instrument based on microwaves, but with much less noise at a level of 1 nm/Hz at Fourier frequencies above 100 mHz. © 2019 authors. Published by the American Physical Society

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Abstract: Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk