Citations

Fractures of the calcaneus with associated locked dislocation of the posterior facet have been previously described. Two patients with a calcaneal fracture with a locked dislocation of a portion of the posterior facet were treated with minimally invasive open reduction and percutaneous screw fixation of the fragment with cannulated screws. Both patients had satisfactory reductions and healed the fractures without any soft-tissue complications. This technique can be a useful addition to the armamentarium of the surgeon treating these injuries, especially in the patient at high risk for wound complications.

Tobacco use adversely affects transplant outcomes such as graft survival, patient survival, and other conditions that alter transplant patient longevity. Especially concerning is tobacco's relationship to cardiovascular disease, the number 1 cause of death in kidney transplant recipients. Many authors conclude that tobacco interventions ought to be provided to patients and sometimes lament that there are no tobacco dependence interventions designed for kidney transplant recipients. European Best Practice Guidelines for Renal Transplantation also support tobacco dependence interventions. The purpose of this article is to describe one institution's experience in implementing the clinical practice guideline for treating tobacco use and dependence within a kidney and pancreas transplant program.

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium ( n Stage1 : 111,666; n Stage2 : 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea ( PPM1J , EDEM3, ACP1, SPEG, EYA4, CYP1A1 , and ATXN2L ; P Stage1 <3.7×10 −7 ), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 ( P =5.4×10 −8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2 -knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.

Abstract Background. We recently published and validated the new serum creatinine (Scr)-based full-age-spectrum equation (FAScrea) for estimating the glomerular filtration rate (GFR) for healthy and kidney–diseased subjects of all ages. The equation was based on the concept of normalized Scr and shows equivalent to superior prediction performance to the currently recommended equations for children, adolescents, adults and older adults. Methods. Based on an evaluation of the serum cystatin C (ScysC) distribution, we defined normalization constants for ScysC (QcysC = 0.82 mg/L for ages &lt;70 years and QcysC = 0.95 mg/L for ages ≥70 years). By replacing Scr/Qcrea in the FAScrea equation with ScysC/QcysC, or with the average of both normalized biomarkers, we obtained new ScysC-based (FAScysC) and combined Scr-/ScysC-based FAS equations (FAScombi). To validate the new FAScysC and FAScombi we collected data on measured GFR, Scr, ScysC, age, gender, height and weight from 11 different cohorts including n = 6132 unique white subjects (368 children, aged ≤18 years, 4295 adults and 1469 older adults, aged ≥70 years). Results. In children and adolescents, the new FAScysC equation showed significantly better performance [percentage of patients within 30% of mGFR (P30) = 86.1%] than the Caucasian Asian Paediatric Adult Cohort equation (P30 = 76.6%; P &lt; 0.0001), or the ScysC-based Schwartz equation (P30 = 68.8%; P &lt; 0.0001) and the FAScombi equation outperformed all equations with P30 = 92.1% (P &lt; 0.0001). In adults, the FAScysC equation (P30 = 82.6%) performed equally as well as the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPIcysC) (P30 = 80.4%) and the FAScombi equation (P30 = 89.9%) was also equal to the combined CKD-EPI equation (P30 = 88.2%). In older adults, FAScysC was superior (P30 = 88.2%) to CKD-EPIcysC (P30 = 84.4%; P &lt; 0.0001) and the FAScombi equation (P30 = 91.2%) showed significantly higher performance than the combined CKD-EPI equation (P30 = 85.6%) (P &lt; 0.0001). Conclusion. The FAS equation is not only applicable to all ages, but also for all recommended renal biomarkers and their combinations.

Abstract Purpose: The MET/HGF pathway regulates cell proliferation and survival and is dysregulated in multiple tumors. Emibetuzumab (LY2875358) is a bivalent antibody that inhibits HGF-dependent and HGF-independent MET signaling. Here, we report dose escalation results from the first-in-human phase I trial of emibetuzumab. Experimental Design: The study comprised a 3+3 dose escalation for emibetuzumab monotherapy (Part A) and in combination with erlotinib (Part A2). Emibetuzumab was administered i.v. every 2 weeks (Q2W) using a flat dosing scheme. The primary objective was to determine a recommended phase II dose (RPTD) range; secondary endpoints included tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity. Results: Twenty-three patients with solid tumors received emibetuzumab monotherapy at 20, 70, 210, 700, 1,400, and 2,000 mg and 14 non–small cell lung cancer (NSCLC) patients at 700, 1,400, and 2,000 mg in combination with erlotinib 150 mg daily. No dose-limiting toxicities and related serious or ≥ grade 3 adverse events were observed. The most common emibetuzumab-related adverse events included mild diarrhea, nausea, and vomiting, and mild to moderate fatigue, anorexia, and hypocalcemia in combination with erlotinib. Emibetuzumab showed linear PK at doses &gt;210 mg. Three durable partial responses were observed, one for emibetuzumab (700 mg) and two for emibetuzumab + erlotinib (700 mg and 2,000 mg). Both of the responders to emibetuzumab + erlotinib had progressed to prior erlotinib and were positive for MET protein tumor expression. Conclusions: Based on tolerability, PK/PD analysis, and preliminary clinical activity, the RPTD range for emibetuzumab single agent and in combination with erlotinib is 700 to 2,000 mg i.v. Q2W. Clin Cancer Res; 23(8); 1910–9. ©2016 AACR.

Turner Syndrome (TS) is a developmental disorder caused by partial or complete loss of one sex chromosome. Bicuspid aortic valve and other left‐sided congenital heart lesions (LSL), including thoracic aortic aneurysms and acute aortic dissections, are 30–50 times more frequent in TS than in the general population. In 454 TS subjects, we found that LSL are significantly associated with reduced dosage of Xp genes and increased dosage of Xq genes. We also showed that genome‐wide copy number variation is increased in TS and identify a common copy number variant (CNV) in chromosome 12p13.31 that is associated with LSL with an odds ratio of 3.7. This CNV contains three protein‐coding genes (SLC2A3, SLC2A14, and NANOGP1) and was previously implicated in congenital heart defects in the 22q11 deletion syndrome. In addition, we identified a subset of rare and recurrent CNVs that are also enriched in non‐syndromic BAV cases. These observations support our hypothesis that X chromosome and autosomal variants affecting cardiac developmental genes may interact to cause the increased prevalence of LSL in TS. © 2016 Wiley Periodicals, Inc.

Soft tissue sarcomas of the foot and ankle are common. Currently, there exist limited data on prognostic variables. The aim of this study was to review our institution’s experience with soft tissue sarcomas of the foot and ankle to identify factors affecting outcomes and survivorship. We reviewed the records of 62 foot and ankle soft tissue sarcomas treated with definitive surgery at our institution between 1992 and 2013. The cohort consisted of 35 males and 27 females with a mean age at diagnosis of 45 years and a mean follow-up of 7 years. The most common tumor subtype was synovial sarcoma (n = 16). The overall limb salvage rate was 53%. Local recurrence was observed in 9 patients and distant metastases in 15 patients. Tumor size ≥3 cm in maximal dimension was the greatest risk factor in mortality. Posttreatment complications occurred in 15 patients. Local recurrence and development of distant disease was relatively common following wide excision of a soft tissue sarcoma of the foot and ankle. Tumors that were ≥3 cm in maximal dimension were associated with a worse overall survival and patients with neoadjuvant radiation were at increased risk of complications. Levels of Evidence: Level IV: Retrospective Case Series

Objectives To quantify associations between inflammatory biomarkers and hippocampal volume ( HV ) and to examine effect modification according to sex, race, and age. Design Cross‐sectional analyses using generalized estimating equations to account for familial clustering; standardized β ‐coefficients adjusted for age, sex, race, and education. Setting Community cohorts in Jackson, Mississippi and Rochester, Minnesota. Participants The Genetic Epidemiology Network of Arteriopathy study. Measurements C‐reactive protein ( CRP ), interleukin‐6 ( IL ‐6), and soluble tumor necrosis factor receptors 1 ( sTNFR ‐1) and 2 ( sTNFR ‐2) from peripheral blood were measured in a sample of 773 non‐Hispanic whites (61% women, aged 60.2 ± 9.8) and 514 African Americans (70% women, aged 63.9 ± 8.1) who also underwent brain magnetic resonance imaging. Biomarkers were standardized and compared according to sex, race and age with HV. Results In the full sample, higher sTNFR ‐1 and sTNFR ‐2 were associated with smaller HV . Each standard deviation ( SD ) increase in sTNFR ‐1 was associated with 59.1 mm 3 (95% confidence interval ( CI ) = −101.4 to −16.7 mm 3 ) smaller HV and each SD increase in sTNFR ‐2 associated with 48.8 mm 3 (95% CI = −92.2 to −5.3 mm 3 ) smaller HV . Relationships were stronger for sTNFR ‐2 in men ( HV = −116.6 mm 3 for each SD increase, 95% CI = −201.0 to −32.1) than women ( HV = −26.0 per SD increase, 95% CI = −72.4–20.5) and sTNFR ‐1 in non‐Hispanic whites ( HV = −84.7 mm 3 per SD increase, 95% CI = −142.2 to −27.1) than African Americans ( HV = −14.1 mm 3 per SD increase, 95% CI = −78.3–50.1). Associations between IL ‐6 or CRP and HV were not supported. Conclusion Higher levels of sTNFR s were associated cross‐sectionally with smaller hippocampi. Longitudinal data are needed to determine whether these biomarkers may help to identify risk of late‐life cognitive impairment.