INTRODUCTION:Based upon the Third National Health and Nutrition Examination Survey data, iron deficiency anemia is the cause of at least 20% of cases of anemia in adults over the age of 65. This is especially relevant in patients undergoing major orthopedic surgery as substantial perioperative blood loss is possible, leading to a high rate of allogeneic blood transfusion in total hip replacements, total knee replacements, and hip fracture repairs.SIGNIFICANCE:The results of this systematic review may be of interest to clinicians and hospital administrators evaluating the clinical efficacy and cost effectiveness of intravenous (IV) iron administration prior to major orthopedic surgery.MATERIALS AND METHODS:The original studies considered for this review included patients who were over 18 years of age, undergoing major orthopedic surgery, and who received an IV iron treatment in the preoperative setting. A total of 1083 articles were identified and reviewed. After removing duplicates, 1031 publications were screened, and 105 full-text studies were assessed for eligibility. A total of 98 were excluded and 7 articles remained which met the criteria for this review. The primary outcome examined in the included studies was the allogeneic blood transfusion rate. The secondary areas of interest were changes in serum hemoglobin, morbidity and mortality, length of stay, and cost effectiveness.RESULTS:This systematic review found little evidence that IV iron therapy is effective at reducing transfusion in patients undergoing major orthopedic surgery.CONCLUSIONS:We do not recommend preoperative IV iron therapy for all patients scheduled for major orthopedic surgery.

Background Double lumen endotracheal tubes (DLT) are commonly used to provide single lung ventilation during thoracic surgery. A fiberoptic bronchoscope (FOB) is typically used to confirm accurate DLT placement. Accounting for initial purchase, maintenance, repair and cleaning, the use of an FOB can cost as much as $312 per procedure. The VivaSight DLT (VS-DLT) incorporates a built-in camera, which is aimed at reducing FOB use and its associated costs. In this study, we compared the rate of FOB use when intubating using either a VS-DLT or a conventional DLT (c-DLT). Methods This is a randomized controlled comparative study performed at a public county teaching hospital. A total of 50 patients were enrolled and randomly assigned to either a c-DLT (n=25) or a VS-DLT (n=25). The primary outcome was the rate of FOB use. Secondary outcomes included time to correct tube placement and incidence of malposition during surgery. Results Use of the VS-DLT required significantly less FOB use (28%) compared to use of the c-DLT (100%). While there was no difference in the ease of intubation, the time to correct tube placement was significantly faster using a VS-DLT (54 vs. 156 s, P<0.001). Additionally, the incidence of tube malposition was significantly reduced in the VS-DLT group. Conclusions This study demonstrated a significantly lower rate of FOB use when using a VS-DLT compared to a c-DLT. Placement of the VS-DLT was significantly quicker and malposition during surgery occurred significantly less than with the c-DLT. While intubating with a VS-DLT provides clinical benefits, it may not result in significant cost reductions when compared to a c-DLT.

Introduction: Based upon the Third National Health and Nutrition Examination Survey data, iron deficiency anemia is the cause of at least 20% of cases of anemia in adults over the age of 65. This is especially relevant in patients undergoing major orthopedic surgery as substantial perioperative blood loss is possible, leading to a high rate of allogeneic blood transfusion in total hip replacements, total knee replacements, and hip fracture repairs. Significance: The results of this systematic review may be of interest to clinicians and hospital administrators evaluating the clinical efficacy and cost effectiveness of intravenous (IV) iron administration prior to major orthopedic surgery. Materials and Methods: The original studies considered for this review included patients who were over 18 years of age, undergoing major orthopedic surgery, and who received an IV iron treatment in the preoperative setting. A total of 1083 articles were identified and reviewed. After removing duplicates, 1031 publications were screened, and 105 full-text studies were assessed for eligibility. A total of 98 were excluded and 7 articles remained which met the criteria for this review. The primary outcome examined in the included studies was the allogeneic blood transfusion rate. The secondary areas of interest were changes in serum hemoglobin, morbidity and mortality, length of stay, and cost effectiveness. Results: This systematic review found little evidence that IV iron therapy is effective at reducing transfusion in patients undergoing major orthopedic surgery. Conclusions: We do not recommend preoperative IV iron therapy for all patients scheduled for major orthopedic surgery. Keywords preoperative , anemia , iron deficiency anemia , intravenous iron , orthopedic surgery , hemoglobin

Heat shock protein-90 (Hsp90) is an essential molecular chaperone in eukaryotes involved in maintaining the stability and activity of numerous signalling proteins, also known as clients. Hsp90 ATPase activity is essential for its chaperone function and it is regulated by co-chaperones. Here we show that the tumour suppressor FLCN is an Hsp90 client protein and its binding partners FNIP1/FNIP2 function as co-chaperones. FNIPs decelerate the chaperone cycle, facilitating FLCN interaction with Hsp90, consequently ensuring FLCN stability. FNIPs compete with the activating co-chaperone Aha1 for binding to Hsp90, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins. Lastly, downregulation of FNIPs desensitizes cancer cells to Hsp90 inhibitors, whereas FNIPs overexpression in renal tumours compared with adjacent normal tissues correlates with enhanced binding of Hsp90 to its inhibitors. Our findings suggest that FNIPs expression can potentially serve as a predictive indicator of tumour response to Hsp90 inhibitors.

The Drosophila porcupine gene is required for secretion of wingless and other Wnt proteins, and sporadic mutations in its unique human ortholog, PORCN , cause a pleiotropic X-linked dominant disorder, focal dermal hypoplasia (FDH, also known as Goltz syndrome). We generated a conditional allele of the X-linked mouse Porcn gene and analyzed its requirement in Wnt signaling and embryonic development. We find that Porcn -deficient cells exhibit a cell-autonomous defect in Wnt ligand secretion but remain responsive to exogenous Wnts. Consistent with the female-specific inheritance pattern of FDH, Porcn hemizygous male embryos arrest during early embryogenesis and fail to generate mesoderm, a phenotype previously associated with loss of Wnt activity. Heterozygous Porcn mutant females exhibit a spectrum of limb, skin, and body patterning abnormalities resembling those observed in human patients with FDH. Many of these defects are recapitulated by ectoderm-specific deletion of Porcn , substantiating a long-standing hypothesis regarding the etiology of human FDH and extending previous studies that have focused on downstream elements of Wnt signaling, such as β-catenin. Conditional deletion of Porcn thus provides an experimental model of FDH, as well as a valuable tool to probe Wnt ligand function in vivo.