Mating causes decreased life span in female Drosophila. Here we report that mifepristone blocked this effect, yielding life span increases up to +68%. Drug was fed to females after mating, in the absence of males, demonstrating function in females. Mifepristone did not increase life span of virgin females or males. Mifepristone reduced progeny production but did not reduce food intake. High-throughput RNA sequencing was used to identify genes up-regulated or down-regulated upon mating, and where the change was reduced by mifepristone. Five candidate positive regulators of life span were identified, including dosage compensation regulator Unr and three X-linked genes: multi sex combs (PcG gene), Dopamine 2-like receptor and CG14215. The 37 candidate negative genes included neuropeptide CNMamide and several involved in protein mobilization and immune response. The results inform the interpretation of experiments involving mifepristone, and implicate steroid hormone signaling in regulating the trade-off between reproduction and life span.
Background Cemented endoprosthetic reconstruction after resection of primary bone sarcomas has been in common use for decades. Although multiple studies have reported the survivorship of primary endoprostheses, implant survivorship after revision surgery is less well established. Given that earlier advances in systemic therapy improved survival of patients with sarcoma, the usage of revision endoprostheses can be expected to increase and, as such, understanding revision implant survivorship will help to inform patient and surgeon expectations. Additionally, as new implants are developed that allow alternative reconstruction options, a normative dataset establishing accurate expectations for revision cemented endoprostheses is a critical benchmark by which to measure progress. Questions/purposes (1) What is the implant survivorship free of all-cause revision for primary and revision cemented distal femoral replacements (DFRs) used in the treatment of malignant or benign tumors? (2) What are the most common indications for revision of primary and revision DFRs in an oncology population with mean follow-up of more than 10 years? (3) How does the indication for revision of a primary DFR affect the subsequent risk for and type of revision DFR complication? (4) What patient, tumor, or implant characteristics are associated with improved survivorship free of revision in cemented DFRs used in patients treated initially for primary malignant or benign tumors? Methods This was a retrospective, comparative study using our institution's longitudinally-maintained database of 806 cemented endoprostheses starting in 1980 and assessed through December 31, 2018. In all, 365 DFRs were inserted during this time, but 14% (51 of 365) were placed for nonprimary bone tumors and 1% (5 of 365) were cementless reconstructions, leaving 309 cemented DFRs. Seventyone percent (218 of 309) were primary implants and 29 percent (91 of 309) were revision implants (used to revise a prior DFR in all patients). During this time period, our strong bias was to use cemented stems and, thus, nearly all of our patients had cemented stems. Six percent (13 of 218) of primary DFRs were implanted more than 2 years before the study end; however, they lacked 2 years of follow-up data and, thus, were considered lost to follow-up, leaving Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research® neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA approval status, of any drug or device before clinical use.
Background As primary total hip arthroplasty volume continues to increase, so will the number of revision total hip arthroplasty (rTHA) procedures. These complex cases represent a significant clinical and financial burden to the health-care system. Methods This was a retrospective review using the National Inpatient Sample. International Classification of Diseases, 9th and 10 th revision codes were used to identify patients who underwent rTHA and create cohorts based on rTHA indications from 2012 to 2018. National and regional trends for length of stay (LOS), cost, and discharge location were evaluated. Results A total of 292,250 rTHA procedures were identified. The annual number of rTHA procedures increased by 28.1% from 2012 to 2018 (37,325 to 47,810). The top 3 indications for rTHA were instability (20.4%), aseptic loosening (17.8%), and infection (11.1%). Over the study period, the proportion of patients discharged to skilled nursing facility decreased from 44.2% to 38% ( P < .001). Hospital LOS decreased on average from 4.8 to 4.4 days ( P < .001). Infections had the highest average LOS (7.3 days) followed by periprosthetic fractures (6.5 days). Hospital costs decreased over the study period, from $25,794 to $24,555 ( P < .001). The proportion of rTHA cases performed at urban academic centers increased (58.0% to 75.3%, P < .001) while the proportion performed at urban nonacademic centers decreased (35.5% to 19.4%, P < .001). Conclusion Instability was the most common indication for rTHA between 2012 and 2018. The proportion of rTHA performed in urban academic centers has increased substantially, away from urban nonacademic centers. While cost and LOS have decreased, significant geographic variability exists.
Background The durability of endoprostheses after limb salvage surgery is influenced by surgical factors (resection length, implant location, and residual bone quality), implant design (modular versus custom design, rotating versus fixed hinge, coating, collars, and the use of cross pins), and host factors (patient's immune status, activity One of the authors (NMB) certifies receipt of personal payments or benefits, during the study period, in an amount of USD 100,001 to USD 1,000,000 from Daiichi Sankyo Inc; in an amount of USD 10,000 to USD 100,000 from Onkos Surgical Inc; and in an amount of USD 10,000 to USD 100,000 from Zimmer Biomet Holdings Inc. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research® neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA approval status, of any drug or device before clinical use.
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