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Defining the tipping point for primary shoulder arthroplasty.

ABSTRACT: Background:Although risk factors for poor outcomes and complications have been studied, there remain limited objective criteria to guide surgeons about the timing of arthroplasty. The purpose of this study was to further characterize the tipping-point scores for a group of patient-reported outcome measures (PROMs) in patients undergoing primary shoulder arthroplasty. Methods:We retrospectively reviewed 5670 primary shoulder arthroplasties (1833 anatomic total shoulder arthroplasties and 3837 reverse shoulder arthroplasties [RSAs]) performed over a 10-year period. Preoperative range of motion, PROMs (American Shoulder and Elbow Surgeons, Simple Shoulder Test, and Shoulder Pain and Disability Index scores), and Constant scores were evaluated. The tipping point for each PROM was evaluated. Univariate and multivariate analyses were performed to assess risk factors for lower tipping points. Results:Patients undergoing RSA demonstrated lower tipping points for all range-of-motion parameters as well as American Shoulder and Elbow Surgeons, Shoulder Pain and Disability Index, and Simple Shoulder Test scores. Female sex was predictive of a lower tipping point prior to shoulder arthroplasty, regardless of implant type. When the total shoulder arthroplasty subgroup was evaluated, both female sex and a higher body mass index were shown to be associated with a lower tipping point. Discussion:The choice to undergo shoulder arthroplasty is a multifactorial decision that encompasses both physical and social factors. Female patients and patients undergoing RSA are more likely to accept slightly worse shoulder function prior to making the decision to undergo shoulder arthroplasty.

SUBMITTER: Schoch BS

PROVIDER: S-EPMC6928298 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Defining the tipping point for primary shoulder arthroplasty.

Schoch Bradley S BS King Joseph J JJ Wright Thomas W TW Vigan Marie M Werthel Jean David JD

JSES open access 20191118 4

<h4>Background</h4>Although risk factors for poor outcomes and complications have been studied, there remain limited objective criteria to guide surgeons about the timing of arthroplasty. The purpose of this study was to further characterize the tipping-point scores for a group of patient-reported outcome measures (PROMs) in patients undergoing primary shoulder arthroplasty.<h4>Methods</h4>We retrospectively reviewed 5670 primary shoulder arthroplasties (1833 anatomic total shoulder arthroplasti ...[more]

PMID: 31891025

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Project description:Determining mechanism-based biomarkers that distinguish adaptive and adverse cellular processes is critical to understanding the health effects of environmental exposures. Shifting from in vivo, low-throughput toxicity studies to high-throughput screening (HTS) paradigms and risk assessment based on in vitro and in silico testing requires utilizing toxicity pathway information to distinguish adverse outcomes from recoverable adaptive events. Little work has focused on oxidative stresses in human airway for the purposes of predicting adverse responses. We hypothesize that early gene expression-mediated molecular changes could be used to delineate adaptive and adverse responses to environmentally-based perturbations. Here, we examined cellular responses of the tracheobronchial airway to zinc (Zn) exposure, a model oxidant. Airway derived BEAS-2B cells exposed to 2–10 µM Zn2+ elicited concentration- and time-dependent cytotoxicity. Normal, adaptive, and cytotoxic Zn2+ exposure conditions were determined with traditional apical endpoints, and differences in global gene expression around the tipping point of the responses were used to delineate underlying molecular mechanisms. Bioinformatic analyses of differentially expressed genes indicate early enrichment of stress signaling pathways, including those mediated by the transcription factors p53 and NRF2. After 4 h, 154 genes were differentially expressed (p <0.01) between the adaptive and cytotoxic Zn2+ concentrations. Nearly 40% of the biomarker genes were related to the p53 signaling pathway with 30 genes identified as likely direct targets using a database of p53 ChIP-seq studies. Despite similar p53 activation profiles, these data revealed widespread dampening of p53 and NRF2-related genes as early as 4 h after exposure at higher, unrecoverable Zn2+ exposures. Thus, in our model early increased activation of stress response pathways indicated a recoverable adaptive event. Overall, this study highlights the importance of characterizing molecular mechanisms around the tipping point of adverse responses to better inform HTS paradigms.

Project description:Background:With an increasing volume of primary total shoulder arthroplasties (TSA), the number of revision TSA cases is expected to increase as well. However, the postoperative medical morbidity of revision TSA has not been clearly described. Questions/Purposes:The purpose of this study was to determine the rate of postoperative complications following revision TSA, relative to primary TSA. In addition, we sought to identify independent predictors of complications, as well as to compare operative time and postoperative length of stay between primary and revision TSA. Methods:Patients who underwent primary/revision TSA between 2005 and 2015 were identified in the American College of Surgeons National Surgical Quality Improvement Program. Differences in complications, readmission rates, operative time, length of stay, and predictors of complications were evaluated using bivariate and multivariate analyses. Results:A total of 10,371 primary TSA (95.4%) and 496 revision TSA cases (4.6%) were identified. The overall complication rate was 6.5% in primary and 10.7% in revision TSA patients (p < 0.001). Multivariate analysis identified an increased risk of any complication (odds ratio 1.73, p < 0.001), major complication (2.08, p = 0.001), and wound infection (3.45, p = 0.001) in revision TSA patients, relative to primary cases. Operative time was increased in revision cases (mean ± standard deviation, 125 ± 62.5), relative to primary (115 ± 47.7, p < 0.001). Age > 75, female sex, history of diabetes or chronic obstructive pulmonary disease, and American Society of Anesthesiologists classification ? 3 were associated with increased risk of any complication. Smoking history was the only significant predictor of wound infection. Conclusion:Revision TSA, in comparison to primary, poses an increased risk of postoperative complications, particularly wound infections. A history of smoking was an independent predictor of wound infections.

Project description:Background & aimsFarnesoid X receptor (FXR) agonists and fibroblast growth factor 19 (FGF19) analogues suppress bile acid synthesis and are being investigated for their potential therapeutic efficacy in cholestatic liver diseases. We investigated whether bile acid synthesis associated with outcomes in 2 independent populations of people with primary sclerosing cholangitis (PSC) not receiving such therapy.MethodsConcentrations of individual bile acids and 7α-hydroxy-4-cholesten-3-one (C4) were measured in blood samples from 330 patients with PSC attending tertiary care hospitals in the discovery and validation cohorts and from 100 healthy donors. We used a predefined multivariable Cox proportional hazards model to evaluate the prognostic value of C4 to predict liver transplantation-free survival and evaluated its performance in the validation cohort.ResultsThe bile acid synthesis marker C4 was negatively associated with total bile acids. Patients with fully suppressed bile acid synthesis had strongly elevated total bile acids and short liver transplantation-free survival. In multivariable models, a 50% reduction in C4 corresponded to increased hazards for liver transplantation or death in both the discovery (adjusted hazard ratio [HR] = 1.24, 95% CI 1.06-1.43) and validation (adjusted HR = 1.23, 95% CI 1.03-1.47) cohorts. Adding C4 to established risk scores added value to predict future events, and predicted survival probabilities were well calibrated externally. There was no discernible impact of ursodeoxycholic acid treatment on bile acid synthesis.ConclusionsBile acid accumulation-associated suppression of bile acid synthesis was apparent in patients with advanced PSC and associated with reduced transplantation-free survival. In a subset of the patients, bile acid synthesis was likely suppressed beyond a tipping point at which any further pharmacological suppression may be futile. Implications for patient stratification and inclusion criteria for clinical trials in PSC warrant further investigation.Lay summaryWe show, by measuring the level of the metabolite C4 in the blood from patients with primary sclerosing cholangitis (PSC), that low production of bile acids in the liver predicts a more rapid progression to severe disease. Many people with PSC appear to have fully suppressed bile acid production, and both established and new drugs that aim to reduce bile acid production may therefore be futile for them. We propose C4 as a test to find those likely to respond to these treatments.

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Defining the tipping point for primary shoulder arthroplasty.

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Defining the tipping point for primary shoulder arthroplasty.

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