Musculoskeletal Health Literacy is Associated With Outcome and Satisfaction of Total Knee Arthroplasty.

BACKGROUND: The purpose of this study was to investigate if there is an association between musculoskeletal health literacy with outcome and satisfaction after total knee arthroplasty (TKA). METHODS: A cross-sectional study was performed at our tertiary center to include patients between one and six years postoperatively after primary TKA. Patients were provided a survey including basic demographics, validated musculoskeletal health literacy scale (Literacy in Musculoskeletal Problems), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and TKA satisfaction (whether they would choose to undergo the same operation again). Patients were categorized as either low or normal health literacy based on number of questions (cutoff 6 out of 9) answered correctly on the Literacy in Musculoskeletal Problems. Statistical analysis included multivariate regression with significance at P < .05. RESULTS: Four hundred fifty-three individuals fully completed the survey of eligible participants. Two hundred ninety-six individuals (65.3%) had normal health literacy, and one hundred fifty-seven individuals (34.7%) had low health literacy. Average WOMAC (/96) was 18.0 ± 19.7 in the low and 12.1 ± 15.4 in the normal health literacy groups. Patients with low health literacy had significantly higher WOMAC (worse function) than those with normal health literacy (P = .001). Patients with normal musculoskeletal health literacy were significantly more likely to undergo the same operation again (P = .01, odds ratio 2.163). CONCLUSION: This study shows that patients with low musculoskeletal health literacy have worse outcome scores and are less likely to be satisfied with their TKA. By identifying these patients preoperatively, emphasis can be placed on enhancing procedure expectations and understanding to improve outcome measures and overall satisfaction.

Routes for breaching and protecting genetic privacy.

We are entering an era of ubiquitous genetic information for research, clinical care and personal curiosity. Sharing these data sets is vital for progress in biomedical research. However, a growing concern is the ability to protect the genetic privacy of the data originators. Here, we present an overview of genetic privacy breaching strategies. We outline the principles of each technique, indicate the underlying assumptions, and assess their technological complexity and maturation. We then review potential mitigation methods for privacy-preserving dissemination of sensitive data and highlight different cases that are relevant to genetic applications.

Fate of the Morbidly Obese Patient Who Is Denied Total Joint Arthroplasty.

BACKGROUND: The purpose of this study is to investigate outcomes of patients denied total hip (THA) or knee arthroplasty (TKA) due to morbid obesity. METHODS: We performed an observational study of patients denied arthroplasty due to morbid obesity. A survey including the Harris Hip Score or pain and function components of the original Knee Society Score (KSS) was conducted with minimum 2-year follow-up. Statistical analysis was performed with parametric testing with significance at P < .05. RESULTS: In total, 125 (4.4%) of 2819 patients were denied THA or TKA due to morbid obesity. Twenty-four (19.2%) met target weight and underwent arthroplasty at our institution. Of the remaining 101 (80.8%) patients, 33 (32.7%) agreed to participate in the survey. None received THA and 6 received TKA elsewhere above target body mass index. Harris Hip Score was significantly higher in the successful weight loss cohort at our institution (70.5 ± 13.4 vs 34.6 ± 13.1). KSS Pain (maximum score of 50) and Function (maximum score of 100) were significantly higher in the successful weight loss cohort at our institution (32.9 ± 16.5; 51.1 ± 19.5) compared to the denied nonoperative cohort (7.2 ± 11.5; 33.0 ± 23.1); however, only KSS Pain was higher when compared to the TKA elsewhere cohort (14.2 ± 18.0; 29.2 ± 38.7). KSS Pain and Function were similar for both denial cohorts regardless of undergoing arthroplasty. CONCLUSION: Nearly 80% of patients denied never met target weight for arthroplasty. Those who met target weight prior to arthroplasty often reported better outcomes. Outcomes were similar when target weight was not met regardless of undergoing arthroplasty.

Redefining genomic privacy: trust and empowerment.

Fulfilling the promise of the genetic revolution requires the analysis of large datasets containing information from thousands to millions of participants. However, sharing human genomic data requires protecting subjects from potential harm. Current models rely on de-identification techniques in which privacy versus data utility becomes a zero-sum game. Instead, we propose the use of trust-enabling techniques to create a solution in which researchers and participants both win. To do so we introduce three principles that facilitate trust in genetic research and outline one possible framework built upon those principles. Our hope is that such trust-centric frameworks provide a sustainable solution that reconciles genetic privacy with data sharing and facilitates genetic research.

Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-κB-mediated mechanism.

Loss of muscle mass, or sarcopenia, is nearly universal in cirrhosis and adversely affects patient outcome. The underlying cross-talk between the liver and skeletal muscle mediating sarcopenia is not well understood. Hyperammonemia is a consistent abnormality in cirrhosis due to impaired hepatic detoxification to urea. We observed elevated levels of ammonia in both plasma samples and skeletal muscle biopsies from cirrhotic patients compared with healthy controls. Furthermore, skeletal muscle from cirrhotics had increased expression of myostatin, a known inhibitor of skeletal muscle accretion and growth. In vivo studies in mice showed that hyperammonemia reduced muscle mass and strength and increased myostatin expression in wild-type compared with postdevelopmental myostatin knockout mice. We postulated that hyperammonemia is an underlying link between hepatic dysfunction in cirrhosis and skeletal muscle loss. Therefore, murine C2C12 myotubes were treated with ammonium acetate resulting in intracellular concentrations similar to those in cirrhotic muscle. In this system, we demonstrate that hyperammonemia stimulated myostatin expression in a NF-κB-dependent manner. This finding was also observed in primary murine muscle cell cultures. Hyperammonemia triggered activation of IκB kinase, NF-κB nuclear translocation, binding of the NF-κB p65 subunit to specific sites within the myostatin promoter, and stimulation of myostatin gene transcription. Pharmacologic inhibition or gene silencing of NF-κB abolished myostatin up-regulation under conditions of hyperammonemia. Our work provides unique insights into hyperammonemia-induced myostatin expression and suggests a mechanism by which sarcopenia develops in cirrhotic patients.

Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves Osseointegration.

BACKGROUND: Innate defense regulator peptide-1018 (IDR-1018) is a 12-amino acid, synthetic, immunomodulatory host defense peptide that can reduce soft tissue infections and is less likely to induce bacterial resistance than conventional antibiotics. However, IDRs have not been tested on orthopaedic infections and the immunomodulatory effects of IDR-1018 have only been characterized in response to lipopolysacharide, which is exclusively produced by Gram-negative bacteria. QUESTIONS/PURPOSES: We sought (1) to more fully characterize the immunomodulatory effects of IDR-1018, especially in response to Staphylococcus aureus; and (2) to determine whether IDR-1018 decreases S aureus infection of orthopaedic implants in mice and thereby protects the implants from failure to osseointegrate. METHODS: In vitro effects of IDR-1018 on S aureus were assessed by determining minimum inhibitory concentrations in bacterial broth without and with supplementation of physiologic ion levels. In vitro effects of IDR-1018 on macrophages were determined by measuring production of monocyte chemoattractant protein-1 (MCP-1) and proinflammatory cytokines by enzyme-linked immunosorbent assay. In vivo effects of IDR-1018 were determined in a murine model of S aureus implant infection by quantitating bacterial burden, macrophage recruitment, MCP-1, proinflammatory cytokines, and osseointegration in nine mice per group on Day 1 postimplantation and 20 mice per group on Day 15 postimplantation. RESULTS: IDR-1018 demonstrated antimicrobial activity by directly killing S aureus even in the presence of physiologic ion levels, increasing recruitment of macrophages to the site of infections by 40% (p = 0.036) and accelerating S aureus clearance in vivo (p = 0.008) with a 2.6-fold decrease in bacterial bioburden on Day 7 postimplantation. In vitro immunomodulatory activity of IDR-1018 included inducing production of MCP-1 in the absence of other inflammatory stimuli and to potently blunt excess production of proinflammatory cytokines and MCP-1 induced by lipopolysaccharide. Higher concentrations of IDR-1018 were required to blunt production of proinflammatory cytokines and MCP-1 in the presence S aureus. The largest in vivo immunomodulatory effect of IDR-1018 was to reduce tumor necrosis factor-α levels induced by S aureus by 60% (p = 0.006). Most importantly, IDR-1018 reduced S aureus-induced failures of osseointegration by threefold (p = 0.022) and increased osseointegration as measured by ultimate force (5.4-fold, p = 0.033) and average stiffness (4.3-fold, p = 0.049). CONCLUSIONS: IDR-1018 is potentially useful to reduce orthopaedic infections by directly killing bacteria and by recruiting macrophages to the infection site. CLINICAL RELEVANCE: These findings make IDR-1018 an attractive candidate to explore in larger animal models to ascertain whether its effects in our in vitro and mouse experiments can be replicated in more clinically relevant settings.

Post-liver transplantation sarcopenia in cirrhosis: a prospective evaluation.

BACKGROUND AND AIM: Pre-transplant sarcopenia (reduced skeletal muscle mass) predicts poor outcome in cirrhosis. In contrast, whether muscle mass increases post-orthotopic liver transplantation (OLT) is not known and was studied prospectively. METHODS: Consecutive patients who underwent a comprehensive nutritional evaluation in a liver transplant nutrition clinic were included. Core abdominal muscle area was measured on abdominal computed tomography obtained pre- and post-OLT. Age- and gender-based controls were used to define sarcopenia. Measures of body composition pre-transplant were correlated with computed tomography measurements. Predictors and clinical impact of post-OLT change in muscle area were examined. In three subjects post-OLT and three controls, expression of genes regulating skeletal muscle mass were quantified. RESULTS: During the study period, 53 patients (M:F 41:12; age 56.9 ± 7.5 years) were followed up after OLT for 19.3 ± 9 months. Five patients died and another five had acute graft rejection. Pre-OLT sarcopenia was present in 33 (66.2%). Pre-transplant clinical characteristics including Child's score, MELD score, and nutritional status or post-transplantation immunosuppression regimen did not predict post-transplant change in muscle mass. New onset post-OLT sarcopenia developed in 14 patients. Loss of muscle mass post-OLT increased risk of diabetes mellitus and a trend toward higher mortality. Skeletal muscle expression of myostatin was higher and that of ubiquitin proteasome proteolytic components lower post-OLT than in controls. CONCLUSIONS: Post-transplantation sarcopenia is common and could not be attributed to pre-transplant characteristics or the type or duration of post-OLT immunosuppression. Post-transplant sarcopenia contributes to adverse consequences and strategies targeting myostatin may be beneficial.

Considerations for governing open foundation models.

Different policy proposals may disproportionately affect the innovation ecosystem.

'On Table' Versus 'Off Table' Direct Anterior Approach Total Hip Arthroplasty: Is There a Difference?

Background: The purpose of this study was to evaluate whether there were differences in patient-reported outcomes, operative times, satisfaction scores, and complications between patients undergoing total hip arthroplasty (THA) performed through a direct anterior approach on a specialized traction table or a regular operating room table. Methods: Patients who underwent a direct anterior approach THA on a specialized table or a regular table with a minimum 1-year follow-up were included. Patient-reported outcome measures and THA satisfaction were recorded. Demographics, complications, and operative times (both in-room and surgical time) were evaluated. Three hundred twenty-two patients were included with 217 (67.4%) undergoing anterior THA on the specialized table and 105 (32.6%) on a regular table. Results: Outcome measures were similar at 4 months and 1 year postoperatively. Average operative time was 87 minutes (range, 50-160) and 90 minutes (range, 35-197) for the specialized table and regular table groups (P = .314). Average total in room time was 123 minutes (range, 87-201) and 120 minutes (range, 62-255) for the specialized table and regular table groups (P = .564). Satisfaction rates between groups did not differ (P = .564). No differences were found in complication rates at 4 months (P = .814) or 1 year (P = .547). Conclusions: This study shows that the direct anterior approach for THA can be safely and efficiently performed on either a specialized traction table or a regular table. Surgeons should continue to utilize the approach and set-up they are most comfortable with to achieve an optimal outcome for the patient.

REFORMS: Consensus-based Recommendations for Machine-learning-based Science.

Machine learning (ML) methods are proliferating in scientific research. However, the adoption of these methods has been accompanied by failures of validity, reproducibility, and generalizability. These failures can hinder scientific progress, lead to false consensus around invalid claims, and undermine the credibility of ML-based science. ML methods are often applied and fail in similar ways across disciplines. Motivated by this observation, our goal is to provide clear recommendations for conducting and reporting ML-based science. Drawing from an extensive review of past literature, we present the REFORMS checklist (recommendations for machine-learning-based science). It consists of 32 questions and a paired set of guidelines. REFORMS was developed on the basis of a consensus of 19 researchers across computer science, data science, mathematics, social sciences, and biomedical sciences. REFORMS can serve as a resource for researchers when designing and implementing a study, for referees when reviewing papers, and for journals when enforcing standards for transparency and reproducibility.

How large language models can reshape collective intelligence.

Collective intelligence underpins the success of groups, organizations, markets and societies. Through distributed cognition and coordination, collectives can achieve outcomes that exceed the capabilities of individuals-even experts-resulting in improved accuracy and novel capabilities. Often, collective intelligence is supported by information technology, such as online prediction markets that elicit the 'wisdom of crowds', online forums that structure collective deliberation or digital platforms that crowdsource knowledge from the public. Large language models, however, are transforming how information is aggregated, accessed and transmitted online. Here we focus on the unique opportunities and challenges this transformation poses for collective intelligence. We bring together interdisciplinary perspectives from industry and academia to identify potential benefits, risks, policy-relevant considerations and open research questions, culminating in a call for a closer examination of how large language models affect humans' ability to collectively tackle complex problems.

Leakage and the reproducibility crisis in machine-learning-based science.

Machine-learning (ML) methods have gained prominence in the quantitative sciences. However, there are many known methodological pitfalls, including data leakage, in ML-based science. We systematically investigate reproducibility issues in ML-based science. Through a survey of literature in fields that have adopted ML methods, we find 17 fields where leakage has been found, collectively affecting 294 papers and, in some cases, leading to wildly overoptimistic conclusions. Based on our survey, we introduce a detailed taxonomy of eight types of leakage, ranging from textbook errors to open research problems. We propose that researchers test for each type of leakage by filling out model info sheets, which we introduce. Finally, we conduct a reproducibility study of civil war prediction, where complex ML models are believed to vastly outperform traditional statistical models such as logistic regression (LR). When the errors are corrected, complex ML models do not perform substantively better than decades-old LR models.

Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis.

Hyperammonemia and sarcopenia (loss of skeletal muscle) are consistent abnormalities in cirrhosis and portosystemic shunting. We have shown that muscle ubiquitin-proteasome components are not increased with hyperammonemia despite sarcopenia. This suggests that an alternative mechanism of proteolysis contributes to sarcopenia in cirrhosis. We hypothesized that autophagy could be this alternative pathway since we observed increases in classic autophagy markers, increased LC3 lipidation, beclin-1 expression, and p62 degradation in immunoblots of skeletal muscle protein in cirrhotic patients. We observed similar changes in these autophagy markers in the portacaval anastamosis (PCA) rat model. To determine the mechanistic relationship between hyperammonemia and autophagy, we exposed murine C(2)C(12) myotubes to ammonium acetate. Significant increases in LC3 lipidation, beclin-1 expression, and p62 degradation occurred by 1 h, whereas autophagy gene expression (LC3, Atg5, Atg7, beclin-1) increased at 24 h. C(2)C(12) cells stably expressing GFP-LC3 or GFP-mCherry-LC3 constructs showed increased formation of mature autophagosomes supported by electron microscopic studies. Hyperammonemia also increased autophagic flux in mice, as quantified by an in vivo autophagometer. Because hyperammonemia induces nitration of proteins in astrocytes, we quantified global muscle protein nitration in cirrhotic patients, in the PCA rat, and in C(2)C(12) cells treated with ammonium acetate. Increased protein nitration was observed in all of these systems. Furthermore, colocalization of nitrated proteins with GFP-LC3-positive puncta in hyperammonemic C(2)C(12) cells suggested that autophagy is involved in degradation of nitrated proteins. These observations show that increased skeletal muscle autophagy in cirrhosis is mediated by hyperammonemia and may contribute to sarcopenia of cirrhosis.

Are immediate postoperative X-Rays valuable in evaluating complications of primary total hip arthroplasty?

PURPOSE: This study aimed to investigate the complications of primary total hip arthroplasty based on immediate postoperative X-rays. The overall quality and cost of X-rays were assessed. METHODS: The institutional database was queried to identify all patients who underwent total hip arthroplasty in a single institution between January 1, 2018, and December 31, 2018. Immediate postoperative X-rays were reviewed to identify the complications such as periprosthetic fractures, dislocation, and fixation failure. The quality and cost of X-ray were assessed. The complications were categorized as "known" and "unknown" according to the intraoperative fluoroscopic results. RESULTS: A total of 518 total hip arthroplasties were included in this study. Based on intraoperative fluoroscopy, periprosthetic fractures were found in 10 (2%) THAs. Compared to the X-rays taken immediately after surgery, 9 periprosthetic fractures (recorded as "known") were found and 1 was not (recorded as "unknown"). There was no significant difference between intraoperative fluoroscopy and X-rays (P > 0.05). Of the 518 X-rays, 225 (43%) were of suboptimal quality. The cost of a single portable pelvic X-ray was $647. CONCLUSION: In total hip arthroplasty, X-rays taken immediately after surgery rarely reveal unknown complications. The X-rays are often of suboptimal quality, have minimal clinical utility, and are less cost-effective.

Surgical Strategies: Necrotizing Fasciitis of the Foot and Ankle Treated With Dermal Regeneration Matrix for Limb Salvage.

Although necrotizing fasciitis is a life-threatening entity that needs expeditious treatment, cases involving the lower extremity are less commonly encountered than in the upper extremity. Surgical intervention is often required and likely lead to amputation (below-knee or above-knee) vs debridement in the lower extremity.Coverage options in the foot and ankle after serial debridements can present many challenges for limb salvage. Patients are often left with large soft tissue defects requiring coverage with a subsequent increase in relative morbidity. Treatment options for coverage in these cases include negative-pressure wound therapy, split-thickness skin grafting, free flap coverage, or higher-level amputation. In the diabetic population, who present with a lower extremity necrotizing infection, limb salvage is often a challenge given the multiple comorbidities associated with these patients including peripheral vascular disease, immunocompromised state, and neuropathy. Optimal treatment strategies for these necrotizing infections in the foot and ankle remain uncertain.We offer a technique tip for utilization of a dermal regeneration matrix to allow coverage of large soft tissue defect with exposed tendon and/or bone without the need for free flap coverage or higher-level amputation, thus allowing for an additional limb salvage option.Level of Evidence: Level V, expert opinion.

Web-Based Perceived Present Control Intervention for Voice Disorders: A Pilot Study.

OBJECTIVE: Voice disorders are common and negatively affect various life domains such as occupational functioning and emotional well-being. Perceived present control, a factor that is amenable to change, may reduce the effect of voice disorders on these outcomes. This pilot study aimed to (1) establish the feasibility, usability, and acceptability of a web-based perceived present control intervention for individuals with voice disorders and (2) gather preliminary data on the effectiveness of the intervention. This study is the first to assess whether a web-based psychological intervention would decrease self-reported voice handicap in this population. METHODS: Participants (N = 20) were recruited from an otolaryngology clinic at a large, Midwest university and the surrounding urban community, and completed a 3-week web-based intervention that incorporated psychoeducation and written exercises on increasing perceived present control. RESULTS: Supporting feasibility, the intervention components had high completion rates (75%-95%). Most participants planned to continue the perceived control exercises after study completion and would recommend the intervention to others, demonstrating usability and acceptability. There was a significant decrease in self-reported voice handicap (Voice Handicap Index-10) from pretest (M = 18.38, standard deviation = 4.41) to post-test (M = 15.22, standard deviation = 4.55) with a large effect size (within-group d = -0.86, P < 0.05). CONCLUSIONS: Focusing on perceived present control as a teachable skill may be a useful addition to voice disorder treatment armamentarium. Future studies will incorporate a comparison group and larger sample sizes to assess further the role of perceived present control interventions in voice care.

Privacy, Ethics, and Data Access: A Case Study of the Fragile Families Challenge.

Stewards of social data face a fundamental tension. On one hand, they want to make their data accessible to as many researchers as possible to facilitate new discoveries. At the same time, they want to restrict access to their data as much as possible to protect the people represented in the data. In this article, we provide a case study addressing this common tension in an uncommon setting: the Fragile Families Challenge, a scientific mass collaboration designed to yield insights that could improve the lives of disadvantaged children in the United States. We describe our process of threat modeling, threat mitigation, and third-party guidance. We also describe the ethical principles that formed the basis of our process. We are open about our process and the trade-offs we made in the hope that others can improve on what we have done.

Semantics derived automatically from language corpora contain human-like biases.

Machine learning is a means to derive artificial intelligence by discovering patterns in existing data. Here, we show that applying machine learning to ordinary human language results in human-like semantic biases. We replicated a spectrum of known biases, as measured by the Implicit Association Test, using a widely used, purely statistical machine-learning model trained on a standard corpus of text from the World Wide Web. Our results indicate that text corpora contain recoverable and accurate imprints of our historic biases, whether morally neutral as toward insects or flowers, problematic as toward race or gender, or even simply veridical, reflecting the status quo distribution of gender with respect to careers or first names. Our methods hold promise for identifying and addressing sources of bias in culture, including technology.