FoxA factors: the chromatin key and doorstop essential for liver development and function.

Pioneer factors are transcriptional regulators with the capacity to bind inactive regions of chromatin and induce changes in accessibility that underpin cell fate decisions. The FOXA family of transcription factors is well understood to have pioneer capacity. Indeed, researchers have uncovered numerous examples of FOXA-dependent epigenomic modulation in developmental and disease processes. Despite the presence of FOXA being essential for correct epigenetic patterning, the need for continued FOXA presence postchromatin modulation has been debated. In a recent study in this issue of Genes & Development, Reizel and colleagues (pp. 1039-1050) show that the tissue-specific ablation of FOXA1/2/3 in the adult mouse liver results in the collapse of the epigenetic profile that maintains the hepatic gene expression profile. Thus, FOXA functions as a key, opening regions of chromatin during development, and as a doorstep, maintaining the established euchromatic structure in adult tissue.

GATA6 is a crucial factor for Myocd expression in the visceral smooth muscle cell differentiation program of the murine ureter.

Smooth muscle cells (SMCs) are a crucial component of the mesenchymal wall of the ureter, as they account for the efficient removal of the urine from the renal pelvis to the bladder by means of their contractile activity. Here, we show that the zinc-finger transcription factor gene Gata6 is expressed in mesenchymal precursors of ureteric SMCs under the control of BMP4 signaling. Mice with a conditional loss of Gata6 in these precursors exhibit a delayed onset and reduced level of SMC differentiation and peristaltic activity, as well as dilatation of the ureter and renal pelvis (hydroureternephrosis) at birth and at postnatal stages. Molecular profiling revealed a delayed and reduced expression of the myogenic driver gene Myocd, but the activation of signaling pathways and transcription factors previously implicated in activation of the visceral SMC program in the ureter was unchanged. Additional gain-of-function experiments suggest that GATA6 cooperates with FOXF1 in Myocd activation and SMC differentiation, possibly as pioneer and lineage-determining factors, respectively.

A PNPLA3-Deficient iPSC-Derived Hepatocyte Screen Identifies Pathways to Potentially Reduce Steatosis in Metabolic Dysfunction-Associated Fatty Liver Disease.

The incidence of nonalcoholic fatty liver disease (NAFLD), or metabolic dysfunction-associated fatty liver disease (MAFLD), is increasing in adults and children. Unfortunately, effective pharmacological treatments remain unavailable. Single nucleotide polymorphisms (SNPs) in the patatin-like phospholipase domain-containing protein (PNPLA3 I148M) have the most significant genetic association with the disease at all stages of its progression. A roadblock to identifying potential treatments for PNPLA3-induced NAFLD is the lack of a human cell platform that recapitulates the PNPLA3 I148M-mediated onset of lipid accumulation. Hepatocyte-like cells were generated from PNPLA3-/- and PNPLA3I148M/M-induced pluripotent stem cells (iPSCs). Lipid levels were measured by staining with BODIPY 493/503 and were found to increase in PNPLA3 variant iPSC-derived hepatocytes. A small-molecule screen identified multiple compounds that target Src/PI3K/Akt signaling and could eradicate lipid accumulation in these cells. We found that drugs currently in clinical trials for cancer treatment that target the same pathways also reduced lipid accumulation in PNPLA3 variant cells.

Leptin-based hexamers facilitate memory and prevent amyloid-driven AMPA receptor internalisation and neuronal degeneration.

Key pathological features of Alzheimer's disease (AD) include build-up of amyloid ß (Aß), which promotes synaptic abnormalities and ultimately leads to neuronal cell death. Metabolic dysfunction is known to influence the risk of developing AD. Impairments in the leptin system have been detected in AD patients, which has fuelled interest in targeting this system to treat AD. Increasing evidence supports pro-cognitive and neuroprotective actions of leptin and these beneficial effects of leptin are mirrored by a bioactive leptin fragment (leptin116-130 ). Here we extend these studies to examine the potential cognitive enhancing and neuroprotective actions of 8 six-amino acid peptides (hexamers) derived from leptin116-130 . In this study, we show that four of the hexamers (leptin116-121, 117-122, 118-123 and 120-125 ) replicate the ability of leptin to promote α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking and facilitate hippocampal synaptic plasticity. Moreover, the pro-cognitive effects of the hexamers were verified in behavioural studies, with the administration of leptin117-122 enhancing performance in episodic memory tasks. The bioactive hexamers replicated the neuroprotective actions of leptin by preventing the acute hippocampal synapto-toxic effects of Aß, and the chronic effects of Aß on neuronal cell viability, Aß seeding and tau phosphorylation. These findings provide further evidence to support leptin and leptin-derived peptides as potential therapeutics for AD.

The Practice Patterns of American Association of Hip and Knee Surgeons for the Management of Chronic Periprosthetic Joint Infection After Total Knee Arthroplasty.

BACKGROUND: The management of periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) has considerable variation. In order to better capture current preferences for the management of PJI, this study sought to poll the current members of American Association of Hip and Knee Surgeons (AAHKS) first to characterize the distribution of practice patterns. METHODS: There were 32 questions in an online survey distributed to members of AAHKS. The questions were multiple choice regarding the management of PJI for TKA. There were 844 out of 2,752 members who completed the survey (response rate of 31%). RESULTS: Most of the members were in private practice (50%) compared to 28% being in an academic setting. On average, members were performing between 6 to 20 PJI cases per year. Two-stage exchange arthroplasty was performed in over 75% of the cases with either a cruciate retaining (CR) or posterior stabilized (PS) primary femoral component used in over 50% of the cases and 62% using an all-polyethylene tibial implant. Most of the members were using vancomycin and tobramycin. Typically, 2 to 3 grams of antibiotics were added per bag of cement regardless of the cement type. When indicated, amphotericin was the most often-used antifungal. Post-operative management had major variability with range of motion, brace use, and weight-bearing restrictions. CONCLUSION: There was variability in the responses from the members of AAHKS, but there was a preference toward performing a two-stage exchange arthroplasty with an articulating spacer using a metal femoral component and an all-polyethylene liner.

FGF2 mediates hepatic progenitor cell formation during human pluripotent stem cell differentiation by inducing the WNT antagonist NKD1.

Fibroblast growth factors (FGFs) are required to specify hepatic fate within the definitive endoderm through activation of the FGF receptors (FGFRs). While the signaling pathways involved in hepatic specification are well understood, the mechanisms through which FGFs induce hepatic character within the endoderm are ill defined. Here we report the identification of genes whose expression is directly regulated by FGFR activity during the transition from endoderm to hepatic progenitor cell. The FGFR immediate early genes that were identified include those encoding transcription factors, growth factors, and signaling molecules. One of these immediate early genes encodes naked cuticle homolog 1 (NKD1), which is a repressor of canonical WNT (wingless-type MMTV integration site) signaling. We show that loss of NKD1 suppresses the formation of hepatic progenitor cells from human induced pluripotent stem cells and that this phenotype can be rescued by using a pharmacological antagonist of canonical WNT signaling. We conclude that FGF specifies hepatic fate at least in large part by inducing expression of NKD1 to transiently suppress the canonical WNT pathway.

Lateral entorhinal cortex lesions impair odor-context associative memory in male rats.

Lateral entorhinal cortex (LEC) has been hypothesized to process nonspatial, item information that is combined with spatial information from medial entorhinal cortex to form episodic memories within the hippocampus. Recent studies, however, have demonstrated that LEC has a role in integrating features of episodic memory prior to the hippocampus. While the precise role of LEC is still unclear, anatomical studies show that LEC is ideally placed to be a hub integrating multisensory information. The current study tests whether the role of LEC in integrating information extends to long-term multimodal item-context associations. In Experiment 1, male rats were trained on a context-dependent odor discrimination task, where two different contexts served as the cue to the correct odor. Rats were pretrained on the task and then received either bilateral excitotoxic LEC or sham lesions. Following surgery, rats were tested on the previously learned odor-context associations. Control rats showed good memory for the previously learned association but rats with LEC lesions showed significantly impaired performance relative to both their own presurgery performance and to control rats. Experiment 2 went on to test whether impairments in Experiment 1 were the result of LEC lesions impairing either odor or context memory retention alone. Male rats were trained on simple odor and context discrimination tasks that did not require integration of features to solve. Following surgery, both LEC and control rats showed good memory for previously learned odors and contexts. These data show that LEC is critical for long-term odor-context associative memory.

Clinical Outcomes Following Distal Femur Replacement for Periprosthetic Distal Femur Fractures: A Systematic Review and Meta-Analysis.

BACKGROUND: Management of periprosthetic distal femur fractures (PDFFs) is often complicated by poor bone quality and limited bone stock making fixation attempts challenging and prone to failure. Distal femoral replacement (DFR) is being used to treat such injuries although outcome data are mostly from small case series. We sought to systematically review the literature on DFR for PDFF to summarize their outcomes. METHODS: PubMed, MEDLINE (EBSCO), and Cochrane Central Database were searched to identify reports of PDFFs treated with DFR. Articles reporting on 5 or more knees were systematically reviewed for clinical function, complications, and mortality. Random effects meta-analysis was used to create summary estimates and publication bias also assessed. RESULTS: Of 287 identified and screened articles, 15 were included, 14 retrospective, reporting on 352 knees. Following DFR, 87% (95% confidence interval [CI] 71-95) of patients were able to ambulate. The mean postoperative Knee Society Score was 80 (95% CI 77-84). The risk of periprosthetic joint infection was 4.3% (95% CI 2.2-8.2). One-year postoperative mortality rate was 10% (95% CI 6-18). There was some evidence of publication bias with a trend toward smaller studies reporting lower infection risk and mortality. CONCLUSION: DFR for PDFFs is associated with high functional outcomes and a relatively modest risk of infection. The periprosthetic joint infection and 1-year mortality rates reported here should be considered lower bounds estimates due to publication bias and loss to follow-up. Further investigation of long-term outcomes following DFR for PDFFs is warranted though short-term functional outcomes are promising.

Self-Reported Health of Severely Obese US Adults With Osteoarthritis.

BACKGROUND: Severe obesity is associated with complications following arthroplasty, leading surgeons to increasingly counsel patients regarding weight loss. For patients seeking arthroplasty, learning that severe obesity may be a relative contraindication to surgery can create a challenging clinical interaction. We sought to describe the self-reported health of United States (US) adults who had severe obesity and osteoarthritis (OA) to better understand patient perspectives. METHODS: The National Health and Nutrition Examination Survey, a nationally representative sample of the US population, was used to identify adult participants who had a body mass index (BMI) over 35 and an OA diagnosis. In total, 889 participants representing a US population of 9,604,722 were included. Self-reported health was dichotomized as poor to fair versus good to excellent. Analyses were weighted to produce national estimates. Associations between obesity severity and patient characteristics with self-reported health were assessed. RESULTS: Of US adults with a BMI over 35 and OA diagnosis, 64% rated their health as good or better. For adults who had a BMI over 45, 55% still reported their health as good or better. The strongest predictors of self-reported health were measures of physical functioning. Only 37% of participants who had much difficulty walking a quarter mile rated their health as good or better compared to 86% without difficulty (P < .001). CONCLUSION: Approximately two-thirds of patients who have severe obesity and OA do not perceive their health as compromised and consider decreased physical function as the primary driver of decreased health. This suggests that counseling about the association between obesity and overall health may improve shared decision making and that patient satisfaction metrics may be difficult to interpret in these clinical situations.

Object and object-memory representations across the proximodistal axis of CA1.

Episodic memory requires information about objects to be integrated into a spatial framework. Place cells in the hippocampus encode spatial representations of objects that could be generated through signaling from the entorhinal cortex. Projections from lateral (LEC) and medial entorhinal cortex (MEC) to the hippocampus terminate in distal and proximal CA1, respectively. We recorded place cells in distal and proximal CA1 as rats explored an environment that contained objects. Place cells in distal CA1 demonstrated higher measures of spatial tuning, stability, and closer proximity of place fields to objects. Furthermore, remapping to object displacement was modulated by place field proximity to objects in distal, but not proximal CA1. Finally, representations of previous object locations were closer to those locations in distal CA1 than proximal CA1. Our data suggest that in cue-rich environments, LEC inputs to the hippocampus support spatial representations with higher spatial tuning, closer proximity to objects, and greater stability than those receiving inputs from MEC. This is consistent with functional segregation in the entorhinal-hippocampal circuits underlying object-place memory.

Age at the Time of Surgery Is Not Predictive of Early Patient-Reported Outcomes After Periacetabular Osteotomy.

BACKGROUND: The clinical success of periacetabular osteotomy (PAO) for the treatment of symptomatic acetabular dysplasia is well-documented. Conflicting evidence exists regarding the correlation of age with clinical outcomes. Hip disability and Osteoarthritis Outcome Score - global (HOOSglobal) is a recently validated patient-reported outcome measure following PAO. The purpose of this study is to asses HOOSglobal and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at early follow-up based on age at the time of PAO. METHODS: A prospective multicenter cohort of 391 patients undergoing PAO with minimum 2-year follow-up (average 4.71 years) were identified. Patients were categorized into 4 age groups: <20 years (N = 131), 20-29 (N = 102), 30-39 (N = 65), and ≥40 (N = 34). A 4 × 2 repeated measures analysis of variance (Age Group × Time) was used to compare preoperative and postoperative HOOSglobal and WOMAC scores between age groups. A multiple linear regression was used to identify predictors of postoperative HOOSglobal scores. RESULTS: HOOSglobal and WOMAC scores increased across all age groups; however, a statistically greater increase in preoperative to postoperative HOOSglobal and WOMAC scores was found in those ≥40 years compared to those <20 (P< .002), 20-29 (P = .01), and 30-39 years (P = .02). Higher preoperative HOOSglobal scores were predictive of greater postoperative HOOSglobal scores (P < .001) but age (P = .65), gender (P = .80), body mass index (P = .50), and Tönnis Classification (P = .07) were not independent predictors of 1-year outcomes. CONCLUSION: The absence of differences in early postoperative patient-reported outcomes across multiple age ranges emphasizes that PAO in the setting of symptomatic acetabular dysplasia can be successful regardless of patient age alone. Therefore, age alone might not be an appropriate selection criterion when evaluating surgical candidates for PAO. LEVEL OF EVIDENCE: II.

A small-molecule screen reveals that HSP90ß promotes the conversion of induced pluripotent stem cell-derived endoderm to a hepatic fate and regulates HNF4A turnover.

We have previously shown that the transcription factor HNF4A is required for the formation of hepatic progenitor cells from endoderm that has been derived from human induced pluripotent stem cells (iPSCs). We reasoned that we could uncover regulatory pathways with new roles in hepatocyte differentiation by identifying cellular processes that regulate HNF4A. We therefore performed a screen of 1120 small molecules with well-characterized mechanisms of action to detect those that affect the abundance of HNF4A in iPSC-derived hepatic progenitor cells. This approach uncovered several small molecules that depleted HNF4A. Of those, we chose to focus on an inhibitor of heat shock protein 90 beta (HSP90ß). We show that mutation of the gene encoding HSP90ß represses hepatocyte differentiation during the formation of hepatocytes from iPSCs. We reveal that HSP90ß, although dispensable for expression of HNF4A mRNA, directly interacts with HNF4A protein to regulate its half-life. Our results demonstrate that HSP90ß has an unappreciated role in controlling hepatic progenitor cell formation and highlight the efficiency of using small-molecule screens during the differentiation of iPSCs to reveal new molecular mechanisms that control hepatocyte formation.

The Use of Human Pluripotent Stem Cells for Modeling Liver Development and Disease.

The use of pluripotent stem cells (PSCs) has transformed the investigation of liver development and disease. Clinical observations and animal models have provided the foundations of our understanding in these fields. While animal models remain essential research tools, long experimental lead times and low throughput limit the scope of investigations. The ability of PSCs to produce large numbers of human hepatocyte-like cells, with a given or modified genetic background, allows investigators to use previously incompatible experimental techniques, such as high-throughput screens, to enhance our understanding of liver development and disease. In this review, we explore how PSCs have expedited our understanding of developmental mechanisms and have been used to identify new therapeutic options for numerous hepatic diseases. We discuss the future directions of the field, including how to further unlock the potential of the PSC model to make it amenable for use with a broader range of assays and a greater repertoire of diseases. Furthermore, we evaluate the current weaknesses of the PSC model and the directions open to researchers to address these limitations. Conclusion: The use of PSCs to model human liver disease and development has and will continue to have substantial impact, which is likely to further expand as protocols used to generate hepatic cells are improved.

Depression and Anxiety Are Associated With Increased Health Care Costs and Opioid Use for Patients With Femoroacetabular Impingement Undergoing Hip Arthroscopy: Analysis of a Claims Database.

PURPOSE: To determine if opioid use and health care costs in the year before and following hip arthroscopy for femoroacetabular impingement (FAI) differ between those with or without depression or anxiety. METHODS: Using the Truven Health Marketscan database, FAI patients who underwent hip arthroscopy between October 2010 and December 2015 were identified (Current Procedural Terminology codes 29914 [femoroplasty], 29915 [acetabuloplasty], and/or 29916 [labral repair]). Patients were excluded if they had incomplete coverage for 1 year either before or following surgery. The number of patients with 1 or more claims related to depression or anxiety during the year before surgery was quantified (International Statistical Classification Diseases and Related Health-9 codes 296, 298, 300, 309, 311). Health care costs in the year before and following hip arthroscopy were compared between those with or without depression or anxiety. We also compared the number of patients in each group who filled a narcotic pain prescription within 180 days before surgery as well as >60 or >90 days after hip arthroscopy. RESULTS: Depression or anxiety claims were seen in 5,208/14,830 patients (35.1%) before surgery. A significantly greater proportion of those with preoperative depression or anxiety filled opioid-related prescriptions in the 6 months before surgery (36.2% vs 25.6%, P < .0001) and both >60 days (31.3% vs 24.7%, P < .0001) and >90 days after surgery (29.5% vs 23.4%, P < .0001). The group with preoperative depression or anxiety had significantly greater health care costs both before ($8,775 vs $5,674, P < .0001) and following surgery ($5,287 vs $3,908, P < .0001). CONCLUSIONS: Both before and following hip arthroscopy, opioid use and health care costs were significantly greater for FAI patients with comorbid depression or anxiety. LEVEL OF EVIDENCE: Level III, retrospective comparative therapeutic study.

Step descent strategy is altered bilaterally despite unilateral muscle strength impairment after total knee arthroplasty.

PURPOSE: Muscle weakness and difficulty descending stairs are common after unilateral total knee arthroplasty (TKA), but the relationship between each is unclear. The purpose of this study was to compare lower extremity muscle strength, lower extremity support moments during step descent, and assess relationships between each. METHODS: The study included 40 subjects (20 post-TKA, 20 control). Knee extensor, hip abductor, and hip external rotator strength were measured and biomechanical analyses of step descent performed. Patients with TKA were assessed 3 and 6 months post-surgery. RESULTS: At 3 and 6 months post-TKA, operated limb hip external rotator and knee extensor strength were impaired compared to the non-operated limb (p < 0.01); however, no between-limb differences were observed during step descent. Compared to the control group, hip external rotator and knee extensor strength, total lower extremity support moment, and knee support moment during step descent were impaired post-TKA (p < 0.05). At 6 months post-TKA, knee extensor and hip external rotator strength correlated with total support moment during step descent (rs = 0.40, 0.41, p < 0.02). Hip abductor and external rotator strength negatively correlated with knee support moment during step descent (rs = - 0.35, - 0.39, p < 0.03). CONCLUSIONS: Persistent operative limb knee extensor and hip external rotator muscle weakness are noted following unilateral TKA. Despite unilateral weakness, bilateral alterations in step descent strategy occur following TKA. Patients with TKA utilize hip musculature to reduce knee muscle demand during step descent, possibly contributing to limitations in long-term step descent performance.

How Has COVID-19 Affected Our Orthopedic Implant Industry Partners? Implications for the Surgeon-Industry Relationship in 2020 and Beyond.

BACKGROUND: The COVID-19 pandemic has had far-reaching societal and financial consequences. The purpose of this study was to evaluate how COVID-19 has affected AAHKS industry partners and the surgeon-industry relationship, emphasizing education, resource allocation, and strategic direction for the second half of 2020. METHODS: AAHKS industry partners were contacted to participate in a blinded survey and optional interview with the AAHKS Industry Relations Committee. Based on the results, a group of AAHKS member surgeons with disparate practice types were asked to postulate on how the COVID-19 pandemic has and will affect their practice and relationship with Industry. RESULTS: AAHKS industry partner responses indicated decreased resource allocation for regional, "other national," and AAHKS annual meetings (67%, 55%, and 30%, respectively). Web-based educational content was expected to increase in 2020 and will likely remain a point of emphasis in 2021 (100% and 70% of responders). For Q3/Q4 2020, a significant emphasis was placed on site of service/outpatient TJA and COVID-19-related safety measures (70% and 90% of responders), as well as increased availability of instrumentation and implants (40% and 60%, respectively). CONCLUSION: The COVID-19 pandemic has altered the orthopedic landscape for the foreseeable future. Survey responses by AAHKS industry partners demonstrate a continued commitment to surgeon education with an increasing shift to a web-based platform. Increased resource allocation for outpatient TJA and COVID-19-related safety measures were significant. Articulating optimal mechanisms to aid industry in supporting surgeons with different practice models to meet demand during the second half of fiscal year 2020 will be critical.

Intraoperative Practice Variability in Total Knee Arthroplasty.

BACKGROUND: Considerable practice variability exists among orthopedic surgeons performing total knee arthroplasty (TKA). The purpose of this study is to understand what TKA surgical and perioperative techniques are standard among high-volume academic knee arthroplasty surgeons. METHODS: A written survey with 59 questions regarding management preferences in TKA was distributed by the 2018 John N. Insall Traveling Fellows to all arthroplasty-trained attending physicians at 13 medical centers, with 45 responses recorded. RESULTS: Surveyed surgeons performed unicompartmental knee arthroplasty (88%) and bilateral TKA (87%). Most surveyed surgeons rarely or never performed outpatient primary TKA (71%). Conventional alignment guides and cemented implants were used by 80% of respondents. Most surgeons used posterior-stabilized implants (67%), followed by cruciate-retaining (20%), ultracongruent (20%), and medial congruent or medial pivot designs (17.8%). Surveyed surgeons frequently or always resurfaced the patella (73%), used a tourniquet for the entire case (73%), and used tranexamic acid for all TKAs (91%). The most common locations for intra-articular anesthetic injection were the arthrotomy (91%), the periosteum (84%), and the medial posterior capsule (82%). Saline (62%) and dilute iodine (47%) were the most common irrigation fluids. The arthrotomy was most commonly closed with running barbed suture (60%) followed by interrupted vicryl (40%). Skin closure was predominantly with running monocryl (60%) followed by staples (29%). Anticoagulation for TKA was primarily aspirin 81 mg BID (60%). CONCLUSION: There was considerable variability among surgeons polled although a strong preference for more conventional and less developmental techniques prevailed.

Low Self-Efficacy and High Kinesiophobia Are Associated With Worse Function in Patients With Femoroacetabular Impingement Syndrome.

CONTEXT: Femoroacetabular impingement syndrome (FAIS) is a painfully debilitating hip condition disproportionately affecting active individuals. Mental health disorders are an important determinant of treatment outcomes for individuals with FAIS. Self-efficacy, kinesiophobia, and pain catastrophizing are psychosocial factors that have been linked to inferior outcomes for a variety of orthopedic conditions. However, these psychosocial factors and their relationships with mental health disorders, pain, and function have not been examined in individuals with FAIS. OBJECTIVE: (1) To examine relationships between self-efficacy, kinesiophobia, pain catastrophizing, pain, and function in patients with FAIS and (2) to determine if these variables differ between patients with and without a self-reported depression and/or anxiety. DESIGN: Cross-sectional. SETTING: University health center. PARTICIPANTS: Fifty-one individuals with FAIS (42 females/9 males; age 35.7 [11.6] y; body mass index 27.1 [4.9] kg/m2). MAIN OUTCOME MEASURES: Participants completed the Pain Self-Efficacy Questionnaire, Tampa Scale for Kinesiophobia, Pain Catastrophizing Scale, visual analog scale for hip pain at rest and during activity, and the 12-item International Hip Outcome Tool. Self-reported depression and/or anxiety were recorded. The relationships between psychosocial factors, pain, and function were examined using Spearman rank-order correlations. Independent t tests and Mann-Whitney U tests were used to evaluate the effect of self-reported depression and/or anxiety on psychosocial factors, pain and function. RESULTS: The 12-item International Hip Outcome Tool was correlated with pain during activity (ρ = -.57, P ≤ .001), Tampa Scale for Kinesiophobia (ρ = -.52, P ≤ .001), and Pain Self-Efficacy Questionnaire (ρ = .71, P ≤ .001). The Pain Self-Efficacy Questionnaire was also correlated with pain at rest (ρ = -.43, P = .002) and pain during activity (ρ = -.46, P = .001). Individuals with self-reported depression and/or anxiety (18/51; 35.3%) had worse self-efficacy and pain catastrophizing (P ≤ .01). CONCLUSION: Self-reported depression and/or anxiety, low self-efficacy, and high kinesiophobia were associated with more hip pain and worse function for patients with FAIS. These findings warrant further examination including psychosocial treatment strategies to improve the likelihood of a successful clinical outcome for this at-risk population.

Greater Rates of Acute Kidney Injury in African American Total Knee Arthroplasty Patients.

BACKGROUND: This retrospective study compared the change in serum creatinine between African American and Caucasian total knee arthroplasty (TKA) patients. The authors hypothesized that African Americans would demonstrate significantly greater change, and that a significantly greater proportion would demonstrate creatinine changes consistent with acute kidney injury (AKI). METHODS: Primary TKAs performed at a single institution between July 2011 and June 2016 were identified: 1035 primary TKAs met inclusion and exclusion criteria (110 African American, 925 Caucasian, excluding Hispanic and Asian patients). None were excluded based on gender, age, body mass index, preoperative diagnosis, or comorbidities. All patients had preoperative and postoperative creatinine levels available in the electronic medical records. Each patient received the same preop and postop protocol for nonsteroidal anti-inflammatory drug use along with other drugs administered including anesthesia. All patients received 1 g of intravenous vancomycin with some patients additionally receiving 1 g of vancomycin powder administered locally at the end of surgery. All patients were controlled for fluid intake and blood loss, along with no patient receiving a transfusion or intravenous contrast. Patient demographics and preoperative/postoperative serum creatinine were recorded and then analyzed for presence of AKI (≥0.3 mg/dL). Preoperative/postoperative serum creatinine concentrations were compared between African American and Caucasian patients using 2 × 2 repeated measures analysis of variance. Prevalence of patients in each group demonstrating AKI was calculated using Fisher's exact test. RESULTS: African American patients had significantly greater serum creatinine preoperatively (1.00 ± 0.26 vs 0.90 ± 0.22, P < .001) and a significantly greater increase postoperatively (0.10 vs 0.03, P < .001). A significantly greater number of African American patients demonstrated AKI (10.9% vs 5.1%, P = .03). Furthermore, a significantly greater number of African American patients stayed in the hospital an additional 2 or more days for renal issues (2.7% vs 0.4%, P = .03). CONCLUSION: Altered renal function was significantly more common in African American TKA patients. Future studies are necessary to determine if tailoring anti-inflammatories, perioperative medications, and preoperative comorbidities reduce the risk of renal injury and/or a longer hospital stay for this subset of patients.