Comparison of Outcomes in High Versus Low Activity Level Patients After Total Joint Arthroplasty.

BACKGROUND: Activity level (AL) recommendations following total joint arthroplasty (TJA) remain controversial. Our purpose was to compare implant survivorship of high activity (HA) and low activity (LA) patients after primary TJA. We hypothesized that there would be no difference in implant survivorship based on AL. METHODS: This was a retrospective 1:1 matched cohort study after primary TJA with minimum 5-year follow-up. High activity patients were designated by the University of California and Los Angeles activity-level rating scale score ≥8 and matched to LA patients based on age (±5), sex, and body mass index (±5). There were 396 HA patients (149 knees and 48 hips) who met inclusion criteria. We analyzed revision rates, adverse events, and radiographic lucencies. RESULTS: Crepitus was the most common adverse events in both HA and LA total knee arthroplasties (TKAs). Adverse events were rare in total hip arthroplasty (THA) cohorts. For both THA and TKA patients, the HA cohort did not have increased reoperations or revisions when compared to the LA cohort. No differences were noted in overall radiographic analysis between HA (16.1%) and LA (12.1%) TKA patients (P = .318), and in THA patients, more radiographic problems were noted in LA (P = .004). CONCLUSION: We found no difference in minimum 5-year postoperative implant survivorship based on AL. This may change AL recommendations after TKA and THA.

Salicylates enhance CRM1 inhibitor antitumor activity by induction of S-phase arrest and impairment of DNA-damage repair.

Chromosome region maintenance protein 1 (CRM1) mediates protein export from the nucleus and is a new target for anticancer therapeutics. Broader application of KPT-330 (selinexor), a first-in-class CRM1 inhibitor recently approved for relapsed multiple myeloma and diffuse large B-cell lymphoma, have been limited by substantial toxicity. We discovered that salicylates markedly enhance the antitumor activity of CRM1 inhibitors by extending the mechanisms of action beyond CRM1 inhibition. Using salicylates in combination enables targeting of a range of blood cancers with a much lower dose of selinexor, thereby potentially mitigating prohibitive clinical adverse effects. Choline salicylate (CS) with low-dose KPT-330 (K+CS) had potent, broad activity across high-risk hematological malignancies and solid-organ cancers ex vivo and in vivo. The K+CS combination was not toxic to nonmalignant cells as compared with malignant cells and was safe without inducing toxicity to normal organs in mice. Mechanistically, compared with KPT-330 alone, K+CS suppresses the expression of CRM1, Rad51, and thymidylate synthase proteins, leading to more efficient inhibition of CRM1-mediated nuclear export, impairment of DNA-damage repair, reduced pyrimidine synthesis, cell-cycle arrest in S-phase, and cell apoptosis. Moreover, the addition of poly (ADP-ribose) polymerase inhibitors further potentiates the K+CS antitumor effect. K+CS represents a new class of therapy for multiple types of blood cancers and will stimulate future investigations to exploit DNA-damage repair and nucleocytoplasmic transport for cancer therapy in general.

Does Individualization of Cup Position Affect Prosthetic or Bone Impingement Following Total Hip Arthroplasty?

BACKGROUND: Spinopelvic (SP) mobility patterns during postural changes affect three-dimensional acetabular component position, the incidence of prosthetic impingement, and total hip arthroplasty (THA) instability. Surgeons have commonly placed the acetabular component in a similar "safe zone" for most patients. Our purpose was to determine the incidence of bone and prosthetic impingement with various cup orientations and determine if a preoperative SP analysis with individualized cup orientation lessens impingement. METHODS: A preoperative SP evaluation of 78 THA subjects was performed. Data were analyzed using a software program to determine the prevalence of prosthetic and bone impingement with a patient individualized cup orientation versus 6 commonly selected cup orientations. Impingement was correlated with known SP risk factors for dislocation. RESULTS: Prosthetic impingement was least with the individualized choice of cup position (9%) versus preselected cup positions (18%-61%). The presence of bone impingement (33%) was similar in all groups and not affected by cup position. Factors associated with impingement in flexion were age, lumbar flexion, pelvic tilt (stand to flexed seated), and functional femoral stem anteversion. Risk factors in extension included standing pelvic tilt, standing SP tilt, lumbar flexion, pelvic rotation (supine to stand and stand to flexed seated), and functional femoral stem anteversion. CONCLUSION: Prosthetic impingement is reduced with individualized cup positioning based on SP mobility patterns. Bone impingement occurred in one-third of patients and is a noteworthy consideration in preoperative THA planning. Known SP risk factors for THA instability correlated with the presence of prosthetic impingement in both flexion and extension.

Loss of the aryl hydrocarbon receptor increases tumorigenesis in p53-deficient mice.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates cell fate via activation of a diverse set of genes. There are conflicting reports describing the role of AhR in cancer. AhR-knockout mice do not develop tumors spontaneously, yet the AhR can act as a tumor suppressor in certain contexts. Loss of tumor suppression by p53 is common in human cancer. To investigate AhR function in the absence of p53, we generated mice lacking both AhR and p53. Mice deficient for AhR and p53 had shortened lifespan, increased tumorigenesis, and an altered tumor spectrum relative to control mice lacking only p53. In addition, knockout of both AhR and p53 resulted in reduced embryonic survival and neonatal fitness. We also examined the consequences of loss of AhR in p53-heterozygous mice and observed a significantly reduced lifespan and enhanced tumor burden. These findings reveal an important role for the AhR as a tumor suppressor in the absence of p53 signaling and support the development of anti-cancer therapeutics that would promote the tumor suppressive actions of the AhR.

Routine Laboratory Tests are not Necessary After Primary Total Joint Arthroplasty: A Prospective Study Utilizing a Selective Algorithmic Approach.

BACKGROUND: Laboratory tests are obtained following total joint arthroplasty (TJA) despite a lack of supporting evidence. No prior study has prospectively analyzed the effect of discontinuing routine laboratory tests. This study aimed to determine whether discontinuing routine laboratory tests in TJA patients resulted in a difference in 90-day complications. METHODS: This was a prospective protocol change study at a high-volume center. Prior to protocol change, patients underwent routine laboratory tests following primary unilateral TJA (control group). After the change, an algorithmic approach was used to selectively order laboratory tests (protocol group). Patients with bleeding disorders, chronic obstructive pulmonary disease, arrhythmia, coronary artery disease, congestive heart failure, chronic renal failure, dementia, abnormal preoperative sodium, potassium, or hemoglobin <10 g/dL were excluded. In-hospital and 90-day data were collected. Student's t-test was used to analyze continuous variables and chi-squared test was used for categorical variables. A pre-hoc analysis examining the primary outcome required 607 patients per group to achieve 80% power. RESULTS: The protocol group included 937 patients, whereas the control group included 891 patients. The protocol group had fewer females and total hip arthroplasties. There were no differences in age, body mass index, American Society of Anesthesiologists classification, tranexamic acid administration, or estimated blood loss between the protocol and control groups. There were also no differences in transfusions, electrolyte corrections, unplanned consults, length of stay, or transfers. The protocol cohort had more fluid boluses and home discharges. There was no difference in 90-day complications between the 2 groups. CONCLUSIONS: This study utilizing an algorithmic approach to laboratory collection demonstrates that discontinuing routine laboratory tests following TJA is safe and effective. We believe this protocol can be implemented for most patients undergoing primary unilateral TJA.

Introduction of diabetic retinopathy screening into an antenatal clinic: Impact on maternal screening and diagnosis rates.

Pregnancy is a risk factor for the development and progression of diabetic retinopathy (DR) in women with pre-gestational diabetes. However, a minority of pregnant women with diabetes adhere to retinal screening recommendations. The introduction of an onsite retinal camera at our tertiary maternity hospital significantly increased the proportion of women who received at least one retinal screen during pregnancy (93.0% vs 54.3%, P < 0.001) and the identification of both DR and DR progression. We conclude that the use of a retinal camera in similar clinics is a feasible option to improve DR screening and diagnosis rates in pregnancy.

Patient-Reported Barriers Are Associated With Receipt of Hepatocellular Carcinoma Surveillance in a Multicenter Cohort of Patients With Cirrhosis.

BACKGROUND: More than 20% of patients with cirrhosis do not receive semi-annual hepatocellular carcinoma (HCC) surveillance as recommended. Few studies have evaluated the effects of patient-level factors on surveillance receipt. METHODS: We administered a telephone survey to a large cohort of patients with cirrhosis from 3 health systems (a tertiary care referral center, a safety-net health system, and Veterans Affairs) to characterize patient knowledge, attitudes, and perceived barriers of HCC surveillance. Multinomial logistic regression was performed to identify factors associated with HCC surveillance receipt (semi-annual and annual vs none) during the 12-month period preceding survey administration. RESULTS: Of 2871 patients approached, 1020 (35.5%) completed the survey. Patients had high levels of concern about developing HCC and high levels of knowledge about HCC. However, patients had knowledge deficits, including believing surveillance was unnecessary when physical examination and laboratory results were normal. Nearly half of patients reported barriers to surveillance, including costs (28.9%), difficulty scheduling (24.1%), and transportation (17.8%). In the year before the survey, 745 patients (73.1%) received 1 or more surveillance examination; 281 received on-schedule, semi-annual surveillance and 464 received annual surveillance. Semi-annual HCC surveillance (vs none) was significantly associated with receipt of hepatology subspecialty care (odds ratio, 30.1; 95% CI, 17.5-51.8) and inversely associated with patient-reported barriers (odds ratio, 0.62; 95% CI, 0.41-0.94). Patterns of associations comparing annual vs no surveillance were similar although the magnitude of effects were reduced. CONCLUSIONS: Patient-reported barriers such as knowledge deficits, costs, difficulty scheduling, and transportation are significantly associated with less frequent receipt of HCC surveillance, indicating a need for patient-centered interventions, such as patient navigation.

Molecular profiling reveals a hypoxia signature in breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently characterized T-cell malignancy that has raised significant patient safety concerns and led to worldwide impact on the implants used and clinical management of patients undergoing reconstructive or cosmetic breast surgery. Molecular signatures distinguishing BIA-ALCL from other ALCLs have not been fully elucidated and classification of BIA-ALCL as a WHO entity remains provisional. We performed RNA sequencing and gene set enrichment analysis comparing BIA-ALCLs to non-BIA-ALCLs and identified dramatic upregulation of hypoxia signaling genes including the hypoxia-associated biomarker CA9 (carbonic anyhydrase-9). Immunohistochemistry validated CA9 expression in all BIA-ALCLs, with only minimal expression in non-BIA-ALCLs. Growth induction in BIA-ALCL-derived cell lines cultured under hypoxic conditions was proportional to up-regulation of CA9 expression, and RNA sequencing demonstrated induction of the same gene signature observed in BIA-ALCL tissue samples compared to non-BIA-ALCLs. CA9 silencing blocked hypoxia-induced BIA-ALCL cell growth and cell cycle-associated gene expression, whereas CA9 overexpression in BIA-ALCL cells promoted growth in a xenograft mouse model. Furthermore, CA9 was secreted into BIA-ALCL cell line supernatants and was markedly elevated in human BIA-ALCL seroma samples. Finally, serum CA9 concentrations in mice bearing BIA-ALCL xenografts were significantly elevated compared to control serum. Together, these findings characterize BIA-ALCL as a hypoxia-associated neoplasm, likely attributable to the unique microenvironment in which it arises. These data support classification of BIA-ALCL as a distinct entity and uncover opportunities for investigating hypoxia-related proteins such as CA9 as novel biomarkers and therapeutic targets in this disease.

Epigenetic regulation of the ITGB4 gene in prostate cancer.

BACKGROUND: Examination of epigenetic changes at the ITGB4 gene promoter reveals altered methylation at different stages of prostate tumour progression and these changes may, in part, explain the complex patterns of gene expression of this integrin observed. Transcriptional re-programming perturbs expression of cell adhesion molecules and underpins metastatic tumour cell behaviour. Decreasing expression of the cell adhesion molecule ITGB4, which encodes the beta subunit of the integrin, alpha6 beta4 (α6ß4), has been correlated with increased tumour aggressiveness and metastasis in multiple tumour types including prostate cancer. Paradoxically, in vitro studies in tumour cell models demonstrate that ITGB4 mediates cell mobility and invasion. Herein we examined whether transcriptional re-programming by methylation influenced ITGB4 gene expression at different stages of prostate cancer progression. Bisulphite sequencing of a large CpG island in the ITGB4 gene promoter identified differentially methylated regions in prostate cancer cell lines representing a localised tumour (22Rv1), lymph node metastasis (LNCaP), and a bone metastasis (PC-3). The highest levels of methylation were observed in the CpG island surrounding the ITGB4 transcription start site in PC-3 cells, and this observation also correlated with higher gene expression of ITGB4 in these cells. Furthermore, PC-3 cells expressed two distinct transcripts, using an alternate transcription start site, which was not detected in other cell lines. In prostate tumour biopsy samples, patterns of methylation across the ITGB4 promoter were similar overall in matched primary and metastatic samples (n = 4 pairs), with a trend toward loss of methylation at specific sites in metastatic lesions.

Evaluation of the PROMIS Upper Extremity Computer Adaptive Test Against Validated Patient-Reported Outcomes in Patients With Basilar Thumb Arthritis.

PURPOSE: The Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity (UE) computer adaptive test was developed to reduce test burden and improve precision. We hypothesized that, in patients with thumb basilar joint arthritis (BJA), (1) PROMIS UE would correlate with established patient-outcomes (PROs), (2) PROMIS UE would require less time and fewer questions than current metrics, (3) there would be no floor or ceiling effects, and (4) PROMIS UE would not correlate with radiographic disease severity. METHODS: Patients presenting with a primary diagnosis of thumb BJA completed the Quick Disabilities of the Arm Shoulder and Hand (QuickDASH), Thumb Disability Examination (TDX), Patient-Rated Wrist Hand Evaluation (PRWHE), and PROMIS UE. Radiographic disease severity as described by the Eaton scoring system was recorded. The relationships among PROs were described with Spearman correlation coefficients. The presence of a floor or ceiling effect was confirmed if greater than 15% of patients achieved the lowest or the highest possible score, respectively. RESULTS: One hundred patients with thumb BJA formed the sample for this study. A good to excellent correlation was identified between PROMIS UE and QuickDASH. There were good correlations between PROMIS UE and TDX as well as PRWHE. The PROMIS UE was significantly less time consuming (average: 58.5 seconds vs QuickDASH, 92.2; TDX, 62.6; and PRWHE, 144.7), and required fewer questions than current metrics (average: 4.9 questions vs QuickDASH, 11; TDX, 20; and, 15). In addition, there were no appreciable floor or ceiling effects. Radiographic disease severity did not correlate with PROMIS UE. CONCLUSIONS: The PROMIS UE has a good to excellent correlation with QuickDASH and good correlations with PRWHE and TDX. In addition, PROMIS UE required less time and fewer questions than established PROs. There were no floor or ceiling effects. Used as a single PRO, PROMIS UE may be a practical alternative to legacy scales in patients with thumb BJA. CLINICAL RELEVANCE: The PROMIS UE PRO instrument may be a valuable addition in the assessment of patients with basilar thumb arthritis.

Bundled Payments Are Effective in Reducing Costs Following Bilateral Total Joint Arthroplasty.

BACKGROUND: Alternative payment models such the Centers for Medicare and Medicaid Services Bundled Payments for Care Improvement (BPCI) initiative have been effective in reducing costs following unilateral total hip (THA) and knee arthroplasty (TKA), but few studies exist on bilateral arthroplasty. This study aimed to determine whether the BPCI program for bilateral THA and TKA reduced episode-of-care costs. METHODS: We retrospectively reviewed a consecutive series of patients who underwent simultaneous bilateral primary THA and TKA between 2015 and 2016. We recorded demographic variables, comorbidities, readmissions, and calculated 90-day episode-of-care costs based on Centers for Medicare and Medicaid Services claims data. We compared data from patients before and after the start of our BPCI program, and performed a multivariate analysis to identify independent risk factors for increased costs. RESULTS: Of 319 patients, 38 underwent bilateral THA (12%) while 287 underwent bilateral TKA (88%). There were 239 patients (74%) in the bundled payment group. Although there was no change in readmission rate (9% vs 8%), the post-BPCI group demonstrated reduced hospital costs ($21,251 vs $18,783), post-acute care costs ($15,488 vs $12,439), and overall 90-day episode-of-care costs ($39,733 vs $34,305). When controlling for demographics, procedure, and comorbidities, our BPCI model demonstrated a per-patient reduction of $5811 in overall claims costs. Additional risk factors for increased episode-of-care costs included age ($516/y increase) and cardiac disease ($5916). CONCLUSION: Our bundled payment program for bilateral THA and TKA was successful with reduction in 90-day episode-of-care costs without placing the patient at higher risk of readmission. Older Medicare beneficiaries and those with cardiac disease should likely not undergo a simultaneous bilateral procedure due to concerns about increased costs.

How Much Does a Readmission Cost the Bundle Following Primary Hip and Knee Arthroplasty?

BACKGROUND: As alternative payment models increase in popularity for total joint arthroplasty (TJA), providers and hospitals now share the financial risk associated with unexpected readmissions. While studies have identified postacute care as a driver for costs in a bundle, the fiscal burden associated with specific causes of readmission is unclear. The purpose of this study is to quantify the additional costs associated with each of the causes of readmission following primary TJA. METHODS: We reviewed a consecutive series of primary TJA patients at our institution from 2015 to 2016 using claims data from the Centers for Medicare and Medicaid Services and Medicare Advantage patients from a single private insurer. We collected demographic data, medical comorbidities, 90-day episode-of-care costs, and readmissions for all patients. Medical records for each readmission were reviewed and classified into 1 of 11 categories. We then compared the mean facility readmission costs, postacute care costs, and overall 90-day episode-of-care costs between the reasons for readmission. RESULTS: Of the 4704 patients, there were 325 readmissions in 286 patients (6.1%), with 50% being readmitted to a different facility than their index surgery hospital. The mean additional cost was $8588 per readmission. Medical reasons accounted for the majority of readmissions (n = 257, 79.1%). However, patients readmitted for revision surgery (n = 68, 20.9%) had the highest mean readmission cost ($15,356, P < .001). Furthermore, readmissions for revision surgery had the highest mean postacute care ($37,207, P = .002) and overall episode-of-care costs ($52,162, P = .003). Risk factors for readmission included age >75 years (odds ratio [OR], 1.85; P < .001), body mass index >35 kg/m2 (OR, 1.63; P = .004), history of congestive heart failure (OR, 2.47; P = .002), diabetes mellitus (OR, 2.0; P < .001), and renal disease (OR, 2.28; P = .005). CONCLUSION: Providers participating in alternative payment models should be cognizant of the increased bundle costs attributed to readmissions, especially due to revision surgery. Improved communication with patients and close postoperative monitoring may help minimize the large percentage of readmissions at different facilities.

A Nurse Navigator Program Is Effective in Reducing Episode-of-Care Costs Following Primary Hip and Knee Arthroplasty.

BACKGROUND: Alternative payment models for total hip arthroplasty (THA) and total knee arthroplasty (TKA) have incentivized providers to deliver higher quality care at a lower cost, prompting some institutions to develop formal nurse navigation programs (NNPs). The purpose of this study was to determine whether a NNP for primary THA and TKA resulted in decreased episode-of-care (EOC) costs. METHODS: We reviewed a consecutive series of primary THA and TKA patients from 2015-2016 using claims data from the Centers for Medicare and Medicaid Services and Medicare Advantage patients from a private insurer. Three nurse navigators were hired to guide discharge disposition and home needs. Ninety-day EOC costs were collected before and after implementation of the NNP. To control for confounding variables, we performed a multivariate regression analysis to determine the independent effect of the NNP on EOC costs. RESULTS: During the study period, 5275 patients underwent primary TKA or THA. When compared with patients in the prenavigator group, the NNP group had reduced 90-day EOC costs ($19,116 vs $20,418 for Medicare and $35,378 vs $36,961 for private payer, P < .001 and P < .012, respectively). Controlling for confounding variables in the multivariate analysis, the NNP resulted in a $1575 per Medicare patient (P < .001) and a $1819 per private payer patient cost reduction (P = .005). This translates to a cost savings of at least $5,556,600 per year. CONCLUSION: The implementation of a NNP resulted in a marked reduction in EOC costs following primary THA and TKA. The cost savings significantly outweighs the added expense of the program. Providers participating in alternative payment models should consider using a NNP to provide quality arthroplasty care at a reduced cost.

Ischemia/Reperfusion Induces Interferon-Stimulated Gene Expression in Microglia.

Innate immune signaling is important in the pathophysiology of ischemia/reperfusion (stroke)-induced injury and recovery. Several lines of evidence support a central role for microglia in these processes. Recent work has identified Toll-like receptors (TLRs) and type I interferon (IFN) signaling in both ischemia/reperfusion-induced brain injury and ischemic preconditioning-mediated neuroprotection. To determine the effects of "ischemia/reperfusion-like" conditions on microglia, we performed genomic analyses on wild-type (WT) and TLR4-/- cultured microglia after sequential exposure to hypoxia/hypoglycemia and normoxia/normoglycemia (H/H-N/N). We observed increased expression of type 1 IFN-stimulated genes (ISGs) as the predominant transcriptomal feature of H/H-N/N-exposed WT, but not TLR4-/-, microglia. Microarray analysis on ex vivo sorted microglia from ipsilateral male mouse cortex after a transient in vivo ischemic pulse also demonstrated robust expression of ISGs. Type 1 IFNs, including the IFN-αs and IFN-ß, activate the interferon-α/ß receptor (IFNAR) complex. We confirmed both in vitro H/H-N/N- and in vivo ischemia/reperfusion-induced microglial ISG responses by quantitative real-time PCR and demonstrated that both were dependent on IFNAR1. We characterized the effects of hypoxia/hypoglycemia on phosphorylation of signal transducer and activator of transcription 1 (STAT1), release of type 1 IFNs, and surface expression of IFNAR1 in microglia. We demonstrated that IFN-ß induces dose-dependent secretion of ISG chemokines in cultured microglia and robust ISG expression in microglia both in vitro and in vivo Finally, we demonstrated that the microglial ISG chemokine responses to TLR4 agonists were dependent on TLR4 and IFNAR1. Together, these data suggest novel ischemia/reperfusion-induced pathways for both TLR4-dependent and -independent, IFNAR1-dependent, type 1 IFN signaling in microglia.SIGNIFICANCE STATEMENT Stroke is the fifth leading cause of death in the United States and is a leading cause of serious long-term disability worldwide. Innate immune responses are critical in stroke pathophysiology, and microglia are key cellular effectors in the CNS response to ischemia/reperfusion. Using a transcriptional analysis approach, we identified a robust interferon (IFN)-stimulated gene response within microglia exposed to ischemia/reperfusion in both in vitro and in vivo experimental paradigms. Using a number of complementary techniques, we have demonstrated that these responses are dependent on innate immune signaling components including Toll-like receptor-4 and type I IFNs. We have also elucidated several novel ischemia/reperfusion-induced microglial signaling mechanisms.

Distinct mechanisms of regulation of the ITGA6 and ITGB4 genes by RUNX1 in myeloid cells.

Integrins are transmembrane adhesion receptors that play an important role in hematopoiesis by facilitating interactions between hematopoietic cells and extracellular matrix components of the bone marrow and hematopoietic tissues. These interactions are important in regulating the function, proliferation, and differentiation of hematopoietic cells, as well as their homing and mobilization in the bone marrow. Not surprisingly altered expression and function of integrins plays a key role in the development and progression of cancer including leukemias. However, the regulation of integrin gene expression is not well characterized and the mechanisms by which integrin genes are disrupted in cancer remain unclear. Here we demonstrate for the first time that a key regulator of hematopoiesis, RUNX1, binds to and regulates the promoters of both the ITGA6 and ITGB4 genes in myeloid cells. The ITGA6 and ITGB4 integrin genes form the α6ß4 integrin receptor. However, our data indicate that RUNX1 functions differently at these two promoters. RUNX1 regulates ITGA6 through a consensus RUNX1 binding motif in its promoter. In contrast, although the ITGB4 promoter is also activated by RUNX1, it does so in the absence of a recognized consensus RUNX1 binding motif. Furthermore, our data suggest that regulation of ITGB4 may involve interactions between the promoter and upstream regulatory elements.

No Difference in Total Episode-of-Care Cost Between Staged and Simultaneous Bilateral Total Joint Arthroplasty.

BACKGROUND: Due to concerns about higher complication rates, surgeons debate whether to perform simultaneous bilateral total joint arthroplasty (BTJA), particularly in the higher-risk Medicare population. Advances in pain management and rehabilitation protocols have called into question older studies that found an overall cost benefit for simultaneous procedures. The purpose of this study was to compare 90-day episode-of-care costs between staged and simultaneous BTJA among Medicare beneficiaries. METHODS: We retrospectively reviewed a consecutive series of 319 simultaneous primary TJAs and 168 staged TJAs (336 procedures) at our institution between 2015 and 2016. We recorded demographics, comorbidities, readmission rates, and 90-day episode-of-care costs based upon Centers for Medicare and Medicaid Services claims data. To control for confounding variables, we performed a multivariate regression analysis to identify independent risk factors for increased costs. RESULTS: Simultaneous patients had decreased inpatient facility costs ($19,402 vs $23,025, P < .001), increased post-acute care costs ($13,203 vs $10,115, P < .001), and no difference in total episode-of-care costs ($35,666 vs $37,238, P = .541). Although there was no difference in readmissions (8% vs 9%, P = .961), simultaneous bilateral patients were more likely to experience a thromboembolic event (2% vs 0%, P = .003). When controlling for demographics, procedure, and comorbidities, a simultaneous surgery was not associated with an increase in episode-of-care costs (P = .544). Independent risk factors for increased episode-of-care costs following BTJA included age ($394 per year increase, P < .001), cardiac disease ($4877, P = .025), history of stroke ($14,295, P = .010), and liver disease ($12,515, P = .016). CONCLUSION: In the Medicare population, there is no difference in 90-day episode-of-care costs between simultaneous and staged BTJA. Surgeons should use caution in performing a simultaneous procedure on older patients or those with a history of stroke, cardiac, or liver disease.

Survivorship and Outcomes in Patients With Multiple Sclerosis Undergoing Total Joint Arthroplasty.

BACKGROUND: Patients with multiple sclerosis (MS) frequently require total joint arthroplasty (TJA). The outcomes of TJA in patients with MS, who are frequently on immunomodulatory medications and physically deconditioned, remain largely unknown. The aim of this study is to elucidate the survivorship and reasons for failure in this patient population. METHODS: A single-institution retrospective review of 108 TJAs (46 knees and 62 hips) was performed from 2000 to 2016. An electronic chart query based on MS medications and International Classification of Diseases, Ninth Revision codes was used to identify this population followed by a manual review to confirm the diagnosis. Outcomes were then assessed using revision for any reason as the primary end point. Functional outcomes were assessed using Short Form 12 scores. Survivorship curves were generated using the Kaplan-Meier method. RESULTS: At an average follow-up of 6.2 years, 19.4% (21/108) of patients required a revision surgery. Instability (5.6%, P = .0278) and periprosthetic joint infection (4.6%, P = .0757) were among the most common reasons for revision. The overall survivorship of TJA at years 2, 5, and 7, respectively, was 96.5% (95% confidence interval [CI], 92.6-100), 86.3% (95% CI, 77.7-94.5), and 75.3% (95% CI, 63.5-87.0). Functional score improvement was less in MS cohort than patients without MS. CONCLUSION: Patients with MS are at increased risk of complications, particularly instability and periprosthetic joint infection. Despite this increased risk of complications, patients with MS can demonstrate improved functional outcomes, but not as much as patients without MS. Patients with MS should be counseled appropriately before undergoing TJA.

Who Goes to Inpatient Rehabilitation or Skilled Nursing Facilities Unexpectedly Following Total Knee Arthroplasty?

BACKGROUND: Inpatient rehabilitation facilities (IRFs) and skilled nursing facilities (SNFs) represent a significant portion of post-operative expenses of bundled payments for total knee arthroplasty (TKA). Although many surgeons no longer routinely send patients to IRFs or SNFs, some patients are unable to be discharged directly home. This study identified patient factors for discharge to post-acute care facilities with an institutional protocol of discharging TKA patients home. METHODS: A retrospective review of patients undergoing primary unilateral TKA at a single institution from 2012 to 2017 was performed. All surgeons discharged patients home as a routine protocol. An electronic query followed by manual review identified discharge disposition, demographic factors, co-morbidities, and other patient factors. In total, 2281 patients were identified, with 9.6% discharged to SNFs or IRFs and 90.4% discharged home. Univariate and multivariate analyses were conducted to create 2 predictive models for patient discharge: pre-operative visit and hospital course. RESULTS: Among 43 variables studied, 6 were found to be significant pre-operative risk factors for a discharge disposition other than home. In descending order, age 75 or greater, female, non-Caucasian race, Medicare status, history of depression, and Charlson Comorbidity Index were predictors for patients going to IRFs. In addition, any in-hospital complications led to a higher likelihood of being discharged to IRFs and SNFs. Both models had excellent predictive assessments with area under curve values of 0.79 and 0.80 for pre-operative visit and hospital course. CONCLUSION: This study identifies pre-operative and in-hospital factors that predispose patients to non-routine discharges, which allow surgeons to better predict patient post-operative disposition.

Total Joint Arthroplasty in Patients With Parkinson's Disease: Survivorship, Outcomes, and Reasons for Failure.

BACKGROUND: Gait instability and muscle rigidity are known characteristics of Parkinson's disease (PD), putting PD patients at risk for complications following total joint arthroplasty (TJA). The outcomes of Parkinson's patients undergoing TJA are largely unknown. This study evaluated the outcomes of TJA in this population. METHODS: A single institution retrospective cohort of 123 TJAs (52 hips, 71 knees) from 2000 to 2016 was reviewed. An electronic chart query was performed using International Classification of Diseases, Ninth revision codes to identify this population. A manual chart review was performed to confirm the diagnosis of PD, survivorship, and reason for failure. A control cohort was matched 2:1 based on age, body mass index, joint, and comorbidities. Outcomes were assessed using revision for any reason as the primary endpoint. Functional outcomes were assessed using Short-Form 12 scores. RESULTS: At an average follow-up of 5.3 years, 23.6% of patients required revision surgery. The most common reasons for revision for total knee arthroplasty (TKA) were periprosthetic infection and for total hip arthroplasty (THA) were periprosthetic fracture and dislocation. Overall survivorship of TJA at years 2, 5, and 10 respectively were 94.9%, 87.9%, and 72.3%. The survivorship of TKA was 95.2%, 89.8%, and 66.2%. THA implant survivorship was 94.3%, 85.3%, and 78.7%. Functional score improvement was less in PD cohort than the control. CONCLUSION: Patients with PD are at increased risk for complications, particularly periprosthetic infection following TKA and periprosthetic fracture and dislocation following THA. Despite this increased risk of complications, patients with PD can demonstrate improved functional outcomes but not as high as patients without PD. Patients with PD should be counseled appropriately prior to undergoing TJA.

The Leukemia Inhibitory Factor Receptor Gene Is a Direct Target of RUNX1.

Activation of cytokine signaling via the leukemia inhibitory factor receptor (LIFR) plays an integral role in hematopoiesis, osteogenesis, and placental development, along with mediating neurotrophic mechanisms. However, the regulatory control of the LIFR gene has remained largely unexplored. Here, we characterize the LIFR gene as a novel target of the RUNX1 transcription factor. The RUNX1 transcription factor is an essential regulator of hematopoiesis and is a frequent target of point mutations and chromosomal alterations in leukemia. RUNX1 regulates hematopoiesis through its control of genes important for hematopoietic cell growth, proliferation, and differentiation, including a number of cytokines and cytokine receptors. LIFR is regulated by two alternate promoters: a placental-specific and a ubiquitously active general promoter. We show that both of these promoters are regulated by RUNX1. However, in myeloid cells LIFR expression is driven solely by the general LIFR promoter with our data indicating that the placental promoter is epigenetically silenced in these cells. While RUNX1 activates the LIFR general promoter, the oncogenic RUNX1-ETO fusion protein generated by the t(8;21) translocation commonly associated with acute myeloid leukemia represses promoter activity. The data presented here establish LIFR as a transcriptional target of RUNX1 and suggest that disruption of RUNX1 activity in myeloid cells may result in altered LIFR signaling in these cells.