High-throughput characterization of functional variants highlights heterogeneity and polygenicity underlying lung cancer susceptibility.

Genome-wide association studies (GWASs) have identified numerous lung cancer risk-associated loci. However, decoding molecular mechanisms of these associations is challenging since most of these genetic variants are non-protein-coding with unknown function. Here, we implemented massively parallel reporter assays (MPRAs) to simultaneously measure the allelic transcriptional activity of risk-associated variants. We tested 2,245 variants at 42 loci from 3 recent GWASs in East Asian and European populations in the context of two major lung cancer histological types and exposure to benzo(a)pyrene. This MPRA approach identified one or more variants (median 11 variants) with significant effects on transcriptional activity at 88% of GWAS loci. Multimodal integration of lung-specific epigenomic data demonstrated that 63% of the loci harbored multiple potentially functional variants in linkage disequilibrium. While 22% of the significant variants showed allelic effects in both A549 (adenocarcinoma) and H520 (squamous cell carcinoma) cell lines, a subset of the functional variants displayed a significant cell-type interaction. Transcription factor analyses nominated potential regulators of the functional variants, including those with cell-type-specific expression and those predicted to bind multiple potentially functional variants across the GWAS loci. Linking functional variants to target genes based on four complementary approaches identified candidate susceptibility genes, including those affecting lung cancer cell growth. CRISPR interference of the top functional variant at 20q13.33 validated variant-to-gene connections, including RTEL1, SOX18, and ARFRP1. Our data provide a comprehensive functional analysis of lung cancer GWAS loci and help elucidate the molecular basis of heterogeneity and polygenicity underlying lung cancer susceptibility.

Deep Learning for Grading Endometrial Cancer.

Endometrial cancer is the fourth most common cancer in women in the United States; the lifetime risk for developing this disease is approximately 2.8%. Precise histologic evaluation and molecular classification of endometrial cancer are important for effective patient management and determining the best treatment modalities. This study introduces EndoNet, which uses convolutional neural networks for extracting histologic features and a vision transformer for aggregating these features and classifying slides based on their visual characteristics into high- and low-grade cases. The model was trained on 929 digitized hematoxylin and eosin-stained whole-slide images of endometrial cancer from hysterectomy cases at Dartmouth-Health. It classifies these slides into low-grade (endometrioid grades 1 and 2) and high-grade (endometrioid carcinoma International Federation of Gynecology and Obstetrics grade 3, uterine serous carcinoma, or carcinosarcoma) categories. EndoNet was evaluated on an internal test set of 110 patients and an external test set of 100 patients from The Cancer Genome Atlas public database. The model achieved a weighted average F1 score of 0.91 (95% CI, 0.86 to 0.95) and an area under the curve of 0.95 (95% CI, 0.89 to 0.99) on the internal test, and 0.86 (95% CI, 0.80 to 0.94) for F1 score and 0.86 (95% CI, 0.75 to 0.93) for area under the curve on the external test. Pending further validation, EndoNet has the potential to support pathologists without the need of manual annotations in classifying the grades of gynecologic pathology tumors.

A theory of hydrogel mechanics that couples swelling and external flow.

Two aspects of hydrogel mechanics have been studied separately in the past. The first is the swelling and deswelling of gels in a quiescent solvent bath triggered by an environmental stimulus such as a change in temperature or pH, and the second is the solvent flow around and into a gel domain, driven by an external pressure gradient or moving boundary. The former neglects convection due to external flow, whereas the latter neglects solvent diffusion driven by a gradient in chemical potential. Motivated by engineering and biomedical applications where both aspects coexist and potentially interact with each other, this work presents a poroelasticity model that integrates these two aspects into a single framework, and demonstrates how the coupling between the two gives rise to novel physics in relatively simple one-dimensional and two-dimensional flows.

Estimating the interfacial permeability for flow into a poroelastic medium.

Boundary conditions between a porous solid and a fluid has been a long-standing problem in modeling porous media. For deformable poroelastic materials such as hydrogels, the question is further complicated by the elastic stress from the solid network. Recently, an interfacial permeability condition has been developed from the principle of positive energy dissipation on the hydrogel-fluid interface. Although this boundary condition has been used in flow computations and yielded reasonable predictions, it contains an interfacial permeability η as a phenomenological parameter. In this work, we use pore-scale models of flow into a periodic array of solid cylinders or parallel holes to determine η as a function of the pore size and porosity. This provides a means to evaluate the interfacial permeability for a wide range of poroelastic materials, including hydrogels, foams and biological tissues, to enable realistic flow simulations.

Mini-Navigation Utilization in THA Results in Shorter Length of Stay, Increased Home Discharge, and Higher Physical Therapy Mobilization Scores Compared to THA Without Navigation.

BACKGROUND: As volume of total hip arthroplasty (THA) continues to increase, the utilization and availability of in-traoperative advanced technologies to arthroplasty surgeons continues to rise as well. Our primary goal was to determine whether the use of a mini navigation technology extended operative times and secondarily if it affected postoperative outcomes following elective THA. METHODS: A single-institution total joint arthroplasty da-tabase was utilized to identify adult patients who underwent elective THA from 2017 to 2019. Baseline demographic data along with surgical operative time, length of stay (LOS) and discharge disposition were collected. The Activity Measure for Post-Acute Care (AM-PAC) was used to determine physi-cal therapy progress. RESULTS: A total of 1,162 THAs were performed of which 69.1% (803) used navigation while 30.9% (359) did not. Baseline demographics including age, sex, body mass index (BMI), insurance, and smoking status were not statistically different between groups. The operative time was shorter in the navigation group compared to THA without navigation (115.1 vs. 118.9 min, p < 0.0001). Mean LOS was signifi-cantly shorter in the navigation THA group as compared to THA without navigation (2.1 vs. 2.6 days, p < 0.0001). Postoperative AM-PAC scores were higher in the navigation group on postoperative day 1 as compared to patients with-out navigation (18.87 vs. 17.52, p < 0.0001). Additionally, a greater percentage of patients were discharged directly home after THA with navigation as compared to THA without navigation (89.54% vs. 83.57%, p < 0.0001). CONCLUSION: Our study demonstrates that hip navigation technology in the setting of THA is associated with reduced operative times and higher AM-PAC mobilization scores. Hip mini navigation technology shortens operative times while improving early patient outcome scores in association with shorter LOS and greater home-based discharge.

Exploring Mechanisms of Lipid Nanoparticle-Mucus Interactions in Healthy and Cystic Fibrosis Conditions.

Mucus forms the first defense line of human lungs, and as such hampers the efficient delivery of therapeutics to the underlying epithelium. This holds particularly true for genetic cargo such as CRISPR-based gene editing tools which cannot readily surmount the mucosal barrier. While lipid nanoparticles (LNPs) emerge as versatile non-viral gene delivery systems that can help overcome the delivery challenge, many knowledge gaps remain, especially for diseased states such as cystic fibrosis (CF). This study provides fundamental insights into Cas9 mRNA or ribonucleoprotein-loaded LNP-mucus interactions in healthy and diseased states by assessing the impact of the genetic cargo, mucin sialylation, mucin concentration, ionic strength, pH, and polyethylene glycol (PEG) concentration and nature on LNP diffusivity leveraging experimental approaches and Brownian dynamics (BD) simulations. Taken together, this study identifies key mucus and LNP characteristics that are critical to enabling a rational LNP design for transmucosal delivery.

The Effect of Marijuana on Postoperative Spine Patients' Emergency Department Visits, Readmission Rates, and Opioid Consumption.

OBJECTIVE: To compare postoperative opioid consumption with patients who tested negative for tetrahydrocannabinol (THC) preoperatively with those who were THC-positive and patients who were positive for THC and any other drug and to compare 90-day rates of postoperative emergency department (ED) visits and 90-day readmission rates, using morphine milligram equivalents (MMEs), for those three patient populations. METHODS: Three patient groups were confirmed with preoperative urine drug screens. Chart reviews were conducted to determine whether there was an ED visit or hospital readmission 90 days from the index procedure. MMEs were calculated for all patients. RESULTS: There were a total of 252 patients in the THC-negative control group, 54 in the THC-positive group, and 47 in the THC-and-opioid-positive group. The 90-day ED visit and 90-day readmission rates were not statistically significant among the groups. Both the multidrug and THC-only-positive patients showed a higher 90-day MME compared with the control patients. DISCUSSION: Our study demonstrates that THC used may increase opioid consumption. The THC patients to be cautious toward are the multidrug user. Although not statistically significant, multidrug patients were noted for a trend toward increased ED visits and readmissions.

Treating Hepatitis C Before Total Knee Arthroplasty is Cost-Effective: A Markov Analysis.

BACKGROUND: Patients who have the hepatitis C virus (HCV) have increased mortality and complication rates following total knee arthroplasty (TKA). Recent advances in HCV therapy have enabled clinicians to eradicate the disease using direct-acting antivirals (DAAs); however, its cost-effectiveness before TKA remains to be demonstrated. The aim of this study was to perform a cost-effectiveness analysis comparing no therapy to DAAs before TKA. METHODS: A Markov model using input values from the published literature was performed to evaluate the cost-effectiveness of DAA treatment before TKA. Input values included event probabilities, mortality, cost, and health state quality-adjusted life-year (QALY) values for patients who have and do not have HCV. Patients who have HCV were modeled to have an increased rate of periprosthetic joint infection (PJI) infection (9.9 to 0.7%). The incremental cost-effectiveness ratio (ICER) of no therapy versus DAA was compared to a willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses were performed to investigate the effects of uncertainty associated with input variables. RESULTS: Total knee arthroplasty in the setting of no therapy and DAA added 8.1 and 13.5 QALYs at a cost of $25,000 and $114,900. The ICER associated with DAA in comparison to no therapy was $16,800/QALY, below the willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses demonstrated that the ICER was affected by patient age, inflation rate, DAA cost and effectiveness, HCV-associated mortality, and DAA-induced reduction in PJI rate. CONCLUSION: Direct-acting antiviral treatment before TKA reduces risk of PJI and is cost-effective. Strong consideration should be given to treating patients who have HCV before elective TKA. LEVEL OF EVIDENCE: Cost-effectiveness Analysis; Level III.

Ulnar Nerve Translocation Following a Routine Distal Radius Fracture.

A 35-year-old right hand dominant male sustained a high energy closed right distal radius fracture with associated generalized paresthesias. Following closed reduction, the patient was found to have an atypical low ulnar nerve palsy upon outpatient follow-up. After continued symptoms and an equivocal wrist MRI the patient underwent surgical exploration. Intraoperatively, the ulnar nerve as well as the ring and small finger flexor digitorum superficialis tendons were found to be translocated around the ulnar head. The nerve and tendons were reduced, the median nerve was decompressed, and the fracture was addressed with volar plating. Post-operatively, the patient continued to have sensory deficits and stiffness of the ring and small fingers. After one year, he reported substantial improvements as demonstrated by full sensation (4.0 mm two-point discrimination) and fixed flexion contractures at the proximal and distal interphalangeal joints of the small finger. The patient returned to work without functional limitations. This case highlights a unique case of ulnar nerve and flexor tendon entrapment following a distal radius fracture. History, physical examination, and a high index of clinical suspicion is essential for proper management of this rare injury. Level of Evidence: V.

Human disease models in drug development.

Biomedical research is undergoing a paradigm shift towards approaches centred on human disease models owing to the notoriously high failure rates of the current drug development process. Major drivers for this transition are the limitations of animal models, which, despite remaining the gold standard in basic and preclinical research, suffer from interspecies differences and poor prediction of human physiological and pathological conditions. To bridge this translational gap, bioengineered human disease models with high clinical mimicry are being developed. In this Review, we discuss preclinical and clinical studies that benefited from these models, focusing on organoids, bioengineered tissue models and organs-on-chips. Furthermore, we provide a high-level design framework to facilitate clinical translation and accelerate drug development using bioengineered human disease models.

A 7-year perspective on femoral neck fracture management in New York State-Do Level 1 trauma centers provide better care?

INTRODUCTION: Patients with femoral neck fractures are at a substantial risk for medical complications and all-cause mortality. Given this trend, our study aims to evaluate postoperative outcomes and the economic profile associated with femoral neck fractures managed at level-1 (L1TC) and non-level-1-trauma centers (nL1TC). METHODS: The SPARCS database was queried for all geriatric patients sustaining atraumatic femoral neck fractures within New York State between 2011 and 2017. Patients were then divided into two cohorts depending on the treating facility's trauma center designation: L1TC versus nL1TC. Patient samples were evaluated for trends and relationships using descriptive analysis, Student's t-tests, and Chi-squared. Multivariable linear-regressions were utilized to assess the effect of trauma center designation and potential confounders on patient mortality and inpatient healthcare expenses. RESULTS: In total, 44,085 femoral neck fractures operatively managed at 161 medical centers throughout New York during a 7-year period. 4,974 fractures were managed at L1TC while 39,111 were treated at nL1TC. Following multivariate regression analysis, management at L1TC was the most significant cost driver, resulting in an average increased cost of $6,330.74 per fracture. CONCLUSION: Our results suggest that femoral neck fractures treated at L1TC have more comorbidities, higher in-hospital mortality, longer LOS, and greater hospital costs.

Zasp52 strengthens whole embryo tissue integrity through supracellular actomyosin networks.

During morphogenesis, large-scale changes of tissue primordia are coordinated across an embryo. In Drosophila, several tissue primordia and embryonic regions are bordered or encircled by supracellular actomyosin cables, junctional actomyosin enrichments networked between many neighbouring cells. We show that the single Drosophila Alp/Enigma-family protein Zasp52, which is most prominently found in Z-discs of muscles, is a component of many supracellular actomyosin structures during embryogenesis, including the ventral midline and the boundary of the salivary gland placode. We reveal that Zasp52 contains within its central coiled-coil region a type of actin-binding motif usually found in CapZbeta proteins, and this domain displays actin-binding activity. Using endogenously-tagged lines, we identify that Zasp52 interacts with junctional components, including APC2, Polychaetoid and Sidekick, and actomyosin regulators. Analysis of zasp52 mutant embryos reveals that the severity of the embryonic defects observed scales inversely with the amount of functional protein left. Large tissue deformations occur where actomyosin cables are found during embryogenesis, and in vivo and in silico analyses suggest a model whereby supracellular Zasp52-containing cables aid to insulate morphogenetic changes from one another.

Treating Hepatitis C Prior to Total Hip Arthroplasty is Cost-effective: A Markov Analysis.

BACKGROUND: Patients infected with the hepatitis C virus (HCV) have high complication rates following total hip arthroplasty (THA). Advances in HCV therapy now enable clinicians to eradicate the disease; however, its cost-effectiveness from an orthopaedic perspective remains to be demonstrated. We sought to conduct a cost-effectiveness analysis comparing no therapy to direct-acting antiviral (DAA) therapy prior to THA among HCV-positive patients. METHODS: A Markov model was utilized to evaluate the cost-effectiveness of treating HCV with DAA prior to THA. The model was powered with event probabilities, mortality, cost, and quality-adjusted life year (QALY) values for patients with and without HCV that were obtained from the published literature. This included treatment costs, successes of HCV eradication, incidences of superficial or periprosthetic joint infection (PJI), probabilities of utilizing various PJI treatment modalities, PJI treatment success/failures, and mortality rates. The incremental cost-effectiveness ratio was compared to a willingness-to-pay threshold of $50,000/QALY. RESULTS: Our Markov model indicates that in comparison to no therapy, DAA prior to THA is cost-effective for HCV-positive patients. THA in the setting of no therapy and DAA added 8.06 and 14.39 QALYs at a mean cost of $28,800 and $115,800. The incremental cost-effectiveness ratio associated with HCV DAA in comparison to no therapy was $13,800/QALY, below the willingness-to-pay threshold of $50,000/QALY. CONCLUSION: Hepatitis C treatment with DAA prior to THA is cost-effective at all current drug list prices. Given these findings, strong consideration should be given to treating patients for HCV prior to elective THA. LEVEL OF EVIDENCE: Cost-effectiveness Analysis; Level III.

Poroelastic modelling reveals the cooperation between two mechanisms for albuminuria.

Albuminuria occurs when albumin leaks abnormally into the urine. Its mechanism remains unclear. A gel-compression hypothesis attributes the glomerular barrier to compression of the glomerular basement membrane (GBM) as a gel layer. Loss of podocyte foot processes would allow the gel layer to expand circumferentially, enlarge its pores and leak albumin into the urine. To test this hypothesis, we develop a poroelastic model of the GBM. It predicts GBM compression in healthy glomerulus and GBM expansion in the diseased state, essentially confirming the hypothesis. However, by itself, the gel compression and expansion mechanism fails to account for two features of albuminuria: the reduction in filtration flux and the thickening of the GBM. A second mechanism, the constriction of flow area at the slit diaphragm downstream of the GBM, must be included. The cooperation between the two mechanisms produces the amount of increase in GBM porosity expected in vivo in a mutant mouse model, and also captures the two in vivo features of reduced filtration flux and increased GBM thickness. Finally, the model supports the idea that in the healthy glomerulus, gel compression may help maintain a roughly constant filtration flux under varying filtration pressure.

Massively parallel reporter assays and variant scoring identified functional variants and target genes for melanoma loci and highlighted cell-type specificity.

The most recent genome-wide association study (GWAS) of cutaneous melanoma identified 54 risk-associated loci, but functional variants and their target genes for most have not been established. Here, we performed massively parallel reporter assays (MPRAs) by using malignant melanoma and normal melanocyte cells and further integrated multi-layer annotation to systematically prioritize functional variants and susceptibility genes from these GWAS loci. Of 1,992 risk-associated variants tested in MPRAs, we identified 285 from 42 loci (78% of the known loci) displaying significant allelic transcriptional activities in either cell type (FDR < 1%). We further characterized MPRA-significant variants by motif prediction, epigenomic annotation, and statistical/functional fine-mapping to create integrative variant scores, which prioritized one to six plausible candidate variants per locus for the 42 loci and nominated a single variant for 43% of these loci. Overlaying the MPRA-significant variants with genome-wide significant expression or methylation quantitative trait loci (eQTLs or meQTLs, respectively) from melanocytes or melanomas identified candidate susceptibility genes for 60% of variants (172 of 285 variants). CRISPRi of top-scoring variants validated their cis-regulatory effect on the eQTL target genes, MAFF (22q13.1) and GPRC5A (12p13.1). Finally, we identified 36 melanoma-specific and 45 melanocyte-specific MPRA-significant variants, a subset of which are linked to cell-type-specific target genes. Analyses of transcription factor availability in MPRA datasets and variant-transcription-factor interaction in eQTL datasets highlighted the roles of transcription factors in cell-type-specific variant functionality. In conclusion, MPRAs along with variant scoring effectively prioritized plausible candidates for most melanoma GWAS loci and highlighted cellular contexts where the susceptibility variants are functional.

Indications for Conversion of Spinal into General Anesthesia During Total Joint Arthroplasty.

INTRODUCTION: Spinal anesthesia (SA) is the preferred method of anesthesia at many centers for total joint arthro- plasty (TJA). However, a small subset of patients fails SA, necessitating a conversion to general anesthesia (GA). This report assesses the patient characteristics associated with failed SA. METHODS: A retrospective study was conducted on patients who underwent SA during their primary TJA between Janu- ary 2015 and December 2016 at our institution. A subset of this group required a conversion from SA to GA. Anesthesia reports were reviewed for the number of attempts at SA and the documented reason for failure. The SA failure cohort was then subdivided into failure categories based on the reasons that had been provided. RESULTS: A total of 5,706 patients were included in this study, 78 of which experienced SA failure. The number of attempts was most strongly associated with SA failure, with three attempts resulting in a five times increased failure rate (OR = 4.73, p = 0.010) and four attempts resulting in 12 times increased failure rate compared to the no failure cohort (OR = 12.3, p < 0.001). Greater than two attempts occurred in 87.5% of the "technical failure" sub-group of the SA failure cohort (p < 0.001). No difference was demon- strated among the other patient characteristics, such as age, sex, body mass index, race, American Society of Anesthesia (ASA) score, and surgical time. CONCLUSIONS: The results suggest that the major predic- tor influencing spinal to general anesthesia conversion was the number of attempts at SA, especially among technical failure cases. Based on the results, it may be appropriate for anesthesiologists to convert to GA after two failed spi- nal attempts. Further studies are warranted to assess this relationship for firm clinical recommendations.

A similarity scaling approach for organ-on-chip devices.

Organ-on-chip devices (OoCs) provide more nuanced insights into (patho)physiological processes of the human body than static tissue models, and are currently the most promising approach to emulating human (patho)physiology in vitro. OoC designs vary greatly and questions remain as to how to maximize biomimicry and clinical translatability of the in vitro findings. Scaling is critical, yet has largely been ad hoc, consisting in matching one or a few variables between the OoC and the target organ. This has limited the predictive value of OoCs. Here, we propose a systematic approach based on the principle of similitude widely used in the physical sciences, and present three case studies from the recent literature to demonstrate how the approach works. A lung-on-a-chip and a liver-on-a-chip both satisfied important similarity criteria, and therefore yielded results that were in good agreement with clinical data. A gut-liver system failed to satisfy a key criterion of kinematic similarity, and yielded unphysiological pharmacokinetic responses in vitro. The similarity scaling approach promises to improve markedly the design and operation of organ- and human-on-chip devices.

Rare germline deleterious variants increase susceptibility for lung cancer.

Although multiple common susceptibility loci for lung cancer (LC) have been identified by genome-wide association studies, they can explain only a small portion of heritability. The etiological contribution of rare deleterious variants (RDVs) to LC risk is not fully characterized and may account for part of the missing heritability. Here, we sequenced the whole exomes of 2777 participants from the Environment and Genetics in Lung cancer Etiology study, a homogenous population including 1461 LC cases and 1316 controls. In single-variant analyses, we identified a new RDV, rs77187983 [EHBP1, odds ratio (OR) = 3.13, 95% confidence interval (CI) = 1.34-7.30, P = 0.008] and replicated two previously reported RDVs, rs11571833 (BRCA2, OR = 2.18; 95% CI = 1.25-3.81, P = 0.006) and rs752672077 (MPZL2, OR = 3.70, 95% CI = 1.04-13.15, P = 0.044). In gene-based analyses, we confirmed BRCA2 (P = 0.007) and ATM (P = 0.014) associations with LC risk and identified TRIB3 (P = 0.009), involved in maintaining genome stability and DNA repair, as a new candidate susceptibility gene. Furthermore, cases were enriched with RDVs in homologous recombination repair [carrier frequency (CF) = 22.9% versus 19.5%, P = 0.017] and Fanconi anemia (CF = 12.5% versus 10.2%, P = 0.036) pathways. Our results were not significant after multiple testing corrections but were enriched in cases versus controls from large scale public biobank resources, including The Cancer Genome Atlas, FinnGen and UK Biobank. Our study identifies novel candidate genes and highlights the importance of RDVs in DNA repair-related genes for LC susceptibility. These findings improve our understanding of LC heritability and may contribute to the development of risk stratification and prevention strategies.

Preoperative Patient Expectation of Discharge Planning is an Essential Component in Total Knee Arthroplasty.

PURPOSE: A better understanding of total knee arthroplasty (TKA) candidate expectations within the perioperative setting will enable clinicians to promote patient-centered practices, optimize recovery times, and enhance quality metrics. In the current study, TKA candidates were surveyed pre- and postoperatively to elucidate the relationship between patient expectations and length of stay (LOS). MATERIAL AND METHODS: This is a prospective study of patients undergoing TKA between December 2017 and August 2018. Patients were electronically administered surveys regarding their discharge plan 10 days pre-/postoperatively. All patients were categorized into three cohorts based on their LOS: 1, 2, and 3+ days. The effect of preoperative discharge education on patient postoperative satisfaction was evaluated. RESULTS: In total, 221 TKAs were included, of which 83 were discharged on postoperative day (POD) 1, 96 on POD-2, and 42 POD-3+. Female gender, increasing body mass index (BMI), and surgical time correlated with increased LOS. Preoperative discussions regarding LOS occurred in 84.62% (187/221) of patients but did correlate with differences in LOS. However, patients discharged on POD-1 were more inclined to same-day surgery preoperatively. Patients discharged on POD-3+ were found to be more uncomfortable regarding their discharge during the preoperative phase. Multivariable regressions demonstrated that preoperative discharge discussion was positively correlated with home discharge. CONCLUSION: Physician-driven discussion regarding patient discharge did not alter patient satisfaction or length of stay but did correlate with improved odds of home discharge. These findings underscore the importance of patient education, shared decision-making, and managing patient expectations.

The Effects of Patient Point of Entry and Medicaid Status on Postoperative Opioid Consumption and Pain After Primary Total Hip Arthroplasty.

INTRODUCTION: Medicaid expansion has allowed more patients to undergo total hip arthroplasty (THA). Given the continued focus on the opioid epidemic, we sought to determine whether patients with Medicaid insurance differed in their postoperative pain and narcotic requirements compared with privately or Medicare-insured patients. METHODS: A single-institution database was used to identify adult patients who underwent elective THA between 2016 and 2019. Patients in the Medicaid group received Medicaid insurance, while the non-Medicaid group was insured commercially or through Medicare. Subgroup analysis was done, separating the private pay from Medicare patients. RESULTS: A total of 5,845 cases were identified: 326 Medicaid (5.6%) and 5,519 non-Medicaid (94.4%). Two thousand six hundred thirty-five of the non-Medicaid group were insured by private payors. Medicaid patients were younger (56.1 versus 63.28 versus 57.4 years; P < 0.001, P < 0.05), less likely to be White (39.1% versus 78.2% versus 76.2%; P < 0.001), and more likely to be active smokers (21.6% versus 8.8% versus 10.5%; P < 0.001). Surgical time (113 versus 96 versus 98 mins; P < 0.001) and length of stay (2.7 versus 1.7 versus 1.4 days; P < 0.001) were longer for Medicaid patients, with lower home discharge (86.5% versus 91.8% versus 97.2%; P < 0.001). Total opioid consumption (178 morphine milligram equivalents [MMEs] versus 89 MME versus 82 MME; P < 0.001) and average MME/day in the first 24 hours and 24 to 48 hours (52.3 versus 44.7 versus 44.45; P < 0.001 and 73.8 versus 28.4 versus 29.8; P < 0.001) were higher for Medicaid patients. This paralleled higher pain scores (2.71 versus 2.31 versus 2.38; P < 0.001) and lower Activity Measure for Post-Acute Care scores (18.77 versus 20.98 versus 21.61; P < 0.001). CONCLUSIONS: Medicaid patients presenting for THA demonstrated worse postoperative pain and required more opioids than their non-Medicaid counterparts. This highlights the need for preoperative counseling and optimization in this at-risk population. These patients may benefit from multidisciplinary intervention to ensure that pain is controlled while mitigating the risk of continuation to long-term opioid use.