Merging Metabolic Modeling and Imaging for Screening Therapeutic Targets in Colorectal Cancer.

Cancer-associated fibroblasts (CAFs) play a key role in metabolic reprogramming and are well-established contributors to drug resistance in colorectal cancer (CRC). To exploit this metabolic crosstalk, we integrated a systems biology approach that identified key metabolic targets in a data-driven method and validated them experimentally. This process involved high-throughput computational screening to investigate the effects of enzyme perturbations predicted by a computational model of CRC metabolism to understand system-wide effects efficiently. Our results highlighted hexokinase (HK) as one of the crucial targets, which subsequently became our focus for experimental validation using patient-derived tumor organoids (PDTOs). Through metabolic imaging and viability assays, we found that PDTOs cultured in CAF conditioned media exhibited increased sensitivity to HK inhibition. Our approach emphasizes the critical role of integrating computational and experimental techniques in exploring and exploiting CRC-CAF crosstalk.

Barriers to resection following neoadjuvant chemotherapy for resectable pancreatic adenocarcinoma: A national and local perspective.

BACKGROUND: Neoadjuvant chemotherapy (NAC) use for pancreatic ductal adenocarcinoma (PDAC) has increased, but some patients never get resection following NAC. METHODS: Data from January 2012 to December 2019 for all clinically resectable patients across two health networks were utilized, as well as data from the ACS NCDB registry. Univariate testing, multivariable logistic regression, and survival analyses were employed to evaluate failure to resection after neo-adjuvant chemotherapy. RESULTS: Of the 10 007 registry patients eligible for resection, the resected group was younger (64.6 vs. 69.5 years; p < 0.001) and had a slightly lower mean comorbidity index (0.41 vs. 0.45; p < 0.001) than the nonsurgical group. The nonsurgical group was composed of a higher percentage of Black and Hispanic patients (17.5 vs. 13.1%; p < 0.001). After adjusting for age and comorbidities, the factors associated with decreased probability of resection after NAC were evaluation at a community hospital (OR 2.4), Black or Hispanic race (OR 1.6), areas of increased high school drop-out rates (OR 1.4), and lack of private health insurance (OR 1.3). The median overall survival for nonsurgery was markedly worse than the surgical cohort (10.6 vs. 26.6 months; p < 0.001). The most frequent reasons for a lack of definitive resection were operative upstaging to unresectable (39.6%), patient preference (14.5%), progression on NAC (13.2%), deconditioning or comorbidity severity (12.5%), and nonreferral to a surgeon (8.8%). CONCLUSIONS: Racial, economic, and educational disparities have a considerable influence on the successful completion of a neoadjuvant approach for resectable PDAC. A comprehensive closed or highly collaborative/communicative multidisciplinary neoadjuvant program is optimal for treatment success and completion.

Evidence-based definition of hypoprolactinemia in European men aged 40-86 years: the European male ageing study.

Empirical evidence for a low normal or reference interval for serum prolactin (PRL) is lacking for men, while the implications of very low PRL levels for human health have never been studied. A clinical state of "PRL deficiency" has not been defined except in relation to lactation. Using data from the European Male Ageing Study (EMAS), we analyzed the distribution of PRL in 3,369 community-dwelling European men, aged 40-80 years at phase-1 and free from acute illnesses. In total, 2,948 and 2,644 PRL samples were collected during phase-1 and phase-2 (3 to 5.7 years later). All samples were analysed in the same centre with the same assay. After excluding individuals with known pituitary diseases, PRL ≥ 35 ng/ml, and PRL-altering drugs including antipsychotic agents, selective serotonin reuptake inhibitors, or dopamine agonists, 5,086 data points (2,845 in phase-1 and 2,241 in phase-2) were available for analysis. The results showed that PRL declined minimally with age (slope = -0.02) and did not correlate with BMI. The positively skewed PRL distribution was log-transformed to a symmetrical distribution (skewness reduced from 13.3 to 0.015). Using two-sigma empirical rule (2[]SD about the mean), a threshold at 2.5% of the lower end of the distribution was shown to correspond to a PRL value of 2.98ng/ml. With reference to individuals with PRL levels of 5-34.9 ng/ml (event rate = 6.3%), the adjusted risk of developing type 2 diabetes increased progressively in those with PRL levels of 3-4.9 ng/ml: event rate = 9.3%, OR (95% CI) 1.59 (0.93-2.71), and more so with PRL levels of 0.3-2.9 ng/ml: event rate = 22.7%, OR 5.45 (1.78-16.62). There was also an increasing trend in prediabetes and diabetes based on fasting blood glucose levels was observed with lower categories of PRL. However, PRL levels were not associated with cancer, cardiovascular diseases, depressive symptoms or mortality. Our findings suggest that a PRL level below 3 ng/ml (64 mlU/l) significantly identifies European men with a clinically-important outcome (of type 2 diabetes), offering a lower reference-value for research and clinical practice.

Prevalence and Characteristics of Adults with Difficult-to-Treat Rheumatoid Arthritis in a Large Patient Registry.

OBJECTIVES: An estimated 5-20% of patients with rheumatoid arthritis (RA) fail multiple treatments and are considered "difficult-to-treat" (D2T), posing a substantial clinical challenge for rheumatologists. A European Alliance of Associations for Rheumatology (EULAR) task force proposed a definition of D2T-RA in 2021. We applied EULAR's D2T definition in a cohort of patients with established RA to assess prevalence and we compared clinical characteristics of participants with D2T-RA with matched comparisons. METHODS: Data from the longitudinal Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) registry was used. Participants were classified as D2T if they met EULAR's definition. A comparison group of non-D2T RA patients were matched 2:1 to every D2T patient, and differences in characteristics were evaluated in descriptive analyses. Prevalence rates of D2T were estimated using Poisson regression. RESULTS: We estimated the prevalence of D2T-RA to be 14.4 (95% CI: 12.8-16.3 per 100 persons) among 1,581 participants with RA, and 22.3 (95% CI: 19.9-25.0 per 100 persons) among 1,021 who were biologic/targeted synthetic DMARD experienced. We observed several differences in demographics, comorbidities, and RA disease activity between D2T-RA and non-D2T RA comparisons. Varying EULAR sub-criteria among all participants in BRASS resulted in a range of D2T-RA prevalence rates, from 0.6-17.5 per 100 persons. CONCLUSION: EULAR's proposed definition of D2T-RA identifies patients with RA who have not achieved treatment targets. Future research should explore heterogeneity in these patients and evaluate outcomes to inform the design of future studies aimed at developing more effective RA management protocols.

Concurrent RB1 Loss and BRCA-Deficiency Predicts Enhanced Immunological Response and Long-Term Survival in Tubo-Ovarian High-Grade Serous Carcinoma.

PURPOSE: To evaluate RB1 expression and survival across ovarian carcinoma histotypes, and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC). EXPERIMENTAL DESIGN: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 primary HGSC to characterize tumors with concurrent BRCA-deficiency and RB1 loss. RESULTS: RB1 loss was associated with longer OS in HGSC, but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared to patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA-deficiency correlated with transcriptional markers of enhanced interferon response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. CONCLUSIONS: Co-occurrence of RB1 loss and BRCA-deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

Family Caregivers' Progress Toward Values Moderates the Associations between Behavioral Symptoms of Dementia, Caregiver Burden, and Depressive Symptoms.

Increasingly, dementia caregiver interventions are informed by acceptance-based approaches such as Acceptance and Commitment Therapy. These interventions promote psychological skills like psychological flexibility and value-based living. Less is known how these constructs interact within well-established caregiver stress processes. We examined a moderated mediation model (N = 161 dementia caregivers; PROCESS Procedure; SPSS Release 4.1), with BPSD frequency (Revised Memory and Behavior Problems Checklist) predicting depressive symptoms (10-item CES-D), mediated via caregiver burden (short Burden inventory). The moderator was the Values Questionnaire, and we controlled for gender, caregiver duration, age, income, and education. Results: revealed that the indirect effect of BPSD on depressive symptoms through caregiver burden was weakened through higher progress toward values (moderated mediation significant at p < .05). Committed action toward values signify caregivers' success at balancing care-related stress with other priorities. Interventions that build skills in values-based living have promise for caregivers, offering healthier ways to adjust to being a caregiver.

Cerebral palsy research network community registry adult surveys on function & pain: Successes, challenges, and future directions.

NARRATIVE SUMMARY: The formation of a patient-reported outcomes registry to provide information about functional changes and pain among adults with cerebral palsy (CP) was identified as a priority to address the gap in knowledge and practice about aging and CP. The Cerebral Palsy Research Network collaborated with consumers, clinicians, and researchers to create an interactive internet platform, MyCP, to host a Community Registry. MyCP also provides educational programming, access to webinars and community forums, and fitness opportunities. The registry hosts surveys on function and pain for adults with CP, which provide cross-sectional and longitudinal data about these important issues. Surveys include previously validated measures with normative values that have been used with other populations and investigator developed questions. Enrollment in the registry is growing but needs to reflect the population of adults with CP, which limits generalizability. Future initiatives involve strategies to increase consumer engagement and enrollment.

Survivorship after adolescent and young adult cancer: Models of care, disparities, and opportunities.

Survivors of adolescent and young adult (AYA, age 15-39 years at diagnosis) cancer are a growing population with the potential to live for many decades after treatment completion. Survivors of AYA cancer are at risk for adverse long-term outcomes including chronic conditions, secondary cancers, impaired fertility, poor psychosocial health and health behaviors, and financial toxicity. Further, survivors of AYA cancer from racially minoritized and low socio-economic status populations experience disparities in these outcomes, including lower long-term survival. Despite these known risks, most survivors of AYA cancer do not receive routine survivorship follow-up care, and research on delivering high-quality, evidence-based survivorship care to these patients is lacking. The need for survivorship care was initially advanced in 2006 by the Institute of Medicine. In 2019, the Quality of Cancer Survivorship Care Framework (QCSCF) was developed to provide an evidence-based framework to define key components of optimal survivorship care. In this commentary focused on survivors of AYA cancer, we apply the QCSCF framework to describe models of care that can be adapted for their unique needs, multi-level factors limiting equitable access to care, and opportunities to address these factors to improve short- and long-term outcomes in this vulnerable population.

A high-density microfluidic bioreactor for the automated manufacturing of CAR T cells.

The manufacturing of autologous chimaeric antigen receptor (CAR) T cells largely relies either on fed-batch and manual processes that often lack environmental monitoring and control or on bioreactors that cannot be easily scaled out to meet patient demands. Here we show that human primary T cells can be activated, transduced and expanded to high densities in a 2 ml automated closed-system microfluidic bioreactor to produce viable anti-CD19 CAR T cells (specifically, more than 60 million CAR T cells from donor cells derived from patients with lymphoma and more than 200 million CAR T cells from healthy donors). The in vitro secretion of cytokines, the short-term cytotoxic activity and the long-term persistence and proliferation of the cell products, as well as their in vivo anti-leukaemic activity, were comparable to those of T cells produced in a gas-permeable well. The manufacturing-process intensification enabled by the miniaturized perfusable bioreactor may facilitate the analysis of the growth and metabolic states of CAR T cells during ex vivo culture, the high-throughput optimization of cell-manufacturing processes and the scale out of cell-therapy manufacturing.

Hospital acquired venous thromboembolism in children with sickle cell disease.

Sickle cell disease (SCD) is well recognized as a hypercoagulablestate, however, it remains unclear whether a subgroup of children with SCD at higher risk of venous thromboembolic event (VTE) during hospitalization may benefit from thromboprophylaxis. Our objectives were to describe the clinical characteristics, outcomes and recurrence of hospital acquired VTE in patients with SCD younger than 21 years. This was a single center retrospective study. Data regarding demographics, reason for admission, location of VTE, risk factors like central venous catheter (CVC), intensive care unit (ICU) admission among others were extracted from electronic medical records over a 10-year study period (2011-2021). Recurrence of VTE at 1 and 5 years was assessed. Descriptive statistics were used as indicated. We identified a total of 20 VTE events over the 10-year study period. Six of these events occurred in those younger than 12 years of age. Fourteen (70%) VTE events occurred in the HbSS or HbSßThal0 genotypes compared to 6 (30%) in HbSC. Most common VTE was isolated pulmonary embolism (PE) (n = 10, 50%). VTE were most often associated with acute chest syndrome (ACS) (n = 14, 70%), ICU admissions (n = 10, 50%) and CVC (n = 5/9, 55%). One patient died from the VTE event. One patient with additional underlying risk factors had a recurrent VTE at 13 months. Our study suggests that ICU admission, ACS and presence of CVC increases the risk of VTE in children and young adults with SCD, but larger studies are indicated to validate our findings.

Evaluating the Base Excision Repair Inhibitor TRC102 and Temozolomide for patients with Recurrent Glioblastoma in the Phase 2 Adult Brain Tumor Consortium Trial BERT.

PURPOSE: Patients with glioblastoma (GBM) have a dismal prognosis. While DNA alkylating agent temozolomide (TMZ) is mainstay of chemotherapy, therapeutic resistance develops rapidly in patients. Base excision repair inhibitor TRC102 (methoxyamine) reverses TMZ resistance in preclinical glioma models. We sought to investigate efficacy and safety of oral TRC102+TMZ for recurrent GBM (rGBM). PATIENTS AND METHODS: A pre-registered (NCT02395692), non-randomized, multicenter, phase 2 clinical trial (BERT) was planned and conducted through the Adult Brain Tumor Consortium (ABTC-1402). Arm 1 included bevacizumab-naïve GBM patients at first recurrence, with primary endpoint of response rates. If sufficient activity was identified, a second arm was planned in bevacizumab-refractory patients. Secondary endpoints were overall survival (OS), progression-free survival (PFS), PFS at six months (PFS-6), and toxicity. RESULTS: Arm 1 enrolled 19 patients with median of two treatment cycles. Objective responses were not observed, hence, arm 2 did not open. Median OS was 11.1 months (95%CI 8.2-17.9). Median PFS was 1.9 months (95%CI 1.8-3.7). PFS-6 was 10.5% (95%CI 1.3-33.1%). Most toxicities were Grade 1-2, with two Grade 3 lymphopenias and one Grade 4 thrombocytopenia. Two patients with PFS ≥17 months and OS >32 months were deemed 'extended survivors'. RNA sequencing of tumor tissue, obtained at diagnosis, demonstrated significantly enriched signatures of DNA damage response (DDR), chromosomal instability (CIN70, CIN25), and cellular proliferation (PCNA25) in 'extended survivors'. CONCLUSIONS: These findings confirm safety and feasibility of TRC102+TMZ for rGBM patients. They also warrant further evaluation of combination therapy in biomarker-enriched trials enrolling GBM patients with baseline hyperactivated DDR pathways.

Artificial Intelligence and Virtual Reality in Headache Disorder Diagnosis, Classification, and Management.

PURPOSE OF REVIEW: This review provides an overview of the current and future role of artificial intelligence (AI) and virtual reality (VR) in addressing the complexities inherent to the diagnosis, classification, and management of headache disorders. RECENT FINDINGS: Through machine learning and natural language processing approaches, AI offers unprecedented opportunities to identify patterns within complex and voluminous datasets, including brain imaging data. This technology has demonstrated promise in optimizing diagnostic approaches to headache disorders and automating their classification, an attribute particularly beneficial for non-specialist providers. Furthermore, AI can enhance headache disorder management by enabling the forecasting of acute events of interest, such as migraine headaches or medication overuse, and by guiding treatment selection based on insights from predictive modeling. Additionally, AI may facilitate the streamlining of treatment efficacy monitoring and enable the automation of real-time treatment parameter adjustments. VR technology, on the other hand, offers controllable and immersive experiences, thus providing a unique avenue for the investigation of the sensory-perceptual symptomatology associated with certain headache disorders. Moreover, recent studies suggest that VR, combined with biofeedback, may serve as a viable adjunct to conventional treatment. Addressing challenges to the widespread adoption of AI and VR in headache medicine, including reimbursement policies and data privacy concerns, mandates collaborative efforts from stakeholders to enable the equitable, safe, and effective utilization of these technologies in advancing headache disorder care. This review highlights the potential of AI and VR to support precise diagnostics, automate classification, and enhance management strategies for headache disorders.

Summer undergraduate biomedical research program for underrepresented minority students in a rural, low-income state.

Introduction: Diversity can enhance the agenda and quality of biomedical research, but a dearth of underrepresented minorities and women serve as biomedical researchers. The study purpose was to examine the impact of the a summer undergraduate research program on self-efficacy in research, scientific communication, and leadership as well as scientific identity, valuing objectives of the scientific community, and intent to pursue a biomedical research career. Methods: Underrepresented minority and female undergraduate students participated in a mentored research experience in a rural, low-income state. Results: Students' self-efficacy in research, scientific communication, and leadership as well as scientific identity, valuing objectives of the scientific community, and intent to pursue a biomedical research career increased post-program compared to pre-program. Conclusion: This study supports implementation of a biomedical summer undergraduate research program for URM and women in a poor, rural, settings.

Forecasting the Economic Burden of Cardiovascular Disease and Stroke in the United States Through 2050: A Presidential Advisory From the American Heart Association.

BACKGROUND: Quantifying the economic burden of cardiovascular disease and stroke over the coming decades may inform policy, health system, and community-level interventions for prevention and treatment. METHODS: We used nationally representative health, economic, and demographic data to project health care costs attributable to key cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia) and conditions (coronary heart disease, stroke, heart failure, atrial fibrillation) through 2050. The human capital approach was used to estimate productivity losses from morbidity and premature mortality due to cardiovascular conditions. RESULTS: One in 3 US adults received care for a cardiovascular risk factor or condition in 2020. Annual inflation-adjusted (2022 US dollars) health care costs of cardiovascular risk factors are projected to triple between 2020 and 2050, from $400 billion to $1344 billion. For cardiovascular conditions, annual health care costs are projected to almost quadruple, from $393 billion to $1490 billion, and productivity losses are projected to increase by 54%, from $234 billion to $361 billion. Stroke is projected to account for the largest absolute increase in costs. Large relative increases among the Asian American population (497%) and Hispanic American population (489%) reflect the projected increases in the size of these populations. CONCLUSIONS: The economic burden of cardiovascular risk factors and overt cardiovascular disease in the United States is projected to increase substantially in the coming decades. Development and deployment of cost-effective programs and policies to promote cardiovascular health are urgently needed to rein in costs and to equitably enhance population health.

Evaluating a multifaceted implementation strategy and package of evidence-based interventions based on WHO PEN for people living with HIV and cardiometabolic conditions in Lusaka, Zambia: protocol for the TASKPEN hybrid effectiveness-implementation stepped wedge cluster randomized trial.

BACKGROUND: Despite increasing morbidity and mortality from non-communicable diseases (NCD) globally, health systems in low- and middle-income countries (LMICs) have limited capacity to address these chronic conditions, particularly in sub-Saharan Africa (SSA). There is an urgent need, therefore, to respond to NCDs in SSA, beginning by applying lessons learned from the first global response to any chronic disease-HIV-to tackle the leading cardiometabolic killers of people living with HIV (PLHIV). We have developed a feasible and acceptable package of evidence-based interventions and a multi-faceted implementation strategy, known as "TASKPEN," that has been adapted to the Zambian setting to address hypertension, diabetes, and dyslipidemia. The TASKPEN multifaceted implementation strategy focuses on reorganizing service delivery for integrated HIV-NCD care and features task-shifting, practice facilitation, and leveraging HIV platforms for NCD care. We propose a hybrid type II effectiveness-implementation stepped-wedge cluster randomized trial to evaluate the effects of TASKPEN on clinical and implementation outcomes, including dual control of HIV and cardiometabolic NCDs, as well as quality of life, intervention reach, and cost-effectiveness. METHODS: The trial will be conducted in 12 urban health facilities in Lusaka, Zambia over a 30-month period. Clinical outcomes will be assessed via surveys with PLHIV accessing routine HIV services, and a prospective cohort of PLHIV with cardiometabolic comorbidities nested within the larger trial. We will also collect data using mixed methods, including in-depth interviews, questionnaires, focus group discussions, and structured observations, and estimate cost-effectiveness through time-and-motion studies and other costing methods, to understand implementation outcomes according to Proctor's Outcomes for Implementation Research, the Consolidated Framework for Implementation Research, and selected dimensions of RE-AIM. DISCUSSION: Findings from this study will be used to make discrete, actionable, and context-specific recommendations in Zambia and the region for integrating cardiometabolic NCD care into national HIV treatment programs. While the TASKPEN study focuses on cardiometabolic NCDs in PLHIV, the multifaceted implementation strategy studied will be relevant to other NCDs and to people without HIV. It is expected that the trial will generate new insights that enable delivery of high-quality integrated HIV-NCD care, which may improve cardiovascular morbidity and viral suppression for PLHIV in SSA. This study was registered at ClinicalTrials.gov (NCT05950919).

Actual cost of electricity: An economic index to overcome levelized cost of electricity limits.

The selection of renewable energy technologies is widely based on the economic index levelized cost of electricity (LCOE). However, the LCOE ignores the potential temporal mismatch between electricity generation and actual grid demand: this aspect is accounted for in the new index named actual cost of electricity (ACOE), here proposed. This index provides a more accurate economic assessment of renewable energy, minimizing the number of assumptions to be made and outlining the benefits of including a storage. The proposed index is tested across ten cases encompassing three renewable technologies: wind, photovoltaic, and concentrated solar power. The outcomes show that the actual renewable electricity generation of a plant can be reduced by 40%-50% when accounting for the actual electricity demand, resulting in an ACOE exceeding the LCOE by up to 100/150 $/MWh. In addition, the ACOE enables the identification of breakthrough conditions that make storage adoption economically feasible.

Common Cause Versus Dynamic Mutualism: An Empirical Comparison of Two Theories of Psychopathology in Two Large Longitudinal Cohorts.

Mental disorders are among the leading causes of global disease burden. To respond effectively, a strong understanding of the structure of psychopathology is critical. We empirically compared two competing frameworks, dynamic-mutualism theory and common-cause theory, that vie to explain the development of psychopathology. We formalized these theories in statistical models and applied them to explain change in the general factor of psychopathology (p factor) from early to late adolescence (N = 1,482) and major depression in middle adulthood and old age (N = 6,443). Change in the p factor was better explained by mutualism according to model-fit indices. However, a core prediction of mutualism was not supported (i.e., predominantly positive causal interactions among distinct domains). The evidence for change in depression was more ambiguous. Our results support a multicausal approach to understanding psychopathology and showcase the value of translating theories into testable statistical models for understanding developmental processes in clinical sciences.

The John Charnley Award: The Impact of Human Leukocyte Antigen (HLA) Genotype on Bacterial Infection Rates and Successful Eradication in Total Hip Arthroplasty.

BACKGROUND: Genetics plays an important role in several medical domains, however, the influence of human leukocyte antigen (HLA) genotype on the development of periprosthetic joint infection (PJI) in total hip arthroplasty (THA) remains unknown. The primary aim of this study was to determine if HLA genotype is associated with the development of bacterial PJI in THA. Secondarily, we evaluated the association between HLA genotype and PJI treatment success. METHODS: A retrospective, matched, case-control study was performed using prospectively collected data from a single institution. A total of 49 patients who underwent primary THA were included, with a mean follow-up of 8.5 years (range, 4.2 to 12.9). The 23 cases (PJI) and 26 controls (no PJI) were matched for age, sex, follow-up, body mass index (BMI), primary diagnosis, and comorbidities (P > 0.05). High-resolution genetic analysis targeting 11 separate HLA loci was performed in all patients using serum samples. The HLA gene frequencies and carriage rates were determined and compared between cohorts. A subgroup analysis of PJI treatment success (18) and failure (5) was performed. Statistical significance was set at P = 0.10 for genetic analysis and at 0.05 for all other analyses. RESULTS: There were four HLA alleles that were significantly associated with the development of PJI. The 3 at-risk alleles included HLA-C*06:02 (OR [odds ratio] 5.25, 95% CI [confidence interval] 0.96 to 28.6, P = 0.064), HLA-DQA1*04:01 (P = 0.096), and HLA-DQB1*04:02 (P = 0.096). The single protective allele was HLA-C*03:04 (OR 0.12, 95% CI 0.01 to 1.10, P = 0.052). There were no specific HLA alleles that were associated with treatment success or failure. CONCLUSION: This study suggests that there are at-risk and protective HLA alleles associated with the development of PJI in THA. To our knowledge, this is the first study to demonstrate an association between patient HLA genotype and the development of PJI. A larger study of the subject matter is necessary and warranted.