Research Spotlight

Huddleston, J. I., 3rd, A. De, H. Jaffri, J. W. Barrington, P. J. Duwelius and B. D. Springer (2021). “Cementless Fixation Is Associated With Increased Risk of Early and All-Time Revision After Hemiarthroplasty But Not After THA for Femoral Neck Fracture: Results From the American Joint Replacement Registry.” Clin Orthop Relat Res 479(10): 2194-2202.

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BACKGROUND: Despite ample evidence supporting cemented femoral fixation for both hemiarthroplasty and THA for surgical treatment of displaced femoral neck fractures, cementless fixation is the preferred fixation method in the United States. To our knowledge, no nationally representative registry from the United States has compared revision rates by fixation for this surgical treatment. QUESTION/PURPOSE: After controlling for relevant confounding variables, is femoral fixation method (cemented or cementless) in hemiarthroplasty or THA for femoral neck fracture associated with a greater risk of (1) all-cause revision or (2) revision for periprosthetic fracture? METHODS: Patients with Medicare insurance who had femoral neck fractures treated with hemiarthroplasty or THA reported in the American Joint Replacement Registry database from 2012 to 2017 and Centers for Medicare and Medicaid Services claims data from 2012 to 2017 were analyzed in this retrospective, large-database study. Of the 37,201 hemiarthroplasties, 42% (15,748) used cemented fixation and 58% (21,453) used cementless fixation. Of the 7732 THAs, 20% (1511) used cemented stem fixation and 80% (6221) used cementless stem fixation. For both the hemiarthroplasty and THA cohorts, most patients were women and had cementless femoral fixation. Early revision was defined as a procedure that occurred less than 90 days from the index procedure. All patients submitted to the registry were included in the analysis. Patient follow-up was limited to the study period. No patients were lost to follow-up. Due to inherent limitations with the registry, we did not compare medical complications, including deaths attributed directly to cemented fixation. A logistic regression model including the index arthroplasty, age, gender, stem fixation method, hospital size, hospital teaching affiliation, and Charlson comorbidity index score was used to determine associations between the index procedure and revision rates. RESULTS: For the hemiarthroplasty cohort, risk factors for any revision were cementless stem fixation (odds ratio 1.42 [95% confidence interval 1.20 to 1.68]; p < 0.001), younger age (OR 0.96 [95% CI 0.95 to 0.97]; p < 0.001), and higher Charlson comorbidity index (OR 1.06 [95% CI 1.02 to 1.11]; p = 0.004). Risk factors for early revision were cementless stem fixation (OR 1.77 [95% CI 1.43 to 2.20]; p < 0.001), younger age (OR 0.98 [95% CI 0.97 to 0.99]; p < 0.001), and higher Charlson comorbidity index (OR 1.09 [95% CI 1.04 to 1.15]; p < 0.001). Risk factors for revision due to periprosthetic fracture were cementless fixation (OR 6.19 [95% CI 3.08 to 12.42]; p < 0.001) and higher Charlson comorbidity index (OR 1.16 [95% CI 1.06 to 1.28]; p = 0.002). Risk factors for early revision due to periprosthetic fracture were cementless fixation (OR 7.38 [95% CI 3.17 to 17.17]; p < 0.001), major teaching hospital (OR 2.10 [95% CI 1.08 to 4.10]; p = 0.03), and higher Charlson comorbidity index (OR 1.20 [95% CI 1.09 to 1.33]; p < 0.001). For the THA cohort, there were no associations. CONCLUSION: These data suggest that cemented fixation should be the preferred technique for most patients with displaced femoral neck fractures treated with hemiarthroplasty. The fact that stem fixation method did not affect revision rates for those patients with displaced femoral neck fractures treated with THA may be due to current practice patterns in the United States. LEVEL OF EVIDENCE: Level III, therapeutic study.

Singal, A. K., R. J. Wong, R. Jalan, S. Asrani and Y. F. Kuo (2021). “Primary biliary cholangitis has the highest waitlist mortality in patients with cirrhosis and acute on chronic liver failure awaiting liver transplant.” Clin Transplant: e14479.

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BACKGROUND: Data are sparse on etiology specific outcomes on waitlist (WL) and post-transplant outcomes among patients with acute on chronic liver failure (ACLF). METHODS AND RESULTS: In a retrospective cohort of 14,774 adults from United network for organ sharing (UNOS) database listed for Liver transplantation (LT) with cirrhosis and ACLF (January 2013-June 2019), 40% were due to alcohol-associated liver disease (ALD), followed by hepatitis C virus (HCV) at 20%, non-alcoholic steatohepatitis (19%), cryptogenic cirrhosis (7%), autoimmune hepatitis (5%), primary sclerosing cholangitis (PSC) at 3%, and 2% each for hepatitis B, primary biliary cholangitis (PBC), and metabolic etiology. Using competing risk analysis, cumulative risk of WL mortality was highest for PBC at 20.5% and lowest for PSC at 13.3%, P < .001. Compared with ALD as reference, WL mortality was higher for PBC (1.45 [1.16-1.82]), and similar for other etiologies, P < .001. Of this cohort, 9650 (65.3%) patients received LT, with 1-year. patient survival of 91.6% for PBC, worst for cryptogenic cirrhosis (89.5%) and best for PSC and ALD (93.4%), P < .001. CONCLUSION: Among listed candidates with ACLF, those with PBC have highest WL mortality 1-year. post-transplant survival was excellent among recipients for PBC. If these findings are validated in prospective studies, liver disease etiology should be considered for LT selection among patients in ACLF.

Serper, M., S. Asrani, L. VanWagner, P. P. Reese, M. Kim and M. S. Wolf (2021). “”Redefining Success After Liver Transplantation: From Mortality Toward Function and Fulfillment”.” Liver Transpl. [Epub ahead of print].

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Liver transplantation (LT), the only cure for end-stage liver disease, is a lifesaving, costly and limited resource. LT recipients (LTRs) are aging with an increasing burden of medical comorbidities. Patient and graft survival exceed 70% at 5 years, however, patient-centered health outcomes beyond survival have received relatively little attention. LTRs must have strong self-management skills to navigate health systems, adhere to clinical monitoring, and take complex, multi-drug regimens. All of these tasks require formidable cognitive abilities for active learning and problem solving. Yet, LTRs are at higher risk for impaired cognition due to high prevalence of pre-transplant hepatic encephalopathy, multiple chronic conditions, alcohol use, physical frailty, sarcopenia, and older age. Cognitive impairment post-transplant may persist and has been causally linked to poor self-management skills, worse physical function, and inferior health outcomes in other healthcare settings, yet its impact after LT is largely unknown. There is a need to study potentially modifiable, post-transplant targets including caregiver support, physical activity, sleep, and treatment adherence to inform future health system responses to promote the long-term health and well-being of LTRs. Prospective, longitudinal data collection that encompasses key socio-demographic, cognitive-behavioral, psychosocial, and medical factors is needed to improve risk prediction and better inform patients and caregiver expectations. Interventions with proactive monitoring, reducing medical complexity, and improved care coordination can be tailored to optimize posttransplant care. CONCLUSIONS: We propose a research agenda focused on understudied, potentially modifiable risk factors to improve the long-term health of LTRs. Our conceptual model accounts for cognitive function, caregiver and patient self-management skills, health behaviors, and patient-centered outcomes beyond mortality. We propose actionable health-system, patient, and caregiver-directed interventions to fill knowledge gaps and improve outcomes.

Panchal, S., M. Serper, T. Bittermann, S. K. Asrani, D. S. Goldberg and N. Mahmud (2021). “The impact of race-adjusted GFR estimation on eligibility for simultaneous liver-kidney transplantation.” Liver Transpl. [Epub ahead of print].

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BACKGROUND: Estimated glomerular filtration rate (eGFR) is adjusted for Black race in commonly used formulas. This has potential implications for access to simultaneous liver-kidney transplant (SLKT), as qualifying criteria rely on eGFR. METHODS: We performed a retrospective study of United Network for Organ Sharing (UNOS) national transplant registry data between 2/28/2002 and 3/31/2019 to evaluate the proportion of Black patients who would be reclassified as meeting SLKT criteria (as defined per current policies) if race adjustment were removed from two prominent eGFR equations (MDRD-4 and CKD-EPI). RESULTS: Of the 7,937 Black patients listed for transplant during the study period, we found that 3.6% would have been reclassified as qualifying for chronic kidney disease (CKD)-related SLKT with removal of race adjustment for MDRD-4, and 3.0% for CKD-EPI; this represented 23.7% and 18.7% increases in SLKT candidacy, respectively. Reclassification impacted women more than men (e.g. 4.5% vs. 3.0% by MDRD-4, p<0.05). In an exploratory analysis, patients meeting SLKT criteria by race unadjusted eGFR equations were significantly more likely to receive liver transplantation alone (LTA) as compared to SLKT. Approximately 2% of reclassified patients required kidney transplantation within one year of LTA, versus 0.3% of non-reclassified patients. DISCUSSION: In conclusion, race adjustment in eGFR equations may impact SLKT candidacy for 3-4% of Black patients listed for LTA overall. Approximately 2% of patients reclassified as meeting SLKT criteria require short-term post-LTA kidney transplantation. These data argue for developing novel algorithms for GFR estimation free of race to promote equity.

Shi, Q. S., D. H. Li, C. Y. Wu, D. Z. Liu, J. Hu, Y. L. Cui, N. Zhao, L. Chen and M. Askar (2021). “Effects of serum from mismatched patients with solid organ transplantation on the activation of microvascular cultures isolated from adipose tissues.” Transpl Immunol 69: 101462.

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BACKGROUND: Aggregating the human leukocyte antigen (HLA) Class I antigens on the endothelial membrane has been known to elicit an activation, an underlying mechanism of chronic rejection in organ transplant recipients. The current study aims at examining the endothelial responses using HLA typed microvascular cultures from human adipose tissues upon exposure to the serum that contain corresponding antibodies collected from mismatched transplant recipients. METHODS: We have successfully cultured 30 microvascular cultures and typed their HLAs. They are functionally competent to respond to inflammatory TNF-α stimulation and the aggregating monoclonal antibody against HLA Class I. The post-transplantation serum was collected either from the recipients with pathologically diagnosed chronic rejection or from the recipients without rejection. We determined their activation either by double-staining the endothelial cells in crude cultures with flow cytometry or by quantifying cytokine releases in purified endothelial cells using ELISA. RESULTS: Under our current protocol, adipose tissue cultures are functionally intact in regard to its responses to TNF-alpha and anti-HLA Class I antibody. We observed that the post-transplantation serum with rejection contained the pathogenic antibodies and led to proinflammatory activation, as demonstrated by not only increased CD54+/CD31+ and CD106+/CD31+ cell counts but also inflammatory cytokine releases including MCP-1, IL-8 and RANTES. CONCLUSION: This methodological study provides the feasibility of examining the pathogenicity of the alloantibodies in mis-transplant serum. Potentially, the endothelial activation elicited as a result of exposure can be used as an alternative readout for chronic rejection. SIGNIFICANCE: We prototype an ex vivo model that enables us to examine whether allogenic antibodies from the recipient can functionally activate microvascular endothelial cells from the donor adipose tissues. This system can be further developed as crossmatch using cellular responses as readouts for chronic rejection for post-transplant surveillance.