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AbstractIntroductionAdverse reactions to pain medication and pain can delay discharge after outpatient knee arthroplasty (TKA). Pharmacogenomics is an emerging tool that might help reduce adverse events by tailoring medication use based on known genetic variations in the CYP genes determining drug metabolism. This study was undertaken to evaluate whether pre-operative pharmacogenomic testing could optimize peri-operative pain management in patients undergoing total knee arthroplasty (TKA).MethodsThis prospective, randomized study was performed in adults undergoing primary TKA. Patients in the experimental group underwent pre-operative pharmacogenomic evaluation and medication adjustments. Medications were not optimized for control patients. The Overall Benefit of Analgesic Score (OBAS) at 24 hours post-op was the primary outcome. Postoperative pain scores (VAS scale), total opioid use, time in recovery, and time to discharge were also compared.Results76 patients enrolled. 93% of patients had a poor-intermediate phenotype for at least one of four CYP genes. OBAS did not differ significantly between the two groups (4.2 control vs. 4.7 experimental; 95% CI −1.1 to 2.1) and was below the minimum clinically important difference of 2.0 points. Furthermore, there were no differences in any OBAS subscale including pain, satisfaction, or nausea. There were no differences in time in the recovery area or to discharge from hospital, or narcotic use.ConclusionsDespite many patients having a poor-intermediate phenotype for a CYP gene, pharmacogenomic testing prior to TKA and medication adjustment did not improve anesthesia or pain management outcomes, time to discharge or mean total opioid use after surgery.

AbstractIntroductionThe optimal alignment technique for total knee replacement (TKR) remains controversial. We previously reported six-month and two-year results of a randomized controlled trial comparing kinematically (KA) versus mechanically (MA) aligned TKR. In the present study, we report 12-year results from this trial.MethodsThe original cohort included 88 TKRs (44 KA using Shape Match patient-specific guides and 44 MA using conventional instrumentation), performed from 2008 to 2009. After IRB approval, the health record of the original 88 patients were queried. Revisions, re-operations, and complications were recorded. The non-deceased patients were contacted via phone. Reoperation and complications were documented via the patient's history. Further, a battery of patient-reported outcome measures (including patient satisfaction, WOMAC, Oxford, KOOS Jr, Forgotten Joint Score, and M-SANE) were obtained.ResultsOf the original 88 patients in the study, 15 patients had a least one reoperation (17%). Patella problems were the most common cause of reoperation accounting for 5/8 reoperations in the KA group versus 3/7 in the MA group. There was no statistically significant difference between the two alignment methods in terms of major and minor complications or reoperations. At the 12-year follow-up, 26 patients died leaving 62 patients for follow-up. Of these, 48 patients (77%) were successfully contacted. The kinematically aligned total knees self-reported better satisfaction (96% versus 82%), but no difference in other patient-reported outcome measures compared to mechanically aligned TKRs.ConclusionKA TKR demonstrates excellent mid to long-term results compared to MA TKR with similar reoperations, complications, and patient-reported outcome measures.

Abstract Introduction Low creatinine to cystatin-C ratio (Cr/Cys-C) may be a biomarker for low-muscle mass. Furthermore, low Cr/Cys-C is associated with decreased overall survival (OS), but to date, has not been examined in patients with renal cell carcinoma (RCC). Our objective is to evaluate associations between low Cr/Cys-C ratio and OS and recurrence-free survival (RFS) in patients with RCC treated with nephrectomy. Methods We performed a retrospective review of patients with RCC treated with nephrectomy. Patients with end-stage renal disease and less than 1-year follow up were excluded. Cr/Cys-C was dichotomized at the median for the cohort (low vs. high). OS and RFS for patients with high versus low Cr/Cys-C were estimated with the Kaplan-Meier method, and associations with the outcomes of interest were modeled using Cox proportional Hazards models. Associations between Cr/Cys-C and skeletal muscle mass were assessed with correlations and logistic regression. Results A total of 255 patients were analyzed, with a median age of 64. Median (IQR) Cr/Cys-C was 1 (0.8-1.2). Low Cr/Cys-C was associated with age, female sex, Eastern Cooperative Oncology Group Performance Status ≥1, TNM stage, and tumor size. Kaplan-Meier and Cox regression analysis demonstrated an association between low Cr/Cys-C and decreased OS (HR = 2.97, 95%CI, 1.12-7.90, P =0.029) and RFS (HR = 3.31, 95%CI, 1.26-8.66, P = .015). Furthermore, a low Cr/Cys-C indicated a 2-3 increase in risk of radiographic sarcopenia. Conclusions Lower Cr/Cys-C is associated with inferior oncologic outcomes in RCC and, pending validation, may have utility as a serum biomarker for the presence of sarcopenia in patients with RCC treated with nephrectomy.

Background and Aims: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. Approach and Results: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of “agree” responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% “agree”). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. Conclusions: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce the prevalence of fatty liver disease and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.

Plasma exchange (PE) is a promising therapeutic option in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). However, the impact of PE on patient survival in these syndromes is unclear. We aimed to systematically investigate the use of PE in patients with ALF and ACLF compared with standard medical therapy (SMT). We searched PubMed/Embase/Cochrane databases to include all studies comparing PE versus SMT for patients ≥ 18 years of age with ALF and ACLF. Pooled risk ratios (RR) with corresponding 95% CIs were calculated by the Mantel-Haenszel method within a random-effect model. The primary outcome was 30-day survival for ACLF and ALF. Secondary outcomes were overall and 90-day survival for ALF and ACLF, respectively. Five studies, including 343 ALF patients (n = 174 PE vs. n = 169 SMT), and 20 studies, including 5,705 ACLF patients (n = 2,856 PE vs. n = 2,849 SMT), were analyzed. Compared with SMT, PE was significantly associated with higher 30-day (RR 1.41, 95% CI 1.06–1.87, p = 0.02) and overall (RR 1.35, 95% CI 1.12–1.63, p = 0.002) survival in ALF patients. In ACLF, PE was also significantly associated with higher 30-day (RR 1.36, 95% CI 1.22–1.52, p < 0.001) and 90-day (RR 1.21, 95% CI 1.10–1.34, p < 0.001) survival. On subgroup analysis of randomized controlled trials, results remained unchanged in ALF, but no differences in survival were found between PE and SMT in ACLF. In conclusion, PE is associated with improved survival in ALF and could improve survival in ACLF. PE may be considered in managing ALF and ACLF patients who are not liver transplant (LT) candidates or as a bridge to LT in otherwise eligible patients. Further randomized controlled trials are needed to confirm the survival benefit of PE in ACLF.

Background/Objective: To share technical pearls of a basic knee arthroscopy in a pediatric patient by presenting tips and tricks used by experienced pediatric arthroscopists. Indications: Knee arthroscopy is a common procedure performed by most orthopedic surgeons. However, technical considerations and equipment should be considered before performing this procedure in a pediatric patient. This video provides information on indications, equipment, and patient positioning, as well as outlining a systematic approach to diagnostic arthroscopy and pertinent pediatric anatomy. Discussion/Conclusion: This video provides an excellent overview as well as specific pathology-dependent considerations for the inexperienced orthopedic surgeon, or the orthopedic surgeon who rarely performs knee arthroscopy. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Objective: To evaluate long-term oncologic outcomes of patients post–living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score. Background: LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC). Methods: Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method. Results: Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% (P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% (P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%. Conclusions: Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.

BACKGROUND: Heart failure remains a global health burden, and patients hospitalized are particularly at risk, but genetic associates for subsequent death or rehospitalization are still lacking. METHODS: The genetic substudy of the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) was used to perform genome-wide association study and transethnic meta-analysis. The overall trial included the patients of self-reported European ancestry (n=2173) and African ancestry (n=507). The end point was death or heart failure rehospitalization within 180 days. Cox models adjusted for 11 a priori predictors of rehospitalization and 5 genetic principal components were used to test the association between single-nucleotide polymorphisms and outcome. Summary statistics from the 2 populations were combined via meta-analysis with the significance threshold considered P <5×10 − 8 . RESULTS: Common variants (rs2342882 and rs35850039 in complete linkage disequilibrium) located in FGD5 were significantly associated with the primary outcome in both ancestry groups (European Americans: hazard ratio [HR], 1.38; P =2.42×10 −6 ; African ancestry: HR, 1.51; P =4.43×10 − 3 ; HR in meta-analysis, 1.41; P =4.25×10 −8 ). FGD5 encodes a regulator of VEGF (vascular endothelial growth factor)-mediated angiogenesis, and in silico investigation revealed several previous genome-wide association study hits in this gene, among which rs748431 was associated with our outcome (HR, 1.20; meta P <0.01). Sensitivity analysis proved FGD5 common variants survival association did not appear to operate via coronary artery disease or nesiritide treatment ( P >0.05); and the signal was still significant when changing the censoring time from 180 to 30 days (HR, 1.39; P =1.59×10 −5 ). CONCLUSIONS: In this multiethnic genome-wide association study of ASCEND-HF, single-nucleotide polymorphisms in FGD5 were associated with increased risk of death or rehospitalization. Additional investigation is required to examine biological mechanisms and whether FGD5 could be a therapeutic target. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00475852.