Preventing Infections in Reverse Shoulder Arthroplasty.

PURPOSE OF REVIEW: Reverse shoulder arthroplasty (rTSA) is a commonly performed procedure to treat degenerative conditions of the shoulder. With its growing utilization, techniques to reliably diagnose and treat prosthetic joint infection (PJI) have become increasingly important. In this review we outline the current research and prevention methods of prosthetic joint infection in rTSA. This includes preoperative considerations, intraoperative, and postoperative treatment algorithms. RECENT FINDINGS: There is currently no established standardized protocol for preoperative infection prevention or post operative management. However, recent studies have identified risk factors for infection, as well as successful prevention techniques that can be implemented to minimize infection risk. Although there is no standardized protocol currently utilized to diagnose and treat shoulder PJI, we outline a potential set of preventative measures and postoperative management strategies that clinicians can use to properly diagnose and treat patients with this difficult condition.

Living Donor Liver Transplantation for Hepatocellular Carcinoma Within and Outside Traditional Selection Criteria: A Multicentric North American Experience.

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.

Significant Reduction in Posttransplant Hepatocellular Carcinoma Recurrence in the Post 6-Mo Waiting Policy Era.

BACKGROUND: In 2015, the United Network for Organ Sharing implemented a policy introducing a 6-mo waiting period before granting model for end-stage liver disease exception points to liver transplant (LT) candidates with hepatocellular carcinoma (HCC). This study analyzes the policy impact on post-LT HCC recurrence. METHODS: This was a United Network for Organ Sharing retrospective cohort study of patients with HCC who underwent LT from January 1, 2010, to May 31, 2019. HCC-specific data included alpha-fetoprotein, tumor characteristics, locoregional therapy (LRT), and explant data used to calculate the Risk Estimation of Tumor Recurrence After Transplant score. The primary exposure was pre-/post-policy era, divided on October 8, 2015. Survival analysis techniques were used to evaluate the unadjusted and sequentially adjusted association between policy era and HCC recurrence, accounting for competing risks. RESULTS: A total of 7940 patients were included, 5879 (74.0%) pre-policy era and 2061 (26.0%) post-policy era. Post-policy patients were older, received more LRT, and had lower alpha-fetoprotein levels and smaller tumor sizes at transplant. Incidence rates of HCC recurrence were 19.8 and 13.7 events per 1000 person-years for pre- and post-policy eras, respectively. Post-policy era was associated with an unadjusted 35% reduction in the risk of HCC recurrence (P < 0.001). After adjusting for recipient, donor, and tumor characteristics at listing this association remained (subhazard ratio 0.69; 95% confidence interval, 0.55-0.86; P = 0.001); however, after additionally adjusting for LRT episodes and Risk Estimation of Tumor Recurrence After Transplant score, there was no longer a statistically significant association (subhazard ratio 0.77; 95% confidence interval, 0.59-1.00; P = 0.054). CONCLUSIONS: We observed a significant reduction in post-LT HCC recurrence after policy implementation. This may be due to waitlist selection of healthier patients, increased LRT utilization, and potential selection of favorable tumor biology.

The effect of shoulder prosthesis stem length on failure due to torsional loading. A biomechanical study in composite humeri.

Background: Shoulder arthroplasty is becoming increasingly common. With evolving implant designs, multiple humeral stem options exist for the surgeon to choose from. New stemless and short-stem systems are modular, remove less native bone stock, and better adapt to patient anatomy. It has been suggested that shorter stem implants may be protective against periprosthetic fracture; however, this has not been mechanistically evaluated. Therefore, this study aimed to biomechanically test synthetic humeri with long-stem, short-stem, and stemless arthroplasty components in a torsional manner to evaluate their response to loading and characterize failure. Methods: Twenty-four synthetic humeri were implanted with long stem, short stem, or stemless uncemented prosthesis, 8 in each group. Humeri were mounted in a custom testing jig with a morse taper interfacing with a mechanical testing system. After a 20N axial force, specimens were torsionally loaded to failure at 15 degrees/sec, with 50 Hz collection. Torque vs. rotation curves were generated for each specimen, and stiffness, yield, ultimate strength, and failure load were measured. ANOVA and post hoc pairwise comparisons were used to assess effect of stem type on mechanical test variable. The association of the stem type with fracture type was analyzed by a Fisher's Exact test. Statistical significance was set at P < .05. Results: During torsional loading, long-stem implants were significantly stiffer than short or stemless implants. The angle of implant yielding was similar across stem designs; however, stemless implants had a lower yield torque. This correlated with a decreased yield energy in stemless compared to short stems as well. Maximum torque and failure torque was also significantly higher in short-stem and long-stem implants compared to stemless. Discussion: Periprosthetic fractures in shoulder arthroplasty are a concern in low-energy trauma, and stem design likely plays a significant role in early implant-bone failure. Our results suggest stemless implants under torsional load fail at lower stress and are less stiff than stemmed implants. The failure mechanism of stemless implants through metaphyseal cancellous bone emphasizes the effect bone quality has on implant fixation. There is likely a balance of torsional stability to survive physiologic loads while minimizing diaphyseal stress and risk of diaphyseal periprosthetic fracture. This combined with revision and fixation options represent decisions the surgeon is faced with when performing shoulder arthroplasty.

Outcomes in liver transplant recipients with nonalcoholic fatty liver disease-related HCC: results from the US multicenter HCC transplant consortium.

NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.

Association between sustained virological response and clinical outcomes in patients with hepatitis C infection and hepatocellular carcinoma.

BACKGROUND: Sustained viral response (SVR) improves survival for patients with hepatitis C (HCV) and hepatocellular carcinoma (HCC) after curative treatment; however, the benefit of SVR in those with active HCC with a significant competing risk of mortality is unknown. This study aimed to evaluate the association between SVR and outcomes in patients with active HCC. METHODS: The authors performed a multicenter, retrospective cohort study including consecutive adults with HCV cirrhosis and treatment-naive HCC diagnosed between 2014 and 2018. Patients were stratified into two groups: active viremia (n = 431) and SVR before HCC diagnosis (n = 135). All patients underwent nonsurgical therapy as their initial treatment and were followed until liver transplantation, last follow-up, or death. The primary outcome was incident or worsening hepatic decompensation within 6 months and the secondary outcome was overall survival. All analyses used inverse probability of treatment weights (IPTW) to account for differences between the nonrandomized cohorts. RESULTS: Post-SVR patients had significantly lower odds of hepatic decompensation compared to viremic patients (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.06-0.59). Results were consistent among subgroups of patients with Child Pugh A cirrhosis (OR, 0.22; 95% CI, 0.04-0.77), Barcelona Clinic Liver Cancer stage B/C HCC (OR, 0.20; 95% CI, 0.04-0.65), and those receiving nonablative HCC therapies (OR, 0.21; 95% CI, 0.07-0.67). However, in IPTW multivariable Cox regression, SVR was not associated with improved survival (hazard ratio, 0.79; 95% CI, 0.56-1.12). CONCLUSIONS: Patients with HCV-related HCC and SVR are less likely to experience hepatic decompensation than viremic patients, suggesting patients with HCC who are undergoing nonsurgical therapies may benefit from DAA treatment.

Multigene Panel Testing in Individuals With Hepatocellular Carcinoma Identifies Pathogenic Germline Variants.

Hepatocellular carcinoma (HCC) has well-defined environmental risk factors. In addition, epidemiologic studies have suggested hereditary risk factors. The goals of this study were to determine the rate of pathogenic and likely pathogenic (P/LP) germline variants in cancer predisposition genes in patients with HCC, possible enrichment of P/LP variants in particular genes, and potential impact on clinical management. MATERIALS AND METHODS: A prospective study at a tertiary medical center enrolled 217 patients with a personal history of HCC. Multigene panel testing was performed for 134 cancer predisposition genes in all patients. The rate of P/LP variants was compared with population rates. A separate retrospective cohort included 219 patients with HCC who underwent testing at a commercial laboratory. RESULTS: In the prospective cohort, P/LP germline variants were identified in 25 of 217 patients with HCC (11.5%). Four patients (1.8%) had P/LP variants in the highly penetrant cancer genes BRCA2 (n = 2), MSH6 (n = 1), and PMS2 (n = 1). In addition, multiple patients had P/LP variants in FANCA (n = 5) and BRIP1 (n = 4), which were significantly enriched in HCC compared with the general population. Detection of P/LP variants led to changes in clinical management in regard to therapy selection, screening recommendations, and cascade testing of relatives. In a separate retrospective analysis of 219 patients with HCC, 30 (13.7%) were positive for P/LP variants including 13 (5.9%) with highly penetrant genes APC (n = 2), BRCA1 (n = 1), BRCA2 (n = 6), MSH2 (n = 2), or TP53 (n = 2). CONCLUSION: P/LP germline variants in cancer predisposition genes were detected in 11%-14% of patients with HCC. Inherited genetics should not be overlooked in HCC as there are important implications for precision treatment, future risk of cancers, and familial cancer risk.

Posttransplant Outcomes in Older Patients With Hepatocellular Carcinoma Are Driven by Non-Hepatocellular Carcinoma Factors.

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.

Management of irreparable massive rotator cuff tears: a systematic review and meta-analysis of patient-reported outcomes, reoperation rates, and treatment response.

BACKGROUND: There is no consensus on the treatment of irreparable massive rotator cuff tears. The goal of this systematic review and meta-analysis was to (1) compare patient-reported outcome scores, (2) define failure and reoperation rates, and (3) quantify the magnitude of patient response across treatment strategies. METHODS: The MEDLINE, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and Scopus databases were searched for studies including physical therapy and operative treatment of massive rotator cuff tears. The criteria of the Methodological Index for Non-randomized Studies were used to assess study quality. Primary outcome measures were patient-reported outcome scores as well as failure, complication, and reoperation rates. To quantify patient response to treatment, we compared changes in the Constant-Murley score and American Shoulder and Elbow Surgeons (ASES) score with previously reported minimal clinically important difference (MCID) thresholds. RESULTS: No level I or II studies that met the inclusion and exclusion criteria were found. Physical therapy was associated with a 30% failure rate among the included patients, and another 30% went on to undergo surgery. Partial repair was associated with a 45% retear rate and 10% reoperation rate. Only graft interposition was associated with a weighted average change that exceeded the MCID for both the Constant-Murley score and ASES score. Latissimus tendon transfer techniques using humeral bone tunnel fixation were associated with a 77% failure rate. Superior capsular reconstruction with fascia lata autograft was associated with a weighted average change that exceeded the MCID for the ASES score. Reverse arthroplasty was associated with a 10% prosthesis failure rate and 8% reoperation rate. CONCLUSION: There is a lack of high-quality comparative studies to guide treatment recommendations. Compared with surgery, physical therapy is associated with less improvement in perceived functional outcomes and a higher clinical failure rate.

Predictors, Presentation, and Treatment Outcomes of Recurrent Hepatocellular Carcinoma After Liver Transplantation: A Large Single Center Experience.

BACKGROUND: Liver transplantation (LT) is an accepted therapeutic option for hepatocellular carcinoma (HCC) in patients with cirrhosis. Despite careful candidate selection, HCC recurrence occurs. We aimed to describe the predictors of recurrence, clinical presentation, and predictors of survival after HCC recurrence post-LT. METHODS: Patients with recurrent HCC after LT between January 1996 and December 2017 were retrospectively reviewed. RESULTS: Of 711 patients, 96 (13.5%) patients had post-LT HCC recurrence. The median time to recurrence was 17.1 months, and the median survival was 10.1 months. Initial recurrence was more often in the graft (34.4%), and most (60.4%) had multiple recurrent lesions, and 26% were in multiple sites. In multivariate analysis, factors associated with shorter survival were poorly differentiated histology in explant (Hazard ratio [HR] = 1.96; p = 0.027), bilirubin ≥1.2 mg/dL (HR = 2.47; p = 0.025), and albumin <3.5 mg/dL (HR = 2.13; p = 0.014) at recurrence, alpha-fetoprotein at recurrence ≥ 1000 ng/mL (HR = 2.96; p = 0.005), and peritoneal disease (HR = 3.20; p = 0.022). There was an increased survival in patients exposed to sirolimus (HR = 0.32; p < 0.0001). CONCLUSIONS: Recurrent HCC after LT is often in extrahepatic sites with a decreased survival in those with poorly differentiated explant pathology, high bilirubin, low albumin, marked elevation of alpha-fetoprotein at recurrence, and peritoneal recurrence. Sirolimus-based immunosuppression may provide benefit.

Risk Factors and Center-Level Variation in Hepatocellular Carcinoma Under-Staging for Liver Transplantation.

Liver transplantation (LT) is curative for most patients with hepatocellular carcinoma (HCC). However, 10%-15% of patients experience HCC recurrence. Patients who are reported as within Milan criteria by imaging are frequently found to be outside the criteria on explant. This under-staging of HCC worsens post-LT outcomes. However, risk factors for under-staging have not been elucidated. Furthermore, it is not known if there is regional or center-level variation in under-staging. We conducted a retrospective analysis of adult patients transplanted for HCC in the United Network for Organ Sharing (UNOS) database between 2012 and 2016. Under-staging was determined on the basis of comparing pre-LT imaging to explant findings. Kaplan-Meier methods and Cox regression were used to evaluate the impact of under-staging on HCC recurrence and post-LT survival. Mixed effects logistic regression was used to identify risk factors for under-staging and to study regional and center-level variation in adjusted analyses. A total of 5424 patients were included in the cohort, of whom 24.9% (n = 1353) were under-staged. Post-LT HCC recurrence and death were significantly associated with under-staging (each P < 0.001). In adjusted analyses, independent predictors of under-staging included age (odds ratio [OR], 1.13 per 10 years; 95% confidence interval [CI], 1.03-1.25), male sex (OR, 1.61; 95% CI, 1.36-1.89), down-staging (OR, 4.03; 95% CI, 2.65-6.11), and pre-LT alpha-fetoprotein (P < 0.001). There was also significant variation in under-staging between UNOS regions and among transplant centers, ranging from 14.8% to 38.1%. We report novel risk factors for HCC under-staging, which worsens post-LT outcomes. Significant center-level and regional variation in under-staging highlights the need for standards that achieve greater uniformity in staging.

Provider Attitudes and Practice Patterns for Direct-Acting Antiviral Therapy for Patients With Hepatocellular Carcinoma.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC. METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses (58.6%). RESULTS: Provider beliefs about risk of HCC recurrence after DAA therapy varied: 48% responded that DAAs reduce risk, 36% responded that DAAs do not change risk, and 16% responded that DAAs increase risk of HCC recurrence. However, most providers believed DAAs to be beneficial to and reduce mortality of patients with complete response to HCC treatment. Accordingly, nearly all providers (94.9%) reported recommending DAA therapy to patients with early-stage HCC who received curative treatment. However, fewer providers recommended DAA therapy for patients with intermediate (72.9%) or advanced (57.5%) HCC undergoing palliative therapies. Timing of DAA initiation varied among providers based on HCC treatment modality: 49.1% of providers reported they would initiate DAA therapy within 3 months of surgical resection whereas 45.9% and 5.0% would delay DAA initiation for 3-12 months and >1 year post-surgery, respectively. For patients undergoing transarterial chemoembolization (TACE), 42.0% of providers would provide DAAs within 3 months of the procedure, 46.7% would delay DAAs until 3-12 months afterward, and 11.3% would delay DAAs more than 1 year after TACE. CONCLUSIONS: Based on a survey sent to hepatology providers, there is variation in provider attitudes and practice patterns regarding use and timing of DAAs for patients with HCC. Further studies are needed to characterize the risks and benefits of DAA therapy in this patient population.

MSCopilot, a new multiple sclerosis self-assessment digital solution: results of a comparative study versus standard tests.

BACKGROUND AND PURPOSE: Assessing patients' disability in multiple sclerosis (MS) requires time-consuming batteries of hospital tests. MSCopilot is a software medical device for the self-assessment of patients with MS (PwMS), combining four tests: walking, dexterity, cognition and low contrast vision. The objective was to validate MSCopilot versus the Multiple Sclerosis Functional Composite (MSFC). METHODS: This multicentre, open-label, randomized, controlled, crossover study enrolled 141 PwMS and 76 healthy controls (HCs). All participants performed MSCopilot and MSFC tests at day 0. To assess reproducibility, 46 PwMS performed the same tests at day 30 ± 3. The primary end-point was the validation of MSCopilot versus MSFC for the identification of PwMS against HCs, quantified using the area under the curve (AUC). The main secondary end-point was the correlation of MSCopilot z-scores with MSFC z-scores. RESULTS: In all, 116 PwMS and 69 HCs were analysed. The primary end-point was achieved: MSCopilot performance was non-inferior to that of MSFC (AUC 0.92 and 0.89 respectively; P = 0.3). MSCopilot and MSFC discriminated PwMS and HCs with 81% and 76% sensitivity and 82% and 88% specificity respectively. Digital and standard test scores were highly correlated (r = 0.81; P < 0.001). The test-retest study demonstrated the good reproducibility of MSCopilot. CONCLUSION: This study confirms the reliability of MSCopilot and its usability in clinical practice for the monitoring of MS-related disability.

Radioembolization-Induced Chronic Hepatotoxicity: A Single-Center Cohort Analysis.

PURPOSE: To identify and characterize the delayed effects of transarterial radioembolization (TARE) on the liver. MATERIALS AND METHODS: A single-institution retrospective analysis was undertaken of all patients who received TARE between 2005 and 2014 and survived at least 1 year from the initial TARE (n = 106). Patients were evaluated for the presence or absence of radioembolization-induced chronic hepatotoxicity (RECHT) occurring at least 6 months after TARE. The mean age of patients was 63 years of age, and the malignancy most commonly treated was neuroendocrine tumor (54%). Adjudication of hepatic decompensation to RECHT versus alternative causes was performed by a multidisciplinary panel of specialists from hepatology, radiation oncology, and interventional radiology. RESULTS: Eight patients were excluded from analysis because of liver transplantation (2) or incomplete data (6). RECHT occurred in 13 of 98 patients (13%), and 5 deaths (5%) occurred from hepatic decompensation. There were a total of 69 toxicity events in patients developing RECHT. The most common events were elevation of alkaline phosphatase (10), decrease in serum albumin (10), and development of ascites (9). RECHT patients had a higher intrahepatic tumor volume (P = .021) and a higher number of hepatic comorbidities leading to cirrhosis (P = .015). CONCLUSIONS: Delayed radiation-induced hepatic toxicity occurred in 13% of patients following radioembolization, with 5 fatalities adjudicated to be a result of the treatment. Tumor involvement of greater than 50% of the liver and cirrhosis were predisposing factors for RECHT.

Identification and characterization of dysregulated P-element induced wimpy testis-interacting RNAs in head and neck squamous cell carcinoma.

It is clear that alcohol consumption is a major risk factor in the pathogenesis of head and neck squamous cell carcinoma (HNSCC); however, the molecular mechanism underlying the pathogenesis of alcohol-associated HNSCC remains poorly understood. The aim of the present study was to identify and characterize P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) and PIWI proteins dysregulated in alcohol-associated HNSCC to elucidate their function in the development of this cancer. Using next generation RNA-sequencing (RNA-seq) data obtained from 40 HNSCC patients, the piRNA and PIWI protein expression of HNSCC samples was compared between alcohol drinkers and non-drinkers. A separate piRNA expression RNA-seq analysis of 18 non-smoker HNSCC patients was also conducted. To verify piRNA expression, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed on the most differentially expressed alcohol-associated piRNAs in ethanol and acetaldehyde-treated normal oral keratinocytes. The correlation between piRNA expression and patient survival was analyzed using Kaplan-Meier estimators and multivariate Cox proportional hazard models. A comparison between alcohol drinking and non-drinking HNSCC patients demonstrated that a panel of 3,223 piRNA transcripts were consistently detected and differentially expressed. RNA-seq analysis and in vitro RT-qPCR verification revealed that 4 of these piRNAs, piR-35373, piR-266308, piR-58510 and piR-38034, were significantly dysregulated between drinking and non-drinking cohorts. Of these four piRNAs, low expression of piR-58510 and piR-35373 significantly correlated with improved patient survival. Furthermore, human PIWI-like protein 4 was consistently upregulated in ethanol and acetaldehyde-treated normal oral keratinocytes. These results demonstrate that alcohol consumption may cause dysregulation of piRNA expression in HNSCC and in vitro verifications identified 4 piRNAs that may be involved in the pathogenesis of alcohol-associated HNSCC.

Performance of PROMIS Global-10 to Legacy Instruments in Patients With Lateral Epicondylitis.

PURPOSE: To validate the Patient-Reported Outcomes Measurement Information System (PROMIS) Global-10 for patients who have lateral epicondylitis requiring surgical treatment in comparison with other gold standard patient-reported outcomes. METHODS: Sixty-two patients with lateral epicondylitis of the elbow were prospectively enrolled before arthroscopic treatment. Inclusion criteria were patients 18 years of age or older with a diagnosis of lateral epicondylitis. Each patient completed the PROMIS Global-10, EuroQol 5 Dimension (EQ-5D), American Shoulder and Elbow Surgeons (ASES) assessment form, Mayo Elbow Performance Score (MEPS), and Quick Disabilities of the Arm, Shoulder and Hand Score (QuickDASH). Spearman correlations were calculated. Bland-Altman agreement tests were conducted between estimated EQ-5D scores from the PROMIS-10 and actual EQ-5D scores. RESULTS: Correlation between the PROMIS-10 and the EQ-5D was excellent (0.72, P < .0001). Bland-Altman 95% limits of agreement for estimated EQ-5D scores ranged from 0.33 below to 0.21 above actual EQ-5D scores. Correlation of the PROMIS-10 physical score was good to excellent with MEPS (0.61, P < .0001) and QuickDASH scores (0.64, P < .0001) and good with the ASES (0.58, P < .0001). Correlation of the PROMIS mental scores was good with QuickDASH (0.50, P < .0001) and poor with ASES (0.26, P = .0492) and MEPS (0.37, P = .0038). CONCLUSIONS: The PROMIS Global-10 physical scores showed good to excellent correlation with gold standard patient-reported outcome instruments, demonstrating it is a reliable tool for outcome assessment in populations with lateral epicondylitis. Despite the excellent correlation with the EQ-5D, the 95% limit of agreement and high variability among the estimated EQ-5D scores derived from the PROMIS-10 suggests that the PROMIS-10 cannot be used as a substitute for actual EQ-5D scores to derive quality-adjusted life years for economic evaluations and cost-effectiveness research. LEVEL OF EVIDENCE: Level II, development of diagnostic criteria on the basis of consecutive patients.