Alberta Hip and Knee Clinic

The dilated cardiomyopathy with ataxia (DCMA) syndrome is a rare mitochondrial disorder caused by mutations in the poorly understood DNAJC19 gene. Cardiac involvement in DCMA ranges from mild conduction abnormalities to early severe myocardial dysfunction. Although evidence suggests that DCMA is linked to abnormalities in mitochondrial function, the molecular underpinnings of this condition are unclear, and there is no way to predict which patients will develop life-threatening disease. To address this, we developed a metabolic flux assay for assessing the metabolic function of mitochondria in fibroblasts derived from DCMA patients. Using this approach, we discovered that DCMA fibroblasts have elevated glutamine uptake, increased glutamate and ammonium secretion, and elevated lactate production. Moreover, we observed that these cellular perturbations were closely correlated with cardiac dysfunction in a blinded cohort of patient cell lines. These findings suggest that glutamine catabolism is abnormal in DCMA and may serve as a predictor of clinical progression.

Anal cancer risk is elevated among people with HIV. Recent anal cancer incidence patterns among people with HIV in the United States and Canada remain unclear. It is unknown how the incidence patterns may evolve. Using data from the North American AIDS Cohort Collaboration on Research and Design, we investigated absolute anal cancer incidence and incidence trends nationally in the United States and Canada and in different US regions. We further estimated relative risk compared with people without HIV, relative risk among various subgroups, and projected future anal cancer burden among American people with HIV. Between 2001 and 2016 in the United States, age-standardized anal cancer incidence declined 2.2% per year (95% confidence interval = ‒4.4% to ‒0.1%), particularly in the Western region (‒3.8% per year, 95% confidence interval = ‒6.5% to ‒0.9%). In Canada, incidence remained stable. Considerable geographic variation in risk was observed by US regions (eg, more than 4-fold risk in the Midwest and Southeast compared with the Northeast among men who have sex with men who have HIV). Anal cancer risk increased with a decrease in nadir CD4 cell count and was elevated among those individuals with opportunistic illnesses. Anal cancer burden among American people with HIV is expected to decrease through 2035, but more than 70% of cases will continue to occur in men who have sex with men who have HIV and in people with AIDS. Geographic variation in anal cancer risk and trends may reflect underlying differences in screening practices and HIV epidemic. Men who have sex with men who have HIV andpeople with prior AIDS diagnoses will continue to bear the highest anal cancer burden, highlighting the importance of precision prevention.

BackgroundThere is an unmet clinical need for minimally invasive diagnostic tests to improve the detection of grade group (GG) ≥3 prostate cancer relative to prostate antigen‐specific risk calculators. We determined the accuracy of the blood‐based extracellular vesicle (EV) biomarker assay (EV Fingerprint test) at the point of a prostate biopsy decision to predict GG ≥3 from GG ≤2 and avoid unnecessary biopsies.MethodsThis study analyzed 415 men referred to urology clinics and scheduled for a prostate biopsy, were recruited to the APCaRI 01 prospective cohort study. The EV machine learning analysis platform was used to generate predictive EV models from microflow data. Logistic regression was then used to analyze the combined EV models and patient clinical data and generate the patients' risk score for GG ≥3 prostate cancer.ResultsThe EV‐Fingerprint test was evaluated using the area under the curve (AUC) in discrimination of GG ≥3 from GG ≤2 and benign disease on initial biopsy. EV‐Fingerprint identified GG ≥3 cancer patients with high accuracy (0.81 AUC) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cutoff, 95% of men with GG ≥3 would have been recommended a biopsy while avoiding 144 unnecessary biopsies (35%) and missing four GG ≥3 cancers (5%). Conversely, a 5% cutoff would have avoided 31 unnecessary biopsies (7%), missing no GG ≥3 cancers (0%).ConclusionsEV‐Fingerprint accurately predicted GG ≥3 prostate cancer and would have significantly reduced unnecessary prostate biopsies.

Background:Compared with general anesthesia, spinal anesthesia has many benefits for patients undergoing total hip (THA) or total knee (TKA) arthroplasty, but few studies have explored rates of morbidity and mortality. We aimed to compare perioperative outcomes by anesthetic type for patients undergoing THA or TKA for osteoarthritis.Methods:We identified patients who underwent primary THA or TKA from the affiliated institute’s database. We calculated inpatient, 30-day, 60-day and 90-day mortality rates, as well as 90-day perioperative complications, readmissions and length of stay (LOS). We compared outcomes between groups using logistic regression and propensity-adjusted multivariate analysis.Results:We included 6100 (52.2%) patients undergoing THA and 5580 (47.8%) undergoing TKA. We found no differences by anesthetic type in mortality rates up to 90 days after surgery. Patients under spinal anesthesia were less likely to need a blood transfusion (THA odds ratio [OR] 0.75, 95% confidence interval [CI] 0.60 to 0.92; TKA OR 0.52, 95% CI 0.40 to 0.67) and were more likely to be discharged home among those who underwent TKA (OR 1.61, 95% CI 1.30 to 2.00). Patients who received spinal anesthesia for THA had a longer LOS (0.28 d, 95% CI 0.17 to 0.39), and patients who received spinal anesthesia for TKA had a shorter LOS than those who received general anesthesia (−0.34 d, 95% CI −0.51 to −0.18). Anesthetic type was not associated with any difference in adverse events.Conclusion:These findings may inform decisions on anesthetic type for total joint arthroplasty, especially for rapid discharge protocols. Further research is needed to understand postoperative pain and functional outcomes between anesthetic types.

The co-occurrence of frailty and cognitive impairment in older (50+ years) persons with HIV (PWH) is common and increases the risk of poor outcomes. In HIV clinics, the most commonly used frailty measures are the frailty phenotype (FP), which requires measuring grip strength and gait speed to implement, and the frailty index (FI) based on comprehensive health data collected on patients. We examined construct and criterion-related validity (as it predicts cognition) of the Clinical Frailty Scale (CFS), a less resource-intensive approach for assessing frailty, in relation to these more commonly used frailty assessments (FP and FI). A total of 143 older (age 50+) PWH (mean age 57 years; 88% male) seen at the Southern Alberta Clinic underwent both frailty screening with the FP, CFS, and FI and neuropsychological testing. Mixed-effects regressions examined the associations between frailty status and cognition. Concordance with the FP was slightly superior for the CFS than the FI. The FP and CFS had similar associations with domain-specific cognitive performance with frail PWH performing worse than nonfrail individuals on tests requiring manual dexterity (Trail Making Part A and B; Symbol Digit; and Grooved Pegboard; P values <0.05). Neither were associated with executive function, learning, or memory performance. The FI was associated with worse fluency, fine motor skills (Grooved Pegboard), and Trail Making Part A. The CFS is a simple screening tool with good construct and criterion-related validity. It was associated with a similar pattern of cognitive deficits as the FP. If confirmed and the associations are extended to other clinically significant characteristics and outcomes, the CFS can be considered as an alternative to the FP and FI in assessing frailty in older PWH.

Previous researchers have suggested that balance control deficits are detected more accurately with dual-task testing than single-task testing. However, it is necessary to examine the clinimetric properties of dual-task testing before employing it in clinical and research settings. To examine and compare the relative and absolute reliability of the Balance Error Scoring System (BESS), Tandem Gait Test (TGT), and Clinical Reaction Time (CRT) under single and dual-task conditions in uninjured active youth and young adults.Study Design: Single-group, repeated-measures study. Twenty-three individuals [9 female; median age 17 years] completed three trials of the BESS, TGT, and CRT under single and dual-task testing conditions during testing session one. Two raters assessed participants to assess inter-rater reliability. Either later on the same day or the following day, the protocol was repeated by one rater to assess intra-rater reliability. The average of three trials was used to calculate intra-rater (between-session) and inter-rater (within-session) intraclass correlation coefficient (ICC), standard error of measurement (SEM), minimal detectable change (MDC), and Cohen's Kappa coefficient for tests as appropriate under both conditions. Bland-Altman plots (mean difference and 95% limits of agreement) were used to assess for a systematic error associated with a learning effect. Only one participant attended the second session on the following day, while 22 participants (95%) attended the second session within four hours after testing session one. Under single-task testing, estimated ICCs, SEMs, MDCs, and Kappa coefficients ranged from 0.24 to 0.99, 0.3 to 23, 0.8 to 64, and 0.03 to 0.64, respectively. Under dual-task testing, estimated ICCs, SEMs, MDCs, and Kappa coefficients ranged from 0.70 to 0.99, 0.4 to 17, 1.1 to 47, and 0.39 to 0.83, respectively. A learning effect was identified for all tests under all conditions. The BESS is the only clinical test that demonstrated acceptable reliability for clinical use under single-task testing conditions. The BESS, TGT, and CRT all demonstrated acceptable reliability for clinical use under dual-task testing conditions. A practice session should be used to reduce the possible learning effect seen. Further studies examining sources of the systematic error observed are needed. 2b.

### Orthop J Sports Med 2018 ;6:2325967118784897 Rotator cuff disorders are the most common cause of shoulder pain in the general population. Unfortunately, the diagnosis of a rotator cuff tear is not always obvious and can present a diagnostic dilemma, especially in the older patients. When uncertainty exists, expensive imaging such as MRI may be required to aid diagnosis. When it comes to the clinical examination of a shoulder, there are an abundance of ‘special tests’, although individually these tests are limited in diagnostic accuracy for rotator cuff tears. Would not it be great if a battery of clinical tests could predict the likelihood of a tear? Such a tool would be convenient for the primary care physician whose access to ultrasound or MRI is often limited and costly. In this analysis of 301 patients, four diagnostic variables: male sex, Jobe’s test (empty can test), lift-off test and external rotation strength ratio were highly predictive of a rotator cuff tear in patients ≥45 years of age with >4 weeks of shoulder pain. Take home message: This diagnostic aid has the potential to improve clinical identification of rotator …

It is not known whether immune dysfunction is associated with increased risk of death after cancer diagnosis in persons with HIV (PWH). AIDS-defining illness (ADI) can signal significant immunosuppression. Our objective was to determine differences in cancer stage and mortality rates in PWH with and without history of ADI. PWH with anal, oropharynx, cervical, lung cancers, or Hodgkin lymphoma diagnoses from January 2000 to December 2009 in the North American AIDS Cohort Collaboration on Research and Design were included. Among 81,865 PWH, 814 had diagnoses included in the study; 341 (39%) had a history of ADI at time of cancer diagnosis. For each cancer type, stage at diagnosis did not differ by ADI (P > 0.05). Mortality and survival estimates for cervical cancer were limited by n = 5 diagnoses. Adjusted mortality rate ratios showed a 30%-70% increase in mortality among those with ADI for all cancer diagnoses, although only lung cancer was statistically significant. Survival after lung cancer diagnosis was poorer in PWH with ADI vs. without (P = 0.0001); the probability of survival was also poorer in those with ADI at, or before other cancers although not statistically significant. PWH with a history of ADI at lung cancer diagnosis had higher mortality and poorer survival after diagnosis compared to those without. Although not statistically significant, the findings of increased mortality and decreased survival among those with ADI (vs. without) were consistent for all other cancers, suggesting the need for further investigations into the role of HIV-related immune suppression and cancer outcomes.