Citations

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.

Objectives: Ulnar Collateral Ligament (UCL) tears are common in baseball players. When non-operative management fails; reconstruction or repair may be necessary to restore physical function. There is no clear consensus regarding the indications for surgery based on magnetic resonance imaging (MRI) tear characteristics, or the indications for selecting repair over reconstruction. The purpose of this study was to define the indications for UCL surgery based on MRI and to elucidate indications for UCL repair vs reconstruction. Methods: Twenty-six orthopaedic surgeons who treat baseball players were surveyed. Forty-five MRIs were reviewed: 15 without UCL tears, 15 with intra-operatively confirmed partial-thickness tears, and 15 with full-thickness tears. Factors investigated included ligament characteristics (peri-ligamentous or osseous edema, ligament hypertrophy, calcification, partial or full-thickness tearing) and location (proximal, mid-substance, or distal). Surgeons were given a clinical scenario and asked whether 1) surgery was indicated and 2) whether repair or reconstruction was recommended. Odds ratios (OR) and 95% confidence intervals (95%CI) helped identify significant predictors for both queries. Results: The odds of recommending surgical treatment compared to non-operative treatment were 2.4x more likely for a proximal partial-thickness tear, 3.2x for distal partial-thickness tear, 5.1x for distal full- thickness tear, and 7.0x for proximal full-thickness tear (p<0.001). Significant indications for repair included distal partial (OR=1.6, 95%CI 1.0, 2.1, p<0.001) and full-thickness tears (OR=1.7, 95%CI 1.1, 2.3, p<0.001). Repair was 3x less likely recommended for mid-substance full-thickness tears (OR=3.0, 95%CI - 5.0, -1.0, p=0.004). Ultrasound stress testing was requested in 78% of partial tears. Conclusions: Among surgeons surveyed, the highest odds for recommending operative treatment were proximal full-thickness tears, then distal full-thickness, distal partial-thickness, and proximal partial- thickness tears. Repair was most appropriate for partial and full-thickness distal tears, but relatively contraindicated for complete mid-substance UCL tears. Ultrasound stress testing was frequently requested for partial tears. Given the lack of consensus among surgeons, future prospective registries are necessary to determine whether these factors associate with clinical outcomes. [Table: see text]

Objectives: While pitch count and rest guidelines have been promoted for youth and adolescent baseball players for nearly two decades, compliance with guidelines remains poorly understood. The purpose of this study was to determine the frequency of compliance with Pitch Smart guidelines, as well as the association between compliance and range of motion, strength, velocity, injury, and pitcher utilization. Methods: This study was a prospective, multi-center study of high school pitchers, encompassing each region of the United States. Pre-season pitchers were surveyed about their compliance with current off- season rest-related guidelines and history of injury. Pre-season, pitchers underwent standardized physical examinations and pitch velocity was measured. During the high school season that followed, both pitch counts and injury incidence were collected. Results: One hundred and fifteen pitchers participated. Based upon pre-season data, 84% of pitchers had previously violated current pitch recommendation guidelines. During the season, 14% had at least one instance of a violation of the current pitch counts guidelines. Across both the pre-season survey and in-season pitch counts, 89% of players had at least one violation of the current Pitch Smart guidelines. While there were no significant differences in range of motion or strength, those pitchers who were non-compliant with guidelines in the pre-season had higher max pitch velocity (mean±standard deviation 74±8 miles per hour vs. 69±5 miles per hour, p=0.009). Pitchers self-reported their peak velocity at 7 MPH greater than the actual measured velocity. Only a single injury occurred during the season, precluding a comparison between groups. There were no significant differences in the incidence of a history of injury between those pitchers who were noncompliant with between-season rest guidelines (p=0.285). Conclusions: Most high school pitchers are non-compliant with current Pitch Smart guidelines, and they tend to overestimate their peak velocity by 7 MPH. Pitchers with greater velocity were at the highest risk for violating current pitch count recommendations. Since both increased throwing volume and pitch velocity are known risk factors for injury, these athletes may be at particular risk for subsequent injury. research is necessary to understand whether taking three consecutive month rest between seasons prevents pitching-related injury.

Objective Interstitial lung disease (ILD) is an important cause of mortality in some patients with rheumatoid arthritis (RA). Patient-level factors may predict which patients with RA are at the highest risk of developing ILD and are therefore candidates for screening for this complication of the underlying disease. Methods A systematic literature review was performed using PubMed, Embase and Scopus over a 10-year period up to July 2021. Publications reporting patient-level factors in patients with RA with and without ILD that were assessed before development of ILD (or were unchanged over time and therefore could be extrapolated to before development of ILD) were retrieved for assessment of evidence. Genetic variation in MUC5B and treatment with methotrexate were not included in the assessment of evidence because these factors have already been widely investigated for association with ILD. Results We found consistent associations of age, sex, smoking status and autoantibodies with development of ILD. For biomarkers such as Krebs von den Lungen 6, which have been shown to be diagnostic for ILD, there were no publications meeting criteria for this study. Conclusions This analysis provides an initial step in the identification of patient-level factors for potential development of a risk algorithm to identify patients with RA who may be candidates for screening for ILD. The findings represent a useful basis for future research leading to an improved understanding of the disease course and improved care for patients with RA at risk of development and progression of ILD.

Background: Parkinson’s disease (PD) most commonly surfaces at middle age. An earlier onset is named early-onset Parkinson’s disease (EOPD), but the exact definition is a matter of ongoing scientific debate. Objective: To investigate 40-year EOPD incidence trends in a population-based cohort of parkinsonism in Olmsted County, Minnesota. Methods: We used the Rochester Epidemiology Project (REP) to identify all incident EOPD cases in Olmsted County, 1976–2015. A movement-disorder specialist reviewed all cases to confirm the EOPD diagnosis. For EOPD definition, we used two age cut-offs: motor-symptom onset at or before 50 and 55 years. Results: EOPD incidence was 1.43/100,000 person-years for ≤55 and 0.55/100,000 for ≤50 years. Men had a higher incidence in both groups [1.84 vs. 1.03 ( p = 0.04); and 0.70 vs. 0.40 ( p = 0.24), respectively]. EOPD incidence of patients with motor-symptom onset before age 55 increased from 1.02/100.000 person-year 1976–1985, to 1.32/100.000 person-year 2006–2015. A similar trend was observed when ≤50 years cut-off was used (0.28/100,000 person-years 1976–1985, to 0.59/100,000 person-year 2006–2015). However, negative binomial regression found no significant change in incidence per 10 years (RR = 1.04 and 1.24 in the two groups). Incidence was consistently higher in men than women. Median time from EOPD-symptom onset to death was shorter in the EOPD ≤55 group (21.9 years) compared to the EOPD ≤50 group (25.6 years). Conclusion: We observed an increased trend in the incidence of EOPD with both cut-off ages. Overall, incidence of EOPD was 1.43 (≤55) and 0.55 (≤50) cases per 100,000 person-years, higher in men.

Abstract Follicular lymphoma (FL) is clinically heterogeneous, with select patients tolerating extended watch-and-wait, whereas others require prompt treatment, suffer progression of disease within 24 months of treatment (POD24), and/or experience aggressive histologic transformation (t-FL). Because our understanding of the relationship between genetic alterations in FL and patient outcomes remains limited, we conducted a clinicogenomic analysis of 370 patients with FL or t-FL (from Cancer and Leukemia Group B/Alliance trials 50402/50701/50803, or real-world cohorts from Washington University School of Medicine, Cleveland Clinic, or University of Miami). FL subsets by grade, stage, watch-and-wait, or POD24 status did not differ by mutation burden, whereas mutation burden was significantly higher in relapsed/refractory (rel/ref) FL and t-FL than in newly diagnosed (dx) FL. Nonetheless, mutation burden in dx FL was not associated with frontline progression-free survival (PFS). CREBBP was the only gene more commonly mutated in FL than in t-FL yet mutated CREBBP was associated with shorter frontline PFS in FL. Mutations in 20 genes were more common in rel/ref FL or t-FL than in dx FL, including 6 significantly mutated genes (SMGs): STAT6, TP53, IGLL5, B2M, SOCS1, and MYD88. We defined a mutations associated with progression (MAP) signature as ≥2 mutations in these 7 genes (6 rel/ref FL or t-FL SMGs plus CREBBP). Patients with dx FL possessing a MAP signature had shorter frontline PFS, revealing a 7-gene set offering insight into FL progression risk potentially more generalizable than the m7–Follicular Lymphoma International Prognostic Index (m7-FLIPI), which had modest prognostic value in our cohort. Future studies are warranted to validate the poor prognosis associated with a MAP signature in dx FL, potentially facilitating novel trials specifically in this high-risk subset of patients.

Abstract Purpose To develop a pharmacist-driven, exploratory pharmacogenomics implementation model with the goal of creating a process for pharmacists to interpret pharmacogenomics results from RIGHT 10K Study samples and provide electronic consults to providers. Summary A train-the-trainer model program was initiated whereby pharmacogenomics pharmacists developed a documentation template and a quick reference guide as a standard guide to train other pharmacists. Pharmacists completed electronic consults (e-consults) reviewing pharmacogenomics results, with reference to drug-gene interactions, for patients with “semi-urgent” and “clinically actionable” results, defined as those indicating a potential for gene-drug interactions to cause major harm and those indicating a potential for an adverse drug reaction or reduced efficacy, respectively. Outcomes measured included the number of consults over time, number and role of pharmacists involved, average time to complete e-consults over time, and gene-drug pairs for semi-urgent consults per month. A total of 395 pharmacists were trained. The total number of e-consults completed was 2,843: 61 semi-urgent and 2,782 clinically actionable consults. The average time spent per consult was 24 minutes, and the average number of e-consults per pharmacist was 7. CYP2C19-clopidogrel was the most common gene-drug pair targeted in semi-urgent consults. Conclusion Pharmacy leaders planning to implement similar pharmacogenomics programs can utilize this data to estimate hiring needs for future pharmacogenomics implementation, while also considering the potential additional cost of developing resources.

Abstract Background Vitamin D supplementation is common practice for neonates and infants due to limited stores of vitamin D at birth. Although not commonly encountered, vitamin D toxicity can occur due to over-supplementation. However, toxic concentrations are often not included in method validation experiments, and assays often are not validated in the neonatal population. Methods We compared serial 25 hydroxy vitamin D [25(OH)D] measurements in pre-term neonates receiving 25(OH)D supplementation and identified 12 patients wherein concentrations of 25(OH)D were above 50 ng/mL (125 nM) that required additional investigations as the 25(OH)D results did not match the clinical picture. Available samples were compared across 4 immunoassay platforms (LIAISON XL, Roche Cobas e602, Abbott Alinity i, and Siemens Centaur XP) and LC–MS/MS. Results Concentrations of 25(OH)D observed on one individual immunoassay platform (LIAISON XL) fluctuated substantially between subsequent blood draws in select neonates with elevated concentrations. Serum samples from these patients showed variable agreement between LC–MS/MS and other immunoassay platforms. These fluctuations were not explained by the presence of 3-epimer-25(OH)D or 24,25(OH)2D. Conclusions Although we were unable to identify a cause for the variable elevated results, our findings suggest that neonatal 25(OH)D measurements alone should not be used for assessment of nutritional monitoring, and that clinical correlation and other laboratory parameters including ionized calcium should be considered.

PURPOSE A multi-cancer detection test using a targeted methylation assay and machine learning classifiers was validated and optimized for screening in prospective, case-controlled Circulating Cell-free Genome Atlas (ClinicalTrials.gov identifier: NCT02889978 ) substudy 3. Here, we report test performance in a subgroup of participants with symptoms suspicious for cancer to assess the test's ability to potentially facilitate efficient diagnostic evaluation in symptomatic individuals. METHODS We evaluated test performance (sensitivity, specificity, and accuracy of cancer signal origin [CSO] prediction accuracy) in participants with clinically presenting cancers (CPCs) and noncancer with underlying medical conditions and among two subgroups (65 years and older and GI cancers). Overall survival (OS) of participants who had a cancer signal detected/not detected was compared with SEER-based expected survival. RESULTS A total of 2,036 cancer and 1,472 noncancer participants were included. Specificity was high in all noncancer participants (99.5% [95% CI, 98.4 to 99.8]). In participants with CPCs, the overall sensitivity was 64.3% (95% CI, 62.2 to 66.4) and the overall accuracy of CSO prediction in true positives was 90.3%. For GI cancers, the overall sensitivity was 84.1% (95% CI, 80.6 to 87.1). In participants 65 years and older, test performance was similar to that of all participants. Individuals with cancers not detected had a significantly better OS than that expected from SEER ( P < .01). CONCLUSION This test detected a cancer signal with high specificity and CSO prediction accuracy and moderate sensitivity in symptomatic individuals, with especially high performance in participants with GI cancers. The survival analysis implied that the cancers not detected were less clinically aggressive than cancers detected by the test, providing prognostic insights to physicians. This multi-cancer detection test could facilitate efficient workup and stratify cancer risk in symptomatic individuals.