Citations

Objectives Viscosupplementation, intra‐articular injection of hyaluronic acid (HA), for knee osteoarthritis has fallen somewhat out of favor, with studies failing to show consistent benefits in pain reduction. Hyaluronic acid must enter the joint space to be beneficial; however, landmark‐guided injection can be substantially inaccurate, especially in obese patients. We aimed to determine whether ultrasound (US) guidance to ensure needle placement for HA knee injection resulted in improved outcomes as reflected by surgery‐free survival compared to landmark‐guided HA knee injection. Methods All community‐dwelling patients in 6 contiguous surrounding counties receiving HA knee injection either by landmark guidance (n = 647) or by US guidance (n = 500) were analyzed for the degree of arthritis, body mass index, follow‐up injection, and subsequent need for knee arthroplasty. A subgroup analysis of obese patients was also performed. Results The US‐ and landmark‐guided HA injection cohorts were similar with respect to sex, body mass index, and the degree of arthritis. Of 1147 patients receiving knee HA injection, 462 subsequently underwent knee arthroplasty. Significantly fewer patients in the US‐guided HA injection cohort went to surgery (33.2%) compared to the landmark‐guided cohort (45.8%; P < .001). The subgroup analysis for obese patients showed even larger differences (34.8% versus 51.8%; P < .001). Conclusions Knee osteoarthritis treatment by viscosupplementation can be optimized by US guidance, ensuring intra‐articular needle placement. Using an objective surgical outcome, our study shows that rethinking viscosupplementation to ensure intra‐articular delivery improves effectiveness. Patients receiving US‐guided knee HA injection were significantly less likely to undergo subsequent knee arthroplasty than patients receiving landmark‐guided HA injection.

Background: Social media use is now a central aspect of adolescent life and development. Little is known about the clinical implications of social media use in children and adolescents presenting in acute crisis for psychiatric admission. This study sought to compare the potential effects of social media use among middle and high school students on outcomes of psychiatric morbidity. It was hypothesized that among social media users, high school students would have greater psychiatric morbidity compared with middle school students. Methods: The research team extracted clinical and demographic data from adolescents (aged 12–17 years) presenting for acute psychiatric admission who also had documented social media use ( N = 56). Educational status, middle school ( n = 21) versus high school ( n = 35), was examined as an independent variable. Psychotropic medication use, self-injurious behavior, suicide risk, and suicidal ideation were examined as dependent variables in logistic regression models. Results: High school students using social media had significantly greater predicted odds of psychotropic medication use and self-injurious behavior compared with students in middle school who used social media. High school students using social media had greater, although not statistically significant, predicted odds of suicide risk and suicidal ideation compared with middle school students using social media. Conclusions: Social media use is likely an important factor to consider in psychiatric evaluations. The present findings suggest that social media use in high school students is associated with greater psychiatric morbidity compared with middle school students. Further research could illuminate the developmental lines of social media use and age-specific risks.

Abstract Context SDHB mutations are found in an increasing number of neoplasms, most notably in paragangliomas and pheochromocytomas (PPGLs). SDHB-PPGLs are slow-growing tumors, but ∼50% of them may develop metastasis. The molecular basis of metastasis in these tumors is a long-standing and unresolved problem. Thus, a better understanding of the biology of metastasis is needed. Objective This study aimed to identify gene methylation changes relevant for metastatic SDHB-PPGLs. Design We performed genome-wide profiling of DNA methylation in diverse clinical and genetic PPGL subtypes, and validated protocadherin γ-C3 (PCDHGC3) gene promoter methylation in metastatic SDHB-PPGLs. Results We define an epigenetic landscape specific for metastatic SDHB-PPGLs. DNA methylation levels were found significantly higher in metastatic SDHB-PPGLs than in SDHB-PPGLs without metastases. One such change included long-range de novo methylation of the PCDHA, PCDHB, and PCDHG gene clusters. High levels of PCDHGC3 promoter methylation were validated in primary metastatic SDHB-PPGLs, it was found amplified in the corresponding metastases, and it was significantly correlated with PCDHGC3 reduced expression. Interestingly, this epigenetic alteration could be detected in primary tumors that developed metastasis several years later. We also show that PCDHGC3 down regulation engages metastasis-initiating capabilities by promoting cell proliferation, migration, and invasion. Conclusions Our data provide a map of the DNA methylome episignature specific to an SDHB-mutated cancer and establish PCDHGC3 as a putative suppressor gene and a potential biomarker to identify patients with SDHB-mutated cancer at high risk of metastasis who might benefit from future targeted therapies.

Background:Lenalidomide plus rituximab (R2) has established efficacy and a tolerable safety profile in patients with previously untreated and relapsed/refractory (R/R) indolent NHL. This includes patients with marginal zone lymphoma (MZL) who are generally treated in a similar manner to follicular lymphoma (FL).Aims:Primary results for the AUGMENT study in R/R FL grade 1–3a and MZL showed significantly improved progression‐free survival (PFS) for R2 over R/placebo in the overall population and in the subgroup analyses, with the exception of the MZL subgroup. Given the small sample size for MZL patients, post hoc analyses of baseline characteristics and univariate/multivariate analyses of PFS were conducted to examine possible explanations for these results.Methods:The phase III AUGMENT study randomized patients 1:1 to R2 (lenalidomide PO 20 mg/day (d), d1–21/28 X12 cycles plus rituximab IV 375 mg/m2 weekly in cycle 1 and d1 of cycles 2–5) or rituximab‐placebo (R/placebo; same dosing schedule). PFS by 2007 IWG (without PET) was the primary endpoint. Post hoc Cox regression models were used for univariate analysis of one risk factor and multivariate analyses including treatment arm and significant risk factors (P < 0.05) from the univariate analyses.Results:A total of 63/358 (18%) MZL patients were part of the overall study population, including n = 14/16 MALT, n = 9/6 splenic, and n = 8/10 nodal MZL subtypes for respective R2 and R/placebo arms. Numerical differences between treatment arms for baseline demographics and disease characteristics for MZL patients favoring the R/placebo arm were: fewer R2 patients had an ECOG score of 0 (55% R2 vs 72% R/placebo), and more R2 (vs R/placebo) patients were older (≥65 y: 68% vs 59%; ≥70 y: 42% vs 38%), were refractory to the last prior regimen (13% vs 3%), had Ann Arbor stage IV disease at enrollment (65% vs 41%), high‐risk MALT‐IPI score (50% vs 19%), elevated LDH (29% vs 19%), B symptoms (13% vs 3%), and high tumor burden per GELF criteria (65% vs 56%). The most common grade 3/4 AEs for MZL patients receiving R2 vs R/placebo, respectively, were neutropenia (47% vs 16%), pneumonia (3% vs 13%), and leukopenia (10% vs 0). A total of 5 deaths occurred in the R2 arm (most associated with progression of disease; 2 deaths occurred early at 3 and 13 days after randomization [one prior to receiving R2 and one 2 days after treatment initiation]) and 2 in the R/placebo arm. Despite worse prognostic features, best response was improved with R2 (vs R/placebo) with ORR = 65% vs 44% (P = 0.13) and CR = 29% vs 13% (P = 0.13), although neither were statistically significant. Improved response rates did not translate into a survival advantage for R2. Median PFS for MZL patients was 20.2 mo R2 vs 25.2 mo R/placebo (HR = 1.00; 95% CI, 0.47–2.13; P = 1.0). Univariate analyses showed that several baseline factors were prognostic for MZL patients (P < 0.05): Ann Arbor stage IV, elevated LDH, and unfit for chemotherapy (Table). Multivariate analyses adjusting for the imbalance in these 3 significant prognostic factors showed an adjusted PFS HR of 0.51 (95% CI, 0.20–1.28) favoring the R2 arm, similar to the PFS HR in the overall population (HR = 0.46; 95% CI, 0.34–0.63). The univariate and multivariate analyses suggested that the imbalance in baseline prognostic factors impacted PFS results for MZL patients.Summary/Conclusion:Overall, these findings suggest that the PFS results in MZL patients were negatively impacted by the imbalance in baseline prognostic factors and more aggressive disease in the R2 over the R/placebo arm.image

Background: The impact of maturation on lower extremity strength and function after anterior cruciate ligament reconstruction (ACLR) may help guide future studies of age-specific rehabilitation. Hypothesis Pediatric ACLR patients would demonstrate higher thigh strength symmetry and knee-related function at return to sport (RTS) compared with adolescent and young adult participants who underwent traditional ACLR. Study Design: Prospective cohort study. Level of Evidence: Level 2. Methods: A total of 144 young athletes at the time of RTS clearance post-ACLR were classified into 3 maturational groups (pediatric, n = 16 with physeal-sparing ACLR [mean age = 12.3 years; range = 9.2-14.6 years]; adolescent, n = 113 [mean age = 16.5 years; range = 14.1-19.8 years]; young adult, n = 15 [mean age = 22.0 years; range = 20.5-24.9 years]). Quadriceps and hamstring strength were measured using an electromechanical dynamometer. Knee-related function was measured using the International Knee Documentation Committee (IKDC) subjective form and single-leg hop tests. The Limb symmetry Index (LSI) was used in calculations for hop and strength tests. Group differences were compared with Kruskal-Wallis tests and Mann-Whitney U post hoc tests. Proportions of participants meeting literature-recommended RTS criterion cutoffs were compared among the groups using chi-square tests. Results: The pediatric group demonstrated higher quadriceps LSI ( P = 0.01), IKDC scores ( P < 0.01), single-hop LSI ( P < 0.01), and crossover-hop LSI ( P = 0.02) compared with the young adult group. In addition, the pediatric group demonstrated higher IKDC scores ( P < 0.01) and single-hop LSI ( P = 0.02) compared with the adolescent group. The adolescent group demonstrated higher IKDC scores ( P < 0.01), single-hop LSI ( P = 0.02), and crossover-hop LSI ( P = 0.03) compared with the young adult group. The proportions of participants meeting all RTS criterion cutoffs were highest in the pediatric group and lowest in the young adult group ( P = 0.03). Conclusion: Young athletes at RTS clearance after pediatric ACLR demonstrated higher quadriceps strength symmetry and knee-related function than adolescents and young adults after traditional ACLR. Clinical Relevance: These findings demonstrate the need for further study regarding the impact of these group differences on longitudinal outcomes after ACLR, including successful RTS and risk of second ACL injury.