Comparison of Minimally Invasive Procedures to Treat Knee Pain Secondary to Osteoarthritis: A Systematic Review and Meta-Analysis.

PURPOSE: To review and indirectly compare the outcomes of genicular artery embolization (GAE), radiofrequency (RF) ablation, and intra-articular (IA) injection for the treatment of knee pain secondary to osteoarthritis (OA). MATERIALS AND METHODS: A literature review of the MEDLINE and Cochrane databases was conducted with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement in June 2020. The visual analog scale (VAS) was recorded at baseline and at all available time points for each therapy. Standard mean differences were calculated at each time point and compared between treatments to assess the magnitude of the treatment effect. RESULTS: All 3 treatments demonstrated significant differences in VAS scores after therapy. RF ablation produced the greatest significant mean reduction in relative VAS score from baseline at 1 year of follow-up (mean, 0.49; 95% confidence interval, 0.4-0.59; P = .03). GAE reported the most significant reductions in VAS scores across all measured time points. Overall, the comparison did not demonstrate a significant difference in VAS scores among patients receiving IA injections, RF ablation, and GAE. CONCLUSIONS: The current evidence does not suggest a significant difference in outcomes among IA injection, RF ablation, and GAE for knee pain secondary to OA.

Cystinuria Complicated by Anuria From Bilateral Obstructing Stones Requiring Bilateral Mini Percutaneous Nephrolithotomy in a 22-Month-Old.

Pediatric nephrolithiasis is increasing in incidence and presents differently compared to adults. We report a case of nephrolithiasis in a pediatric patient, presenting with complaints of emesis, anuria, hematuria, and abdominal distension, leading to a diagnosis of bilateral obstructing cystine stones requiring bilateral percutaneous nephrolithotomy. Pediatric patients with anuria should be evaluated for bilateral nephrolithiasis as an etiology. Calculous anuria requires prompt recognition of the pathologic process and relief of the obstruction with close follow-up and supportive care until definitive stone management. Bilateral percutaneous nephrolithotomy can provide definitive surgical intervention without significant morbidity.

Effect of Insurance Reimbursement Status on Pre- and Postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) Scores After Arthroscopic Rotator Cuff Repair.

BACKGROUND: Previous studies reported inferior patient-reported outcomes (PROs) after arthroscopic rotator cuff repair for patients receiving workers' compensation (WC) relative to patients with commercial insurance. The extent to which alternative insurance reimbursement, including Medicaid and Medicare, influences outcomes after arthroscopic rotator cuff repair remains understudied. HYPOTHESIS: Compared with patients with commercial insurance reimbursement, patients with WC or government-issued reimbursement would report lower pre- and postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) scores, report higher pre- and postoperative PROMIS Depression (D) and Pain Interference (PI) scores, and experience smaller levels of improvement in all PROMIS domains with surgical intervention. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Demographic and surgical data were extracted from the medical record, and PROMIS domains were prospectively collected. Patients were divided into cohorts based on insurance reimbursement status. Differences between insurance-based cohorts for baseline variables, pre- and postoperative PROMIS scores, and change from baseline to final follow-up (delta) for PROMIS scores were evaluated using Kruskal-Wallis or chi-square tests. Mixed-effects linear regression models were performed to assess the influence of insurance while controlling for other variables. Survival analysis was performed to determine time to achieve minimal clinically important difference (MCID) for each PROMIS domain per cohort. RESULTS: 1252 patients underwent arthroscopic rotator cuff repair, met inclusion criteria, and completed PROMIS questionnaires. Statistically significant differences were noted in demographic variables including age (P < .001), sex (P < .001), ethnicity (P < .001), and body mass index (P < .001) between insurance-based cohorts. Unadjusted analysis revealed significantly higher PF scores and lower PI and D scores for the group with commercial insurance relative to those with Medicare, Medicaid, and WC at 6- and 12-month follow-up (P < .01 all comparisons), except for the Medicare versus commercial subcohort analysis for PI at 6 months (P = .28). These differences persisted for the Medicare, Medicaid, and WC groups (P < .03 all comparisons) after adjustment for confounding variables in linear regression. CONCLUSIONS: The baseline characteristics of patients undergoing arthroscopic rotator cuff repair differed based on insurance reimbursement. Patients with commercial insurance reported improved physical function, decreased pain interference, and improved mood (less depression) relative to patients with government-issued and WC insurance, with maximum improvement 6 to 12 months postoperatively. There were few significant differences between insurance groups in change of PROMIS scores from preoperative to postoperative intervals, indicating that differences in the baseline demographic and surgical characteristics of these groups accounted for differences in response to surgery.

Use of Area Deprivation Index to Predict Minimal Clinically Important Difference for Patient Reported Outcomes Measurement Information System After Arthroscopic Rotator Cuff Repair.

BACKGROUND: Socioeconomic disparities correlate with worse outcomes after arthroscopic rotator cuff repair. However, use of a surrogate to describe socioeconomic disadvantage has been a challenge. The Area Deprivation Index (ADI) is a tool that encompasses 17 socioeconomic variables into a single metric based on census location. HYPOTHESIS: Higher ADI would result in a worse minimal clinically important difference (MCID) for the Patient Reported Outcomes Measurement Information System (PROMIS) and have less improvement in range of motion (ROM) following arthroscopic rotator cuff repair (ARCR). STUDY DESIGN: Cohort study; Level of evidence, 3. METHOD: A retrospective review was performed for patients who underwent arthroscopic rotator cuff repair. Patients in the most socioeconomically disadvantaged quartile (ADIHigh) were compared with the least disadvantaged quartile (ADILow) in the ability to reach MCID. Demographic and surgical features were assessed for attainment of MCID. RESULTS: In total 1382 patients were identified who underwent ARCR, of which a total of 306 patients met final inclusion criteria. A higher percentage of patients within the ADIHigh cohort identified as "Black" or "other" race and had government-issued insurance compared with the ADILow cohort (P < .05). The ADIHigh cohort had significantly worse postoperative forward flexion compared with the ADILow cohort (145.0°± 32.5° vs 156.3°± 23.4°; P = .001) despite starting with comparable preoperative ROM (P = .17). Logistic regression showed that ADI was the only variable significant for predicting achievement of MCID for all 3 PROMIS domains, with the ADIHigh cohort having significantly worse odds of achieving MCID Physical Function (odds ratio [OR], 0.31; P = .001), Pain Interference (OR, 0.21; P = .001), and Depression (OR, 0.28; P = .001). Meanwhile, age, sex, body mass index, and smoking history were nonsignificant. Moreover, "other" for race and Medicare insurance were significant for achievement of MCID Depression but not Physical Function or Pain Interference. Finally, ADI was the main feature for predictive logistic regression modeling. CONCLUSION: ADI served as the only significant predictor for achieving MCID for all 3 PROMIS domains after arthroscopic rotator cuff repair. Patients who face high levels of socioeconomic disadvantage have lower rates of achieving MCID. In addition, patients with greater neighborhood disadvantage demonstrated significantly worse improvement in active forward flexion. Further investigation is required to understand the role of ADI on physical therapy compliance and to identify the barriers that prevent equitable postoperative care.

Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.

Ninety-seven percent of drug-indication pairs that are tested in clinical trials in oncology never advance to receive U.S. Food and Drug Administration approval. While lack of efficacy and dose-limiting toxicities are the most common causes of trial failure, the reason(s) why so many new drugs encounter these problems is not well understood. Using CRISPR-Cas9 mutagenesis, we investigated a set of cancer drugs and drug targets in various stages of clinical testing. We show that-contrary to previous reports obtained predominantly with RNA interference and small-molecule inhibitors-the proteins ostensibly targeted by these drugs are nonessential for cancer cell proliferation. Moreover, the efficacy of each drug that we tested was unaffected by the loss of its putative target, indicating that these compounds kill cells via off-target effects. By applying a genetic target-deconvolution strategy, we found that the mischaracterized anticancer agent OTS964 is actually a potent inhibitor of the cyclin-dependent kinase CDK11 and that multiple cancer types are addicted to CDK11 expression. We suggest that stringent genetic validation of the mechanism of action of cancer drugs in the preclinical setting may decrease the number of therapies tested in human patients that fail to provide any clinical benefit.

FLP-1 neuropeptides modulate sensory and motor circuits in the nematode Caenorhabditis elegans.

Parasitic nematodes infect over one quarter of the population worldwide, causing morbidity in over one billion people. Current anthelmintic drugs are beginning to lose effectiveness due to the presence of resistant strains. We are interested in the role of neuropeptides, which regulate behaviors in all organisms, as another possible target for anthelmintic drugs. FMRFamide-related peptides (FaRPs) are a family of neuropeptides that are conserved throughout the animal kingdom. In particular, nematodes contain the largest family of FaRPs identified thus far and many of these FaRPs are identical among different nematode species; FaRPs in nematodes are collectively referred to as FLPs (FMRFamide-like peptides). However, little is known about the function of these FLPs. We are using the non-parasitic nematode Caenorhabditis elegans as a model for examining FLPs in nematodes. C. elegans contains at least 31 flp genes that encode 72 potential FLPs. Among the flp genes, flp-1 is one of the few that is universally found in nematodes. FLP-1 neuropeptides were previously reported to be involved in sensory and motor functions. However, previous alleles of flp-1 also disrupted a neighboring gene, daf-10. To understand the phenotypes of flp-1, new alleles that specifically disrupt flp-1 were characterized. The previously reported locomotory and egg-laying defects were found to be due to loss of flp-1, while the osmolarity defect is due to loss of daf-10. In addition, loss of flp-1 and daf-10 both cause several phenotypes that increase in severity in the double mutants by disrupting different neurons in the neural circuits.