Mechanistic regulation of planarian shape during growth and degrowth.

Adult planarians can grow when fed and degrow (shrink) when starved while maintaining their whole-body shape. It is unknown how the morphogens patterning the planarian axes are coordinated during feeding and starvation or how they modulate the necessary differential tissue growth or degrowth. Here, we investigate the dynamics of planarian shape together with a theoretical study of the mechanisms regulating whole-body proportions and shape. We found that the planarian body proportions scale isometrically following similar linear rates during growth and degrowth, but that fed worms are significantly wider than starved worms. By combining a descriptive model of planarian shape and size with a mechanistic model of anterior-posterior and medio-lateral signaling calibrated with a novel parameter optimization methodology, we theoretically demonstrate that the feedback loop between these positional information signals and the shape they control can regulate the planarian whole-body shape during growth. Furthermore, the computational model produced the correct shape and size dynamics during degrowth as a result of a predicted increase in apoptosis rate and pole signal during starvation. These results offer mechanistic insights into the dynamic regulation of whole-body morphologies.

Editorial Commentary: Older Patients Without Degenerative Joint Disease Can Have Excellent Outcomes After Hip Arthroscopy.

Early research on hip arthroscopy for femoroacetabular impingement syndrome identified patient age as a risk factor for poor outcomes and heightened revision rates. However, more recent research challenges this dogma. Disparities between chronologic and physiologic age exist among patients. In addition, orthopaedic pathology (such as degenerative chondral or labral pathology) can correlate with age, so the use of age, and using age as a predictor of outcome, may be biased by this confounding effect. Older patients without degenerative joint disease can have excellent outcomes after hip arthroscopy. Recent research shows that patients older than the age of 40 years undergoing hip arthroscopy for femoroacetabular impingement syndrome demonstrate outcomes comparable with younger patients at 10-year follow-up. However, older patients were at greater risk for conversion to total hip arthroplasty. In our experience, in the absence of joint degeneration, patients older than the age of 40 years experience predictable and durable relief following arthroscopic management of femoroacetabular impingement syndrome. These outcomes result from sound surgical indications, appropriate preoperative counseling, and meticulous surgical technique. We ought not replace joints we can preserve, and age is not the most determinative factor regarding outcome of otherwise well-indicated and performed hip arthroscopy.

Relationship between quantitative strength and functional outcomes in the phase 2 FORTITUDE-ALS trial.

OBJECTIVE: To assess the relationship among measurements of strength, function, and quality of life in an amyotrophic lateral sclerosis (ALS) clinical trial. METHODS: In the FORTITUDE-ALS clinical trial (NCT03160898), 456 participants in the full-analysis set were treated with either reldesemtiv or placebo for 12 weeks; this post hoc analysis included all participants regardless of treatment assignments. Assessments included slow vital capacity (SVC), the ALS Functional Rating Scale-Revised (ALSFRS-R), and the 5-item ALS Assessment Questionnaire (ALSAQ-5). Muscle strength was measured quantitatively with hand-held dynamometry, and grip strength with a dedicated dynamometer. The relationship between strength and ALSFRS-R fine and gross motor domain scores, or responses to ALSAQ-5 questions on hand function and walking, was assessed with Spearman's rank correlation. The relationship between mean upper- or lower-extremity muscle strength and specific ALSFRS-R domains was modeled using principal-components analysis. RESULTS: Upper-extremity muscle strength and hand grip were highly correlated with ALSFRS-R fine motor scores and the ALSAQ-5 hand function question. Similarly, lower-extremity strength correlated well with ALSFRS-R gross motor domain and the ALSAQ-5 walking question. For SVC, correlation was poor with the ALSFRS-R respiratory domain, but stronger with the total score, potentially reflecting the insensitivity of the respiratory questions in the scale. Upper- and lower-extremity strength were both strong predictors of ALSFRS-R domain scores. CONCLUSIONS: In this analysis of data from an ALS clinical trial, muscle strength quantified by dynamometry was strongly correlated with functional capacity. These results suggest that muscle strength directly relates to specific functions of importance to people with ALS.

Secondary Hip Labral Reconstruction Yields Inferior Minimum 2-Year Functional Outcomes to Primary Reconstruction Despite Comparable Intraoperative Labral Characteristics.

PURPOSE: To compare intraoperative labral characteristics and minimum 2-year functional outcomes of allograft labral reconstruction in primary versus revision hip arthroscopy across multiple orthopaedic centers. METHODS: A retrospective multicenter hip arthroscopy registry was queried for patients with completed labral reconstruction surgeries from January 2014 to March 2023 with completed 2-year international Hip Outcome Tool-12 (iHOT-12) reports. Age, sex, and major intraoperative variables also were collected. Patients were placed in cohorts based on whether their arthroscopic allograft labral reconstruction was a primary procedure or secondary procedure (reconstruction following failed hip arthroscopy). One-way analysis of variance was performed on continuous variables. χ2 test was performed on categorical variables. Achievement of minimal clinically important difference (MCID), Patient Acceptable Symptom State (PASS), and Substantial Clinical Benefit (SCB) also was assessed. RESULTS: In total, 77 patients met the inclusion and exclusion criteria and had complete information. The primary reconstruction group (n = 50) was significantly older than the secondary reconstruction group (n = 27) (47.5 ± 10.5 vs 39.1 ± 8.8 years; P = .001). In both cohorts, most patients had labral bruising, advanced labral degeneration, and/or grade III complexity of labral tearing. There was no difference in any recorded intraoperative findings (P = .160, P = .783, P = .357, respectively). Each cohort experienced significant improvement in iHOT-12 scores (P < .0001). However, patients undergoing secondary labral reconstruction reported inferior iHOT-12 scores (60.1 ± 29.2 vs 74.8 ± 27.0; P = .030). Patients undergoing primary reconstruction were more likely to reach MCID, PASS, and nearly normal SCB (92 vs 66.7%, P = .024; 68.0 vs 40.7%, P = .021; 76.0 vs 48.1%, P = .014, respectively). CONCLUSIONS: Primary and secondary allograft labral reconstruction show clinical improvement, but primary reconstruction demonstrates better outcomes and greater percentage of patients reaching MCID, PASS, and nearly normal SCB than reconstruction in the revision setting. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic case-control study.

COURAGE-ALS: a randomized, double-blind phase 3 study designed to improve participant experience and increase the probability of success.

Objective: To determine the target population and optimize the study design of the phase 3 clinical trial evaluating reldesemtiv in participants with amyotrophic lateral sclerosis (ALS).Methods: We evaluated the phase 2 study of reldesemtiv, FORTITUDE-ALS, to inform eligibility criteria and design features that would increase trial efficiency and reduce participant burden of the phase 3 trial.Results: In FORTITUDE-ALS, the effect of reldesemtiv was particularly evident among participants in the intermediate- and fast-progressing tertiles for pre-study disease progression. These participants most often had symptom onset ≤24 months and an ALS Functional Rating Scale-Revised (ALSFRS-R) total score ≤44 at baseline. Compared with the overall FORTITUDE-ALS population, the subgroup meeting these criteria declined by fewer ALSFRS-R points at 12 weeks (difference of least-squares mean [SE] versus placebo 1.84 [0.49] and 0.87 [0.35] for the overall population). These inclusion criteria will be used for the phase 3 clinical trial, COURAGE-ALS, in which the primary outcome is the change in ALSFRS-R total score at week 24. We also measure durable medical equipment use and evaluate strength in muscles expected to change rapidly. To reduce participant burden, study visits are often remote, and strength evaluation is simplified to reduce time and effort.Conclusions: In COURAGE-ALS, the phase 3 clinical trial to evaluate reldesemtiv, the sensitivity of detecting a potential treatment effect may be increased by defining eligibility criteria that limit the proportion of participants who have slower disease progression. Implementing remote visits and simplifying strength measurements will reduce both site and participant burden.ClinicalTrials.gov identifiers: NCT03160898 (FORTITUDE-ALS) and NCT04944784 (COURAGE-ALS).

Health utilities and quality-adjusted life years for patients with amyotrophic lateral sclerosis receiving reldesemtiv or placebo in FORTITUDE-ALS.

AIMS: To estimate the health utilities and quality-adjusted life years (QALYs) in patients with amyotrophic lateral sclerosis (ALS) receiving reldesemtiv versus placebo in FORTITUDE-ALS. MATERIALS AND METHODS: We performed a post hoc analysis of clinical trial data from FORTITUDE-ALS (NCT03160898). This Phase IIb, double-blind, randomized, dose-ranging, placebo-controlled, parallel-group, 12-week trial evaluated reldesemtiv in patients with ALS. Health utilities from the five-level version of the EuroQol five-dimensional questionnaire (EQ-5D-5L) were estimated using ALS Functional Rating Scale-Revised (ALSFRS-R) scores collected during the trial. QALYs were estimated using the area under the curve method. RESULTS: The full analysis set consisted of 456 patients (reldesemtiv n = 342, placebo n = 114), who received at least one dose of the double-blind study drug, and had ALSFRS-R assessed at baseline and at least one post-baseline assessment. The difference in EQ-5D-5L utility least-squares (LS) mean change from baseline to week 12 for reldesemtiv versus placebo, adjusted for baseline values, was statistically significant (0.03, 95% confidence interval [CI]: 0.01, 0.05; p = .0008). The incremental QALY of reldesemtiv versus placebo adjusted for baseline utility values showed a modest, but statistically significant, difference (0.004, 95% CI: 0.001, 0.007; p = .0058). CONCLUSIONS: This post hoc analysis of FORTITUDE-ALS suggests that reldesemtiv showed a modest but significant benefit in health utilities and QALYs compared with placebo. Future long-term studies that include direct collection of EQ-5D-5L data will be needed to confirm our findings. CLINICALTRIALS.GOV IDENTIFIER: NCT03160898.

MiToS and King's staging as clinical outcome measures in ALS: a retrospective analysis of the FORTITUDE-ALS trial.

OBJECTIVE: To evaluate the Milano-Torino staging (MiToS) and King's staging systems as potential outcome measures for clinical trials in amyotrophic lateral sclerosis (ALS) by assessing these outcomes in FORTITUDE-ALS. METHODS: This was a post hoc analysis of the phase 2b FORTITUDE-ALS trial (NCT03160898), a double-blind, randomized, dose-ranging, placebo-controlled, parallel-group study of reldesemtiv in patients with ALS. The treatment period was 12 weeks, with a follow-up assessment at week 16. Patients were retrospectively classified into MiToS and King's stages. Outcomes were the mean time maintaining baseline stage and risk of progression from the baseline stage to a later stage. RESULTS: The full analysis set consisted of 456 patients randomized 3:1 (reldesemtiv n = 342, placebo n = 114) who received at least one dose of double-blind study drug and had at least one post-baseline assessment. At baseline, MiToS and King's stages were balanced between the reldesemtiv and placebo groups: >99% of patients were in MiToS stage 0 or 1 and King's stage 1, 2 or 3. Time of maintaining the baseline stage was similar in both groups, for each staging system. The two staging systems exhibited considerably disparate results for risk of progression from baseline to a later stage: hazard ratio (HR) = 0.62 (95% confidence interval [CI] 0.38, 0.99) for MiToS and HR = 0.96 (95% CI 0.63, 1.44) for King's. CONCLUSION: This exploratory analysis showed the feasibility of MiToS and King's staging as potential outcome measures in ALS. Additional studies of these staging systems are needed to further explore their utility in ALS clinical trials.

Editorial Commentary: The Importance of Capsular Closure Following Hip Arthroscopy-Leave No Trace: An Outdoorsman's Ramblings.

After a decade-long paradigm shift and an evidence-based enormous increase in the prevalence of hip arthroscopic procedures, hip capsular closure following arthroscopy, once a rare procedure, is now performed in the majority of surgical cases. This results from improved surgeon experience, refined surgical technologies and techniques and an explosion of research regarding stability of the hip joint. Once viewed as inherently stable, it is become clear that meticulous capsular management and closure can not only maintain joint stability but is a treatment for and/or prevents micro-instability. Recent research shows that hip capsular closure can improve outcomes and return to sport rates in the highest demand athletes having hip arthroscopy. Close the capsule!

Symptom duration predicts inferior mid-term outcomes following hip arthroscopy.

INTRODUCTION: Studies have demonstrated a negative relationship between the length of time with symptoms and patient-reported outcome measures in primary hip arthroscopy. Our aim was to expand the generalizability of this finding with a multi-center cohort. METHODS: A multi-center hip arthroscopy registry was queried for patients undergoing primary hip arthroscopy from 2014 to 2017. Patients were stratified according to whether pre-operative symptom duration exceeded two years or did not exceed two years. A Wilcoxon rank sum test was performed for differences in two year post-operative outcome scores. Logistic regression models analyzed the influence of symptom duration on achieving clinically meaningful thresholds (minimum clinically important difference, patient-acceptable symptom state, substantial clinical benefit) when controlling for baseline scores, age, BMI, and sex. RESULTS: Seven hundred forty-four patients met the inclusion criteria, from which 620 had complete outcomes information. The mean ± SD 2-year iHOT-12 scores of patients with symptom duration greater than two years (69 ± 26) were significantly lower than patients with symptom duration less than two years (77 ± 23) (Dunn test, p < 0.001). Chronic duration of pain was a negative predictor of achieving iHOT-12 MCID (0.47 [0.31-0.72]), PASS (0.53 [0.37-0.76]), and SCB (0.67 [0.47-0.94]). CONCLUSION: When controlling for differences in baseline demographic factors and pre-operative iHOT-12 scores, patients with chronic pain report poorer functional outcomes at mid-term follow-up. These results suggest that chronic pain predicts inferior outcomes from primary hip arthroscopy and that surgical intervention at earlier time points may be beneficial in achieving better outcomes.

Relationship of Average Outcomes Scores and Change in Status Requires Further Interpretation Between 1 and 2 Years Following Hip Arthroscopy.

BACKGROUND: Previous studies have demonstrated a clinically impactful change in patients between 1 and 2 years after hip arthroscopy. Assessment of differences in patient-specific factors between patients who remain the same and those who change (ie, either improve or decline) could provide valuable outcome information for orthopaedic surgeons treating those patients. PURPOSE: To identify patients who experienced change in functional status between 1 and 2 years after hip arthroscopy for femoroacetabular impingement syndrome and assess differences in patient-specific factors between those who improved, remained the same, or declined in functional status. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Prospectively collected data for patients who underwent hip arthroscopy at 1 of 7 centers were analyzed retrospectively at 1 year and 2 years postoperatively. Patients were categorized as "improved,""remained the same," or "declined" between 1- and 2-year follow-up based on the 12-item International Hip Outcome Tool (iHOT-12) minimal clinically important difference (MCID) value. A 1-way analysis of variance was used to assess differences in iHOT-12 scores, age, body mass index (BMI), alpha angle, and center-edge angle (CEA) between groups. Chi-square analyses were used to assess differences in the proportions of male and female patients in the outcome groups. RESULTS: The study included 753 patients (515 women and 238 men), whose mean ± SD age was 34.7 ± 12 years. Average 1-year (±1 month) and 2-year (±2 months) iHOT-12 scores for all patients were 73.7 and 74.9, respectively. Based on the calculated MCID of ±11.5 points, 162 (21.5%) patients improved, 451 (59.9%) remained the same, and 140 (18.6%) declined in status between 1- and 2-year follow-up. Those who improved between 1 and 2 years had lower 1-year iHOT-12 scores (P < .0005). We found no difference in age, BMI, alpha angle, CEA, or sex between groups (P > .05). CONCLUSION: Between 1- and 2-year follow-up assessments, 21.5% of patients improved and 18.6% declined in self-reported functional status. Those with iHOT-12 scores indicating abnormal function at 1 year improved beyond the MCID at 2 years follow-up. Thus, any decisions about the failure or success of arthroscopic hip procedures should not be made until at least the 2-year follow-up. Failing to thrive at 1-year follow-up may not accurately predict outcomes at year 2 or beyond. This could potentially decrease the perceived need for revision surgery in patients who do not thrive before 2-year follow-up.

Primary Arthroscopic Labral Management: Labral Repair and Complete Labral Reconstruction Both Offer Durable, Promising Results at Minimum 5-Year Follow-up.

BACKGROUND: Increased understanding of the acetabular labrum's role in hip joint biomechanics has led to a greater focus on the conservation and restoration of normal labral anatomic characteristics; however, labral repair is often not possible in the setting of severe intrasubstance damage or deficiency. PURPOSE: To compare 5-year postoperative patient-reported outcomes between hips treated with primary complete arthroscopic labral reconstruction and those treated with primary labral repair. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All hips that underwent primary labral repair or reconstruction by the senior surgeon between January 2015 and December 2015 were included. Hips that had undergone a previous intra-articular procedure were excluded. Visual analog scales and patient-reported outcome (PRO) instruments were completed by patients within 1 week before surgery as a baseline measurement, between 22 and 26 months postoperatively for 2-year outcomes, and between 58 and 62 months for 5-year outcomes. PRO scores collected included the modified Harris Hip Score (mHHS), the 12-Item International Hip Outcome Tool, and the visual analog scale for pain and satisfaction. Pain and satisfaction were assessed using visual analog scales. RESULTS: A total of 68 primary labral repairs and 62 primary complete labral reconstructions were included in the final analysis. Patients in the reconstruction cohort were older (38.3 vs 29.9 years; P < .001), had a higher incidence of severe labral tearing (62.90% vs 5.88%; P < .001), required a greater number of concomitant procedures (P < .001), and were more likely to have Beck grade III or IV chondral damage (12.94% vs 1.47%; P < .001). Both groups demonstrated statistically significant increases in outcome scores at minimum 5-year follow-up. Patients who underwent labral reconstruction had a significantly greater increase in mHHS from the preoperative assessment to latest follow-up compared with patients undergoing labral repair (27.43 vs 17.13; P = .04). No statistically significant differences between the 2 cohorts were found in achievement of minimal clinically important difference, Patient Acceptable Symptom State, maximum outcome improvement, and substantial clinical benefit at latest follow-up (P > .05). In total, 2 patients in the repair cohort and 3 patients in the reconstruction cohort required revision arthroscopy (P = .574). Further, 1 patient from each group converted to arthroplasty (P = .947). CONCLUSION: The results of this study suggest that primary complete labral reconstruction is a viable surgical option for hips with moderate to severe labral pathology. At minimum 5-year follow-up, labral reconstruction produced similar outcomes to labral repair despite less favorable preoperative patient characteristics in the reconstruction cohort.

In situ probe and inhibitory RNA synthesis using streamlined gene cloning with Gibson assembly.

The synthesis of single-stranded riboprobes or double-stranded RNAs for in situ hybridization and gene knockdowns often use vectors that require time-consuming plasmid restriction digests and inefficient gel purifications. Here, we present a faster protocol for the simultaneous plasmid restriction digestion and Gibson assembly of vectors for the synthesis of both riboprobes and double-stranded RNAs for in situ and RNA interference experiments, respectively. We illustrate the protocol with planaria in situ and RNAi assays, but it is applicable to any organism.

Acetabular Cartilage Lesions Predict Inferior Mid-Term Outcomes for Arthroscopic Labral Repair and Treatment of Femoroacetabular Impingement Syndrome.

PURPOSE: To analyze the effect of acetabular chondrosis at a minimum of 2 years following hip arthroscopy in patients undergoing labral repair and treatment of femoroacetabular impingement. METHODS: From 2014 to 2017, patients undergoing arthroscopic labral repair were prospectively enrolled in a multicenter hip arthroscopy registry. The registry was retrospectively queried for primary labral repair patients with complete 2-year outcomes and a Tonnis grade of less than 2. Patients were grouped according to severity of articular cartilage damage noted intraoperatively using the Beck classification system: none, low-grade (Grade 1 or 2), or high-grade (Grade 3 or 4) damage. A Kruskal-Wallis test and post hoc Dunn's test with Holm correction compared 2-year postoperative outcome scores of the iHOT-12 scale between groups. The proportion of patients in each cohort who achieved the clinically significant thresholds of the minimum clinically important difference (MCID), patient-acceptable symptom scale, and substantial clinical benefit (SCB) were analyzed. Multivariate logistic regression models identified predictors of achieving clinical thresholds while controlling for demographic variation. RESULTS: 422 patients met inclusion criteria, from which 347 completed 2-year outcomes. All groups experienced improvement in iHOT-12 scores from baseline to follow-up (P < .001). iHOT-12 scores at follow-up were inferior for Low-Grade Damage and High-Grade Damage Groups relative to the No Damage Group (P = .04; P = .03). When accounting for age, body mass index, gender, and preoperative iHOT-12 scores in logistic regression models, the presence of high-grade lesions was a negative predictor for achieving SCB (OR [95% CI], 0.54 [0.29-0.96]) and low-grade lesions a negative predictor for achieving MCID (0.50 [0.27-0.92]. Among patients with high-grade lesions, there was no significant difference in 2-year iHOT-12 scores between those undergoing chondroplasty (n = 50) and those undergoing microfracture (n = 14) (P = .14). CONCLUSIONS: Acetabular cartilage damage portends inferior patient-reported outcomes 2 years after primary labral repair and treatment of femoroacetabular impingement. The presence of cartilage lesions was a negative predictor of individual achievement of several clinical thresholds. LEVEL OF EVIDENCE: III, Retrospective comparative cohort.

Labral Degeneration Predicts Inferior Mid-Term Outcomes in Hip Labral Repair: A Multicenter Comparative Analysis.

PURPOSE: To analyze and compare the mid-term outcomes of hip arthroscopy for patients with and without labral degeneration from multiple orthopaedic centers. The purpose of this research is to develop an understanding of the impacts of labral degeneration on patient outcomes following arthroscopic treatment of labral tears. METHODS: A prospective multicenter hip arthroscopy registry was queried for primary surgeries from January 2014 to October 2017 with completed 2-year International Hip Outcome Tool-12 (iHOT-12) reports. Patients were placed into cohorts based on the presence or absence of labral degeneration noted intraoperatively during hip arthroscopy. Degeneration was defined as yellowing, ossification, or calcification present in at least 50% of the labrum. Differences in baseline variation between groups were assessed with a Wilcoxon rank-sum test or χ2 test. Two-year outcomes were assessed with iHOT-12. Multivariate logistic regression models were fitted while controlling for age, body mass index, sex, and preoperative iHOT-12 scores to identify significant predictors of achieving the clinically significant thresholds of minimal clinically important difference, substantial clinical benefit, and patient-acceptable symptom scale. RESULTS: In total, 735 patients met inclusion criteria, of whom 613 had complete outcomes information. Relative to the control group, the labral degeneration group was significantly older (mean age 44 ± 11 years vs 33 ± 12 years; P < .01). Both groups experienced statistically significant improvement in iHOT-12 scores from baseline to final follow-up (P < .001); however, patients with labral degeneration reported inferior 2-year iHOT-12 scores when compared with patients without degeneration (P < .001). In the logistic regression models, labral degeneration was a significant negative predictor of achieving iHOT-12 minimal clinically important difference (odds ratio [OR] 0.47; 95% confidence interval [95% CI] 0.28-0.79), patient acceptable symptom state (OR 0.50; 95 CI 0.32-0.77), and substantial clinical benefit (OR 0.58; 95% CI 0.37-0.89). CONCLUSIONS: The results of our study conclude that patients with nondegenerative labral tissue at the time of repair have superior patient-reported outcomes at mid-term follow-up. The presence of labral degeneration was a negative predictor of achieving clinically significant thresholds after controlling for patient age, body mass index, sex, and baseline iHOT-12 scores. LEVEL OF EVIDENCE: III, retrospective comparative prognostic trial.

Prescription and acceptance of durable medical equipment in FORTITUDE-ALS, a study of reldesemtiv in ALS: post hoc analyses of a randomized, double-blind, placebo-controlled clinical trial.

Objective: To evaluate the possible effect of reldesemtiv, a fast skeletal muscle troponin activator, on prescription and acceptance of durable medical equipment (DME) in the FORTITUDE-ALS trial. Methods: Health economic outcome information was collected in FORTITUDE-ALS (NCT03160898); sites recorded if and when DME, specifically manual or power wheelchairs, gastrostomy tubes, noninvasive ventilators, or augmentative language devices, was prescribed by a physician and accepted by the patient (DME-PAP) during the trial. Acceptance was defined as the patient agreeing the item was needed. Cox regression analysis compared time to DME-PAP for each reldesemtiv dose with placebo. Post hoc analyses evaluated all reldesemtiv doses compared with placebo. Results: At least one DME item was prescribed and accepted by 33/114 (28.9%) of placebo patients, 19/112 (17.0%) of patients receiving reldesemtiv 150 mg bid, 24/113 (21.2%) receiving 300 mg bid, and 29/117 (24.8%) receiving 450 mg bid. The proportion of new DME-PAP was significantly lower in patients receiving reldesemtiv 150 mg bid vs placebo (17.0% vs 28.9%, p = 0.032). The hazard ratio versus placebo for accepting at least one DME item for all reldesemtiv doses combined was 0.61 (confidence interval: 0.39, 0.96, p = 0.032). 25% of placebo patients were prescribed and agreed to obtain a DME item by 84 days; this threshold was met for reldesemtiv-treated patients at 120 days. Conclusions: Results suggest ALS patients receiving reldesemtiv may have lower risk of and delayed need for DME related to impaired mobility, breathing, swallowing, or speaking; this delay is consistent with other measures indicating delay in disease progression.

Multicenter Outcomes After Primary Hip Arthroscopy: A Comparative Analysis of Two-Year Outcomes After Labral Repair, Segmental Labral Reconstruction, or Circumferential Labral Reconstruction.

PURPOSE: (1) To report minimum 2-year follow-up patient-reported outcome measures in patients undergoing labral repair (LR), segmental labral reconstruction (SLR), or circumferential labral reconstruction (CLR) in the primary setting; and (2) to compare minimum 2-year follow-up patient-reported outcome measures among these groups. METHODS: A retrospective review of a prospectively maintained multicenter database of patients undergoing hip arthroscopy was performed. Inclusion criteria were patients undergoing hip arthroscopy for treatment of labral tear and femoroacetabular impingement syndrome between January 2014 and October 2017, and completion of minimum 2-year postoperative outcome scores. Exclusion criteria were patients undergoing revision hip surgery, labral treatment limited to debridement, lateral center-edge angle <20°, osteoarthritis (Tönnis grade > 1), slipped capital femoral epiphysis, workers compensation status, and patients undergoing concomitant gluteus medius and/or minimus repair. Labral reconstruction patients were matched (1:3) with labral repair patients on age, sex, and body mass index. The labral reconstruction group was further stratified into SLR, and CLR groups. Patient demographic characteristics and clinical outcomes including Hip Outcome Score - Activities of Daily Living, Hip Outcome Score - Sport Subscale, modified Harris Hip Score, international Hip Outcome Tool, and visual analog scale for pain were analyzed, as well as achievement of the minimal clinical improvement difference (MCID). A P-value less than .05 indicated statistical significance. RESULTS: A total of 416 patients were included (LR, n = 312; SLR, n = 53; CLR, n = 51). The age, body mass index, and sex of the matched cohort were 42.3 ± 11.2 years, 24.7 ± 3.7, and 55.0% female. At a minimum of 2-year after hip arthroscopic surgery, no differences were found in preoperative, postoperative, or the delta visual analog scale for pain, modified Harris Hip Score, Hip Outcome Score - Activities of Daily Living, Hip Outcome Score - Sport Subscale, or international Hip Outcome Tool. Subsequently, the proportion of patients achieving the MCID and the PASS at latest follow-up were analyzed. This analysis revealed that no significant differences in the rate of MCID or PASS achievement for any outcome measure existed based on labral treatment. CONCLUSIONS: In this multicenter study on labral treatment in the primary setting, patients undergoing LR, SLR, and CLR demonstrated no difference in preoperative or postoperative scores, nor the proportion of patients achieving clinically significant outcome improvement. LEVEL OF EVIDENCE: III; therapeutic outcome study with controls.

The Use of Larval Sea Stars and Sea Urchins in the Discovery of Shared Mechanisms of Metazoan Whole-Body Regeneration.

The ability to regenerate is scattered among the metazoan tree of life. Further still, regenerative capacity varies widely within these specific organisms. Numerous organisms, all with different regenerative capabilities, have been studied at length and key similarities and disparities in how regeneration occurs have been identified. In order to get a better grasp on understanding regeneration as a whole, we must search for new models that are capable of extensive regeneration, as well as those that have been under sampled in the literature. As invertebrate deuterostomes, echinoderms fit both of these requirements. Multiple members regenerate various tissue types at all life stages, including examples of whole-body regeneration. Interrogations in two highly studied echinoderms, the sea urchin and the sea star, have provided knowledge of tissue and whole-body regeneration at various life stages. Work has begun to examine regeneration in echinoderm larvae, a potential new system for understanding regenerative mechanisms in a basal deuterostome. Here, we review the ways these two animals' larvae have been utilized as a model of regeneration.

Multicenter Outcomes After Revision Hip Arthroscopy: Comparative Analysis of 2-Year Outcomes After Labral Repair Versus Labral Reconstruction.

BACKGROUND: There is a paucity of literature evaluating patient outcomes in patients undergoing revision labral repair and labral reconstruction. PURPOSE: To compare outcomes in patients undergoing revision hip arthroscopy for treatment of labral tears by labral repair or labral reconstruction. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective review of a prospectively maintained multicenter database of patients undergoing hip arthroscopy was performed. An a priori power analysis determined that a total of 62 patients were required. Patients undergoing revision hip arthroscopy for labral tears with completed 2-year outcome scores were included. Patients undergoing primary hip arthroscopy, labral debridement, concomitant gluteal repair, and patients with hip dysplasia (lateral center-edge angle <20°) were excluded. Patients were grouped into revision labral repair and labral reconstruction groups. Patient demographics and patient-reported outcomes (PROs) including Hip Outcome Score - Activities of Daily Living, Hip Outcome Score - Sport Subscale, modified Harris Hip Score, international Hip Outcome Tool-12, visual analog scale for pain and satisfaction, and achievement of minimal clinically important difference (MCID) and Patient Acceptable Symptom State (PASS) were analyzed. RESULTS: A total of 40 patients underwent revision labral repair and 55 patients underwent labral reconstruction. Patients undergoing revision labral repair were younger (mean age, 30.0 ± 10.7 years vs 34.4 ± 9.7 years; P = .048), had lower rates of labral degeneration (25.0% vs 62.7%; P = .004), and had lower rates of severe complexity of tears (21.1% vs 66.0%; P = .003). However, the labral repair group had higher rates of articular cartilage damage (62.5% vs 33.3%; P = .009). There were no differences in any preoperative or 2-year postoperative PROs. Furthermore, no differences were seen in achievement of MCID or PASS in any PRO. CONCLUSION: In this multicenter study on revision hip arthroscopy, patients undergoing revision labral repair were younger and had better labral characteristics but greater cartilage damage compared with patients undergoing labral reconstructions. Despite these differences, patients who underwent labral repair reported similar outcomes to those undergoing labral reconstruction.