Amita Health

PURPOSE Single-agent PD-1 blockade exhibits limited efficacy in epithelial ovarian cancer (EOC). We evaluated ipilimumab plus nivolumab compared with nivolumab alone in women with persistent or recurrent EOC. METHODS Eligibility criteria included measurable disease, 1-3 prior regimens, and platinum-free interval (PFI) < 12 months. Participants were randomly allocated to intravenous nivolumab (every 2 weeks) or induction with nivolumab plus ipilimumab for 4 doses (every 3 weeks), followed by every-2-week maintenance nivolumab for a maximum of 42 doses. The primary null hypothesis was equal probability of objective response within 6 months of random allocation in each arm. RESULTS One hundred patients were allocated to receive either nivolumab (n = 49), or nivolumab plus ipilimumab (n = 51), with PFI of < 6 months in 62%. Six (12.2%) responses occurred within 6 months in the nivolumab group and 16 (31.4%) in the nivolumab plus ipilimumab group (odds ratio, 3.28; 85% CI, 1.54 to infinity; P = .034). The median progression-free survival (PFS) was 2 and 3.9 months in the nivolumab and nivolumab plus ipilimumab groups, respectively, with a PFI-stratified hazard ratio of 0.53 (95% CI, 0.34 to 0.82); the respective hazard ratio for death was 0.79 (95% CI, 0.44 to 1.42). Grade ≥ 3 related adverse events occurred in 33% of patients in the nivolumab group and 49% in the combination group, with no treatment-related deaths. PD-L1 expression was not significantly associated with response in either treatment group. CONCLUSION Compared with nivolumab alone, the combination of nivolumab and ipilimumab in EOC resulted in superior response rate and longer, albeit limited, PFS, with toxicity of the combination regimen comparable to prior reports. Additional combination studies to enhance durability of the dual regimen are warranted.

BACKGROUND The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear. METHODS We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ≥8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days. RESULTS The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, -0.3 percentage points; 95% confidence interval, -6.4 to 5.9; P = 0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months. CONCLUSIONS Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE ClinicalTrials.gov number, NCT02509078.).

BACKGROUND: Massively parallel DNA sequencing of cell-free fetal DNA from maternal blood can detect fetal chromosomal abnormalities. Although existing algorithms focus on the detection of fetal trisomy 21 (T21), these same algorithms have difficulty detecting trisomy 18 (T18). METHODS: Blood samples were collected from 1014 patients at 13 US clinic locations before they underwent an invasive prenatal procedure. All samples were processed to plasma, and the DNA extracted from 119 samples underwent massively parallel DNA sequencing. Fifty-three sequenced samples came from women with an abnormal fetal karyotype. To minimize the intra- and interrun sequencing variation, we developed an optimized algorithm by using normalized chromosome values (NCVs) from the sequencing data on a training set of 71 samples with 26 abnormal karyotypes. The classification process was then evaluated on an independent test set of 48 samples with 27 abnormal karyotypes. RESULTS: Mapped sites for chromosomes of interest in the sequencing data from the training set were normalized individually by calculating the ratio of the number of sites on the specified chromosome to the number of sites observed on an optimized normalizing chromosome (or chromosome set). Threshold values for trisomy or sex chromosome classification were then established for all chromosomes of interest, and a classification schema was defined. Sequencing of the independent test set led to 100% correct classification of T21 (13 of 13) and T18 (8 of 8) samples. Other chromosomal abnormalities were also identified. CONCLUSION: Massively parallel sequencing is capable of detecting multiple fetal chromosomal abnormalities from maternal plasma when an optimized algorithm is used.

What's already known about this topic? Noninvasive prenatal testing for detection of trisomies 21, 18, and 13 is clinically available and is reported to have a false positive rate of 1% or less This technology utilizes massively parallel shotgun sequencing of cell‐free DNA, of maternal and placental origin, present in maternal plasma What does this study add? Unexplained abnormal noninvasive prenatal testing results should prompt consideration of a maternal source of the abnormal cell‐free DNA, such as malignancy

The 1997 discovery of free fetal DNA in maternal plasma launched clinical researchers' efforts to establish a reliable method for non-invasive prenatal testing for fetal genetic conditions. Various methods, including, but not limited to, massively parallel sequencing (MPS) and selective analysis of cell-free fetal DNA in maternal plasma, have recently been developed as highly sensitive and specific noninvasive screening tools for common fetal chromosome aneuploidies. Incorporating these new noninvasive technologies into clinical practice will impact the current prenatal screening paradigm for fetal aneuploidy, in which genetic counseling plays an integral role. The National Society of Genetic Counselors (NSGC) currently supports Noninvasive Prenatal Testing/Noninvasive Prenatal Diagnosis (NIPT/NIPD) as an option for patients whose pregnancies are considered to be at an increased risk for certain chromosome abnormalities. NSGC urges that NIPT/NIPD only be offered in the context of informed consent, education, and counseling by a qualified provider, such as a certified genetic counselor. Patients whose NIPT/NIPD results are abnormal, or who have other factors suggestive of a chromosome abnormality, should receive genetic counseling and be given the option of standard confirmatory diagnostic testing.

OBJECTIVE: The aim of this study is to report the experience of noninvasive prenatal DNA testing using massively parallel sequencing in an accredited clinical laboratory. METHODS: Laboratory information was examined for blood samples received for testing between February and November 2012 for chromosome 21 (Chr21), Chr18, and Chr13. Monosomy X (MX) testing was available from July 2012 for cystic hygroma indication. Outcomes were collected from providers on samples with positive results. RESULTS: There were 5974 samples tested, and results were issued within an average of 5.1 business days. Aneuploidy was detected in 284 (4.8%) samples (155 Chr21, 66 Chr18, 19 Chr13, 40 MX, and four double aneuploidy). Follow-ups are available for 245/284 (86%), and 77/284 (27.1%) are confirmed, including one double-aneuploidy case concordant with cytogenetics from maternal malignancy. Fourteen (0.2%) discordant (putative false-positive) results (one Chr21, six Chr18, three Chr13, three MX, and one Chr21/13) have been identified. Five (0.08%) false-negative cases are reported (two trisomy 21, two trisomy 18, and one MX). In 170 (2.8%) cases, the result for a single chromosome was indefinite. CONCLUSIONS: This report suggests that clinical testing of maternal cell-free DNA for fetal aneuploidy operates within performance parameters established in validation studies. Noninvasive prenatal testing is sensitive to biological contributions from placental and maternal sources.

Rigorous and reproducible methodology of controlling for bias is essential for high-quality, evidence-based studies. Propensity score matching (PSM) is a valuable way to control for bias and achieve pseudo-randomization in retrospective observation studies. The purpose of this review is to 1) provide a clear conceptual framework for PSM, 2) recommend how to best report its use in studies, and 3) offer some practical examples of implementation. First, this article covers the concepts behind PSM, discusses its pros and cons, and compares it with other methods of controlling for bias, namely, hard/exact matching and regression analysis. Second, recommendations are given for what to report in a manuscript when PSM is used. Finally, a worked example is provided, which can also serve as a template for the reader's own studies. A study's conclusions are only as strong as its methods. PSM is an invaluable tool for producing rigorous and reproducible results in observational studies. The goal of this article is to give practicing clinical physicians not only a better understanding of PSM and its implications but the ability to implement it for their own studies. STUDY DESIGN: Review.

Recent research examining infants' understanding of intentional action claims to be studying the early origins or precursors of children's later theories of mind If these infant understandings are continuous with later preschool achievements, there should be empirical connections between the two. We provide initial evidence that infants' social attention predicts later social cognition. Specifically, 14-month-olds' habituation to human intentional action significantly predicts later preschool mentalistic construal of persons, as measured on a Theory of Mind Scale.

PURPOSE: To assess mid- to long-term patient-reported outcomes (PROs) of hip arthroscopy as well as the rates of secondary surgery and to identify indications for surgery and noted predictors of failure. METHODS: A systematic review of the current literature was performed with the terms "hip arthroscopy," "outcomes," "patient-reported outcomes," "mid-term," "5-year," "long-term," and "10-year" in the PubMed, Cochrane, and Embase databases in April of 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data for study characteristics, patient demographics, follow-up time, indications for surgery, PROs, predictors of failure or unfavorable PROs, and rates of secondary hip preservation surgery and conversion to total hip arthroplasty were collected. RESULTS: Thirteen articles were included. Four studies were level III and 9 were level IV. In total, 1571 hips were included, and the average follow-up time ranged from 60 to 240 months. The most common indications for hip arthroscopy were labral tears and femoroacetabular impingement syndrome. Twelve studies reported on PROs and all reported improvement at latest follow-up. The most reported on scores were the modified Harris Hip Score, Harris Hip Score, and the Hip Outcome Score-Sport Specific Subscale. When grouped based on average follow-up time, the conversion rates at the 5- and 10-year time points ranged from 3.0% to 17.9% and 2.4% to 32.5%, respectively. One study with 20-year follow-up reported a conversion rate of 41.0%. Osteoarthritis and increased age were the most cited predictors for secondary surgery or decreased PROs. CONCLUSIONS: At mid- to long-term follow-up, patients who underwent primary hip arthroscopy demonstrated improvement in several PROs. There was great variability in rates for revision surgery and conversion to total hip arthroplasty. The most common indications for hip arthroscopy were labral tears and femoroacetabular impingement syndrome. Osteoarthritis and increased age were the most cited predictors for unfavorable outcomes. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and IV studies.

BACKGROUND: Epilepsy is one of the most common neurological disorders in childhood. However, classical antiepileptic drugs are linked with drug toxicity and cognitive function impairment in children. Hence, it is essential to develop a novel therapy to solve this problem. Currently, studies indicate regulating the nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated ferroptosis pathway represents a potential advanced therapy for seizures. Hence, the present study aimed to explore whether quercetin, a natural polyphenol, could alleviate seizure-induced neuron death and preserve cognitive function by inhibiting Nrf2-mediated ferroptosis. METHODS: Kainic acid-induced epileptic mice model, morris water maze (MWM) test, cell counting kit-8 (CCK-8) assays, western blotting analysis, enzyme-linked immunosorbent assay, flow cytometry, quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence staining, and RNA sequencing analysis were employed to explore the potential mechanisms by which quercetin exerts protective effects on seizure-induced neuron death in kainic acid-induced epileptic mice model and glutamate-induced HT22 neuronal cell death. RESULTS: Our findings suggested the association between the Nrf2-mediated ferroptosis pathway and seizures in a clinical setting. Quercetin pretreatment alleviates seizure-like behaviors and cognitive impairment in KA-induced epileptic mice. Additionally, in vitro, co-treatment with quercetin effectively exerts neuroprotective effects in glutamate-induced HT22 neuronal cell death. These protective effects were also closely linked to regulating the Nrf2-mediated ferroptosis pathway. Furthermore, bioinformatic profiling revealed that the SIRT1/Nrf2/SLC7A11/GPX4 pathway plays a crucial role in the Glu-induced HT22 cell death pretreated with quercetin. CONCLUSIONS: These findings indicated that quercetin effectively protects against seizure-induced neuron death in vivo and in vitro and alleviates cognitive function impairment via the SIRT1/Nrf2/SLC7A11/GPX4 pathway.

BACKGROUND AND PURPOSE: The optimal management of patients with acute basilar artery occlusion (BAO) is uncertain. We aimed to evaluate the safety and efficacy of endovascular thrombectomy (EVT) compared to medical management (MM) for acute BAO through a meta-analysis of randomized controlled trials (RCTs). METHODS: We performed a systematic review and meta-analysis of RCTs of patients with acute BAO. We analyzed the pooled effect of EVT compared to MM on the primary outcome (modified Rankin Scale [mRS] of 0-3 at 3 months), secondary outcome (mRS 0-2 at 3 months), symptomatic intracranial hemorrhage (sICH), and 3-month mortality rates. For each study, effect sizes were computed as odds ratios (ORs) with random effects and Mantel-Haenszel weighting. RESULTS: Four RCTs met inclusion criteria including 988 patients. There were higher odds of mRS of 0-3 at 90 days in the EVT versus MM group (45.1% vs. 29.1%, OR 1.99, 95% confidence interval [CI] 1.04-3.80; P=0.04). Patients receiving EVT had a higher sICH compared to MM (5.4% vs. 0.8%, OR 7.89, 95% CI 4.10-15.19; P<0.01). Mortality was lower in the EVT group (35.5% vs. 45.1%, OR 0.64, 95% CI 0.42-0.99; P=0.05). In an analysis of two trials with BAO patients and National Institutes of Health Stroke Scale (NIHSS) <10, there was no difference in 90-day outcomes between EVT versus MM. CONCLUSION: In this systematic review and meta-analysis, EVT was associated with favorable outcome and decreased mortality in patients with BAO up to 24 hours from stroke symptoms compared to MM. The treatment effect in BAO patients with NIHSS <10 was less certain. Further studies are of interest to evaluate the efficacy of EVT in basilar occlusion patients with milder symptoms.

BACKGROUND: Although hip arthroscopy has been shown to have favorable results, there is a paucity of literature describing predictive factors of 5-year clinical outcomes. PURPOSE: To identify predictive factors of midterm outcomes after hip arthroscopy in a cohort of 1038 patients whose outcomes at minimum 2-year follow-up were previously reported. In addition, to provide a comparison of short- and midterm predictive factors in outcome measures after hip arthroscopy. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Data were prospectively collected and retrospectively reviewed on all patients undergoing hip arthroscopy between February 2008 and June 2012. Patients were included if they had minimum 5-year follow-up on 2 patient-reported outcomes: Nonarthritic Hip Score (NAHS) and modified Harris Hip Score. Patients were excluded if they had any previous ipsilateral hip conditions. Using bivariate and multivariate analyses, we analyzed the effect of 36 pre- and intraoperative variables on the NAHS, modified Harris Hip Score, and conversion to total hip arthroplasty. RESULTS: A total of 1038 patients met the inclusion criteria for the 2-year study, and 860 met our listed inclusion criteria for the 5-year study. The mean follow-up time was 62.0 months (range, 60.0-120.0 months). The bivariate analysis identified 10 variables (4 categorical and 6 continuous) that were predictive of 5-year postoperative NAHS. For the multivariate analysis, 7 variables were identified as being significant: preoperative NAHS, body mass index (BMI), age, lateral joint space, alpha angle, revision hip arthroscopy, and acetabular microfracture. These 7 variables were also predictive in the bivariate analysis. Age, BMI, revision hip arthroscopy, Tönnis grade, sex, trochanteric bursectomy, femoral head cartilage damage, and acetabular inclination were significant predictors of conversion to total hip arthroplasty. CONCLUSION: This study reports favorable midterm clinical outcomes in the largest cohort of hip arthroscopies with minimum 5-year follow-up in the literature to date. Seven variables were identified as being significant predictors of postoperative NAHS in the bivariate and multivariate analyses: preoperative NAHS, BMI, age, lateral joint space, alpha angle, revision hip arthroscopy, and acetabular microfracture. Of these, preoperative NAHS, BMI, age, and revision hip arthroscopy were predictive of 2- and 5-year postoperative NAHS. These predictive factors may prove useful to clinicians in determining indications for hip arthroscopy and counseling patients on its expected outcomes.

Moderate to severe pain occurs in many cancer patients during their clinical course and may stem from the primary pathology, metastasis, or as treatment side effects. Uncontrolled pain using conservative medical therapy can often lead to patient distress, loss of productivity, shorter life expectancy, longer hospital stays, and increase in healthcare utilization. Various publications shed light on strategies for conservative medical management for cancer pain and a few international publications have reviewed limited interventional data. Our multi-institutional working group was assembled to review and highlight the body of evidence that exists for opioid utilization for cancer pain, adjunct medication such as ketamine and methadone and interventional therapies. We discuss neurolysis via injections, neuromodulation including targeted drug delivery and spinal cord stimulation, vertebral tumor ablation and augmentation, radiotherapy and surgical techniques. In the United States, there is a significant variance in the interventional treatment of cancer pain based on fellowship training. As a first of its kind, this best practices and interventional guideline will offer evidenced-based recommendations for reducing pain and suffering associated with malignancy.

BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. PATIENTS AND METHODS: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. RESULTS: A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54-0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis. CONCLUSIONS: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile.

PURPOSE: (1) To report minimum 2-year patient-reported outcome (PRO) scores of primary circumferential acetabular labral reconstruction using anterior tibialis allograft and the knotless pull-through technique in the setting of femoroacetabular impingement syndrome (FAIS) and irreparable labral tears and (2) to compare these PROs with a matched-pair primary labral repair group. METHODS: Data were prospectively collected and retrospectively reviewed. Patients were included if they underwent primary circumferential labral reconstruction with anterior tibialis tendon allograft during February 2016 to April 2017 for irreparable labral tears and FAIS and had preoperative and minimum 2-year follow-up for modified Harris Hip Score (mHHS), Hip Outcome Score-Sport-Specific Subscale, Non-arthritic Hip Score, International Hip Outcome Tool 12 (iHOT-12), 12-Item Short Form Health Survey physical component and mental component, Veterans RAND 12-Item Health Survey physical component and mental component, and visual analog scale for pain. The exclusion criteria were previous ipsilateral hip conditions or surgical procedures, Tönnis grade 2 or higher, or dysplasia (lateral center-edge angle ≤ 18°). Labral tears were considered irreparable if the labrum appeared (1) to be mostly or completely calcified and (2) to be inadequate (nonviable) and not amenable for labral repair. The reconstruction group was matched 1:3 based on age, sex, and body mass index to a benchmark control group of hips undergoing labral repair from the same period. The minimal clinically important difference and patient acceptable symptomatic state for the mHHS and iHOT-12 score were calculated. RESULTS: A total of 37 hips (37 patients) underwent circumferential labral reconstruction. There were 19 female patients (51.4%) and 18 male patients (48.6%). The mean age was 45.6 ± 11.6 years, and the average body mass index was 27.1 ± 5. At minimum 2-year follow-up, the circumferential labral reconstruction group showed statistically significant improvements in the mHHS, Non-arthritic Hip Score, Hip Outcome Score-Sport-Specific Subscale, iHOT-12 score, and visual analog scale score. All hips in the reconstruction group were successfully matched to 111 labral repair hips. At latest follow-up, improvements in all PROs between the 2 groups were comparable. The revision rates were 0% and 3.6% in the reconstruction and repair groups, respectively. CONCLUSIONS: After primary hip arthroscopy, primary circumferential labral reconstruction using anterior tibialis allograft and the knotless pull-through technique in the setting of FAIS and irreparable labral tears resulted in significant improvements in several PROs at minimum 2-year follow-up and high patient satisfaction. Primary circumferential labral reconstruction reached comparable functional outcomes to those of a benchmark matched-pair primary labral repair control group. LEVEL OF EVIDENCE: Level III, case-control study.

PURPOSE: The purpose of this study was to improve the interpretability of the Nonarthritic Hip Score (NAHS) by determining the minimal clinically important difference (MCID), patient acceptable symptomatic state (PASS), and substantial clinical benefit (SCB) after hip arthroscopy for femoroacetabular impingement. The secondary aim was to identify variables associated with achievement of the thresholds. METHODS: Patients who underwent hip arthroscopy for femoroacetabular impingement and completed postoperative questionnaires between August 2019 and March 2020 were included. Patients were excluded if they underwent previous ipsilateral hip surgery, underwent gluteus medius repair, or had a previous hip condition. The MCID, PASS, and SCB thresholds were calculated for the NAHS at minimum 1-, 2-, and 5-year follow-up. Distribution- and anchor-based methods with receiver operating characteristic analysis were used to determine the thresholds. Multivariate logistic regression was performed to determine predictors of achieving the MCID and PASS. RESULTS: The study included 343 hips with an average follow-up period of 48 months. On the basis of the distribution-based approach, the MCID was 8.7 using a method in which the standard deviation of the baseline score was divided by 2. By use of a method in which the standard deviation of the change score was divided by 2, MCID scores of 9.1, 8.3, and 12.6 resulted at a minimum of 1, 2, and 5 years, respectively. The PASS thresholds for these time points were 81.9, 85.6, and 81.9. The absolute SCB thresholds were 91.9, 94.4, and 93.1 and the change score thresholds were 30.6, 24.4, and 29.3 for a minimum of 1, 2, and 5 years, respectively. The preoperative NAHS was positively associated with achievement of the PASS and inversely related to achievement of the MCID. CONCLUSIONS: This study provides important clinical thresholds for the NAHS. These thresholds were determined for minimum 1-, 2-, and 5-year time points. The MCID was determined as 8.7, the PASS ranged between 81.9 and 85.6, and the absolute SCB value ranged from 91.9 to 94.4. The preoperative NAHS was found to be positively associated with achievement of the PASS and inversely related to achievement of the MCID. LEVEL OF EVIDENCE: Level IV, retrospective case series.

PURPOSE: To determine the respective percent thresholds for achieving the maximal outcome improvement (MOI) for the modified Harris Hip Score (mHHS), the Nonarthritic Hip Score (NAHS), the visual analog scale (VAS) for pain, and the International Hip Outcome Tool-12 (iHOT-12) that were associated with satisfaction following hip arthroscopy for femoroacetabular impingement syndrome and labral tear, and to identify preoperative predictors of reaching the mHHS, NAHS, VAS, and the iHOT-12 thresholds for achieving the MOI. METHODS: An anchor question was provided to patients who underwent hip arthroscopy between April 2008 and April 2019. Patients were included if they answered the anchor question and had minimum 1-year follow-up. Patients were excluded if they had a previous ipsilateral hip surgery, a Tönnis grade >1, hip dysplasia, or a previous hip condition. Receiver operating characteristic analysis was used to determine the thresholds for the percentage of the MOI predictive of satisfaction. Multivariate logistic regression was used to determine predictors of achieving the MOI threshold. RESULTS: In total, 407 hips (375 patients) were included, with 279 female patients (68.6%). The average age, body mass index, and follow-up time were 38.8 ± 13.7 years, 26.6 ± 5.8, and 51.8 ± 33.2 months, respectively. Satisfaction with the current state of their hip was reported in 77.9% (317) of the cases. It was determined that 54.8%, 52.5%, 55.5%, and 55.8% of MOI were the thresholds for maximal predictability of satisfaction for mHHS, NAHS, VAS, and iHOT-12, respectively. Predictors of achieving MOI were not identified. CONCLUSIONS: Following hip arthroscopy in the context of femoroacetabular impingement syndrome and labral tear, the thresholds for achieving the MOI for the mHHS, NAHS, VAS for pain, and iHOT-12 were 54.8%, 52.5%, 55.5%, and 55.8% respectively. No preoperative predictors of achieving the MOI were identified. LEVEL OF EVIDENCE: IV, case-series.

Objective: To update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy (GE) with second- and third-generation antiepileptic drugs (AEDs). Methods: The 2004 AAN criteria was used to systematically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Results: Several second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic–clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy. Recommendations: Lamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years with new-onset focal epilepsy. Unless there are compelling adverse-effect–related concerns, ethosuximide (ETS) or valproic acid (VPA) should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (Level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent FDA strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval.

PURPOSE: To analyze the effect of gracilis harvest on hamstring strength, patient-reported outcomes, and anterior knee laxity after anterior cruciate ligament (ACL) reconstruction. METHODS: A systematic review of the literature was performed to identify studies comparing the results of semitendinosus (ST) versus semitendinosus-gracilis (ST-G) harvest for ACL reconstruction. A meta-analysis using a random effects model was performed to determine overall pooled estimates of effect for the influence of additional gracilis harvest on hamstring strength, patient-reported outcomes, and anterior knee laxity after ACL reconstruction. RESULTS: Twelve studies were identified and included in the review. ST-G harvest was noted to decrease hamstring isokinetic strength at 60° per second by 3.85% relative to isolated ST harvest (P = .01). Decreased isometric strength was also noted in the ST-G harvest group at both 90° of flexion (mean difference: 5.55%; P = .03) and 105° to 110° of flexion (mean difference: 13.68%; P = .003). Active knee flexion angle loss was also noted to be greater in the ST-G harvest group (mean difference: 3.91°; P = .006). No differences were found in isokinetic strength at 180° to 240° per second (mean difference: 3.20%; P = .08), patient-reported outcome scores (mean difference: 1.87 points; P = .06), or anterior knee laxity (mean difference: 0.03 mm; P = .78) based on gracilis harvest. CONCLUSIONS: The addition of gracilis harvest to an isolated ST harvest for ACL reconstruction results in statistically significant, but likely not clinically relevant differences in isokinetic and isometric hamstring strength as well as patient-reported outcomes. Hamstring strength deficits may be larger at higher flexion angles. LEVEL OF EVIDENCE: Level III, systematic review of level I-III studies.

PURPOSE: To investigate the correlation between hip capsular management (repair or reconstruction) and biomechanical results in the setting of femoroacetabular impingement and microinstability. METHODS: A search of the PubMed and Embase databases was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included studies focused on hip biomechanics related to capsular release, repair of I- and T-capsulotomy, or capsular reconstruction. Studies were assessed for external/internal rotation of the femur, femoral head translation, rotational torque, and distraction force. Articles were excluded if they discussed treatment of the hip capsule related to surgical dislocation, mini-open surgery, arthroplasty, reorientation osteotomy, or traumatic dislocation. RESULTS: Twenty-four biomechanical studies were included that evaluated rotation/translation (11 studies), distraction (3 studies), the capsular role in microinstability (simulated with anterior capsule pie crusting [2 studies] and cyclical loading [2 studies]), allograft reconstruction (3 studies), and anatomic properties (3 studies). Repair and reconstruction demonstrated improvements in maximum distractive force, total ROM, and torsional stability when compared to capsular release. Significant differences were observed between capsular repair and release in total ROM in the coronal plane with improved stability in the repair groups (standardized mean difference [SMD]: -1.3°, 95% confidence interval [CI] -1.68 , -0.854; P < .001). There was significantly increased total motion in the coronal plane in the capsular laxity state compared to the native state (SMD: 1.4° (95% CI 0.32, 2.49; P = .012). CONCLUSIONS: Biomechanical evidence supports closure of the capsule after hip arthroscopy to reverse the significant effects of capsulotomy. Simulated capsule laxity models created altered joint motion and translation. Capsule reconstruction appears to restore the hip to its native capsule state. CLINICAL RELEVANCE: Investigating the biomechanical outcomes of capsular repair and reconstruction will help surgeons better understand the rationale and implications of these capsular management strategies.