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Abstract Introduction REM sleep behavior disorder (RBD) is characterized by disruptive, violent dream enactment behaviors (DEB), necessitating symptomatic treatment to prevent injury and reduce DEB frequency and severity. Melatonin and clonazepam are regarded as RBD therapeutic mainstays, although outcomes data remains limited. We surveyed RBD patients to determine their outcomes following melatonin, clonazepam, and melatonin-clonazepam combination therapy. Methods Mayo Clinic RBD Patient Registry participants received an electronic survey concerning treatment type(s) and dose(s), efficacy, and adverse effects. The primary outcome was treatment efficacy, determined by comparing DEB frequency/severity ratings on a visual analog scale (VAS). Adverse effects severity was assessed by Likert scales. We comparatively analyzed VAS before and after treatment and adverse effects between treatments using non-parametric statistical tests. Results Sixty-eight of 109 patients responded (62.3%; 64 had analyzable data) with a mean age of 67.7 years. Fifty-seven (85%) were men, with mean RBD symptom duration of 13.9 years. Patients receiving each treatment were: melatonin=30, clonazepam=8, and combination=12; 14 received other or no treatment. Baseline VAS ratings were similar between groups. Only melatonin (p=0.003) and combination therapy (p=0.039) improved VAS ratings; clonazepam monotherapy did not improve VAS. Only melatonin monotherapy was reported to lower VAS compared to untreated patients (p=0.02). Optimally effective mean dosages were melatonin 9.95±5.06 mg and clonazepam 0.81±0.48 mg. Patient frequencies reporting one or more moderately-severe side effect(s) were similar between melatonin (15%), clonazepam (7%), and combination therapies (9%). Twenty-five (36.8%) patients had received only one medication trial, while 41.2% required more than one medication. Of these, 15 (22.1%) tried 2 and 13 (19.1%) tried 3 or more treatments. Conclusion Melatonin therapy at an approximate mean 10 mg dosage improved patient-reported DEB frequency/severity on VAS, compared between both previous intraindividual baseline ratings and with untreated patients, while clonazepam monotherapy did not, without differential adverse effects. Clonazepam monotherapy data were limited. These data inform future prospective melatonin symptomatic therapy trials for RBD. Additionally, 41.2% required more than one RBD pharmacological treatment, suggesting a current therapeutic gap and unmet need for future development of biologically-informed, evidence-based symptomatic RBD therapeutics. Support (if any):

Abstract Introduction Idiopathic/isolated REM sleep behavior disorder (iRBD) is a prodromal alpha-synucleinopathy characterized by dream enactment behavior and REM sleep without atonia (RSWA). We sought to define quantitative RSWA diagnostic thresholds in the North American Prodromal Synucleinopathy (NAPS) Consortium cohort. We analyzed RSWA between iRBD patients across participating NAPS sleep centers, compared to normative controls, and hypothesized that previous diagnostic RSWA thresholds were overestimates. Methods All digital polysomnography files were converted to European Data Format and scored at a central laboratory (Mayo Clinic) which standardized display scoring montages, channel sensitivities, and filtering, and scripted computational analyses for visual scoring. RSWA was quantitatively analyzed in the submentalis (SM) and anterior tibialis (AT) muscles in iRBD (n=86) patients and controls (n=118) utilizing well validated visual (Mayo) and automated (RAI) methods. Parametric statistics were used to compare RSWA metrics, and RSWA thresholds were developed using receiver operating characteristic curves. Results RSWA was significantly higher for the RAI and all visual individual and combined muscle activity metrics in iRBD compared to controls (all p<0.001). Average SM phasic measures were: 14.2% (Mayo), 17.9% (McGill), 18.5% (UCLA), and 9.4% (Washington University). Average AT phasic measures at each site were: 26.7% (Mayo), 17.1% (McGill), 23.3% (UCLA), and 17.4% (Washington University). Average SM/AT ‘any’ measures at each site were: 45.4% (Mayo), 35.9% (McGill), 53.4% (UCLA), and 23.5% (Washington University). Overall cohort RBD diagnostic thresholds (AUC, specificity/sensitivity) were: SM phasic 4.9% (90.0, 82.2%/83.7%); AT phasic 7.6% (88.7%, 82.2%/81.4%) and combined SM/AT ‘any’ 13% (94.6, 83.9%/96.5%). Conclusion RSWA thresholds in the NAPS cohort were substantially lower than previously reported, suggesting previously overestimated diagnostic RSWA thresholds due to smaller, enriched patient samples and overfit statistical modeling. Confirmation of these findings in the complete NAPS cohort (n=300 iRBD patients across all 10 NAPS centers) is planned. Support (if any):

Objective: Preeclampsia is a cardiovascular complication characterised by the new onset of hypertension and proteinuria or other end-organ dysfunction. Currently there are no effective treatments for preeclampsia except delivery of the placenta and the baby, often pre-term. Administration of mesenchymal stem cells (MSCs) has shown therapeutic potential in pre-clinical models of preeclampsia. In this study, we aimed to identify novel placental miRNAs in preeclampsia which could be targeted by MSCs or their extracellular vesicles (MSC-EVs). Design and method: Human MSCs were isolated from abdominal fat tissue during caesarean section and cultured for 48 h. Human umbilical cord endothelial cells (HUVEC) were co-cultured with MSCs from pregnancies with or without preeclampsia (n = 3) up to 90 h and angiogenesis assessed using tubule formation assay in IncuCyteu live cell imaging system. Using separate patient samples, miRNA was isolated from placentae from women with and without preeclampsia (n = 2) and miRNA next generation sequencing (miRNAseq) performed. The expression of two miRNAs identified in miRNAseq (miRNA-183–5p and miRNA-203a-3p) were measured in HUVEC cells exposed to 24 h hypoxia (1%) or normoxia (21%) in the presence of MSC conditioned medium (MSC-CM) or MSC-EVs. Results: MSCs isolated from women with preeclampsia demonstrated impaired pro-angiogenic profile compared to MSCs derived from normotensive pregnancies measured by the network length (mm/m2) of HUVECs following 66 h, 72 h, 78 h, 84 h and 90 h of exposure to MSC-CM (n = 3, p = 0.001). The results of miRNAseq identified a number of aberrantly expressed miRNAs including mir-183–5p (logFC = -2.8, p = 0.001) and mir-203a-3p (logFC = -6.7, p = 0.001). Following exposure of HUVECs to hypoxia, mir-183–5p was significantly increased by approximately 8-fold (p = 0.001) whereas mir-203a-3p showed no change in expression. MSC-CM and MSC-EVs were both capable of ameliorating this increase in mir-183–5p as a result of hypoxia (p = 0.01, MSC-CM; p = 0.001, MSC-EVs). Conclusions: In patients with preeclampsia, MSCs show impaired angiogenic function, potentially leading to inappropriate placental development and angiogenesis in pregnancy. Administration of healthy MSCs or associated MSC-EVs could have a therapeutic potential in the treatment of preeclampsia and the mechanism could involve novel mir-183–5p as a treatment target.

Abstract BACKGROUND: Recurrent isocitrate dehydrogenase (IDH) 1 mutations are observed in 6-10% of patients with acute myeloid leukemia (AML). Ivosidenib (AG-120), a potent, selective, oral, small-molecule inhibitor of the mutant IDH1 (mIDH1) protein, is a promising therapeutic candidate for the treatment of patients with mIDH1 AML. Through inhibition of mIDH1, ivosidenib suppresses the abnormal production of the oncometabolite 2-hydroxyglutarate (2-HG), leading to clinical responses via differentiation of malignant cells. AIM: To report safety and efficacy data from the first-in-human phase 1 study of ivosidenib in patients with mIDH1 advanced hematologic malignancies including relapsed/refractory (R/R) AML (NCT02074839). This is the first report of data from the 4 expansion cohorts, with a total of 258 patients treated on study. METHODS: The ongoing phase 1 study assesses the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and clinical activity of ivosidenib in mIDH1 hematologic malignancies. Enrollment was completed on May 8, 2017. During dose escalation, patients received ivosidenib as a single agent orally once daily (QD) or twice daily (BID) in 28-day cycles. The MTD was not reached and 500 mg QD was selected as the recommended dose to be tested in 4 expansion cohorts: R/R AML (Arms 1 and 4, where Arm 1 patients are those with relapse after transplantation, second or later relapse, resistance to initial induction or reinduction treatment, or relapse within 1 year of initial treatment, and Arm 4 patients have R/R AML but are not eligible for Arm 1); untreated AML (Arm 2); and other advanced hematologic malignancies including myelodysplastic syndrome (MDS) (Arm 3). Updated safety data will be presented for all patients. Efficacy outcomes will be presented for all R/R AML patients treated at 500 mg QD across the dose escalation and expansion cohorts who received their first dose of ivosidenib at least 6 months prior to the analysis cut-off date of May 12, 2017, as well as for the poorest prognosis Arm 1 subset. Efficacy data for all treated patients from the other expansion cohorts (untreated AML and other advanced hematologic malignancies including MDS) will also be presented. RESULTS: In all, 258 patients (78 in dose escalation, 180 in expansion) were treated with ivosidenib. As of May 12, 2017, 62 of 258 (24%) patients were continuing on treatment. The median duration of exposure to ivosidenib was 3.5 months (range 0.1-33.5). Twenty-two (8.5%) patients discontinued treatment to proceed to allogeneic stem cell transplantation. Treatment was well tolerated; the most common adverse events (AEs) (n=258) of any grade irrespective of causality occurring in ≥20% of patients were diarrhea (33%), leukocytosis (30%), nausea (30%), fatigue (29%), febrile neutropenia (25%), dyspnea (24%), anemia (23%), QT prolongation (23%), peripheral edema (22%), pyrexia (21%), and decreased appetite (20%). The majority of these AEs were grades 1-2 and reported as unrelated to treatment. Differentiation syndrome (DS) was observed in 29 of 258 (11.2%) patients, including grade ≥3 DS in 14 (5.4%); study drug was held owing to DS in 11 patients (4.3%), and no instances of DS led to permanent treatment discontinuation or death. The primary efficacy endpoint for R/R AML is the CR+CRh rate, i.e., the rate of complete remission (CR according to modified IWG 2003 criteria plus CR with partial hematologic recovery, defined as CR except absolute neutrophil count >0.5 × 109/L [500/µL] and platelet count >50 × 109/L [50,000/µL]). Among 125 Arm 1 R/R AML patients receiving ivosidenib 500 mg QD across dose escalation and expansion who received their first dose at least 6 months prior to the analysis cutoff date, the CR+CRh rate was 30.4% (95% CI 22.5%, 39.3%), including CR in 27 (21.6%) and CRh in 11 (8.8%) patients. Median duration of CR+CRh was 8.2 months (95% CI 5.5, 12.0), and duration of CR was 9.3 months (95% CI 5.6, 18.3). The overall response rate (CR+CRi/CRp+PR+MLFS) was 41.6% (95% CI 32.9%, 50.8%) (52/125 patients). CONCLUSION: Ivosidenib monotherapy is well tolerated in patients with mIDH1 AML and other advanced hematologic malignancies. In a high-risk, molecularly defined R/R AML patient population with unmet medical need, ivosidenib induced durable remissions and improved patient outcomes. These findings support the role of ivosidenib as an effective, oral, targeted treatment for patients with mIDH1 AML. Disclosures DiNardo: Celgene: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Agios: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. De Botton: Pfizer: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Servier: Honoraria; Agios: Honoraria, Research Funding. Stein: GSK: Other: Advisory Board, Research Funding; Constellation Pharma: Research Funding; Seattle Genetics: Research Funding; Agios Pharmaceuticals, Inc.: Consultancy, Research Funding; Celgene Corporation: Consultancy, Other: Travel expenses, Research Funding; Pfizer: Consultancy, Other: Travel expenses; Novartis: Consultancy, Research Funding. Roboz: AbbVie, Agios, Amgen, Amphivena, Array Biopharma Inc., Astex, AstraZeneca, Celator, Celgene, Clovis Oncology, CTI BioPharma, Genoptix, Immune Pharmaceuticals, Janssen Pharmaceuticals, Juno, MedImmune, MEI Pharma, Novartis, Onconova, Pfizer, Roche Pharmace: Consultancy; Cellectis: Research Funding. Mims: Novartis: Honoraria. Pollyea: Takeda, Ariad, Alexion, Celgene, Pfizer, Pharmacyclics, Gilead, Jazz, Servier, Curis: Membership on an entity's Board of Directors or advisory committees; Agios, Pfizer: Research Funding. Altman: Syros: Consultancy; NCCN: Other: Educational speaker; BMS: Consultancy; Celgene: Consultancy; Astellas: Consultancy; Ceplene: Consultancy; Janssen Pharmaceuticals: Consultancy; Novartis: Consultancy; ASH: Other: Educational speaker. Collins: Celgene Corporation: Research Funding; Agios: Research Funding; Arog: Research Funding; BMS: Research Funding. Mannis: Curis: Honoraria; Juno: Research Funding; Agios: Research Funding; Amgen: Honoraria. Uy: GlycoMimetics: Consultancy; Novartis: Consultancy, Other: Travel Suppport; Boehringer Ingelheim: Consultancy. Fathi: Juno: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Medimmune: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Stein: Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy. Erba: Celgene: Consultancy, Other: Chair, Scientific Steering Committee , Speakers Bureau; Incyte: all research support paid to University of Alabama, Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Other: all research support paid to University of Alabama, Research Funding; Daiichi Sankyo: Consultancy, Other: all research support paid to University of Alabama, Research Funding; ImmunoGen: Consultancy, Other: all research support paid to University of Alabama, Research Funding; MacroGen: Consultancy; Ono: Consultancy; Pfizer: Consultancy; Seattle Genetics: Consultancy, Other: all research support paid to University of Alabama, Research Funding; Sunesis: Consultancy; Millennium/Takeda: Consultancy, Other: all research support paid to University of Alabama, Research Funding; Agios: Other: all research support paid to University of Alabama, Research Funding; Juno: Other: all research support paid to University of Alabama, Research Funding; Astellas: Other: all research support paid to University of Alabama, Research Funding; Celator: Other: all research support paid to University of Alabama, Research Funding; Janssen: Other: all research support paid to University of Alabama, Research Funding; Glycomimetics: Other: Chair, Data and Safety Monitoring Committee. Traer: ImmunoGen: Consultancy; Tolero: Consultancy; Notable Labs: Equity Ownership. Stuart: Pharmacyclics LLC, an AbbVie Company: Research Funding; Amgen: Consultancy, Honoraria; Agios: Research Funding; Celator/Jazz: Research Funding; Sunesis: Consultancy, Honoraria, Other: Travel Support, Research Funding; Bayer: Research Funding; Novartis: Research Funding; Incyte: Research Funding; ONO: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; MedImmune: Research Funding; Cantex: Research Funding; Astellas: Research Funding. Arellano: Cephalon Oncology: Research Funding. Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees. Yen: Agios: Employment, Equity Ownership. Kapsalis: Agios: Employment, Equity Ownership. Liu: Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Goldwasser: Agios: Employment, Equity Ownership. Agresta: Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Attar: Agios: Employment, Equity Ownership. Stone: Novartis: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Abbvie: Consultancy; Fuji Film: Consultancy; Jazz: Consultancy; Astellas: Consultancy; Pfizer: Consultancy; Arog: Consultancy; Ono: Consultancy; Agios: Consultancy; Sumitomo: Consultancy. Kantarjian: ARIAD: Research Funding; Bristol-Meyers Squibb: Research Funding; Delta-Fly Pharma: Research Funding; Amgen: Research Funding; Pfizer: Research Funding; Novartis: Research Funding.

Abstract Background: Sapacitabine is a novel oral nucleoside analogue with a unique ability to induce single-strand DNA breaks after incorporation into DNA, leading to production of double-strand DNA breaks and/or G2 cell cycle arrest. In AML cell lines, the active metabolite of sapacitabine, CNDAC, is synergistic with hypomethylating agents (HMAs) particularly when treated with HMAs first. In a pilot study, there were 6 CRs and 2 PRs in 25 patients treated with sapacitabine in alternating cycles with decitabine. This global randomized phase 3 study evaluated the survival benefit of this treatment strategy vs. decitabine monotherapy. Methods: Decitabine 20 mg/m2 was administered intravenously daily x 5 days of a 4-week cycle (for the control arm and odd cycles of the study arm) alternating with sapacitabine 300 mg p.o. b.i.d. x 3 days/week x 2 weeks of a 4-week cycle (even cycles of the study arm). The safety of these doses was further evaluated in the lead-in phase of the phase 3 study to confirm the findings from the pilot study. Eligible patients were ≥70 years with untreated AML and unsuitable for or unwilling to receive standard induction chemotherapy. Patients who had received HMAs for prior MDS or MPD were excluded. Results: For 482 patients randomized to receive decitabine/sapacitabine (n=241) vs. decitabine only (n=241), randomization was stratified by the presence of antecedent MDS or MPN, peripheral white blood cell count (WBC <10,000 vs. ≥10,000) and bone marrow blast percentage (≥50% vs. < 50%). Median age was 77 years (range 70-90), and 317 patients had de novo AML (66%), 165 secondary AML (34%). WBC was ≥10,000 in 161 patients (33%) and >40,000 in 59 patients (12%); 194 patients (40%) had unfavorable cytogenetic risk by SWOG criteria. Disease characteristics were well balanced in both arms. In total, 13.7% of patients achieved CR, more on the study arm vs. control (16.6% vs. 10.8%). A total of 37.3% treated patients received ≥5 cycles of treatment, similar on both arms, as were 30- and 60-day death rates. Median overall survival was 5.9 months on the study arm vs. 5.7 months on control arm, which did not reach a statistically significant difference. In the subgroup of patients with <10,000 WBC (n=321), median overall survival was higher on the study arm vs. control arm (8.0 months vs. 5.8 months), as was CR rate (21.5% vs. 8.6%). Grade 3 or higher adverse events (regardless of causality) that occurred in >10% patients were thrombocytopenia, anemia, neutropenia, pneumonia, febrile neutropenia, sepsis, and disease progression. Conclusion: The regimen of sapacitabine administered in alternating cycles with decitabine was active and well tolerated but it did not significantly improve overall survival as compared to decitabine monotherapy. Further analyses are being conducted to characterize the subgroups of patients who appeared to have benefited from this treatment regimen and the potential cost savings associated with the use of an oral drug. Disclosures Kantarjian: Amgen: Research Funding; Pfizer: Research Funding; Delta-Fly Pharma: Research Funding; ARIAD: Research Funding; Bristol-Meyers Squibb: Research Funding; Novartis: Research Funding. Goldberg: Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Research Funding, Speakers Bureau; Celgene: Speakers Bureau; COTA: Employment, Equity Ownership; Pfizer: Honoraria; Ariad: Speakers Bureau; Jazz: Speakers Bureau. Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees. Strickland: Boehringer Ingelheim: Consultancy; Daiichi Sankyo: Consultancy; CTI BioPharma: Consultancy; Tolero Pharmaceuticals: Consultancy; Sunesis Pharamaceuticals: Consultancy, Research Funding; Baxalta: Consultancy; Alexion Pharmaceuticals: Consultancy; Astellas Pharma: Honoraria. Rubenstein: Alexion Pharmaceuticals: Speakers Bureau. Arellano: Cephalon Oncology: Research Funding. Schiller: bluebird bio: Research Funding; mateon therapeutics: Research Funding. Gaidano: Roche: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Montesinos: Celgene Corporation: Honoraria, Research Funding. Rizzieri: Shire: Research Funding; Erytech: Research Funding. Subramanian: Boehringer-Ingelheim, Lilly, BMS, Astra-Zeneca, Pfizer, Biocept: Consultancy, Speakers Bureau. Buyse: IDDI: Employment, Equity Ownership. Chiao: Cyclacel LTD: Employment, Equity Ownership.

Background: Left atrial appendage (LAA) occlusion provides an alternative to oral anticoagulation for thromboembolic risk reduction in patients with nonvalvular atrial fibrillation. Since regulatory approval in 2015, the WATCHMAN device has been the only LAA closure device available for clinical use in the United States. The PINNACLE FLX study (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) evaluated the safety and effectiveness of the next-generation WATCHMAN FLX LAA closure device in patients with nonvalvular atrial fibrillation in whom oral anticoagulation is indicated, but who have an appropriate rationale to seek a nonpharmaceutical alternative. Methods: This was a prospective, nonrandomized, multicenter US Food and Drug Administration study. The primary safety end point was the occurrence of one of the following events within 7 days after the procedure or by hospital discharge, whichever was later: death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring cardiac surgery. The primary effectiveness end point was the incidence of effective LAA closure (peri-device flow ≤5 mm), as assessed by the echocardiography core laboratory at 12-month follow-up. Results: A total of 400 patients were enrolled. The mean age was 73.8±8.6 years and the mean CHA 2 DS 2 -VASc score was 4.2±1.5. The incidence of the primary safety end point was 0.5% with a 1-sided 95% upper CI of 1.6%, meeting the performance goal of 4.2% ( P <0.0001). The incidence of the primary effectiveness end point was 100%, with a 1-sided 95% lower CI of 99.1%, again meeting the performance goal of 97.0% ( P <0.0001). Device-related thrombus was reported in 7 patients, no patients experienced pericardial effusion requiring open cardiac surgery, and there were no device embolizations. Conclusions: LAA closure with this next-generation LAA closure device was associated with a low incidence of adverse events and a high incidence of anatomic closure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02702271.

Purpose To evaluate both the potential causes and resultant outcomes in patients in whom subchondral insufficiency fracture of the knee (SIFK) develops after arthroscopy. Methods We performed a retrospective review of all patients with a magnetic resonance imaging diagnosis of SIFK after arthroscopic meniscectomy and chondroplasty over a 12‐year period. Results A total of 28 patients were included, with a mean age of 61 years and mean follow‐up period of 5.7 years. SIFK showed a predilection for the medial compartment (n = 25, 89%), specifically the medial femoral condyle (n = 21, 75%). In 7 patients (25%), SIFK developed in both the femoral condyle and tibial plateau in the ipsilateral compartment. Fifteen patients (54%) went on to conversion to arthroplasty at a mean of 0.72 years. The rate of survival free of conversion to arthroplasty was 57%, 45%, and 40% at 1 year, 2 years, and 5 years, respectively. Furthermore, 63% of patients with a meniscal tear and SIFK in the same compartment went on to arthroplasty ( P = .04). There was an increased risk of conversion to arthroplasty if SIFK was present in both the femur and tibia in the same compartment ( P = .04). A higher Kellgren‐Lawrence grade at the time of the SIFK diagnosis increased the likelihood of eventual arthroplasty ( P = .03). The presence of SIFK in both the femur and tibia in the ipsilateral compartment, an increased Kellgren‐Lawrence grade, and a meniscal tear or prior meniscectomy in the same compartment as SIFK were associated with an increased risk of eventual arthroplasty. Conclusions Post‐arthroscopic SIFK most commonly occurs in the medial compartment, particularly in patients who underwent a prior meniscectomy. The presence of meniscal root and radial tears in these patients is notable (75%). Ultimately, there is a high rate of progression of arthrosis (33%) and eventual conversion to arthroplasty. Level of Evidence Level IV, case series.

Abstract The brain vital signs framework is a portable, objective, neurophysiological evaluation of brain function at point-of-care. We investigated brain vital signs at pre- and post-season for age 14 or under (Bantam) and age 16–20 (Junior-A) male ice hockey players to (i) further investigate previously published brain vital sign results showing subconcussive cognitive deficits and (ii) validate these findings through comparison with head-impact data obtained from instrumented accelerometers. With a longitudinal study design, 23 male ice hockey players in Bantam (n = 13; age 13.63 ± 0.62) and Tier II Junior-A (n = 10; age 18.62 ± 0.86) divisions were assessed at pre- and post-season. None were diagnosed with a concussion during the season. Cognitive evoked potential measures of Auditory sensation (N100), Basic attention (P300) and Cognitive processing (N400) were analysed as changes in peak amplitudes and latencies (six standard scores total). A regression analysis examined the relationship between brain vital signs and the number of head impacts received during the study season. Significant pre/post differences in brain vital signs were detected for both groups. Bantam and Junior-A players also differed in number of head impacts (Bantam: 32.92 ± 17.68; Junior-A: 195.00 ± 61.08; P &lt; 0.001). Importantly, the regression model demonstrated a significant linear relationship between changes in brain vital signs and total head impacts received (R = 0.799, P = 0.007), with clear differences between the Bantam and Junior-A groups. In the absence of a clinically diagnosed concussion, the brain vital sign changes appear to have demonstrated the compounding effects of repetitive subconcussive impacts. The findings underscored the importance of an objective physiological measure of brain function along the spectrum of concussive impacts.

ObjectivePatients with meniscal tears reporting meniscal symptoms such as catching or locking have traditionally undergone arthroscopy. The present study was undertaken to investigate whether patients with meniscal tears who report meniscal symptoms have greater improvement with arthroscopic partial meniscectomy (APM) than physical therapy (PT).MethodsWe used data from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial, which randomized participants with knee osteoarthritis (OA) and meniscal tear to APM or PT. The frequency of each meniscal symptom (clicking, catching, popping, intermittent locking, giving way, swelling) was measured at baseline and 6 months. We used linear regression models to determine whether the difference in improvement in Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score at 6 months between patients treated with APM versus PT was modified by the presence of each meniscal symptom. We also determined the percentage of participants with resolution of meniscal symptoms by treatment group.ResultsWe included 287 participants. The presence (versus absence) of any of the meniscal symptoms did not modify the improvement in KOOS pain score between APM versus PT by >0.5 SD (all P interaction >0.05). APM led to greater resolution of intermittent locking and clicking than PT (locking 70% versus 46%, clicking 41% versus 25%). No difference in resolution of the other meniscal symptoms was observed.ConclusionMeniscal symptoms were not associated with improved pain relief. Although symptoms of clicking and intermittent locking had a greater reduction in the APM group, the presence of meniscal symptoms in isolation should not inform clinical decisions surrounding APM versus PT in patients with meniscal tear and knee OA.