Citations

Abstract Rationale Less invasive, nonsurgical approaches are needed to treat severe emphysema. Objectives To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management. Methods In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control). Measurements and Main Results The primary efficacy outcome was the difference in mean FEV1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment (n = 113) or control (n = 59). Mean FEV1 showed statistically significant improvements between the treatment and control groups—between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060–0.141) and 0.099 L (95% BCI, 0.048–0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax. Conclusions In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Objectives: Hip arthroscopy is becoming more advanced and commonly performed. However, significant controversy exists regarding whether high grade acetabular cartilage lesions should be treated with debridement or microfracture. In addition, patients treated with microfracture are subject to extended partial weight-bearing rehabilitation in order to mitigate risk of subchondral plate fracture and protect fibrocartilage tissue formation. The purpose of this study was to determine the mid-term patient-reported outcomes and failure rate and patient-reported outcomes of Grade 3 and 4 acetabulum labrum articular disruption (ALAD) lesions managed with microfracture or debridement. Methods: Primary arthroscopic labral repair cases at two centers from November 2008 to April 2016 were reviewed in patients aged < 55 years with unipolar ALAD Grade 3 and 4 pathology. Patients undergoing microfracture and debridement were compared using visual analog pain scale (VAS), modified Harris Hip Score (mHHS), and Hip Outcome Score - Sports Specific Subscale (HOS-SSS) to determine predictors of outcomes and failure. Results: 127 hips in 123 patients (47 M, 76 F, mean age 34.7 ± 11.1) undergoing debridement (n = 95) or microfracture (n = 32) were followed for a mean of 4.9 years (range 2.0 - 8.5). Patients undergoing debridement achieved 3.5 point mean improvements in VAS (p < 0.01), 20.9 point improvements in mHHS (p < 0.01), and 25.5 point improvements in HOS-SSS (p < 0.01), which was statistically similar to that observed in microfracture patients (p ≥ 0.19). Five-year survival free of revision surgery was 83.0% in the debridement group and 85.6% in the microfracture group (p = 0.85). Cartilage treatment technique was found not to be predictive of revision risk during both univariate (p = 0.84) and multivariate (p = 0.84) analysis. Conclusion: Patients undergoing debridement of high grade unipolar acetabular cartilage lesions demonstrate similar patient reported outcome scores and revision rates compared to patients undergoing microfracture. These outcomes support debridement of acetabular lesions in order to optimize recovery while maintaining established positive outcomes following hip arthroscopy. [Table: see text]

Objectives: Participation in National Collegiate Athletic Association (NCAA) football is at an all-time high. This population experiences a substantial injury burden with many of these injuries affecting the upper extremities. The NCAA has adopted a data-driven decision-making process when providing recommendations for protecting player safety. The purpose of this study was to describe the epidemiology of hand and wrist injury in NCAA football in an effort to provide meaningful data for tailoring effective injury prevention strategies. Methods: An epidemiologic study utilizing the NCAA Injury Surveillance Program (NCAA-ISP) database was performed to investigate rates and patterns of hand and wrist injury in NCAA varsity football teams participating in the NCAA-ISP from 2009 to 2014. Descriptive statistics were used to present demographic data. Injury rates were calculated per 1000 athlete-exposures (AEs) using statistical cross-referencing between injury-level and event-level data. Injury mechanism and severity, as measured by time-loss from play, were determined and compared between exposure factors such as player position, player seniority, and practice versus game setting. Results: 725 hand and wrist injuries were captured in 899,225 AEs. The observed practice hand and wrist injury rate was 0.51 injuries per thousand AEs, which was significantly lower than the game injury rate of 3.60 (p < 0.01). Comparing player demographics for injuries sustained during practice as opposed to game time revealed significant differences based on player year, player position, activity performed at the time of injury, and mechanism of injury (p < 0.01, Figure 1). Player-on-player contact was the most common injury mechanism reported with blocking being the most common activity at injury. Of all sustained injuries, 71.4% resulted in no time loss from competition whereas 9.8% of injuries resulted in greater than 7 days of time loss. On average, fracture resulted in the greatest time loss from competition (8.3 ± 24.0 days for injuries sustained in practice setting, 7.7 ±15.8 days for injuries sustained in game setting). When comparing injury by location, hand injury resulted in greater time loss (3.7 ± 15.1, 4.4 ± 13.8) than to nail/subungual (0±0, 0±0), finger (1.6 ± 6.7, 1.1 ± 4.2), and wrist injury (1.2 ± 3.8, 1.8 ± 4.9). Conclusion: This study characterizes the incidence of NCAA football hand and wrist injuries in both practice and game settings and demonstrates the relatively low rate of injuries leading to loss of playing time. Hand and wrist injury was found to be significantly more common in games when compared to practice. Offensive linemen were the most commonly affected players in the cohort, with most injuries occurring during game time compared to practice. This study provides valuable prognostic data regarding expected time loss from play on a per injury pattern basis. Further investigation on specific injury subtypes and expected time loss as a result of these injures would provide trainers, players, and coaches with useful information on an expected post-injury recovery and rehabilitation timeline. [Figure: see text]

Objectives: Little is known about the natural history and long-term outcome of a surgically treated symptomatic lateral discoid meniscus. The goals of this study were to describe the rate and factors associated with recurrent lateral meniscus tears and progression to symptomatic lateral compartment osteoarthritis (OA) in patients surgically treated for a symptomatic lateral discoid meniscus. Patients with surgically treated lateral discoid meniscus have a high incidence of meniscus re-tear and progression to lateral compartment OA. Methods: A large, geographic database was reviewed to identify and confirm patients presenting with symptomatic lateral discoid meniscus between 1998 and 2015. Charts were reviewed to document treatment and outcomes at a minimum clinical follow-up of two years. Results: 70 discoid meniscus patients (30 F, 40 M) with a mean age of 27 years (Range: 2.0-66.0) were followed for an average of 5.8 years (Range 2.0-23.7). Sixty patients underwent surgical management: 49 (82%) patients underwent partial lateral meniscectomy and 11 (18%) underwent meniscus repair (including saucerization). Tear-free survival following surgery was 93% at 2 years, 69% at 5 years, and 40% at 8 years. Overall progression to symptomatic lateral compartment OA in the surgical group was 10% at 2 years, 23% at 5 years, and 48% at 8 years. Of those patients who developed lateral compartment OA, 55% (11/20) had a Kellgren-Lawrence score 2 or greater at last radiographic follow-up. Young age and open growth plates were associated with increased incidence of postoperative re-tear (HR: 0.96, CI: 0.93-0.99, p = 0.01). Increased age at diagnosis and BMI ≥ 30 were associated with increased risk of progression to lateral compartment OA on final radiographs. Conclusion: Patients with a surgically treated lateral discoid meniscus tear had a high rate of recurrent meniscus tear at long-term follow-up (60% at 8 years) that was associated with young age. Approximately 48% of surgically treated patients developed symptomatic lateral compartment OA at eight years from initial presentation. The risk of progression to OA increased with older age at diagnosis and BMI ≥ 30.

Cirrhotic cardiomyopathy (CCM) is cardiac dysfunction in patients with end‐stage liver disease in the absence of prior heart disease. First defined in 2005 during the World Congress of Gastroenterology, CCM criteria consisted of echocardiographic parameters to identify subclinical cardiac dysfunction in the absence of overt structural abnormalities. Significant advancements in cardiovascular imaging over the past 14 years, including the integration of myocardial deformation imaging into routine clinical practice to identify subclinical cardiovascular dysfunction, have rendered the 2005 CCM criteria obsolete. Therefore, new criteria based on contemporary cardiovascular imaging parameters are needed. In this guidance document, assembled by a group of multidisciplinary experts in the field, new core criteria based on contemporary cardiovascular imaging parameters are proposed for the assessment of CCM. This document provides a critical assessment of the diagnosis of CCM and ongoing assessment aimed at improving clinical outcomes, particularly surrounding liver transplantation. Key points and practice‐based recommendations for the diagnosis of CCM are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.

Background: Little is known about the natural history of a surgically treated symptomatic lateral discoid meniscus. The goals of this study were to describe the rate and factors associated with recurrent lateral meniscal tears and progression to symptomatic lateral compartment osteoarthritis (OA) in patients surgically treated for a symptomatic lateral discoid meniscus. Hypothesis: Patients with surgically treated lateral discoid meniscus have a high incidence of meniscal retear and progression to lateral compartment OA. Study Design: Case series; Level of evidence, 4. Methods: A large geographic database was reviewed to identify and confirm patients presenting with symptomatic lateral discoid meniscus between 1998 and 2015. Charts were reviewed to document treatment and outcomes at a minimum clinical follow-up of 2 years. Results: A total of 59 patients (27 females, 32 males) with a mean age of 25.7 years (range, 4.0-66.0 years) underwent surgical management of a discoid lateral meniscus and were evaluated for a mean of 5.6 years (range, 2.0-23.7 years). Of these, 48 (82%) patients underwent partial lateral meniscectomy, with 24 patients undergoing concurrent saucerization. Eleven (18%) underwent meniscal repair. Tear-free survival following surgery was 41% at 8 years. Progression to symptomatic lateral compartment OA was 50% at 8 years. Young age (hazard ratio, 0.96; 95% CI, 0.93-0.99; P = .01) and open growth plates (hazard ratio, 3.19; 95% CI, 1.15-8.88; P = .03) were associated with increased incidence of postoperative retear. Older age at diagnosis and body mass index ≥30 kg/m 2 were associated with increased risk of progression to lateral compartment OA on final radiographs. Conclusion: Patients with a surgically treated lateral discoid meniscal tear had a high rate of recurrent meniscal tear (59% at 8 years). Approximately 50% of surgically treated patients developed symptomatic lateral compartment OA at 8 years from diagnosis.

Background Clinical characteristics and outcomes of takotsubo syndrome ( TTS ) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short‐ and long‐term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short‐ and long‐term mortality. A subanalysis was performed comparing long‐term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long‐term mortality was higher in patients with malignancy ( P <0.001), while short‐term outcome was comparable ( P =0.17). In a subanalysis, long‐term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies ( P =0.13). Malignancy emerged as an independent predictor of long‐term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS , and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL : http://www.clinicaltrial.gov . Unique identifier: NCT 01947621.

26 Background: NKTR-262 is a novel intratumoral prodrug designed to promote tumor antigen release, an immune stimulatory environment, and antigen presentation. NKTR-214 increases CD8+ T cells and NK cells in the tumor microenvironment. The combination of NKTR-262 with NKTR-214 accesses innate and adaptive immunity to provide an abscopal response and systemic tumor immunity. The Phase 1b/2 REVEAL trial is enrolling. Methods: In a 3+3 Phase 1 design, pts who are relapsed/refractory to ≥1 CPI receive escalating doses of intratumoral (IT) NKTR-262 followed by combined q3w treatment of IT NKTR-262 and fixed-dose intravenous (IV) NKTR-214 (0.006 mg/kg). Phase 1 will evaluate PK, safety, efficacy, and determine recommended Phase 2 dose. Scans are conducted every 9 wks (± 1 wk). Peripheral blood (PB) and tumor tissue are collected to measure biomarkers of immune activation. In Phase 2 expansion, NKTR-262 + NKTR-214 ± IV nivolumab (360 mg) will be assessed in specific tumor cohorts of IO-naïve and experienced pts. Results: As of 06 Nov 2018, 11 pts had received at least one cycle of NKTR-262 + NKTR-214 therapy. 7/11 pts were efficacy evaluable with at least one on-treatment scan (4 MEL, 2 SARC, 1 CRC). 2/4 R/R melanoma pts had uPRs with 100% (scan 2) and 40% (scan 1) reductions in target lesions per RECIST 1.1, respectively. Both patients remain on treatment. Two SARC pts had stable disease at scan 1. No pts experienced G3 or higher TRAEs or immune-related adverse events (AEs). Most common G1-2 AEs were transient flu-like symptoms. Gene expression analysis of tumor and PB show dose-dependent induction (4 to 16-fold) of TLR target genes. Consistent with the mechanism of action for NKTR-214, PB flow cytometry shows an average 13-fold increase from baseline in Ki67+ CD8+T cells in 6 pts. Conclusions: NKTR-262 + NKTR-214 engage the immune activation cascade from local tumor antigen production to anti-tumor T cell response. Initial dose levels of NKTR-262 with fixed-dose NKTR-214 were well-tolerated with early evidence of clinical activity. These data support continued evaluation of the combination +/- nivolumab. Clinical trial information: NCT03435640.