Concomitant rotator cuff repair and instability surgery provide good patient-reported functional outcomes in patients aged 40 years or older with shoulder dislocation.

BACKGROUND: Recurrent anterior shoulder dislocation in patients aged ≥ 40 years is not as rare as once thought. The mechanism of instability in this patient population is different-more likely to be attributed to rotator cuff pathology-compared with that in younger individuals. With an increasingly aging active population, surgical management has a rising role in preventing morbidity associated with recurrent instability. Our purpose was to evaluate outcomes of anterior shoulder instability repair (ie, Bankart or bony Bankart repair) with and without rotator cuff repair (RCR) in patients aged ≥ 40 years. METHODS: We conducted a retrospective chart review of all patients aged ≥ 40 years who underwent surgical repair for anterior shoulder instability from 2008-2016. Patients were categorized into 4 cohorts: Bankart repair only, bony Bankart repair only, Bankart repair with concomitant RCR, and bony Bankart repair with concomitant RCR. Demographic and history-of-instability data were collected. Clinical and functional outcomes assessed included the Single Assessment Numeric Evaluation score, American Shoulder and Elbow Surgeons score, Penn Shoulder Score, visual analog scale score for pain, Western Ontario Shoulder Instability Index score, and patient satisfaction score. RESULTS: A total of 146 patients were included in this study, with 103 patients (71%) having ≥2-year outcome scores. Outcome scores were not significantly different among groups. For patients who underwent Bankart repair only, bony Bankart repair only, Bankart repair with RCR, and bony Bankart repair with RCR, the Single Assessment Numeric Evaluation scores were 80.8 ± 19.7, 90.0 ± 10.7, 79.3 ± 29.4, and 87.2 ± 10.6, respectively (P = .284); American Shoulder and Elbow Surgeons scores, 83.8 ± 19.7, 92.4 ± 17.4, 82.5 ± 25.6, and 85.6 ± 12.7, respectively (P = .114); Penn Shoulder Scores for function, 84.5 ± 17.9, 90.9 ± 15.3, 83.6 ± 25.1, and 95.7 ± 13.0, respectively (P = .286); and Western Ontario Shoulder Instability Index scores, 481.0 ± 519.5, 292.1 ± 414.3, 548.9 ± 690.5, and 320.6 ± 258.7, respectively (P = .713). Age at the time of surgery significantly differed between cohorts (P < .001). No patients had recurrence of instability during the study period. CONCLUSION: Similar functional outcomes can be achieved in the surgical management of anterior instability in patients aged ≥ 40 years. Rotator cuff tears should be suspected and repaired in patients with anterior instability, especially those aged ≥ 50 years.

Early radiographic failure of reverse total shoulder arthroplasty with structural bone graft for glenoid bone loss.

INTRODUCTION: Structural glenoid bone grafting in reverse total shoulder arthroplasty (RSA) has previously been reported to have good functional outcomes and low complication rates. We have observed different complication rates and hypothesized that baseplate fixation and severity of deformity may be predictors of early failure. METHODS: We retrospectively identified 44 patients who underwent RSA with structural bone grafting for glenoid bone defects. All patients had preoperative and postoperative (Grashey and axillary) radiographs at a minimum of 1 year after surgery and within 3 months of surgery for evaluation of implant and graft positioning. Clinical data and outcome scores were collected at the same intervals. RESULTS: There were 61% females and 39% males, with an average age of 74 ± 8 years at the time of surgery. The median final radiographic follow-up was 20 months, with 37 primary RSA and 7 revision RSA. Graft resorption was found in 11 of 44 patients (25%), and radiographic failure was found in 11 of 44 patients (25%) at a median of 8 months (range 3-51 months). Forward elevation, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Single Assessment Numeric Evaluation (SANE), and Simple Shoulder Test (SST) scores all significantly improved postoperatively (P < .0001). Radiographic baseplate failure was associated with graft resorption (P = .002), more retroversion correction (P = .02), and worse SANE scores at final follow-up (P = .01). DISCUSSION/CONCLUSION: RSA with structural bone graft improved range of motion and function, but there was a larger than previously reported baseplate loosening rate. This early radiographic loosening appeared to be associated with graft resorption, retroversion correction, and worse outcome scores.

The effect of an orthopedic specialty hospital on operating room efficiency in shoulder arthroplasty.

BACKGROUND: Operating room (OR) time is a major cost to the health care system. Therefore, increasing OR efficiency to save time may be a cost-saving tool. This study analyzed OR efficiency in shoulder arthroplasty at an orthopedic specialty hospital (OSH) and a tertiary referral center (TRC). METHODS: All primary shoulder arthroplasties performed at our OSH and TRC were identified (2013-2015). Manually matched cohorts from the OSH and TRC were compared for OR times. Three times (minutes) were recorded: anesthesia preparation time (APT; patient in room to skin incision), surgical time (ST; skin incision to skin closed), conclusion time (CT; skin closed to patient out of room). RESULTS: There were 136 primary shoulder arthroplasties performed at the OSH and matched with 136 at the TRC. OSH and TRC patients were similar in age (P = .95), body mass index (P = .97), Charlson Comorbidity Index (P = 1.000), sex (P = 1.000), procedure (P = 1.000), insurance status (P = .714), discharge destination (P = .287), and diagnoses (P = .354). These matched populations had similar ST (OSH: 110.0 ± 26.6 minutes, TRC: 113.4 ± 28.7 minutes; P = .307). APT (39.2 ± 8.0 minutes) and CT (7.6 ± 3.8 minutes) were shorter in the OSH patients than APT (46.3 ± 8.8 minutes; P < .001) and CT (11.2 ± 4.7 minutes; P < .001) in TRC patients. Total nonoperative time (sum of APT and CT) at the OSH (46.8 ± 8.9 minutes) was shorter than at the TRC (57.5 ± 10.4 minutes; P < .001). CONCLUSIONS: Despite similar patient populations and case complexity, the OR efficiency at an OSH was superior to a TRC. Further analysis is needed to determine the financial implications of this superior OR efficiency.

Incidence of and Risk Factors for Knee Collateral Ligament Injuries With Proximal Tibia Fractures: A Study of 32,441 Patients.

Proximal tibia fractures are associated with concurrent collateral ligament injuries. Failure to recognize these injuries may lead to chronic knee instability. The purpose of this study was to identify risk factors for concurrent collateral ligament injuries with proximal tibia fractures and their association with inpatient outcomes. A total of 32,441 patients with proximal tibia fractures were identified in the 2011-2012 National Trauma Data Bank. A total of 1445 (4.5%) had collateral ligament injuries, 794 (2.4%) had injuries to both collateral ligaments, 456 (1.4%) had a medial collateral ligament injury only, and 195 (0.6%) had a lateral collateral ligament injury only. On multivariate analysis, risk factors found to be associated with collateral ligament injuries included distal femur fracture (odds ratio, 2.1), pedestrian struck by motor vehicle (odds ratio, 2.0), obesity (odds ratio, 1.6), young age (odds ratio, 1.9 for 18 to 29 years vs 40 to 49 years), motorcycle accident (odds ratio, 1.5), and Injury Severity Score of 20 or higher (odds ratio, 1.4). In addition, patients with simultaneous injuries to both collateral ligaments had higher odds of inpatient adverse events (odds ratio, 1.51) and longer hospital stay (mean, 2.27 days longer). The risk factors reported by this study can be used to identify patients with proximal tibia fractures who may warrant more careful and thorough evaluation and imaging of their knee collateral ligaments. [Orthopedics. 2018; 41(2):e268-e276.].

Shoulder Injuries in Men's Collegiate Lacrosse, 2004-2009.

BACKGROUND: Men's lacrosse has been one of the fastest growing team sports in the United States, at both the collegiate and high school levels. Uniquely, it combines both continuous overhead and contact activity. Thus, an understanding of its injury epidemiology and mechanisms is vital. Shoulder injuries have been shown to be common in the sport, but thus far there has been no dedicated analysis of these injuries with which to better inform injury prevention strategies. STUDY DESIGN: Descriptive epidemiology study. METHODS: All athlete exposures (AEs) and shoulder injuries reported to the National Collegiate Athletic Association (NCAA) Injury Surveillance System for intercollegiate men's lacrosse athletes from 2004-2005 through 2008-2009 were collected. Type of injury was documented and the injury incidence per 1000 AEs was calculated. Event type, injury mechanism, specific injury, outcome, and time lost were recorded. Statistical analysis was performed using 95% CIs, calculated based on a normal approximation to Poisson distribution. RESULTS: There were a total of 124 observed shoulder injuries during 229,591 monitored AEs. With weights, this estimates 1707 shoulder injuries over 2,873,973 AEs, for an incidence of 0.59 per 1000 AEs (95% CI, 0.56-0.62). The incidence of shoulder injury during competition was 1.89 per 1000 AEs (95% CI, 1.76-2.02), compared with 0.35 per 1000 AEs (95% CI, 0.33-0.38) during practice. Acromioclavicular joint injuries were most common (0.29 per 1000 AEs; 95% CI, 0.27-0.31). Labral injuries and instability events were also frequent (0.11 per 1000 AEs; 95% CI, 0.10-0.13). Player-to-player contact caused 57% of all shoulder injuries, with 25% due to contact with the playing surface. The average time lost was 11.0 days, with 41.9% of all shoulder injuries requiring ≥10 days. Clavicle fractures and posterior shoulder dislocation were particularly severe, with no athletes returning to play during the same season. CONCLUSION: Shoulder injuries are common in NCAA men's lacrosse and are an important source of lost playing time. Acromioclavicular injuries were the most frequent injury in this series, but labral and instability injuries were also common. In this increasingly popular contact sport, an understanding of the epidemiology and mechanism of shoulder injuries may be used to improve protective equipment and develop injury prevention.

Distinct GAB2 signaling pathways are essential for myeloid and lymphoid transformation and leukemogenesis by BCR-ABL1.

Tyrosine kinase inhibitors (TKIs) directed against BCR-ABL1, the product of the Philadelphia (Ph) chromosome, have revolutionized treatment of patients with chronic myeloid leukemia (CML). However, acquired resistance to TKIs is a significant clinical problem in CML, and TKI therapy is much less effective against Ph(+)B-cell acute lymphoblastic leukemia (B-ALL). BCR-ABL1, via phosphorylated Tyr177, recruits the adapter GRB2-associated binding protein 2 (GAB2) as part of a GRB2/GAB2 complex. We showed previously that GAB2 is essential for BCR-ABL1-evoked myeloid transformation in vitro. Using a genetic strategy and mouse models of CML and B-ALL, we show here that GAB2 is essential for myeloid and lymphoid leukemogenesis by BCR-ABL1. In the mouse model, recipients of BCR-ABL1-transducedGab2(-/-)bone marrow failed to develop CML-like myeloproliferative neoplasia. Leukemogenesis was restored by expression of GAB2 but not by GAB2 mutants lacking binding sites for its effectors phosphatidylinositol 3-kinase (PI3K) or SRC homology 2-containing phosphotyrosine phosphatase 2 (SHP2). GAB2 deficiency also attenuated BCR-ABL1-induced B-ALL, but only the SHP2 binding site was required. The SHP2 and PI3K binding sites were differentially required for signaling downstream of GAB2. Hence, GAB2 transmits critical transforming signals from Tyr177 to PI3K and SHP2 for CML pathogenesis, whereas only the GAB2-SHP2 pathway is essential for lymphoid leukemogenesis. Given that GAB2 is dispensable for normal hematopoiesis, GAB2 and its effectors PI3K and SHP2 represent promising targets for therapy in Ph(+)hematologic neoplasms.

Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036.

Acquired resistance to ABL1 tyrosine kinase inhibitors (TKIs) through ABL1 kinase domain mutations, particularly the gatekeeper mutant T315I, is a significant problem for patients with chronic myeloid leukemia (CML). Using structure-based drug design, we developed compounds that bind to residues (Arg386/Glu282) ABL1 uses to switch between inactive and active conformations. The lead "switch-control" inhibitor, DCC-2036, potently inhibits both unphosphorylated and phosphorylated ABL1 by inducing a type II inactive conformation, and retains efficacy against the majority of clinically relevant CML-resistance mutants, including T315I. DCC-2036 inhibits BCR-ABL1(T315I)-expressing cell lines, prolongs survival in mouse models of T315I mutant CML and B-lymphoblastic leukemia, and inhibits primary patient leukemia cells expressing T315I in vitro and in vivo, supporting its clinical development in TKI-resistant Ph(+) leukemia.

Structure of human phosphatidylcholine transfer protein in complex with its ligand.

Phosphatidylcholines (PtdChos) comprise the most common phospholipid class in eukaryotic cells. In mammalian cells, these insoluble molecules are transferred between membranes by a highly specific phosphatidylcholine transfer protein (PC-TP) belonging to the steroidogenic acute regulatory protein related transfer (START) domain superfamily of hydrophobic ligand-binding proteins. The crystal structures of human PC-TP in complex with dilinoleoyl-PtdCho or palmitoyl-linoleoyl-PtdCho reveal that a single well-ordered PtdCho molecule occupies a centrally located tunnel. The positively charged choline headgroup of the lipid engages in cation-pi interactions within a cage formed by the faces of three aromatic residues. These binding determinants and those for the phosphoryl group may be exposed to the lipid headgroup at the membrane-water interface by a conformational change involving the amphipathic C-terminal helix and an Omega-loop. The structures presented here provide a basis for rationalizing the specificity of PC-TP for PtdCho and may identify common features used by START proteins to bind their hydrophobic ligands.

Human phosphatidylcholine transfer protein: purification, crystallization and preliminary X-ray diffraction data.

We have expressed, purified and crystallized recombinant human phosphatidylcholine transfer protein (PC-TP) and selenomethionyl PC-TP bound to dilinoleoyl phosphatidylcholine. The biochemical properties of native and selenomethionyl PC-TP were indistinguishable, and the two proteins crystallized under similar conditions. Both native and selenomethionyl PC-TP crystallized in two distinct space groups and diffracted X-rays to 2.4 A resolution.