Teaching Impact on Telestroke Nurse Recognition of Large Vessel Occlusion Computerized Tomography Perfusion Patterns.

Background and Purpose- A distinguishing feature of our Stroke Network is telestroke nurses who remotely facilitate evaluations. To enable expeditious transfer of large vessel occlusion (LVO) acute ischemic stroke patients presenting to nonthrombectomy centers, the telestroke nurses must immediately identify color thresholded computerized tomography perfusion (CTP) patterns consistent with internal carotid artery (ICA), middle cerebral artery (MCA) segment 1(M1), and MCA segment 2 (M2) LVO acute ischemic stroke. Methods- We developed a 6-month series of tutorials and tests for 16 telestroke nurses, focusing on CTP pattern recognition consistent with ICA, M1, or M2 LVO acute ischemic stroke. We simultaneously conducted a prospective cohort study to evaluate the impact of this intervention. Results- Telestroke nurses demonstrated good accuracy in detecting ICA, M1, or M2 LVO during the first 3 months of teaching (83%-94% accurate). This significantly improved during the last 3 months (99%-100%), during which the likelihood of correctly identifying the presence of any one of these LVOs exceeded that of the first 3 months (P<0.001). There was a higher probability of correctly identifying any CTP pattern as consistent with either an ICA, M1, or M2 occlusion versus other types of occlusions or nonocclusions (odds ratio, 5.22 [95% CI, 3.2-8.5]). Over time, confidence for recognizing CTP patterns consistent with an ICA, M1, or M2 LVO did not differ significantly. Conclusions- A series of tutorials and tests significantly increased the likelihood of telestroke nurses correctly identifying CTP patterns consistent with ICA, M1, or M2 LVOs, with the benefit of these tutorials and test reviews peaking and plateauing at 4 months.

Developing and Monitoring a Standard-of-Care Chimeric Antigen Receptor (CAR) T Cell Clinical Quality and Regulatory Program.

As the world of cellular therapy expands to include immune effector cell (IEC) products such as commercial chimeric antigen receptor (CAR) T cells, quality management (QM) professionals are faced with creating either new IEC stand-alone programs or expand existing hematopoietic cell transplantation (HCT) programs to promote patient safety and be aligned with quality, regulatory, and accreditation requirements. The team professionals at City of Hope (COH) recently expanded the quality HCT program to include IEC products and, in doing so, implemented new regulatory infrastructure while maintaining high quality patient care. At COH, we developed the quality structure of our cellular therapy program through collaborations between quality, regulatory, and CAR T patient care committees, which included physicians and nurse coordinators. To ensure the quality of our program, we monitor data collection and reporting, perform quarterly proactive audits of, for example, outcome analysis, and measure selected end-points for benchmarking purposes. QM professionals play a critical role in the monitoring and evaluation processes and provide guidance on how to implement accreditation requirements and what impact the requirements may have on care management. Here we describe the process by which COH expanded our HCT QM program to include IEC therapy. We share examples of how we developed our overall program structure and other key items such as how we addressed patient care management and accreditation to apprise other programs that wish to create and/or expand existing programs.

Optimization of IL13Rα2-Targeted Chimeric Antigen Receptor T Cells for Improved Anti-tumor Efficacy against Glioblastoma.

T cell immunotherapy is emerging as a powerful strategy to treat cancer and may improve outcomes for patients with glioblastoma (GBM). We have developed a chimeric antigen receptor (CAR) T cell immunotherapy targeting IL-13 receptor α2 (IL13Rα2) for the treatment of GBM. Here, we describe the optimization of IL13Rα2-targeted CAR T cells, including the design of a 4-1BB (CD137) co-stimulatory CAR (IL13BBζ) and a manufacturing platform using enriched central memory T cells. Utilizing orthotopic human GBM models with patient-derived tumor sphere lines in NSG mice, we found that IL13BBζ-CAR T cells improved anti-tumor activity and T cell persistence as compared to first-generation IL13ζ-CAR CD8+ T cells that had shown evidence for bioactivity in patients. Investigating the impact of corticosteroids, given their frequent use in the clinical management of GBM, we demonstrate that low-dose dexamethasone does not diminish CAR T cell anti-tumor activity in vivo. Furthermore, we found that local intracranial delivery of CAR T cells elicits superior anti-tumor efficacy as compared to intravenous administration, with intraventricular infusions exhibiting possible benefit over intracranial tumor infusions in a multifocal disease model. Overall, these findings help define parameters for the clinical translation of CAR T cell therapy for the treatment of brain tumors.

Preoperative patient expectations of elective reverse shoulder arthroplasty.

BACKGROUND: The purpose of this study was to determine patients' preoperative expectations before primary elective reverse shoulder arthroplasty (RSA). We hypothesized that younger patients, patients with better preoperative function, patients with shoulder osteoarthritis (OA), and patients with no prior joint replacements would have higher expectations of RSA. METHODS: We prospectively studied 333 primary RSAs performed for cuff tear arthropathy (n = 242), OA (n = 68), or post-traumatic arthritis (n = 23). Expectations were assessed preoperatively using the Hospital for Special Surgery's shoulder surgery expectations survey. Preoperative patient-reported measures were assessed with the American Shoulder and Elbow Surgeons shoulder score; Shoulder Activity Scale score; Short Form 12 mental component and physical component scores; and visual analog scale scores for pain, fatigue, and general health. A Poisson regression model was performed to control for potential confounding variables. RESULTS: Relief of night-time pain, relief of daytime pain, improvement in self-care, improvement in the ability to drive or put on a seat belt, and improvement in the ability to perform daily activities were reported as "very important" by approximately half of patients. No association was found between age and overall expectations. Multivariate analysis showed that better preoperative Shoulder Activity Scale and Short Form 12 physical component scores were associated with greater expectations (P < .001). OA was associated with greater expectations compared with cuff tear arthropathy (P < .001). A history of either contralateral RSA or any joint replacement was associated with lower expectations (P < .001). CONCLUSION: Patients have the highest expectations for pain relief and the performance of simple tasks after RSA. Patients with higher preoperative function, OA, and no previous joint replacements have greater expectations of RSA.

PROMIS physical function underperforms psychometrically relative to American Shoulder and Elbow Surgeons score in patients undergoing anatomic total shoulder arthroplasty.

BACKGROUND: The purpose of this study was to evaluate the psychometric properties of the Patient-Reported Outcomes Measurement Information System (PROMIS) physical function computer adaptive test (PF-CAT) relative to the American Shoulder and Elbow Surgeons (ASES) score in patients with glenohumeral osteoarthritis undergoing primary anatomic total shoulder arthroplasty (TSA). METHODS: A retrospective study of an institutional TSA registry was performed. Preoperative PROMIS PF-CAT and ASES scores were collected. Floor and ceiling effects were determined, and convergent validity was established through Pearson correlations. Rasch partial credit modeling was used for psychometric analysis of the validity of PF-CAT and ASES question items. Person-item maps were generated to characterize the distribution of question responses along the latent dimension of shoulder disability. RESULTS: Responses from 179 patients (184 shoulders) were included. PF-CAT had a moderate correlation to ASES (r = 0.487; P < .001), with no floor or ceiling effects; ASES had a 1.1% floor effect and no ceiling effect. With iterative Rasch model item-reduction analysis eliminating poorly fitting question items, all possible PF-CAT items were eliminated after 6 iterations. With ASES, just 1 function question item was dropped. Person-item maps showed ASES to be superior to PROMIS PF-CAT psychometrically, with sequential and improved coverage of the latent dimension of shoulder disability. CONCLUSION: Despite moderate correlation with ASES, PROMIS PF-CAT demonstrated inferior validity and psychometric properties in patients undergoing TSA. PF-CAT should not replace the ASES in this population of patients.

Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL.

Myeloablative autologous hematopoietic stem cell transplantation (HSCT) is a mainstay of therapy for relapsed intermediate-grade B-cell non-Hodgkin lymphoma (NHL); however, relapse rates are high. In phase 1 studies designed to improve long-term remission rates, we administered adoptive T-cell immunotherapy after HSCT, using ex vivo-expanded autologous central memory-enriched T cells (TCM) transduced with lentivirus expressing CD19-specific chimeric antigen receptors (CARs). We present results from 2 safety/feasibility studies, NHL1 and NHL2, investigating different T-cell populations and CAR constructs. Engineered TCM-derived CD19 CAR T cells were infused 2 days after HSCT at doses of 25 to 200 × 10(6) in a single infusion. In NHL1, 8 patients safely received T-cell products engineered from enriched CD8(+) TCM subsets, expressing a first-generation CD19 CAR containing only the CD3ζ endodomain (CD19R:ζ). Four of 8 patients (50%; 95% confidence interval [CI]: 16-84%) were progression free at both 1 and 2 years. In NHL2, 8 patients safely received T-cell products engineered from enriched CD4(+) and CD8(+) TCM subsets and expressing a second-generation CD19 CAR containing the CD28 and CD3ζ endodomains (CD19R:28ζ). Six of 8 patients (75%; 95% CI: 35-97%) were progression free at 1 year. The CD4(+)/CD8(+) TCM-derived CD19 CAR T cells (NHL2) exhibited improvement in expansion; however, persistence was ≤28 days, similar to that seen by others using CD28 CARs. Neither cytokine release syndrome nor delayed hematopoietic engraftment was observed in either trial. These data demonstrate the safety and feasibility of CD19 CAR TCM therapy after HSCT. Trials were registered at www.clinicaltrials.gov as #NCT01318317 and #NCT01815749.

Patellofemoral Cartilage Lesions Treated With Particulated Juvenile Allograft Cartilage: A Prospective Study With Minimum 2-Year Clinical and Magnetic Resonance Imaging Outcomes.

PURPOSE: To analyze the functional outcomes of patients treated with particulated juvenile articular cartilage (PJAC) for symptomatic articular cartilage lesions in the patellofemoral joint, correlates clinical outcomes with magnetic resonance imaging (MRI) appearance of the repair tissue using cartilage-sensitive quantitative T2-mapping. METHODS: All patients treated with PJAC for patellofemoral lesions were identified and prospectively followed with clinical outcome scores (International Knee Documentation Committee [IKDC], Knee Outcome Survey-Activities of Daily Living [KOS-ADL], and Marx Activity Scale [MAS]). Postoperative MRI scans using quantitative T2 mapping were obtained and interpreted by an independent musculoskeletal radiologist. RESULTS: Twenty-seven patients treated with PJAC for 30 full-thickness patellofemoral cartilage lesions were identified; mean postoperative follow-up was 3.84 years. Improvements from pre- to postoperative mean IKDC (45.9 vs 71.2, P < .001) and KOS-ADL (60.7 vs 78.8, P < .001) scores were observed; no significant change in MAS was seen (7.04 vs 7.17, P = .97). Advanced age, history of previous surgery, lesion location (patella vs trochlea), or concomitant tibial tubercle osteotomy did not affect outcome scores. Greater body mass index was associated with less improvement in KOS-ADL score. No patients required reoperation for graft-related issues. Lesion fill exceeding 67% by MRI assessment was noted in 69.2% of lesions; depth of lesion fill did not correlate with clinical outcomes. Quantitative T2-mapping revealed prolonged relaxation time at the graft site compared with adjacent normal cartilage at both deep and superficial zones. CONCLUSIONS: This study found significantly improved pain and function in patients treated with PJAC for symptomatic patellofemoral articular cartilage defects. No patients required reoperation for graft-related issues. Postoperative MRI revealed majority lesion fill in more than 69% of patients, but persistent morphologic differences between graft site and normal adjacent cartilage remain. Though we support PJAC use in this setting to improve patient subjective outcomes, improved appearance on postoperative imaging was not found to provide additional clinical benefit. LEVEL OF EVIDENCE: Level IV, case series.

Minimal Clinically Important Difference and Substantial Clinical Benefit After Revision Hip Arthroscopy.

PURPOSE: To define minimal clinically important difference (MCID) and substantial clinical benefit (SCB) in revision hip arthroscopy. METHODS: The modified Harris Hip Score (mHHS), the Hip Outcome Score (HOS), and the international Hip Outcome Tool (iHOT-33) were administered to revision hip arthroscopy patients. At 1 year postoperatively, patients graded their hip function based on anchor responses. SCB was defined as both a net change and an absolute value. Receiver operating characteristic analysis with area under the curve was used to confirm psychometric values. A distribution-based method was used for MCID. RESULTS: Forty-nine patients were included with a mean age of 29.7 (±8.6) years. The most common indication for revision hip arthroscopy was residual femoroacetabular impingement (FAI; N = 34; 69.4%) followed by capsular management (N = 8; 16.3%). At 1-year follow-up, 34 patients reported feeling improved. Outcome score change corresponding to MCID and SCB net change for the mHHS, HOS Activities of Daily Living (ADL), HOS Sports, and iHOT-33 was 7.9/23.1, 7.9/16.2, 13.1/25.0, and 12.8/25.5, respectively. A higher proportion of patients with residual FAI achieved MCID compared with patients with other diagnoses. On the preoperative HOS ADL, HOS Sports, and iHOT-33, patients scoring below 67.7 (0.78), 55.6 (0.81), and 35.7 (0.73) were significantly more likely to achieve SCB postoperatively. Thirty-four patients (73.9%) were classified as receiving physical function improvement, and on the HOS Sports, MCID was achieved by 65% whereas 43% met the SCB criteria. CONCLUSIONS: MCID values ranged from 7.9 on the mHHS and the HOS ADL to 13.1 on the HOS Sports. SCB net change ranged from 16.2 on the HOS ADL to 25.2 on the iHOT-33, whereas absolute SCB ranged from 82.4 on the iHOT-33 to 84.7 on the mHHS. Residual FAI and capsular management were the most common indications for revision surgery with patients who underwent surgery for the former found to be most likely to achieve clinically significant improvement. LEVEL OF EVIDENCE: Level IV, case series.

Return to sport after shoulder arthroplasty: a systematic review and meta-analysis.

PURPOSE: With increasing incidence and indications for shoulder arthroplasty, there is an increasing emphasis on the ability to return to sports. The main goal of this study was to determine the rate of return to sport after shoulder arthroplasty. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to perform this systematic review and meta-analysis. A search was performed on MEDLINE, Scopus, EMBASE, and the Cochrane Library. The quality of the included studies was evaluated according to the Methodological Index for Nonrandomized Studies checklist. The main judgement outcome was the rate of return to sports activity after shoulder arthroplasty and the level of play upon return (identical or higher/lower level). RESULTS: Thirteen studies were reviewed, including 944 patients (506 athletes), treated with shoulder arthroplasty at an average follow-up of 5.1 years (range, 0.5-12.6 years). The most common sports were swimming (n = 169), golf (n = 144), fitness sports (n = 71), and tennis (n = 63). The overall rate of return to sport was 85.1% (95% CI, 76.5-92.3%), including 72.3% (95% CI, 60.6-82.8%) returning to an equivalent or improved level of play, after 1-36 months. Patients undergoing anatomic total shoulder arthroplasty returned at a significantly higher rate (92.6%) compared to hemiarthroplasty (71.1%, p = 0.02) or reverse total shoulder arthroplasty (74.9%, p = 0.003). CONCLUSION: Most patients are able to return to one or more sports following shoulder arthroplasty, with anatomic total shoulder arthroplasty having the highest rate of return. LEVEL OF EVIDENCE: IV.

Effect of preoperative patient expectations on outcomes after reverse total shoulder arthroplasty.

BACKGROUND: The purpose of this study was to determine the effect of preoperative expectations on outcomes after reverse shoulder arthroplasty (RSA). We hypothesized that patients with greater expectations would have better outcomes. METHODS: Patients undergoing primary RSA completed the Hospital for Special Surgery's Shoulder Expectations Survey preoperatively. Preoperative and 2-year postoperative clinical outcomes were measured with the American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form, Shoulder Activity Scale (SAS), 36-Item Short Form Health Survey (SF-36), and visual analog scales (VASs). Pearson correlations were used to assess the relationship between the number of expectations and outcomes. Differences in outcomes between those with higher and lower levels of expectations for each expectation question were assessed by independent samples t test. Multivariable linear regression analysis was used to control for potential confounding factors. RESULTS: We evaluated 135 patients at 2 years postoperatively. Patients had higher expectations for relieving pain, improving self-care, improving ability to perform daily activities, and improving ability to drive or put on a seatbelt. Patients with a greater number of high expectations preoperatively did not have better ASES, SAS, or VAS pain scores postoperatively. However, higher expectations for relieving nighttime pain was associated with ASES (ß = 7.0, P = .048) and VAS pain scores (ß = -5.9, P = .047) as well as 2-year improvement of VAS pain (ß = -6.1, P = .039). Higher expectations for improving the ability to participate in nonoverhead sports was associated with improvements in SAS (ß = 2.8, P = .020). CONCLUSION: A higher level of expectations for relief of nighttime pain and improving ability to participate in nonoverhead sports is associated with improved outcomes after RSA.

Risk factors for failing to achieve improvement after anatomic total shoulder arthroplasty for glenohumeral osteoarthritis.

BACKGROUND: Although anatomic total shoulder arthroplasty (TSA) successfully improves pain and function, not all patients improve clinically. This study was conducted to determine patient-related factors for failure to achieve improvement after primary TSA for osteoarthritis at 2 years postoperatively. METHODS: This prospective study reviewed an institutional shoulder registry for consecutive patients who underwent primary TSA for osteoarthritis from 2007 to 2013 with baseline and 2-year postoperative American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form scores. A failed outcome was defined as (1) a failure to reach the ASES minimal clinically important difference of 16.1 points or (2) revision surgery within 2 years of the index procedure, or both. Univariate and multivariable analyses of clinical and demographic patient factors were performed using logistic regression. RESULTS: Of 459 arthroplasties that met inclusion criteria, 411 were deemed successful by the aforementioned criteria, and 48 (10.5%) failed to achieve a desirable outcome. Clinical risk factors associated with failure included previous surgery to the shoulder (P = .047), presence of a torn rotator cuff (P = .025), and presence of diabetes (P = .036), after adjusting for age, sex, race, and body mass index. A higher preoperative ASES score at baseline was associated with failure (P < .001). CONCLUSION: Previous shoulder surgery, a rotator cuff tear requiring repair during TSA, presence of diabetes, surgery on the nondominant arm, and a higher baseline ASES score were associated with a higher risk of failing to achieve improvement after anatomic TSA.

Arthroscopic Treatment of Femoroacetabular Impingement in Adolescents Provides Clinically Significant Outcome Improvement.

PURPOSE: To define minimal clinically important difference (MCID) and substantial clinical benefit (SCB) for adolescents undergoing arthroscopic femoroacetabular impingement (FAI) surgery. METHODS: A prospective institutional hip preservation registry was reviewed to identify hip arthroscopies performed for FAI. Patients with pre-existing hip conditions such as slipped capital femoral epiphysis and Legg-Calve-Perthese were excluded. Included patients were 18 years and younger. The modified Harris Hip Score (mHHS), the Hip Outcome Score (HOS), and the international Hip Outcome Tool (iHOT-33) were administered as part of the registry. MCID was calculated using a distribution-based method, and SCB was calculated using a physical function anchor question. Receiver operating characteristic analysis with area under the curve (AUC) was used for psychometric analyses. RESULTS: Forty-seven adolescents were identified. The majority of patients were female (n = 32, 68.1%) with a mean age of 16.5 (±1.1) years. The MCID (% achieving) for the mHHS, HOS activities of daily living (ADL), HOS Sport, and iHOT-33 was 9.5 (85%), 9.8 (79%), 12.1 (85%), and 10.7 (94%), respectively. Ninety-two percent of adolescents reported some form of improved hip physical ability on the anchor question. The following 1-year absolute outcome scores were significantly representative of an SCB state on the mHHS, HOS ADL, HOS Sport, and mHHS, respectively (AUC): 93.5 (0.79), 98.5 (0.84), 96.9 (0.81), and 85.9 (0.76). CONCLUSIONS: Adolescents undergoing arthroscopic FAI surgery achieve clinically significant outcome improvement. We found that the vast majority of adolescents achieve MCID on hip-specific patient-reported outcome tools. However, although adolescents readily achieve MCID, a considerable improvement in postoperative outcome score is often needed to perceive a substantial benefit (SCB). The available hip outcome tools may be subject to ceiling effects for measuring clinically significant outcome improvement in adolescents. LEVEL OF EVIDENCE: Level IV, case series.

Comparative Influence of Sport Type on Outcome After Anterior Cruciate Ligament Reconstruction at Minimum 2-Year Follow-up.

PURPOSE: To investigate differences between sport types for patient-reported outcome after anterior cruciate ligament reconstruction (ACLR). METHODS: Included patients were enrolled as part of a prospective institutional ACL registry. Inclusion criteria were preoperative self-identification as a competitive athlete, maximum score on the preoperative Marx Activity Scale, and minimum 2-year follow-up. Demographic, intraoperative, and outcome data were extracted from the registry. Outcome tools administered as part of the registry included International Knee Documentation Committee (IKDC), Lysholm-Tegner Scales, Marx Activity Scale (MAS), and 12-Item Short Form Health Survey (SF-12). RESULTS: A total of 294 patients with a mean age of 25.5 years (standard deviation 12.1) met the study inclusion criteria; mean follow-up was 3.7 years. Included sports categories were soccer (n = 92; 31.3%), skiing (n = 67; 22.8%), basketball (n = 56; 19.1%), lacrosse (n = 38; 12.9%), football (n = 29; 9.9%), and Tennis (n = 12; 4.1%). At baseline, compared with other sports, lacrosse players have higher outcome scores while skiers had lower scores. At 2-year follow-up, however, across all outcome tools, football players demonstrated significantly higher outcome scores than all other athletes (IKDC, 93.2, P = .001; Lysholm, 93.2, P = .03; MAS, 13.1, P = .03; SF-12 Mental Component Summary, 57.9, P = .0002). Conversely, at 2-year follow-up, soccer players demonstrated a significantly lower Lysholm (86.7, P = .02) and a trend toward lower IKDC (85.6, P = .09) scores. CONCLUSIONS: Patient-reported outcomes after ACLR among active athletes are comparable. Football players demonstrate quantitatively higher outcome scores whereas soccer players have lower scores. However, these outcome score differences may not be clinically significant and may be subject to confounding variables. Continued attention should be paid to understanding sport-specific outcome after ACLR. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

What Change in American Shoulder and Elbow Surgeons Score Represents a Clinically Important Change After Shoulder Arthroplasty?

BACKGROUND: The American Shoulder and Elbow Surgeons (ASES) questionnaire was developed to provide a standardized method for evaluating shoulder function. Previous studies have determined the clinical responsiveness of this outcome measure for heterogenous populations or patients with nonoperatively treated rotator cuff disease. Currently, to our knowledge, no studies exist that establish the clinically relevant change in the ASES score after shoulder arthroplasty. QUESTIONS/PURPOSES: We asked: (1) What are the minimal clinically important difference (MCID) and substantial clinical benefit (SCB) for the ASES score after primary and reverse shoulder arthroplasties? (2) Are the MCID and SCB for the ASES score different between primary and reverse shoulder arthroplasties? (3) What patient-related factors are associated with achieving the MCID and SCB after total shoulder arthroplasty and reverse shoulder arthroplasty? METHODS: A longitudinally maintained institutional shoulder arthroplasty registry was retrospectively queried for patients who underwent primary shoulder arthroplasty, including anatomic or reverse total shoulder arthroplasty from 2007 to 2013, with a minimum 2-year followup. Seven hundred ninety-four patients were identified and eligible; 304 of these patients did not have 2 years of followup or complete datasets, resulting in a study cohort of 490 patients (62% of the 794 potentially eligible). The MCID and SCB of the ASES score for these patients was calculated using an anchor-based method, using four different anchors measuring satisfaction with work, activities, overall, and activity from the SF-36. The MCID (anchored to somewhat satisfied) and SCB (very satisfied) of the ASES score were calculated for the entire cohort and stratified by arthroplasty type. Multivariate logistic regression of patient-related factors that influence the MCID and SCB achievement was performed. RESULTS: The MCID for all patients combined ranged from 6.3 to 13.5; for the overall satisfaction anchor, the MCID was 13.5 ± 4.5 (95% CI, 4.8-22.3). The SCB for the overall cohort ranged from 12.0 to 36.6; for the overall satisfaction anchor, the SCB was 36.6 ± 3.8 (95% CI, 29.1-44.1). There were no differences in the MCID of the ASES score between anatomic and reverse shoulder arthroplasty for any of the anchors (p = 0.159-0.992) or the SCB for any of the anchors (p = 0.467-0.977). Combining anatomic and reverse shoulder arthroplasty in one group, higher preoperative ASES score (odds ratio [OR], 0.96; 95% CI, 0.94-0.98; p < 0.001), having a reverse shoulder arthroplasty (OR, 0.36; 95% CI, 0.16-0.85; p = 0.016), and having rheumatoid arthritis were independent predictors of not achieving an MCID for the ASES 2 years after surgery. Higher preoperative ASES score (OR, 0.91; 95% CI, 0.89-0.92; p < 0.001), a diagnosis of rotator cuff tear arthropathy (OR, 0.14; 95% CI, 0.07-0.30; p < 0.001), a diagnosis of back pain (OR, 0.42; 95% CI, 0.24-0.71); p = 0.002), and living alone (OR, 0.36; 95% CI, 0.19-0.69; p = 0.002) were all independent predictors of not achieving SCB after shoulder arthroplasty. CONCLUSIONS: Patients with glenohumeral arthritis or rotator cuff tear arthropathy who undergo primary conventional total or reverse shoulder arthroplasty and have at least a nine-point improvement in their ASES score experience a clinically important change, whereas those who have at least a 23-point improvement in their ASES score experience a substantial clinical benefit. High preoperative function was associated with a decreased likelihood of achieving clinically important change after total shoulder arthroplasty. LEVEL OF EVIDENCE: Level III, therapeutic study.

T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia.

Induction treatments for acute myeloid leukemia (AML) have remained largely unchanged for nearly 50 years, and AML remains a disease of poor prognosis. Allogeneic hematopoietic cell transplantation can achieve cures in select patients and highlights the susceptibility of AML to donor-derived immunotherapy. The interleukin-3 receptor α chain (CD123) has been identified as a potential immunotherapeutic target because it is overexpressed in AML compared with normal hematopoietic stem cells. Therefore, we developed 2 chimeric antigen receptors (CARs) containing a CD123-specific single-chain variable fragment, in combination with a CD28 costimulatory domain and CD3-ζ signaling domain, targeting different epitopes on CD123. CD123-CAR-redirected T cells mediated potent effector activity against CD123+ cell lines as well as primary AML patient samples. CD123 CAR T cells did not eliminate granulocyte/macrophage and erythroid colony formation in vitro. Additionally, T cells obtained from patients with active AML can be modified to express CD123 CARs and are able to lyse autologous AML blasts in vitro. Finally, CD123 CAR T cells exhibited antileukemic activity in vivo against a xenogeneic model of disseminated AML. These results suggest that CD123 CAR T cells are a promising immunotherapy for the treatment of high-risk AML.

Mortality after large artery occlusion acute ischemic stroke.

Despite randomized trials showing a functional outcome benefit in favor of endovascular therapy (EVT), large artery occlusion acute ischemic stroke is associated with high mortality. We performed a retrospective analysis from a prospectively collected code stroke registry and included patients presenting between November 2016 and April 2019 with internal carotid artery and/or proximal middle cerebral artery occlusions. Ninety-day mortality status from registry follow-up was corroborated with the Social Security Death Index. A multivariable logistic regression model was fitted to determine demographic and clinical characteristics associated with 90-day mortality. Among 764 patients, mortality rate was 26%. Increasing age (per 10 years, OR 1.48, 95% CI 1.25-1.76; p < 0.0001), higher presenting NIHSS (per 1 point, OR 1.05, 95% CI 1.01-1.09, p = 0.01), and higher discharge modified Rankin Score (per 1 point, OR 4.27, 95% CI 3.25-5.59, p < 0.0001) were independently associated with higher odds of mortality. Good revascularization therapy, compared to no EVT, was independently associated with a survival benefit (OR 0.61, 95% CI 0.35-1.00, p = 0.048). We identified factors independently associated with mortality in a highly lethal form of stroke which can be used in clinical decision-making, prognostication, and in planning future studies.

Feedback cues improve the alignment and technique of children performing ACL injury prevention exercises.

OBJECTIVES: The appropriateness of neuromuscular training exercises across different age groups has not yet been investigated, particularly in younger children. The purpose of this study was to determine which neuromuscular training exercises can be performed with proper neutral alignment in various age groups. METHODS: Seven exercises were selected for evaluation in children ranging from 8 to 17 years of age who were recruited from schools and youth sports organisations. Participants completed two trials of each exercise and were judged on maintaining neutral body alignment after receiving visual/verbal instruction on the first trial and feedback cues on the second trial. Three evaluators judged each exercise, which was deemed as correct when at least two evaluators agreed that neutral alignment was maintained. Comparisons were made across ages and between sex using the χ² test or Fisher's exact test. The proportions of participants who performed the exercise correctly were also compared before and after feedback cues were provided. RESULTS: A total of 360 participants were evaluated (8-11 years: 165, 54% female; 12-15 years: 136, 40% female, 16-17 years: 59, 53% female). There were no significant differences in performance across ages and sex for nearly all exercises. The majority of children were not able to complete the exercises with proper alignment. The use of feedback cues significantly increased the proportion of participants who correctly completed the exercise (p<0.001). CONCLUSIONS: These results demonstrate the importance of training coaches and physical education teachers to provide cues that reinforce proper technique during anterior cruciate ligament injury prevention exercises. Children should perform common neuromuscular training exercises with feedback on proper technique. LEVEL OF EVIDENCE: IV (case series).

Preoperative ASES Scores Can Predict Substantial Clinical Benefit at 2 Years Following Total Shoulder Arthroplasty.

Preoperative patient-reported outcome measures (PROMs) have been shown to influence outcomes after total shoulder arthroplasty (TSA), although little is known about this relationship. An institutional shoulder arthroplasty registry was retrospectively queried for preoperative and 2-year postoperative 12-Item Short Form Health Survey (SF-12) and American Shoulder and Elbow Surgeons (ASES) scores for patients who underwent anatomic TSA (aTSA) or reverse TSA (rTSA). Preoperative PROMs were evaluated for their effect on patient achievement of minimal clinically important improvement (MCII) and substantial clinical benefit (SCB). In total, 451 aTSA patients and 93 rTSA patients had preoperative and 2-year follow-up scores. A total of 91.7% and 70.4% of patients achieved MCII and SCB at 2 years, respectively (P<.001). Preoperative ASES scores were more predictive of achieving SCB than MCII (area under the curve [AUC], 0.83 vs 0.71). When accounting for mental and emotional health, the predictive ability of SF-12 physical component threshold values improved (AUC, 0.68). Preoperative threshold PROMs were found to accurately predict achievement of clinically significant outcomes at 2 years. Considering mental and emotional health improved the accuracy of these predictions. These data will assist surgeons and patients alike in setting expectations for outcomes after TSA. [Orthopedics. 2021;44(4):e509-e514.].

Intrasession repeatability and intersession reproducibility of peripapillary OCTA vessel parameters in non-glaucomatous and glaucomatous eyes.

OBJECTIVE: To compare intrasession repeatability versus intersession reproducibility of the peripapillary vessel parameters using optical microangiography-based optical coherence tomography angiography (OCTA) in non-glaucomatous and glaucomatous eyes. METHODS: In an observational, longitudinal study, peripapillary OCTA scans were collected to evaluate intrasession repeatability and intersession reproducibility using within-eye coefficient of variation (CVW) and intraclass correlation coefficient (ICC). Images were quantified using a custom research-oriented quantification software calculating vessel area density (VAD) and flux and a commercially developed, clinic-oriented quantification software (Cirrus 11.0, Carl Zeiss Meditec) calculating perfusion density (PD) and flux index (FI). Effect of signal strength on the reliability of OCTA parameters was also evaluated. RESULTS: Among 120 non-glaucomatous eyes, intrasession CVW were 4.2% for VAD, 5.3% for flux, 1.5% for PD and 2.0% for FI. The intersession CVW were 6.5% for VAD, 8.0% for flux, 2.0% for PD and 3.2% for FI. The intrasession ICC ranged from 0.928 to 0.945, and intersession ICC ranged from 0.811 to 0.866. From 118 glaucomatous eyes, intrasession CVW was 9.0% for VAD, 10.3% for flux, 1.7% for PD and 2.3% for FI. The intersession CVW was 12.1% for VAD, 14.2% for flux, 2.3% for PD and 3.5% for FI. The intrasession ICC ranged from 0.904 to 0.972, and intersession ICC ranged from 0.855 to 0.955. Signal strength was significantly positively associated with OCTA vessel parameters (p<0.0001) for both groups. CONCLUSION: Peripapillary OCTA vessel parameters had greater intrasession repeatability compared to intersession reproducibility in both non-glaucomatous and glaucomatous eyes. The built-in commercially developed quantification software demonstrated greater agreement than the custom research-oriented quantification software.