Lu, Yining

AbstractPurposeOvernight admission following anterior cruciate ligament reconstruction has implications on clinical outcomes as well as cost benefit, yet there are few validated risk calculators for reliable identification of appropriate candidates. The purpose of this study is to develop and validate a machine learning algorithm that can effectively identify patients requiring admission following elective anterior cruciate ligament (ACL) reconstruction. MethodsA retrospective review of a national surgical outcomes database was performed to identify patients who underwent elective ACL reconstruction from 2006 to 2018. Patients admitted overnight postoperatively were identified as those with length of stay of 1 or more days. Models were generated using random forest (RF), extreme gradient boosting (XGBoost), linear discriminant classifier (LDA), and adaptive boosting algorithms (AdaBoost), and an additional model was produced as a weighted ensemble of the four final algorithms.ResultsOverall, of the 4,709 patients included, 531 patients (11.3%) required at least one overnight stay following ACL reconstruction. The factors determined most important for identification of candidates for inpatient admission were operative time, anesthesia type, age, gender, and BMI. Smoking history, history of COPD, and history of coagulopathy were identified as less important variables. The following factors supported overnight admission: operative time > 200 min, age < 35.8 or > 53.5 years, male gender, BMI < 25 or > 31.2 kg/m2, positive smoking history, history of COPD and the presence of preoperative coagulopathy. The ensemble model achieved the best performance based on discrimination assessed via internal validation (AUC = 0.76), calibration, and decision curve analysis. The model was integrated into a web‐based open‐access application able to provide both predictions and explanations.ConclusionModifiable risk factors identified by the model such as increased BMI, operative time, anesthesia type, and comorbidities can help clinicians optimize preoperative status to prevent costs associated with unnecessary admissions. If externally validated in independent populations, this algorithm could use these inputs to guide preoperative screening and risk stratification to identify patients requiring overnight admission for observation following ACL reconstruction.Level of evidenceIV.

Background There is increased emphasis on properly allocating healthcare resources to optimize value within orthopedic surgery. Establishing time to maximal medical improvement (MMI) can inform clinical decision-making and practice guidelines. Purpose We sought (1) to evaluate the time to MMI as predicted by commonly used patient-reported outcome measures (PROMs) for evaluation of shoulder stabilization and (2) to evaluate typical time to return to sports and employment following surgery. Methods A systematic review of the Medline database was conducted to identify outcome studies reporting sequential follow-up at multiple time points, up to a minimum of 2 years after shoulder stabilization surgery. The included studies examined the outcomes of arthroscopic or open surgical techniques on anterior instability. Clinically significant improvements were evaluated utilizing the minimal clinically important difference specific to each PROM. Secondary outcomes included range of motion, return to sport/work, and recurrent instability. Results Ten studies comprising 590 surgically managed cases of anterior shoulder instability were included (78% arthroscopic, 22% open). Clinically significant improvements in PROMs were achieved up to 1 year post-operatively for Rowe, Western Ontario Instability Index (WOSI), American Shoulder and Elbow Surgeons (ASES), and Simple Shoulder Test (SST) scores. For the three most utilized tools (Rowe, WOSI, ASES), the majority of improvement occurred in the first 6 post-operative months. Clinically significant improvements in Constant Score and Oxford Shoulder Instability Score (OSIS) were achieved up to 6 months and 2 years after surgery, respectively. No clinically significant improvements were achieved on the Disabilities of the Arm, Shoulder, and Hand (DASH) tool. Conclusion Maximal medical improvement as determined by commonly utilized PROMs occurs by 1 year after operative management of anterior shoulder instability. The DASH tool does not appear to demonstrate a reliable time frame for clinically significant outcome improvement.

Purpose (1) To determine the area of posterior cruciate ligament (PCL) insertion sites on the lateral wall of the medial femoral condyle (LWMFC) that demonstrates the least amount of length change through full range of motion (ROM) and (2) to identify a range of flexion that would be favorable for graft tensioning for single‐bundle (SB) and double‐bundle (DB) PCL reconstruction. Methods Six fresh‐frozen cadaveric knees were obtained. Three‐dimensional computed tomography point‐cloud models were obtained from 0° to 135°. A point grid was placed on the LWMFC and the tibial PCL facet. Intra‐articular length was calculated for each point on the femur to the tibia at all flexion angles and grouped to represent areas for bone tunnels of SB and DB PCLR. Normalized length changes were evaluated. Results Femoral tunnel location and angle of graft fixation were significant contributors to mean, minimum, and maximum normalized length of the PCL (all p < .001). Tibial tunnel location was not significant in any case (all p < .22). A femoral tunnel in the location of the posteromedial bundle of the PCL resulted in the least length change at all tibial positions (maximum change 13%). Fixation of the anterolateral bundle in extension or at 30° flexion resulted in significant overconstraint of the PCL graft. The femoral tunnel location for a SB PCLR resulted in significant laxity at lower ranges of flexion. Conclusion PCL length was significantly dependent on femoral tunnel position and angle of fixation, whereas tibial tunnel position did not significantly contribute to observed differences. All PCL grafts demonstrated anisometry, with the anterolateral bundle being more anisometric than the posteromedial bundle. For DB PCLR, the posteromedial bundle demonstrated the highest degree of isometry throughout ROM, although no area of the LWMFC was truly isometric. The anterolateral bundle should be fixed at 90° to avoid overconstraint, and SB PCLR demonstrated significant laxity at lower ranges of flexion. Clinical Relevance Surgeons can apply the results of this investigation to surgical planning in PCLR to optimize isometry, which may ultimately reduce graft strain and the risk of graft failure. Additionally, DB PCLR demonstrated superiority compared with SB PCLR regarding graft isometry, as significant laxity was encountered at lower ranges of flexion in SB PCLRs. Fixation of the ALB at 90° flexion should be performed to avoid overconstraint in knee extension.

Purpose The purpose of this study is to define the impact of preoperative opioid use on postoperative opioid use, patient‐reported outcomes, and revision rates in a cohort of patients receiving arthroscopic shoulder surgery. Methods Patients who underwent shoulder arthroscopy were identified from an institutional database. Inclusion criteria were completion of preoperative and postoperative patient‐reported outcome measures (PROMs) at 1‐year follow‐up and completion of a questionnaire on use of opioids and number of pills per day. Outcomes assessed included postoperative PROM scores, postoperative opioid use, persistent pain, and achievement of the patient acceptable symptomatic state. A matched cohort analysis was performed to evaluate the impact of opioid use on achievement of postoperative outcomes, whereas a multivariate regression was performed to determine additional risk factors. Receiver operating characteristic curves were used to establish threshold values in oral morphine equivalents (OMEs) that predicted each outcome. Results A total of 184 (16.3%) patients were included in the opioid use (OU) group and 1,058 in the no opioid use (NOU) group. The OU and NOU groups showed statistically significant differences in both preoperative and postoperative scores across all PROMs ( P < .001). Multivariate logistic regression identified preoperative opioid use as a significant predictor of reduced achievement of the patient acceptable symptomatic state (odds ratio [OR], 0.69, 95% confidence interval [CI], 0.29‐0.83, P = .008), increased likelihood of endorsing persistent pain (OR, 1.73, 95% CI, 1.17‐2.56, P = .006), and increased opioid use at 1 year (OR, 21.3, 95% CI, 12.2‐37.2, P < .001). Consuming a high dosage during the perioperative period increased risk of revision surgery (OR, 8.59, 95% CI, 2.12‐34.78, P < .003). Results were confirmed by matched cohort analysis. Receiver operating characteristic analysis found that total OME >1430 mg/d in the perioperative period (area under the curve, 0.76) and perioperative daily OME >32.5 predicted postoperative opioid consumption (area under the curve, 0.79). Conclusions Patients with a history of preoperative opioid use can achieve significant improvements in patient‐reported outcomes after arthroscopic shoulder surgery. However, preoperative opioid use negatively impacts patients’ level of satisfaction and is a significant predictor of pain and continued opioid usage. Level of evidence Level III, retrospective cohort study

Abstract Medulloblastoma (MB) is a pediatric brain tumor comprising of four molecular subgroups, with Group 3 and 4 tumors characterized by particularly poor prognosis. While research has advanced our understanding of MB, there is still a pressing need for new knowledge of the functional processes underlying its progression due to a scarcity of therapeutics. Recent studies have identified Orthodenticle homeobox 2 (Otx2), a cerebellar transcription factor, to be highly expressed in MB Group 3/4 subtypes. Datamining studies from Northcott and Robinson datasets revealed co-expression of Otx2 and c-Myc in Group 3/4 tumors. DAB staining conducted in human MB specimens showed increased expression of Otx2 and c-Myc. Colocalization studies confirmed datamining results. Next, we used a clinical Otx2 inhibitor, all-trans retinoic acid (ATRA), in a PDX cell line, P9, and in UW228 cells. Western blot analysis demonstrated reduced levels of c-Myc along with Otx2. In another experiment, we used the c-Myc/Max inhibitor 10058-F4 and observed comparable results to Otx2 inhibition. Real time PCR and immunocytochemistry experiments confirmed the aforementioned results. Further, treatment with ATRA and 10058-F4 showed reduced proliferation and migratory abilities in p9 and UW228 when compared to their respective controls. Mass spectrometry conducted on immune-precipitated Otx2 in P9 cells revealed a plethora of novel interaction partners that drive tumor growth and progression. In addition, western blot analysis in ATRA treated cells showed reduced expression of Max, suggestive of the existence of a feedback loop that link with Otx2 and c-Myc. Collectively our studies highlight Otx2 as a potential contributor to the malignant phenotype and describe its role in mediating the aggressiveness of Group 3/4 medulloblastoma. Citation Format: Yining Lu, Maheedhara R. Guda, Swapna Asuthkar, Ian Purvis, Collin M. Labak, Neha Jain, David J. Daniels, Sarah E. Martin, Andrew J. Tsung, Kiran K. Velpula. Otx2 and c-Myc association drives tumor progression in medulloblastoma molecular subtypes 3/4 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3537. doi:10.1158/1538-7445.AM2017-3537