Evaluation of the Learning Curve When Transitioning From Posterolateral to Direct Anterior Hip Arthroplasty: A Consecutive Series of 1000 Cases.

BACKGROUND: The direct anterior approach (DAA) for primary hip replacement has been gaining more attention and widespread use in recent years. There are a number of published studies evaluating the learning curve when a surgeon changes technique; these studies typically look at complications during the initial cases. This study examines procedure and total operating room (OR) time along with all complications for a surgeon transitioning from the posterolateral approach (PA) to DAA. METHODS: A retrospective review of a single surgeon series of 1000 initial DAA procedures. Total OR time, procedure time, and complications were collected and analyzed. One-way analysis of variance and post hoc least significant difference tests were used for statistical analysis. RESULTS: There was an initial increase in both procedure and OR times compared with the mature PA, by 34% and 30%, respectively. The procedure time became statistically equivalent to the mature PA time after the 400th DAA case, and significantly shorter after the 850th case. The total OR time became statistically equivalent after the 900th DAA case. There were 18 early (<90 days) and 18 late reoperations performed in this series with a nonsignificant trend toward femoral complications occurring early in the series. Minimum follow-up time was 2 years. CONCLUSION: There was an initial increase in both total OR time and procedure time when an experienced surgeon introduced the DAA. By the end of the series, procedure time was significantly shorter and total OR time was equivalent. Complications overall were low and femoral complications decreased with time.

The feedback-related negativity signals salience prediction errors, not reward prediction errors.

Modulations of the feedback-related negativity (FRN) event-related potential (ERP) have been suggested as a potential biomarker in psychopathology. A dominant theory about this signal contends that it reflects the operation of the neural system underlying reinforcement learning in humans. The theory suggests that this frontocentral negative deflection in the ERP 230-270 ms after the delivery of a probabilistic reward expresses a prediction error signal derived from midbrain dopaminergic projections to the anterior cingulate cortex. We tested this theory by investigating whether FRN will also be observed for an inherently aversive outcome: physical pain. In another session, the outcome was monetary reward instead of pain. As predicted, unexpected reward omissions (a negative reward prediction error) yielded a more negative deflection relative to unexpected reward delivery. Surprisingly, unexpected pain omission (a positive reward prediction error) also yielded a negative deflection relative to unexpected pain delivery. Our data challenge the theory by showing that the FRN expresses aversive prediction errors with the same sign as reward prediction errors. Both FRNs were spatiotemporally and functionally equivalent. We suggest that FRN expresses salience prediction errors rather than reward prediction errors.

Training Graduate Students to Enter Fieldwork Data Using Asynchronous Online Instruction.

The curr ent study aimed to evaluate the effects of asynchronous online instruction on correct fieldwork data entry for graduate students in behavior analysis preparing to sit for the BACB exam. Previous research has been conducted on using synchronous instructional methods to teach fieldwork data entry. To our knowledge, this is the first examination of a completely asynchronous approach to teaching the new Behavior Analysis Certification Board (BACB) fieldwork requirements (BACB, 2020a). Experimenters focused on the completion of daily fieldwork activities, as well as the completion of monthly fieldwork forms. Participants were 22 graduate students beginning their fieldwork experiences in pursuit of their board certified behavior analyst credential. Most participants did not reach the mastery criterion in baseline after only reviewing the fieldwork resources provided by the BACB for both phases. After undergoing training, all participants scored above the mastery criterion in their completion of both their daily fieldwork logs and monthly forms. • Fieldwork trainees taught to fill in Trackers and monthly forms. • Asynchronous online instruction used to teach data entry using mock fieldwork scenarios. • 18 of 18 participants in the Tracker Training improved from baseline. • 18 of 20 participants in the Monthly Forms Training improved from baseline. • Correct responding for 15 participants generalized to a novel scenario. Data suggest that asynchronous online instruction is an effective method to teach fieldwork data entry. • Social validity data suggest favorable views of the training.

Teaching Graduate Students to Identify and Adhere to Practicum Requirements.

A critical component of becoming eligible to sit for the Behavior Analyst Certification Board (BACB) exam is the completion of fieldwork experience hours according to the BACB Experience Standards (2018). The accrual of experience hours must meet stringent criteria and is strongly recommended to be documented using the BACB Fieldwork Tracker. Thirteen graduate students in behavior analysis were taught to enter data into the BACB Fieldwork Tracker using mock fieldwork scenarios. Training was conducted using group behavioral skills training. The training occurred remotely using both synchronous and asynchronous components. Of the 13 participants, 11 showed improvement from baseline, and 10 met and maintained performance at mastery levels at the end of the study. Social validity scores indicated that most participants felt the training was helpful, and they reported lower levels of fieldwork accrual-related stress following training (81.8% and 72.7%, respectively). Limitations and areas for future research are discussed.

Preoperative chemotherapy in clinically node positive muscle invasive bladder cancer: Radiologic variables can predict response.

PURPOSE: To evaluate pathologic downstaging after radical cystectomy and pelvic lymph node dissection for clinically lymph node positive urothelial bladder cancer and to determine optimal preoperative imaging variables in predicting pathologic nodal status. METHODS: We identified all patients with clinically lymph node positive urothelial bladder cancer who underwent radical cystectomy and extended pelvic lymph node dissection with intent to cure at our institution. Patients were stratified based on pathologic node status to determine clinical associations and survival outcomes. Pre and post-chemotherapy CT scans were reviewed to characterize lymph node size and morphology. We also sought to determine associations between post-chemotherapy radiology variables and pathologic response. RESULTS: We identified 130 patients with clinically node positive bladder cancer, out of which 76 (58.5%) received induction chemotherapy. Thirty three (43.4%) had pathologic T downstaging following chemotherapy, compared to 7 (12.9%) patients who had surgery alone (P< 0.0001). A complete nodal response (pN0) occurred in 31 (40.8%) patients post-chemotherapy, while 6 (11.1%) of those who received cystectomy alone ended up being pN0 (P< 0.0001). Median overall survival and recurrence-free survival were shorter in patients with pN+ versus pN0 disease (1.9 years vs. 12.8 years, P= 0.016 and 1.2 years vs. 4.3 years, P= 0.013, respectively). Review of 29 post chemotherapy CT scans showed that patients with pathologic nodal involvement had a greater median number of enlarged nodes (3.5 vs. 1, P= 0.038) and a greater median size of largest node (8.5 mm vs. 6.0 mm, P= 0.021) on imaging compared to those with complete pN0. Each 1 mm increase in size of the largest node on post-chemotherapy CT scan increased the chance of having pN+ disease by 1.57 (95% CI 1.02-2.44, P= 0.043). Using a median node size of 8 mm as a cut-off to predict pN+ disease provided a sensitivity and specificity of 72% and 80%, respectively (c-index = 0.761, P= 0.014). The positive predictive value for this cut-off was 87% (95% CI 58%-98%) and negative predictive value was 62% (32%-85%). CONCLUSION: Patients with clinically node positive bladder cancer may have significant pN0 after induction chemotherapy. Our data suggest a post-chemotherapy CT scan with an 8 mm nodal size cut-off may be a better predictor of pathologic nodal status than more traditional measures.

Soluble CD80 Protein Delays Tumor Growth and Promotes Tumor-Infiltrating Lymphocytes.

Tumor cells use various immune-suppressive strategies to overcome antitumor immunity. One such method is tumor expression of programmed death ligand-1 (PD-L1), which triggers apoptotic death or anergy upon binding programmed death-1 (PD-1) on T cells. Our previous in vitro cellular studies with human and mouse PD-L1+ tumor cells demonstrated that a soluble form of the costimulatory molecule CD80 prevented PD-L1-mediated immune suppression and restored T-cell activation by binding PD-L1 and blocking interaction with PD-1. We now report that in vivo treatment of established syngeneic PD-L1+ CT26 colon carcinoma and B16F10 melanoma tumors with CD80-Fc delays tumor growth and promotes tumor-infiltrating T cells. Studies with PD-1-/- and CD28-/- mice demonstrate that soluble CD80 acts in vivo by simultaneously neutralizing PD-1 suppression and activating through CD28. We also report that soluble CD80 mediates its effects by activating transcription factors EGR1-4, NF-κB, and MAPK, downstream signaling components of the CD28 and T-cell receptor pathways. Soluble CD80 binds to CTLA-4 on activated human peripheral blood mononuclear cells. However, increasing quantities of CTLA-4 antagonist antibodies do not increase T-cell activation. These results indicate that soluble CD80 does not suppress T-cell function through CTLA-4 and suggest that CTLA-4 acts as a decoy receptor for CD80, rather than functioning as a suppressive signaling receptor. Collectively, these studies demonstrate that soluble CD80 has therapeutic efficacy in vivo in mouse tumor systems and that its effects are due to its ability to inhibit PD-1-mediated suppression while concurrently activating T cells through CD28. Cancer Immunol Res; 6(1); 59-68. ©2017 AACR.

CD3xPDL1 bi-specific T cell engager (BiTE) simultaneously activates T cells and NKT cells, kills PDL1+ tumor cells, and extends the survival of tumor-bearing humanized mice.

Bi-specific T cell engagers (BiTEs) activate T cells through CD3 and target activated T cells to tumor-expressed antigens. BiTEs have shown therapeutic efficacy in patients with liquid tumors; however, they do not benefit all patients. Anti-tumor immunity is limited by Programmed Death 1 (PD1) pathway-mediated immune suppression, and patients who do not benefit from existing BiTES may be non-responders because their T cells are anergized via the PD1 pathway. We have designed a BiTE that activates and targets both T cells and NKT cells to PDL1+ cells. In vitro studies demonstrate that the CD3xPDL1 BiTE simultaneously binds to both CD3 and PDL1, and activates healthy donor CD4+ and CD8+ T cells and NKT cells that are specifically cytotoxic for PDL1+ tumor cells. Cancer patients' PBMC are also activated and cytotoxic, despite the presence of myeloid-derived suppressor cells. The CD3xPDL1 BiTE significantly extends the survival time and maintains activated immune cell levels in humanized NSG mice reconstituted with human PBMC and carrying established human melanoma tumors. These studies suggest that the CD3xPDL1 BiTE may be efficacious for patients with PDL1+ solid tumors, in combination with other immunotherapies that do not specifically neutralize PD1 pathway-mediated immune suppression.