Stem cell dynamics and cellular heterogeneity across lineage subtypes of castrate-resistant prostate cancer.

To resist lineage-dependent therapies such as androgen receptor inhibition, prostate luminal epithelial adenocarcinoma cells often adopt a stem-like state resulting in lineage plasticity and phenotypic heterogeneity. Castrate-resistant prostate adenocarcinoma can transition to neuroendocrine (NE) and occasionally to amphicrine, co-expressed luminal and NE, phenotypes. We developed castrate-resistant prostate cancer (CRPC) patient-derived organoid models that preserve heterogeneity of the originating tumor, including an amphicrine model displaying a range of luminal and NE phenotypes. To gain biological insight and to identify potential treatment targets within heterogeneous tumor cell populations, we assessed the lineage hierarchy and molecular characteristics of various CRPC tumor subpopulations. Transcriptionally similar stem/progenitor (St/Pr) cells were identified for all lineage populations. Lineage tracing in amphicrine CRPC showed that heterogeneity originated from distinct subclones of infrequent St/Pr cells that produced mainly quiescent differentiated amphicrine progeny. By contrast, adenocarcinoma CRPC progeny originated from St/Pr cells and self-renewing differentiated luminal cells. Neuroendocrine prostate cancer (NEPC) was composed almost exclusively of self-renewing St/Pr cells. Amphicrine subpopulations were enriched for secretory luminal, mesenchymal, and enzalutamide treatment persistent signatures that characterize clinical progression. Finally, the amphicrine St/Pr subpopulation was specifically depleted with an AURKA inhibitor, which blocked tumor growth. These data illuminate distinct stem cell (SC) characteristics for subtype-specific CRPC in addition to demonstrating a context for targeting differentiation-competent prostate SCs.

Validation of a 3D-Printed Percutaneous Injection Laryngoplasty Simulator: A Randomized Controlled Trial.

OBJECTIVE: Simulation may be a valuable tool in training laryngology office procedures on unsedated patients. However, no studies have examined whether existing awake procedure simulators improve trainee performance in laryngology. Our objective was to evaluate the transfer validity of a previously published 3D-printed laryngeal simulator in improving percutaneous injection laryngoplasty (PIL) competency compared with conventional educational materials with a single-blinded randomized controlled trial. METHODS: Otolaryngology residents with fewer than 10 PIL procedures in their case logs were recruited. A pretraining survey was administered to participants to evaluate baseline procedure-specific knowledge and confidence. The participants underwent block randomization by postgraduate year to receive conventional educational materials either with or without additional training with a 3D-printed laryngeal simulator. Participants performed PIL on an anatomically distinct laryngeal model via trans-thyrohyoid and trans-cricothyroid approaches. Endoscopic and external performance recordings were de-identified and evaluated by two blinded laryngologists using an objective structured assessment of technical skill scale and PIL-specific checklist. RESULTS: Twenty residents completed testing. Baseline characteristics demonstrate no significant differences in confidence level or PIL experience between groups. Senior residents receiving simulator training had significantly better respect for tissue during the trans-thyrohyoid approach compared with control (p < 0.0005). There were no significant differences in performance for junior residents. CONCLUSIONS: In this first transfer validity study of a simulator for office awake procedure in laryngology, we found that a previously described low-cost, high-fidelity 3D-printed PIL simulator improved performance of PIL amongst senior otolaryngology residents, suggesting this accessible model may be a valuable educational adjunct for advanced trainees to practice PIL. LEVEL OF EVIDENCE: NA Laryngoscope, 134:318-323, 2024.

A Novel Low-Cost, Open-Source, Three-Dimensionally Printed Thyroplasty Simulator.

OBJECTIVE: Training of surgical procedures on awake patients, such as medialization thyroplasty, poses challenges to educators and trainees. Three-dimensionally (3D)-printed simulators provide opportunity to practice in low-stakes settings. We present the first 3D-printed thyroplasty simulator incorporating a cartilaginous framework, endolaryngeal soft tissue housed in a 3D-printed manikin with endoscopic visualization. METHODS: Male and female laryngeal cartilages and endolarynx molds were 3D printed from an existing open-source design. Cartilage models were made of heat-treated polylactic acid (HTPLA), a material chosen for its thermal stability, allowing drilling. They were combined with molded silicone endolarynges modeling glottic insufficiency. Larynges were set in a 3D-printed head-and-neck manikin with an attached borescope for internal visualization similar to distal chip laryngoscopy. Eight laryngologists evaluated the simulator by drilling a thyroplasty window, inserting an implant for medialization, and rating the model using a modified Michigan Standard Simulation Experience Scale (1 = strongly disagree, 5 = strongly agree). RESULTS: The model was well rated in educational value (mean 4.7, standard deviation [SD] 0.3), fidelity (mean 3.8, SD 0.2), and overall value (mean 4.8, SD 0.5). Qualitative assessment concluded the model was anatomically realistic and that HTPLA was a good approximation of the density and texture of thyroid cartilage. The materials for one larynx cost $4.09. CONCLUSION: This high-fidelity 3D-printed simulator demonstrates educational value for thyroplasty training. The low-cost, open-source design has broad implications for universal access to this simulator platform.

Transoral endoscopic vestibular approach Sistrunk procedure: First reported case series.

BACKGROUND: Standard of care for management of thyroglossal duct cysts (TGDCs) is a Sistrunk procedure performed through a transcervical incision. We describe the first series of Sistrunk procedures performed through a transoral endoscopic vestibular approach, eliminating a visible external scar. METHODS: The transoral endoscopic vestibular approach to the Sistrunk (TEVAS) was performed in patients with TGDCs meeting inclusion criteria who desired a scarless approach. RESULTS: Six patients (five females and one male) underwent TEVAS, with a mean age of 38 years (range 16-56 years) and a mean TGDC size of 1.8 cm (range 1.1-2.4 cm). Mean operative time was approximately 5 h (range 2-8 h). There were no surgical complications or recurrences. CONCLUSIONS: For appropriately selected patients, the TEVAS is an alternative to open neck surgery that provides improved cosmesis while maintaining successful resection outcomes. More data on outcomes including complications and recurrences are needed as additional case information is collected.

Effects of an opioid stewardship program on opioid consumption and related outcomes after multilevel lumbar spine fusion: a pre- and postimplementation analysis of 268 patients.

OBJECTIVE: Opioid stewardship programs combine clinical, regulatory, and educational interventions to minimize inappropriate opioid use and prescribing for orthopedic and spine surgery. Most evaluations of stewardship programs quantify effects on prescriber behavior, whereas patient-relevant outcomes have been relatively neglected. The authors evaluated the impact of an opioid stewardship program on perioperative opioid consumption, prescribing, and related clinical outcomes after multilevel lumbar fusion. METHODS: The study was based on a retrospective, quasi-experimental, pretest-posttest design in 268 adult patients who underwent multilevel lumbar fusion in 2016 (preimplementation, n = 141) or 2019 (postimplementation, n = 127). The primary outcome was in-hospital opioid consumption (morphine equivalent dose [MED], mg). Secondary outcomes included numeric rating scale pain scores (0-10), length of stay (LOS), incidence of opioid-induced side effects (gastrointestinal, nausea/vomiting, respiratory, sedation, cognitive), and preoperative and discharge prescribing. Outcomes were measured continuously during the hospital admission. Differences in outcomes between the epochs were assessed in bivariable (Wilcoxon signed-rank or Fisher's exact tests) and multivariable (Wald's chi-square test) analyses. RESULTS: In bivariable analyses, there were significant decreases in preoperative opioid use (46% vs 28% of patients, p = 0.002), preoperative opioid prescribing (MED 30 mg [IQR 20-60 mg] vs 20 mg [IQR 11-39 mg], p = 0.003), in-hospital opioid consumption (MED 329 mg [IQR 188-575 mg] vs 199 mg [100-372 mg], p < 0.001), the incidence of any opioid-related side effect (62% vs 50%, p = 0.03), and discharge opioid prescribing (MED 90 mg [IQR 60-135 mg] vs 60 mg [IQR 45-80 mg], p < 0.0001) between 2016 and 2019. There were no significant differences in postanesthesia care unit pain scores (4 [IQR 3-6] vs 5 [IQR 3-6], p = 0.33), nursing floor pain scores (4 [IQR 3-5] vs 4 [IQR 3-5], p = 0.93), or total LOS (118 hours [IQR 81-173 hours] vs 103 hours [IQR 81-132 hours], p = 0.21). On multivariable analysis, the opioid stewardship program was significantly associated with decreased discharge prescribing (Wald's chi square = 9.45, effect size -52.4, 95% confidence interval [CI] -86 to -19.0, p = 0.002). The number of lumbar levels fused had the strongest effect on total opioid consumption during the hospital stay (Wald's chi square = 16.53, effect size = 539, 95% CI 279.1 to 799, p < 0.001), followed by preoperative opioid use (Wald's chi square = 44.04, effect size = 5, 95% CI 4 to 7, p < 0.001). CONCLUSIONS: A significant decrease in perioperative opioid prescribing, consumption, and opioid-related side effects was found after implementation of an opioid stewardship program. These gains were achieved without adverse effects on pain scores or LOS. These results suggest the major impact of opioid stewardship programs for spine surgery may be on changing prescriber behavior.

Trends in Patient, Physician, and Public Perception of Ulnar Collateral Ligament Reconstruction Using Social Media Analytics.

BACKGROUND: Social media posts regarding ulnar collateral ligament (UCL) injuries and reconstruction surgeries have increased in recent years. PURPOSE: To analyze posts shared on Instagram and Twitter referencing UCL injuries and reconstruction surgeries to evaluate public perception and any trends in perception over the past 3 years. STUDY DESIGN: Cross-sectional study. METHODS: A search of a 3-year period (August 2016 and August 2019) of public Instagram and Twitter posts was performed. We searched for >22 hashtags and search terms, including #TommyJohn, #TommyJohnSurgery, and #tornUCL. A categorical classification system was used to assess the sentiment, media format, perspective, timing, accuracy, and general content of each post. Post popularity was measured by number of likes and comments. RESULTS: A total of 3119 Instagram posts and 267 Twitter posts were included in the analysis. Of the 3119 Instagram posts analyzed, 34% were from patients, and 28% were from providers. Of the 267 Twitter posts analyzed, 42% were from patients, and 16% were from providers. Although the majority of social media posts were of a positive sentiment, over the past 3 years, there was a major surge in negative sentiment posts (97% increase) versus positive sentiment posts (9% increase). Patients were more likely to focus their posts on rehabilitation, return to play, and activities of daily living. Providers tended to focus their posts on education, rehabilitation, and injury prevention. Patient posts declined over the past 3 years (-28%), whereas provider posts increased substantially (110%). Of posts shared by health care providers, 4% of posts contained inaccurate or misleading information. CONCLUSION: The majority of patients who post about their UCL injury and reconstruction on social media have a positive sentiment when discussing their procedure. However, negative sentiment posts have increased significantly over the past 3 years. Patient content revolves around rehabilitation and return to play. Although patient posts have declined over the past 3 years, provider posts have increased substantially with an emphasis on education.