Adaptor protein-3 produces synaptic vesicles that release phasic dopamine.

The burst firing of midbrain dopamine neurons releases a phasic dopamine signal that mediates reinforcement learning. At many synapses, however, high firing rates deplete synaptic vesicles (SVs), resulting in synaptic depression that limits release. What accounts for the increased release of dopamine by stimulation at high frequency? We find that adaptor protein-3 (AP-3) and its coat protein VPS41 promote axonal dopamine release by targeting vesicular monoamine transporter VMAT2 to the axon rather than dendrites. AP-3 and VPS41 also produce SVs that respond preferentially to high-frequency stimulation, independent of their role in axonal polarity. In addition, conditional inactivation of VPS41 in dopamine neurons impairs reinforcement learning, and this involves a defect in the frequency dependence of release rather than the amount of dopamine released. Thus, AP-3 and VPS41 promote the axonal polarity of dopamine release but enable learning by producing a distinct population of SVs tuned specifically to high firing frequency that confers the phasic release of dopamine.

Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma.

BACKGROUND: In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown. METHODS: In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point was progression-free survival. RESULTS: Among 357 patients in the RVD-alone group and 365 in the transplantation group, at a median follow-up of 76.0 months, 328 events of disease progression or death occurred; the risk was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% confidence interval [CI], 1.23 to 1.91; P<0.001); median progression-free survival was 46.2 months and 67.5 months. The percentage of patients with a partial response or better was 95.0% in the RVD-alone group and 97.5% in the transplantation group (P = 0.55); 42.0% and 46.8%, respectively, had a complete response or better (P = 0.99). Treatment-related adverse events of grade 3 or higher occurred in 78.2% and 94.2%, respectively; 5-year survival was 79.2% and 80.7% (hazard ratio for death, 1.10; 95% CI, 0.73 to 1.65). CONCLUSIONS: Among adults with multiple myeloma, RVD plus ASCT was associated with longer progression-free survival than RVD alone. No overall survival benefit was observed. (Funded by the National Heart, Lung, and Blood Institute and others; DETERMINATION ClinicalTrials.gov number, NCT01208662.).

Kinematic metrics and surgeon experience in robotic cholecystectomies: a pilot study on breaking down technical performance.

BACKGROUND: Recent studies have correlated surgical skill measured by video-based assessment with improved clinical outcomes. Certain automated measures of operative performance in robotic surgery can be gathered beyond video review called objective performance indicators (OPIs). We explore the relationship between OPIs, surgeon experience, and postoperative recovery, hypothesizing that more efficient dissection will be associated with experience. METHODS: Fifty-six robotic cholecystectomies between February 2022 and March 2023 were recorded at a large tertiary referral center. Surgeon experience and clinical outcomes data from the EMR were obtained for all 56 cases with 10 completing the QOL survey. Two steps of robotic cholecystectomies were reviewed: dissection of Calot's triangle (DCT) and dissection of the gallbladder from the liver (DGL). Postoperative recovery was measured using the SF-36 well-being survey. Univariate analysis was conducted using Pearson's coefficient. RESULTS: Increased operative experience was associated with more efficient camera and instrument movements. DCT had 7 and DGL had 31 of 41 OPIs that correlated with experience. With respect to DGL, more experienced surgeons had reduced step duration and instrument path length and increased camera and instrument speeds. CONCLUSIONS: Several OPIs correlate with surgical experience and may form the basis of more instructive feedback for trainees and less experienced surgeons in improving intraoperative technique.

Deep mutational scanning and massively parallel kinetics of plasminogen activator inhibitor-1 functional stability to probe its latency transition.

Plasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor superfamily of proteins, is unique among serine protease inhibitors for exhibiting a spontaneous conformational change to a latent or inactive state. The functional half-life for this transition at physiologic temperature and pH is ∼1 to 2 h. To better understand the molecular mechanisms underlying this transition, we now report on the analysis of a comprehensive PAI-1 variant library expressed on filamentous phage and selected for functional stability after 48 h at 37 °C. Of the 7201 possible single amino acid substitutions in PAI-1, we identified 439 that increased the functional stability of PAI-1 beyond that of the WT protein. We also found 1549 single amino acid substitutions that retained inhibitory activity toward the canonical target protease of PAI-1 (urokinase-like plasminogen activator), whereas exhibiting functional stability less than or equal to that of WT PAI-1. Missense mutations that increase PAI-1 functional stability are concentrated in highly flexible regions within the PAI-1 structure. Finally, we developed a method for simultaneously measuring the functional half-lives of hundreds of PAI-1 variants in a multiplexed, massively parallel manner, quantifying the functional half-lives for 697 single missense variants of PAI-1 by this approach. Overall, these findings provide novel insight into the mechanisms underlying the latency transition of PAI-1 and provide a database for interpreting human PAI-1 genetic variants.

Carbon-11-Labeled Methionine PET/CT in Patients With FDG-Occult Multiple Myeloma: A Prospective Pilot Study.

In a pilot study (ClinicalTrials.gov NCT02646085), seven patients with treated multiple myeloma and negative FDG PET/CT underwent amino acid imaging with 11C-methionine PET/CT. In five participants, 11C-methionine PET/CT showed focal uptake corresponding with lytic lesions; two to 18 lesions were found (SUVmax, 2.8-6.4). Findings indicated a potential role for 11C-methionine PET/CT in detecting residual disease after negative FDG PET/CT, thereby guiding further treatment.

Kinematic data profile and clinical outcomes in robotic inguinal hernia repairs: a pilot study.

BACKGROUND: Surgical training requires clinical knowledge and technical skills to operate safely and optimize clinical outcomes. Technical skills are hard to measure. The Intuitive Data Recorder (IDR), (Sunnyvale, CA) allows for the measurement of technical skills using objective performance indicators (OPIs) from kinematic event data. Our goal was to determine whether OPIs improve with surgeon experience and whether they are correlated with clinical outcomes for robotic inguinal hernia repair (RIHR). METHODS: The IDR was used to record RIHRs from six surgeons. Data were obtained from 98 inguinal hernia repairs from February 2022 to February 2023. Patients were called on postoperative days 5-10 and asked to take the Carolina Comfort Scale (CCS) survey to evaluate acute clinical outcomes. A Pearson test was run to determine correlations between OPIs from the IDR with a surgeon's yearly RIHR experience and with CCS scores. Linear regression was then run for correlated OPIs. RESULTS: Multiple OPIs were correlated with surgeon experience. Specifically, for the task of peritoneal flap exploration, we found that 23 OPIs were significantly correlated with surgeons' 1-year RIHR case number. Total angular motion distance of the left arm instrument had a correlation of - 0.238 (95% CI - 0.417, - 0.042) for RIHR yearly case number. Total angular motion distance of right arm instrument was also negatively correlated with RIHR in 1 year with a correlation of - 0.242 (95% CI - 0.420, - 0.046). For clinical outcomes, wrist articulation of the surgeon's console positively correlated with acute sensation scores from the CCS with a correlation of 0.453 (95% CI 0.013, 0.746). CONCLUSIONS: This study defines multiple OPIs that correlate with surgeon experience and with outcomes. Using this knowledge, surgical simulation platforms can be designed to teach patterns to surgical trainees that are associated with increased surgical experience and with improved postoperative outcomes.

ScreenLife Capture: An open-source and user-friendly framework for collecting screenomes from Android smartphones.

As our interactions with each other become increasingly digitally mediated, there is growing interest in the study of people's digital experiences. To better understand digital experiences, some researchers have proposed the use of screenomes. This involves the collection of sequential high-frequency screenshots which provide detailed objective records of individuals' interaction with screen devices over time. Despite its usefulness, there remains no readily available tool that researchers can use to run their own screenome studies. To fill this gap, we introduce ScreenLife Capture, a user-friendly and open-source software to collect screenomes from smartphones. Using this tool, researchers can set up smartphone screenome studies even with limited programming knowledge and resources. We piloted the tool in an exploratory mixed-method study of 20 college students, collecting over 740,000 screenshots over a 2-week period. We found that smartphone use is highly heterogeneous, characterized by threads of experiences. Using in-depth interviews, we also explored the impact that constant background surveillance of smartphone use had on participants. Participants generally had slight psychological discomfort which fades after a few days, would suspend screen recording for activity perceived to be extremely private, and recounted slight changes in behavior. Implications for future research is discussed.

Quality of life, psychological distress, and prognostic perceptions in patients with multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is an incurable hematologic malignancy requiring long-term, continuous therapy. Despite its chronic and unrelenting course, studies examining quality of life (QOL), psychological distress, and perceptions of prognosis by line of therapy are lacking. METHODS: The authors conducted a cross-sectional, multisite study of patients undergoing treatment for MM (excluding maintenance) between June 2020 and January 2021. The authors conducted purposeful sampling and recruited patients to 3 cohorts based on lines of therapy: 1) newly diagnosed receiving first-line therapy; 2) 2 to 3 lines; and 3) 4 or more lines. Patients completed validated questionnaires to assess their QOL, fatigue, psychological distress, and perceptions of prognosis. RESULTS: A total of 180 patients with MM were enrolled (newly diagnosed [n = 60], 2 to 3 lines [n = 60], and ≥4 lines of therapy [n = 60]). QOL, symptom burden, and fatigue scores did not differ by lines of therapy. There were no statistically significant differences in psychological distress by line of therapy. The rates of clinically significant depression, anxiety, and post-traumatic stress disorder symptoms were 23.9% (43 of 180), 23.9% (43 of 180), and 24.4% (44 of 180), respectively. Most patients (84.7%, 149 of 176) reported that their oncologist told them their cancer was incurable, but only 30.6% (53 of 173) acknowledged that they were terminally ill, and 42.0% (73 of 174) reported that they thought their cancer was incurable. CONCLUSIONS: Patients with MM undergoing treatment experience impaired QOL and elevated psychological distress across the disease continuum, regardless of line of therapy. A substantial proportion of patients with MM have significant misperceptions about their prognosis and the curability of their illness despite reporting being informed of the prognosis by their oncologist. LAY SUMMARY: This study discusses 180 patients with MM (newly diagnosed [n = 60], 2-3 lines [n = 60], and ≥4 lines of therapy [n = 60]). Quality of life, symptom burden, and fatigue scores do not differ by lines of therapy. There are also no statistically significant differences in psychological distress by line of therapy. The rates of clinically significant depression, anxiety, and post-traumatic stress disorder symptoms are 23.9%, 23.9%, and 24.4%, respectively. Most patients (84.7%) report that their oncologist told them their cancer was incurable, but only 30.6% acknowledge that they are terminally ill, and 42.0% report that they thought their cancer was incurable.

Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma.

BACKGROUND: Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options. METHODS: We administered oral selinexor (80 mg) plus dexamethasone (20 mg) twice weekly to patients with myeloma who had previous exposure to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). The primary end point was overall response, defined as a partial response or better, with response assessed by an independent review committee. Clinical benefit, defined as a minimal response or better, was a secondary end point. RESULTS: A total of 122 patients in the United States and Europe were included in the modified intention-to-treat population (primary analysis), and 123 were included in the safety population. The median age was 65 years, and the median number of previous regimens was 7; a total of 53% of the patients had high-risk cytogenetic abnormalities. A partial response or better was observed in 26% of patients (95% confidence interval, 19 to 35), including two stringent complete responses; 39% of patients had a minimal response or better. The median duration of response was 4.4 months, median progression-free survival was 3.7 months, and median overall survival was 8.6 months. Fatigue, nausea, and decreased appetite were common and were typically grade 1 or 2 (grade 3 events were noted in up to 25% of patients, and no grade 4 events were reported). Thrombocytopenia occurred in 73% of the patients (grade 3 in 25% and grade 4 in 33%). Thrombocytopenia led to bleeding events of grade 3 or higher in 6 patients. CONCLUSIONS: Selinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies. (Funded by Karyopharm Therapeutics; STORM ClinicalTrials.gov number, NCT02336815.).

Near-wall velocities of particles suspended in shear flow and a streamwise electric field.

Particles with a diameter of ∼0.5 µm in a dilute (volume fractions φ∞  < 4 × 10-3 ) suspension assemble into highly elongated structures called "bands" under certain conditions in combined Poiseuille and electroosmotic flows in opposite directions through microchannels at particle-based Reynolds numbers Rep  < < 1. The particles are first concentrated near, then form "bands" within ∼6 µm of, the channel wall. The experiments described here examine the near-wall dynamics of individual "tracer" particles during the initial concentration, or accumulation, of particles, and the steady-state stage when the particles have formed relatively stable bands at different near-wall shear rates and electric field magnitudes. Surprisingly, the near-wall upstream particle velocities are found to be consistently greater in magnitude than the expected values based on the particles being convected by the superposition of both flows and subject to electrophoresis, which is in the same direction as the Poiseuille flow. However, the particle velocities scale linearly with the change in electric field magnitude, suggesting that the particle dynamics are dominated by linear electrokinetic phenomena. If this discrepancy with theory is only due to changes in particle electrophoresis, electrophoresis is significantly reduced to values as small as 20%-50% of the Smoluchowski relation, or well below previous model predictions, even for high particle potentials.

Surgical coaching in obstetrics and gynecology: an evidence-based strategy to elevate surgical education and promote lifelong learning.

The American Board of Medical Specialties, of which the American Board of Obstetrics and Gynecology is a member, released recommendations in 2019 reimagining specialty certification and highlighting the importance of individualized feedback and data-driven advances in clinical practice throughout the physicians' careers. In this article, we presented surgical coaching as an evidence-based strategy for achieving lifelong learning and practice improvement that can help to fulfill the vision of the American Board of Medical Specialties. Surgical coaching involves the development of a partnership between 2 surgeons in which 1 surgeon (the coach) guides the other (the participant) in identifying goals, providing feedback, and facilitating action planning. Previous literature has demonstrated that surgical coaching is viewed as valuable by both coaches and participants. In particular, video-based coaching involves reviewing recorded surgical cases and can be integrated into the physicians' busy schedules as a means of acquiring and advancing both technical and nontechnical skills. Establishing surgical coaching as an option for continuous learning and improvement in practice has the potential to elevate surgical performance and patient care.

Phase 2 studies of lenalidomide, subcutaneous bortezomib, and dexamethasone as induction therapy in patients with newly diagnosed multiple myeloma.

There are limited prospective data on lenalidomide, subcutaneous bortezomib, and dexamethasone (RsqVd) in transplant-eligible/transplant-ineligible patients with newly diagnosed multiple myeloma. Reliable biomarkers for efficacy and toxicity are required to better tailor therapy. Two parallel studies were conducted by Cancer Trials Ireland (CTI; NCT02219178) and the Dana-Farber Cancer Institute (DFCI; NCT02441686). Patients received four 21-day cycles of RsqVd and could then receive either another 4 cycles of RsqVd or undergo autologous stem cell transplant. Postinduction/posttransplant, patients received lenalidomide maintenance, with bortezomib included for high-risk patients. The primary endpoint was overall response rate (ORR) after 4 cycles of RsqVd. Eighty-eight patients were enrolled and 84 treated across the two studies; median age was 64.7 (CTI study) and 60.0 years (DFCI study), and 59% and 57% had stage II-III disease. Pooled ORR after 4 cycles in evaluable patients was 93.5%, including 48.1% complete or very good partial responses (CTI study: 91.9%, 59.5%; DFCI study: 95.0%, 37.5%), and in the all-treated population was 85.7% (44.0%). Patients received a median of 4 (CTI study) and 8 (DFCI study) RsqVd cycles; 60% and 31% of patients (CTI study) and 33% and 51% of patients (DFCI study) underwent transplant or received further RsqVd induction, respectively. The most common toxicity was peripheral neuropathy (pooled: 68%, 7% grade 3-4; CTI study: 57%, 7%; DFCI study: 79%, 7%). Proteomics analyses indicated elevated kallikrein-6 in good versus poor responders, decreased midkine in good responders, and elevated macrophage inflammatory protein 1-alpha in patients who stopped treatment from neurotoxicity, suggesting predictive biomarkers warranting further investigation.

High levels of von Willebrand factor with reduced specific activities in hospitalized patients with or without COVID-19.

The COVID-19 pandemic is often accompanied by severe respiratory illness and thrombotic complications. Von Willebrand Factor (VWF) levels are highly elevated in this condition. However, limited data are available on the qualitative activity of VWF in COVID-19. We measured plasma VWF levels quantitatively (VWF antigen) and qualitatively (ristocetin-induced platelet agglutination, glycoprotein IbM (GPIbM) binding, and collagen binding). Consistent with prior reports, VWF antigen levels were significantly elevated in hospitalized patients with or without COVID-19. The GPIbM and collagen binding activity-to-antigen ratios were significantly reduced, consistent with qualitative changes in VWF in COVID-19. Of note, critically ill hospitalized patients without COVID-19 had similar reductions in VWF activity-to-antigen ratios as patients with COVID-19. Our data suggest that qualitative changes in VWF in COVID-19 may not be specific to COVID-19. Future studies are warranted to determine the mechanisms responsible for qualitative changes in VWF in COVID-19 and other critical illnesses.• VWF levels were increased in COVID-19 compared to healthy controls.• VWF activity-to-antigen ratios were decreased in COVID-19 compared to healthy controls.• There were no differences in VWF activity-to-antigen ratios between hospitalized patients with or without COVID-19.• These findings are consistent with qualitative changes in VWF in systemic inflammation which are not specific to COVID-19.• Future studies are needed to define possible roles of changes in conformation or multimer length in the qualitative changes in VWF in systemic inflammation.

The in vivo endothelial cell translatome is highly heterogeneous across vascular beds.

Endothelial cells (ECs) are highly specialized across vascular beds. However, given their interspersed anatomic distribution, comprehensive characterization of the molecular basis for this heterogeneity in vivo has been limited. By applying endothelial-specific translating ribosome affinity purification (EC-TRAP) combined with high-throughput RNA sequencing analysis, we identified pan EC-enriched genes and tissue-specific EC transcripts, which include both established markers and genes previously unappreciated for their presence in ECs. In addition, EC-TRAP limits changes in gene expression after EC isolation and in vitro expansion, as well as rapid vascular bed-specific shifts in EC gene expression profiles as a result of the enzymatic tissue dissociation required to generate single-cell suspensions for fluorescence-activated cell sorting or single-cell RNA sequencing analysis. Comparison of our EC-TRAP with published single-cell RNA sequencing data further demonstrates considerably greater sensitivity of EC-TRAP for the detection of low abundant transcripts. Application of EC-TRAP to examine the in vivo host response to lipopolysaccharide (LPS) revealed the induction of gene expression programs associated with a native defense response, with marked differences across vascular beds. Furthermore, comparative analysis of whole-tissue and TRAP-selected mRNAs identified LPS-induced differences that would not have been detected by whole-tissue analysis alone. Together, these data provide a resource for the analysis of EC-specific gene expression programs across heterogeneous vascular beds under both physiologic and pathologic conditions.

Interpreting Electrodiagnostic Studies for the Management of Nerve Injury.

Nerve injuries are common after trauma and can be life-altering for patients. Electrodiagnostic studies are the gold standard for diagnosing and prognosticating nerve injuries. However, most surgeons are not trained in the interpretation of these studies; rather, they rely on the interpretation provided by the electrodiagnostician, who in turn is unlikely to be trained in nerve reconstruction. This discrepancy between the interpretation of these studies and the management of nerve injuries can lead to suboptimal surgical planning and patient outcomes. This review aims to provide a framework for surgeons to take a more active role in collaborating with their colleagues in electrodiagnostic medicine in the interpretation of these studies, with an ultimate goal of improved patient care. The basics of nerve conduction studies, electromyography, and relevant terminology are reviewed. The relationship between the concepts of demyelination, axon loss, Wallerian degeneration, nerve regeneration, collateral sprouting, and clinical function are explained within the framework of the Seddon and Sunderland nerve injury classification system. The natural evolution of each degree of nerve injury over time is illustrated, and management strategies are suggested.

Observations of the near-wall accumulation of suspended particles due to shear and electroosmotic flow in opposite directions.

On the basis of previous studies, the particles in a dilute (volume fractions φ∞ < 4 × 10-3 ) suspension in combined Poiseuille and electroosmotic "counterflow" at flow Reynolds numbers Re ≤ 1 accumulate, then assemble into structures called "bands," within ∼6 µm of the channel wall. The experimental studies presented here use a small fraction of tracer particles labeled with a different fluorophore from the majority "bulk" particles to visualize the dynamics of individual particles in a φ∞ = 1.7 × 10-3  suspension. The results at two different near-wall shear rates and three electric field magnitudes E show that the near-wall particles are concentrated about 150-fold when the bands start to form, and are then concentrated about 200-fold to a maximum near-wall volume fraction of ∼0.34. The growth in the near-wall particles during this accumulation stage appears to be exponential. This near-wall particle accumulation is presumably driven by a wall-normal "lift" force. The observations of how the particles accumulate near the wall are compared with recent analyses that predict that suspended particles subject to shear flow and a dc electric field at small particle Reynolds numbers experience such a lift force. A simple model that assumes that the particles are subject to this lift force and Stokes drag suggests that the force driving particles toward the wall, of O(10-17 N), is consistent with the time scales for particle accumulation observed in the experiments.

Examining the Moderating Effect of Parenting Style and Parental Guidance on Children's Beliefs about Food: A Test of the Parenting Style-as-Context Model.

Research examining the effect of parenting practices on child food consumption has often neglected the role in which global aspects of parenting - such as parenting style - play in shaping children's dietary behaviors. To address this gap, the parenting style-as-context model was used to examine the moderating effects of parenting style - defined as the perceived emotional climate communicated to children by their parents - on the association between parental guidance of food consumption and children's beliefs surrounding food. A cross-sectional survey of 1,113 child/adolescent participants between the ages of 9 and 18 was conducted to test the theoretical propositions derived from the parenting style-as-context model. Results suggest desirable relationships between different dimensions of parental guidance of food consumption on children's beliefs surrounding foods were stronger among children who were under an authoritative parenting style compared to other parenting styles. The results offer some support for the parenting style-as-context model and has theoretical and practical implications for research targeted at understanding the role parents play in inculcating healthy dietary habits among children.

Promoting Healthier Eating via Parental Communication: Development and Validation of the Active and Restrictive Parental Guidance Questionnaire (PARQ).

Parents are important sources of influence in the development of healthy eating among children and adolescents. Besides gatekeeping and modeling, parents serve as health educators and promoters, using intentional and persuasive communication to encourage healthier eating preferences and behaviors in children. Despite this, a lack of reliable and valid measures has limited the research on how parent-driven interpersonal communication about foods influence child food consumption outcomes. Building on the research in parental mediation of media consumption, and parenting practices in public health nutrition, this study details the development and validation of the active and restrictive parental guidance questionnaire with a sample of 246 children and adolescents at the scale development phase and another sample of 1,113 children and adolescents at the scale validation phase. Findings show that parents employ four communicative strategies to encourage a healthier diet: active guidance, general discussion, preventive restrictive guidance, and promotive restrictive guidance. The new measure was shown to have good validity and measurement model fit. Implications for future research are discussed.

Video-based Learning in Surgery: Establishing Surgeon Engagement and Utilization of Variable-duration Videos.

OBJECTIVE: To measure surgeon engagement and preferred video duration in a video-based learning program for nerve surgery. BACKGROUND: Educational videos can improve, standardize, and democratize best practices in surgery. To improve care internationally, educators must optimize their videos for learning. However, surgeon engagement and optimal video duration remain undefined. METHODS: A YouTube channel and a video-based learning website, PASSIO Education (passioeducation.com), were examined from 2011 to 2017. We assessed views, geographic location, audience engagement (average percent of video watched), audience retention (percent of viewers at each timepoint), and usage of short (median 7.4, range 4.1-20.3 min) and long (median 17.2, range 6.1-47.7 min) video formats for the same procedures. A survey of PASSIO Education membership examined preferred video duration. RESULTS: Our 117 nerve surgery videos attained over 3 million views with 69% originating outside of the United States. While YouTube achieved more international exposure, PASSIO Education attained a greater mean engagement of 48.4% (14.3% absolute increase, P < 0.0001). Surveyed surgeons (n = 304) preferred longer videos when preparing for infrequent or difficult cases compared with routine cases (P < 0.0001). Engagement declined with video duration, but audience retention between short and long video formats was correlated (τB = 0.52, P < 0.0001). CONCLUSIONS: For effective spread of best practices, we propose the joint use of YouTube for audience outreach and a surgeon-focused platform to maximize educational value. Optimal video duration is surgeon- and case-dependent and can be addressed through offering multiple video durations and interactive viewing options.