Association of Crowd-Sourced Assessment of Technical Skills (CSATSTM) and Outcomes of Robotic Assisted Radical Prostatectomy.

OBJECTIVE: To investigate if use of the Crowd-Sourced Assessment of Technical Skills (CSATSTM) platform and video peer review with constructive feedback is associated with improvement in technical skill and patient outcomes for robotic-assisted laparoscopic prostatectomy (RALP). METHODS: Five fellowship-trained urologists voluntarily submitted RALP cases for CSATSTM Global Evaluative Assessment of Robotic Skills (GEARS) scoring and expert narrative review between April 15, 2022 - April 30, 2023. Surgeon-selected and randomly-selected cases were reviewed. Surgeons underwent local peer review of videos with constructive feedback. Change in GEARS scores and frequency of post-operative outcomes over the 12-month periods before and during the study were analyzed in logistic regression models. Bias was assessed with sensitivity analysis comparing surgeon-selected to randomly-selected cases. RESULTS: GEARS scores for randomly-selected versus surgeon-selected cases did not differ significantly. Overall GEARS score correlated positively with annual surgical RALP volume (r=0.39, p=0.003) and negatively with years in practice (r=-0.34, p=0.01). After adjusting for confounders, there was no significant improvement in overall GEARS Score (0.01±0.02/month, p=0.48); but likelihood of sepsis (Odds Ratio 0.07, 95% CI 0.01-1.00, p=0.05) and pelvic fluid collection (Odds Ratio 0.09, 95% CI 0.01-0.99, p=0.049) were significantly decreased during the intervention period (n=165) compared to the prior 12 months (n=144). No outcome increased in likelihood (p>0.05). CONCLUSIONS: Integration of CSATSTM and local video peer review is associated with significant improvement in patient outcomes after RALP, despite no significant change in surgeons' GEARS scores. This is the first study demonstrating improvement in patient RALP outcomes after implementation of such a paradigm in practicing surgeons.

Risk Factors and Contemporary Management Options for Pain and Discomfort Experienced During a Prostate Biopsy.

PURPOSE OF REVIEW: Prostate fusion biopsy, an innovative imaging modality for diagnosing prostate cancer, presents certain challenges for patients including discomfort and emotional distress, leading to nonadherence to treatment and follow-ups. To inform clinicians and offer pain relief alternatives to patients, this review delves into the risk factors for increased pain and modern management options to alleviate pain during prostate biopsy. RECENT FINDINGS: Individual responses to pain vary, and the overall experience of pain during a prostate biopsy has been contributed to numerous factors such as patient age, prostate volume, previous biopsy experience, and more. As a result, several strategies aim to mitigate pain during in-office procedures. Notably, techniques including pharmacological analgesics, hand holding, heating pads, entertainment/virtual reality, and distraction have shown significant efficacy. Existing studies explore risk factors influencing pain intensity during prostate biopsy and effective pain management strategies. This review consolidates available information to guide clinicians in enhancing patient comfort and thus, encourage surveillance adherence.

Male DAT Val559 Mice Exhibit Compulsive Behavior under Devalued Reward Conditions Accompanied by Cellular and Pharmacological Changes.

Identified across multiple psychiatric disorders, the dopamine (DA) transporter (DAT) Ala559Val substitution triggers non-vesicular, anomalous DA efflux (ADE), perturbing DA neurotransmission and behavior. We have shown that DAT Val559 mice display a waiting impulsivity and changes in cognitive performance associated with enhanced reward motivation. Here, utilizing a within-subject, lever-pressing paradigm designed to bias the formation of goal-directed or habitual behavior, we demonstrate that DAT Val559 mice modulate their nose poke behavior appropriately to match context, but demonstrate a perseverative checking behavior. Although DAT Val559 mice display no issues with the cognitive flexibility required to acquire and re-learn a visual pairwise discrimination task, devaluation of reward evoked habitual reward seeking in DAT Val559 mutants in operant tasks regardless of reinforcement schedule. The direct DA agonist apomorphine also elicits locomotor stereotypies in DAT Val559, but not WT mice. Our observation that dendritic spine density is increased in the dorsal medial striatum (DMS) of DAT Val559 mice speaks to an imbalance in striatal circuitry that might underlie the propensity of DAT Val559 mutants to exhibit compulsive behaviors when reward is devalued. Thus, DAT Val559 mice represent a model for dissection of how altered DA signaling perturbs circuits that normally balance habitual and goal-directed behaviors.

Behaviorally penetrant, anomalous dopamine efflux exposes sex and circuit dependent regulation of dopamine transporters.

Virtually all neuropsychiatric disorders display sex differences in prevalence, age of onset, and/or clinical symptomology. Although altered dopamine (DA) signaling is a feature of many of these disorders, sex-dependent mechanisms uniquely responsive to DA that drive sex-dependent behaviors remain unelucidated. Previously, we established that anomalous DA efflux (ADE) is a prominent feature of the DA transporter (DAT) variant Val559, a coding substitution identified in two male-biased disorders: attention-deficit/hyperactivity disorder and autism spectrum disorder. In vivo, Val559 ADE induces activation of nigrostriatal D2-type DA autoreceptors (D2ARs) that magnifies inappropriate, nonvesicular DA release by elevating phosphorylation and surface trafficking of ADE-prone DAT proteins. Here we demonstrate that DAT Val559 mice exhibit sex-dependent alterations in psychostimulant responses, social behavior, and cognitive performance. In a search for underlying mechanisms, we discovered that the ability of ADE to elicit D2AR regulation of DAT is both sex and circuit-dependent, with dorsal striatum D2AR/DAT coupling evident only in males, whereas D2AR/DAT coupling in the ventral striatum is exclusive to females. Moreover, systemic administration of the D2R antagonist sulpiride, which precludes ADE-driven DAT trafficking, can normalize DAT Val559 behavioral changes unique to each sex and without effects on the opposite sex or wildtype mice. Our studies support the sex- and circuit dependent capacity of D2ARs to regulate DAT as a critical determinant of the sex-biased effects of perturbed DA signaling in neurobehavioral disorders. Moreover, our work provides a cogent example of how a shared biological insult drives alternative physiological and behavioral trajectories as opposed to resilience.

Serotonin transporter inhibition and 5-HT2C receptor activation drive loss of cocaine-induced locomotor activation in DAT Val559 mice.

Dopamine (DA) signaling dysfunction is believed to contribute to multiple neuropsychiatric disorders including attention-deficit/hyperactivity disorder (ADHD). The rare DA transporter (DAT) coding substitution Ala559Val found in subjects with ADHD, bipolar disorder and autism, promotes anomalous DA efflux in vitro and, in DAT Val559 mice, leads to increased reactivity to imminent handling, waiting impulsivity, and enhanced motivation for reward. Here, we report that, in contrast to amphetamine and methylphenidate, which induce significant locomotor activation, cocaine administration to these mice elicits no locomotor effects, despite retention of conditioned place preference (CPP). Additionally, cocaine fails to elevate extracellular DA. Given that amphetamine and methylphenidate, unlike cocaine, lack high-affinity interactions with the serotonin (5-HT) transporter (SERT), we hypothesized that the lack of cocaine-induced hyperlocomotion in DAT Val559 mice arises from SERT blockade and augmented 5-HT signaling relative to cocaine actions on wildtype animals. Consistent with this idea, the SERT blocker fluoxetine abolished methylphenidate-induced locomotor activity in DAT Val559 mice, mimicking the effects seen with cocaine. Additionally, a cocaine analog (RTI-113) with greater selectivity for DAT over SERT retains locomotor activation in DAT Val559 mice. Furthermore, genetic elimination of high-affinity cocaine interactions at SERT in DAT Val559 mice, or specific inhibition of 5-HT2C receptors in these animals, restored cocaine-induced locomotion, but did not restore cocaine-induced elevations of extracellular DA. Our findings reveal a significant serotonergic plasticity arising in the DAT Val559 model that involves enhanced 5-HT2C signaling, acting independently of striatal DA release, capable of suppressing the activity of cocaine-sensitive motor circuits.