The selective D3Receptor antagonist VK4-116 reverses loss of insight caused by self-administration of cocaine in rats.

Chronic psychostimulant use causes long-lasting changes to neural and cognitive function that persist after long periods of abstinence. As cocaine users transition from drug use to abstinence, a parallel transition from hyperactivity to hypoactivity has been found in orbitofrontal-striatal glucose metabolism and striatal D2/D3-receptor activity. Targeting these changes pharmacologically, using highly selective dopamine D3-receptor (D3R) antagonists and partial agonists, has shown promise in reducing drug-taking, and attenuating relapse in animal models of cocaine and opioid use disorder. However, much less attention has been paid to treating the loss of insight, operationalized as the inability to infer likely outcomes, associated with chronic psychostimulant use. Here we tested the selective D3R antagonist VK4-116 as a treatment for this loss in rats with a prior history of cocaine use. Male and female rats were first trained to self-administer cocaine or a sucrose liquid for 2 weeks. After 4 weeks of abstinence, performance was assessed using a sensory preconditioning (SPC) learning paradigm. Rats were given VK4-116 (15 mg/kg, i.p.) or vehicle 30 min prior to each SPC training session, thus creating four drug-treatment groups: sucrose-vehicle, sucrose-VK4-116, cocaine-vehicle, cocaine-VK4-116. The control groups (sucrose-vehicle, sucrose-VK4-116) showed normal sensory preconditioning, whereas cocaine use (cocaine-vehicle) selectively disrupted responding to the preconditioned cue, an effect that was reversed in the cocaine-VK4-116 group, which demonstrating responding to the preconditioned cue at levels comparable to controls. These preclinical findings demonstrate that highly selective dopamine D3R antagonists, particularly VK4-116, can reverse the long-term negative behavioral consequences of cocaine use.

Perioperative use of low dose haloperidol safely reduces episodes of postoperative nausea/vomiting and length of stay following elective minimally invasive bariatric surgery.

INTRODUCTION: While total intravenous anesthesia (TIVA) protocols include Dexamethasone and Ondansetron prophylaxis, bariatric patients continue to be considered at particularly high risk for postoperative nausea/vomiting (PONV). A multimodal approach for prophylaxis is recommended by the Bariatric Enhanced Recovery After Surgery (ERAS) Society however, there remains a lack of consensus on the optimal strategy to manage PONV in these patients. Haloperidol has been shown at low doses to have a therapeutic effect in treatment of refractory nausea and in PONV prophylaxis in other high risk surgical populations. We sought to investigate its efficacy as a prophylactic medication for PONV in the bariatric population and to identify which perioperative strategies were most effective at reducing episodes of PONV. METHODS: An institutional bariatric database was created by retrospectively reviewing patients undergoing elective minimally invasive bariatric procedures from 2018 to 2022. Demographic data reviewed included age, gender, preoperative body mass index (BMI), ethnicity, and primary language. Primary endpoints included patient reported episodes of PONV, total doses of Ondansetron administered, need for a second antiemetic (rescue medication), complication rate (most commonly readmission within 30 days), and length of stay. Fisher's exact test, Mann-Whitney test, and ANOVA were used to evaluate the effect of perioperative management on various endpoints. RESULTS: A total of 475 patients were analyzed with Haloperidol being utilized in 15.8% of all patients. Patients receiving Haloperidol were less likely to require Ondansetron outside of the immediate perioperative period (34.7% vs. 49.8%, p = 0.02), experienced less PONV (41.3% vs. 64.3%, p = 0.01) and also had a decreased median length of stay (27.3 vs. 35.8 h, p < 0.0001). CONCLUSIONS: Addition of low dose Haloperidol to Bariatric ERAS protocols decreases incidence of PONV and the need for additional antiemetic coverage resulting in a significantly shorter length of stay, increasing the likelihood of safe discharge on postoperative day 1.

The selective D3-Receptor antagonist VK4-116 effectively treats behavioral inflexibility in rats caused by self-administration and withdrawal from cocaine.

Chronic psychostimulant use can cause long lasting changes to neural and cognitive function that persist even after long periods of abstinence. As cocaine users transition from drug use to abstinence, a parallel transition from hyperactivity to hypoactivity has been found in orbitofrontal-striatal glucose metabolism, and striatal D2/D3 receptor activity. Targeting these changes pharmacologically, using highly selective dopamine D3 receptor (D3R) antagonists and partial agonists, has shown significant promise in reducing drug-taking, and attenuating relapse in animal models of cocaine and opioid use disorder. However, much less attention has been focused on treating inflexible and potentially maladaptive non-drug behaviors following chronic psychostimulant use. Here we tested the selective D3R antagonist VK4-116 as a treatment for the long-term behavioral inflexibility in abstinent male and female rats with a prior history of chronic cocaine use. Rats were first trained to self-administer cocaine (0.75 mg/kg/reinforcer) or a sucrose liquid (10%, .04 mL/reinforcer) for 2 weeks (FR1 schedule, max 60 reinforcers in 3 hrs/ day), followed by 4 weeks of abstinence. Cognitive and behavioral flexibilities were then assessed using a sensory preconditioning (SPC) learning paradigm. Rats were given an VK4-116 (15 mg/kg, i.p.) or vehicle 30 mins prior to each SPC training session, thus creating four drug-treatment groups: sucrose-vehicle, sucrose-VK4-116, cocaine-vehicle, cocaine-VK4-116. The control groups (sucrose-vehicle, sucrose-VK4-116) demonstrated significant evidence of flexible SPC behavior, whereas cocaine use (cocaine-vehicle) disrupted SPC behavior. Remarkably, the D3R antagonist VK4-116 mitigated this cocaine deficit in the cocaine-VK4-116 group, demonstrating flexible SPC to levels comparable to the control groups. These preclinical findings demonstrate that highly selective dopamine D3R antagonists, particularly VK4-116, show significant promise as a pharmacological treatment for the long-term negative behavioral consequences of cocaine use disorder.

Otolaryngology consultations for COVID-19 patients: A retrospective cohort study of indications, interventions, and considerations.

OBJECTIVE: To identify differences in inpatient otolaryngology consultations and interventions for patients based on COVID-19. METHODS: Records were reviewed for all patients for whom otolaryngology was consulted at a high-volume tertiary care hospital from April 30, 2020 to October 1, 2020. Demographic information, length of stay, COVID-19 status, indication for consultation, and otolaryngology interventions were recorded. Statistical analysis was performed using R software. RESULTS: Bleeding composed a significantly higher proportion of otolaryngology consults in COVID-19 positive patients (28% vs. 8.4%, p<0.0001). Management of bleeding was the most common procedure performed in positive patients (n=37, 35%), and they had a higher median number of interventions performed when compared to bleeding patients who tested negative (1, IQR 1-2 vs. 1, IQR 0-1, p=0.04). COVID-19 positive patients with bleeding were more likely to expire than those with other indications for otolaryngology consultation (50% vs. 7%, p<0.001). CONCLUSION: Bleeding and associated interventions comprised the predominant discrepancy between COVID-19 positive and negative patients in our cohort. We encourage routine use of simple and cost-effective methods to decrease risk of bleeding.

Perceptions, training experiences, and preferences of surgical residents toward laparoscopic simulation training: a resident survey.

INTRODUCTION: Simulation training for surgical residents can shorten learning curves, improve technical skills, and expedite competency. Several studies have shown that skills learned in the simulated environment are transferable to the operating room. Residency programs are trying to incorporate simulation into the resident training curriculum to supplement the hands-on experience gained in the operating room. Despite the availability and proven utility of surgical simulators and simulation laboratories, they are still widely underutilized by surgical trainees. Studies have shown that voluntary use leads to minimal participation in a training curriculum. Although there are several simulation tools, there is no clear evidence of the superiority of one tool over the other in skill acquisition. The purpose of this study was to explore resident perceptions, training experiences, and preferences regarding laparoscopic simulation training. Our goal was to profile resident participation in surgical skills simulation, recognize potential barriers to voluntary simulator use, and identify simulation tools and tasks preferred by residents. Furthermore, this study may help to inform whether mandatory/protected training time, as part of the residents' curriculum is essential to enhance participation in the simulation laboratory. METHODS: A cross-sectional study on general surgery residents (postgraduate years 1-5) at Yale University School of Medicine and the University of Toronto via an online questionnaire was conducted. Overall, 67 residents completed the survey. The institutional review board approved the methods of the study. RESULTS: Overall, 95.5% of the participants believed that simulation training improved their laparoscopic skills. Most respondents (92.5%) perceived that skills learned during simulation training were transferrable to the operating room. Overall, 56.7% of participants agreed that proficiency in a simulation curriculum should be mandatory before operating room experience. The simulation laboratory was most commonly used during work hours; lack of free time during work hours was most commonly cited as a reason for underutilization. Factors influencing use of the simulation laboratory in order of importance were the need for skill development, an interest in minimally invasive surgery, mandatory/protected time in a simulation environment as part of the residency program curriculum, a recommendation by an attending surgeon, and proximity of the simulation center. The most preferred simulation tool was the live animal model followed by cadaveric tissue. Virtual reality simulators were among the least-preferred (25%) simulation tools. Most residents (91.0%) felt that mandatory/protected time in a simulation environment should be introduced into resident training protocols. CONCLUSIONS: Mandatory and protected time in a simulation environment as part of the resident training curriculum may improve participation in simulation training. A comprehensive curriculum, which includes the use of live animals, cadaveric tissue, and virtual reality simulators, may enhance the laparoscopic training experience and interest level of surgical trainees.

A rare cause of submandibular swelling in a 12-year-old child: pleomorphic adenoma.

Pleomorphic adenoma is rare in pediatric populations, where viral and congenital problems are the usual culprits responsible for submandibular masses. We report the case of a 12-year-old child who presented with a painless right submandibular mass that had developed over the course of 4 months. The patient denied fever, erythema, and edema. The mass was diagnosed as a branchial cleft cyst before complete excision was performed. The pattern and etiology of a pleomorphic adenoma in children differs from those in adults. In children, it requires prompt and correct diagnosis to keep morbidity and mortality at a minimum.

Do laparoscopic skills transfer to robotic surgery?

BACKGROUND: Identifying the set of skills that can transfer from laparoscopic to robotic surgery is an important consideration in designing optimal training curricula. We tested the degree to which laparoscopic skills transfer to a robotic platform. METHODS: Fourteen medical students and 14 surgery residents with no previous robotic but varying degrees of laparoscopic experience were studied. Three fundamentals of laparoscopic surgery tasks were used on the laparoscopic box trainer and then the da Vinci robot: peg transfer (PT), circle cutting (CC), and intracorporeal suturing (IS). A questionnaire was administered for assessing subjects' comfort level with each task. RESULTS: Standard fundamentals of laparoscopic surgery scoring metric were used and higher scores indicate a superior performance. For the group, PT and CC scores were similar between robotic and laparoscopic modalities (90 versus 90 and 52 versus 47; P > 0.05). However, for the advanced IS task, robotic-IS scores were significantly higher than laparoscopic-IS (80 versus 53; P < 0.001). Subgroup analysis of senior residents revealed a lower robotic-PT score when compared with laparoscopic-PT (92 versus 105; P < 0.05). Scores for CC and IS were similar in this subgroup (64 ± 9 versus 69 ± 15 and 95 ± 3 versus 92 ± 10; P > 0.05). The robot was favored over laparoscopy for all drills (PT, 66.7%; CC, 88.9%; IS, 94.4%). CONCLUSIONS: For simple tasks, participants with preexisting skills perform worse with the robot. However, with increasing task difficulty, robotic performance is equal or better than laparoscopy. Laparoscopic skills appear to readily transfer to a robotic platform, and difficult tasks such as IS are actually enhanced, even in subjects naive to the technology.

Construct and face validity of a virtual reality-based camera navigation curriculum.

INTRODUCTION: Camera handling and navigation are essential skills in laparoscopic surgery. Surgeons rely on camera operators, usually the least experienced members of the team, for visualization of the operative field. Essential skills for camera operators include maintaining orientation, an effective horizon, appropriate zoom control, and a clean lens. Virtual reality (VR) simulation may be a useful adjunct to developing camera skills in a novice population. No standardized VR-based camera navigation curriculum is currently available. We developed and implemented a novel curriculum on the LapSim VR simulator platform for our residents and students. We hypothesize that our curriculum will demonstrate construct and face validity in our trainee population, distinguishing levels of laparoscopic experience as part of a realistic training curriculum. METHODS: Overall, 41 participants with various levels of laparoscopic training completed the curriculum. Participants included medical students, surgical residents (Postgraduate Years 1-5), fellows, and attendings. We stratified subjects into three groups (novice, intermediate, and advanced) based on previous laparoscopic experience. We assessed face validity with a questionnaire. The proficiency-based curriculum consists of three modules: camera navigation, coordination, and target visualization using 0° and 30° laparoscopes. Metrics include time, target misses, drift, path length, and tissue contact. We analyzed data using analysis of variance and Student's t-test. RESULTS: We noted significant differences in repetitions required to complete the curriculum: 41.8 for novices, 21.2 for intermediates, and 11.7 for the advanced group (P < 0.05). In the individual modules, coordination required 13.3 attempts for novices, 4.2 for intermediates, and 1.7 for the advanced group (P < 0.05). Target visualization required 19.3 attempts for novices, 13.2 for intermediates, and 8.2 for the advanced group (P < 0.05). Participants believe that training improves camera handling skills (95%), is relevant to surgery (95%), and is a valid training tool (93%). Graphics (98%) and realism (93%) were highly regarded. CONCLUSIONS: The VR-based camera navigation curriculum demonstrates construct and face validity for our training population. Camera navigation simulation may be a valuable tool that can be integrated into training protocols for residents and medical students during their surgery rotations.

Transvaginal NOTES hybrid cholecystectomy.

BACKGROUND: Initial reports confirm the safety and feasibility of natural orifice transluminal eendoscopic surgery (NOTES) transvaginal hybrid cholecystectomy (TVC). Benefits of TVC include no visible scars, less pain, and shorter recovery. The authors describe a single surgeon's initial experience with TVC through his first 20 cases. METHOD: Under direct visualization from a 5-mm umbilical trochar, a 12-mm trocar, or in 2 cases a SILS port was introduced through the posterior vagina into the cul-de-sac. The gallbladder was visualized using an endoscope introduced through the vaginal port. Using extracorporeal stay sutures for retraction, the cystic duct and artery were dissected free, clipped, and divided. The gallbladder was then removed through the vaginal port. RESULTS: Twenty patients underwent a successful TVC. The average age was 34.9 years (21-55 years), average body mass index was 29.9 kg/m2 (18.3-38.1 kg/m2), and the mean operative time was 71.4 minutes (42-116 minutes). CONCLUSION: TVC is a safe, feasible, and attractive alternative to traditional 4-port laparoscopic cholecystectomy.

Video assisted thoracoscopic resection of a posterior mediastinal Castleman's tumor.

Castleman's disease (CD) or angiofollicular lymph node hyperplasia is a rare spectrum of lymphoproliferative disorders. CD tumors are commonly localized in the mediastinum and are usually asymptomatic. The mainstay of treatment is surgical resection and has typically been performed using open thoracotomy. Few reports in the literature describe video assisted thoracoscopic resection of these tumors. The differential diagnosis for mediastinal masses is extensive, and CD tumors, although uncommon, should be considered. We describe a case report of a posterior mediastinal Castleman's tumor adherent to the esophagus, which was resected thoracoscopically and review the literature.