Evaluation of a novel virtual reality Immersive Clinical Experience to enhance medical education curriculum.

Medical students often find the transition to clerkship challenging and stressful. The use of virtual reality (VR) technologies such as screen-based learning, 360-video and immersive VR using head-mount-devices is becoming more utilized in medical education. Immersive technologies in particular have been shown to lead to greater enthusiasm and provide higher knowledge gain for students compared to screen-based VR. The University of British Columbia Faculty of Medicine has developed a novel immersive patient experience using VR to enhance the clinical skills program and evaluate student perception regarding its formal integration into curricula. Students reported positive feedback on the experience, and interest in more immersive learning opportunities in future sessions. VR technology has the potential to enhance medical education and provide a safe immersive learning environment to build clinical acumen.

Les étudiants en médecine trouvent souvent la transition vers l'externat difficile et stressante. L'utilisation des technologies de réalité virtuelle (RV), telles que l'apprentissage sur écran, la vidéo à 360° et la RV immersive à l'aide de dispositifs de tête, est de plus en plus répandue dans le secteur de la formation médicale. On a démontré que les technologies immersives, en particulier, suscitent un plus grand enthousiasme et permettent aux étudiants d'acquérir davantage de connaissances que la RV sur écran. La Faculté de médecine de l'Université de la Colombie-Britannique a mis au point une nouvelle expérience immersive du patient en utilisant la RV pour améliorer le programme de compétences cliniques et évaluer la perception des étudiants concernant son intégration formelle dans les programmes d'études. Les étudiants ont fait part de leurs réactions positives à l'égard de l'expérience et de leur intérêt pour des possibilités d'apprentissage plus immersives dans les sessions futures. La technologie de la RV a le potentiel d'améliorer la formation médicale et de fournir un environnement d'apprentissage immersif sûr pour développer le sens clinique.

The Genotype and Phenotypes in Families (GPF) platform manages the large and complex data at SFARI.

The exploration of genotypic variants impacting phenotypes is a cornerstone in genetics research. The emergence of vast collections containing deeply genotyped and phenotyped families has made it possible to pursue the search for variants associated with complex diseases. However, managing these large-scale datasets requires specialized computational tools tailored to organize and analyze the extensive data. GPF (Genotypes and Phenotypes in Families) is an open-source platform ( https://github.com/iossifovlab/gpf ) that manages genotypes and phenotypes derived from collections of families. The GPF interface allows interactive exploration of genetic variants, enrichment analysis for de novo mutations, and phenotype/genotype association tools. In addition, GPF allows researchers to share their data securely with the broader scientific community. GPF is used to disseminate two large-scale family collection datasets (SSC, SPARK) for the study of autism funded by the SFARI foundation. However, GPF is versatile and can manage genotypic data from other small or large family collections. Our GPF-SFARI GPF instance ( https://gpf.sfari.org/ ) provides protected access to comprehensive genotypic and phenotypic data for the SSC and SPARK. In addition, GPF-SFARI provides public access to an extensive collection of de novo mutations identified in individuals with autism and related disorders and to gene-level statistics of the protected datasets characterizing the genes' roles in autism. Here, we highlight the primary features of GPF within the context of GPF-SFARI.

Tympanomastoidectomy versus parenteral antibiotic therapy for pediatric otorrhea.

OBJECTIVE: To evaluate the efficacy of tympanomastoidectomy versus parenteral antibiotic therapy for otorrhea as a result of chronic suppurative otitis media (CSOM) without cholesteatoma in the pediatric population. METHODS: A retrospective review of 221 patients treated for otorrhea at a tertiary academic pediatric hospital was performed to evaluate the impact of tympanomastoidectomy versus parenteral antibiotic therapy on resolution of otorrhea. Inclusion criteria were age 0-18 years, prior treatment with otic and/or oral antibiotic, prior history of tympanostomy tube placement for recurrent otitis media, history of otorrhea, treatment with tympanomastoidectomy or parenteral antibiotic therapy, and follow-up of at least 1 month after intervention. Time to resolution was compared between the two modalities adjusting for age, bilateral ear disease status, and comorbidities using a Cox proportional hazard model. RESULTS: Eighty-three ears from 58 children met the inclusion criteria. Ears that initially underwent tympanomastoidectomy had a significantly shorter time to resolution of symptoms (median time to resolution) 9 months (95 % confidence interval CI: 6.2-14.8) vs. 48.5 months (95 % lower CI 9.4, p = 0.006). On multivariate analysis, however, only bilateral ear disease status was independently associated with time to resolution of symptoms (hazard ratio 0.4, 95 % CI 0.2-0.9, p = 0.03). There was no statistically significant difference in the rate of treatment-related complications when comparing tympanomastoidectomy to parenteral antibiotic therapy (p = 0.37). CONCLUSION: When adjusting for age, bilateral ear disease status, and comorbidities, there does not appear to be a significant difference in time to resolution of symptoms when comparing parenteral antibiotic therapy to tympanomastoidectomy. An informed discussion regarding risks and benefits of each approach should be employed when deciding on the next step in management for patients with CSOM who have failed more conservative therapies.

Outcomes of Squamous Cell Carcinoma of the Lip Treated With Mohs Micrographic Surgery: A Retrospective Cohort Study.

BACKGROUND: Cutaneous squamous cell carcinomas (cSCCs) of the lip have been reported to be at higher risk for poorer post-treatment outcomes. OBJECTIVE: To examine outcomes of patients with SCC of the lip treated with Mohs micrographic surgery (MMS) and identify factors for recurrence. MATERIALS AND METHODS: This retrospective review of a single tertiary referral center's Mohs case logs from 2010 to 2019 identified cases of lip SCC. Clinicopathologic characteristics and outcomes (local recurrence [LR], metastasis, and disease-specific death) were reviewed. RESULTS: One hundred ninety cases of SCC of the lip were identified and demonstrated that MMS offered a disease-free survival of 96.8% over an average follow-up period of 42 months. Younger age (61 vs 74 years p = .006), increased MMS stages ( p = .009), and higher American Joint Committee on Cancer and Brigham and Women's Hospital T stages were risk factors for LR. Immunosuppression, large tumor size, mucosal lip involvement, aggressive histology, and perineural invasion were not associated with LR. CONCLUSION: The results of this study show that SCC of the lip behaved similarly to cSCC outside the lip area, and that both primary and recurrent lesions can be treated effectively with MMS.

Approaches to Tumors of the Nail Unit and Genitalia.

The nail unit and genitalia represent rare locations where malignant tumors may arise. Human papillomavirus has emerged as a causative agent of the development of the most common malignancies in these sites. Tissue preservation with surgery is of utmost importance, and tissue-sparing approaches are increasingly emphasized in the dermatology, urology, and gynecology literature. In addition to its tissue-sparing nature, Mohs micrographic surgery allows the complete evaluation of histologic margins to ensure tumor extirpation and may be the ideal treatment modality. The authors herein present approaches for the evaluation and treatment of malignant tumors of the nail unit and genitalia.

Mohs micrographic surgery for periocular skin cancer: a single-institution experience.

Periocular skin cancers require both effective and tissue-sparing treatment to minimize morbidity and preserve eyelid and lacrimal system function. We aim to define outcomes of periocular tumors treated with Mohs micrographic surgery (MMS) and factors associated with poor outcomes after surgery. This is a retrospective cohort study of all periocular tumors treated with MMS at an academic, large metropolitan-based referral center from January 1, 2013 to December 31, 2018. For 316 tumors from 307 patients, 75.3% of cases were basal cell carcinoma (BCC) (n = 238), 20.9% were squamous cell carcinoma (SCC) (n = 66), 2.5% were melanoma (n = 8), and 1.3% were primary adnexal carcinoma (n = 4). Over a mean follow-up of 47 months (range 12-108 months), local recurrence of two BCCs was observed. There were no recurrences for SCC, adnexal carcinoma, or melanoma. For BCC, previously treated tumors had higher risk for recurrence after MMS. AJCC 8 T stage was not associated with poor outcomes after MMS for periocular carcinoma or melanoma. Mohs micrographic surgery offers excellent cure rates for periocular cutaneous tumors. For basal cell carcinoma, previously treated lesions were associated with additional recurrence after MMS.

Cost effectiveness of melanoma in situ resection and repair by dermatology compared to non-dermatology specialties at a single institution.

Melanoma-in-situ (MIS) is treated with surgical resection by many specialties. Dermatologists perform these procedures in outpatient settings while others often employ operating rooms and general anesthesia. We hypothesized that MIS managed by dermatology was less costly than that managed by other specialties. All cases of MIS treated at our institution over a 3-year period were evaluated retrospectively for demographic and clinical characteristics and categorized by treating specialty. Estimated cost information was determined using records of charges billed. The mean total cost for MIS treated with wide local excision (WLE) by dermatologists was $1089 (CI = $941-1237) versus all other specialties at $5172 (CI = $2419-7925) (p < 0.001). MIS treated with Mohs micrographic surgery and repaired by dermatology (mean = $2325, CI = $2241-2409) was also less expensive than MIS treated by other specialties with WLE (p < 0.001). The results suggest MIS is significantly less costly to patients and the health care system when treatment is performed by dermatologists compared to other surgical specialties. This is likely due to dermatologists performing the procedures in less expensive outpatient settings.

A Call to Evaluate Manual Dexterity of Prospective Surgical Trainees.

INTRODUCTION: This study assesses the correlation between academic grades and gross and fine motor skills in prospective surgical trainees. METHODS: Forty-seven General Surgery Residency applicants and 32 medical students with prospective surgical interests were recruited. Manual dexterity (MD) was assessed through six tasks: O'Connor Tweezer Dexterity Test and Minnesota Manual Dexterity Test; Peg Transfer Test Fundamentals of Laparoscopic Surgery (box); Ring and Rail, Thread the Ring and Suture Sponge (da Vinci Surgical Simulator). RESULTS: Medical students with higher academic scores had longer completion times for the peg transfer test (P = 0.013). Individuals who played musical instruments and perceived themselves to have "Excellent" MD and motor coordination (MC) were more likely to score higher on the Thread the Ring test (P = 0.007; P = 0.009 ,respectively). Those who perceived themselves to have "Mediocre" MD and MC performed the worst on the: O'Connor Tweezer Dexterity Test (P = 0.023). CONCLUSIONS: Preliminary data suggest that MD ability correlates with neither high United States Medical Licensing Examination scores nor high academic grades; however, previous experience playing a musical instrument and high self-ratings of MD/MC may be associated with better test performance.

Hearing loss caused by CMV infection is correlated with reduced endocochlear potentials caused by strial damage in murine models.

Congenital cytomegalovirus (CMV) infection is a significant cause of neonatal hearing loss. However, at the cochlear level, the anatomical lesions and pathophysiological mechanisms that underlie hearing loss are still not clearly understood. In murine models of CMV infection, we have observed early damage to the capillary networks in stria vascularis, as well as hearing loss manifested in ABR threshold elevations. Our experimental hypothesis is that strial damage causes a reduced endocochlear potential (EP) resulting in impaired haircell activation and consequent hearing loss. We have studied strial damage, EP, and ABR threshold elevations in two mouse models (BALB/c and C57BL6 strains) infected with murine CMV. Neonatal (P3) pups were inoculated with murine CMV (2µl of 200pfu) by intra cerebral injection. Control mice were saline injected. At 6 weeks, ABR thresholds to tonal stimuli at 8, 16 and 32 kHz were determined for each ear. At 8 weeks a sub-group of treated and control animals was prepared for study of cochlear capillary networks using scanning electron microscopy of corrosion cast specimens. In a second group, at 8 weeks, EP measurements from both cochleas were made. We report that in both mouse strains, CMV infection caused capillary loss in the stria vascularis, initially at the cochlear apex, and extending to lower cochlear turns in some subjects. After CMV infection, in both BALB/c and C57BL6 mice, reduced EPs and ABR threshold elevations were observed, and there was a within-animal correlation between loss of EP and ABR threshold elevations across the sound frequencies tested. These results suggest that CMV induced damage to stria vascularis results in EP reduction that is correlated with ABR threshold elevations. Extrapolating to the human condition, we suggest that strial damage and its physiological consequences may contribute to the initial hearing loss in congenital CMV infection. The early involvement of cochlear capillary damage may encourage a focus on therapeutic interventions that can prevent vascular damage, or subsequently promote vascular healing or angiogenesis.

A rapid influenza diagnostic test based on detection of viral neuraminidase activity.

Current methods used for diagnosis of acute infection of pathogens rely on detection of nucleic acids, antigens, or certain classes of antibodies such as IgM. Here we report a virus enzyme assay as an alternative to these methods for detection of acute viral infection. In this method, we used a luciferin derivative as the substrate for detection of the enzyme activity of influenza viral neuraminidase as a means for diagnosis of influenza. The resulting commercial test, the qFLU Dx Test, uses a different supply chain that does not compete with those for the current tests. The assay reagents were formulated as a master mix that accommodated both the neuraminidase and luciferase reactions, thereby enabling rapid and prolonged production of stable light signal in the presence of influenza virus in the sample. The assay was evaluated using depository throat swab specimens. As expected, the assay exhibited similar detection rates for all influenza types and subtypes except for A(H7N9), which exhibited lower detection rate due to lower viral titer in the specimens. When throat swab specimens were diluted with the sample buffer of the test kit and tested with the qFLU Dx Test. The sensitivity and specificity were 82.41% (95% confidence interval: 79.66-85.84%) and 95.39% (95% confidence interval: 94.32-96.46%), respectively, for these diluted specimens in comparison to a real-time polymerase chain reaction assay. The uniqueness of the qFLU Dx Test as an enzymatic assay makes it highly complementary with currently available methods.

Modelling the impact of nucleolin expression level on the activity of F3 peptide-targeted pH-sensitive pegylated liposomes containing doxorubicin.

Strategies targeting nucleolin have enabled a significant improvement in intracellular bioavailability of their encapsulated payloads. In this respect, assessment of the impact of target cell heterogeneity and nucleolin homology across species (structurally and functionally) is of major importance. This work also aimed at mathematically modelling the nucleolin expression levels at the cell membrane, binding and internalization of pH-sensitive pegylated liposomes encapsulating doxorubicin and functionalized with the nucleolin-binding F3 peptide (PEGASEMP), and resulting cytotoxicity against cancer cells from mouse, rat, canine, and human origin. Herein, it was shown that nucleolin expression levels were not a limitation on the continuous internalization of F3 peptide-targeted liposomes, despite the saturable nature of the binding mechanism. Modeling enabled the prediction of nucleolin-mediated total doxorubicin exposure provided by the experimental settings of the assessment of PEGASEMP's impact on cell death. The former increased proportionally with nucleolin-binding sites, a measure relevant for patient stratification. This pattern of variation was observed for the resulting cell death in nonsaturating conditions, depending on the cancer cell sensitivity to doxorubicin. This approach differs from standard determination of cytotoxic concentrations, which normally report values of incubation doses rather than the actual intracellular bioactive drug exposure. Importantly, in the context of development of nucleolin-based targeted drug delivery, the structural nucleolin homology (higher than 84%) and functional similarity across species presented herein, emphasized the potential to use toxicological data and other metrics from lower species to infer the dose for a first-in-human trial.

Gadolinium-based contrast agent for Magnetic Resonance Imaging as a predictor of postmeningitic hearing loss in children.

OBJECTIVE: To determine if Gadolinium-based enhanced Magnetic Resonance Imaging (GdMRI) can be used to predict sensorineural hearing loss (SNHL) in pediatric patients diagnosed with bacterial meningitis. STUDY: Design: Retrospective chart review. SETTING: Primary Children's Hospital, Salt Lake City, Utah. SUBJECTS: and Methods: We studied forty-two pediatric patients diagnosed with bacterial meningitis who underwent brain GdMRI during their index hospital admission and for whom ear specific audiometric data were available (August 2008-July 2018). A pediatric neuroradiologist, blinded to both disease and audiometric data, rated cochlear enhancement of each GdMRI (0-3; none to markedly enhanced). RESULTS: Ear specific MRI scores were statistically significantly related to ear specific hearing outcomes (p < 0.01). SNHL occurred in 19 out of 82 ears (12 out of 42 patients; 2 ears were excluded due to pre-existing SNHL in one ear and inability to read the GdMRI on the other ear). Ten of 19 ears (53%) that developed SNHL showed mild/moderate/marked enhancement (MRI score of 1, 2, or 3 respectively). Fifty-three of the 63 unaffected ears (84%) showed no enhancement (MRI score of 0). Ten of 13 (77%) ears that developed severe to profound SNHL showed mild/moderate/marked enhancement. GdMRI was 58% sensitive and 84% specific in predicting which ears would develop SNHL. GdMRI was 77% sensitive and 84% specific in identifying severe to profound SNHL. CONCLUSION: Our study demonstrates that GdMRI is a promising tool for predicting specifically severe-profound hearing loss in pediatric patients following bacterial meningitis infection.

GenomeDiver: a platform for phenotype-guided medical genomic diagnosis.

PURPOSE: Making a diagnosis from clinical genomic sequencing requires well-structured phenotypic data to guide genotype interpretation. A patient's phenotypic features can be documented using the Human Phenotype Ontology (HPO), generating terms used to prioritize genes potentially causing the patient's disease. We have developed GenomeDiver to provide a user interface for clinicians that allows more effective collaboration with the clinical diagnostic laboratory, with the goal of improving the success of the diagnostic process. METHODS: GenomeDiver uses genomic data to prompt reverse phenotyping of patients undergoing genetic testing, enriching the amount and quality of structured phenotype data for the diagnostic laboratory, and helping clinicians to explore and flag diseases potentially causing their patient's presentation. RESULTS: We show how GenomeDiver communicates the clinician's informed insights to the diagnostic lab in the form of HPO terms for interpretation of genomic sequencing data. We describe our user-driven design process, the engineering of the software for efficiency, security and portability, and examples of the performance of GenomeDiver using genomic testing data. CONCLUSION: GenomeDiver is a first step in a new approach to genomic diagnostics that enhances laboratory-clinician interactions, with the goal of directly engaging clinicians to improve the outcome of genomic diagnostic testing.