The Changing Landscape of Treatment for Cystic Fibrosis Related Diabetes.

Objective: Patients with Cystic Fibrosis related diabetes [CFRD] are treated with insulin and high calorie diets to maintain body mass. The combined CFTR modulator elexacaftor/tezacaftor/ivacaftor [ETI] decreases pulmonary exacerbations and improves nutritional status. We reviewed the effects of ETI on BMI, HbA1c and diabetes regimen in patients with CFRD over a period of three years. Methods: Data of previously CFTR-modulator-naïve patients with CFRD and pancreatic insufficiency on ETI therapy were retrieved from an electronic health record database. Patients were followed for a mean duration of 2.7 ± 0.8 years after ETI initiation. Data pertaining to weight, BMI, HbA1c and diabetes regimen were collected at 6 months, 12 months, 2 years and at 3 years post-ETI initiation. Patients were then dichotomized based on their baseline BMI into a low BMI group and an "at target" BMI group. The effects of ETI on changes in weight, BMI, A1c and diabetes regimen were compared in both groups over a period of three years. Results: Twenty-seven patients with CFRD (15 men/12 women), age 30.6 ± 11.5 (SD) years, BMI 22.4 ± 4.0 kg/m2, were included. Fifteen patients had low BMI (<22 kg/m2 for women, <23 kg/m2 for men) and 12 patients had at target BMI (≥22 kg/m2for women, ≥BMI 23 kg/m2 for men). Patients with low BMI had an increase in their BMI from 19.5 ± 1.7 to 21.4 ± 2.2 kg/m2 at one year (p = 0.002), and 21.8 ± 1.8 kg/m2 at three years (p = 0.004) after ETI initiation. Four patients (out of 15) in the low BMI group had achieved normal BMI by the end of study follow up. There was no change in weight in the at target BMI group. HbA1c and basal insulin requirements did not change in either group. Five patients started non-insulin therapies. Conclusion: BMI increased after ETI therapy in CFRD patients with low BMI, but not in those with at target BMI. The use of non-insulin therapies is increasing in CFRD and should be evaluated in future studies.

Severe Dysphagia With Eosinophilic Esophagitis Pattern of Injury Related to Pembrolizumab Therapy.

While immune checkpoint inhibitor (ICI) therapies are effective treatments for many cancers, ICI therapies are associated with immune-related adverse events. We present a 67-year-old man with non-small cell lung carcinoma, who developed severe dysphagia with biopsies from an esophagogastroduodenoscopy showing histopathology consistent with eosinophilic esophagitis while on ICI maintenance therapy with pembrolizumab. The patient's symptoms worsened despite standard therapy. However, he had complete resolution of dysphagia symptoms once pembrolizumab was discontinued. While immune-related adverse events affecting the gastrointestinal system are increasingly recognized, ICI-associated eosinophilic esophagitis is a rare entity.

Estimating the United States Patient Population Size Meeting Audiologic Candidacy for Cochlear Implantation.

OBJECTIVE: This study aimed to estimate the size of the United States candidacy pool meeting expanded Center for Medicare Services criteria for cochlear implantation. STUDY DESIGN: Retrospective cross-sectional. SETTING: Tertiary care center. METHODS: Preimplantation audiometric data from 486 patients seen at a single academic medical center were collected retrospectively and used to generate a predictive model of AzBio score based on audiometric pure tone thresholds. This model was then used to estimate nationally representative cochlear implantation (CI)-candidacy using pure tone averages included in the National Health and Nutrition Examination Survey. Qualitative and quantitative analyses were performed. RESULTS: We find that the estimated prevalence of CI candidacy in individuals 65 years of age or older is expected to more than double with a change in the CI candidacy criteria from ≤40% to ≤60% (from 1.42%, 95% confidence interval [1.33, 1.63] to 3.73% [2.71, 6.56]) on speech testing. We also found the greatest absolute increase in candidacy in the 80+ age group, increasing from 4.14% [3.72, 5.1] of the population meeting the ≤40% criteria to 12.12% [9.19, 18.35] meeting the ≤60% criteria. CONCLUSION: The United States population size meeting expanded CMS audiologic criteria for cochlear implantation is estimated to be 2.5 million adults and 2.1 million age 65 or older. Changing the CI candidacy criteria from ≤40% to ≤60% on CI testing has the greatest effect on the eligible patient population in the >65-year-old age group. The determination of utilization rates in newly eligible patients will require further study.

GABA decrease is associated with degraded neural specificity in the visual cortex of glaucoma patients.

Glaucoma is an age-related neurodegenerative disease of the visual system, affecting both the eye and the brain. Yet its underlying metabolic mechanisms and neurobehavioral relevance remain largely unclear. Here, using proton magnetic resonance spectroscopy and functional magnetic resonance imaging, we investigated the GABAergic and glutamatergic systems in the visual cortex of glaucoma patients, as well as neural specificity, which is shaped by GABA and glutamate signals and underlies efficient sensory and cognitive functions. Our study shows that among the older adults, both GABA and glutamate levels decrease with increasing glaucoma severity regardless of age. Further, our study shows that the reduction of GABA but not glutamate predicts the neural specificity. This association is independent of the impairments on the retina structure, age, and the gray matter volume of the visual cortex. Our results suggest that glaucoma-specific decline of GABA undermines neural specificity in the visual cortex and that targeting GABA could improve the neural specificity in glaucoma.

Lesions to Caudomedial Nidopallium Impair Individual Vocal Recognition in the Zebra Finch.

Many social animals can recognize other individuals by their vocalizations. This requires a memory system capable of mapping incoming acoustic signals to one of many known individuals. Using the zebra finch, a social songbird that uses songs and distance calls to communicate individual identity (Elie and Theunissen, 2018), we tested the role of two cortical-like brain regions in a vocal recognition task. We found that the rostral region of the Cadomedial Nidopallium (NCM), a secondary auditory region of the avian pallium, was necessary for maintaining auditory memories for conspecific vocalizations in both male and female birds, whereas HVC (used as a proper name), a premotor areas that gates auditory input into the vocal motor and song learning pathways in male birds (Roberts and Mooney, 2013), was not. Both NCM and HVC have previously been implicated for processing the tutor song in the context of song learning (Sakata and Yazaki-Sugiyama, 2020). Our results suggest that NCM might not only store songs as templates for future vocal imitation but also songs and calls for perceptual discrimination of vocalizers in both male and female birds. NCM could therefore operate as a site for auditory memories for vocalizations used in various facets of communication. We also observed that new auditory memories could be acquired without intact HVC or NCM but that for these new memories NCM lesions caused deficits in either memory capacity or auditory discrimination. These results suggest that the high-capacity memory functions of the avian pallial auditory system depend on NCM.SIGNIFICANCE STATEMENT Many aspects of vocal communication require the formation of auditory memories. Voice recognition, for example, requires a memory for vocalizers to identify acoustical features. In both birds and primates, the locus and neural correlates of these high-level memories remain poorly described. Previous work suggests that this memory formation is mediated by high-level sensory areas, not traditional memory areas such as the hippocampus. Using lesion experiments, we show that one secondary auditory brain region in songbirds that had previously been implicated in storing song memories for vocal imitation is also implicated in storing vocal memories for individual recognition. The role of the neural circuits in this region in interpreting the meaning of communication calls should be investigated in the future.

Cognitive functioning in children with atopic dermatitis: Pilot observations.

Atopic dermatitis (AD) is a common and chronic inflammatory skin disease that can adversely affect quality of life and carry significant burdens on physical, emotional, and social health. Recent evidence suggests that AD may also impair cognition, including attention and memory. In a pilot study of six children with AD, we administered a comprehensive battery of assessments to evaluate cognition and behavior and found that this approach was feasible and practical, which will enable the conduct of future larger-scale studies to characterize the impact of AD on cognitive function.

Is antibiotic prophylaxis necessary after endoscopic ultrasound-guided fine-needle aspiration of pancreatic cysts?

BACKGROUND/AIMS: Current society guidelines recommend antibiotic prophylaxis for 3 to 5 days after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic cystic lesions (PCLs). The overall quality of the evidence supporting this recommendation is low. In this study, we aimed to assess cyst infection and adverse event rates after EUS-FNA of PCLs among patients treated with or without postprocedural prophylactic antibiotics. METHODS: We retrospectively reviewed all patients who underwent EUS-FNA of PCLs between 2015 and 2019 at two large-volume academic medical centers with different practice patterns of postprocedural antibiotic prophylaxis. Data on patient demographics, cyst characteristics, fine-needle aspiration technique, periprocedural and postprocedural antibiotic prophylaxis, and adverse events were retrospectively extracted. RESULTS: A total of 470 EUS-FNA procedures were performed by experienced endosonographers for the evaluation of PCLs in 448 patients, 58.7% of whom were women. The mean age was 66.3±12.8 years. The mean cyst size was 25.7±16.9 mm. Postprocedural antibiotics were administered in 274 cases (POSTAB+ group, 58.3%) but not in 196 cases (POSTAB- group, 41.7%). None of the patients in either group developed systemic or localized infection within the 30-day follow-up period. Procedure-related adverse events included mild abdominal pain (8 patients), intra-abdominal hematoma (1 patient), mild pancreatitis (1 patient), and perforation (1 patient). One additional case of pancreatitis was recorded; however, the patient also underwent endoscopic retrograde cholangiopancreatography. CONCLUSION: The incidence of infection after EUS-FNA of PCLs is negligible. Routine use of postprocedural antibiotics does not add a significant benefit.

Projective Bisector Mirror (PBM): Concept and Rationale.

Our world is full of cameras, whether they are installed in the environment or integrated into mobile devices such as mobile phones or head-mounted displays. Displaying external camera views in our egocentric view with a picture-in-picture approach allows us to understand their view; however, it would not allow us to correlate their viewpoint with our perceived reality. We introduce Projective Bisector Mirrors for visualizing a camera view comprehensibly in the egocentric view of an observer with the metaphor of a virtual mirror. Our concept projects the image of a capturing camera onto the bisecting plane between the capture and the observer camera. We present extensive mathematical descriptions of this novel paradigm for multi-view visualization, discuss the effects of tracking errors and provide concrete implementation for multiple exemplary use-cases.

Immune checkpoint inhibitor-related gastrointestinal toxicity in patients with malignancy involving the luminal gastrointestinal tract and its impact on cancer outcomes.

Background: Immune checkpoint inhibitors (ICI) are known to cause immune-related adverse events (irAE) with the gastrointestinal (GI) tract among the most affected. Our knowledge of GI irAE in patients with luminal GI malignancies is poor. We aimed to characterize the incidence, clinical features, treatment, and outcomes of these GI irAEs. Methods: This was a retrospective study of patients with malignancies involving the luminal GI tract and GI irAEs at MD Anderson Cancer Center from January 2010 to June 2020. Clinical data were collected and analyzed. Results: Eighteen patients with luminal GI tract malignancies treated with ICIs had evidence of GI irAEs based on clinical symptoms and/or histology. The predominant GI irAE symptom was diarrhea (78%). Ten had non-ulcerative inflammation (56%) and 5 had ulcerative inflammation (28%) on endoscopy. Histologically, 3 patients (17%) had evidence of acute inflammation, 4 (22%) had chronic inflammation, and 9 (50%) had both. Ten patients (56%) received immunosuppressant treatment, which included steroids alone (n=2, 20%), steroids with biologics (infliximab or vedolizumab) (n=7, 70%), or biologics alone (n=1, 10%), with clinical remission in all cases. Of the 6 patients who previously had stable or ICI-responsive cancer and received immunosuppressants, none developed progression of GI luminal malignancy during the study period. Conclusions: GI irAEs occurred in 2.4% of patients treated with ICI for cancer involving the luminal GI tract. Immunosuppressant therapies (e.g., vedolizumab) appear to be effective for GI irAEs, showing no association with further GI luminal cancer progression, recurrence, or a subsequent poor response to ICI therapy.

"Hybrid" scientific conference: lessons learned from the digital annual meeting of the CARS international conference during the Covid-19 pandemic.

OBJECTIVES: Due to the coronavirus disease 2019 (Covid-19) pandemic, all scientific conferences in the year 2020 had to be adapted in their form of presence to accommodate for safety regulations, postponed, or canceled entirely. As organizers of the annual Computer Assisted Radiology & Surgery International Conference & Exhibition (CARS)-Conference 2020, we decided to hold a "hybrid" conference, i.e., a virtual conference with partial presence to mitigate the drawbacks of a purely virtual conference. It is the purpose of this paper to describe the results and experience gained by our first hybrid conference. METHODS: Besides technical necessities like an online conferencing tool, we introduced additional personal namely the technical chairs and communication officers ensuring a smooth flow of presentations. To measure the success of the hybrid conference, we assessed various parameters during the conference (e.g., counting of adverse events, delays, and no-shows) and sent a questionnaire to participants for evaluation after the conference. RESULTS: We offered four types of presentation formats, whereas the majority of speakers presented their pre-produced videos including live discussions. Significant delays in sessions occurred during the morning sessions, which could be reduced during lunch breaks. The analysis of the influence of the distribution of the audience's location/time zone toward the attendance rate showed a high relevance for the American zone and only little influence for the Asian-Pacific region. Based on the questionnaire, 60% of responders considered the hybrid approach as superior and 12% as inferior to purely virtual conferences. CONCLUSIONS: Most scientific associations in 2020 had to struggle with a dramatic change: Regular, traditional meetings with personal communication and exchange, networking, and creation of new visions became obsolete almost instantly. As an alternative, virtual conferences became increasingly popular, and are offering additional advantages (e.g., reduction of cost for travel, lodging, and time on transit). To overcome the drawbacks of purely virtual conferences, we introduced a hybrid concept for the CARS-Congress. While certainly, those with the privilege to take part personally on-site did benefit most from the hybrid format. Facing upcoming waves of the Covid-19 Pandemic, with ongoing changes to the regulations on meetings and transit, hybrid conferences are a viable option for scientific conferences for the future.

Duplicated Reality for Co-located Augmented Reality Collaboration.

When two or more users attempt to collaborate in the same space with Augmented Reality, they often encounter conflicting intentions regarding the occupation of the same working area and self-positioning around such without mutual interference. Augmented Reality is a powerful tool for communicating ideas and intentions during a co-assisting task that requires multi-disciplinary expertise. To relax the constraint of physical co-location, we propose the concept of Duplicated Reality, where a digital copy of a 3D region of interest of the users' environment is reconstructed in real-time and visualized in-situ through an Augmented Reality user interface. This enables users to remotely annotate the region of interest while being co-located with others in Augmented Reality. We perform a user study to gain an in-depth understanding of the proposed method compared to an in-situ augmentation, including collaboration, effort, awareness, usability, and the quality of the task. The result indicates almost identical objective and subjective results, except a decrease in the consulting user's awareness of co-located users when using our method. The added benefit from duplicating the working area into a designated consulting area opens up new interaction paradigms to be further investigated for future co-located Augmented Reality collaboration systems.

Medical Augmented Reality: Definition, Principle Components, Domain Modeling, and Design-Development-Validation Process.

Three decades after the first set of work on Medical Augmented Reality (MAR) was presented to the international community, and ten years after the deployment of the first MAR solutions into operating rooms, its exact definition, basic components, systematic design, and validation still lack a detailed discussion. This paper defines the basic components of any Augmented Reality (AR) solution and extends them to exemplary Medical Augmented Reality Systems (MARS). We use some of the original MARS applications developed at the Chair for Computer Aided Medical Procedures and deployed into medical schools for teaching anatomy and into operating rooms for telemedicine and surgical guidance throughout the last decades to identify the corresponding basic components. In this regard, the paper is not discussing all past or existing solutions but only aims at defining the principle components and discussing the particular domain modeling for MAR and its design-development-validation process, and providing exemplary cases through the past in-house developments of such solutions.

Modeling Gene Expression: Lac operon.

Gene regulation is an essential process for cell development, having a profound effect in dictating cell functions. Bacterial genes are often regulated through inducible systems like the Lac operon which plays an important role in cell metabolism. An accurate model of its regulation can reveal the dynamics of gene expression. In this paper, a mathematical model of this system is constructed by focusing on regulation by the Lac repressor. The results show, as expected, that the concentration of lactose approaches zero while glucose concentration approaches the initial concentration of lactose by the action of ß-galactosidase, expressed by the Lac operon. Addition of PD control improves stability of the system, with the phase margin increasing from 45° to 90°. Modeling the dynamics of gene expression in inducible operons like Lac operon can be essential for its applications in the production of recombinant proteins and its potential usage in gene therapy.

Hairless regulates heterochromatin maintenance and muscle stem cell function as a histone demethylase antagonist.

Skeletal muscle possesses remarkable regenerative ability because of the resident muscle stem cells (MuSCs). A prominent feature of quiescent MuSCs is a high content of heterochromatin. However, little is known about the mechanisms by which heterochromatin is maintained in MuSCs. By comparing gene-expression profiles from quiescent and activated MuSCs, we found that the mammalian Hairless (Hr) gene is expressed in quiescent MuSCs and rapidly down-regulated upon MuSC activation. Using a mouse model in which Hr can be specifically ablated in MuSCs, we demonstrate that Hr expression is critical for MuSC function and muscle regeneration. In MuSCs, loss of Hr results in reduced trimethylated Histone 3 Lysine 9 (H3K9me3) levels, reduced heterochromatin, increased susceptibility to genotoxic stress, and the accumulation of DNA damage. Deletion of Hr leads to an acceleration of the age-related decline in MuSC numbers. We have also demonstrated that despite the fact that Hr is homologous to a family of histone demethylases and binds to di- and trimethylated H3K9, the expression of Hr does not lead to H3K9 demethylation. In contrast, we show that the expression of Hr leads to the inhibition of the H3K9 demethylase Jmjd1a and an increase in H3K9 methylation. Taking these data together, our study has established that Hr is a H3K9 demethylase antagonist specifically expressed in quiescent MuSCs.

Avatars for Teleconsultation: Effects of Avatar Embodiment Techniques on User Perception in 3D Asymmetric Telepresence.

A 3D Telepresence system allows users to interact with each other in a virtual, mixed, or augmented reality (VR, MR, AR) environment, creating a shared space for collaboration and communication. There are two main methods for representing users within these 3D environments. Users can be represented either as point cloud reconstruction-based avatars that resemble a physical user or as virtual character-based avatars controlled by tracking the users' body motion. This work compares both techniques to identify the differences between user representations and their fit in the reconstructed environments regarding the perceived presence, uncanny valley factors, and behavior impression. Our study uses an asymmetric VR/AR teleconsultation system that allows a remote user to join a local scene using VR. The local user observes the remote user with an AR head-mounted display, leading to facial occlusions in the 3D reconstruction. Participants perform a warm-up interaction task followed by a goal-directed collaborative puzzle task, pursuing a common goal. The local user was represented either as a point cloud reconstruction or as a virtual character-based avatar, in which case the point cloud reconstruction of the local user was masked. Our results show that the point cloud reconstruction-based avatar was superior to the virtual character avatar regarding perceived co-presence, social presence, behavioral impression, and humanness. Further, we found that the task type partly affected the perception. The point cloud reconstruction-based approach led to higher usability ratings, while objective performance measures showed no significant difference. We conclude that despite partly missing facial information, the point cloud-based reconstruction resulted in better conveyance of the user behavior and a more coherent fit into the simulation context.