Stromal Keratitis Associated With CMV Anterior Uveitis.

PURPOSE: Human cytomegalovirus (CMV) has commonly been reported as a cause of anterior uveitis and corneal endotheliitis. Unlike its other herpetic family members, herpes simplex virus and varicella zoster virus, involvement of the corneal stroma in CMV is uncommon. In this case series, we describe patients with CMV stromal keratitis. METHODS: This was a retrospective chart review of patients seen at a tertiary referral center from 1999 to 2023 with stromal keratitis who tested positive for CMV by directed polymerase chain reaction of aqueous fluid or corneal tissue. RESULTS: This series describes 5 patients, 4 of whom presented with anterior uveitis and stromal keratitis and were confirmed to be positive for CMV through the polymerase chain reaction of aqueous fluid. The fifth patient experienced recurrent corneal graft failures, with the most recent failed graft being positive for CMV based on immunohistochemical stains of the corneal stroma. The average age of patients was 62 years (range 36-80 years). Only 1 patient (20%) exhibited elevated intraocular pressure with stellate keratic precipitates at the initial presentation, whereas 3 other patients (60%) had a known history of glaucoma. CONCLUSIONS: Uveitis specialists are well aware of CMV as a cause of recurrent, hypertensive anterior uveitis but should also consider CMV in cases featuring stromal keratitis. The corneal endothelium may serve as a reservoir for both anterior uveitis and development of corneal stromal inflammation as demonstrated by the immunohistopathology exhibited in 1 case.

Convolution Neural Network Algorithm for Shockable Arrhythmia Classification Within a Digitally Connected Automated External Defibrillator.

Background Diagnosis of shockable rhythms leading to defibrillation remains integral to improving out-of-hospital cardiac arrest outcomes. New machine learning techniques have emerged to diagnose arrhythmias on ECGs. In out-of-hospital cardiac arrest, an algorithm within an automated external defibrillator is the major determinant to deliver defibrillation. This study developed and validated the performance of a convolution neural network (CNN) to diagnose shockable arrhythmias within a novel, miniaturized automated external defibrillator. Methods and Results There were 26 464 single-lead ECGs that comprised the study data set. ECGs of 7-s duration were retrospectively adjudicated by 3 physician readers (N=18 total readers). After exclusions (N=1582), ECGs were divided into training (N=23 156), validation (N=721), and test data sets (N=1005). CNN performance to diagnose shockable and nonshockable rhythms was reported with area under the receiver operating characteristic curve analysis, F1, and sensitivity and specificity calculations. The duration for the CNN to output was reported with the algorithm running within the automated external defibrillator. Internal and external validation analyses included CNN performance among arrhythmias, often mistaken for shockable rhythms, and performance among ECGs modified with noise to mimic artifacts. The CNN algorithm achieved an area under the receiver operating characteristic curve of 0.995 (95% CI, 0.990-1.0), sensitivity of 98%, and specificity of 100% to diagnose shockable rhythms. The F1 scores were 0.990 and 0.995 for shockable and nonshockable rhythms, respectively. After input of a 7-s ECG, the CNN generated an output in 383±29 ms (total time of 7.383 s). The CNN outperformed adjudicators in classifying atrial arrhythmias as nonshockable (specificity of 99.3%-98.1%) and was robust against noise artifacts (area under the receiver operating characteristic curve range, 0.871-0.999). Conclusions We demonstrate high diagnostic performance of a CNN algorithm for shockable and nonshockable rhythm arrhythmia classifications within a digitally connected automated external defibrillator. Registration URL: https://clinicaltrials.gov/ct2/show/NCT03662802; Unique identifier: NCT03662802.

Wild type cardiac amyloidosis: is it time to order a nuclear technetium pyrophosphate SPECT imaging study?

Transthyretin (ATTR) amyloidosis is a debilitating systemic disease often associated with symptomatic cardiac involvement. Diagnosis has dramatically changed with the advent of Technetium-99 m pyrophosphate (Tc-PYP) single-photon emission computed tomography (SPECT). With the ability to diagnose ATTR amyloidosis noninvasively and offer newer therapies, it is increasingly important to identify which patients should be referred for this testing. Relative apical sparing of longitudinal strain on echocardiogram can be potentially used to screen such patients. We sought to describe electrocardiogram (ECG) and echocardiogram (TTE) findings, including relative apical sparing of longitudinal strain, in ATTR amyloidosis patients diagnosed non-invasively with 99mTc-PYP imaging. This was a single-center, retrospective study with 64 patients who underwent 99mTc-PYP imaging between June 2016 and February 2019. Relative apical longitudinal strain was calculated from left ventricular longitudinal strain (LV LS) values. No ECG parameters were meaningfully associated with of 99 m Tc-PYP positive patients. LV mass index (p = 0.001), IVSd (p < 0.001), and LVPWd (< 0.001) demonstrated a highly significant difference between positive and negative 99mTc-PYP groups. 99mTc-PYP positive patients had a higher relative apical sparing of LV LS (p < 0.001), and notably, no 99mTc-PYP negative patient had a ratio > 1.0. The finding of relative apical sparing of longitudinal strain can reliably guide clinicians in triaging which patients to consider ordering 99mTc-PYP imaging for the noninvasive diagnosis of wild type cardiac amyloidosis. A patient with clinically suggestive features and an LV LS relative apical sparing ratio > 0.8 can be considered for 99mTc-PYP imaging to evaluate for ATTR cardiac amyloidosis.

A Novel Earbud Detects Aortic Stenosis Murmur Before and After Transcatheter Aortic Valve Replacement.

Noninvasive infrasonic hemodynography using the MindMics earbuds captures low-frequency acoustic vibrations throughout the cardiac cycle. In an n-of-1 analysis, we propose a new method of assessing severe aortic stenosis by using infrasonic hemodynography to detect its characteristic systolic ejection murmur before and after transcatheter aortic valve replacement.

In-ear infrasonic hemodynography with a digital health device for cardiovascular monitoring using the human audiome.

Human bodily mechanisms and functions produce low-frequency vibrations. Our ability to perceive these vibrations is limited by our range of hearing. However, in-ear infrasonic hemodynography (IH) can measure low-frequency vibrations (<20 Hz) created by vital organs as an acoustic waveform. This is captured using a technology that can be embedded into wearable devices such as in-ear headphones. IH can acquire sound signals that travel within arteries, fluids, bones, and muscles in proximity to the ear canal, allowing for measurements of an individual's unique audiome. We describe the heart rate and heart rhythm results obtained in time-series analysis of the in-ear IH data taken simultaneously with ECG recordings in two dedicated clinical studies. We demonstrate a high correlation (r = 0.99) between IH and ECG acquired interbeat interval and heart rate measurements and show that IH can continuously monitor physiological changes in heart rate induced by various breathing exercises. We also show that IH can differentiate between atrial fibrillation and sinus rhythm with performance similar to ECG. The results represent a demonstration of IH capabilities to deliver accurate heart rate and heart rhythm measurements comparable to ECG, in a wearable form factor. The development of IH shows promise for monitoring acoustic imprints of the human body that will enable new real-time applications in cardiovascular health that are continuous and noninvasive.

Transcatheter aortic valve replacement: a palliative approach to infective endocarditis.

An 88-year-old man with small lymphocytic lymphoma presented to the hospital with shortness of breath and was diagnosed with heart failure. Serial blood cultures and echocardiography revealed Staphylococcus epidermidis endocarditis, complicated by severe aortic regurgitation. Despite intravenous antibiotic therapy and aggressive intravenous diuresis therapy in the hospital, he decompensated into cardiogenic shock, requiring invasive haemodynamic monitoring and inotrope therapy. With multidisciplinary discussion involving the patient and his children, there was a joint decision that at his advanced age, he would not pursue surgical aortic valve replacement and instead proceed with a transcatheter aortic valve replacement (TAVR) with palliative intent. He underwent TAVR with subsequent symptomatic and functional improvement as well as resolution of cardiogenic shock.

Retrospective analysis of post-tracheostomy complications.

OBJECTIVE: To elucidate patient, disease, and surgical factors that are significantly associated with 90-day tracheostomy complications, readmissions, and mortality. STUDY DESIGN: Retrospective case series with chart review. SETTING: A single academic tertiary care center between 2011 and 2018. METHODS: Patients who underwent tracheostomy by any technique for any indication were included. Demographic, disease, and operative details were examined. Multivariable analysis was performed to determine factors associated with 90-day complications, 90-day readmissions, and overall mortality. RESULTS: 697 patients were included. 75% of patients had severe comorbidity (ACE-27 score of 3).1 Patients were intubated for 12 days prior to tracheostomy placement on average. The primary indication was ventilator dependence due to critical illness (85%). 74% were performed open and 26% percutaneous. 10% of patients had a tracheostomy-related complication within 90 days. Complications occurred at a median of post-operative day 11, and hemorrhage was most common (n = 35). 14 patients required immediate return to the operating room, and 3 patients died of their complication, all within 3 days of tracheostomy placement. 40% of patients undergoing tracheostomy died within 30 days. In multivariable analysis, only a documented difficult tracheostomy placement was significantly associated with a 90-day complication. CONCLUSIONS: While complications after tracheostomy are infrequent, they are often severe. A heightened level of preparedness to immediately manage accidental tracheostomy decannulation or hemorrhage is required for patients with a difficult tracheostomy placement. 30-day mortality is high, which reinforces the need for multi-disciplinary evaluation, including palliative care, to determine appropriate candidacy for tracheostomy.

Ocular phenotype in a patient with PAX2 gene mutation-associated papillorenal syndrome.

BACKGROUND: Papillorenal syndrome is an autosomal dominant disorder associated with mutations in the gene PAX2 and often presents with characteristic and specific optic disc findings, frequently with renal dysplasia. In at least half of cases, an identifiable mutation in the PAX2 gene can be detected. We report the ocular findings in a second case of papillorenal syndrome with the c.350 G > C (p.Arg117Pro) mutation detected within the PAX2 gene. METHODS: A case report of papillorenal syndrome due to PAX2 mutation. Complete ophthalmologic examination was performed as well as color fundus photography, fundus autofluorescence, and optical coherence tomography (OCT). Genetic testing was performed using a next-generation sequencing with CNV calling (NGS-CNV) panel test containing 55 genes associated with nephrotic syndrome or focal segmental glomerulosclerosis. RESULTS: An 11-year-old boy who presented with hypertension and proteinuria was found to have stage IV chronic kidney disease. Presenting visual acuity was 20/25 in the right eye and 20/20 in the left eye. The fundus exam showed bilateral centrally excavated optic discs with absent central retinal vessels and a compensatory multiplicity of cilioretinal vessels, characteristic and specific for papillorenal syndrome. OCT showed outer retinal atrophy and macular schisis. Genetic testing identified the likely pathogenic c.350 G > C (p.Arg117Pro) mutation in PAX2. CONCLUSIONS: We report the first description, to our knowledge, of the clinical presentation, ocular and systemic findings, and ophthalmic imaging in an individual with papillorenal syndrome associated with the PAX2 c.350 G > C (p.Arg117Pro) mutation. Our case adds to the current understanding of papillorenal syndrome and demonstrates that this condition is associated with a pathognomonic optic disc appearance and significant renal disease.

Addressing depression and behavioral health needs through a digital program at scale.

Depression and anxiety disorders are prevalent mental health conditions; yet they are often unrecognized, under-addressed and/or under-treated, and specialty treatment for these conditions is oftentimes difficult to access. By acting either as a bridge to therapy or as a form of therapy, digital tools, such as those that provide internet-based cognitive behavioral therapy (iCBT), may help clinicians support their patients' mental health needs. At one academic health system, a digital mental health program was deployed in primary care and outpatient behavioral health programs to help patients meet needs identified through screening or clinical visits. Over the first two years of operation, 138 clinicians (40% of eligible clinicians) prescribed the program to 2,228 unique patients, from which 1,117 (48.9%) enrolled. Patients who enrolled tended to be younger and healthier than non-enrollees. On average, enrolled patients spent 114.6 minutes within the iCBT program. Clinical improvement was assessed using pre- and post PHQ-9 and GAD-7 scores for depression and anxiety, respectively. Pre/Post scores were compared using Wilcoxon Rank Sum test. Patients with at least moderate depression had an average 23% reduction in PHQ-9 scores (median change -3(interquartile range 7), p<0.001) and those with at least moderate anxiety had a 26% reduction in GAD-7 scores (-4(7), p<0.001). Improvements were clinically and statistically significant. Future steps include performing a cost analysis to understand whether models utilizing iCBT are net cost-saving for health systems.

Active Cell Appearance Model Induced Generative Adversarial Networks for Annotation-Efficient Cell Segmentation and Identification on Adaptive Optics Retinal Images.

Data annotation is a fundamental precursor for establishing large training sets to effectively apply deep learning methods to medical image analysis. For cell segmentation, obtaining high quality annotations is an expensive process that usually requires manual grading by experts. This work introduces an approach to efficiently generate annotated images, called "A-GANs", created by combining an active cell appearance model (ACAM) with conditional generative adversarial networks (C-GANs). ACAM is a statistical model that captures a realistic range of cell characteristics and is used to ensure that the image statistics of generated cells are guided by real data. C-GANs utilize cell contours generated by ACAM to produce cells that match input contours. By pairing ACAM-generated contours with A-GANs-based generated images, high quality annotated images can be efficiently generated. Experimental results on adaptive optics (AO) retinal images showed that A-GANs robustly synthesize realistic, artificial images whose cell distributions are exquisitely specified by ACAM. The cell segmentation performance using as few as 64 manually-annotated real AO images combined with 248 artificially-generated images from A-GANs was similar to the case of using 248 manually-annotated real images alone (Dice coefficients of 88% for both). Finally, application to rare diseases in which images exhibit never-seen characteristics demonstrated improvements in cell segmentation without the need for incorporating manual annotations from these new retinal images. Overall, A-GANs introduce a methodology for generating high quality annotated data that statistically captures the characteristics of any desired dataset and can be used to more efficiently train deep-learning-based medical image analysis applications.

A Quality Initiative for Reducing Postoperative Hypothermia for Neonatal Intensive Care Unit Surgical Patients.

INTRODUCTION: The association between hypothermia in the neonatal intensive care unit (NICU) patients and morbidity and mortality is well described. Neonates are at higher risk of perioperative hypothermia when compared to older children. Previous studies showed that quality improvement tools reduced postoperative hypothermia in NICU patients, but none showed sustained improvement at incidence rates of <10%. As a single institution, we aimed to reduce the percentage of postoperative temperatures < 36°C in NICU patients from 10% to 6% over 6 months and sustain for 6 months. METHODS: An interdisciplinary team created a key driver diagram and implemented interventions, including monthly reporting of postoperative hypothermia incidence to the anesthesiologists, individual feedback sessions with the anesthesiologists, use of a perioperative checklist, and continuous axillary temperature monitoring of the infant throughout the perioperative period. Data were collected retrospectively using a chart review of electronic medical records. The primary outcome was the percentage of hypothermic patients (T < 36°C) based on the first postoperative temperature taken in the NICU. We tracked this measure using a statistical control chart and evaluated it using Plan-Do-Study-Act cycles. RESULTS: From February 1, 2016 to May 30, 2018, data were collected for 554 patients (pre-intervention: 242 and post-intervention: 312). The percentage of surgical patients who returned to the NICU hypothermic decreased from 9.7% to 2.5% (P < 0.002)-a change sustained for greater than 12 months. CONCLUSIONS: Quality improvement tools are useful in reducing postoperative hypothermia in NICU surgical patients and in maintaining these results.

Synaptic Kalirin-7 and Trio Interactomes Reveal a GEF Protein-Dependent Neuroligin-1 Mechanism of Action.

The RhoGEFs Kalirin-7 and Trio are regulators of synaptic plasticity, and their dysregulation is associated with a range of neurodevelopmental and neurodegenerative disorders. Although studies have implicated both Kalirin and Trio in certain diseases, such as tauopathies, they remarkably differ in their association with other disorders. Using unbiased proteomics, we identified interactomes of Kalirin-7 and Trio to ascertain distinct protein association networks associated with their respective function and revealed groups of proteins that preferentially interact with a particular RhoGEF. In comparison, we find Trio interacts with a range of axon guidance and presynaptic complexes, whereas Kalirin-7 associates with several synaptic adhesion molecules. Specifically, we show Kalirin-7 is an interactor of the cell adhesion molecule neuroligin-1 (NLGN1), and NLGN1-dependent synaptic function is mediated through Kalirin-7 in an interaction-dependent manner. Our data reveal not only the interactomes of two important disease-related proteins, but also provide an intracellular effector of NLGN1 function.

Deriving Visual Cues from Deep Learning to Achieve Subpixel Cell Segmentation in Adaptive Optics Retinal Images.

Direct visualization of photoreceptor cells, specialized neurons in the eye that sense light, can be achieved using adaptive optics (AO) retinal imaging. Evaluating photoreceptor cell morphology in retinal diseases is important for monitoring the onset and progression of blindness, but segmentation of these cells is a critical first step. Most segmentation approaches focus on cell region extraction, without directly considering cell boundary localization. This makes it difficult to track cells that have ambiguous boundaries, which result from low image contrast, anisotropic cell regions, or densely-packed cells whose boundaries appear to touch each other. These are all characteristics of the AO images that we consider here. To address these challenges, we develop an AOSeg-Net method that uses a multi-channel U-Net to predict the spatial probabilities of the cell boundary and obtain cell centroid and region distribution information as a means for facilitating cell segmentation. Five-color theorem guarantees the separation of any touching cells. Finally, a region-based level set algorithm that combines all of these visual cues is used to achieve subpixel cell segmentation. Five-fold cross-validation on 428 high resolution retinal images from 23 human subjects showed that AOSegNet substantially outperformed the only other existing approach with Dice coefficients [%] of 84.7 and 78.4, respectively, and average symmetric contour distances [µm] of 0.59 and 0.80, respectively.

Active Appearance Model Induced Generative Adversarial Network for Controlled Data Augmentation.

Data augmentation is an important strategy for enlarging training datasets in deep learning-based medical image analysis. This is because large, annotated medical datasets are not only difficult and costly to generate, but also quickly become obsolete due to rapid advances in imaging technology. Image-to-image conditional generative adversarial networks (C-GAN) provide a potential solution for data augmentation. However, annotations used as inputs to C-GAN are typically based only on shape information, which can result in undesirable intensity distributions in the resulting artificially-created images. In this paper, we introduce an active cell appearance model (ACAM) that can measure statistical distributions of shape and intensity and use this ACAM model to guide C-GAN to generate more realistic images, which we call A-GAN. A-GAN provides an effective means for conveying anisotropic intensity information to C-GAN. A-GAN incorporates a statistical model (ACAM) to determine how transformations are applied for data augmentation. Traditional approaches for data augmentation that are based on arbitrary transformations might lead to unrealistic shape variations in an augmented dataset that are not representative of real data. A-GAN is designed to ameliorate this. To validate the effectiveness of using A-GAN for data augmentation, we assessed its performance on cell analysis in adaptive optics retinal imaging, which is a rapidly-changing medical imaging modality. Compared to C-GAN, A-GAN achieved stability in fewer iterations. The cell detection and segmentation accuracy when assisted by A-GAN augmentation was higher than that achieved with C-GAN. These findings demonstrate the potential for A-GAN to substantially improve existing data augmentation methods in medical image analysis.

Association Between Magnetic Resonance Imaging in Anesthetized Children and Hypothermia.

INTRODUCTION: There is a myriad of factors that can lead to temperature derangements in anesthetized children undergoing magnetic resonance imaging (MRI). Temperature abnormalities in pediatric patients are associated with increased morbidity and mortality. Although some reports have looked at this topic, to our knowledge, no studies have continuously monitored temperature throughout the MRI scan. The purpose of this study is to determine the impact of MRI on body temperature for anesthetized children undergoing MRI using continuous temperature measurement, identify patient risk factors to develop temperature abnormalities, and determine the effect of temperature derangements on perianesthetic complications. METHODS: This retrospective, single-center study evaluated 285 pediatric outpatients from January 1, 2018, to March 31, 2018, who were less than 8 years old and underwent anesthesia for an MRI scan. Temperature, postanesthesia care unit length of stay, and demographic data were collected retrospectively using chart review and data extraction from electronic medical records. Statistical analyses included unpaired t test, chi-square test, and simple and multiple linear regressions. RESULTS: Sixty-three percent (179/285) of children in our study had a median temperature less than 36°C during their MRI scan. There were no patients who had a median temperature greater than 38°C during their MRI scan. There were no identifiable patient risk factors for the development of hypothermia. Those who developed hypothermia did not have an increased rate of perianesthetic complications. CONCLUSION: MRI in anesthetized children is associated with hypothermia but does not correlate with any significant perianesthetic complications.

Long-term high-altitude hypoxia influences pulmonary arterial L-type calcium channel-mediated Ca2+ signals and contraction in fetal and adult sheep.

Long-term hypoxia (LTH) has a profound effect on pulmonary arterial vasoconstriction in the fetus and adult. Dysregulation in Ca2+ signaling is important during the development of LTH-induced pulmonary hypertension. In the present study, we tested the hypothesis that L-type Ca2+ channels (CaL), which are voltage dependent and found in smooth, skeletal, and cardiac muscle, are important in the adaptation of pulmonary arterial contractions in postnatal maturation and in response to LTH. Pulmonary arteries were isolated from fetal or adult sheep maintained at low or high altitude (3,801 m) for >100 days. The effects were measured using an L-type Ca2+ channel opener FPL 64176 (FPL) in the presence or absence of an inhibitor, Nifedipine (NIF) on arterial contractions, intracellular Ca2+ oscillations, and ryanodine receptor-driven Ca2+ sparks. FPL induced pulmonary arterial contractions in all groups were sensitive to NIF. However, when compared with 125 mM K+, FPL contractions were greater in fetuses than in adults. FPL reduced Ca2+ oscillations in myocytes of adult but not fetal arteries, independently of altitude. The FPL effects on Ca2+ oscillations were reversed by NIF in myocytes of hypoxic but not normoxic adults. FPL failed to enhance Ca2+ spark frequency and had little impact on spatiotemporal firing characteristics. These data suggest that CaL-dependent contractions are largely uncoupled from intracellular Ca2+ oscillations and the development of Ca2+ sparks. This raises questions regarding the coupling of pulmonary arterial contractility to membrane depolarization, attendant CaL facilitation, and the related associations with the activation of Ca2+ oscillations and Ca2+ sparks.