An Analysis of Surgical Factors Associated with Clinically Significant Eyelid Edema (CSEE) in Patients Undergoing Blepharoplasty: Lid Crease Techniques Associated with CSEE.

PURPOSE: Severe postoperative edema after eyelid surgery can have negative clinical and psychological effects. In this study, we investigated whether surgical factors, including surgical techniques and suture type, were associated with clinically significant eyelid edema (CSEE). METHODS: A chart review was performed on 269 patients who underwent upper eyelid blepharoplasty with or without external levator advancement by 2 surgeons at a single institution between January 2021 and December 2022. Postoperative photos were graded by 2 physicians for eyelid edema using a standardized grading scale ranging from 0 (no edema) to 3 (severe edema). CSEE was defined either as having a grade of 3 at any point postoperatively or any grade that was 1 or greater after 90 days postoperatively. Logistic regression controlling for race was used for analysis; the statistical significance level was defined as p < 0.05. RESULTS: Of 269 patients, 56 developed CSEE. Of those who underwent blepharoplasty with mini crease enhancement (closure with every other bite incorporating levator aponeurosis), 40.5% developed CSEE versus 12.5% of those without (p < 0.001). Patients with lid crease formation using buried interrupted sutures had greater CSEE than those with externalized interrupted sutures removed at 1 week (43.8% versus 11.5%, p < 0.01). There was no increased risk of CSEE with additional procedures performed versus blepharoplasty alone. CONCLUSIONS: Patients who underwent blepharoplasty with mini crease enhancement, where more than 4 sutures are placed from skin to levator, and/or had buried suture lid crease formation had greater rates of CSEE.

Debt Inequity Among Clients of a Community Mental Health Center.

Debt is an overlooked social determinant of health that reinforces systems of discrimination. This study examined the impact of debt among individuals with serious mental illness. Individuals with serious mental illness who identified as Black, Indigenous, or other people of color carried a disproportionate amount of debt, often from attempting to meet basic needs. Increased levels of debt were associated with symptoms of depression. Addressing debt inequity is essential to both financial justice and mental health recovery.

Demographic and physiological factors associated with clinically significant eyelid edema in patients following upper eyelid surgery.

PURPOSE: To investigate demographic and physiological variables associated with clinically significant edema after upper eyelid surgery. METHODS: A retrospective chart review was performed on patients who underwent blepharoplasty or external levator advancement with or without lid crease formation between January 2018 and January 2021 at the University of Southern California. Age, sex, pertinent medical history (medications causing edema and comorbidities), and pertinent surgical procedures were all collected. Postoperative photos were graded by two independent physician graders on a newly developed photographic scale ranging from 0 (no edema) to 3 (severe edema). Clinically significant edema of the eyelids was defined as Grade 3 edema at any postoperative point or ≥ Grade 1 edema after 90 days post operation. Patients without postoperative photos were excluded. Mann-Whitney U test, Fisher's exact test, and χ2 test were used to compare groups with and without significant edema. All analyses were conducted using SAS version 9.4 (SAS Institute Inc.) with α=0.05. RESULTS: Out of 217 patients, East Asian participants had higher odds of developing edema than White participants (odds ratio, 7.92; CI, 3.15-19.93, p < 0.0001) and Hispanic participants (odds ratio, 3.47; CI, 1.51-7.97, p = 0.003). Southeast Asian participants also had higher odds of developing CSEE than White participants (odds ratio, 6.19; CI, 1.71-22.43, p = 0.006). Fifty-four (24.9%) patients had clinically significant edema. Although BMI, medical comorbidities, medication use, and age did not affect edema, there was a statistically significant relationship between race and incidence of edema (p = 0.0001). Those in the CSEE group were also more likely to require reoperation (p = 0.0143). CONCLUSIONS: There is a statistically significant relationship between Asian race and the incidence of clinically significant eyelid edema. CSEE is associated with a higher incidence of reoperation.

Anterior segment biometric measurements explain misclassifications by a deep learning classifier for detecting gonioscopic angle closure.

BACKGROUND/AIMS: To identify biometric parameters that explain misclassifications by a deep learning classifier for detecting gonioscopic angle closure in anterior segment optical coherence tomography (AS-OCT) images. METHODS: Chinese American Eye Study (CHES) participants underwent gonioscopy and AS-OCT of each angle quadrant. A subset of CHES AS-OCT images were analysed using a deep learning classifier to detect positive angle closure based on manual gonioscopy by a reference human examiner. Parameter measurements were compared between four prediction classes: true positives (TPs), true negatives (TNs), false positives (FPs) and false negatives (FN). Logistic regression models were developed to differentiate between true and false predictions. Performance was assessed using area under the receiver operating curve (AUC) and classifier accuracy metrics. RESULTS: 584 images from 127 participants were analysed, yielding 271 TPs, 224 TNs, 77 FPs and 12 FNs. Parameter measurements differed (p<0.001) between prediction classes among anterior segment parameters, including iris curvature (IC) and lens vault (LV), and angle parameters, including angle opening distance (AOD). FP resembled TP more than FN and TN in terms of anterior segment parameters (steeper IC and higher LV), but resembled TN more than TP and FN in terms of angle parameters (wider AOD). Models for detecting FP (AUC=0.752) and FN (AUC=0.838) improved classifier accuracy from 84.8% to 89.0%. CONCLUSIONS: Misclassifications by an OCT-based deep learning classifier for detecting gonioscopic angle closure are explained by disagreement between anterior segment and angle parameters. This finding could be used to improve classifier performance and highlights differences between gonioscopic and AS-OCT definitions of angle closure.

An integrative web-based software tool for multi-dimensional pathology whole-slide image analytics.

Objective.In the era of precision medicine, human tumor atlas-oriented studies have been significantly facilitated by high-resolution, multi-modal tissue based microscopic pathology image analytics. To better support such tissue-based investigations, we have developed Digital Pathology Laboratory (DPLab), a publicly available web-based platform, to assist biomedical research groups, non-technical end users, and clinicians for pathology whole-slide image visualization, annotation, analysis, and sharing via web browsers.Approach.A major advancement of this work is the easy-to-follow methods to reconstruct three-dimension (3D) tissue image volumes by registering two-dimension (2D) whole-slide pathology images of serial tissue sections stained by hematoxylin and eosin (H&E), and immunohistochemistry (IHC). The integration of these serial slides stained by different methods provides cellular phenotype and pathophysiologic states in the context of a 3D tissue micro-environment. DPLab is hosted on a publicly accessible server and connected to a backend computational cluster for intensive image analysis computations, with results visualized, downloaded, and shared via a web interface.Main results.Equipped with an analysis toolbox of numerous image processing algorithms, DPLab supports continued integration of community-contributed algorithms and presents an effective solution to improve the accessibility and dissemination of image analysis algorithms by research communities.Significance.DPLab represents the first step in making next generation tissue investigation tools widely available to the research community, enabling and facilitating discovery of clinically relevant disease mechanisms in a digital 3D tissue space.

Effect of Temporal Artery Biopsy Length and Laterality on Diagnostic Yield.

BACKGROUND: Giant cell arteritis (GCA) is the most common vasculitis in adults and is associated with significant morbidity and mortality. Temporal artery biopsy (TAB) remains the gold standard for diagnosis in the United States; however, practices vary in the length of artery obtained and whether bilateral simultaneous biopsies are obtained. METHODS: Retrospective chart review of all TABs performed at the Johns Hopkins Wilmer Eye Institute between July 1, 2007, and September 30, 2017. RESULTS: Five hundred eighty-six patients underwent TAB to evaluate for GCA. Of 404 unilateral biopsies, 68 (16.8%) were positive. Of 182 patients with bilateral biopsies, 25 (13.7%) had biopsies that were positive and 5 patients (2.7%) had biopsies that were discordant, meaning only 1 side was positive. There was no significant difference in the average postfixation length of positive and negative TAB specimens (positive mean length 1.38 ± 0.61 cm, negative mean length 1.39 ± 0.62 cm, P = 0.9). CONCLUSIONS: There is no significant association between greater length of biopsy and a positive TAB result in our data. Although the rate of positive results was not higher in the bilateral group compared with the unilateral group, 2.7% of bilateral biopsies were discordant, similar to previously published rates. Overall, this suggests that initial bilateral biopsy may increase diagnostic yield, albeit by a small amount.

Metastatic neuroendocrine tumors mimicking as primary ocular disease.

PURPOSE: To report two cases of metastatic neuroendocrine tumors masquerading as primary ocular disease. OBSERVATIONS: Case 1 is a 38-year-old man who was referred with subacute onset diplopia and fluctuating ptosis suggestive of myasthenia gravis. Case 2 is a 21-year-old man who presented with blurry vision and was found to have a pigmented ciliary body mass and retinal detachment suggestive of uveal melanoma. Both patients were ultimately diagnosed with metastatic neuroendocrine tumors. CONCLUSIONS AND IMPORTANCE: Neuroendocrine tumors, though rare and infrequently metastatic to the eye and orbit, can initially present with ocular signs. A broad differential and careful consideration of ocular and systemic symptoms are critical in such challenging cases.

Glaucoma Expert-Level Detection of Angle Closure in Goniophotographs With Convolutional Neural Networks: The Chinese American Eye Study.

PURPOSE: To compare the performance of a novel convolutional neural network (CNN) classifier and human graders in detecting angle closure in EyeCam (Clarity Medical Systems, Pleasanton, California, USA) goniophotographs. DESIGN: Retrospective cross-sectional study. METHODS: Subjects from the Chinese American Eye Study underwent EyeCam goniophotography in 4 angle quadrants. A CNN classifier based on the ResNet-50 architecture was trained to detect angle closure, defined as inability to visualize the pigmented trabecular meshwork, using reference labels by a single experienced glaucoma specialist. The performance of the CNN classifier was assessed using an independent test dataset and reference labels by the single glaucoma specialist or a panel of 3 glaucoma specialists. This performance was compared to that of 9 human graders with a range of clinical experience. Outcome measures included area under the receiver operating characteristic curve (AUC) metrics and Cohen kappa coefficients in the binary classification of open or closed angle. RESULTS: The CNN classifier was developed using 29,706 open and 2,929 closed angle images. The independent test dataset was composed of 600 open and 400 closed angle images. The CNN classifier achieved excellent performance based on single-grader (AUC = 0.969) and consensus (AUC = 0.952) labels. The agreement between the CNN classifier and consensus labels (κ = 0.746) surpassed that of all non-reference human graders (κ = 0.578-0.702). Human grader agreement with consensus labels improved with clinical experience (P = 0.03). CONCLUSION: A CNN classifier can effectively detect angle closure in goniophotographs with performance comparable to that of an experienced glaucoma specialist. This provides an automated method to support remote detection of patients at risk for primary angle closure glaucoma.

Pig Brains Have Homologous Resting-State Networks with Human Brains.

Many neurological and psychiatric diseases in humans are caused by disruptions to large-scale functional properties of the brain, including functional connectivity. There has been growing interest in discovering the functional organization of brain networks in larger animal models. As a result, the use of translational pig models in neuroscience has significantly increased in the past decades. The gyrencephalic pig brain resembles the human brain more in anatomy, growth, and development than the brains of commonly used small laboratory animals such as rodents. In this work, resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) data were acquired from a group of pigs (n = 12). rs-fMRI data were analyzed for resting-state networks (RSNs) by using independent component analysis and sparse dictionary learning. Six RSNs (executive control, cerebellar, sensorimotor, visual, auditory, and default mode) were detected that resemble their counterparts in human brains, as measured by Pearson spatial correlations and mean ratios. Supporting evidence of the validity of these RSNs was provided through the evaluation and quantification of structural connectivity measures (mean diffusivity, fractional anisotropy, fiber length, and fiber density) estimated from the DTI data. This study shows that as a translational, large animal model, pigs demonstrate great potential for mapping connectome-scale functional connectivity in experimental modeling of human brain disorders.

Delay in pediatric epilepsy surgery: A caregiver's perspective.

The timing of epilepsy surgery is complex, and there is not a structured pathway to help families decide whether to continue medical management or pursue surgical treatment. We surveyed caregivers of pediatric epilepsy surgery patients. Fifty-eight respondents answered the majority of questions. Thirty caregivers wished their child had undergone epilepsy surgery earlier compared with twenty who felt surgery was done at the appropriate time, and eight were unsure. In retrospect, caregivers who wished their child's surgery had been performed sooner had a significantly longer duration of epilepsy prior to the surgery [44.1±71.7 (months±standard deviation (SD), N=27)], compared with those who felt content with the timing of the surgery [12.8±14.1 (months±SD, N=20), p=0.0034]. Caregivers were willing to accept a lower likelihood of seizure freedom than their physician reported was likely. Most caregivers were willing to accept deficits in all domains surveyed; caregivers had high acceptance of motor deficits, cognitive deficits, behavioral change, and language loss. Future studies are needed to focus on how to improve the education of caregivers and neurologists about the benefits and risks of epilepsy surgery and accelerate the pipeline to epilepsy surgery to improve caregiver satisfaction.

Fulminant Hepatic Failure and Fatal Cerebral Edema Following Clostridium perfringens Bacteremia: Case Report and Review of Literature.

Clostridium perfringens (CP) bacteremia is a rare but rapidly fatal infection. Only 36 cases of CP bacteremia with gas containing liver abscesses on image studies have been reported in the literature since 1990. In this report, we describe a 65-year-old diabetic male with CP bacteremia which progressed into fulminant hepatic failure with subsequent fatal cerebral edema.

Large Unilateral Adrenal Mass with Surrounding Brown Fat: A Case Report.

Pheochromocytomas are rare tumors derived from chromaffin cells located in the adrenal and extra adrenal tissues. Pheochromocytomas are diagnosed biochemically and localized using different imaging modalities. The definitive management is surgical resection. Brown adipose tissues are normally present during fetal development, with regression over time. Brown adipose tissues are thermogenic and usually located in the neck, mediastinum, and retroperitoneum. Here, we report a case of a unilateral pheochromocytoma surrounded by brown fat. The abnormal stimulation of brown fat noted on positive emission tomography scan (PET) resolved after the pheochromocytoma was resected.

Natural History Of an Untreated Type 1 Endoleak: A Case Report.

We present a case of giant abdominal aortic aneurysm greater than 17 cm complicated by an endoleak, demonstrating the natural history of an untreated Type 1 endoleak.

Anal Melanoma in an Elderly Woman Masquerading as Hemorrhoid.

Anal melanoma is a rare and aggressive neoplasm of the anal canal seen in the elderly population in the six or seventh decade of their lives. Presentation is usually nonspecific and diagnosis is often delayed or missed initially. The management is surgical and prognosis is poor. Here we present a case of anal melanoma in an elderly patient masquerading as hemorrhoid.

Allergic mechanisms of Eosinophilic oesophagitis.

Eosinophilic oesophagitis (EoE) is characterized by oesophageal dysfunction and oesophageal eosinophilia refractory to proton-pump-inhibitor treatment. EoE is a food allergy, as elimination of food trigger(s) abrogates the disease, while trigger reintroduction causes recurrence. The allergic mechanism of EoE involves both IgE and non-IgE processes. There is a break in oral tolerance, the immune mechanism allowing enteric exposure to food and micro-organisms without causing deleterious immune responses. Changes in life-style, alterations in gut flora and use of antibiotics may be increasing disease prevalence. Mouse models of EoE and human studies revealed the role of regulatory T-cells and iNKT-cells in the pathogenesis. Th2-cytokines like IL-4, IL-5 and IL-13, and other cytokines like TGFß and TSLP are involved, but perhaps no one cytokine is critically important for driving the disease. Control of EoE may require a pharmaceutical approach that blocks more than one target in the Th2-inflammatory pathway.

Broad spectrum assessment of the epitope fluctuation--Immunogenicity hypothesis.

Prediction of immunogenicity is a substantial barrier in vaccine design. Here, a molecular dynamics approach to assessing the immunogenicity of nanoparticles based on structure is presented. Molecular properties of epitopes on nonenveloped viral particles are quantified via a set of metrics. One such metric, epitope fluctuation (and implied flexibility), is shown to be inversely correlated with immunogenicity for each of a broad spectrum of nonenveloped viruses. The molecular metrics and experimentally determined immunogenicities for these viruses are archived in the open-source vaccine computer-aided design database. Results indicate the promise of computer-aided vaccine design to bring greater efficiency to traditional lab-based vaccine discovery approaches.

Altered microglial response to Aß plaques in APPPS1-21 mice heterozygous for TREM2.

BACKGROUND: Recent genome-wide association studies linked variants in TREM2 to a strong increase in the odds of developing Alzheimer's disease. The mechanism by which TREM2 influences the susceptibility to Alzheimer's disease is currently unknown. TREM2 is expressed by microglia and is thought to regulate phagocytic and inflammatory microglial responses to brain pathology. Given that a single allele of variant TREM2, likely resulting in a loss of function, conferred an increased risk of developing Alzheimer's disease, we tested whether loss of one functional trem2 allele would affect Aß plaque deposition or the microglial response to Aß pathology in APPPS1-21 mice. RESULTS: There was no significant difference in Aß deposition in 3-month old or 7-month old APPPS1-21 mice expressing one or two copies of trem2. However, 3-month old mice with one copy of trem2 exhibited a marked decrease in the number and size of plaque-associated microglia. While there were no statistically significant differences in cytokine levels or markers of microglial activation in 3- or 7-month old animals, there were trends towards decreased expression of NOS2, C1qa, and IL1a in 3-month old TREM2+/- vs. TREM2+/+ mice. CONCLUSIONS: Loss of a single copy of trem2 had no effect on Aß pathology, but altered the morphological phenotype of plaque-associated microglia. These data suggest that TREM2 is important for the microglial response to Aß deposition but that a 50% decrease inTREM2 expression does not affect Aß plaque burden.

Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria.

Mutations in Pten-induced kinase 1 (PINK1) are linked to early-onset familial Parkinson's disease (FPD). PINK1 has previously been implicated in mitochondrial fission/fusion dynamics, quality control, and electron transport chain function. However, it is not clear how these processes are interconnected and whether they are sufficient to explain all aspects of PINK1 pathogenesis. Here we show that PINK1 also controls mitochondrial motility. In Drosophila, downregulation of dMiro or other components of the mitochondrial transport machinery rescued dPINK1 mutant phenotypes in the muscle and dopaminergic (DA) neurons, whereas dMiro overexpression alone caused DA neuron loss. dMiro protein level was increased in dPINK1 mutant but decreased in dPINK1 or dParkin overexpression conditions. In Drosophila larval motor neurons, overexpression of dPINK1 inhibited axonal mitochondria transport in both anterograde and retrograde directions, whereas dPINK1 knockdown promoted anterograde transport. In HeLa cells, overexpressed hPINK1 worked together with hParkin, another FPD gene, to regulate the ubiquitination and degradation of hMiro1 and hMiro2, apparently in a Ser-156 phosphorylation-independent manner. Also in HeLa cells, loss of hMiro promoted the perinuclear clustering of mitochondria and facilitated autophagy of damaged mitochondria, effects previously associated with activation of the PINK1/Parkin pathway. These newly identified functions of PINK1/Parkin and Miro in mitochondrial transport and mitophagy contribute to our understanding of the complex interplays in mitochondrial quality control that are critically involved in PD pathogenesis, and they may explain the peripheral neuropathy symptoms seen in some PD patients carrying particular PINK1 or Parkin mutations. Moreover, the different effects of loss of PINK1 function on Miro protein level in Drosophila and mouse cells may offer one explanation of the distinct phenotypic manifestations of PINK1 mutants in these two species.