A 15 month experience with a primary care-based telemedicine screening program for diabetic retinopathy.

BACKGROUND: Using telemedicine for diabetic retinal screening is becoming popular especially amongst at-risk urban communities with poor access to care. The goal of the diabetic telemedicine project at Temple University Hospital is to improve cost-effective access to appropriate retinal care to those in need of close monitoring and/or treatment. METHODS: This will be a retrospective review of 15 months of data from March 2016 to May 2017. We will investigate how many patients were screened, how interpretable the photographs were, how often the photographs generated a diagnosis of diabetic retinopathy (DR) based on the screening photo, and how many patients followed-up for an exam in the office, if indicated. RESULTS: Six-hundred eighty-nine (689) digital retinal screening exams on 1377 eyes of diabetic patients were conducted in Temple's primary care clinic. The majority of the photographs were read to have no retinopathy (755, 54.8%). Among all of the screening exams, 357 (51.8%) triggered a request for a referral to ophthalmology. Four-hundred forty-nine (449, 32.6%) of the photos were felt to be uninterpretable by the clinician. Referrals were meant to be requested for DR found in one or both eyes, inability to assess presence of retinopathy in one or both eyes, or for suspicion of a different ophthalmic diagnosis. Sixty-seven patients (9.7%) were suspected to have another ophthalmic condition based on other findings in the retinal photographs. Among the 34 patients that were successfully completed a referral visit to Temple ophthalmology, there was good concordance between the level of DR detected by their screening fundus photographs and visit diagnosis. CONCLUSIONS: Although a little more than half of the patients did not have diabetic eye disease, about half needed a referral to ophthalmology. However, only 9.5% of the referral-warranted exams actually received an eye exam. Mere identification of referral-warranted diabetic retinopathy and other ophthalmic conditions is not enough. A successful telemedicine screening program must close the communication gap between screening and diagnosis by reviewer to provide timely follow-up by eye care specialists.

Low-dose 5-aza-2'-deoxycytidine pretreatment inhibits experimental autoimmune encephalomyelitis by induction of regulatory T cells.

Forkhead box P3 (Foxp3) is the major transcription factor controlling the development and function of regulatory T (Treg) cells. Previous studies have indicated epigenetic regulation of Foxp3 expression. Here, we investigated whether the deoxyribonucleic acid (DNA) methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-Aza) applied peripherally could modulate central nervous system (CNS) inflammation, by using a mouse experimental autoimmune encephalomyelitis (EAE) model. We found that disease activity was inhibited in a myelin oligodendrocyte glycoprotein (MOG) peptide-induced EAE mouse briefly pretreated with low-dose (0.15 mg/kg) 5-Aza, ameliorating significant CNS inflammatory responses, as indicated by greatly decreased proinflammatory cytokines. On the contrary, control EAE mice expressed high levels of IFN-γ and interleukin (IL)-17. In addition, 5-Aza treatment in vitro increased GFP expression in CD4(+)GFP(-) T cells isolated from GFP knock-in Foxp3 transgenic mice. Importantly, 5-Aza treatment increased Treg cell numbers, in EAE mice, at both disease onset and peak. However, Treg inhibition assays showed 5-Aza treatment did not enhance per-cell Treg inhibitory function, but did maintain a lower activation threshold for effector cells in EAE mice. In conclusion, 5-Aza treatment prevented EAE development and suppressed CNS inflammation, by increasing the number of Treg cells and inhibiting effector cells in the periphery.

Sextus chest radiograph severity score correlates to clinical outcomes in patients with COVID-19: A cross-sectional study.

ABSTRACT: The value of chest radiography (CXR) in detection and as an outcome predictor in the management of patients with coronavirus disease-2019 (COVID-19) has not yet been fully understood.To validate a standardized CXR scoring system and assess its prognostic value in hospitalized patients found to have COVID-19 by imaging criteria and to compare it to computed tomography (CT).In this cross-sectional chart review study, patients aged 18-years or older who underwent chest CT at a single institution with an imaging-based diagnosis of COVID-19 between March 15, 2020 to April 15, 2020 were included. Each patient's CXR and coronal CT were analyzed for opacities in a 6-zonal assessment method and aggregated into a "Sextus score." Inter-reader variability and correlation between CXR and coronal CT images were investigated to validate this scoring system. Univariable and multiple logistic regression techniques were used to investigate relationships between CXR scores and clinical parameters in relation to patient outcomes.One hundred twenty-four patients (median [interquartile range] age 58.5 [47.5-69.0] years, 72 [58%] men, 58 [47%] Blacks, and 35 [28%] Hispanics) were included. The CXR Sextus score (range: 0-6) was reliable (inter-rater kappa = 0.76; 95% confidence interval [CI]: 0.69-0.83) and correlated strongly with the CT Sextus score (Spearman correlation coefficient = 0.75, P < .0001). Incremental increases of CXR Sextus scores of 2 points were found to be an independent predictor of intubation (adjusted odds ratio [95% CI]: 4.49 [1.98, 10.20], P = .0003) and prolonged hospitalization (≥10 days) (adjusted odds ratio [95% CI]: 4.06 [1.98, 8.32], P = .0001).The CXR Sextus score was found to be reproducible and CXR-CT severity scores were closely correlated. Increasing Sextus scores were associated with increased risks for intubation and prolonged hospitalization for patients with COVID-19 in a predominantly Black population. The CXR Sextus score may provide insight into identifying and monitoring high-risk patients with COVID-19.

Incidental COVID-19 in the radiology department: Radiographic findings of COVID-19 in asymptomatic patient undergoing CT staging for breast cancer.

A 59-year-old incarcerated woman who was diagnosed with invasive ductal carcinoma in 2016 was brought in for evaluation of the breast cancer. Upon evaluation of the computed tomography chest for breast cancer restaging, diffuse bilateral ground glass opacities and a reverse halo sign in the right lower lobe concerning for atypical viral pneumonia were discovered. The patient was afebrile, had an oxygen saturation of 100%, and denied chest pain as well as shortness of breath. On physical exam, she exhibited decreased breath sounds bilaterally and expiratory wheezing. She later received a COVID-19 test, which came back positive. Infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also known as COVID-19) may remain asymptomatic in the initial phase, leading to under-recognition and incidental detection on procedures for standard clinical indications. Hospitals, in particular diagnostic imaging services, should prepare accordingly in regard to health precautions while keeping in mind the potential discrepancies between clinical presentation and resultant radiologic patterns. This awareness should be heightened in patients at higher risk (ie, prisoners). Furthermore, by acting upon the incidental detection of this virus during its early stages, subsequent steps could help prevent the spread of the virus.

Chewing gum does not induce context-dependent memory when flavor is held constant.

This study examined the effect of chewing gum on memory when flavor is held constant. Four separate groups of participants (total n=101) completed a word recall task. At learning and recall, participants either chewed a piece of gum or sucked a sweet. Each participant completed the memory task twice, once with abstract words and once with concrete words. A significant effect of word type (concrete vs. abstract) was found, however recall performance was not improved by matched oral activity at learning and recall. The results cast further doubt on the ability of chewing gum to induce context-dependent memory effects.

Simultaneous delivery of hydrophobic small molecules and siRNA using Sterosomes to direct mesenchymal stem cell differentiation for bone repair.

The use of small molecular drugs with gene manipulation offers synergistic therapeutic efficacy by targeting multiple signaling pathways for combined treatment. Stimulation of mesenchymal stem cells (MSCs) with osteoinductive small molecule phenamil combined with suppression of noggin is a promising therapeutic strategy that increases bone morphogenetic protein (BMP) signaling and bone repair. Our cationic Sterosome formulated with stearylamine (SA) and cholesterol (Chol) is an attractive co-delivery system that not only forms stable complexes with small interfering RNA (siRNA) molecules but also solubilizes hydrophobic small molecules in a single vehicle, for directing stem cell differentiation. Herein, we demonstrate the ability of SA/Chol Sterosomes to simultaneously deliver hydrophobic small molecule phenamil and noggin-directed siRNA to enhance osteogenic differentiation of MSCs both in in vitro two- and three-dimensional settings as well as in a mouse calvarial defect model. These results suggest a novel liposomal platform to simultaneously deliver therapeutic genes and small molecules for combined therapy. STATEMENT OF SIGNIFICANCE: Application of phenamil, a small molecular bone morphogenetic protein (BMP) stimulator, combined with suppression of natural BMP antagonists such as noggin is a promising therapeutic strategy to enhance bone regeneration. Here, we present a novel strategy to co-deliver hydrophobic small molecule phenamil and noggin-targeted siRNA via cationic Sterosomes formed with stearylamine (SA) and high content of cholesterol (Chol) to enhance osteogenesis and bone repair. SA/Chol Sterosomes demonstrated high phenamil encapsulation efficiency, supported sustained release of encapsulated drugs, and significantly reduced drug dose requirements to induce osteogenic differentiation of mesenchymal stem cells (MSCs). Simultaneous deliver of phenamil and noggin siRNA in a single vehicle synergistically enhanced MSC osteogenesis and calvarial bone repair. This study suggests a new non-phospholipid liposomal formulation to simultaneously deliver small molecules and therapeutic genes for combined treatment.