Switch to faricimab after initial treatment with aflibercept in eyes with diabetic macular edema.

PURPOSE: To assess the effectiveness of a switch to faricimab in individuals affected by DME and previously treated with aflibercept. METHODS: In this retrospective, single-center study, DME patients previously treated with at least 3 injections of aflibercept then switched to faricimab were enrolled. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline, at the time of the switch and at 6 months follow-up. At transition to faricimab, patients were categorized as "good visual responders" (≥ 5 letters from baseline) or "poor visual responders" (< 5 letters), and as "good anatomical responders" (any reduction in edema compared to baseline) or "poor anatomical responders" (no reduction or worsening of edema). Changes in BCVA and CST were recorded at 6 months after the switch to faricimab. RESULTS: 100 eyes of 100 patients (61 female, 61%) were switched to faricimab after a mean of 6.8 ± 3.3 aflibercept injections. At the 6 months follow-up, only "poor visual responders" (N = 62) demonstrated a meaningful increase in BCVA (Δswitch-6M = + 5 letters; P = 0.007), coupled with a reduction in CST (Δswitch-6M = - 67.9 µm; P = 0.004); participants with "poor anatomical response" upon transitioning exhibited a significant functional gain (Δswitch-6M = + 4.5 letters; p = 0.05) but limited CST enhancements (Δswitch-6M = - 95.1 µm; p = 0.05). CONCLUSIONS: Faricimab shows a positive impact on anatomical and functional metrics in DME cases refractory to aflibercept.

Role of CaMKII in diabetes induced vascular injury and its interaction with anti-diabetes therapy.

Diabetes mellitus is a metabolic disorder denoted by chronic hyperglycemia that drives maladaptive structural changes and functional damage to the vasculature. Attenuation of this pathological remodeling of blood vessels remains an unmet target owing to paucity of information on the metabolic signatures of this process. Ca2+/calmodulin-dependent kinase II (CaMKII) is expressed in the vasculature and is implicated in the control of blood vessels homeostasis. Recently, CaMKII has attracted a special attention in view of its chronic upregulated activity in diabetic tissues, yet its role in the diabetic vasculature remains under investigation.This review highlights the physiological and pathological actions of CaMKII in the diabetic vasculature, with focus on the control of the dialogue between endothelial (EC) and vascular smooth muscle cells (VSMC). Activation of CaMKII enhances EC and VSMC proliferation and migration, and increases the production of extracellular matrix which leads to maladaptive remodeling of vessels. This is manifested by activation of genes/proteins implicated in the control of the cell cycle, cytoskeleton organization, proliferation, migration, and inflammation. Endothelial dysfunction is paralleled by impaired nitric oxide signaling, which is also influenced by CaMKII signaling (activation/oxidation). The efficiency of CaMKII inhibitors is currently being tested in animal models, with a focus on the genetic pathways involved in the regulation of CaMKII expression (microRNAs and single nucleotide polymorphisms). Interestingly, studies highlight an interaction between the anti-diabetic drugs and CaMKII expression/activity which requires further investigation. Together, the studies reviewed herein may guide pharmacological approaches to improve health-related outcomes in patients with diabetes.

Exploring Quality Differences in Telemedicine Between Hospital Outpatient Departments and Community Clinics: Cross-sectional Study.

BACKGROUND: Telemedicine is a care delivery modality that has the potential to broaden the reach and flexibility of health care services. In the United Arab Emirates, telemedicine services are mainly delivered through either integrated hospital outpatient department (OPDs) or community clinics. However, it is unknown if patients' perceptions of, and satisfaction with, telemedicine services differ between these two types of health care systems during the COVID-19 pandemic. OBJECTIVE: We aimed to explore the differences in patients' perceptions of, and satisfaction with, telemedicine between hospital OPDs and community clinics during the COVID-19 pandemic. We also aimed to identify patient- or visit-related characteristics contributing to patient satisfaction with telemedicine. METHODS: In this cross-sectional study that was conducted at Abu Dhabi health care centers, we invited outpatients aged 18 years or over, who completed a telemedicine visit during the COVID-19 pandemic, to participate in our study. Patients' perceptions of, and satisfaction with, telemedicine regarding the two system types (ie, hospital OPDs and community clinics) were assessed using an online survey that was sent as a link through the SMS system. Regression models were used to describe the association between patient- and visit-related characteristics, as well as the perception of, and satisfaction with, telemedicine services. RESULTS: A total of 515 patients participated in this survey. Patients' satisfaction with telemedicine services was equally high among the settings, with no statistically significant difference between the two setting types (hospital OPDs: 253/343, 73.8%; community clinics: 114/172, 66.3%; P=.19). Video consultation was significantly associated with increased patient satisfaction (odds ratio [OR] 2.57, 95% CI 1.04-6.33; P=.04) and patients' support of the transition to telemedicine use during and after the pandemic (OR 2.88, 95% CI 1.18-7.07; P=.02). Patients who used video consultations were more likely to report that telemedicine improved access to health care services (OR 3.06, 95% CI 1.71-8.03; P=.02), reduced waiting times and travel costs (OR 4.94, 95% CI 1.15-21.19; P=.03), addressed patients' needs (OR 2.63, 95% CI 1.13-6.11; P=.03), and eased expression of patients' medical concerns during the COVID-19 pandemic (OR 2.19, 95% CI 0.89-5.38; P=.09). Surprisingly, middle-aged patients were two times more likely to be satisfied with telemedicine services (OR 2.12, 95% CI 1.09-4.14; P=.03), as compared to any other age group in this study. CONCLUSIONS: These findings suggest that patient satisfaction was unaffected by the health system setting in which patients received the teleconsultations, whether they were at hospitals or community clinics. Video consultation was associated with increased patient satisfaction with telemedicine services. Efforts should be focused on strategic planning for enhanced telemedicine services, video consultation in particular, for both emergent circumstances, such as the COVID-19 pandemic, and day-to-day health care delivery.

Interaction of SARS-CoV-2 with cardiomyocytes: Insight into the underlying molecular mechanisms of cardiac injury and pharmacotherapy.

SARS-CoV-2 causes respiratory illness with a spectrum of systemic complications. However, the mechanism for cardiac infection and cardiomyocyte injury in COVID-19 patients remains unclear. The current literature supports the notion that SARS-CoV-2 particles access the heart either by the circulating blood cells or by extracellular vesicles, originating from the inflamed lungs, and encapsulating the virus along with its receptor (ACE2). Both cardiomyocytes and pericytes (coronary arteries) express the necessary accessory proteins for access of SARS-CoV-2 particles (i.e. ACE2, NRP-1, TMPRSS2, CD147, integrin α5ß1, and CTSB/L). These proteins facilitate the SARS-CoV-2 interaction and entry into the pericytes and cardiomyocytes thus leading to cardiac manifestations. Subsequently, various signaling pathways are altered in the infected cardiomyocytes (i.e. increased ROS production, reduced contraction, impaired calcium homeostasis), causing cardiac dysfunction. The currently adopted pharmacotherapy in severe COVID-19 subjects exhibited side effects on the heart, often manifested by electrical abnormalities. Nonetheless, cardiovascular adverse repercussions have been associated with the advent of some of the SARS-CoV-2 vaccines with no clear mechanisms underlining these complications. We provide herein an overview of the pathways involved with cardiomyocyte in COVID-19 subjects to help promoting pharmacotherapies that can protect against SARS-CoV-2-induced cardiac injuries.