The Antiviral Effects of 2-Deoxy-D-glucose (2-DG), a Dual D-Glucose and D-Mannose Mimetic, against SARS-CoV-2 and Other Highly Pathogenic Viruses.

Viral infection almost invariably causes metabolic changes in the infected cell and several types of host cells that respond to the infection. Among metabolic changes, the most prominent is the upregulated glycolysis process as the main pathway of glucose utilization. Glycolysis activation is a common mechanism of cell adaptation to several viral infections, including noroviruses, rhinoviruses, influenza virus, Zika virus, cytomegalovirus, coronaviruses and others. Such metabolic changes provide potential targets for therapeutic approaches that could reduce the impact of infection. Glycolysis inhibitors, especially 2-deoxy-D-glucose (2-DG), have been intensively studied as antiviral agents. However, 2-DG's poor pharmacokinetic properties limit its wide clinical application. Herein, we discuss the potential of 2-DG and its novel analogs as potent promising antiviral drugs with special emphasis on targeted intracellular processes.

Use of the SAPIEN 3 Transcatheter Heart Valve in High-Risk Scenarios.

The transcatheter aortic valve replacement procedure is used in patients with aortic stenosis. Transcatheter aortic valve replacement devices are quite versatile; thus, they are increasingly being used for nonaortic applications, such as tricuspid valve-in-valve implantation. This case series describes a transcatheter aortic valve replacement procedure in 4 patients with anatomic challenges (eg, aortic tortuosity, high valvular calcium burden, highly calcified bicuspid valve, low coronary artery takeoff, left main coronary artery occlusion, and large aortic annulus) and a fifth patient who had a failed tricuspid bioprosthesis and underwent a tricuspid valve-in-valve implantation with the Edwards SAPIEN 3 transcatheter heart valve (Edwards Lifesciences). All procedures required adjustments to the standard protocol, and each procedure was successful. The critical, technical adjustments in the deployment technique and preprocedural planning of the procedures are detailed to provide a road map for other cardiologists who encounter similar challenges.

Clinicopathological correlations in heart transplantation recipients complicated by death or re-transplantation.

Purpose: This study aimed to identify and correlate pathological findings with clinical outcomes in patients after orthotopic heart transplantation (OHT) who either died or underwent a re-transplantation. Methodology and study design: Single-center retrospective analysis of primary OHT patients who died or were re-transplanted between October 2012 and July 2021. Clinical data were matched with corresponding pathological findings from endomyocardial biopsies on antibody-mediated rejection, cellular rejection, and cardiac allograft vasculopathy. Re-assessment of available tissue samples was performed to investigate acute myocardial injury (AMI) as a distinct phenomenon. These were correlated with clinical outcomes, which included severe primary graft dysfunction. Patients were grouped according to the presence of AMI and compared. Results: We identified 47 patients with truncated outcomes after the first OHT. The median age was 59 years, 36 patients (76%) were male, 25 patients (53%) had a prior history of cardiac operation, and 21 patients (45%) were supported with a durable assist device before OHT. Of those, AMI was identified in 22 (47%) patients (AMI group), and 25 patients had no AMI (non-AMI group). Groups were comparable in baseline and perioperative data. Histopathological observations in AMI group included a non-significant higher incidence of antibody-mediated rejection Grade 1 or higher (pAMR ≥ 1) (32% vs. 12%, P = 0.154), and non-significant lower incidence of severe acute cellular rejection (ACR ≥ 2R) (32% vs. 40%, P = 0.762). Clinical observations in the AMI group found a significantly higher occurrence of severe primary graft dysfunction (68% vs. 20%, P = 0.001) and a highly significant shorter duration from transplantation to death or re-transplantation (42 days [IQR 26, 120] vs. 1,133 days [711-1,664], P < 0.0001). Those patients had a significantly higher occurrence of cardiac-related deaths (64% vs. 24%, P = 0.020). No difference was observed in other outcomes. Conclusion: In heart transplant recipients with a truncated postoperative course leading to either death or re-transplantation, AMI in endomyocardial biopsies was a common pathological phenomenon, which correlated with the clinical occurrence of severe primary graft dysfunction. Those patients had significantly shorter survival times and higher cardiac-related deaths. The presence of AMI suggests a truncated course after OHT.

Use of Transthoracic Echocardiogram to Detect Left Ventricular Thrombi.

BACKGROUND: The presence of a left ventricular thrombus (LVT) poses a risk of thromboembolic complications and excludes patients from undergoing left ventricular assist device (LVAD) implantation without the aid of cardiopulmonary bypass (CPB). Transthoracic echocardiography (TTE) and transesophageal echocardiography are used to detect LVT in patients with heart disease; however, the detection validity of these imaging studies has not been definitively elucidated. METHODS: A retrospective analysis of patients with end-stage heart failure who underwent LVAD implantation from May 2012 to August 2018 in a single center was completed. To be included, patients' medical records had to have presurgical TTE and transesophageal echocardiographic images, as well as intraoperative digital and visual exploration observations. A total of 301 patients underwent LVAD implantation; 239 of these patients had an LVAD implanted with the use of CPB. A total of 230 patients had complete data sets and were included in the analysis. RESULTS: Preoperative TTE identified LVT in 23 of the 230 patients (10%); 15 patients (6.5%) had LVT confirmed by surgical intraventricular visualization. Of the patients with visual LVT confirmation, preoperative TTE identified an LVT in all but 1 case (93%; 14 of 15). Preoperative TTE of LVT had a high sensitivity (94%) and specificity (96%), as well as high negative predictive value (99%). CONCLUSIONS: The results of this study show that preoperative TTE is highly accurate for LVT detection. The high negative predictive value could have significant implications for the choice of surgical procedure because with TTE, surgeons can reasonably determine whether LVAD placement procedure can be attempted without CPB support.

In vitro anti-influenza activity of in silico repurposed candidate drug cycrimine.

BACKGROUND: Due to the limitations of current antiviral therapies because of drug resistance and the emergence of new circulating viral strains, novel effective antivirals are urgently needed. Results of the previous drug repurposing by virtual screening of DrugBank revealed the anticholinergic drug cycrimine as a possible inhibitor of the influenza virus infection. METHODS: In this study we examined the potential antiviral activity of cycrimine in vitro. RESULTS: The experimental results showed the anti-influenza activity of cycrimine against two different influenza A subtypes in cell culture. CONCLUSIONS: The findings of this study suggest cycrimine as a potential therapeutic agent for influenza.