Search

Background: For more than a year, health systems all over the world have been combating the global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first described in the city of Wuhan in China, presenting as an atypical infection of the lower respiratory tract. Methods: COVID-19 is characterized by multisystemic involvement, and mortality is attributed mainly to the respiratory system involvement, which may lead to severe acute respiratory distress syndrome and respiratory failure. Several COVID-19-associated complications are being increasingly reported, including arterial and venous thromboembolic events that may lead to amputation of the affected limbs. So far, a large number of reports have described hypercoagulability crises leading to amputation of the lower limbs. However, a search of the National Library of Medicine (MEDLINE) revealed no cases of urgent upper limb amputation in COVID-19 patients. Results: This article describes a novel case of upper limb ischemia in a COVID-19 patient, with rapid progression to hand necrosis, requiring urgent through-arm amputation of the upper limb. Conclusions: This case emphasizes the need for anticoagulant therapy in COVID-19 patients and to maintain a constant awareness of the possible thromboembolic COVID-19-related sequelae.

Lower circulating levels of glycine are consistently reported in association with cardiovascular disease (CVD), but the causative role and therapeutic potential of glycine in atherosclerosis, the underlying cause of most CVDs, remain to be established. Here, following the identification of reduced circulating glycine in patients with significant coronary artery disease (sCAD), we investigated a causative role of glycine in atherosclerosis by modulating glycine availability in atheroprone mice. We further evaluated the atheroprotective potential of DT-109, a recently identified glycine-based compound with dual lipid/glucose-lowering properties. Glycine deficiency enhanced, while glycine supplementation attenuated, atherosclerosis development in apolipoprotein E-deficient (Apoe−/−) mice. DT-109 treatment showed the most significant atheroprotective effects and lowered atherosclerosis in the whole aortic tree and aortic sinus concomitant with reduced superoxide. In Apoe−/− mice with established atherosclerosis, DT-109 treatment significantly reduced atherosclerosis and aortic superoxide independent of lipid-lowering effects. Targeted metabolomics and kinetics studies revealed that DT-109 induces glutathione formation in mononuclear cells. In bone marrow-derived macrophages (BMDMs), glycine and DT-109 attenuated superoxide formation induced by glycine deficiency. This was abolished in BMDMs from glutamate-cysteine ligase modifier subunit-deficient (Gclm−/-) mice in which glutathione biosynthesis is impaired. Metabolic flux and carbon tracing experiments revealed that glycine deficiency inhibits glutathione formation in BMDMs while glycine-based treatment induces de novo glutathione biosynthesis. Through a combination of studies in patients with CAD, in vivo studies using atherosclerotic mice and in vitro studies using macrophages, we demonstrated a causative role of glycine in atherosclerosis and identified glycine-based treatment as an approach to mitigate atherosclerosis through antioxidant effects mediated by induction of glutathione biosynthesis.

Abstract Background Euglycemic diabetic ketoacidosis is an uncommon but life-threatening complication associated with the use of sodium-glucose cotransporter 2 inhibitors that causes lower than expected blood glucose levels typically seen in diabetic ketoacidosis. Case presentation We present a case of 64-year-old Caucasian male patient previously diagnosed with type 2 diabetes treated with a sodium-glucose cotransporter 2 inhibitor who developed severe ketoacidosis. Serum glucose levels on initial presentation were slightly above normal baseline level. The patient was revealed to have latent autoimmune diabetes in adults. Conclusion This case highlights the importance of prescribing sodium-glucose cotransporter 2 inhibitors to the correct patient population and the significance of accurately differentiating between various types of diabetes.

Summary: Dysregulated glycine metabolism is emerging as a common denominator in cardiometabolic diseases, but its contribution to atherosclerosis remains unclear. In this study, we demonstrate impaired glycine-oxalate metabolism through alanine-glyoxylate aminotransferase (AGXT) in atherosclerosis. As found in patients with atherosclerosis, the glycine/oxalate ratio is decreased in atherosclerotic mice concomitant with suppression of AGXT. Agxt deletion in apolipoprotein E-deficient (Apoe−/−) mice decreases the glycine/oxalate ratio and increases atherosclerosis with induction of hepatic pro-atherogenic pathways, predominantly cytokine/chemokine signaling and dysregulated redox homeostasis. Consistently, circulating and aortic C-C motif chemokine ligand 5 (CCL5) and superoxide in lesional macrophages are increased. Similar findings are observed following dietary oxalate overload in Apoe−/− mice. In macrophages, oxalate induces mitochondrial dysfunction and superoxide accumulation, leading to increased CCL5. Conversely, AGXT overexpression in Apoe−/− mice increases the glycine/oxalate ratio and decreases aortic superoxide, CCL5, and atherosclerosis. Our findings uncover dysregulated oxalate metabolism via suppressed AGXT as a driver and therapeutic target in atherosclerosis.

Background. Abdominal aortic aneurysm (AAA) and acute coronary syndrome (ACS) share common risk factors. Objectives. To assess the abdominal aortic diameter (AAD) among patients with ACS using transthoracic echocardiography (TTE). Methods. Patients with ACS admitted to our intensive cardiac care unit from December 2013 to June 2014 were screened prospectively for AAA via AAD measurement in the subcostal TTE view. AAA was defined as an aneurysm with a transverse diameter of ≥30 mm. Results. Sixty seven patients were included. The male-to-female sex ratio was 7 : 1. The vast majority of patients were admitted due to STEMI (73%), and the rest were equally divided as NSTEMI and unstable angina. The mean patient age was 58.4 ± 10.4 years. AAD measurements were feasible in 57 patients (85%); among them, AAA was diagnosed in six patients (10.5%). The average additional time required to measure the abdominal aorta was 4 ± 1 min. All patients with AAA were men and had a higher prevalence of smoking (83.3% vs. 60.6%, p