The Role of Endothelial Progenitor Cells in Atherosclerosis and Impact of Anti-Lipemic Treatments on Endothelial Repair

Cardiovascular complications are associated with advanced atherosclerosis. Although atherosclerosis is still regarded as an incurable disease, at least in its more advanced stages, the discovery of endothelial progenitor cells (EPCs), with their ability to replace old and injured cells and differentiate into healthy and functional mature endothelial cells, has shifted our view of atherosclerosis as an incurable disease, and merged traditional theories of atherosclerosis pathogenesis with evolving concepts of vascular biology. EPC alterations are involved in the pathogenesis of vascular abnormalities in atherosclerosis, but many questions remain unanswered. Many currently available drugs that impact cardiovascular morbidity and mortality have shown a positive effect on EPC biology. This review examines the role of endothelial progenitor cells in atherosclerosis development, and the impact standard antilipemic drugs, including statins, fibrates, and ezetimibe, as well as more novel treatments such as proprotein convertase subtilisin/kexin type 9 (PCSK9) modulating agents and angiopoietin-like proteins (Angtpl3) inhibitors have on EPC biology

Functional changes in the central nervous system: An early but unrecognized complication of type 1 diabetes mellitus.

Purpose: Diabetic neuropathy is a chronic and disabling condition that affects a significant number of individuals with diabetes mellitus (DM). Long considered a disease of the peripheral nervous system, there is now increasing evidence of central nervous system (CNS) involvement. Recent advances in neuroimaging methods have improved our understanding of how diabetic neuropathy affects the CNS. The aim of this study was to explore the relationship between cerebrospinal fluid (CSF) concentration of polyols, plasma glucose, and 18-fluordeoxyglucose (18-FDG) uptake correlation in the CNS of Type 1 diabetes mice models. Materials and Methods: We conducted a study using two different Type 1 DM mice models: Streptozotocin induced and non-obese diabetic (NOD) mice models. Positron emission tomography with 18-FDG was used to determine glucose uptake in the frontal cortex and hippocampus. CSF samples were taken from the cisterna magna, while polyol species in the CSF were determined using gas chromatographic/mass spectrometric assays by Sigma Aldrich. Results: The concentration of CSF myoinositol was significantly higher in NOD mice compared to controls (P = 0.001). The 18-FDG uptake was significantly attenuated in NOD mice compared to controls. CSF-myoinositol negatively correlated with 18-FDG uptake in the hippocampal area (ρ = −0.571, P = 0.003) and frontal cortex (ρ = −0.521, P = 0.044). Conclusion: We demonstrated that in the early course of Type 1 DM, there are functional changes in the CNS, precisely in the frontal cortex and hippocampal region, evidenced by elevated myoinositol, which might reflect the initiation of cerebral tissue damage. Whether this suggests that hyperglycemia is toxic for the brain needs further investigation

The impact of hyperosmolarity on long-term outcome in patients presenting with severe hyperglycemic crisis: a population based study

AIMS: We compared characteristics of patients with hyperglycemic hyperosmolar state (HHS) and patients with severe hyperglycemia without the signs of hyperosmolarity and ketoacidosis; analyzed long-term all-cause mortality and potential prognostic factors. ----- METHODS: The studied population included 261 749 adults. HHS was diagnosed in patients with plasma glucose >33.0 mmol/L, ketonuria 320 mmol/L. Patients with plasma glucose >33.0 mmol/L, ketonuria <1+ and serum osmolarity <320 mmol/L were considered as controls (nHHS). ----- RESULTS: During the 5-year period, we observed 68 episodes of HHS in 66 patients and 51 patients with nHHS. Patients with HHS were significantly older, had lower BMI, higher serum C-reactive protein and used diuretics and benzodiazepines more frequently. Mortality rates one, three and 12 months after admission were 19.0, 32.1 and 35.7% in the HHS group, and 4.8, 6.3 and 9.4% in the nHHS group (P<0.001). However, after adjustment for patient age, these differences were not statistically significant. In multivariate Cox regression in HHS group, mortality was positively associated with age, male gender, leukocyte count, amylase, presence of dyspnea and altered mental status, and the use of benzodiazepines, ACE inhibitors and sulphonylureas, while it was inversely associated with plasma glucose, bicarbonate, and the use of thiazides and statins. A nomogram derived from these variables had an accuracy of 89% in predicting lethal outcome. ----- CONCLUSIONS: Infection, use of furosemide and benzodiazepines may be important precipitating factors of HHS. Prospective clinical trials are mandatory to analyze the safety of ACE-inhibitors and benzodiazepines in elderly patients with diabetes

Dose-volume derived nomogram as a reliable predictor of radiotherapy-induced hypothyroidism in head and neck cancer patients

Background The aim of this study was to determine the possible predictive value of various dosimetric parameters on the development of hypothyroidism (HT) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. ----- Patients and methods This study included 156 patients with HNSCC who were treated with (chemo)radiotherapy in a primary or postoperative setting between August 2012 and September 2017. Dose-volume parameters as well as V10 toV70, D02 to D98, and the VS10 to VS70 were evaluated. The patients’ hormone status was regularly assessed during follow-up. A nomogram (score) was constructed, and the Kaplan-Maier curves and Log-Rank test were used to demonstrate the difference in incidence of HT between cut-off values of specific variables. ----- Results After a median follow-up of 23.0 (12.0–38.5) months, 70 (44.9%) patients developed HT. In univariate analysis, VS65, Dmin, V50, and total thyroid volume (TTV) had the highest accuracy in predicting HT. In a multivariate model, HT was associated with lower TTV (OR 0.31, 95% CI 0.11–0.87, P = 0.026) and Dmin (OR 9.83, 95% CI 1.89–108.08, P = 0.042). Hypothyroidism risk score (HRS) was constructed as a regression equation and comprised TTV and Dmin. HRS had an AUC of 0.709 (95% CI 0.627–0.791). HT occurred in 13 (20.0%) patients with a score 7.1. ----- Conclusions The dose volume parameters VS65, Dmin, V50, and TTV had the highest accuracy in predicting HT. The HRS may be a useful tool in detecting patients with high risk for radiation-induced hypothyroidism