Thyroid hormones and platelet activation in COVID-19 patients.

PURPOSE: To retrospectively describe the association between thyroid hormones (TH) and platelet activation, as represented by mean platelet volume (MPV), in a cohort of patients hospitalized for COVID-19 with no known thyroid disease, and to correlate these data with the severity of COVID-19 and the occurrence of death/ARDS (Acute Respiratory Distress Syndrome). METHODS: 103 patients with real-time polymerase chain reaction (RT-PCR) testing-confirmed COVID-19 and hospitalized were enrolled. Serum samples were collected from patients upon admission before starting any treatment. Chi-squared test was used to determine the association between euthyroid sick syndrome (ESS) and COVID-19 severity. Multivariate logistic regression was performed to evaluate the best independent predictors of COVID-19 deaths/ARDS. RESULTS: 39/103 (37.9%) of patients were found to have ESS, and this condition was an independent predictor for the severity of COVID-19 (p = 0.003). Lower TSH and lower FT3/FT4 ratio correlated with higher MPV (p = 0,001 and p = 0.010), with an opposite trend with respect to what has been documented in non-COVID patients. Increasing MPV and lower FT3 significantly increased the risk, in COVID-19 patients, of an adverse outcome of death/ARDS. CONCLUSION: Increased platelet activation, as represented by increased MPV, has already been reported to correlate with COVID-19 severity, possibly as a consequence of cytokine release. We demonstrated, in a cohort of 103 patients with COVID-19, that MPV is inversely correlated to TH levels, in particular in the case of ESS, where downregulation of TH axis may occur in case of systemic cytokine inflammation and more severe outcomes (death/ARDS). That ESS itself may directly cause platelet activation, as demonstrated by higher MPV in these patients, is an interesting hypothesis which deserves further investigation.

Soluble sST2 biomarker analysis for fibrosis development in atrial fibrillation. A case control study.

ABSTRACT: Objectives. Atrial fibrillation (AF) is a clinically relevant supra-ventricular arrhythmia which represents an independent risk factor for development of heart failure and ischemic stroke. The present study aims at the investigation of the possible clinical role of the soluble sST2 biomarker to evaluate the fibrosis in a group of patients with first diagnosed or permanent AF. The possible association with the left atrium size is also studied. Materials and Methods. The serum concentrations of the biomarker have been measured in a group of 58 patients (mean age 83.6 ± 6.0 years) and 40 individuals, assumed healthy and without AF, constituted the control group. The analysis is carried out by means of a high-sensitivity enzyme-linked immunosorbent assay. Results. The mean concentration of sST2 is 26.1 (22.7-30.5) ng/mL in the AF group, while in the control is 17.3 (15.7-18.9) ng/mL. Remarkable differences have been obtained for the two subsets with first diagnosed (23 (21.2-24) ng/mL) and permanent AF (30.5 (28.6-32) ng/mL). The analysis has been completed with a trans thoracic echocardiographic exam to evaluate the left atrium size and the left ventricular ejection fraction. Conclusions. The sST2 serum concentrations are found to be higher in the permanent AF with respect to the cases where the AF is of new onset or follow a paroxysmal pattern. The results support the adoption of the marker to evaluate the degree of fibrosis related to the left atrium of fibrillating patients. A positive association has been proved between the left atrium size and the sST2 concentrations.

[Comparison of plasma matrix metalloproteases 2, 3, 9 in breast carcinomas and fibroadenomas]. / Confronto dei valori plasmatici delle metalloproteasi della matrice 2, 3, 9 in pazienti con carcinomi e fibroadenomi mammari.

Tumor cell infiltration causes the remodelling of peritumoral tissues, determined by an increased lytic activity of extracellular matrix exerted by the neoplastic invasive phenotype. Among the principal lytic enzymes produced by tumor cells and mainly involved in invasion process there are the matrix metalloproteases (MMPs). The Authors compared the plasmatic values of MMPs 2, 3, 9 from patients with breast carcinomas and fibroadenomas in order to evaluate whether there was a significant difference between the two groups of patients. MMPs 2, 3, 9 values were quantified by ELISA test from plasma collected 24 hours before surgery in 50 breast carcinomas and 30 fibroadenomas. MMP2 mean value from the patients with carcinomas resulted significantly higher as compared to that from the patients with fibroadenomas; while for MMP 3 and 9 mean values was not possible to find a significant difference between the two groups of malignant and benign breast tumors. These data confirm the main role played by MMPs during the tumor invasion process. Therefore, it is possible to propose the future inclusion of MMP2 test, together to other biological and clinical data, for prognostic evaluation of neoplastic breast lesions.

Preconditioning effects of levosimendan in coronary artery bypass grafting--a pilot study.

BACKGROUND: The calcium sensitizer levosimendan protects against myocardial ischaemia and reperfusion injury in animal models. METHODS: The present pilot study investigated whether a short infusion before coronary artery bypass grafting (CABG) would protect the myocardium and improve postoperative haemodynamics. Twenty-four patients with stable angina undergoing elective CABG surgery were randomized to receive either placebo or levosimendan (24 microg kg(-1)) infused i.v. over a 10 min period just before placing the patient on cardiopulmonary bypass. RESULTS: Perioperative haemodynamic variables, concentrations of cardiac troponin I over the 48 h postoperative period, and clinical outcomes were assessed. There were no adverse effects related to levosimendan. Compared with control patients, levosimendan-treated patients had lower postoperative troponin I concentrations (P<0.05) and a higher cardiac index (P<0.05). CONCLUSION: Patients receiving a short infusion of levosimendan before CABG showed evidence of less myocardial damage, suggestive of a preconditioning effect. Larger outcome studies are thus indicated to confirm benefit.

Endocrinological diagnosis in sexology.

Endocrine factors represent an important and potentially treatable cause of sexual dysfunction. The availability of a correct endocrinological diagnosis allows correct identification of most cases of sexual dysfunction in which the endocrine apparatus is involved. Not only the most frequent causes of endocrine sexual dysfunction, such as hypogonadism and hyperprolactinemia, but almost all extra-gonadal endocrinopathies (hyper- and hypothyroidism, hyper- and hypocortisolism, steroidal secreting tumors, etc.) may play a role to a greater or lesser extent in sexual function. It is therefore necessary that the diagnostic process for sexual dysfunctions of an endocrine nature be as integrated and wide as possible, especially as such pathologies are usually extremely responsive to medical or surgical therapy.

Comparative rates of androgen production and metabolism in Caucasian and Chinese subjects.

Clinically apparent prostate cancer occurs more commonly among Caucasians living in Western countries than in Chinese in the Far East. Prior studies demonstrated diminished facial and body hair and lower levels of plasma 3 alpha-androstanediol glucuronide and androsterone glucuronide in Chinese than in Caucasian men. Based upon these findings, investigators postulated that Chinese men could have diminished 5 alpha-reductase activity with a resultant decrease in prostate tissue dihydrotestosterone levels and clinically apparent prostate cancer. An alternative hypothesis suggests that decreased 3 alpha-androstanediol glucuronide and androsterone glucuronide levels might reflect reduced production of androgenic ketosteroid precursors as a result of genetic or environmental factors. The present study examined 5 alpha-reductase activity, androgenic ketosteroid precursors, and the influence of genetic and environmental/dietary factors in groups of Chinese and Caucasian men. We found no significant differences in the ratios of 5 beta-:5 alpha-reduced urinary steroids (a marker of 5 alpha-reductase activity) between Chinese subjects living in Beijing, China, and Caucasians living in Pennsylvania. To enhance the sensitivity of detection, we used an isotopic kinetic method to directly measure 5 alpha-reductase activity and found no difference in testosterone to dihydrotestosterone conversion ratios between groups. Then, addressing the alternative hypothesis, we found that the Caucasian subjects excreted significantly higher levels of individual and total androgenic ketosteroids than did their Chinese counterparts. To distinguish genetic from environmental/dietary factors as a cause of these differences, we compared Chinese men living in Pennsylvania and a similar group living in Beijing, China. We detected a reduction in testosterone production rates and total plasma testosterone and sex hormone-binding levels, but not in testosterone MCRs in Beijing Chinese as a opposed to those living in Pennsylvania. Comparing Pennsylvania Chinese with their Caucasian counterparts, we detected no significant differences in total testosterone, free and weakly bound testosterone, sex hormone-binding globulin levels, and testosterone production rates. Taken together, these studies suggest that environmental/dietary, but not genetic, factors influence androgen production and explain the differences between Caucasian and Chinese men.

Structural alterations in erythrocytes from patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by inflammation of deep lung and pulmonary hypoxemia. In order to investigate if the clinical manifestations of this disease can be correlated to specific alterations in red blood cell (RBC) morphology, the erythrocytes from 12 COPD patients and 12 control subjects were obtained and examined by scanning electron microscopy (SEM), fluorescence microscopy and electron paramagnetic resonance (EPR) spectroscopy. The results demonstrate that the RBCs from COPD patients are greatly altered with respect to control erythrocytes. Specifically, SEM analysis revealed important shape changes while light fluorescence microscopy demonstrated microfilament network (actin and spectrin) redistribution. Finally, EPR spectroscopy, using the paramagnetic spin label 5-nitroxystearate, revealed an increase in membrane order (rigidity) in the erythrocytes of COPD patients with respect to controls. When taken together and when compared to the morphological variations present in the RBCs of other ill patients (i.e., diabetics), the data presented in this report seem to suggest that changes in erythrocyte shape and rheological properties play a key role in RBC dysfunction in the course of COPD.

Effect of inorganic phosphate on hypoxanthine transport in isolated brain microvessels.

In isolated brain microvessels, used as an in vitro model of the blood-brain barrier, the rate of hypoxanthine uptake was modulated by the presence of inorganic phosphate. A single high-capacity, low-affinity transport system was apparently active in a phosphate-free medium (Vmax = 840 pmol/mg protein/min, Km = 750/uM); in the presence of 10 mM phosphate, there was also a low-capacity, high-affinity system (Vmax = 47 pmol/mg protein/min, Km = 27/uM). The phosphate-dependent component was inactive in the absence of glucose or of Na+ ions, or upon addition of phloretine (but was scarcely affected by 2,4-dinitrophenol). This activity was apparently coupled to the intracellular phosphoribosyltransferase-catalyzed conversion of purines into the corresponding nucleotides: when inorganic phosphate was present in the suspending medium, labeled hypoxanthine was transported with higher efficiency and was readily converted to inosine monophosphate and to other related nucleotides. In the absence of phosphate ions, hypoxanthine was instead metabolized to xanthine and uric acid.