A new COVID-19 prediction scoring model for in-hospital mortality: experiences from Turkey, single center retrospective cohort analysis.

OBJECTIVE: Although many studies reported prognostic factors proceeding to severity of COVID-19 patients, in none of the article a prediction scoring model has been proposed. In this article a new prediction tool is presented in combination of Turkish experience during pandemic. MATERIALS AND METHODS: Laboratory and clinical data of 397 over 798 confirmed COVID-19 patients from Gülhane Training and Research Hospital electronic medical record system were included into this retrospective cohort study between the dates of 23 March to 18 May 2020. Patient demographics, peripheral venous blood parameters, symptoms at admission, in hospital mortality data were collected. Non-survivor and survivor patients were compared to find out a prediction scoring model for mortality. RESULTS: There was 34 [8.56% (95% CI:0.06-0.11)] mortality during study period. Mean age of patients was 57.1±16.7 years. Older age, comorbid diseases, symptoms, such as fever, dyspnea, fatigue and gastrointestinal and WBC, neutrophil, lymphocyte count, C-reactive protein, neutrophil-to-lymphocyte ratio of patients in non-survivors were significantly higher. Univariate analysis demonstrated that OR for prognostic nutritional index (PNI) tertile 1 was 18.57 (95% CI: 4.39-78.65, p<0.05) compared to tertile 2. Performance statistics of prediction scoring method showed 98% positive predictive value for criteria 1. CONCLUSIONS: It is crucial to constitute prognostic clinical and laboratory parameters for faster delineation of patients who are prone to worse prognosis. Suggested prediction scoring method may guide healthcare professional to discriminate severe COVID-19 patients and provide prompt intensive therapies which is highly important due to rapid progression leading to mortality.

Polidocanol (Lauromacrogol 400) has anti-angiogenic effects in vitro and in vivo.

OBJECTIVE: Polidocanol is the most frequently used sclerosant for sclerotherapy all around the world. Our experimental research aims to find out the angiogenic effects of Polidocanol. MATERIALS AND METHODS: Angiogenic activity of polidocanol was examined in vivo in the chick chorioallantoic membrane (CAM) model, cell viability assay (human umbilical vein endothelial cells - HUVECs) and in vitro tube formation assay of HUVECs. RESULTS: In CAM assay, a significant decrease on CAM vessel growth was observed after the application of polidocanol solutions. Vessel growth inhibition was strongly dose-dependent. There was a cytotoxic effect on HUVECs in the presence of polidocanol observed with MTT assay (p < 0.05). In the tube formation assay, statistically significant decrease in tube formation was observed in polidocanol group. It was found that polidocanol had an anti-angiogenic effect (p < 0.05). The results provide evidence that polidocanol decreases angiogenesis and has a cytotoxic effect on ECs. CONCLUSIONS: These results provide evidence that Polidocanol (lauromacrogol 400) have strong anti-angiogenic effects in vitro and in vivo. Further researches needed to reveal early and long-term effects of polidocanol in the human vascular system and new treatment approach as an anti-angiogenic therapy.

Comparison of angiogenic and proliferative effects of three commonly used agents for pulmonary artery hypertension (sildenafil, iloprost, bosentan): is angiogenesis always beneficial?

OBJECTIVE: Pulmonary artery hypertension (PAH) is devastating disease that has very serious outcomes. Dysregulated angiogenesis is one of the main responsible courses in pathophysiology of disease. Our experimental research intends to find out and compare the angiogenic effects of medications used sildenafil, iloprost, and bosentan in the treatment of PAH. MATERIALS AND METHODS: This study was performed in Department of Biochemistry and Cancer and Stem Cell Research Laboratory of our institutes between August and October 2014. Angiogenic activity of sildenafil, iloprost, and bosentan were examined in vivo in chick chorioallantoic membrane (CAM) model and in vitro tube formation assay of human umbilical vein endothelial cells (HUVECs). Proliferative activity of these three agents was also determined through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on HUVECs. RESULTS: In CAM assay, when compared to the control and drug groups, treatment with sildenafil solutions resulted in a significant dose-dependent increase (budding, sprouting, extravasation) on CAM vessel growth. While there was no significant proliferative effect with iloprost and bosentan, presence of sildenafil caused a statistically significant proliferation on HUVECs following 24 and 48 h incubation (p < 0.05) compared to the control group. Comparing the tube length/area ratio values, there was statistically significant increase in sildenafil group with respect to the other 2 groups (p < 0.05). Iloprost and bosentan did not show a significant effect. CONCLUSIONS: The results provide evidence that sildenafil but not iloprost and bosentan induces angiogenesis in vitro and in vivo. Dysregulated angiogenesis, as an important pathophysiological part in the progression of PAH, may be triggered by the chronic ingestion of sildenafil in the long treatment period and may cause negative effects.

Aspartame induces angiogenesis in vitro and in vivo models.

Angiogenesis is the process of generating new blood vessels from preexisting vessels and is considered essential in many pathological conditions. The purpose of the present study is to evaluate the effect of aspartame on angiogenesis in vivo chick chorioallantoic membrane (CAM) and wound-healing models as well as in vitro 2,3-bis-2H-tetrazolium-5-carboxanilide (XTT) and tube formation assays. In CAM assay, aspartame increased angiogenesis in a concentration-dependent manner. Compared with the control group, aspartame has significantly increased vessel proliferation (p < 0.001). In addition, in vivo rat model of skin wound-healing study showed that aspartame group had better healing than control group, and this was statistically significant at p < 0.05. There was a slight proliferative effect of aspartame on human umbilical vein endothelial cells on XTT assay in vitro, but it was not statistically significant; and there was no antiangiogenic effect of aspartame on tube formation assay in vitro. These results provide evidence that aspartame induces angiogenesis in vitro and in vivo; so regular use may have undesirable effect on susceptible cases.

The role of visfatin in the pathogenesis of gestational diabetes mellitus.

AIM: The objective of the present study was to evaluate the role of visfatin in gestational diabetes mellitus. MATERIALS AND METHODS: Forty-five pregnant women at 24 to 28 weeks' gestation were assigned to consume an initial screening test using a 1-h 50-g glucose load, and then a 3-h 100-g glucose load. The study group consisted of 23 patients who were diagnosed with gestational diabetes mellitus and the control group consisted of 22 healthy pregnant women. We studied the levels of visfatin and the other parameters of inflammation, glucose and lipid metabolism between the 24th and 28th week of gestation and also between the 6th and 10th week after delivery. RESULTS: Plasma visfatin and glucose levels at 60 min after a 50-g and a 100-g glucose load between the 24th and 28th week of gestation were significantly higher in the gestational diabetes group than in the control group. There were no statistical differences in visfatin levels between the groups at 6-10 weeks post-partum. CONCLUSION: Visfatin levels were significantly elevated in women with gestational diabetes mellitus and during the course of pregnancy and increased visfatin concentrations were reduced within 6 to 10 weeks after delivery.

Importance of urinary measurement of glutathione S-transferase in renal dysfunction patients after on- and off-pump coronary artery bypass surgery.

BACKGROUND: Acute renal failure (ARF) occurring after on-pump and off-pump cardiac surgery was assessed by urinary alpha glutathione S-transferase measurement (alpha-GST) in patients who already had renal dysfunction. METHODS: Fifty-one patients with plasma creatinine levels ranging between 1.5 and 2.0 mg/dL were included in the study. On-pump coronary artery bypass was performed in 25 of them, and off-pump surgery in the other 25 patients. Urinary alpha-GST levels, plasma creatinine levels, creatinine clearance and fractional excretion of sodium were measured. RESULTS: Urinary alpha-GST levels were found to be significantly increased at 24 hours postoperatively. A weak correlation was detected between alpha-GST levels and plasma creatinine, creatinine clearance and fractional excretion of sodium. Preoperative and postoperative 24 hour levels showed a positive predictive value for the occurrence of acute renal failure. CONCLUSIONS: Tubular damage produced by cardiopulmonary bypass is not the only factor associated with postoperative ARF. Because factors independent of pump usage can adversely affect renal function, excluding pump usage alone is not sufficient to prevent postoperative ARF in patients who have preoperative renal dysfunction.

Effect of poly (2-methoxyethyl acrylate)-coated oxygenators on haemolysis.

Blood contact with artificial device surfaces and mechanical trauma are two major factors for haemolysis. Poly(2-methoxyethyl acrylate) (PMEA) is an amphiphilic polymer with a polyethylene chain that is hydrophobic and a mildly hydrophilic tail. PMEA coating has showed positive effects on protein adsorption, platelet loss, platelet aggregation and post-operative bleeding in previous studies. In this study, effects of poly(2-metoxyethyl acrylate) (PMEA)-coated oxygenators on haemolysis was investigated. PMEA-coated (SX18-Capiox) oxygenators were used. Desorbed erythrocyte, free haemoglobin indirect bilirubin and total bilirubin quantities from fibre samples of oxygenators were studied. Erythrocyte, total bilirubin and direct bilirubin values were measured from blood aliquots taken in five different times during cardiopulmonary by-pass (CPB); baseline (T1), during CPB (T2), at the end of CPB (T3), after protamine injection (T4) and in intensive care (T5). In both coated and non-coated oxygenators haemolysis rate was in clinically acceptable safety range. Average desorbed free haemoglobin was 6663 mg/dl from coated and 29.405 mg/dl from non-coated fibres. Average desorbed total bilirubin was 0.0068 mg/dl from coated and 0.023 mg/dl from noncoated fibres. We observed less haemolysis, as reflected by lower desorbed free haemoglobin and indirect bilirubin from coated oxygenators and less decrease in blood erythrocyte number. Blood bilirubin concentration was low in the coated group when compared to the control group. This study describes the relationship between PMEA coating and haemolysis at the blood contacting surface. PMEA coating reduces red blood cell damage during extracorporeal circulation.

The effects of analytical factors on second trimester risk estimations.

OBJECTIVE: Triple test with measured maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol combination as a routine procedure for fetal Down's syndrome, trisomy 18 and neural tube defect screening has some intrinsic problems, such as precision. The aim of this study was to evaluate the effect of analytical variation of triple test on prenatal risk estimation. METHOD: Five different serum pools were prepared and triple test was performed seven times for within run and five times for between run precision determination. RESULT: Within run and between run, precision values of risk estimations by measuring the same sample for Triple test were calculated to be 7.9-21.4% and 14.1-31.0% for trisomy 21, 13.2-23.7% and 14.2-15.1% for trisomy 18, 47.2 and 42.0 % for neural tube defect, respectively. CONCLUSION: These results demonstrated that analytical variations have great impact on second trimester risk estimation procedures; therefore, triple test analyses should be carried out in laboratories using strict internal and external quality control programs. Moreover, triple test results should always be interpreted by considering analytical and biological variations.

Soluble CD40 ligand levels in patients with hypertension.

CD40 ligand interaction with its receptor (CD40) not only mediates lymphocyte communication, but also associates with chronic inflammation and atherothrombosis. High soluble CD40L (sCD40L) levels were reported in dyslipidemia, diabetes mellitus, and coronary disease. So far, there are no data about sCD40L levels in hypertension. We investigated sCD40L and high sensitive C reactive protein (hsCRP) levels in 30 nonobese young hypertensive men and 30 matched controls. sCD40L and hsCRP levels were not different, and there were no correlations between blood pressure and sCD40L or hsCRP levels. These results might indicate lack of any inflammatory state in new onset hypertension.

Metformin in the treatment of patients with non-alcoholic steatohepatitis.

BACKGROUND: Increased insulin resistance is the major pathogenic mechanism in the development of non-alcoholic steatohepatitis. AIM: To investigate the therapeutic effect of metformin, a well-known insulin-sensitizing agent, in the treatment of non-alcoholic steatohepatitis. METHODS: Thirty-six patients with non-alcoholic steatohepatitis were randomized into two groups. The first group was given lipid and calorie-restricted dietary treatment alone, and the second group was given metformin 850 mg b.d. plus dietary treatment, for 6 months. The changes in biochemical, sonographic and histological parameters were compared. RESULTS: The mean serum alanine/aspartate aminotransferase, insulin and C-peptide levels decreased and the index of insulin resistance improved significantly from baseline in the group given metformin. The mean changes in these parameters in the metformin group were significantly greater than those in the group given dietary treatment alone. Although more patients in the metformin group showed improvement in the necro-inflammatory activity, compared with the group given dietary treatment alone, no significant differences in necro-inflammatory activity or fibrosis were seen between the groups. CONCLUSION: The data suggest that improvement of the insulin sensitivity with metformin may improve the liver disease in patients with non-alcoholic steatohepatitis.

State of the art of new data on the role of magnesium in brain injury: clinical interest of measurements of total and ionized magnesium.

Despite many research studies on traumatic brain injury, few markers have been applicable to diagnose trauma at tissue concentration. Today, the importance of the magnesium ion in posttraumatic homeostasis of brain is a well-known reality. Magnesium concentration affects a number of secondary injury factors including neurotransmitter release, ion changes, oxidative stress, protein synthesis, and energy metabolism. There are many experimental and clinical studies relating to magnesium status in brain injury. It was considered by some authors that only the total form of magnesium should be measured in brain injury. However, recent studies point out that measurement of the ionized form also aids in the intervention of patients with brain trauma. This review aims to explain the role of magnesium in brain injury and to assess the real status of magnesium through pertinent tests.

The midnight-to-morning urinary cortisol increment method is not reliable for the assessment of hypothalamic-pituitary-adrenal insufficiency in patients with end-stage kidney disease.

A previous study reported that the midnight-to-morning urinary cortisol increment method could be used to reliably assess the insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis. The principal aim of the present study is to verify whether the midnight-to-morning urinary cortisol increment is a reliable method for the assessment of the HPA axis in patients with various degrees of impaired kidney function. Fifty-six clinically stable patients with chronic kidney disease (CKD) and 14 healthy subjects were enrolled in the present study. Patients with CKD were divided on the basis of glomerular filtration rate (GFR) into the following arbitrary groups: mild (GFR: 60-89 ml/min/1.73 m2, no.=15), moderate (GFR: 30-59 ml/min/1.73 m2, no.=12) and severe kidney insufficiency (GFR: 15-29 ml/min/1.73 m2, no.=13), and hemodialysis patients. Plasma cortisol and ACTH levels were measured. The HPA axis was assessed by short Synacthen test and overnight dexamethasone suppression test. Double voided urine samples were collected at midnight and waking in the patients and the controls. Urinary free cortisol (UFC) and creatinine levels were measured and the UFC/creatinine ratio (Cort/Cr) was calculated. Then, the Cort/Cr increment was calculated as the morning Cort/Cr minus the midnight Cort/Cr. Baseline plasma cortisol levels were not significantly different between two groups. However, we found that CKD patients had significantly greater plasma ACTH levels than controls. The patients with CKD had also significantly lower morning UFC levels than controls and there was a progressive fall in morning UFC levels with decreasing GFR. The assessment of the HPA axis in patients with GFR lower than 29 ml/min was hampered by falsely abnormal responses to the midnight-to-morning urinary cortisol increment method. Plasma cortisol responded normally to exogenously administered ACTH, while plasma cortisol was suppressed by overnight dexamethasone administration in all patients with CKD. In conclusion, this method is not a reliable test for assessment of the HPA insufficiency in patients with GFR lower than 29 ml/min.

Hypertonic saline in hydatid disease.

The objective of this study was to determine the scolicidal effects of saline in different concentrations using different exposure times and to examine whether hypertonic saline can be used to irrigate the abdomen when there is a free intraperitoneal perforation of hydatid disease. Various concentrations of saline solutions (0.09%, 3.0%, 6.5%, 10%, 15%, 20%, 25%, 30%) were added to concentrated echinococcus granulosus sediments for the following times: 1, 2, 3, 4, 5, 10, 15, 30, 45, and 60 minutes. Normal (0.09%), 3.0%, and 6.5% saline resulted in high viability ratios after 60 minutes' exposure. Complete lethality for 10%, 15%, 20%, 25%, and 30% saline occurred at the end of 75, 10, 6, 3, and 3 minutes, respectively. During the second part of the study, 20 Sprague-Dawley rats were used for abdominal saline irrigation in four groups: 30% NaCl for 3 minutes; 20% NaCl for 6 minutes; intravenous isotonic dextrose water and furosemide plus 30% NaCl irrigation for 3 minutes; the same prophylactic therapy plus 20% NaCl irrigation for 6 minutes. Sodium and chloride values rose significantly (20-30%) shortly after hypertonic saline irrigation in each group (p < 0.01). Support with isotonic dextrose and furosemide before irrigation did not have any beneficial effect on biochemical values or mortality. The 24- and 48-hour mortality rates were 70% and 90%, respectively. These studies illustrate that the scolicidal effect of hypertonic saline is limited in low concentrations, but an increase in the concentration can augment its adverse effects. Peritoneal irrigation with hypertonic saline should be avoided for intraabdominal perforated hydatid disease. Therefore, we concluded that hypertonic saline is not a good scolicidal agent to prevent recurrence of hydatid disease.

Improved glycemic control increases fasting plasma acylation-stimulating protein and decreases leptin concentrations in type II diabetic subjects.

Acylation-stimulating protein is an adipocyte-derived protein that has recently been suggested to play an important role in the regulation of triglyceride storage. To date, little information has been reported with regard to fasting acylation-stimulating protein levels and its relation to metabolic control, leptin, and/or lipids in subjects with diabetes mellitus. We therefore evaluated fasting acylation-stimulating protein, leptin, and lipid levels before and 4 months after improving glycemic control with sulfonylurea treatment in a group of poorly controlled obese women with type 2 diabetes and in age- and body mass index-matched nondiabetic obese women. Fasting plasma acylation-stimulating protein (49.67 +/- 19.73 vs. 48.49 +/- 20.70 nmol/liter) and leptin concentrations (33.7 +/- 23.2 vs. 26.2 +/- 10.6 ng/ml) were not significantly different between the groups. Improvement of glycemic control produced parallel falls in fasting blood glucose and hemoglobin A1c. Plasma leptin concentrations were also significantly reduced (33.69 +/- 23.2 vs. 22.73 +/- 11.26 ng/ml; P = 0.036), whereas fasting acylation-stimulating protein concentrations were significantly increased after treatment (48.49 +/- 20.70 vs. 72,82 +/- 29,72 nmol/liter; P = 0.004). Nevertheless, lipids and apolipoprotein B did not significantly improve. We could not find any correlation between elevated acylation-stimulating protein levels and changes in body mass index, glucose, insulin, hemoglobin A1c, leptin, or lipid levels. Similarly, the decrement in circulating leptin levels observed after treatment did not correlate with changes in the levels of glucose, insulin, hemoglobin A1c, or any lipid parameters. We conclude that improved glycemic control increases fasting acylation-stimulating protein and decreases leptin concentrations, but not corrects critical lipid abnormalities in type 2 obese diabetic subjects. Moreover, altered plasma acylation-stimulating protein levels are not associated with changes in body mass index or lipid, leptin, insulin, or glucose levels. Thus, our findings suggest that improved glycemic control or insulin resistance is not responsible for abnormal fatty acid trapping, and failure of lipids to improve after treatment in our patients is consistent with the acylation-stimulating protein resistance concept.

Octreotide administration in diabetic rats: effects on renal function and morphology.

The effects of synthetic somatostatin analogue, octreotide, on fractional kidney weight (FKW), urinary protein excretion (UPE), creatinine clearance (Cl(cre)) and renal morphological changes were studied in alloxan-diabetic and non-diabetic rats comparatively. Diabetic rats were treated with twice daily s.c. injections of octreotide (2x2.5 microg) for 90 days. Untreated diabetic and non-diabetic animals were used as reference. The body weights and blood glucose levels of the animals were followed-up throughout the study period. After 90 days, FKW and renal morphology were evaluated. When compared to octreotide-treated diabetic group (O-D: 1.96+/-0. 23), normal control rats (NC: 1.24+/-0.05) showed a lower FKW (P<0. 05) and the FKW value of non-treated diabetic controls (DC: 2.74+/-0. 17) were significantly higher (P<0.05). Cl(cre) values were calculated at 45th and 90th days. At the 45th day, Cl(cre) values (ml/min) of O-D group (0.75+/-0.06) and NC group (0.56+/-0.09) were significantly lower than non-treated DC group (1.05+/-0.1) (P<0.05). However, at the 90th day no significant difference in Cl(cre) was observed. At the 45th day, UPE (mg/dl/day) was significantly higher in non-treated DC group (1000.45+/-392.38) when compared to NC group (236+/-36.59) (P<0.005) and UPE levels of O-D group were only slightly lower than that of non-treated diabetic group. At the 90th day, no significant beneficial effect of octreotide on UPE was observed. Octreotide did not prevent the histopathological changes related to diabetes. In conclusion, 5 microg/day octreotide administrations to diabetic rats for 90 days prevented renal weight increase but this treatment were insufficient to decrease the histopathological changes, UPE and increased Cl(cre).