IL-6 and SAA-Strong Predictors for the Outcome in COVID-19 CKD Patients.

In this prospective study, we assessed biomarkers of inflammation (IL-6 and SAA) from the serum of 120 COVID-19 patients, of whom 70 had chronic kidney disease. All the samples were taken at emergency-department (ED) admission. Our goal was to relate the biomarkers to the results of death and acute kidney injury. All the patients underwent chest computer tomography to estimate the severity score (0-5), which was performed at hospital admission. Finally, biomarkers were also evaluated in a healthy control group and in non-COVID-19-CKD patients. IL-6 and SAA were statistically different between the subgroups, i.e., they were significantly increased in patients with COVID-19. Both of the biomarkers (IL-6 and SAA) were independently associated with mortality, AKI and a higher grade of pathological changes in the lung's parenchyma. Both high baseline levels of IL-6 and SAA on hospital admission were highly correlated with a later ventilatory requirement and mortality, independent of hospital stay. Mortality was found to be significantly higher when the chest CT severity score was 3-4, compared with a severity score of 0-2 (p < 0.0001). Conclusions: at the admission stage, IL-6 and SAA are useful markers for COVID-19 patients with CKD.

Pioglitazone and the Risk of Bladder Cancer: A Meta-Analysis.

People with type 2 diabetes are at increased risk of bladder cancer. Pioglitazone is said to increase it further, although published evidence is mixed. We conducted a meta-analysis to determine if any link between the use of pioglitazone and an increased risk of bladder cancer can be found. A comprehensive literature search was conducted through electronic databases as well as registries for data of clinical trials to identify studies that investigate the effect of pioglitazone on bladder cancer in diabetic patients. We used the risk ratio (RR) and the hazard ratio (HR) provided by the studies to illustrate the risk of occurrence of bladder cancer in the experimental group compared to that in the control group. Fourteen studies using RR and 12 studies using HR were included in the analysis. The overall RR was 1.13 with 95% CI (0.96-1.33) with low heterogeneity among the studies using RR, suggesting that no connection exists between use of pioglitazone and the risk of bladder malignancy. The summary HR was 1.07 (0.96-1.18) allowing us to affirm that there is no link between long-term use of pioglitazone and bladder cancer. Our results support the hypothesis of no difference in the incidence of bladder cancer among the pioglitazone group and the nonuser group. Our conclusion is that the explanation of hypothetically increased risk of bladder malignancy should be attributed to other factors. FUNDING: Tchaikapharma High Quality Medicines Inc.

Mortality in Cushing's syndrome: data from 386 patients from a single tertiary referral center.

OBJECTIVE: Data on the incidence, mortality, and causes of death in patients with Cushing's syndrome (CS) are scarce, due to the rarity of CS. The aim of the study was to analyze mortality in a large cohort of patients of all etiologies and to determine the cause of death. DESIGN: This was a retrospective study of patients with CS, treated over a period of 45 years in the main tertiary referral center in Bulgaria. METHODS: Three hundred and eighty-six patients with CS of all etiologies were included. The main outcome measures were the standardized mortality ratio (SMR) and the cause of death. RESULTS: Mean (S.D.) age at diagnosis was 3813 years; 84% of patients were women; mean follow-up was 85 months (rangE: 0-494 months). The SMR in the CS cohort was 4.05 (95% CI 2.50-5.80) (P<0.0001). The following subgroups did not have a significantly increased SMR: patients with Cushing's disease SMR - 1.88 (95% CI 0.69-4.08), adrenal adenomas 1.67 (95% CI 0.20-6.02), and ACTH-independent bilateral adrenal hyperplasia 1.14 (95% CI 0.21-6.34). Patients with adrenal carcinomas, ectopic CS, and those with CS of undetermined etiology had significantly increased SMR: 48.00 (95% CI 30.75-71.42), 13.33 (95% CI 0.00-24.59), and 4.00 (95% CI 0.48-14.45) respectively (P<0.0001). The significant predictors for mortality were active disease at death, age, male sex, etiology of the disease, and the overall duration of active disease. The major causes of death were vascular events (40%) - cardiovascular 29%, and cerebrovascular 11% - followed by infections (12%). CONCLUSIONS: Patients with CS have increased mortality due to vascular events and infections.

Transforming growth factor ß1 is not a reliable biomarker for valvular fibrosis but could be a potential serum marker for invasiveness of prolactinomas (pilot study).

BACKGROUND: Transforming growth factor ß1 (TGFß1) signaling pathway is crucial for both human fibrogenesis and tumorigenesis. OBJECTIVE: This study aimed to investigate the usefulness of TGFß1 and matrix metalloproteinase 2 (MMP2) as potential circulating markers for fibrotic valvular heart disease (FVHD) and invasiveness as well as of Fetuin A as a marker for calcification in patients with prolactinomas. DESIGN: The study population consisted of 147 subjects divided into four groups: 30 dopamine agonist (DA)-treated prolactinoma patients with proven FVHD and three control groups with normal echocardiograms: 43 DA-treated patients, 26 naïve patients, and 48 healthy subjects. RESULTS: We observed significantly higher serum TGFß1 levels in all three patient groups than in the healthy subjects (21.4 ± 8.86 vs 19.1 ± 9.03 vs 20.7±11.5 vs 15.8 ± 7.2 ng/ml; P=0.032). Moreover, TGFß1 levels were significantly higher in patients with macroprolactinomas and invasive prolactinomas than in those with microprolactinomas and noninvasive tumors respectively. In addition, a strong positive linear relationship between TGFß1 levels and invasiveness score (ρ=0.924; P<0.001) and a moderate correlation between TGFß1 levels and tumor volume (r=0.546; P<0.002) were observed in patients with invasive prolactinomas. By contrast, prolactin (PRL) levels exhibited a better correlation with tumor volume (r=0.721; P<0.001) than with invasiveness score (ρ=0.436; P<0.020). No significant difference was observed in Fetuin A levels between patients with FVHD and healthy controls. Results concerning MMP2 were unclear. CONCLUSIONS: TGFß1, MMP2, and Fetuin A are not reliable biomarkers for valvular fibrosis and calcification in DA-treated patients with prolactinomas, but TGFß1 may represent a useful serum marker for tumor invasiveness. The simultaneous determination of TGFß1 and PRL levels could improve the noninvasive assessment of prolactinoma behavior.

Increased prevalence of subclinical cardiac valve fibrosis in patients with prolactinomas on long-term bromocriptine and cabergoline treatment.

BACKGROUND: In contrast to cabergoline, evidence-based information about a possible profibrotic effect of bromocriptine in prolactinoma patients is extremely limited. OBJECTIVE: To assess the prevalence of valvular lesions among patients on long-term bromocriptine or cabergoline therapy. DESIGN: Case-control study. METHODS: A transthoracic echocardiographic evaluation was performed in 334 subjects divided into four groups: 103 cabergoline treated, 55 bromocriptine treated, 74 naïve patients, and 102 controls. RESULTS: Clinically relevant valve regurgitations were equally prevalent in all investigated groups whereas subclinical valve fibrosis was significantly more frequent in both bromocriptine- and cabergoline-treated patients (40 vs 43.6 vs 21.6 vs 23.5%; P=0.004). The odds ratio (OR) for developing valvular fibrosis was 2.27 (95% CI 1.17-4.41; P=0.016) for cabergoline and 2.66 (95% CI 1.22-5.78; P=0.014) for bromocriptine groups compared with subjects not exposed to dopamine agonists (DAs). A significantly higher pulmonary arterial pressure corresponding to the longer treatment duration was observed among patients taking bromocriptine compared with cabergoline-treated subjects. CONCLUSIONS: Long-term treatment with cabergoline and bromocriptine seems not to be associated with an increased risk of clinically significant valve disease but possible subclinical lesions should be expected. An echocardiographic examination is recommended at the beginning and periodically during therapy with DAs acting as full or partial agonists of 5-hydroxytrytamine 2B receptors (cabergoline and bromocriptine). Bromocriptine seems not to be a safe alternative for patients receiving cabergoline treatment who have preexisting or diagnosed abnormalities suggesting valvular, interstitial myocardial, or pulmonary fibrosis. Further studies are needed to investigate the possible impact of DA treatment on pulmonary arterial pressure.

Prognostic value of some ovarian reserve tests in poor responders.

BACKGROUND: The objective of this study was to determine the prognostic value of the basal estradiol (E2) and inhibin-B levels, the antral follicle count (AFC), and the clomiphene citrate challenge test (CCCT) of ovarian response in controlled ovarian hyperstimulation (COH), in an outcome with normal follicle-stimulating hormone (FSH) concentration in the early follicular phase of the menstrual cycle. METHODS: Fifty-two patients undergoing IVF treatment were included in the study. Blood samples were collected for assessment of basal E2, FSH, and inhibin-B levels. Transvaginal ultrasound of an unstimulated cycle was performed to determine the mean antral follicle count (AFC). Serum FSH concentration was measured again on day 10 for CCCT performance. RESULTS: The mean values of women's age, and basal and day 10 FSH levels were significantly higher in cancelled cycles than in the control group, whereas basal inhibin-B and AFC were significantly higher in the latter. The mean basal E2 concentration was similar in both groups. The results from the logistic regression analysis show that CCCT (cut-off point FSH > 12.5 mIU/ml; AUCROC = 0.90) was a better single predictor of poor ovarian response than AFC (AUCROC = 0.85) and inhibin-B (AUCROC = 0.79) with a correct prediction for CCCT (86.5%), antral follicle count (84.6%), and for inhibin-B (82.7%). CONCLUSIONS: In women with normal basal FSH level, the determination of E2 has no prognostic value for the outcome of poor responders. However, CCCT, AFC, and inhibin-B tests, when applied separately, produce good prognostic values. CCCT is the best single predictor of poor ovarian response, followed by antral follicle count and basal inhibin-B values. In spite of that, CCCT does not add significantly to the simpler AFC ultrasound test in the prediction of poor ovarian response.

Circulating vascular endothelial growth factor and active renin concentrations and prostaglandin E2 urinary excretion in patients with adrenal tumours.

OBJECTIVES: The aim of the present study was to determine vascular endothelial growth factor (VEGF), prostaglandin E(2) (PGE(2)) and active renin levels in patients with hormonally active adrenal tumours. DESIGN: The study was comprised of 16 patients with primary aldosteronism, 13 patients with active Cushing's syndrome due to adrenal adenomas, 8 patients with adrenal carcinomas, 19 patients with phaeochromocytoma and 19 healthy volunteers. METHODS: Active renin in plasma was determined by a two-site immunoradiometric assay. VEGF in sera samples and PGE(2) in 24-h urine were measured by ELISA. RESULTS: VEGF was significantly elevated in all the four groups of patients as compared with the controls. VEGF levels in patients with Cushing's syndrome were higher than those in patients with primary aldosteronism. Patients with adrenal carcinomas had the highest VEGF levels and the differences reached significance as compared with patients with primary aldosteronism and phaeochromocytoma. PGE(2) levels were not significantly different among groups. Active renin was significantly the lowest in patients with primary aldosteronism and significantly the highest in patients with phaeochromocytoma compared with the controls. Active renin in patients with primary aldosteronism was significantly lower than in those with Cushing's syndrome, phaeochromocytoma and adrenal carcinoma. CONCLUSIONS: Our data indicated that the mean level of VEGF in patients with all investigated adrenal tumours was significantly higher than in healthy controls. The cortisol-producing tumours appear to have increased angiogenic potential. Angiogenesis is probably associated not only with malignancy but also with functional activity of the adrenal tumors.