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Background: Primary aldosteronism (PA) is the most frequent form of potentially reversible hypertension and coronary-pulmonary fistulas are increasingly recognized during routine coronary angiography or multidetector computed tomography for analysis of chest pain in hypertensive patients. Aldosterone hypersecretion has been associated with endothelial proliferation and pathological remodeling of the heart and arteries, though coronary artery fistulas have never been reported in patients with PA. Case presentation: The authors report the first case of PA with dilated cardiomyopathy unusually associated with electrocardiographic changes after normalization of hypokalemia and with the finding of a coronary-pulmonary fistula during coronary angiography. The clinical presentation and our diagnosis and treatment decision-making in the COVID-19 era are discussed below. Conclusions: Our case suggests a potential link between hypertensive patients with coronary artery fistulas and PA.

The Aldosteronoma Resolution Score (ARS) is the most studied scoring system for predicting the high likelihood of hypertension cure after adrenalectomy for unilateral primary aldosteronism (PA). However, the ARS's accuracy in PA patients worldwide is uncertain. We aimed to perform a meta-analysis of the accuracy, discrimination, and calibration of the ARS using stratum-specific likelihood ratios (SSLR) by organizing available data from cohort studies. We searched PubMed, Embase (Ovid), the Cochrane CENTRAL, Web of Science to November 2021 according to PRISMA statement. The quality assessment used adapted TRIPOD and PROBAST criteria. Thirteen studies comprising 2158 PA patients from North America (43%), Europe (32%), Asia (22%), and other continents, were included. The pooled estimate of the area under the receiver operating characteristic curve for all studies was 0.77 (95% CI: 0.73-0.81), and the ratio of the observed to expected complete resolution of hypertension (CRH) for all studies was 0.9 (95% CI: 0.8-1.0). The summary estimates of the SSLR for all studies were 0.31, 0.89, and 3.1, for the low (ARS 0-1), medium (ARS 2-3), and high-likelihood group (ARS 4-5) of CRH, respectively. However, substantial heterogeneity existed among studies. Follow-up period, and adrenalectomy AVS (adrenal vein sampling)-guided served as potential sources of heterogeneity for quantitative studies, which were measurement and reference standard for qualitative studies selection. In conclusion, in patients with unilateral PA, the ARS is currently an accurate prediction tool, the easiest and cheapest, for identifying long-term high likelihood of CRH after adrenalectomy, particularly when the adrenalectomy is AVS-guided.

Primary aldosteronism is the most frequent forms of curable hypertension and elevated aldosterone levels have been associated with endothelial proliferation and pathological remodeling of the heart and arteries; however, coronary arterial abnormalities have never been reported in patients with primary aldosteronism. We report the case of a 53-year-old Caucasian obese man (BMI 37 Kg/m 2 ) with recent history of hypertension, fatigue and subjective dyspnea who was admitted to our hospital after performing an outpatient echocardiography that showed hypertensive and ischemic heart disease in dilated phase (LVEDVI 95 mL/m 2 ; LVEF 43%). His laboratory results showed hypokalemia (3 mmol/L) and an elevated aldosterone-renin ratio [(294 ng/L)/(1μU/mL)]. After case confirmation with saline infusion test, the abdominal CT scan showed a subcentimeter adenoma in the right adrenal gland. Surprisingly we noticed that, after oral potassium correction, the electrocardiogram revealed a symmetrical T-wave inversion and subsequently a coronary angiography detected a coronary artery fistula between the left anterior descending artery and the pulmonary artery in the absence of significant stenosis. In the Italy's CoViD-19 pandemic full spread, we preferred to postpone the diagnosis of the lateralization of aldosterone hypersecretion by adrenal vein sampling and we started a mineralocorticoid receptor antagonist with a clinical follow-up of cardiovascular symptoms for the optimal treatment of coronary artery fistula. After about two months of follow-up, the patient remains asymptomatic with good blood pressure control, normal potassium levels and significant echocardiographic improvement (LVEDVI 67 mL/m 2 ; LVEF 51%). Our case highlights a possible association between hypertensive patients with coronary artery fistulas and primary aldosteronism. We recommend cardiologists and clinicians to maintain a high level of suspicion of primary aldosteronism in these patients.

We recently demonstrated in an immortalized thyroid cell line that integrin stimulation by fibronectin (FN) simultaneously activates two signaling pathways: Ras/Raf/MAPK kinase (Mek)/Erk and calcium Ca2+/calcium calmodulin-dependent kinase II (CaMKII). Both signals are necessary to stimulate Erk phosphorylation because CaMKII modulates Ras-induced Raf-1 activity. In this study we present evidence that extends these findings to normal human thyroid cells in primary culture, demonstrating its biological significance in a more physiological cell model. In normal thyroid cells, immobilized FN-induced activation of p21Ras and Erk phosphorylation. This pathway was responsible for FN-induced cell proliferation. Concurrent increase of intracellular Ca2+ concentration and CaMKII activation was observed. Both induction of p21Ras activity and increase of intracellular Ca2+ concentration were mediated by FN binding to alphavbeta3 integrin. Inhibition of the Ca2+/CaMKII signal pathway by calmodulin or CaMKII inhibitors completely abolished the FN-induced Erk phosphorylation. Binding to FN induced Raf-1 and CaMKII to form a protein complex, indicating that intersection between Ras/Raf/Mek/Erk and Ca2+/CaMKII signaling pathways occurred at Raf-1 level. Interruption of the Ca2+/CaMKII signal pathway arrested cell proliferation induced by FN. We also analyzed thyroid tumor cell lines that displayed concomitant aberrant integrin expression and signal transduction. These data confirm that integrin activation by FN in normal thyroid cells generates Ras/Raf/Mek/Erk and Ca2+/CaMKII signaling pathways and that both are necessary to stimulate cell proliferation, whereas in thyroid tumors integrin signaling is altered.

Role of different dialysis membranes in the release of interleukin-6-soluble receptor in uremic patients.BackgroundInterleukin-6 (IL-6) exerts its actions through a cell-surface receptor system that consists of two transmembrane subunits: the IL-6 binding glycoprotein gp 80 (IL-6R) and the signal-transducing component (gp 130). Soluble forms of the IL-6R (sIL-6R) are generated by shedding of the membrane-associated proteins. The sIL-6R binds the ligand IL-6 with comparable affinity as the membrane-associated IL-6R and enhances the actions of IL-6.MethodsOur aim was to evaluate the role of both uremia and different dialysis membranes on peripheral blood mononuclear cell (PBMC) release (either in absence or in presence of mitogen stimulation) and plasma levels of sIL-6R. Ten patients chronically dialyzed with cuprophan membranes (CU), eight patients on regular dialysis treatment with polymethylmethacrylate (PMMA) membranes, 11 uremic nondialyzed patients (UR), and 12 healthy subjects (CON) were included in the study.ResultsPBMCs harvested from CU spontaneously released significantly (P < 0.01) greater amounts of sIL-6R (881.8 ± 80.1 pg/mL), as compared with CON (267.5 ± 26.5 pg/mL), UR (258.4 ± 38.1 pg/mL), and PMMA (288.4 ± 24.6 pg/mL). Under mitogenic stimulation, the sIL-6R release was significantly (P < 0.01) increased in all groups. The greater PBMC production of sIL-6R in CU was followed by significantly (P < 0.01) higher levels of circulating soluble receptors (48.7 ± 2.5 ng/mL, 60%), as compared with CON (30.5 ± 1.9 ng/mL). UR also showed high circulating levels of sIL-6R (53.3 ± 5.9 ng/mL), probably secondary to an impaired urinary excretion. Circulating levels of sIL-6R in PMMA were comparable to CON (30.3 ± 3.3 ng/mL). Either the absence of monocyte activation or the adsorption of sIL-6R on the hydrophobic PMMA surface could explain this finding.ConclusionsThese results suggest an important role for poor dialysis biocompatibility of CU on the release of sIL-6R, which increases sIL-6R plasma levels, thereby enhancing the inflammatory effects of IL-6.

The expression of the beta1 family of integrins was determined in thyroid follicular cells from patients with Graves' disease (GD). Integrin expression was quantitated by flow fluorocytometry of single cell suspensions with antibodies against the common beta1 chain and the alpha1-alpha6 subunits. Results indicated that also in thyroid glands of GD, as previously observed in nodular goiters, two follicular cell populations with different patterns of beta1 integrin expression coexist (VLAalpha3beta1 and VLAalpha1,3,5,6beta1). The VLAalpha1,3,5,6beta1 thyrocyte population in GD was more abundant than in nodular goiters, ranging from 40 to 70% of the total follicular cells and the overall expression of the beta1 integrins was a two-fold higher. In thyrocytes from patients with GD cultured in vitro, alpha3 and alpha2 expression was regulated by cell-to-cell contact as previously described in normal thyroid cells, while the expression of alpha1, alpha5 and alpha6 was quickly lost during the culture. Our data suggest that the integrin profile of the VLAalpha1,3,5,6beta1 thyrocyte population in GD is induced by micro-environmental conditions rather than being the expression of a constitutive phenotype.