Primary aldosteronism is recognized as the most frequent cause of secondary hypertension, and its screening is expected to become a routine evaluation in most patients with hypertension. The interference of antihypertensive therapies with the aldosterone-to-renin ratio during screening process is a major confounder. Renin-angiotensin-aldosterone system Triple-A analysis is a novel liquid chromatography/tandem mass spectrometry diagnostic assay that allows simultaneous quantification of aldosterone, equilibrium Ang I (angiotensin I), and Equilibrium Ang II in a single sample of serum. We performed a comparative evaluation of the diagnostic performance of the aldosterone-to-Ang II ratio and 5 renin-based diagnostic ratios, differing in methods to determine aldosterone levels and renin activity in a cohort of 110 patients with hypertension (33 patients with confirmed primary aldosteronism and 77 with essential hypertension). All ratios showed comparable areas under the curves ranging between 0.924 and 0.970 without significant differences between each other. The evaluation of the Ang II-to-Ang I ratio revealed persistent drug intake in some patients as cause for suppressed renin-based diagnostic ratios, while aldosterone-to-Ang II ratio remained unaffected. The Youden index optimal cutoff value for the aldosterone-to-Ang II ratio was 6.6 ([pmol/L]/[pmol/L]) with a sensitivity of 90% and a specificity of 93%, proving noninferiority compared with the aldosterone-to-renin ratio while pointing to the potential for an interference-free application in patients under ACE (angiotensin-converting enzyme) inhibitor therapy. This study shows for the first time the accuracy and reliability of renin-angiotensin-aldosterone system triple-A analysis for the screening of primary aldosteronism that can be applied in clinical routine.

Context Identification of patients with endocrine forms of hypertension (EHT) (primary hyperaldosteronism [PA], pheochromocytoma/paraganglioma [PPGL] and Cushing syndrome [CS]) provides the basis to implement individualized therapeutic strategies. Targeted metabolomics (TM) have revealed promising results in profiling cardiovascular diseases and endocrine conditions associated with hypertension. Objective Use TM to identify distinct metabolic patterns between primary hypertension (PHT) and EHT and test its discriminating ability. Design Retrospective analyses of PHT and EHT patients from a European multicentre study (ENSAT-HT). TM was performed on stored blood samples using liquid chromatography mass spectrometry. To identify discriminating metabolites a “classical approach” (CA) (performing a series of univariate and multivariate analyses) and a “machine learning approach” (MLA) (using Random Forest) were used. Patients The study included 282 adult patients (52% female; mean age 49 years) with proven PHT (n=59) and EHT (n=223 with 40 CS, 107 PA and 76 PPGL), respectively. Results From 155 metabolites eligible for statistical analyses, 31 were identified discriminating between PHT and EHT using the CA and 27 using the MLA, of which 15 metabolites (C9, C16, C16:1, C18:1, C18:2, arginine, aspartate, glutamate, ornithine, spermidine, lysoPCaC16:0, lysoPCaC20:4, lysoPCaC24:0, PCaeC42:0, SM C18:1, SM C20:2) were found by both approaches. The ROC curve built on the top 15 metabolites from the CA provided an area under the curve (AUC) of 0.86, which was similar to the performance of the 15 metabolites from MLA (AUC 0.83). Conclusions TM identifies distinct metabolic pattern between PHT and EHT providing promising discriminating performance.

Prognosis after mild traumatic brain injury (MTBI) on oral anticoagulant therapy (OAT) is uncertain. We evaluated the rate of immediate and delayed traumatic intracranial hemorrhage (ICH) comparing vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs) and the safety of a clinical management protocol. In this single-center prospective observational study, we enrolled 220 patients on OAT with MTBI. After a first negative CT scan, asymptomatic patients underwent a close neurological observation; if neurologically stable, they were discharged without a second CT scan and followed up for 1 month. Out of the 220 patients, 206 met the inclusion criteria. 23 of them (11.2%) had a positive first CT scan for ICH. Only 1 (0.5%, 95% CI 0.0-1.4%) died because of ICH; no one required neurosurgical intervention. The observed prevalence rate of immediate ICH resulted statistically higher in VKAs-treated patients compared to those treated with DOACs (15.7 vs. 4.7%, RR 3.34, 95% CI 1.18-9.46, P < 0.05). In the 1-month follow-up, 5 out of the 183 patients with a negative CT scan were lost. Out of the remaining 178 patients, only 3 showed a delayed ICH (1.7%, 95% CI 0.0-3.6%), 1 of them died (0.6%, 95% CI 0.5-1.7%) and the others did not require neurosurgical intervention. DOACs resulted safer than VKAs also in the setting of MTBI. In our observation, the rate of delayed hemorrhage was relatively low. Patients presenting with a negative first CT scan and without neurological deterioration could be safely discharged after a short period of in-ward observation with a low rate of complications and without a second CT scan.

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time. Therefore, we herein review recent advances in relevant studies, including histopathological and molecular analyses, to summarize the current status of potential prognostic factors in patients with PHEO/PGL.