BACKGROUND. Patients with coronavirus disease 2019 (COVID-19) develop pneumonia generally associated with lymphopenia and a severe inflammatory response due to uncontrolled cytokine release. These mediators are transcriptionally regulated by the JAK/STAT signaling pathways, which can be disabled by small molecules. METHODS. We treated a group of patients (n = 20) with baricitinib according to an off-label use of the drug. The study was designed as an observational, longitudinal trial and approved by the local ethics committee. The patients were treated with 4 mg baricitinib twice daily for 2 days, followed by 4 mg per day for the remaining 7 days. Changes in the immune phenotype and expression of phosphorylated STAT3 (p-STAT3) in blood cells were evaluated and correlated with serum-derived cytokine levels and antibodies against severe acute respiratory syndrome–coronavirus 2 (anti–SARS-CoV-2). In a single treated patient, we also evaluated the alteration of myeloid cell functional activity. RESULTS. We provide evidence that patients treated with baricitinib had a marked reduction in serum levels of IL-6, IL-1β, and TNF-α, a rapid recovery of circulating T and B cell frequencies, and increased antibody production against the SARS-CoV-2 spike protein, all of which were clinically associated with a reduction in the need for oxygen therapy and a progressive increase in the P/F (PaO₂, oxygen partial pressure/FiO₂, fraction of inspired oxygen) ratio. CONCLUSION. These data suggest that baricitinib prevented the progression to a severe, extreme form of the viral disease by modulating the patients’ immune landscape and that these changes were associated with a safer, more favorable clinical outcome for patients with COVID-19 pneumonia. TRIAL REGISTRATION. ClinicalTrials.gov NCT04438629. FUNDING. This work was supported by the Fondazione Cariverona (ENACT Project) and the Fondazione TIM.

BACKGROUND: Hypertension is a major global health issue. Aldosterone synthase inhibitors (ASIs) have emerged as a promising therapeutic strategy for blood pressure control. METHODS: A thorough search of the MEDLINE and Embase databases up to March 30, 2024, identified randomized trials comparing ASIs with a placebo for hypertension treatment. Data extraction was done independently by 2 authors. Both random-effects (Restricted maximum likelihood) and fixed-effects meta-analyses were conducted to account for diversity and study size, respectively. Risk ratios for binary outcomes and mean differences for continuous outcomes were calculated. RESULTS: Seven randomized controlled trials involving 1440 patients (mean age, 60 years; 39% women) were included. The analysis showed that ASIs reduced office systolic blood pressure by 6.3 mm Hg ([95% CI, –8.8 to –3.8]; P <0.0001) and diastolic blood pressure by 2.2 mm Hg ([95% CI, –4.2 to –0.2]; P =0.03). The risk ratio for adverse events was 1.1 ([95% CI, 0.9–1.2]; P =0.3), with a similar trend for serious adverse events (risk ratio, 1.0 [95% CI, 0.5–2.3]; P =0.95). No treatment-related deaths occurred. However, the risk of hyperkalemia was higher with ASIs (risk ratio, 2.5 [95% CI, [1.2–5.4]; P <0.02). CONCLUSIONS: ASIs effectively reduce systolic and diastolic blood pressure in hypertensive patients and have a tolerable safety profile. The increased risk of hyperkalemia requires careful monitoring. These findings suggest ASIs are a potential treatment option for hypertension, pending further research in larger studies.

Due to the widespread use of the aldosterone to renin ratio (ARR), primary aldosteronism is currently recognized as a frequent cause of secondary hypertension. After a positive screening, primary aldosteronism diagnosis needs confirmation by an inhibitory test such as intravenous saline load (ivSLT). The aim of the present study was to investigate the role of female hormones in primary aldosteronism diagnosis, by evaluating possible differences by sex on ARR screening, on the rate of ivSLT response and analyzing the influence of free and oral contraceptive-induced menstrual cycle on ARR. We examined ARR in 103 healthy normotensive volunteers, 81 hypertensive patients who underwent ivSLT, 33 healthy women during free menstrual cycle and after oral contraceptive therapy. A significantly higher proportion of normotensive women than men had an elevated ARR (13.6 versus 2.3%, P < 0.05). In 44 out of 81 hypertensive patients, diagnosis of primary aldosteronism was confirmed by ivSLT. Patients with positive and negative ivSLT differed only for sex distribution: 85.2% of men had the primary aldosteronism diagnosis confirmed, compared with 38.9% of women. In healthy women, renin and aldosterone concentrations increased from the follicular to luteal phase of menstrual period, with unchanged ARR. By contrast, renin nearly halved, aldosterone slightly decreased and ARR doubled after oral contraceptive therapy. ARR screening fails to predict positive ivSLT in most (60.2%) hypertensive women as compared with 14.8% of hypertensive men. ARR is more often increased in normotensive women than men. Oral contraceptive may affect ARR contributing to the diagnostic inaccuracy in women.

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BACKGROUND: Primary aldosteronism (PA) is a common curable cause of secondary hypertension that significantly increases left ventricular mass (LVM) and predisposes patients to adverse cardiovascular outcomes. Although adrenalectomy and medical therapy with mineralocorticoid receptor antagonists (MRAs) are both used to treat PA, their long-term comparative efficacy in reversing cardiac structural changes remains debated. METHODS: We systematically searched MEDLINE and Embase for prospective and retrospective clinical trials published up to November 22, 2024, with a minimum follow-up of 6 months that reported changes in LVM in patients with PA treated with adrenalectomy or MRAs. Data were independently extracted by 2 reviewers, and risk-of-bias assessments were conducted using standardized tools. The primary outcome was the percentage reduction in indexed LVM; secondary outcomes included changes in cardiac remodeling, and systolic and diastolic function parameters. RESULTS: Seventeen studies comprising 1696 patients (49% adrenalectomy, 51% MRA therapy) were analyzed. Adrenalectomy yielded a significantly greater indexed LVM reduction (mean difference, −3.5% [95% CI, −4.9% to −2.2%]; P <0.0001) and a 32% reduction in left ventricular hypertrophy risk ratio, compared with a 19% reduction with MRAs. Meta-regression revealed that shorter hypertension duration predicted greater LVM regression following adrenalectomy, whereas high dietary sodium attenuated MRA effects. In addition, left ventricular ejection fraction improved modestly after adrenalectomy. CONCLUSIONS: Adrenalectomy provides superior long-term regression of LVM and left ventricular hypertrophy compared with MRAs in PA, supporting its use as the first-line treatment for unilateral PA. Future research should compare emerging nonsteroidal MRAs and aldosterone synthase inhibitors to further optimize cardiac remodeling outcomes.