Drug-resistant hypertension (RH) is a very high-risk condition involving many hypertensive patients, in whom primary aldosteronism (PA) is commonly overlooked. Hence, we aimed at determining if (1) adrenal vein sampling (AVS) can identify PA in RH patients, who are challenging because of receiving multiple interfering drugs; (2) AVS-guided adrenalectomy can resolve high blood pressure (BP) resistance to treatment in these patients. Based on a pilot study we selected from 1016 consecutive patients referred to our Centre for 'difficult-to-treat' hypertension those with RH, for an observational prospective cohort study. We excluded those non-adherent to treatment (by therapeutic drug monitoring) and those with pseudo-RH (by 24-h BP monitoring), which left 110 patients who met the European Society of Cardiology/European Society of Hypertension (ESC/ESH) 2013 definition for RH. Of these patients, 77 were submitted to AVS, who showed unilateral PA in 27 (mean age 55 years; male/female 19/8). Therefore, these patients underwent AVS-guided laparoscopic unilateral adrenalectomy, which resolved RH in all: 20% were clinically cured in that they no longer needed any antihypertensive treatment; 96% were biochemically cured. Systolic and diastolic BP fell from 165/100 ± 26/14 mmHg at baseline, to 132/84 ± 14/9 mmHg at 6 months after surgery (P<10-4 for both) notwithstanding the fall of number and defined daily dose (DDD) of antihypertensive drugs required to achieve BP control (P<10-4 for both). A prominent regression of cardiac and renal damage was also observed. Thus, the present study shows the feasibility of identifying PA by AVS in RH patients, and of resolving high BP resistance to treatment in these patients by AVS-guided adrenalectomy.
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Mol Ther
January 2025
Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School; 30625 Hannover, NI, Germany. Electronic address:
Antibody-mediated rejection (AMR) remains a major complication after solid organ transplantation (SOT). Current treatment options are inefficient and result in drastic impairment of the general immunity. To selectively eliminate responsible alloreactive B cells characterized by anti-donor-HLA B-cell receptors (BCRs), we generated T cells overcoming rejection by antibodies (CORA-Ts) engineered with a novel chimeric receptor comprising a truncated donor-HLA molecule as antigen recognition domain.
View Article and Find Full Text PDFJ Clin Med
January 2025
Department of Nephrology, Dialysis and Internal Diseases, Medical University of Warsaw, 02-097 Warsaw, Poland.
Hypertension in chronic kidney disease patients is very common. The definition of resistant hypertension in the general population is as follows: uncontrolled blood pressure (BP) on three or more hypotensive agents in adequate doses, or when patients are on four or more hypotensive agent categories irrespective of the BP control, with diuretics included in the therapy. However, these resistant hypertension definitions do not apply to the setting of end-stage kidney disease.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Physiology, Faculty of Medicine, Semmelweis University, 37-47 Tűzoltó Street, 1094 Budapest, Hungary.
The octapeptide angiotensin II (Ang II) is a circulating hormone as well as a locally formed agonist synthesized by the angiotensin-converting enzyme (ACE) of endothelial cells. It forms a powerful mechanism to control the amount and pressure of body fluids. All main effects are directed to save body salt and water and ensure blood pressure under basic conditions and in emergencies.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Immunobiology and Environment Microbiology, Medical University of Gdansk, 80-210 Gdansk, Poland.
Obesity and its related diseases, such as type 2 diabetes (T2DM), cardiovascular disease (CVD), and metabolic fatty liver disease (MAFLD), require new diagnostic markers for earlier detection and intervention. The aim of this study is to demonstrate the potential of metabolomics as a tool for identifying biomarkers associated with obesity and its comorbidities in every age group. The presented systematic review makes an important contribution to the understanding of the potential of metabolomics in identifying biomarkers of obesity and its complications, especially considering the influence of branched-chain amino acids (BCAAs), amino acids (AAs) and adipokines on the development of T2DM, MAFLD, and CVD.
View Article and Find Full Text PDFLancet Microbe
December 2024
Institute of Infectious Diseases and Tropical Medicine, LMU University Hospital, LMU Munich, Germany; German Center for Infection Research, Munich Partner Site, Munich, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology, Infection, and Pandemic Research, Munich, Germany; Unit Global Health, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. Electronic address:
Background: The broad use of bedaquiline and pretomanid as the mainstay of new regimens to combat tuberculosis is a risk due to increasing bedaquiline resistance. We aimed to assess the safety, bactericidal activity, and pharmacokinetics of BTZ-043, a first-in-class DprE1 inhibitor with strong bactericidal activity in murine models.
Methods: This open-label, dose-expansion, randomised, controlled, phase 1b/2a trial was conducted in two specialised tuberculosis sites in Cape Town, South Africa.
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