Global Leadership Initiative on Malnutrition-Diagnosed Malnutrition in Lung Transplant Candidates.

BACKGROUND AND AIMS: Malnutrition in lung transplantation (LT) candidates increases postoperative morbidity and mortality. Early diagnosis of malnutrition could attenuate adverse prognostic factors. This study aimed to assess the prevalence of nutritional risk and malnutrition using GLIM criteria in LT candidates and clinically characterize those with malnutrition. METHODS: A prospective longitudinal study was conducted from 2000 to 2020 of LT candidates who underwent complete nutritional assessment (nutritional screening, anthropometry, bioelectrical impedance, blood laboratory tests and malnutrition diagnosis using GLIM criteria). RESULTS: Obstructive diseases (45.6%), interstitial diseases (36.6%) and cystic fibrosis/non-cystic fibrosis bronchiectasis (15.4%) were the main conditions assessed for LT. Of the 1060 candidates evaluated, 10.6% were underweight according to BMI, 29% were at risk of malnutrition and 47% were diagnosed with malnutrition using GLIM criteria. Reduced muscle mass was the most frequent GLIM phenotypic criterion. Malnutrition was more prevalent in patients with cystic fibrosis/non-cystic fibrosis bronchiectasis (84.5%) and obstructive (45.4%) and interstitial (31.3%) diseases. GLIM criteria detected some degree of malnutrition in all diseases requiring LT and identified patients with higher CRP levels and worse respiratory function, anthropometric measurements and visceral protein and lipid profiles. CONCLUSIONS: LT candidates present a high prevalence of malnutrition using the GLIM algorithm. GLIM criteria detected malnutrition in all diseases requiring LT and defined patients with worse clinical-analytical profiles.

Effect of Polymorphisms in CYP2C9 and CYP2C19 on the Disposition, Safety and Metabolism of Progesterone Administrated Orally or Vaginally.

INTRODUCTION: Exogenous progesterone is prescribed for a variety of conditions with endogenous progesterone deficiency, e.g. menstrual alterations, primary or secondary infertility or premenopause. To the best of our knowledge, no pharmacogenetic studies have been published in relation to exogenous progesterone pharmacokinetic safety or progesterone metabolites so far. METHODS: Candidate-gene study where we evaluated whether five single-nucleotide polymorphisms (CYP2C9*2, *3, CYP2C19*2, *3 and *17) were related to the pharmacokinetics, safety and metabolism of progesterone in 24 healthy volunteers who received a 200-mg progesterone formulation either orally or vaginally. RESULTS: The vaginal formulation had an average AUCt value approximately 18 times greater than the oral formulation. CYP2C19 intermediate metabolizers (IM) consistently showed higher adjusted AUCt and adjusted Cmax than extensive metabolizers (EM) (P < 0.05); CYP2C9 EM incongruently exhibited higher adjusted Cmax and longer half-life than IM (p < 0.05). CONCLUSION: This is the first study that reports variability in progesterone disposition according to the CYP2C19 and CYP2C9 phenotype. We suggest that CYP2C19 may condition progesterone disposition and that it may be more relevant than CYP2C9. This study lays the foundations for further in-depth research to evaluate the pharmacogenetics of progesterone. TRIAL REGISTRATION: EudraCT numbers are 2012-005105-43 and 2012-005011-10.