BACKGROUND: To investigate the association between altered sex hormone expression and long-term right ventricular (RV) adaptation and progression of right heart failure in a Dutch cohort of... Show moreBACKGROUND: To investigate the association between altered sex hormone expression and long-term right ventricular (RV) adaptation and progression of right heart failure in a Dutch cohort of Pulmonary Arterial Hypertension (PAH)-patients across a wide range of ages. METHODS: In this study we included 279 PAH-patients, of which 169 females and 110 males. From 59 patients and 21 controls we collected plasma samples for sex hormone analysis. Right heart catheterization (RHC) and/or cardiac magnetic resonance (CMR) imaging was performed at baseline. For longitudinal data analysis, we selected patients that underwent a RHC and/or CMR maximally 1.5 years prior to an event (death or transplantation, N = 49). RESULTS: Dehydroepiandrosterone-sulfate (DHEA-S) levels were reduced in male and female PAHpatients compared to controls, whereas androstenedione and testosterone were only reduced in female patients. Interestingly, low DHEA-S and high testosterone levels were correlated to worse RV function in male patients only. Subsequently, we analyzed prognosis and RV adaptation in females stratified by age. Females < 45years had best prognosis in comparison to females & GE;55years and males. No differences in RV function at baseline were observed, despite higher pressure-overload in females < 45years. Longitudinal data demonstrated a clear distinction in RV adaptation. Although females < 45years had an event at a later time point, RV function was more impaired at end-stage disease. CONCLUSIONS: Sex hormones are differently associated with RV function in male and female PAHpatients. DHEA-S appeared to be lower in male and female PAH-patients. Females < 45years could persevere pressure-overload for a longer time, but had a more severe RV phenotype at end-stage disease.J Heart Lung Transplant 2022;41:445-457 (c) 2021 The Author(s). Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Show less
Dirks, N.F.; Ackermans, M.T.; Martens, F.; Cobbaert, C.M.; Jonge, R. de; Heijboer, A.C. 2021
With the upcoming EU regulation on the use of in-vitro diagnostic devices, a critical evaluation of the current status of our in-house developed LC-MS/MS methods is timely and of great relevance.... Show moreWith the upcoming EU regulation on the use of in-vitro diagnostic devices, a critical evaluation of the current status of our in-house developed LC-MS/MS methods is timely and of great relevance. Recently, much attention has been devoted to the need for better specification of analytical and clinical performance. Appropriate reporting of the actual achieved analytical performance is an important determinant of the clinical performance and subsequent clinical effectiveness of a test. We advocate for the application of CLSI C62-A guidelines for method validation and suggest some adaptations for analytical validation of in-house developed LC-MS/MS methods for endogenous substances. Additionally, we underline the importance of well-equipped reviewers and standardized method description, including the presentation of figural evidence of obtained method performance. Achieving this ensures future quality of our in-house developed LC-MS/MS methods. Show less
Blood for determining 25-hydroxyvitamin D-3 [25(OH)D-3] is usually obtained through venipuncture although, as an alternative for serum, dried blood spot (DBS) can be considered. The aim of this... Show moreBlood for determining 25-hydroxyvitamin D-3 [25(OH)D-3] is usually obtained through venipuncture although, as an alternative for serum, dried blood spot (DBS) can be considered. The aim of this proof-of-concept study was to investigate levels of agreement between measurements of 25(OH)D-3 obtained with DBS compared with serum. 301 Chinese participants were included who completed 25(OH)D-3 measurement from DBS and from simultaneously collected blood samples obtained by venipuncture. Measurements of both DBS and serum 25(OH)D-3 were performed using liquid chromatography followed by tandem mass spectrometry. Agreement between the two methods was assessed with Passing and Bablok regression analysis and Bland-Altman plot.Measurements showed a good correlation (Pearson's correlation coefficient r = 0.929, P < 0.001) between the two methods. After recalculating for a 13% difference, a regression equation of DBS 25(OH)D-3 = -1.91 + 1.00 serum 25(OH)D-3 was found in Passing and Bablok regression analysis. Bland-Altman analysis showed a fixed bias of 1.7 nmol/L; upper and lower limit of agreement was 24.1 nmol/L and -20.7 nmol/L, respectively.Sensitivity of recalculated DBS for 25(OH)D-3 concentrations < 30 and < 50 nmol/L was 87.8% and 91.1%, respectively, and specificity was 89.2% and 83.1%, respectively.In conclusion, a good agreement was found between the measurement of 25(OH)D-3 obtained with DBS compared with serum. DBS may possibly be used in a future screening program, but it is less suitable for individualized vitamin D status assessment. Show less
Blood for determining 25-hydroxyvitamin D3 [25(OH)D3] is usually obtained through venipuncture although, as an alternative for serum, dried blood spot (DBS) can be considered. The aim of this proof... Show moreBlood for determining 25-hydroxyvitamin D3 [25(OH)D3] is usually obtained through venipuncture although, as an alternative for serum, dried blood spot (DBS) can be considered. The aim of this proof-of-concept study was to investigate levels of agreement between measurements of 25(OH)D3 obtained with DBS compared with serum. 301 Chinese participants were included who completed 25(OH)D3 measurement from DBS and from simultaneously collected blood samples obtained by venipuncture. Measurements of both DBS and serum 25(OH)D3 were performed using liquid chromatography followed by tandem mass spectrometry. Agreement between the two methods was assessed with Passing and Bablok regression analysis and Bland-Altman plot. Measurements showed a good correlation (Pearson’s correlation coefficient r=0.929, P < 0.001) betweenthe two methods. After recalculating for a 13% difference, a regression equation of DBS 25(OH)D3 = -1.91+1.00 serum 25(OH)D3 was found in Passing and Bablok regression analysis. Bland-Altman analysis showed a fixed bias of 1.7 nmol/L; upper and lower limit of agreement was 24.1 nmol/L and -20.7 nmol/L, respectively. Sensitivity of recalculated DBS for 25(OH)D3 concentrations<30 and<50 nmol/L was 87.8% and 91.1%, respectively, and specificity was 89.2% and 83.1%, respectively. In conclusion, a good agreement was found between the measurement of 25(OH)D3 obtained with DBS compared with serum. DBS may possibly be used in a future screening program, but it is less suitable for individualized vitamin D status assessment. Show less
Berg, M.H. van den; Overbeek, A.; Lambalk, C.B.; Kaspers, G.J.L.; Bresters, D.; Heuvel-Eibrink, M.M. van den; ... ; DCOG LATER-VEVO Study Grp 2018
Introduction: Vitamin D is essential for bone health since it stimulates the intestinal absorption of calcium and phosphorus from the gut, both necessary for bone mineralization. However, vitamin D... Show moreIntroduction: Vitamin D is essential for bone health since it stimulates the intestinal absorption of calcium and phosphorus from the gut, both necessary for bone mineralization. However, vitamin D deficiency is highly prevalent among several non-Western immigrant populations in the Netherlands. To date, there are no data available of the vitamin D status in the Chinese population residing in the Netherlands. Therefore, an observational study was performed to determine 25-hydroxyvitamin D (25(OH)D) concentrations and to assess potential determinants of low vitamin D status. Methods: Subjects, aged 18 years and older, with a Chinese background and residing in the Netherlands were invited to participate in the study. A questionnaire was used to assess general characteristics and lifestyle habits. Fasting blood samples were obtained in March 2014 to measure serum 25(OH)D concentration, and analysed by liquid chromatography tandem mass spectrometry. Results: 418 subjects participated in the study, 104 men and 314 women. The mean age for both men and women was 56 years. Serum 25(OH)D concentration < 50 nmol/L was more prevalent in men than in women (67.9% and 53.1%, respectively; p = 0.008). The percentage of serum 25(OH)D concentration < 25 nmol/L in men and women was 5.8% and 10.9%, respectively. Multiple logistic regression analysis, adjusted for age and gender, revealed that non-use of vitamin D supplements and fewer days per week of physical activity were significant predictors of serum 25(OH)D levels below 50 nmol/L. Conclusions: Within the Chinese population living in the Netherlands, serum 25(OH)D concentration was below 50 nmol/L in 68% of men and 53% of women. Use of vitamin D supplements by Chinese people in the Netherlands was highly protective against low 25(OH)D levels. Show less
Er zijn steeds meer aanwijzingen dat neuropeptiden in de hypothalamus en maagdarmhormonen die hun werking hebben op de hypothalamus en betrokken zijn bij de regulatie van voedselinname, ook... Show moreEr zijn steeds meer aanwijzingen dat neuropeptiden in de hypothalamus en maagdarmhormonen die hun werking hebben op de hypothalamus en betrokken zijn bij de regulatie van voedselinname, ook betrokken zouden kunnen zijn bij de regulatie van insuline gevoeligheid. Daarom hebben we eerst de effecten van voedselstatus zelf op insuline gevoeligheid gekarakteriseerd en vervolgens gekeken naar de effecten van een aantal signalen voor voedselstatus binnen de maagdarm-brein as op insuline gevoeligheid. Insuline gevoeligheid in lever, spier en vetweefsel hebben we in alle studies in wildtype muizen gemeten met een hyperinsulinemische euglycemische clamp in combinatie met radioisotopen. De studies die uitgevoerd zijn binnen dit proefschrift laten zien dat samenwerking tussen het maagdarmstelsel en het brein niet alleen een belangrijke rol speelt bij de regulatie van voedselinname reguleert, maar ook bij de regulatie van de insuline gevoeligheid van het glucose metabolisme in de lever en perifere weefsels, zoals spier en vetweefsel, afhankelijk en onafhankelijk van voedingsstatus. Op deze manier kan op ieder moment de weefsel-specifieke insuline gevoeligheid nauwkeurig worden gereguleerd, afhankelijk en onafhankelijk van voedingsstatus. Deze eigenschappen maken dat maagdarmhormonen mogelijk ideale nieuwe farmaceutische aangrijpingspunten zijn voor de behandeling van obesitas en type II diabetes mellitus. Show less
