Thyroglobulin as a functional biomarker of iodine status in a cohort study of pregnant women in the United Kingdom

Background Though iodine deficiency in pregnancy is a matter of public-health concern, a functional measure of iodine status is lacking. The thyroid-specific protein, thyroglobulin (Tg), which reflects thyroid size, has shown promise as a functional measure in studies of children and adults, but data in pregnancy are sparse. In a cohort of mildly-to-moderately iodine-deficient pregnant women, we aimed to explore whether serum Tg is a sensitive functional biomarker of iodine status and to examine longitudinal change in Tg with gestational age. Method 230 pregnant women were recruited at an ante-natal clinic at 12 weeks of gestation to the Selenium in PRegnancy INTervention (SPRINT) study, in Oxford, UK. Repeated measures of urinary iodine-to-creatinine ratio, serum TSH and Tg at 12, 20, and 35 weeks of gestation were collected. Women were dichotomised by their iodine-to-creatinine ratio, (<150 or ≥150 μg/g) to group them broadly as iodine-deficient or iodine-sufficient. Women with thyroid antibodies were excluded; data and samples were available for 191 women. Results Median Tg concentration was 21, 19, and 23 μg/L in the first, second, and third trimesters, respectively. In a linear mixed model, controlling for confounders, Tg was higher in the <150 μg/g than in the ≥150 μg/g group (p<0.001) but there was no difference in TSH (p=0.27). Gestational week modified the effect of iodine status on TSH (p=0.01) and Tg (p=0.012); Tg did not increase with gestational week in the ≥150 μg/g group but did in the <150 μg/g group, and TSH increased more steeply in the <150 μg/g group. Conclusions Low iodine status (<150 μg/g) in pregnancy is associated with higher serum Tg, suggesting that the thyroid is hyper-stimulated by iodine deficiency, which causes it to enlarge. Tg is a more sensitive biomarker of iodine status in pregnancy than is TSH

Association of endocrine disrupting chemicals exposure with human chorionic gonadotropin concentrations in pregnancy

Data availability: The authors do not have permission to share data.Supplementary material is available online at https://www.sciencedirect.com/science/article/pii/S0160412023003641#s0105 .Copyright © 2023 The Author(s). Background: Human chorionic gonadotropin (hCG) is produced by the placenta and plays an essential role in the maintenance of pregnancy. Endocrine disrupting chemicals (EDCs) have the potential to interfere with functions related to the production and secretion of hCG; however associations between exposure to EDCs and hCG concentrations in humans remain to be elucidated. Objectives: To investigate the association of urinary, serum and plasma concentrations of EDCs during pregnancy with serum hCG concentrations. Methods: We utilized data form the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. We investigated the association of 26 EDCs measured in early pregnancy urine or blood with serum hCG concentrations using multi-variable adjusted linear regression models per EDC and Weighted Quantile Sum (WQS) regression with repeated holdout validation for the EDCs mixture. Results: In 2,039 included women, higher exposure to bisphenol A was associated with lower hCG (beta [95% CI]: −0.06 [−0.11 to −0.002]) while higher triclosan exposure was associated with a higher hCG (0.02 [0.003 to 0.04]). Higher exposure to several phthalates, including mono-ethyl and mono-butyl phthalates (MEP and MBP) as well as metabolites of di-2-ethylhexyl phthalate (DEHP) was associated with a lower hCG (beta [95% CI] for sum of DEHP metabolites: −0.13 [−0.19 to −0.07]). Likewise, higher exposure to several polychlorinated biphenyls (PCBs) was associated with a lower hCG. In the WQS regression, each quartile increase in the EDCs mixture was associated with −0.27 lower hCG (95% CI: −0.34 to −0.19). Discussion: Higher exposure to several EDCs during pregnancy was associated with a lower hCG; and despite the small effect sizes, still indicating that the exposure may negatively affect production or secretion of hCG by the placenta. Our results provide the impetus for future experimental studies to investigate the placenta as a target organ for adverse effects of EDCs.This project has been supported by the Exchange in Endocrinology Expertise (3E) program of the European Union of Medical Specialists (UEMS), Section and Board of Endocrinology and the ATHENA project, funded under the European Union’s Horizon 2020 Programme for research, technological development and demonstration, grant agreement no. 825161. The SELMA study was funded by grants from the Swedish Research Council (Formas). The sample analysis were supported by Region Skåne and the Medical Faculty at Lund University, Sweden

Therapeutic drug monitoring van adalimumab bij patiënten met inflammatoire darmziekten

\u3cbr/\u3e\u3cbr/\u3e \u3cp\u3eOBJECTIVE: Adalimumab (ADA) trough levels correlate with clinical remission. Despite suggestions that therapeutic drug monitoring of ADA can optimize treatment in this population, it is not yet implemented in clinical practice. This study was conducted to provide more insight in ADA trough levels and antibodies to adalimumab (ATA) in an inflammatory bowel disease (IBD) population already treated with adalimumab. DESIGN: We carried out a prospective cohort study in IBD outpatients already treated with adalimumab. METHODS: Patient demographics were collected from the electronic hospital information system. Blood was drawn for determination of ADA trough levels and ATAs. Disease activity indices for Crohn's disease and ulcerative colitis and quality of life scores were obtained by a questionnaire. RESULTS: A total of 92 patients was included. ADA levels varied from &lt; 0.1 to 20.2 mg/L. Mean ADA level was 7.7 mg/L (SD = 4.5), 4 patients developed ATAs. ADA levels ≤ 5 mg/L were demonstrated in 27 patients (29%). The ADA level was not significantly associated with remission [P = 0.391). Quality of life score correlated with ADA level (P = 0.031). CONCLUSION: Therapeutic drug monitoring in inflammatory bowel disease outpatients revealed large interindividual differences in adalimumab trough levels. These levels were subtherapeutic in nearly a third of patients. We think, despite no significant correlation was found between adalimumab trough level and disease activity, therapeutic drug monitoring has the potential to individualize treatment in inflammatory bowel disease patients using adalimumab.\u3c/p\u3

Therapeutic drug monitoring van adalimumab bij reumatologische patiënten

\u3cp\u3eOBJECTIVE and DESIGN Adalimumab (ADA) is effective in the treatment of rheumatoid arthritis IRA), ankylosing spondylitis (ASI and psoriatic arthritis (PsA). Despite suggestions that therapeutic drug monitoring (TDM) of ADA can optimize treatment of this population, it is not routinely implemented in clinical practice. We therefore carried out a prospective observational cohort study by measuring ADA levels in a population of patients with rheumatic diseases and related those levels to disease activity. METHODS Patient demographics were collected from the electronic hospital information system. Blood drawn before the regular outpatient visit was used for determination of ADA trough levels and antibodies against ADA (ATA). Objectified disease activity measurements were obtained at the appointment: DAS28 for RA, ASDAS for AS, and clinical assessment for SpA. RESULTS A total of 17A patients was included. ADA levels varied from less than 0.1 to 22.0 mg/L. The mean ADA level was 6.8 mg/L (standard deviation = 4.2). 5 patients (2,9%) developed ATA. The ADA level was significantly associated with remission (P = 0.002). The mean ADA level was 7.6 mg/L in patients in remission and 5.1 mg/L in patients with active disease. Use of immunosuppressants, frequency of administration, and body mass index were identified as significant covariates. CONCLUSION TDM of ADA demonstrated large interindividual differences in ADA levels. ADA trough levels were significantly associated with disease activity. TDM has the potential to individualize treatment and further research needs to show if it increases cost-effectiveness of this expensive therapy.\u3c/p\u3

A value proposition for trough level-based anti-TNFα drug dosing

\u3cp\u3eTreatment of inflammatory bowel diseases and rheumatic disorders with anti-tumor necrosis factor alpha (TNFα) drugs is expensive, while a significant proportion of patients does not show adequate clinical response. Therapeutic drug monitoring (TDM) enables patient-specific anti-TNFα therapy. The role of laboratory tests in clinical care has recently been described in a value proposition framework. It describes care processes, stakeholders, costs, risks, benefits and patient outcomes based on the use of a laboratory test in a clinical care pathway. We have applied this concept to the use of TDM for anti-TNFα drugs, describing evidence that supports the intervention and its cost effectiveness, steps that need to be adjusted in the care pathway, possible treatment algorithms and measures to assess adoption of this framework into clinical practice. For effective TDM, an assay for measurement of drug levels together with appropriate target ranges and an anti-drug-antibody assay have to be implemented. Also, instead of only reporting the drug concentration, laboratorians, pharmacists and clinicians should deliver added value by introducing a TDM-based treatment algorithm into clinical practice. Thus, to maximize effectiveness of TDM of anti-TNFα therapy in routine care, adjustment of current care pathways and cooperation of many stakeholders are needed.\u3c/p\u3

Oxytocin levels in the saliva of preterm infant twins during Kangaroo care

\u3cp\u3eBackground and purpose: To investigate whether Kangaroo care (KC) influences the salivary oxytocin (OT) concentration in preterm infants, and which correlates affect the OT response. Methods: Eleven twin pairs participated in a study in which we collected saliva using cotton swabs twice a day, once during KC and once during baseline conditions (lying in bed or incubator). The total study duration was five days. The saliva of twin siblings were pooled to obtain vials with sufficient volumes of either saliva collected during KC or at baseline. OT levels were measured using a radio-immuno assay. The infants’ state of comfort and parent-infant interaction were examined using previously developed Likert-scales, amongst other correlates such as the KC duration, gestational age and birth weight. Results: During KC, OT was lower compared to baseline (mean 1.39 pg/ml (SD 0.58 pg/ml) versus 2.40 pg/ml (SD 1.64 pg/ml), p = 0.03). Comfort at baseline and parent-infant interaction seemed to influence OT responses. Conclusion: The OT concentration in the pooled saliva of preterm infant twins decreased during KC. This response of the OT system might be explained by stress during baseline.\u3c/p\u3

Therapeutic drug monitoring (TDM) as a tool in the switch from infliximab innovator to biosimilar in rheumatic patients:results of a 12-month observational prospective cohort study

\u3cp\u3eThe objective of this study is to apply therapeutic drug monitoring (TDM) as an objective tool to monitor the switch from infliximab innovator (INX) to infliximab biosimilar (INB) in our diverse rheumatic cohort in daily clinical practice. All rheumatic patients on INX treatment (Remicade®) and ≥18 years were switched to INB (Inflectra®) as part of routine care, but in a controlled setting. Patients were monitored by taking blood samples just before the first infusion of INB (T1), and after the second (T2), fourth (T3), and seventh (T4) infusion of INB. T4 reflects the patients’ status after ∼12 months. Infliximab trough levels, antibodies-to-infliximab (ATI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and validated disease activity scores (if possible) were measured. Our population consisted of 27 patients with seven different rheumatic diseases who had received INX for 143 (58–161) months (median (IQR)). Half of the patients (52%) received concomitant immunosuppressives. We found widely varying infliximab levels, with only 56% within the proposed therapeutic range of 1–5 μg/mL. One patient had very high ATI levels (&gt;880 au/mL), and two had low ATI levels (≤30 au/mL). After switching to INB, seven patients (26%) discontinued the therapy, partially due to subjective reasons. No difference in infliximab levels, CRP levels, and disease activity scores was found between the four time points (p ≥ 0.2460). In conclusion, no pharmacokinetic or clinical differences were found between INX and INB in our diverse rheumatic cohort. TDM is a helpful tool to monitor patients switching from INX to INB.\u3c/p\u3

Chiral amplification in columns of self-assembled N,N′,N″-Tris((S)-3,7-dimethyloctyl)benzene-1,3,5-tricarboxamide in dilute solution

Remarkable control of chirality within a long and stable columnar self-assembly of N,N',N¿-Tris((S)-3,7-dimethyloctyl)benzene-1,3,5-tricarboxamide in dilute solution is achieved by strong, unidirectional hydrogen bonding and cooperative side-chain interactions; IR and CD-spectroscopy have been used to elucidate these features