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Subjects at risk for major mood disorders have a higher risk to develop autoimmune thyroid disease (AITD) and vice-versa, implying a shared pathogenesis. In mood disorder patients, an abnormal profile of hematopoietic/neuronal growth factors is observed, suggesting that growth/differentiation abnormalities of these cell lineages may predispose to mood disorders. The first objective of our study was to investigate whether an aberrant profile of these hematopoietic/neuronal growth factors is also detectable in subjects at risk for AITD. A second objective was to study the inter relationship of these factors with previously determined and published growth factors/cytokines in the same subjects. We studied 64 TPO-Ab-negative females with at least 1 first- or second-degree relative with AITD, 32 of whom did and 32 who did not seroconvert to TPO-Ab positivity in 5-year follow-up. Subjects were compared with 32 healthy controls (HCs). We measured serum levels of brain-derived neurotrophic factor (BDNF), Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2), Epidermal Growth Factor (EGF) and IL-7 at baseline. BDNF was significantly lower (8.2 vs 18.9 ng/ml, P<0.001), while EGF (506.9 vs 307.6 pg/ml, P = 0.003) and IGFBP-2 (388.3 vs 188.5 ng/ml, P = 0.028) were significantly higher in relatives than in HCs. Relatives who seroconverted in the next 5 years had significantly higher levels of SCF than non-seroconverters (26.5 vs 16.7 pg/ml, P = 0.017). In a cluster analysis with the previously published growth factors/cytokines SCF clustered together with IL-1β, IL-6 and CCL-3, of which high levels also preceded seroconversion. Relatives of AITD patients show aberrant serum levels of 4 hematopoietic/neuronal growth factors similar to the aberrancies found in mood disorder patients, suggesting that shared growth and differentiation defects in both the hematopoietic and neuronal system may underlie thyroid autoimmunity and mood disorders. A distinct pattern of four inter correlating immune factors in the relatives preceded TPO-Ab seroconversion in the next 5 years.

Levothyroxine replacement treatment in hypothyroidism is unable to restore physiological thyroxine and triiodothyronine concentrations in serum and tissues completely. Normal serum thyroid stimulating hormone (TSH) concentrations reflect only pituitary euthyroidism and, therefore, novel biomarkers representing tissue-specific thyroid state are needed. MicroRNAs (miRNAs), small non-coding regulatory RNAs, exhibit tissue-specific expression patterns and can be detectable in serum. Previous studies have demonstrated differential expression of (precursors of) miRNAs in tissues under the influence of thyroid hormone. To study if serum miRNA profiles are changed in different thyroid states. We studied 13 athyroid patients (6 males) during TSH suppressive therapy and after 4 weeks of thyroid hormone withdrawal. A magnetic bead capture system was used to isolate 384 defined miRNAs from serum. Subsequently, the TaqMan Array Card 3.0 platform was used for profiling after individual target amplification. Mean age of the subjects was 44.0 years (range 20-61 years). Median TSH levels were 88.9 mU/l during levothyroxine withdrawal and 0.006 mU/l during LT4 treatment with a median dosage of 2.1 μg/kg. After normalization to allow inter-sample analysis, a paired analysis did not demonstrate a significant difference in expression of any of the 384 miRNAs analyzed on and off LT4 treatment. Although we previously showed an up-regulation of pri-miRNAs 133b and 206 in hypothyroid state in skeletal muscle, the present study does not supply evidence that thyroid state also affects serum miRNAs in humans.

Despite the well-recognized clinical features resulting from insufficient or excessive thyroid hormone (TH) levels in humans, it is largely unknown which genes are regulated by TH in human tissues. To study the effect of TH on human gene expression profiles in whole blood, mainly consisting of T3 receptor (TR) α-expressing cells. We performed next-generation RNA sequencing on whole blood samples from eight athyroid patients (four females) on and after 4 weeks off levothyroxine replacement. Gene expression changes were analyzed through paired differential expression analysis and confirmed in a validation cohort. Weighted gene coexpression network analysis (WGCNA) was applied to identify thyroid state-related networks. We detected 486 differentially expressed genes (fold-change >1.5; multiple testing corrected P value < 0.05), of which 76% were positively and 24% were negatively regulated. Gene ontology (GO) enrichment analysis revealed that three biological processes were significantly overrepresented, of which the process translational elongation showed the highest fold enrichment (7.3-fold, P = 1.8 × 10-6). WGCNA analysis independently identified various gene clusters that correlated with thyroid state. Further GO analysis suggested that thyroid state affects platelet function. Changes in thyroid state regulate numerous genes in human whole blood, predominantly TRα-expressing leukocytes. In addition, TH may regulate gene transcripts in platelets.

Thyroid hormone importantly affects the cardiovascular system. However, evaluation of stroke volume (SV) and its determinants is confounded by variations in volume status that occur along different thyroid states. This study applied the pressure‐volume (PV) framework to obtain relatively load‐independent estimates of cardiac function in hypothyroidism as compared to euthyroidism. Ten athyroid patients were assessed echocardiographically after 4 weeks in deep hypothyroid state, and again after supplementation with oral Levothyroxine (LT4) for 3 months. Thyroid hormone levels were assessed and noninvasive pressure‐volume (PV) analysis based on dedicated repeated echocardiograms was performed. Changes were assessed using paired tests. Results are presented as medians and interquartile ranges. Hypothyroidism was associated with reduced stroke volume (SV: 67.6 ± 17 vs. 75.7 ± 20.6 mL, P = 0.024), preload (end‐diastolic volume, EDV: 122.6 ± 32.5 vs. 135.7 ± 33.6 mL, P = 0.004), and contractility (end‐systolic elastance, Ees: 1.7 ± 0.33 vs. 2.58 ± 1.33 mmHg/mL, P = 0.01). Afterload was constant (effective arterial elastance, Ea: 1.66 ± 0.32 vs. 1.79 ± 0.52 mmHg/mL, P = 0.43) and the total energy spent was lower (PVA∙HR: 86.7 ± 28 vs. 110.9 ± 32.1 J, P = 0.04). Hemodynamic manifestations of frank hypothyroidism in humans are characterized by reduced preload and contractility, and unchanged total afterload. LT4 therapy increased work efficiency and heart rate, but not the net energy expenditure. Noninvasive PV analysis may be useful to follow‐up different thyroid states. First noninvasive, relatively load‐independent PV analysis measuring the hemodynamic changes in patients exposed to a standardized period of deep hypothyroidism followed by thyroxine (LT4) supplementation.

IntroductionThe quality and accessibility of the Dutch healthcare system are under increasing pressure. There is a growing demand for healthcare services due to factors like an ageing population and an increase in the number of chronically ill people. Unfortunately, we also have to deal with a chronic staff shortage. One of the solutions is a greater efficiency aiming at providing more healthcare with the same amount of resources and numbers of staff. In 2023, 6.4% of our patients (which means 3314 patients) did not come to their appointment on the outpatient clinic (no show).AimOur aim was to improve the attendance to the clinic to increase efficiency and save costs.We analysed the distribution of no-show patients among the internal medicine subspecialties. 3.3% of the oncology patients, 4.7% of the haematology, 4.7% of the nephrology and 9.2% of the endocrinology patients did not show-up.InterventionsAlmost all our patients have to draw blood before an appointment. Patients who do not visit the lab usually do not come to their appointment as well. We hypothesized that a possible intervention could be to call these patients to remind them on their appointment.To deal with staff shortage, we introduced Robotic Process Automation (RPA). Patients can schedule their appointments without intervention from hospital employees through RPA. They receive a lab form via their electronic patient record (mijn ASZ) with instructions. Medical assistants check if lab results are present a few days before the scheduled appointment. A telephone team was established in July 2024 to call patients with missing lab results in the evening. They were asked to draw blood and were reminded on their appointment. We measured no-show numbers monthly, before and after our intervention and performed a student’s T-Test.ResultsFrom July –December 2024 our telephone team reached 1746 (61.2%) patients and left a voicemail for 878 (30.7%) patients. 230 (8.1%) patients were not reached at all. Reported reasons for not drawing blood: lack of a computer or login codes, not having received lab forms, difficulty accessing lab forms or being unaware of the appointment.We measured a significant reduction of no-show numbers after our intervention (N=1558 in Q 3+4 2023 versus N=1168 in Q 3+4 in 2024; p< 0.005, table 1). We calculated that our outpatient clinic capacity increased with 97.5 hrs. We calculated that we gained € 117.000 by reducing no-show numbers, while the costs of the telephone team were € 13.995.Abstract 35 Table 1No show numbers before (quarter 3+4 2023) and after (2024) intervention * p<0.005 Q 3 + 4 2023 Q 3 + 4 2024 Total patients (N) 25057 30226 No-show patients (N): 1558 (6%) 1168 (4%)* −390 (−25%) • New patients (N) 208 147 −61 (−29%) • follow-up patients (N) 1350 1021 −329 (−24%) ConclusionsNo-show numbers can be reduced with a special telephone team and appropriate selection of patients. RPA can help to improve processes in health care, but we have to keep in mind not all patients are digitally skilled.

Objective: To compare sexual well being in women with pelvic organ prolapse before and after vaginal reconstructive surgery. Methods: Sixty-seven women, mean age 61 (36-85) years, who underwent vaginal reconstructive surgery, were asked to complete detailed questionnaires before and after surgery. In addition, they underwent a physical examination using the Pelvic Organ Prolapse Quantification (POPQ), before surgery and at follow-up. Results: Mean duration of follow-up was 14.4 months (6.6-27.6 months). The overall satisfaction with the operation was high with a mean of 7.5 on a visual analogue scale from 0 to 10. There was a significant improvement of dyspareunia after vaginal reconstructive surgery. The ability to have intercourse, the satisfaction with intercourse as well as the frequency of intercourse also improved although not significantly. Urine loss during intercourse improved significantly. Conclusion: Vaginal reconstructive surgery for pelvic organ prolapse has a positive effect on the sexual well being of the afflicted women.[PUBLICATION ABSTRACT]

The objective of this study was to estimate the prevalence of nocturia in incontinent women in a urogynaecologic practice and its association with the quality of life and to estimate the prevalences of the pathophysiological categories among nocturics. From 1 January 2002, all patients with complaints of urinary incontinence were analysed according to a specific protocol: multichannel urodynamic testing, a 1-h International Incontinence Society (ICS) pad test and a 3-day frequency-volume (FV) chart. From 1 June 2002, subjects had to fill in a standardised quality of life questionnaire as well. Nocturia was defined as two or more micturitions per night calculated from the FV chart. Evaluable FV charts were received from111 patients, and 72 patients completed the questionnaires correctly. The overall prevalence of nocturia was 48.6% (confidence interval: 43.9-53.3%). Nocturia had a negative impact on several aspects of the quality of life. The maximum voided volume was significantly (p=0.005) less in nocturics. The 24-h frequency was higher in nocturics (p=0.001). Nocturics lost more urine during the pad test (p=0.039). The multivariate logistic regression analysis showed that the greater the proportion of 24-h urine excreted at night, the greater the odds of having nocturia and that the lesser the maximum voided volume, the greater the odds of having nocturia. The majority (92.7%) of the nocturics can be classified into one of the responsible pathophysiologic categories: nocturnal polyuria in 51.2%, a low functional bladder capacity in 14.6%, a combination of both in 9.8%, polyuria in 4.9% and a combination of polyuria and nocturnal polyuria in 12.2% of the cases. Nocturia is a frequent symptom among urinary incontinent patients, with a negative impact on several aspects of the quality of life. With a FV chart, nocturics can be classified into one of the responsible pathophysiologic categories in the majority (92.7%) of the cases.[PUBLICATION ABSTRACT]

Background Thyroid cancer (TC) patients are understudied but appear to be at risk for poor physical and psychosocial outcomes. Knowledge of the course and determinants of these deteriorated outcomes is lacking. Furthermore, little is known about mediating biological mechanisms. Objectives The WaTCh-study aims to; Examine the course of physical and psychosocial outcomes. Examine the association of demographic, environmental, clinical, physiological, and personality characteristics to those outcomes. In other words, who is at risk? Reveal the association of mediating biological mechanisms (inflammation, kynurenine pathway) with poor physical and psychological outcomes. In other words, why is a person at risk? Design and methods Newly diagnosed TC patients from 13 Dutch hospitals will be invited. Data collection will take place before treatment, and at 6, 12 and 24 months after diagnosis. Sociodemographic and clinical information is available from the Netherlands Cancer Registry. Patients fill-out validated questionnaires at each time-point to assess quality of life, TC-specific symptoms, physical activity, anxiety, depression, health care use, and employment. Patients are asked to donate blood three times to assess inflammation and kynurenine pathway. Optionally, at each occasion, patients can use a weighing scale with bioelectrical impedance analysis (BIA) system to assess body composition; can register food intake using an online food diary; and can wear an activity tracker to assess physical activity and sleep duration/quality. Representative Dutch normative data on the studied physical and psychosocial outcomes is already available. Impact WaTCh will reveal the course of physical and psychosocial outcomes among TC patients over time and answers the question who is at risk for poor outcomes, and why. This knowledge can be used to provide personalized information, to improve screening, to develop and provide tailored treatment strategies and supportive care, to optimize outcomes, and ultimately increase the number of TC survivors that live in good health.