Measuring Platinum Levels in Hair in Women with Silicone Breast Implants and Systemic Symptoms.

It has been suggested that compounds present in silicone breast implants (eg, silicone particles or heavy metals such as platinum) migrate into the body and can cause systemic symptoms in susceptible women, causing what is known as breast implant illness. This pilot study investigates possible associations between hair platinum levels in patients with breast implants and breast implant illness, and evaluates its possible use for diagnostic purposes. Methods: Patients were included from the silicone outpatient clinic at Amsterdam University Medical Centre. Platinum concentration in hair samples of 10 women with breast implants and systemic symptoms (group A) was compared with that in 10 women with breast implants but no symptoms (group B), and a control group of 10 women without implants or symptoms (group C), using laser ablation inductively coupled plasma mass spectrometry. Radiological imaging was used to assess implant ruptures or silicone leakage. Results: A median platinum concentration of 0.09 µg per kg [IQR 0.04-0.15] was found in group A, 0.08 µg per kg [IQR 0.04-0.12] in group B, and 0.04 µg per kg [IQR 0.02-0.13] in group C, with no statistical significant difference between the groups (Kruskal-Wallis test, P = 0.43). No correlation between radiologically proven implant leakage and platinum level was found. Conclusions: There was no statistically significant difference in hair platinum levels in women with or without silicone breast implants or breast implant illness. Therefore, based on this pilot study, we do not recommend this test for clinical use. Given the small sample size, more research is required to fully assess its possible use for diagnostic purposes.

Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the cardiac muscle, frequently caused by mutations in MYBPC3. However, little is known about the upstream pathways and key regulators causing the disease. Therefore, we employed a multi-omics approach to study the pathomechanisms underlying HCM comparing patient hearts harboring MYBPC3 mutations to control hearts. RESULTS: Using H3K27ac ChIP-seq and RNA-seq we obtained 9310 differentially acetylated regions and 2033 differentially expressed genes, respectively, between 13 HCM and 10 control hearts. We obtained 441 differentially expressed proteins between 11 HCM and 8 control hearts using proteomics. By integrating multi-omics datasets, we identified a set of DNA regions and genes that differentiate HCM from control hearts and 53 protein-coding genes as the major contributors. This comprehensive analysis consistently points toward altered extracellular matrix formation, muscle contraction, and metabolism. Therefore, we studied enriched transcription factor (TF) binding motifs and identified 9 motif-encoded TFs, including KLF15, ETV4, AR, CLOCK, ETS2, GATA5, MEIS1, RXRA, and ZFX. Selected candidates were examined in stem cell-derived cardiomyocytes with and without mutated MYBPC3. Furthermore, we observed an abundance of acetylation signals and transcripts derived from cardiomyocytes compared to non-myocyte populations. CONCLUSIONS: By integrating histone acetylome, transcriptome, and proteome profiles, we identified major effector genes and protein networks that drive the pathological changes in HCM with mutated MYBPC3. Our work identifies 38 highly affected protein-coding genes as potential plasma HCM biomarkers and 9 TFs as potential upstream regulators of these pathomechanisms that may serve as possible therapeutic targets.

Trends in suicide death risk in transgender people: results from the Amsterdam Cohort of Gender Dysphoria study (1972-2017).

OBJECTIVE: This study explored the overall suicide death rate, the incidence over time, and the stage in transition where suicide deaths were observed in transgender people. METHODS: A chart study, including all 8263 referrals to our clinic since 1972. Information on death occurrence, time, and cause of death was obtained from multiple sources. RESULTS: Out of 5107 trans women (median age at first visit 28 years, median follow-up time 10 years) and 3156 trans men (median age at first visit 20 years, median follow-up time 5 years), 41 trans women and 8 trans men died by suicide. In trans women, suicide deaths decreased over time, while it did not change in trans men. Of all suicide deaths, 14 people were no longer in treatment, 35 were in treatment in the previous two years. The mean number of suicides in the years 2013-2017 was higher in the trans population compared with the Dutch population. CONCLUSIONS: We observed no increase in suicide death risk over time and even a decrease in suicide death risk in trans women. However, the suicide risk in transgender people is higher than in the general population and seems to occur during every stage of transitioning. It is important to have specific attention for suicide risk in the counseling of this population and in providing suicide prevention programs.

Prospective evaluation of hematocrit in gender-affirming hormone treatment: results from European Network for the Investigation of Gender Incongruence.

In trans persons on gender-affirming hormonal treatment, a decrease (in trans women) or increase (in trans men) in hematocrit is often observed. Reference ranges for evaluation of hematocrit levels in trans persons have not been established. This prospective cohort study is part of the European Network for the Investigation of Gender Incongruence (ENIGI). At the Ghent and Amsterdam sites, we included 625 hormone-naïve trans persons. Gender-affirming hormonal treatment was initiated at the first visit. In trans men, serum hematocrit (Hct) levels increased during the first year (+4.9 Hct %, 95% CI 3.82-5.25), with the most pronounced increase during the first 3 months (+2.7 Hct %, 95% CI 1.94-3.29). Trans men receiving testosterone esters had a larger increase in serum hematocrit levels compared to trans men receiving testosterone undecanoate (Δ 0.8 Hct %). Of 192 trans men, 22 (11.5%) developed serum hematocrit levels ≥50.0%. Trans men on testosterone undecanoate were less likely to develop hematocrit levels ≥50% or ≥52%, compared to trans men on testosterone esters, and were less likely to develop hematocrit levels ≥50%, compared to trans men on testosterone gel. In trans women, serum hematocrit had dropped by 4.1 Hct % (95% CI 3.50-4.37) after 3 months, after which only small decreases were observed. In conclusion, serum hematocrit levels can be found in the reference range of the perceived gender as from 3 months after the initiation of gender-affirming hormonal treatment.

Changes in regional body fat, lean body mass and body shape in trans persons using cross-sex hormonal therapy: results from a multicenter prospective study.

OBJECTIVE: Cross-sex hormonal therapy (CHT) in trans persons affects their total body fat and total lean body mass. However, it is unknown how separate body regions are affected and whether these changes alter body shape. Therefore, the aim of this study was to determine the effects on body fat and lean body mass in separate body regions and on body shape after one year of CHT. DESIGN AND METHODS: In a multicenter prospective study at university hospitals, 179 male-to-female gender dysphoric persons, referred to as transwomen, and 162 female-to-male gender dysphoric persons, referred to as transmen, were included. All underwent whole-body dual-energy X-ray absorptiometry and anthropometric measurements before and after one year of CHT. RESULTS: In transwomen, increases in body fat ranged from +18% (95% CI: 13%;23%) in the android region to +42% (95% CI: 37%;46%) in the leg region and +34% (95% CI: 29%;38%) in the gynoid region. In transmen, changes in body fat ranged from -16% (95% CI: -19;-14%) in the leg region and -14% in the gynoid region (95% CI: -16%;-12) to no change in the android region (+1%, 95% CI: -3%;5%). Waist-to-hip ratio (WHR) decreased in transwomen (-0.03, 95% CI: -0.04;-0.02) mainly due to an increase in hip circumference (+3.2 cm, 95% CI: 2.3;4.0). Transmen have a decrease in hip circumference (-1.9 cm, 95% CI: -3.1;-0.7) resulting in an increase in WHR (+0.01, 95% CI: 0.00;0.02). CONCLUSIONS: CHT causes a more feminine body fat distribution and a lower WHR in transwomen and a more masculine body fat distribution with a lower hip circumference in transmen.

Postoperative pain assessment in hospitalised patients: National survey and secondary data analysis.

BACKGROUND: Measuring pain is important for the adequate pain management of postoperative patients. The actual compliance with pain assessment in postoperative patients after implementation of a national safety program is unknown. OBJECTIVES: The aim of this study is to examine the compliance with pain assessment in postoperative patients after implementation of a national safety program, according to the national quality indicators for pain assessment in postoperative patients. Furthermore, organisational factors associated with this compliance were determined. STUDY DESIGN: In this study, two data sources were used: 1) data from an evaluation study of the Dutch Hospital Patient Safety Program; and 2) data from a questionnaire survey. METHODS: The compliance with two different pain process indicators was determined: 1) 3 pain measurements a day, all three full days after surgery; and 2) ≥1 pain measurement a day, all three full days after surgery. Multilevel logistic regression analysis was used to investigate the association between organisational factors in hospitals and compliance with pain process indicators. RESULTS: Data of 3895 patient records from 16 hospitals was included in this study. In 12% of the postoperative patients, pain was measured 3 times a day, all three full days after surgery. In 53% of the postoperative patients, pain was measured ≥1 time a day, all three full days after surgery. Compliance was highest in general hospitals compared to tertiary teaching and academic hospitals, and was statistically significantly higher at the surgery and surgical oncology department compared to the other departments. CONCLUSIONS: Low compliance was shown with pain assessment in postoperative patients, according to the process indicator pain after surgery in Dutch hospitals. This suggests that the implementation of measuring pain in hospitals is still insufficient.

Hypertension in older patients, a retrospective cohort study.

BACKGROUND: It is unknown to what extent General Practitioners (GPs) manage hypertension (HT) differently in older patients, as compared to younger age groups. The purpose of our study was to compare HT management in older patients to younger age groups. METHODS: We performed a retrospective cohort study of patients of 159 GP's practices in the Integrated Primary Care Information (IPCI) database. The study period lasted from September 2010 through December 2012. The study population consisted of all patients aged 60 years or older with at least one blood pressure (BP) measurement during the inclusion period, without pre-existent HT, diabetes mellitus (DM) or atherosclerotic cardiovascular disease at time of study start. Study outcomes were a diagnosis of HT within one month after cohort entry and the use of antihypertensive medication within 4 months after cohort entry in HT diagnosed patients. We compared the incidence of outcomes between the age groups, stratified by systolic blood pressure (SBP). Logistic regression analysis was used to assess the influence of age-adjusted SBP Z-scores, age and gender on the outcomes. RESULTS: We included 19,500 patients from 159 GP's practices of whom 1,181 (6.1 %) were newly diagnosed with HT. Corrected for age-adjusted SBP, older patients were less likely to be diagnosed with HT (odds ratio per year age increase 0.98, p < 0.001). Corrected for age-adjusted SBP, no significant effect of age on the probability of treatment in newly diagnosed HT patients was observed (p = 0.82). CONCLUSIONS: This study showed that GPs are less inclined to diagnose HT with increasing patient age, but do not withhold treatment when they diagnose HT in older patients.

Women with silicone breast implants and unexplained systemic symptoms: a descriptive cohort study.

BACKGROUND: Since their introduction, the safety of silicone breast implants has been under debate. Although an association with systemic diseases was never established, women continuously blamed implants for their unexplained systemic symptoms. In 2011, a pattern of symptoms caused by systemic reactions to adjuvants (e.g. vaccines, silicone) was identified: 'autoimmune syndrome induced by adjuvants' (ASIA). Our aim was to collect a cohort of women with silicone breast implants and unexplained systemic symptoms to identify a possible pattern and compare this with ASIA. METHODS: Women with silicone breast implants and unexplained systemic symptoms were invited through national media to visit a special outpatient clinic in Amsterdam. All were examined by experienced consultant physicians and interviewed. Chest X-ray and laboratory tests were performed. RESULTS: Between March 2012 and 2013, 80 women were included, of which 75% reported pre-existent allergies. After a symptom-free period of years, a pattern of systemic symptoms developed, which included fatique, neurasthenia, myalgia, arthralgia and morning stiffness in more than 65% of women. All had at least two major ASIA criteria and 79% fulfilled ≥ 3 typical clinical ASIA manifestations. After explantation, 36 out of 52 women experienced a significant reduction of symptoms. CONCLUSIONS: After excluding alternative explanations, a clear pattern of signs and symptoms was recognised. Most women had pre-existent allergies, suggesting that intolerance to silicone or other substances in the implants might cause their symptoms. In 69% of women, explantation of implants reduced symptoms. Therefore, physicians should recognise this pattern and consider referring patients for explantation.

Concurrent bio-electricity and biomass production in three Plant-Microbial Fuel Cells using Spartina anglica, Arundinella anomala and Arundo donax.

In a Plant Microbial Fuel Cell (P-MFC) three plants were tested for concurrent biomass and bio-electricity production and maximization of power output. Spartina anglica and Arundinella anomala concurrently produced biomass and bio-electricity for six months consecutively. Average power production of the P-MFC with S. anglica during 13weeks was 16% of the theoretical maximum power and 8% during 7weeks for A. anomala. The P-MFC with Arundo donax, did not produce electricity with a stable output, due to break down of the system. The highest obtained power density in a P-MFC was 222mW/m(2) membrane surface area with S. anglica, over twice as high as the highest reported power density in a P-MFC. High biomass yields were obtained in all P-MFC's, with a high root:shoot ratio, probably caused nutrient availability and anaerobia in the soil. Power output maximization via adjusting load on the system lead to unstable performance of the P-MFC.

Generic computer-based questionnaires: an extension to OpenSDE.

Development of computer-based questionnaires (CQs) has been an ongoing challenge since the 1960s. The added value of such CQs for data collection and the acceptance by patients have been well documented. Many questionnaire projects, however, were temporary due to dedicated software, limited funding, and lack of integration with medical information systems. Also, the use of a fixed dedicated database makes integration cumbersome, as change in content requires change to the data model. Since much of the functional requirement of CQs is not dependent on content, the challenge is to both separate functionality and database structure from content. Following these principles, we extended OpenSDE, a generic application for structured data entry, with a tool to construct and run CQs as an alternative way of data input. We propose the combination of a generic building tool and a content-independent data model as an effective strategy to tackle the above-mentioned problems in CQ development.

[Missed infections in immigrant children]. / Gemiste pathogenen bij immigrerende kinderen.

Three African children who migrated to the Netherlands developed serious infections after they arrived. The first patient, a girl of 3 years adopted from the Zaire, was discovered to be a chronic hepatitis B carrier. Advice to vaccinate her whole adoption family was not followed. Her adoptive mother became infected with hepatitis B. The second patient, an Ethiopian girl of 13 years, was not adequately screened for infections on arrival. She was a chronic hepatitis B carrier and infected her adoptive mother. Seven years later she developed pulmonary tuberculosis with cavity formation and infected four contacts. The third patient, a 15-year-old political refugee from Zaire, who developed paediatric aids and later died of it, was not screened according to the screening protocol advised for immigrating children. All immigrating children should be fully and adequately screened for infectious diseases upon arrival in the Netherlands.

18q- and 18q+ mosaicism in a mentally retarded boy.

A mentally retarded boy was found to have an unusual chromosomal mosaicism [46,XY, del(18) (q22)/46,XY,iso psu dic(18)(q23)]. The clinical manifestations are compatible with the 18q- syndrome. The chromosome alteration was defined by high resolution banding and fluorescence in situ hybridization (FISH). A mechanism to explain the origin of the two cell lines is presented and discussed.