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Objective Maternal diabetes in pregnancy is associated with structural anomalies of the fetal heart, as well as hypertrophy and functional impairment. This systematic review and meta‐analysis aimed to estimate the effect of maternal diabetes on fetal cardiac function as measured by prenatal echocardiography. Methods We performed a search of the EMBASE, PubMed and The Cochrane Library databases, from inception to 4 July 2019, for studies evaluating fetal cardiac function using echocardiography in pregnancies affected by diabetes compared with uncomplicated pregnancies. Outcome measures were cardiac hypertrophy and diastolic, systolic and overall cardiac function as assessed by various ultrasound parameters. The quality of the studies was assessed using the Newcastle–Ottawa Scale. Data on interventricular septal (IVS) thickness, myocardial performance index (MPI) and E/A ratio were pooled for the meta‐analysis using random‐effects models. For pregnancies with diabetes, results were reported overall and according to whether diabetes was pregestational (PDM) or gestational (GDM). Results were also stratified according to the trimester in which fetal cardiac assessment was performed. Results Thirty‐nine studies were included, comprising data for 2276 controls and 1925 women with pregnancy affected by diabetes mellitus (DM). Of these, 1120 had GDM, 671 had PDM and in 134 cases diabetes type was not specified. Fetal cardiac hypertrophy was more prevalent in diabetic pregnancies than in non‐diabetic controls in 21/26 studies, and impaired diastolic function was observed in diabetic pregnancies in 22/28 studies. The association between DM and systolic function was inconsistent, with 10/25 studies reporting no difference between cases and controls, although more recent studies measuring cardiac deformation, i.e. strain, did show decreased systolic function in diabetic pregnancies. Of the studies measuring overall fetal cardiac function, the majority (14/21) found significant impairment in diabetic pregnancies. Results were similar when stratified according to GDM or PDM. These effects were already present in the first trimester, but were most profound in the third trimester. Meta‐analysis of studies performed in the third trimester showed, compared with controls, increased IVS thickness in both PDM (mean difference, 0.75 mm (95% CI, 0.56–0.94 mm)) and GDM (mean difference, 0.65 mm (95% CI, 0.39–0.91 mm)) pregnancies, decreased E/A ratio in PDM pregnancies (mean difference, –0.09 (95% CI, –0.15 to –0.03)), no difference in E/A ratio in GDM pregnancies (mean difference, –0.01 (95% CI, –0.02 to 0.01)) and no difference in MPI in either PDM (mean difference, 0.04 (95% CI, –0.01 to 0.09)) or GDM (mean difference, 0.03 (95% CI, –0.01 to 0.06)) pregnancies. Conclusions The findings of this review show that maternal diabetes is associated with fetal cardiac hypertrophy, diastolic dysfunction and overall impaired myocardial performance on prenatal ultrasound, irrespective of whether diabetes is pregestational or gestational. Further studies are needed to demonstrate the relationship with long‐term outcomes. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Background and Aims: Advanced endoscopic resection techniques for complex colorectal polyps have evolved significantly over the past decade, leading to a management shift from surgical to endoscopic resection as the preferred treatment. However, in practice, interhospital consultation and appropriate referral management remain challenging, leading to unnecessary surgical resections. To support regional care for patients with complex colorectal polyps, facilitate peer consultations, and lower thresholds for referrals, an expert panel consultation platform was initiated in the northwestern region of the Netherlands. Methods: We initiated a regional expert panel in the northwestern region of the Netherlands for patients with complex colorectal polyps and studied the implementation, adaption, and clinical impact. All panel consultations between June 2019 and May 2021 were retrospectively analyzed, and user satisfaction among panel members was evaluated. Results: Eighty-eight patients with complex colorectal polyps from 11 of 15 participating centers (73.3%) were discussed in our panel. The most common reason for panel consultation was suspicion of invasive cancer in 36.4% (n = 32). After panel consultation, 43.2% of the consulting endoscopists (n = 38) changed their initial treatment strategy, and in 63.6% (n = 56) patients were referred to another endoscopy center. Of 26 cases submitted with a primary proposal for surgical treatment, surgery was avoided in 7 (26.9%). User satisfaction was rated high in most participating centers (91.7%). Conclusions: Our study shows that implementation of and consultation with a regional expert panel can be a valuable tool for endoscopists to guide and optimize treatment of complex colorectal polyps and facilitate interhospital referrals in a regional network.

Statement of problem Whether the precision of fit of computer-aided design and computer-aided manufacturing (CAD-CAM) complete crowns is affected by the finish line configuration is unclear. Purpose The purpose of this in vitro study was to evaluate the marginal and internal fit of CAD-CAM ceramic crowns made from lithium disilicate based on 3 different finish lines (rounded shoulder, chamfer, feather-edge). Materials and methods Thirty anterior lithium disilicate complete crowns (n=10 per finish line group) were fabricated by following a completely digital workflow based on digital scans made with the TRIOS scanner. The crowns were adhesively cemented on duplicate dies of the respective prepared Typodont teeth, and the marginal gap, absolute marginal discrepancy, and internal gap were evaluated by using microcomputed tomography (μCT). A total of 66 values were obtained for each specimen from sagittal and transaxial sections, and a rendering software program was used to calculate the volume of the cement gap for each specimen by means of 3D region growing. Two-way ANOVA, Tukey post hoc tests with Bonferroni correction, and the Kruskal-Wallis test were used to compare the values between the experimental groups (α=.05). Results Marginal gap and absolute marginal discrepancy values were statistically significantly different between groups. In ascending order, marginal gap values were 23 ±14 μm for rounded shoulder, 54 ±28 μm for chamfer, and 96 ±36 μm for feather-edge finish lines. Absolute marginal discrepancy values were 96 ±34 μm for rounded shoulder, 124 ±37 μm for chamfer, and 157 ±34 μm for feather-edge finish lines. Internal gap values were 111 ±14 μm for feather-edge, 136 ±22 μm for chamfer, and 168 ±25 μm for rounded shoulder finish lines. The differences in cement volume between groups were not statistically significant (P=.200). Conclusions All 3 finish lines produced marginal gaps within the range of clinically accep table values. Lithium disilicate CAD crowns with a rounded shoulder finish line had the best marginal fit but the poorest internal fit, and lithium disilicate CAD crowns with a feather-edge finish line had the best internal fit but the poorest marginal fit.

ObjectiveThe aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these outcomes.DesignWe performed a multicentre retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. Our primary aim was to assess infection rate and our secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies.ResultsWe included 1000 children born to 626 mothers (381 (61%) Crohn’s disease, 225 (36%) ulcerative colitis and 20 (3%) IBD unclassified). In total, 196 (20%) had intrauterine exposure to anti-tumour necrosis factor-α (anti-TNF-α) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNF-α and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. We did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during the pregnancy without affecting birth outcomes and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population.ConclusionIn our study, we found no association between in utero exposure to anti-TNF-α and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies.

BACKGROUND: The LIR!C trial showed that laparoscopic ileocaecal resection is a cost-effective treatment that has similar quality-of-life outcomes to treatment with infliximab, an anti-tumour necrosis factor (TNF) drug. We aimed to compare long-term outcomes of both interventions and identify baseline factors associated with the duration of treatment effect in each group.METHODS: In this retrospective follow-up study, we collected data from patients who participated in the LIR!C trial, a multicentre randomised controlled trial that compared quality of life after surgical resection versus infliximab in adult patients with non-stricturing and immunomodulator-refractory ileocaecal Crohn's disease. From Jan 1 to May 1, 2018, we collected follow-up data from the time from enrolment in the LIR!C trial until the last visit at either the gastrointestinal surgeon or gastroenterologist. In this study, outcomes of interest were need for surgery or repeat surgery or anti-TNF therapy, duration of treatment effect, and identification of factors associated with the duration of treatment effect. Duration of treatment effect was defined as the time without need for additional Crohn's disease-related treatment (corticosteroids, immunomodulators, biologics, or surgery).FINDINGS: We collected long-term follow-up data for 134 (94%) of 143 patients included in the LIR!C trial, of whom 69 were in the resection group and 65 were in the infliximab group. Median follow-up was 63·5 months (IQR 39·0-94·5). In the resection group, 18 (26%) of 69 patients started anti-TNF therapy and none required a second resection. 29 (42%) patients in the resection group did not require additional Crohn's disease-related medication, although 14 (48%) of these patients were given prophylactic immunomodulator therapy. In the infliximab group, 31 (48%) of 65 patients had a Crohn's disease-related resection, and the remaining 34 patients maintained, switched, or escalated their anti-TNF therapy. Duration of treatment effect was similar in both groups, with a median time without additional Crohn's disease-related treatment of 33·0 months (95% CI 15·1-50·9) in the resection group and 34·0 months (0·0-69·3) in the infliximab group (log-rank p=0·52). In both groups, therapy with an immunomodulator, in addition to the allocated treatment, was associated with duration of treatment effect (hazard ratio for resection group 0·34 [95% CI 0·16-0·69] and for infliximab group 0·49 [0·26-0·93]).INTERPRETATION: These findings further support laparoscopic ileocaecal resection as a treatment option in patients with Crohn's disease with limited (affected segment ≤40 cm) and predominantly inflammatory terminal ileitis for whom conventional treatment is not successful.FUNDING: None.

Myotubular myopathy, also called X-linked centronuclear myopathy (XL-CNM), is a severe congenital disease targeted for therapeutic trials. To date, biomarkers to monitor disease progression and therapy efficacy are lacking. The Mtm1−/y mouse is a faithful model for XL-CNM, due to myotubularin 1 (MTM1) loss-of-function mutations. Using both an unbiased approach (RNA sequencing [RNA-seq]) and a directed approach (qRT-PCR and protein level), we identified decreased Mstn levels in Mtm1−/y muscle, leading to low levels of myostatin in muscle and plasma. Myostatin (Mstn or growth differentiation factor 8 [Gdf8]) is a protein released by myocytes and inhibiting muscle growth and differentiation. Decreasing Dnm2 by genetic cross with Dnm2+/− mice or by antisense oligonucleotides blocked or postponed disease progression and resulted in an increase in circulating myostatin. In addition, plasma myostatin levels inversely correlated with disease severity and with Dnm2 mRNA levels in muscles. Altered Mstn levels were associated with a generalized disruption of the myostatin pathway. Importantly, in two different forms of CNMs we identified reduced circulating myostatin levels in plasma from patients. This provides evidence of a blood-based biomarker that may be used to monitor disease state in XL-CNM mice and patients and supports monitoring circulating myostatin during clinical trials for myotubular myopathy., Graphical Abstract, X-linked centronuclear myopathy (XL-CNM) is a severe congenital disease targeted for therapeutic trials. The authors identified decreased plasma myostatin levels in XL-CNM patients and mice. Decreasing Dnm2 in mice blocked or postponed disease progression and resulted in an increase in circulating myostatin, supporting monitoring circulating myostatin in XL-CNM clinical trials.

Background: In the Netherlands, people with severe cognitive deficits due to Korsakoff syndrome are generally admitted to a specialized nursing home. Professional caregivers experience that these residents are often not aware of their deficits, and consequently, their willingness to accept care is relatively low. However, these residents need permanent support when performing daily tasks due to severe cognitive deficits. The combination of objective care needs and low subjective responsiveness makes caring for people with Korsakoff syndrome a complex undertaking. It is unknown how professional caregivers deal with this complex task and how they manage the associated ethical challenges. Objectives: The aim of this study was to explore the professional caregivers’ perspectives on good care for residents with Korsakoff syndrome. Methods: A qualitative study design was used. Data were collected via semi-structured interviews. The Framework Method was used for the thematic analyses of the interview data. Participants and research context: Five specialized nursing homes participated in this study. Twelve professional caregivers, including nurses, nursing assistants, and support workers, were selected based on the ability to provide rich information on the study topics and to capture a variety of demographic and professional characteristics. Ethical considerations: The institutional review board of the VU University Medical Center Amsterdam approved the research protocol. The study was conducted in accordance with the ethical principles for medical research involving human subjects. Findings: Three perspectives on good care emerged: (1) making daily life a joint effort, (2) being steadfast, and (3) treating with respect. Discussion and conclusion: Professional caregivers try to achieve responsiveness in people with Korsakoff syndrome in three different ways. These perspectives reflect fundamentally different views on the care relationship and the autonomy of the resident. By elucidating the three perspectives, we hope to promote the practitioners’ reflection on their own ideas about good care for people with Korsakoff syndrome.

BACKGROUND The International Consortium for Health Outcomes Measurement has published a set of patient-centered outcome measures for pregnancy and childbirth (PCB set), including patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs). To establish value-based pregnancy and childbirth care, the PCB set was implemented in the Netherlands, using the outcomes on the patient level for shared decision-making and on an aggregated level for quality improvement. OBJECTIVE This study aims to report first outcomes, experiences, and practice insights of implementing the PCB set in clinical practice. METHODS In total, 7 obstetric care networks across the Netherlands, each consisting of 1 or 2 hospitals and multiple community midwifery practices (ranging in number from 2 to 18), implemented the PROM and PREM domains of the PCB set as part of clinical routine. This observational study included all women participating in the clinical project. PROMs and PREMs were assessed with questionnaires at 5 time points: 2 during pregnancy and 3 post partum. Clinical threshold values (alerts) supported care professionals interpreting the answers, indicating possibly alarming outcomes per domain. Data collection took place from February 2020 to September 2021. Data analysis included missing (pattern) analysis, sum scores, alert rates, and sensitivity analysis. RESULTS In total, 1923 questionnaires were collected across the 5 time points: 816 (42.43%) at T1 (first trimester), 793 (41.23%) at T2 (early third trimester), 125 (6.5%) at T3 (maternity week), 170 (8.84%) at T4 (6 weeks post partum), and 19 (1%) at T5 (6 months post partum). Of these, 84% (1615/1923) were filled out completely. Missing items per domain ranged from 0% to 13%, with the highest missing rates for depression, pain with intercourse, and experience with pain relief at birth. No notable missing patterns were found. For the PROM domains, relatively high alert rates were found both in pregnancy and post partum for incontinence (469/1798, 26.08%), pain with intercourse (229/1005, 22.79%), breastfeeding self-efficacy (175/765, 22.88%), and mother-child bonding (122/288, 42.36%). Regarding the PREM domains, the highest alert rates were found for birth experience (37/170, 21.76%), shared decision-making (101/982, 10.29%), and discussing pain relief ante partum (310/793, 39.09%). Some domains showed very little clinical variation; for example, role of the mother and satisfaction with care. CONCLUSIONS The PCB set is a useful tool to assess patient-reported outcomes and experiences that need to be addressed over the whole course of pregnancy and childbirth. Our results provide opportunities to improve and personalize perinatal care. Furthermore, we could propose several recommendations regarding methods and timeline of measurements based on our findings. This study supports the implementation of the PCB set in clinical practice, thereby advancing the transformation toward patient-centered, value-based health care for pregnancy and childbirth.

Pathogenesis of viral infections of the central nervous system (CNS) is poorly understood, and this is partly due to the limitations of currently used preclinical models. Brain organoid models can overcome some of these limitations, as they are generated from human derived stem cells, differentiated in three dimensions (3D), and can mimic human neurodevelopmental characteristics. Therefore, brain organoids have been increasingly used as brain models in research on various viruses, such as Zika virus, severe acute respiratory syndrome coronavirus 2, human cytomegalovirus, and herpes simplex virus. Brain organoids allow for the study of viral tropism, the effect of infection on organoid function, size, and cytoarchitecture, as well as innate immune response; therefore, they provide valuable insight into the pathogenesis of neurotropic viral infections and testing of antivirals in a physiological model. In this review, we summarize the results of studies on viral CNS infection in brain organoids, and we demonstrate the broad application and benefits of using a human 3D model in virology research. At the same time, we describe the limitations of the studies in brain organoids, such as the heterogeneity in organoid generation protocols and age at infection, which result in differences in results between studies, as well as the lack of microglia and a blood brain barrier.

ObjectivesTo gain insight into the experiences of women with completing and discussing patient-reported outcome measures (PROM) and patient-reported experience measures (PREM), and tailoring their care based on their outcomes.DesignA mixed-methods prospective cohort study.SettingSeven obstetric care networks in the Netherlands that implemented a set of patient-centred outcome measures for pregnancy and childbirth (PCB set), published by the International Consortium for Health Outcomes Measurement.ParticipantsAll women, receiving the PROM and PREM questionnaires as part of their routine perinatal care, received an invitation for a survey (n=460) and an interview (n=16). The results of the survey were analysed using descriptive statistics; thematic inductive content analysis was applied on the data from open text answers and the interviews.ResultsMore than half of the survey participants (n=255) felt the need to discuss the outcomes of PROM and PREM with their care professionals. The time spent on completing questionnaires and the comprehensiveness of the questions was scored ‘good’ by most of the survey participants. From the interviews, four main themes were identified: content of the PROM and PREM questionnaires, application of these outcomes in perinatal care, discussing PREM and data capture tool. Important facilitators included awareness of health status, receiving personalised care based on their outcomes and the relevance of discussing PREM 6 months post partum. Barriers were found in insufficient information about the goal of PROM and PREM for individual care, technical problems in data capture tools and discrepancy between the questionnaire topics and the care pathway.ConclusionsThis study showed that women found the PCB set an acceptable and useful instrument for symptom detection and personalised care up until 6 months post partum. This patient evaluation of the PCB set has several implications for practice regarding the questionnaire content, role of care professionals and congruity with care pathways.