Developmental and epileptic encephalopathy 56 due to YWHAG variants: 12 new cases and review of the literature.

Background And Objectives: Developmental and epileptic encephalopathy 56 (DEE-56) is caused by pathogenic variants in YWHAG and is characterized by early-onset epilepsy and neurodevelopmental delay. This study reports on a cohort of DEE-56 individuals, correlating antiseizure medication usage and comorbidities, to aid in understanding disease evolution.

Methods: We analyzed data from thirty-nine individuals aged 3-40 years with YWHAG variants, including 12 previously unreported individuals (2 of these with recurrent distal 7q11.

Comparison of OBGYN postgraduate curricula and assessment methods between Canada and the Netherlands: an auto-ethnographic study.

Introduction: Although the Dutch and the Canadian postgraduate Obstetrics and Gynecology (OBGYN) medical education systems are similar in their foundations [programmatic assessment, competency based, involving CanMED roles and EPAs (entrustable professional activities)] and comparable in healthcare outcome, their program structures and assessment methods considerably differ.

Materials And Methods: We compared both countries' postgraduate educational blueprints and used an auto-ethnographic method to gain insight in the effects of training program structure and assessment methods on how trainees work. The research questions for this study are as follows: what are the differences in program structure and assessment program in Obstetrics and Gynecology postgraduate medical education in the Netherlands and Canada? And how does this impact the advancement to higher competency for the postgraduate trainee?

Results: We found four main differences.

IVF versus IUI with ovarian stimulation for unexplained infertility: a collaborative individual participant data meta-analysis.

Background: IVF and IUI with ovarian stimulation (IUI-OS) are widely used in managing unexplained infertility. IUI-OS is generally considered first-line therapy, followed by IVF only if IUI-OS is unsuccessful after several attempts. However, there is a growing interest in using IVF for immediate treatment because it is believed to lead to higher live birth rates and shorter time to pregnancy.

Genetic diagnostic yield in an 11-year cohort of craniosynostosis patients.

Craniosynostosis may present in isolation, 'non-syndromic', or with additional congenital anomalies/neurodevelopmental disorders, 'syndromic'. Clinical focus shifted from confirming classical syndromic cases to offering genetic testing to all craniosynostosis patients. This retrospective study assesses diagnostic yield of molecular testing by investigating prevalences of chromosomal and monogenic (likely) pathogenic variants in an 11-year cohort of 1020 craniosynostosis patients.

Case Report and Review of the Literature: Congenital Diaphragmatic Hernia and Craniosynostosis, a Coincidence or Common Cause?

Congenital diaphragmatic hernia (CDH) is a life-threatening birth defect that presents as either an isolated diaphragm defect or as part of a complex disorder with a wide array of anomalies (complex CDH). Some patients with complex CDH display distinct craniofacial anomalies such as craniofrontonasal dysplasia or craniosynostosis, defined by the premature closure of cranial sutures. Using clinical whole exome sequencing (WES), we found a missense variant in a patient with a left-sided congenital diaphragmatic hernia as well as sagittal suture craniosynostosis.

A Retrospective Analysis of Female Müllerian Duct Anomalies in Association With Congenital Renal Abnormalities.

Study Objective: Müllerian (paramesonephric) duct anomalies (MDAs) are associated with several coexisting congenital abnormalities, including renal abnormalities. Although congenital renal abnormalities may remain asymptomatic, the consequences should not be underestimated. In both the literature and clinical practice, it remains necessary to improve awareness of the co-occurrence of different congenital renal abnormalities in women with MDAs.

Gynecological Surveillance and Surgery Outcomes in Dutch Lynch Syndrome Carriers.

Lynch syndrome (LS) is caused by pathogenic germline variants in DNA mismatch repair (MMR) genes, predisposing female carriers for endometrial cancer (EC) and ovarian cancer (OC). Since gynecological LS surveillance guidelines are based on little evidence, we assessed its outcomes. Data regarding gynecological tumors, surveillance, and (risk-reducing) surgery were collected from female LS carriers diagnosed in our center since 1993.

The Management of Peutz-Jeghers Syndrome: European Hereditary Tumour Group (EHTG) Guideline.

The scientific data to guide the management of Peutz-Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients. Methods: Literature searches were performed using MEDLINE, Embase, and Cochrane.

The new pan-European post-specialty training curriculum in Paediatric and Adolescent Gynaecology.

Interest in the field of Paediatric and Adolescent Gynaecology (PAG) has increased substantially over the last decade. Currently there is minimal consensus on how to interpret and validate professional experience, medical knowledge and surgical skills for doctors (accredited in Obstetrics and Gynaecology) who have an interest in and wish to achieve sub-specialisation in PAG. The challenge for the future of PAG is to create a framework of guidelines and references which in turn culminates in improvement and harmonisation in PAG healthcare delivery.

Raloxifene augmentation in men and women with a schizophrenia spectrum disorder: A study protocol.

Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women.

The diagnostic value of magnetic resonance imaging in differentiating benign and malignant pediatric ovarian tumors.

Background: The diagnostic workup of ovarian tumors in children and adolescents is challenging because preserving fertility, in addition to oncological safety, is of particular importance in this population. Therefore, a thorough preoperative assessment of ovarian tumors is required.

Objective: To investigate the diagnostic value of MR imaging in differentiating benign from malignant ovarian tumors in children and adolescents.

Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer.

Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylation in vitro and in vivo. Immunofluorescence microscopy and ATAC-See revealed the association of this modification with active chromatin.

MR imaging in discriminating between benign and malignant paediatric ovarian masses: a systematic review.

Objectives: The use of magnetic resonance (MR) imaging in differentiation between benign and malignant adnexal masses in children and adolescents might be of great value in the diagnostic workup of sonographically indeterminate masses, since preserving fertility is of particular importance in this population. This systematic review evaluates the diagnostic value of MR imaging in children with an ovarian mass.

Methods: The review was made according to the PRISMA Statement.

Yield of Lynch Syndrome Surveillance for Patients With Pathogenic Variants in DNA Mismatch Repair Genes.

Background & Aims: Patients with Lynch syndrome are offered the same colorectal cancer (CRC) surveillance programs (colonoscopy every 2 years), regardless of the pathogenic DNA mismatch repair gene variant the patient carries. We aimed to assess the yield of surveillance for patients with these variants in MLH1, MSH2, MSH6, and PMS2.

Methods: We analyzed data on colonoscopy surveillance, including histopathology analysis, from all patients diagnosed with Lynch syndrome (n = 264) at a single center.

From prescription to guidance: a European framework for generic competencies.

In postgraduate medical education, required competencies are described in detail in existing competency frameworks. This study proposes an alternative strategy for competency-based medical education design, which is supported by change management theories. We demonstrate the value of allowing room for re-invention and creative adaptation of innovations.

A qualitative study on harmonization of postgraduate medical education in Europe: negotiating flexibility is key.

Introduction: International harmonization of postgraduate medical education is gaining importance in the globalization of medical education. Harmonization is regarded as the establishment of common standards in education, while maintaining regional or local freedom to adapt training to contexts. During the development of a harmonized curriculum, tensions between standardization and contextualization may surface.

Improving the training of the future gynaecologist: development of a European curriculum in Obstetrics and Gynaecology (EBCOG-PACT).

The European Board & College of Obstetrics and Gynaecology has initiated improvement of the European standards of training in Obstetrics and Gynaecology through the project called 'EBCOG-PACT'. In this project, a pan-European curriculum for postgraduate training in Obstetrics and Gynaecology has been developed. The curriculum is societally responsive, and based on the latest medical educational methodology.

Routine Molecular Analysis for Lynch Syndrome Among Adenomas or Colorectal Cancer Within a National Screening Program.

Background & Aims: It is important to identify individuals with Lynch syndrome because surveillance programs can reduce their morbidity and mortality from colorectal cancer (CRC). We assessed the diagnostic yield of immunohistochemistry to detect Lynch syndrome in patients with advanced and multiple adenomas within our national CRC screening program.

Methods: We performed a prospective study of all participants (n = 1101; 55% male; median age, 66 years; interquartile range, 61-70 years) referred to the Erasmus MC in The Netherlands after a positive result from a fecal immunohistochemical test, from December 2013 to December 2016.

Evaluation of current prediction models for Lynch syndrome: updating the PREMM5 model to identify PMS2 mutation carriers.

Until recently, no prediction models for Lynch syndrome (LS) had been validated for PMS2 mutation carriers. We aimed to evaluate MMRpredict and PREMM5 in a clinical cohort and for PMS2 mutation carriers specifically. In a retrospective, clinic-based cohort we calculated predictions for LS according to MMRpredict and PREMM5.

What European gynaecologists need to master: Consensus on medical expertise outcomes of pan-European postgraduate training in obstetrics & gynaecology.

Objective: European harmonisation of training standards in postgraduate medical education in Obstetrics and Gynaecology is needed because of the increasing mobility of medical specialists. Harmonisation of training will provide quality assurance of training and promote high quality care throughout Europe. Pan-European training standards should describe medical expertise outcomes that are required from the European gynaecologist.

Suspected Lynch syndrome associated MSH6 variants: A functional assay to determine their pathogenicity.

Lynch syndrome (LS) is a hereditary cancer predisposition caused by inactivating mutations in DNA mismatch repair (MMR) genes. Mutations in the MSH6 DNA MMR gene account for approximately 18% of LS cases. Many LS-associated sequence variants are nonsense and frameshift mutations that clearly abrogate MMR activity.

Cost-effectiveness of routine screening for Lynch syndrome in endometrial cancer patients up to 70years of age.

Purpose: To assess cost-effectiveness of routine screening for Lynch Syndrome (LS) in endometrial cancer (EC) patients ≤70years of age.

Methods: Consecutive EC patients ≤70years of age were screened for LS by analysis of microsatellite instability, immunohistochemistry and MLH1 hypermethylation. Costs and health benefit in life years gained (LYG) included surveillance for LS carriers among EC patients and relatives.

Small-bowel Surveillance in Patients With Peutz-Jeghers Syndrome: Comparing Magnetic Resonance Enteroclysis and Double Balloon Enteroscopy.

Background And Study Aims: Small-bowel surveillance with polypectomy of polyps ≥15 mm prevents complications in patients with Peutz-Jeghers syndrome (PJS). We aimed to compare magnetic resonance enteroclysis (MRE) and double balloon enteroscopy (DBE) for diagnostic yield of these polyps and for patient preference.

Materials And Methods: PJS patients prospectively underwent MRE followed by proximal DBE within 20 weeks.

Paving the road for a European postgraduate training curriculum.

The 'Project for Achieving Consensus in Training' has been initiated by the European Board & College of Obstetrics and Gynaecology to harmonise training in Obstetrics and Gynaecology throughout Europe. In this project called the EBCOG-PACT, a state of the art pan-European training curriculum will be developed. Implementation of a pan-European curriculum will enhance harmonisation of both quality standards of women's healthcare practice and standards of postgraduate training.

Cost-effectiveness of routine screening for Lynch syndrome in colorectal cancer patients up to 70 years of age.

Purpose: To assess the cost-effectiveness of routine Lynch syndrome (LS) screening among colorectal cancer (CRC) patients ≤70 years of age.

Methods: A population-based series of CRC patients ≤70 years of age was routinely screened for LS. We calculated life years gained (LYG) and incremental cost-effectiveness ratios (ICERs) for different age cutoffs and comparing age-targeted screening with the revised Bethesda guidelines.