Prediction of molecular subclasses of uveal melanoma by deep learning using routine haematoxylin-eosin-stained tissue slides.

Aims: Uveal melanoma has a high propensity to metastasize. Prognosis is associated with specific driver mutations and copy number variations, and these can only be obtained after genetic testing. In this study we evaluated the efficacy of patient outcome prediction using deep learning on haematoxylin and eosin (HE)-stained primary uveal melanoma slides in comparison to molecular testing.

The enigma of sclera-specific autoimmunity in scleritis.

Scleritis is a severe and painful ophthalmic disorder, in which a pathogenic role for collagen-directed autoimmunity was repeatedly suggested. We evaluated the presence of sclera-specific antibodies in a large cohort of patients with non-infectious scleritis. Therefore, we prospectively collected serum samples from 121 patients with non-infectious scleritis in a multicenter cohort study in the Netherlands.

MR imaging for the quantitative assessment of brain iron in aceruloplasminemia: A postmortem validation study.

Aims: Non-invasive measures of brain iron content would be of great benefit in neurodegeneration with brain iron accumulation (NBIA) to serve as a biomarker for disease progression and evaluation of iron chelation therapy. Although magnetic resonance imaging (MRI) provides several quantitative measures of brain iron content, none of these have been validated for patients with a severely increased cerebral iron burden. We aimed to validate R* as a quantitative measure of brain iron content in aceruloplasminemia, the most severely iron-loaded NBIA phenotype.

Expression of HDACs 1, 3 and 8 Is Upregulated in the Presence of Infiltrating Lymphocytes in Uveal Melanoma.

In Uveal Melanoma (UM), an inflammatory phenotype is strongly associated with the development of metastases and with chromosome 3/BAP1 expression loss. As an increased expression of several Histone Deacetylases (HDACs) was associated with loss of chromosome 3, this suggested that HDAC expression might also be related to inflammation. We analyzed HDAC expression and the presence of leukocytes by mRNA expression in two sets of UM (Leiden and TCGA) and determined the T lymphocyte fraction through ddPCR.

Refractory Stage M Ganglioneuroblastoma With Bone Metastases and a Favorable, Chronic Course of Disease: Description of a Patient Cohort.

Refractory stage M neuroblastoma (NB) is associated with a poor prognosis and a progressive course of disease. Here, we describe a unique group of patients with a discrepant clinical course. Seven histologically confirmed ganglioneuroblastoma (GNB) (n=6) and differentiating NB (n=1) patients were identified who were diagnosed with stage M disease based on iodine-123-metaiodobenzylguanidine avid bone metastases.

Genetics of Ocular Melanoma: Insights into Genetics, Inheritance and Testing.

Ocular melanoma consists of posterior uveal melanoma, iris melanoma and conjunctival melanoma. These malignancies derive from melanocytes in the uveal tract or conjunctiva. The genetic profiles of these different entities differ from each other.

Biallelic Variants in , Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy.

Background: Pediatric cardiomyopathies are a clinically and genetically heterogeneous group of heart muscle disorders associated with high morbidity and mortality. Although knowledge of the genetic basis of pediatric cardiomyopathy has improved considerably, the underlying cause remains elusive in a substantial proportion of cases.

Methods: Exome sequencing was used to screen for the causative genetic defect in a pair of siblings with rapidly progressive dilated cardiomyopathy and death in early infancy.

Aberrant MicroRNA Expression and Its Implications for Uveal Melanoma Metastasis.

Uveal melanoma (UM) is the most frequently found primary intra-ocular tumor in adults. It is a highly aggressive cancer that causes metastasis-related mortality in up to half of the patients. Many independent studies have reported somatic genetic changes associated with high metastatic risk, such as monosomy of chromosome 3 and mutations in .

Asymptomatic intraprosthetic dual mobility cup dislocation with increased metal ion levels.

With the increased use of dual-mobility cups (DMCs) in total-and revision hip arthroplasties, surgeons can expect an increase of known and new complications. During routine follow-up, we observed an asymptomatic patient with an intraprosthetic-dislocation (IPD) and elevated levels of serum metal ions (1.8 ppb of cobalt and 28.

Relocation of inadequate resection margins in the wound bed during oral cavity oncological surgery: A feasibility study.

Background: Specimen-driven intraoperative assessment of the resection margins provides immediate feedback if an additional excision is needed. However, relocation of an inadequate margin in the wound bed has shown to be difficult. The objective of this study is to assess a reliable method for accurate relocation of inadequate tumor resection margins in the wound bed after intraoperative assessment of the specimen.

Craniosynostosis affects the majority of mucopolysaccharidosis patients and can contribute to increased intracranial pressure.

Background: The mucopolysaccharidoses are multisystem lysosomal storage diseases characterized by extensive skeletal deformities, including skull abnormalities. The objective of this study was to determine the incidence of craniosynostosis in the different mucopolysaccharidosis (MPS) types and its clinical consequences.

Methods: In a prospective cohort study spanning 10 years, skull imaging and clinical evaluations were performed in 47 MPS patients (type I, II, VI, and VII).

Mucolipidosis type III, a series of adult patients.

Background: Mucolipidosis type III α/β or γ (MLIII) are rare autosomal recessive diseases, in which reduced activity of the enzyme UDP-N-acetyl glucosamine-1-phosphotransferase (GlcNAc-PTase) leads to intra-lysosomal accumulation of different substrates. Publications on the natural history of MLIII, especially the milder forms, are scarce. This study provides a detailed description of the disease characteristics and its natural course in adult patients with MLIII.

Raman spectroscopy for assessment of bone resection margins in mandibulectomy for oral cavity squamous cell carcinoma.

Objectives: The aim of this study was to investigate the potential of Raman spectroscopy for detection of oral cavity squamous cell carcinoma (OCSCC) in bone resection surfaces during mandibulectomy.

Materials & Methods: Raman mapping experiments were performed on fresh mandible resection specimens from patients treated with mandibulectomy for OCSCC. A tumour detection algorithm was created based on water concentration and the high-wavenumber range (2800 cm-3050 cm) of the Raman spectra.

Expression and inhibition of BRD4, EZH2 and TOP2A in neurofibromas and malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNST) are rare, highly aggressive sarcomas that can occur spontaneously or from pre-existing plexiform neurofibromas in neurofibromatosis type1 (NF1) patients. MPNSTs have high local recurrence rates, metastasize easily, are generally resistant to therapeutic intervention and frequently fatal for the patient. Novel targeted therapeutic strategies are urgently needed.

Raman spectroscopy for cancer detection and cancer surgery guidance: translation to the clinics.

Oncological applications of Raman spectroscopy have been contemplated, pursued, and developed at academic level for at least 25 years. Published studies aim to detect pre-malignant lesions, detect cancer in less invasive stages, reduce the number of unnecessary biopsies and guide surgery towards the complete removal of the tumour with adequate tumour resection margins. This review summarizes actual clinical needs in oncology that can be addressed by spontaneous Raman spectroscopy and it provides an overview over the results that have been published between 2007 and 2017.

Risk and relevance of open lung biopsy in pediatric ECMO patients: the Dutch experience.

Background: Open lung biopsy can help differentiate between reversible and irreversible lung disease and may guide therapy. To assess the risk-benefit ratio of this procedure in pediatric extracorporeal membrane oxygenation (ECMO) patients, we reviewed data of all patients who underwent an open lung biopsy during ECMO in one of the two pediatric ECMO centers in a nationwide study in the Netherlands.

Results: In nineteen neonatal and six pediatric patients (0-15.

Water Concentration Analysis by Raman Spectroscopy to Determine the Location of the Tumor Border in Oral Cancer Surgery.

Adequate resection of oral cavity squamous cell carcinoma (OCSCC) means complete tumor removal with a clear margin of more than 5 mm. For OCSCC, 85% of the surgical resections appear inadequate. Raman spectroscopy is an objective and fast tool that can provide real-time information about the molecular composition of tissue and has the potential to provide an objective and fast intraoperative assessment of the entire resection surface.

Malignant pleural mesothelioma with lacrimal gland metastasis.

Purpose: To describe a rare clinical case of biopsy-proven metastatic mesothelioma of the lacrimal gland which responded well to chemo and radiation therapy.

Methods: Interventional case report.

Results: A 55-year-old woman with an untreated malignant biopsy-proven pleural mesothelioma presented with right proptosis, diplopia and hypoglobus.