The bench is closer to the bedside than we think: Uncovering the ethical ties between preclinical researchers in translational neuroscience and patients in clinical trials.

Millions of people worldwide currently suffer from serious neurological diseases and injuries for which there are few, and often no, effective treatments. The paucity of effective interventions is, no doubt, due in large part to the complexity of the disorders, as well as our currently limited understanding of their pathophysiology. The bleak picture for patients, however, is also attributable to avoidable impediments stemming from quality concerns in preclinical research that often escape detection by research regulation efforts.

Evaluation of gold fiducial marker manual localisation for magnetic resonance-only prostate radiotherapy.

Background: The use of intraprostatic gold fiducial markers (FMs) ensures highly accurate and precise image-guided radiation therapy for patients diagnosed with prostate cancer thanks to the ease of localising FMs on photon-based imaging, like Computed Tomography (CT) images. Recently, Magnetic Resonance (MR)-only radiotherapy has been proposed to simplify the workflow and reduce possible systematic uncertainties. A critical, determining factor in the accuracy of such an MR-only simulation will be accurate FM localisation using solely MR images.

Excessive Extracellular ATP Desensitizes P2Y2 and P2X4 ATP Receptors Provoking Surfactant Impairment Ending in Ventilation-Induced Lung Injury.

Stretching the alveolar epithelial type I (AT I) cells controls the intercellular signaling for the exocytosis of surfactant by the AT II cells through the extracellular release of adenosine triphosphate (ATP) (purinergic signaling). Extracellular ATP is cleared by extracellular ATPases, maintaining its homeostasis and enabling the lung to adapt the exocytosis of surfactant to the demand. Vigorous deformation of the AT I cells by high mechanical power ventilation causes a massive release of extracellular ATP beyond the clearance capacity of the extracellular ATPases.

Development and validation of an admission prediction tool for emergency departments in the Netherlands.

Objective: Early prediction of admission has the potential to reduce length of stay in the ED. The aim of this study is to create a computerised tool to predict admission probability.

Methods: The prediction rule was derived from data on all patients who visited the ED of the Rijnstate Hospital over two random weeks.

Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study.

An international, multicenter registry was established to collect retrospective and prospective clinical data on patients with pyruvate kinase (PK) deficiency, the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Medical history and laboratory and radiologic data were retrospectively collected at enrollment for 254 patients with molecularly confirmed PK deficiency. Perinatal complications were common, including anemia that required transfusions, hyperbilirubinemia, hydrops, and prematurity.

Specific airway resistance is a better outcome parameter in bronchial provocation testing compared to FEV in patients with bronchial asthma.

Objectives: Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR). A bronchial provocation test (BPT) is used to test for AHR. However forced expiratory volume in one second (FEV), used as outcome parameter is effort-related, in contrast to specific airway resistance (sRaw).

[MRI-guided brachytherapy in prostate cancer].

The number of patients treated for prostate cancer by radiotherapy treatment has increased substantially over recent decades. However, after both external radiotherapy and brachytherapy, a subset of patients still develops recurrent disease during follow-up. In many patients these recurrences are often limited to one localisation in the prostate.

[Platelet function tests: tailored antiplatelet therapy for vascular patients?].

- Platelet aggregation inhibitors, also known as antiplatelet therapy (APT), are prescribed for the prevention of secondary cardiovascular events (CVE) after endovascular revascularization procedures.- Platelet aggregation inhibitors are not equally effective in all patients. The phenomenon of high residual platelet reactivity despite APT is called 'high on-treatment platelet reactivity' (HTPR); it bears an increased risk of secondary CVE.

Availability of hepatitis C diagnostics and therapeutics in European and Eurasia countries.

Background: Treatment with direct acting antiviral agents (DAAs) has provided sustained virological response rates in >95% of patients with chronic hepatitis C virus (HCV) infection. However treatment is costly and market access, reimbursement and governmental restrictions differ among countries. We aimed to analyze these differences among European and Eurasian countries.

Rupture of the posterior cul-de-sac during trial of labour after caesarean section.

Rupture of the vaginal wall in unobstructed labour is a rare entity in the developed world. This case report describes rupture of the posterior cul-de-sac in a healthy 34-year-old multiparous woman attempting trial of labour after caesarean section. The woman presented to the labour ward at term with spontaneous onset of contractions.

Declining Hepatitis C Virus (HCV) Incidence in Dutch Human Immunodeficiency Virus-Positive Men Who Have Sex With Men After Unrestricted Access to HCV Therapy.

Background: Direct-acting antivirals (DAAa) cure hepatitis C virus (HCV) infections in 95% of infected patients. Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) has been high for >10 years.

On the (im)possibility of reconstructing plasmids from whole-genome short-read sequencing data.

To benchmark algorithms for automated plasmid sequence reconstruction from short-read sequencing data, we selected 42 publicly available complete bacterial genome sequences spanning 12 genera, containing 148 plasmids. We predicted plasmids from short-read data with four programs (PlasmidSPAdes, Recycler, cBar and PlasmidFinder) and compared the outcome to the reference sequences. PlasmidSPAdes reconstructs plasmids based on coverage differences in the assembly graph.

[Awareness during focal epileptic seizures].

Not all epileptic seizures are accompanied by loss of awareness. Focal aware seizures provide an opportunity to predict the location of the epileptic source in the brain. The impact of these seizures is often underestimated, especially if someone has previously had seizures with loss of awareness.

Feasibility of MR-only proton dose calculations for prostate cancer radiotherapy using a commercial pseudo-CT generation method.

A magnetic resonance (MR)-only radiotherapy workflow can reduce cost, radiation exposure and uncertainties introduced by CT-MRI registration. A crucial prerequisite is generating the so called pseudo-CT (pCT) images for accurate dose calculation and planning. Many pCT generation methods have been proposed in the scope of photon radiotherapy.

Evaluation of an automatic MR-based gold fiducial marker localisation method for MR-only prostate radiotherapy.

An MR-only radiotherapy planning (RTP) workflow would reduce the cost, radiation exposure and uncertainties introduced by CT-MRI registrations. In the case of prostate treatment, one of the remaining challenges currently holding back the implementation of an RTP workflow is the MR-based localisation of intraprostatic gold fiducial markers (FMs), which is crucial for accurate patient positioning. Currently, MR-based FM localisation is clinically performed manually.

Computed Tomography and MR Imaging in Crystalline-Induced Arthropathies.

Crystalline-induced arthropathies impose substantial morbidity but can be challenging to diagnose, especially in early phases. The most common crystalline arthropathies are gout (monosodium urate deposition), calcium pyrophosphate dihydrate deposition, and hydroxyapatite deposition disease. Computed tomography (CT) and MR imaging provide 3-dimensional information on osseous structures, periarticular soft tissue, and tophi with superior spatial resolution.

The Eyesi simulator in training ophthalmology residents: results of a pilot study on self-efficacy, motivation and performance.

Purpose: To describe ophthalmology residents' motivation and self-efficacy during cataract surgery training and to assess the relationship of self-efficacy and motivation on both simulator (Eyesi) and real-life surgical performance.

Methods: Prospective cohort study using a within-subject design. Eight residents were asked to fill out questionnaires on self-efficacy and motivation towards the Eyesi simulator and real-life cataract surgery at three different moments.

Antegrade Dissection and Reentry as Part of the Hybrid Chronic Total Occlusion Revascularization Strategy: A Subanalysis of the RECHARGE Registry (Registry of CrossBoss and Hybrid Procedures in France, the Netherlands, Belgium and United Kingdom).

Background: Development of the CrossBoss and Stingray devices for antegrade dissection and reentry (ADR) of chronic total occlusions has improved historically suboptimal outcomes. However, the outcomes, safety, and failure modes of the technique have to be studied in a larger patient cohort. This preplanned substudy of the RECHARGE registry (Registry of CrossBoss and Hybrid Procedures in France, the Netherlands, Belgium and United Kingdom) aims to evaluate the value and use of ADR and determine its future position in contemporary chronic total occlusion intervention.

[Anticholinergic syndrome caused by contaminated herbal tea; acting swiftly to identify the source].

Background: Despite good manufacturing practice and quality control, consumer products can become contaminated. In some cases, this can result in severe and life-threatening intoxication with potentially fatal consequences.

Case Description: A 27-year-old man and a 28-year-old pregnant woman presented to the Emergency Department with severe anticholinergic syndrome after using a marshmallow root (Althaea officinalis) herbal remedy, mixed into hot chocolate drink, to reduce symptoms of common cold.

[Hepatopulmonary syndrome. A consideration in patients with liver disease accompanied by dyspnoea and hypoxaemia].

Background: Hepatopulmonary syndrome is a severe complication of liver disease, with greatly increased mortality. The syndrome is characterized by increased blood-flow, intrapulmonary vasodilatation and angiogenesis, leading to effects including the formation of shunts. This leads to a decrease in arterial oxygen pressure.

Is sweat chloride predictive of severity of cystic fibrosis lung disease assessed by chest computed tomography?

Background: Cystic Fibrosis (CF) lung disease is characterized by a marked heterogeneity. Sweat chloride-level is a functional marker of the CF Transmembrane Regulator (CFTR) protein and could be an important predictor of later disease severity.

Methods: In this retrospective analysis children from the Rotterdam CF clinic with available sweat chloride level at diagnosis and at least one routine spirometry-controlled volumetric chest CT scan in follow-up were included.

Towards a contemporary, comprehensive scoring system for determining technical outcomes of hybrid percutaneous chronic total occlusion treatment: The RECHARGE score.

Objectives: This study sought to create a contemporary scoring tool to predict technical outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) from patients treated by hybrid operators with differing experience levels.

Background: Current scoring systems need regular updating to cope with the positive evolutions regarding materials, techniques, and outcomes, while at the same time being applicable for a broad range of operators.

Methods: Clinical and angiographic characteristics from 880 CTO-PCIs included in the REgistry of CrossBoss and Hybrid procedures in FrAnce, the NetheRlands, BelGium and UnitEd Kingdom (RECHARGE) were analyzed by using a derivation and validation set (2:1 ratio).

[Transient monocular vision loss].

Transient monocular vision loss (TMVL) caused by temporary disturbance of blood flow to the retina is a harbinger of future vascular complications. The diagnosis may be difficult, not only because it is solely dependent on history taking, but also because the range of monocular visual symptoms a patient may experience is wide. The classic pattern of a sudden black or grey visual field, or a curtain that is drooping in front of one eye, easily fits in the diagnosis of TMVL; however, coloured vision or flashes should not always be considered as benign.

[Bitten by an exotic venomous snake].

Background: Patients who have been bitten by an exotic venomous snake are at risk of severe morbidity and a fatal outcome following an incorrect risk-assessment. Treatment with an antivenom can be necessary and can turn out to be lifesaving. In the Netherlands there are only a few cases of bites from exotic venomous snakes each year.