The effect of three years of TNFα blocking therapy on markers of bone turnover and their predictive value for treatment discontinuation in patients with ankylosing spondylitis: a prospective longitudinal observational cohort study.

Introduction: The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS).

Methods: This is a prospective cohort study of 111 consecutive AS outpatients who started TNF-α blocking therapy. Clinical assessments and BTM were assessed at baseline, three and six months, as well as at one, two, and three years.

Long-term visual functioning after eclampsia.

Objective: Complete neurocognitive recovery after eclampsia has been questioned with the expression of neurocognitive deficits by affected women and demonstration of cerebral white matter lesions on magnetic resonance imaging years after eclampsia. We hypothesized that formerly eclamptic women may experience impaired vision-related quality of life (QOL) and visual field loss as a result of the presence of such lesions in the cerebral visual areas.

Methods: Using the National Eye Institute Visual Function Questionnaire-39/Nederlands questionnaire, vision-related QOL was compared between formerly eclamptic women and control participants after normotensive pregnancies.

A diagnostic program for patients suspected of having lung cancer.

Background: A standardized diagnostic program, initiated to reduce the length of the diagnostic track and to improve application of diagnostic tools for patients referred with suspicious abnormalities on standard chest radiographs, was evaluated.

Methods: The findings on integrated positron emission tomography/computed tomography (PET-CT) determined the choice of invasive investigations to be performed the same day. Diagnostic results, time courses, and number and sorts of applied invasive investigations were assessed.

Complications following lung surgery in the Dutch-Belgian randomized lung cancer screening trial.

Objectives: To assess the complication rate in participants of the screen arm of the NELSON lung cancer screening trial who underwent surgical resection and to investigate, based on a literature review, whether the complication rate, length of hospital stay, re-thoracotomy and mortality rates after a surgical procedure were different from those of the non-screening series, taking co-morbidity into account.

Methods: Between April 2004 and December 2008, 198 subjects underwent thoracic surgery. Co-morbid conditions were retrieved from the medical records.

The impact of a pulmonary-artery-catheter-based protocol on fluid and catecholamine administration in early sepsis.

Objective. The pulmonary artery catheter (PAC) remains topic of debate. Despite abundant data, it is of note that many trials did not incorporate a treatment protocol.

Rare thoracic cancers, including peritoneum mesothelioma.

Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002, registered in 89 population-based cancer registries (CRs) and followed-up to 31st December 2003. Over 17,688 cases of rare thoracic cancers were selected based on the list of the RACECARE project.

Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer.

Unlabelled: While genomically targeted therapies have improved outcomes for patients with lung adenocarcinoma, little is known about the genomic alterations which drive squamous cell lung cancer. Sanger sequencing of the tyrosine kinome identified mutations in the DDR2 kinase gene in 3.8% of squamous cell lung cancers and cell lines.

Vasopressin release is enhanced by the Hemocontrol biofeedback system and could contribute to better haemodynamic stability during haemodialysis.

Background: Haemodialysis with the Hemocontrol biofeedback system (HHD) is associated with improved haemodynamic stability compared with standard haemodialysis (HD) (SHD). Although the beneficial effect of HHD on haemodynamic stability is generally explained by its effect on blood volume, we questioned whether additional factors could play a role. Since HHD is associated with higher initial dialysate sodium concentrations and ultrafiltration (UF) rate, we studied whether the beneficial effect of HHD on haemodynamic stability may be explained by an increased release of the vasoconstrictor arginine vasopressin (AVP).

The role of conventional bronchoscopy in the workup of suspicious CT scan screen-detected pulmonary nodules.

Background: Up to 50% of the participants in CT scan lung cancer screening trials have at least one pulmonary nodule. To date, the role of conventional bronchoscopy in the workup of suspicious screen-detected pulmonary nodules is unknown. If a bronchoscopic evaluation could be eliminated, the cost-effectiveness of a screening program could be enhanced and the potential harms of bronchoscopy avoided.

Unraveling the regulatory mechanisms underlying tissue-dependent genetic variation of gene expression.

It is known that genetic variants can affect gene expression, but it is not yet completely clear through what mechanisms genetic variation mediate this expression. We therefore compared the cis-effect of single nucleotide polymorphisms (SNPs) on gene expression between blood samples from 1,240 human subjects and four primary non-blood tissues (liver, subcutaneous, and visceral adipose tissue and skeletal muscle) from 85 subjects. We characterized four different mechanisms for 2,072 probes that show tissue-dependent genetic regulation between blood and non-blood tissues: on average 33.

Long-term excess mortality for survivors of non-small cell lung cancer in the Netherlands.

Introduction: Most patients diagnosed with non-small cell lung cancer (NSCLC) die within the first few years after diagnosis. However, only little is known about those who have survived these first years. We aimed to study conditional 5-year relative survival rates for NSCLC patients during long-term follow-up.

The influence of maternal and paternal factors on time to pregnancy--a Dutch population-based birth-cohort study: the GECKO Drenthe study.

Background: Both maternal and paternal factors have been suggested to influence a couple's fecundity. To investigate this, we examined the role of several maternal and paternal lifestyle and socio-demographic factors as determinants of time to pregnancy (TTP) in a Dutch birth-cohort.

Methods: Groningen Expert Center for Kids with Obesity (GECKO) Drenthe is a population-based birth-cohort study of children born between April 2006 and April 2007 in Drenthe, a province of The Netherlands.

Safety and efficacy of first-line bevacizumab plus chemotherapy in elderly patients with advanced or recurrent nonsquamous non-small cell lung cancer: safety of avastin in lung trial (MO19390).

Introduction: Safety of Avastin in Lung (MO19390) was an international, open-label, single-arm study, which assessed the safety and efficacy of first-line bevacizumab (Avastin®) in combination with standard chemotherapy in patients (n = 2212) with advanced or recurrent non-small cell lung cancer (NSCLC). A preplanned subgroup analysis was performed to examine these outcomes in elderly patients older than 65 years.

Methods: Eligible patients with nonsquamous NSCLC received up to six cycles of bevacizumab (7.

Progress in standard of care therapy and modest survival benefits in the treatment of non-small cell lung cancer patients in the Netherlands in the last 20 years.

Introduction: Lung cancer is the leading cause of cancer mortality worldwide. We analyzed changes in treatment and their potential effect on survival of non-small cell lung cancer (NSCLC) patients in the Netherlands.

Methods: All NSCLC patients diagnosed during 1989-2009 (n=147,760) were selected from the population-based Netherlands Cancer Registry.

Multi-feature-based plaque characterization in ex vivo MRI trained by registration to 3D histology.

We present a new method for automated characterization of atherosclerotic plaque composition in ex vivo MRI. It uses MRI intensities as well as four other types of features: smoothed, gradient magnitude and Laplacian images at several scales, and the distances to the lumen and outer vessel wall. The ground truth for fibrous, necrotic and calcified tissue was provided by histology and μCT in 12 carotid plaque specimens.

[New 'targeted therapy' for lung cancer].

Patients with non-small cell lung cancer with specific mutations for which so-called 'targeted therapy' is available are likely to have a favourable tumour response. The first patient, a man aged 64 with an activating epidermal growth factor receptor (EGFR) mutation, had a longstanding tumour response on erlotinib, an EGFR tyrosine kinase inhibitor (TKI). After 16 months on treatment, there was still no progression of the disease.

Biliary atresia in the Netherlands: outcome of patients diagnosed between 1987 and 2008.

Objective: To examine the outcome of biliary atresia (BA) and to identify prognostic factors using a national database.

Study Design: All children born between January 1987 and December 2008 who underwent the Kasai surgical procedure for BA were retrieved from the Netherlands Study Group on Biliary Atresia Registry database. Outcomes were measured in terms of clearance of jaundice (bilirubin <1.

The prevalence of chromosomal abnormalities in subgroups of infertile men.

Background: The prevalence of chromosomal abnormalities is assumed to be higher in infertile men and inversely correlated with sperm concentration. Although guidelines advise karyotyping infertile men, karyotyping is costly, therefore it would be of benefit to identify men with the highest risk of chromosomal abnormalities, possibly by using parameters other than sperm concentration. The aim of this study was to evaluate several clinical parameters in azoospermic and non-azoospermic men, in order to assess the prevalence of chromosomal abnormalities in different subgroups of infertile men.

Modest improvements of survival for patients with small cell lung cancer aged 45 to 59 years only, diagnosed in the Netherlands, 1989 to 2008.

Introduction: Lung cancer was a major epidemic in the last decades; 10 to 15% of lung cancer consists of small cell lung cancer (SCLC). Several changes in the diagnostic and treatment procedures took place during the last 20 years. This article focuses on trends in incidence, treatment, and survival of SCLC observed since the 1990 s.

Randomized, placebo-controlled phase III study of docetaxel plus carboplatin with celecoxib and cyclooxygenase-2 expression as a biomarker for patients with advanced non-small-cell lung cancer: the NVALT-4 study.

Purpose: Cyclooxygenase-2 (COX-2) protein expression in patients with non-small-cell lung cancer (NSCLC) may be not only a prognostic marker but also predictive for COX-2 inhibition. We hypothesized that COX-2 expression is associated with shorter survival and that celecoxib, being a potent COX-2 inhibitor, increases tumor response and survival.

Patients And Methods: A phase III study was performed in patients with stage IIIb/IV NSCLC who had pathologic confirmation, no prior chemotherapy, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function.

Impact of the HYPITAT trial on doctors' behaviour and prevalence of eclampsia in the Netherlands.

We questioned if participation in the HYPITAT trial (induction of labour versus expectant monitoring in women with gestational hypertension or pre-eclampsia at term) impacted implementation of its results and subsequently maternal health. We identified women with hypertensive disease from the Perinatal Registry, and distinguished the period before, during and after the trial. We included 43 641 women.

Percutaneous ultrasound-guided biopsies in the evaluation of thoracic tumours after PET-CT: a prospective diagnostic study.

Background: Lesions detected by positron emission tomography-computed tomography (PET-CT) during the analysis of thoracic tumours are often impalpable at physical examination, and subsequent ultrasound (US) may aid in finding these lesions for pathologic evaluation.

Objectives: The success rate of percutaneous US-guided biopsies of palpable and non-palpable lesions and the impact on tumour stage were studied prospectively.

Methods: Lesions, significant for diagnosis and disease stage, with metabolic activity on PET-CT and presumed appropriate for percutaneous approach under US guidance were selected for cytologic aspiration or tissue core biopsies.

The role of the ¹⁸f-fluorodeoxyglucose-positron emission tomography scan in the Nederlands Leuvens Longkanker screenings Onderzoek lung cancer screening trial.

Background: In computed tomography lung cancer screening programs, up to 30% of all resections are futile.

Objective: To investigate whether a preoperative positron emission tomography (PET) after a conclusive or inconclusive nonsurgical workup will reduce the resection rate for benign disease in test-positive participants of a lung cancer screening program.

Methods: ¹⁸F-Fluorodeoxyglucose-PET scans were made in 220 test positives.

Trans-eQTLs reveal that independent genetic variants associated with a complex phenotype converge on intermediate genes, with a major role for the HLA.

For many complex traits, genetic variants have been found associated. However, it is still mostly unclear through which downstream mechanism these variants cause these phenotypes. Knowledge of these intermediate steps is crucial to understand pathogenesis, while also providing leads for potential pharmacological intervention.

Prediction of progression to a high risk situation in women with gestational hypertension or mild pre-eclampsia at term.

Objective: To evaluate whether progression to a high-risk situation is predictable in women with gestational hypertension (GH) or mild pre-eclampsia (PE) at term.

Methods: Women with a singleton pregnancy, a fetus in cephalic position, between 36 and 41 weeks of gestation, complicated by GH or mild PE that were managed expectantly, were selected from the HYPITAT trial. We evaluated the predictability of progression to a high-risk situation.