Lipids in hepatic glycogen storage diseases: pathophysiology, monitoring of dietary management and future directions.

Lipids in hepatic glycogen storage diseases: pathophysiology, monitoring of dietary management and future directions.

J Inherit Metab Dis. 2015 Jan 30;

Authors: Derks TG, van Rijn M

Abstract

Hepatic glycogen storage diseases (GSD) underscore the intimate relationship between carbohydrate and lipid metabolism. The hyperlipidemias in hepatic GSD reflect perturbed intracellular metabolism, providing biomarkers in blood to monitor dietary management. In different types of GSD, hyperlipidemias are of a different origin. Hypertriglyceridemia is most prominent in GSD type Ia and associated with long-term outcome morbidity, like pancreatitis and hepatic adenomas. In the ketotic subtypes of GSD, hypertriglyceridemia reflects the age-dependent fasting intolerance, secondary lipolysis and increased mitochondrial fatty acid oxidation. The role of high protein diets is established for ketotic types of GSD, but non-traditional dietary interventions (like medium-chain triglycerides and the ketogenic diet) in hepatic GSD are still controversial and necessitate further studies. Patients with these rare inherited disorders of carbohydrate metabolism meet several criteria of the metabolic syndrome, therefore close monitoring for cardiovascular diseases in ageing GSD patients may be justified.

PMID: 25633903 [PubMed - as supplied by publisher]

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Quality of life in adulthood after resection of a sacrococcygeal teratoma in childhood: a Dutch multicentre study.

Quality of life in adulthood after resection of a sacrococcygeal teratoma in childhood: a Dutch multicentre study.

Arch Dis Child Fetal Neonatal Ed. 2015 Jan 29;

Authors: Kremer ME, Dirix M, Koeneman MM, van Baren R, Heij HA, Wijnen MH, Wijnen RM, van der Zee DC, van Heurn LW

Abstract

OBJECTIVE: Children treated for sacrococcygeal teratoma (SCT) may experience functional sequelae later in life. It is not known whether SCT and associated problems affect the patient’s general quality of life (QoL). In a national survey, we evaluated general QoL in adults treated for SCT during childhood and compared the results to reference values for the Dutch population.

DESIGN: The records of patients aged ≥18 years treated for an SCT in one of the six paediatric surgical centres in the Netherlands from 1970 to 1993 were retrospectively reviewed; patient characteristics were retrieved from medical records. General QoL was evaluated using the Short Form 36 Health Survey (SF-36). The means of the eight SF-36 domain scores of patients treated for SCT were compared to reference values for the Dutch population (n=757, aged 18-43 years). Linear regression analysis was used to adjust for differences in baseline characteristics between both groups.

RESULTS: 46 of 51 patients treated for SCT during childhood (90.2%), with a mean age of 26.3 years (range 18.3-41.1), returned completed SF-36 questionnaires. Their scores on all SF-36 subcategories were equivalent to those of the Dutch reference population. No significant differences in the scores of the SF-36 subcategories were found after linear regression analysis adjusting for differences in age, sex and living status between both groups.

CONCLUSIONS: The long-term QoL of patients treated for SCT during childhood does not differ from that of the general population. Moreover, patients do not show impairment in social, physical or emotional functioning in adulthood.

PMID: 25634960 [PubMed - as supplied by publisher]

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Genome-wide analysis reveals two novel mosaic regions containing an ACME with an identical DNA sequence in the MRSA ST398-t011 and MSSA ST8-t008 isolates.

Genome-wide analysis reveals two novel mosaic regions containing an ACME with an identical DNA sequence in the MRSA ST398-t011 and MSSA ST8-t008 isolates.

J Antimicrob Chemother. 2015 Jan 28;

Authors: Sabat AJ, Ilczyszyn WM, van Rijen M, Akkerboom V, Sinha B, Kluytmans J, Miedzobrodzki J, Grundmann H, Friedrich AW

Abstract

OBJECTIVES: The presence of the arginine catabolic mobile element (ACME) in Staphylococcus aureus has been reported to enhance the colonization of the human host. The aim of this study was to determine the genetic organization of composite islands harbouring ACME.

METHODS: Two ACME-positive S. aureus isolates obtained during two different surveys conducted in the Netherlands and Poland were characterized in this study. The isolates were analysed by spa typing, DNA microarrays and whole-genome sequencing.

RESULTS: The two isolates harboured a truncated yet fully functional ACME type II with an identical nucleotide sequence, but differed in their adjacent mobile genetic elements. The first strain was a livestock-associated ST398-t011 MRSA, which had a staphylococcal cassette chromosome mec (SCCmec) composite island composed of SCCpls adjacent to orfX followed by ACME type II and SCCmec type IVa. The second ACME-positive isolate was an ST8-t008 MSSA. Its composite island showed an SCC-like element carrying the ccrC gene followed by ACME II.

CONCLUSIONS: This is the first report of an ACME in a livestock-associated MRSA ST398. It is also the first presentation of an ACME composite island structure in an MSSA isolate. Our findings indicate an extensive mosaicism of composite islands in S. aureus, which has implications for the transmissibility among humans and thus for public health.

PMID: 25634990 [PubMed - as supplied by publisher]

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IL-22-STAT3 Pathway Plays a Key Role in the Maintenance of Ileal Homeostasis in Mice Lacking Secreted Mucus Barrier.

IL-22-STAT3 Pathway Plays a Key Role in the Maintenance of Ileal Homeostasis in Mice Lacking Secreted Mucus Barrier.

Inflamm Bowel Dis. 2015 Jan 29;

Authors: Sovran B, Loonen LM, Lu P, Hugenholtz F, Belzer C, Stolte EH, Boekschoten MV, van Baarlen P, Kleerebezem M, de Vos P, Dekker J, Renes IB, Wells JM

Abstract

BACKGROUND:: Muc2-deficient mice show no signs of ileal pathology but the mechanisms remained unknown.

METHODS:: Wild-type (WT), Muc2, and Muc2 mice were killed at 2, 4, and 8 weeks of age. Total RNA from ileum was used for full genome transcriptome analysis and qPCR. Microbiota composition was determined using a mouse intestinal chip (MITChip). Morphological and immunohistological studies were performed on segments of ileum.

RESULTS:: The ileum was colonized by more diverse microbiota in young (week 4) WT than in Muc2 mice, and composition was influenced by genotype. Weaning was associated with major changes in the transcriptome of all mice, and the highest number of differentially expressed genes compared with adults, reflecting temporal changes in microbiota. Although the spatial compartmentalization of bacteria was compromised in Muc2 mice, gene set enrichment analysis revealed a downregulation of Toll-like receptor, immune, and chemokine signaling pathways compared to WT mice. The predicted effects of enhanced IL-22 signaling were identified in the Muc2 transcriptome as the upregulation of epithelial cell proliferation altered expression of mitosis and cell-cycle control pathways. This is consistent with increased villus length and number of Ki67 epithelial cells in Muc2 mice. Additionally, expression of the network of IL-22 regulated defense genes, including Fut2, Reg3β, Reg3γ, Relmb, and the Defensin Defb46 were increased in Muc2 mice.

CONCLUSIONS:: These findings highlight a role for the IL-22-STAT3 pathway in maintaining ileal homeostasis when the mucus barrier is compromised and its potential as a target for novel therapeutic strategies in inflammatory bowel disease.

PMID: 25636123 [PubMed - as supplied by publisher]

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Onderzoek naar materiaal en methode gebruikt door Nederlandse tandartsen bij endontische behandeling.

Aim To gather information about which materials and methods Dutch dentists use to
perform endodontic treatment.
Materials and Methods On November 6, 2009 during a general dental conference in the
Netherlands a questionnaire was handed out to 341 dentists. After de conference, the
questionnaires where retaken. Different aspects of the endodontic treatment were
discussed in the questionnaire. On the basis of the questionnaire were different areas of the
endodontic treatment evaluated. Ways of referring, assess complexity of endodontic
treatment, performing operative endodontic treatment and post-graduate training in
endodontics. To analyze the data Spearmans correlation, non-parametric and parametric
tests were used. The level of significance was set at 0.05.
Results Of the 110 (32.2%) returned questionnaires 102 (29.9%) were complete and
therefore useful. The majority of the respondents are general dental practitioners (96.1%).
23.8% used the DETI/CEB score, with no significant difference between experienced and
inexperienced respondents (p>0.05). Inexperienced respondents refer an endodontic
treatment more often than experienced colleagues (p<0.05). In the presence of preoperative
pain endodontic treatment is performed over several visits (p<0.001). 65.3% of the
respondents used rubber dam during endodontic treatment, and recently graduated
respondents used rubber dam more frequently than experienced colleagues (p<0.001). No
significant difference was found in the use of mechanical rotary instruments and hand
preparation in relation to years of experience (p = 0.85). 90.6% of the respondents used a
special endodontic handpiece or engine during the mechanical preparation. Cold lateral
compaction was used by 56.9% of the respondents in comparison with other filling
technologies. The majority of the respondents (97.1%) used sodium hypochlorite as
disinfectant. More than half of the respondents used preparation and filling technologies
recommended during a course or conference.
Conclusion Practicing dentists in the Netherlands use conventional endodontic preparation,
filling and disinfection methods. The pre-operative assessment of the difficulty of an
endodontic treatment and the use of rubber dam are not routinely applied.

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Een pilot studie naar de microbiele diversiteit van biofilm, gerelateerd aan caries

Biofilms in the human caries process exhibit marked diversity. PCR based denaturing gradient gel electrophoresis (DGGE) surveys microbial diversity by displaying PCR- nerated 16S rRNA fragments from micro-organisms in a biofilm24.
The objective of this study was to use Denaturing Gradient Gel Electrophoresis (DGGE) to study the shift in microbial composition in the different groups: enamel versus dentine lesions, 1 week old
versus 20 weeks old biofilm and primary versus secondary caries lesions. We hypothesized a microbial diversity in all of the groups, because of the differences in substrate (enamel, dentine,
restored and unrestored) and the time in the caries process.
We investigated the biofilm on restored and unrestored dentin and enamel samples in an in situ study in 8 subjects after 1 and 20 weeks (Thomas RZ et al., 2008). The 62 biofilm samples (originally 64,
two were lost in the time) were used for DGGE analysis. Mter DNA extraction, part of the 16SrRNA gene was amplified by PCR and separated by DGGE, resulting in banding patterns roughly representing single species. Shifts in microbial diversity were determined by counting the coefficient
of similarity (Cs%), Zijnge et al [2003]. A Cs% more than 85 was the norm for no differences in the microbial diversity, Zijnge et al. [2003].
Similar banding patterns and different microbial diversity were found for biofilm from enamel versus dentine lesions and primary versus secondary caries lesions. The coefficient of similarity for enamel versus dentine lesions was 64% and for primary versus secondary lesions 79% (enamel) and 84%(dentine).
Significance differences were found in the banding patterns from 1 week old compared to a 20 weeks old biofilm (P=0.03) with a low coefficient of similarity (24% ).
These findings suggest that there is a microbial diversity between enamel versus dentine lesions,
1 week old versus 20 weeks old biofilm and primary versus secondary caries lesions. Further investigation is needed to detect the micro-organisms which determines the differences in the microbial diversity.

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De invloed van een endodontisch behandeld gebitselement op eennaastgelegen implantaat

Aim: a systematic literature study with the purpose to investigate the risks for implants placed
adjacent to an endodontically treated natural tooth.
Methodology: the Medline database, the Scopus database and the Picarta database were
searched for relevant publications in English or Dutch language. The articles about retrograde
peri-implantitis were evaluated on internal validity. Also, the methodological quality of these
articles was evaluated by supplementary criteria.
Results: the search resulted in 22 relevant articles: 8 articles about epidemiology, 2 about
prognosis of implants. The remaining articles, 2 retrospective studies, 1 review of case reports
and 9 case reports concern the relationship between apical periodontitis and peri-implantitis.
It is demonstrated that in elements with an adequate rootcanal filling 11,8 to 25,2% still
shows apical periodontitis. For elements with an inadequate rootcanal filling this percentage
lies between 22,8 and 61,8 %. The prevalence ofperi-implantitis is 8,9 %. For the prevalence
of retrograde peri-implantitis a percentage of 2 % was found. The survival rate of implants is
93-100 %. Concerning recently placed implants most authors conclude that there is a
relationship between peri-implantitis and an endodontically treated adjacent tooth. Two
authors point out that there is a possible relationship and only one author concludes that there
is no relationship. Concerning osseointegrated implants one author concluded that there is a
possible relationship, two authors conclude that there is no relationship and two authors
conclude that there is a relationship. Thus, there seems to be little agreement between the
authors.
Conclusion: it is not possible to demonstrate a higher risk for retrograde peri-implantitis
when an implant is placed adjacent to an endodontically treated tooth.

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Tandheelkundige behandeling en antitrombotica : Onderzoek naar verschil in aanpak tussen tandartsen

Objective: The aim of this thesis is to examine whether there are differences between
dentists working in the Netherlands regarding the treatment of patients who take
antithrombotic medication.
Methods: Research data made available by the Dutch Dental Association (NMT)
were used. In November 2008 512 so-called ‘Omnibus dentists’ were contacted by
mail, with a request to fill out a questionnaire on the web. Furthermore, an additional
random sample of 1000 dentists, of whom an e-mail address was known, were asked
to do the same. The net sample consists of 1442 dentists, of whom 487 (34°/o) have
(partly) filled out the questionnaire and returned it. The research data were processed
upon a data file using the IBM computer program SPSS Statistics 16 ®. This data file
was used in order to answer the main question of this thesis. Differences between
dentists were analyzed by making a distinction between a number of personal and
practice characteristics. These characteristics include age, sex, place of graduation,
region of residence, cooperation with colleagues, recording in the Dutch Quality
Register for Dentists (KRT), number of dental units in the practice, number of patients
visiting the practice annually, number of hours per week fellow dentist(s) work in the
practice, number of hours per week dental assistant(s) work in the practice, number
of hours per week dental hygienist(s) work in the practice. Statistical tests were
performed using IBM SPSS Statistics 16®: Chi-Square test, paired t test and analysis
of variance (ANOVA). Differences between groups were considered significant if p
<0.05.
Results: Based on this study, which can be considered representative of the
population dentists in the Netherlands, it can be concluded that there are some
significant differences between dentists in treating patients who take antithrombotic
medication. Dentists working in larger practices tend to record the medical
anamneses of patients more often. Dentists with age below 35 years and female
dentists tend to record the ASA-score of a patient more often. Dentists who are
enrolled in the Dutch Quality Register for Dentists (KRT) are more familiar with the
International Normalized Ratio (INR). Female dentists tend to contact the medical
specialist more frequently when they render invasive treatment with a risk of bleeding
in patients who take antithrombotic medication.
Conclusion: The knowledge of dentists on the use of antithrombotic medication by
patients and the dental interaction should be improved. A national evidence-based
guideline, which is currently under development, would dispel doubts among dentists.

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De initiele coagulerende werking van PU gemodificeerd met 55% PEG

Background: Haemostatic agents widely used are gelatin and collagen. Their animal derived
origin, may cause severe diseases like CJD or BSE. Polyurethane foam combined with
Polyethylene Glycol (PEG), which is a fully synthetic and biodegradable haemostatic agent, will
prevent this risk. It has been already tested in in vitro and in vivo studies to a certain extent. It has
been proved that polyurethane foam enhances coagulation. The aim of this study is to discover
the way this effect on the haemostasis is accomplished and especially how important the role of
thrombocytes is in reaching coagulation.
Patients and Methods: This in vitro study is divided into two parts. The first part is an experiment
conducted with blood of 6 donors. Four samples were tested at the same time. The blood was
divided into four cups. In one cup Polyurethane foam was added, in a different one collagen
(Hemocollageme®) and in another cup gelatin (Spongostan®). The last cup was used as a control
test, to which no material was added. Hereafter, the cups were placed in a coagulation machine
for two minutes. After those two minutes the test materials were removed and a hemocytometric
apparatus was used to count the free thrombocytes that were still present in the blood.
The second part of this study was a test performed with human pool plasma, which is free of
thrombocytes, bought at a blood bank (Sanquin, Groningen). Again, four samples were tested at
the same time. In this part the pool plasma was divided into four cups. The same haemostatic
materials were used as in the first part of this study; Polyurethane foam, Hemocollagene® and
Spongostan®. The last cup was used as a control test. The samples were incubated for 15 minutes
in the coagulation machine. After these 15 minutes, the test materials were removed and the cups
were placed back into the coagulation machine. This machine measured the time to heamostasis
of the pool plasma.
Both parts of the study were also performed with Polyurethane foam with a different percentage
of PEG.
Results: A contact time of two minutes of Polyurethane foam and collagen with human whole
blood led to a significantly lower amount of free thrombocytes compared to using no material.
Both materials also showed a significantly faster coagulation of human pool plasma compared
with the control group ‘no material’.
When both tests were done with Polyurethane foam with a different concentration of PEG, there
were no significant differences found. Nevertheless, there seems to be an optimum for the best
aggregation ofthrombocytes laying around 25% free PEG. In the coagulation machine
Polyurethane foam with 0% free PEG initiated the best coagulation time.
Conclusion: In contradiction to the literature, collagen in this study initiated a better coagulation
and accomplished more aggregation of thrombocytes than gelatin.
Polyurethane foam with 25% free PEG initiates a significantly higher amount of aggregation of
thrombocytes in human whole blood and a significantly faster coagulation of pool plasma
compared with using no test material. The working mechanism of the haemostatic capacity of
Polyurethane foam is based on the cellular component as well as the intrinsic route of the
molecular component of the coagulation cascade. This is probably initiated through the
negatively loaded surface.
Because of this working mechanism, polyurethane foam seems promising for use in patients who
use thrombocyte aggregation inhibitor, as well as by patients who use coumarin derivatives.

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Het effect van xylitol op preventie van tandcaries:een systematisch literatuuroverzicht

Caries is still a common disease among children and adults. Sometimes preventive
means fail to improve oral health. Products containing xylitol have been advanced as
a significant alternative treatment for caries active patients. Xylitol is a naturallyoccurring
sugar alcohol and is part of the sugar alcohols (polyols). Although there is
evidence that xylitol is non-cariogenic, there is some scepticism about its cariostatic
nature. There are several different mechanisms proposed by which xylitol oral
products might work. The aim of this systematic review is to help clarify how effective
this proposed treatment is. Criteria for considering studies were established before
searching. The search was conducted in the following databases: Medline, Embase
en The Cochrane Library (Central Register of Controlled Trials) and hand searching
through journals was done. After selection six articles were used for data collection
and quality assessment. It was decided not to perform meta-analysis because of
insufficient comparability of the studies; difference in xylitol intervention, control
groups, methods of caries diagnosis, etc. The most important results are that there is
a significant caries reduction when using xylitol containing products compared to
using nothing and that there’s no difference in caries prevalence between xylitol gum
users and control gum users. This means that it is unclear whether the caries
inhibitory effect of xylitol containing products is caused by the presence of xylitol in
these products. Conclusion: there’s not enough evidence to support the use of xylitol
as preventive treatment. More research is needed to learn more about this topic.

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Recurrence of coiled intracranial aneurysms; wall shear stress in pre- and post-coiling aneurysms.

Introduction.
Recurrence is a significant problem in intracranial aneurysms treated with endovascular coiling. Currently there is no method for predicting recurrence of treated aneurysms. Previous studies associated high wall shear stress (WSS) and blood flow velocity near remnant necks of aneurysms with recurrence. Because, aneurysms with high WSS after treatment are associated with recurrence, we investigated whether pre-treatment WSS patterns can predict post-treatment WSS. If high WSS patterns before treatment are indicative for the origination of high WSS patterns after treatment, this measurement can be used to steer treatment.
Method.
For this retrospective observational cohort study we studied 13 patients with endovascular coiled aneurysms with recurrence. Computational Fluid Dynamics (CFD) simulations were performed to simulate blood flow in patient-specific vascular models based on 3DRA image and DSA data and by using patient specific velocities profiles measured by phase-contrast MRI. The mean WSS near the neck before and after endovascular coiling was compared. Statistical analysis was performed using the Wilcoxon-signed rank test.
Results.
Post-treatment mean WSS increased in all 13 patients compared to pre-treatment mean WSS. The median difference of pre- and post-treatment mean WSS was 5.75 [IQR: 2.43 - 0.34]. This difference was statistically significant (p=0.001)
Conclusion.
Pre-treatment WSS cannot be used to predict post-treatment WSS values, and therefore cannot be used to predict long-term outcome after endovascular coiling of intracranial aneurysms.

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The value of duplex ultrasound in detection of stenosis in fistulae with an absolute blood flow <400 ml/min and/or ≥20% decrease.

Background
The arteriovenous fistula (AVF) is the most widely used method of vascular access for long-term hemodialysis. A well-functioning mature AVF is essential for the maintenance of hemodialysis in patients with end stage renal disease (ESRD). However, the complication rate related to AVF remains high. The most common cause of fistula failure is thrombosis caused by stenosis. The best predictor for stenosis is a decrease in blood flow. Several imaging modalities are available for evaluation of dysfunctional hemodialysis fistulae. Angiography is the gold standard, and duplex ultrasound is also widely used for detection of access stenoses. Duplex ultrasound is non-invasive and low risk. The purpose of this study was to evaluate the value of duplex ultrasound in detection of significant (≥50%) stenoses in fistulae with an absolute blood flow <400 ml/min and/or ≥20% decrease.
Patients and Methods
Patients that underwent construction of an AVF in the period of January 1, 2007 until December 31, 2012 at the Scheper Hospital Emmen (SZE) were included in this study. Patients were further selected by duplex ultrasounds requested for a significant change in blood flow rate (flow <400 ml/min and/or ≥20% decrease) measured by transonic flow meter (TFM) in the period of January 1, 2007 until June 30, 2014. Concordance between duplex ultrasound and angiography results were analyzed.
Results
The study included 227 patients, 55 of which had shown a significant change in blood flow rate and were assessed using duplex ultrasound. In the total group of 55 patients, 102 duplex ultrasounds were made of which 85 (83.3%) detected a significant stenosis. A stenosis was confirmed in 75 of the 85 performed angiographies. The other ten patients had sufficient blood flow or diameter to continue the use of AVF, or underwent surgical revision, or were deceased before angiography could be performed. In the study group, two patients had a negative duplex ultrasound, though angiography had been performed and had detected a significant stenosis.
The predictive value of significant change in blood flow in detecting a stenosis in AVF was also investigated. With a sensitivity of 69% and a specificity of 20% the predictive value of significant change in blood flow in finding a stenosis was poor.
Conclusion
Duplex ultrasound can clearly assess the presence of AVF stenosis after a significant change in blood flow has been detected. It provides information about the location and type of stenosis, as well as the location for injection during percutaneous transluminal angioplasty. It is a non-invasive and safe technique. However, the two negative duplex ultrasounds with positive angiograms can raise debate concerning the value of duplex ultrasound in detecting stenoses. A next study should be a randomized control trial, where duplex ultrasound will be compared with angiography.

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Triage of patients with obscure gastrointestinal bleeding by capsule endoscopy.

Background and aim:
Capsule endoscopy (CE) is the first-line diagnostic method for patients with obscure gastrointestinal bleeding (OGIB). Nevertheless, a substantial number of patients
have non-diagnostic CE findings and there is still no consensus in literature about the best
policy in this specific subgroup. This study collected long-term data on patients with OGIB who underwent CE with or without subsequent balloon-assisted enteroscopy (BAE). Our main aim was to determine the role of CE in triage of patients with OGIB.
Patients and methods:
578 patients were enrolled in this retrospective study. CE was performed after a negative conventional work-up of OGIB by upper endoscopy and colonoscopy. CE results were classified as diagnostic (positive) or non-diagnostic (negative) results. Clinical characteristics were analyzed to find predictors associated with rebleeding within 2 years. Subsequent BAE was performed in 104 patients for diagnostic and therapeutic
purposes.
Results:
Positive CE results were found in 28% (159/578) of cases, including 7 small bowel
tumors. 3 tumors were missed by initial CE. The diagnosis was made within maximally 20
days by other modalities, including BAE. A hemoglobin (Hb) of ≤5.0 mmol/L at onset of
OGIB was an independent factor associated with an increased risk for rebleeding after a nondiagnostic CE (hazard ratio= 4.831[3.034-7.693], p=0.000). Premenopausal women (2/46) had a significantly lower risk for rebleeding compared to postmenopausal women (34/161) (p=0.008). The diagnostic yield of subsequent BAE guided by a positive CE result was significantly enhanced towards 74% (52/70), whereas after a non-diagnostic CE a diagnosis was made in only 9% (3/34) of patients.
Conclusions:
A diagnostic CE provides a directing role for endoscopic interventions in patients with OGIB. In patients who present with a low Hb level at onset of OGIB, further examination is recommendable, even after a non-diagnostic CE procedure. Premenopausal women can be considered as low-risk group for rebleeding after a negative CE examination.
Despite the fact that CE is the first-line method for visualization of the small bowel, the miss rate for small bowel tumors is still considerably. BAE can be an useful tool in cases with a high clinical suspicion.

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Liver Fatty Acid Binding Protein. a marker for traumatic liver injury.

Introduction
Currently, there is no laboratory test available which predicts the extent of traumatic liver injury. By many, a computed tomography (CT) scan is considered the golden standard for evaluating the presence and extent of such injury. However, a CT scan is not without risk, as it makes use of ionizing radiation and transport to and from the CT room takes time and endangers the patient. Aim of this study was to test if the plasma concentration of the protein Liver Fatty Acid Binding Protein (L-FABP) is an accurate diagnostic marker for the presence or absence of liver injury in a poly trauma patient during the initial admission and during the first two days after trauma. Secondary aim is to analyze whether plasma and urine L-FABP levels correlate with commonly used liver function tests and grade of injury on CT scan or preoperatively during the initial admission and/or during the first 48 hours after trauma.
Methods
This study is part of a large prospective cohort study on markers for gut wall integrity in trauma. Inclusion criteria were: age > 18 years, A-trauma, free abdominal fluid as seen on FAST-echo or CT-scan on admission at the shock room and injury seen in damage control surgery i.e. laparotomy. Plasma samples were obtained upon arrival at the shock room, three hours post trauma, and after 24 and 48 hours. CT-scans of all patients were (re)scored by a radiologist according to the Organ Injury Scale (OIS) of the AAST. ELISA technique was used to analyze plasma samples. Medians of L-FABP were compared between patients with or without liver injury, using Mann-Whitney test. L-FABP was correlated to liver function tests and OIS grades of liver injury, by using Pearsons or Spearmans test, depending on normal distribution or not. The optimal cut-off point for L-FABP as marker for the presence of liver injury was defined with help of ROC curves.
Results
We included 62 patients. There were 48 (77.4%) males and 14 (22.6%) females. The mean age was 39 years (SD±16.7). Overall mortality rate was 22.6% (n=14). The injury mechanism was blunt force trauma in 56 patients (90.3) and penetrating trauma in 6 patients (9.7%). L-FABP was significantly raised in patients with liver injury compared to patients without liver injury upon arrival at the shock room: 244.5 ng/ml in patients with and 75.6 ng/ml in patients without liver injury, (p = 0.03). Correlation of L-FABP with the OIS liver injury classes was (0.320, p = 0.05) upon admission. The strongest correlation of ALT and AST to L-FABP was found three hours after trauma, 0.786 (p < 0.01) and 0.807 (p < 0.01) respectively. At the chosen cut-off point (418.34 ng/ml), the sensitivity of L-FABP was 44% specificity was 90%, NPV was 77% and PPV was 70%
Conclusion
L-FABP is a relatively good test to rule out traumatic liver injury. L-FABP was unable to discriminate between the different grades of liver injury during initial admission to the shockroom and 48 hours afterwards.

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The challenge of approaching loneliness. Determinants of social and emotional loneliness and the approach of nurses towards loneliness problems among community-dwelling elderly.

Introduction
Loneliness has been conceptualized as a bi-dimensional construct and previous studies showed that social and emotional loneliness have different potential causes and risk factors. Only few studies have examined determinants of the dimensions separately. Also, little is known about how health caregivers approach lonely elderly. This study has examined determinants of social and emotional loneliness and explored the approach of nurses towards loneliness problems among community-dwelling elderly.
Methods
In this cross-sectional study data of the Functional decline in Transition (FIT) study, which investigated the effectiveness of proactive care for community-dwelling elderly on physical function, were used. Demographic, health-related, psychological and social characteristics and loneliness scores of elderly (n=417) were collected for backward multivariable linear regression analysis. All documentation of home visits by a nurse, of older people with loneliness score ≥3 on the De Jong Gierveld scale (n=294) was collected. Frequencies and types of interventions for loneliness and reasons for no intervention were investigated.
Results
Determinants of social loneliness were poor frequency of seeing people, income discomfort, not receiving informal care and poor chances of going on trips. Determinants of emotional loneliness were poor frequency of seeing people, marital status, income discomfort, depressive symptoms, poor chances of going on trips and hearing problems. Within the group of loneliness score≥3, in 59% (174/294) there was mention of loneliness. In 32% (94/294) an intervention was initiated, most often social activities (30%) and support/home visit by a nurse (25%). In 44% (35/80) reason for no intervention was that the elderly did not feel lonely or did not consider it a problem.
Conclusion
This study indicates that social and emotional loneliness have many common determinants. Increasing social contacts seems to be beneficial for both dimensions. This questions the value of approaching loneliness bi-dimensionally in clinical practice. Future prospective research is needed to investigate risk factors for and consequences of social and emotional loneliness. Nurses frequently do not address loneliness problems among elderly. Most nurses seem to be aware, though, of different pathways leading to loneliness. Elderly often reject interventions. Qualitative research is needed to investigate which factors limit health caregivers to initiate interventions and which factors limit elderly to accept interventions for loneliness problems.

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Drug survival for acitretin and cyclosporine in patients with chronic hand eczema.

Background
Long-term data on the use of acitretin and cyclosporine in patients with chronic hand eczema in daily practice are lacking.
Objectives
The primary objective was to describe drug survival for acitretin and cyclosporine in a retrospective long-term multicenter daily practice cohort of patients with chronic hand eczema. The secondary objective was to identify determinants of drug survival for acitretin and cyclosporine in general and separately for discontinuation due to adverse events or ineffectiveness of treatment.
Methods
Data of all patients treated with systemic therapy for hand eczema between the 1st of January 1994 and the 1st of June 2014 were collected. All first treatment episodes of acitretin and cyclosporine were included. Drug survival was analyzed by Kaplan-Meier survival curves and split for two reasons for discontinuation: adverse events and ineffectiveness. Determinants of drug survival were analyzed using univariate Cox regression analysis and multivariate Cox regression analysis with backward selection.
Results
In total, data of 267 patients was collected and 120 patients with a first episode of acitretin and 102 patients with a first episode of cyclosporine were included. The overall drug survival of acitretin was 35.4%, 23.2% and 16.3% after 1, 2 and 4 years respectively, with a median drug survival of 0.5 years. The overall drug survival of cyclosporine was 48.2%, 26.3% and 13.1% after 1, 2 and 4 years respectively, with a median drug survival of 0.9 years. Reasons for discontinuation of acitretin were adverse events (37.5%), ineffectiveness (16.7%), both adverse events and ineffectiveness (5.0%) and other reasons (8.3%). The reasons for discontinuation of cyclosporine were adverse events (43.1%), ineffectiveness (17.6%) both adverse events and ineffectiveness (4.9%) and other reasons (2.9%). Patients with a good response at treatment after 3 months (PGA score 1) had a longer overall drug survival of acitretin and cyclosporine. Males also had a longer overall drug survival of cyclosporine and patients with prior immunosuppressive therapy had a shorter overall drug survival of cyclosporine.
Conclusions
This is the first daily practice study analyzing drug survival of acitretin and cyclosporine in the treatment of chronic hand eczema. Drug survival of cyclosporine in particular, was longer than expected based on previous studies (median 0.9 years). Because no serious adverse events or complications occurred during this longer treatment, maintenance therapy with cyclosporine for a longer period should be considered in future treatment of patients with chronic hand eczema. Most important determinant of longer overall drug survival of acitretin and cyclosporine was a good response at treatment after 3 months (PGA score 1).

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The effects of intraperitoneal and subcutaneous insulin administration on sex hormone-binding globulin concentrations in patients with type 1 diabetes mellitus.

Introduction
In adults with type 1 diabetes mellitus (T1DM) elevated concentrations of sex hormone-binding globulin (SHBG) have been reported. SHBG is produced in the liver and secreted into the (portal) circulation where it binds and transports androgens and oestrogens inactively, thus regulating their availability for target tissues and cells. These elevated SHBG concentrations may be due to low portal insulin concentrations and a subsequent impaired hepatic SHBG synthesis. With continuous intraperitoneal infusion (CIPII) higher portal levels of insulin can be achieved as compared to subcutaneous (SC) insulin therapy. The aim of this study was to analyse the effect of the route of insulin administration, CIPII versus SC, on SHBG-concentrations in T1DM patients.
Research design and methods
Post-hoc analysis of SHBG in samples derived from an open-labelled cross-over trial where patients with T1DM were randomized into receiving CIPII through an implantable pump (MIP2007C, Medtronic) followed by SC insulin therapy or vice versa. Both treatment phases were 6 months in duration with a cross-over phase of 4 weeks in between to minimize the carry-over effects of CIPII. Measurements were performed at baseline and at the start, halfway, and end of both treatment phases. In order to gain information on steroid and gonadotropin function; testosterone, estradiol, LH- and FSH-concentrations were also measured and the free-androgen index (FAI) was calculated.
To calculate the mean difference between the two therapies with a 95% confidence interval (CI), the linear mixed models analysis which takes treatment order into account was used according to the Hills-Armitage principle. This accounts for any period effect.
Results
Twenty patients with a mean (±standard deviation (SD)) age of 43 (±13) years, diabetes duration of 23 (±11) years and HbA1C 72 (±12) mmol/mol were analysed. The estimated mean change in SHBG was -10.3 nmol/L (95% confidence interval (CI) -17.4, -3.2 nmol/L; p = 0.007) during the CIPII phase and -3.7 nmol/L (95% CI -12.0, 4.6 nmol/L; p = 0.359) during the SC phase. When taking the effect of treatment order into account, the estimated mean difference between the CIPII treatment phase and the SC treatment phase was -6.6 nmol/L (95% CI -17.5, 4.3 nmol/L; p = 0.219). Furthermore, the estimated mean change in testosterone was -3.2 nmol/L (95% CI -5.5, -0.8 nmol/L; p = 0.0123) during the CIPII treatment phase and -1.2 nmol/L (95% CI -3.7, 1.3 nmol/L; p = 0.325) during the SC treatment phase. The difference in change during the CIPII and SC treatment phase and the estimated mean change between the CIPII treatment phase and the SC treatment phase was non-significant for estradiol, LH, FSH and FAI.
Conclusions
In patients with T1DM, SHBG and testosterone concentrations decreased significantly during CIPII therapy while there were no changes during SC insulin therapy. Nevertheless, the difference in change between the two routes of insulin administration was not significant; possibly due to a small sample size. The results of this study support the hypothesis that portal insulin concentration have an effect on circulating SHBG concentrations. This finding could lead to further research on the effects of CIPII insulin on SHBG, steroids and associated pathology in T1DM.

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Flowcytometrische detectie van urineweginfecties bij patiënten met koorts.

Background:
Fast and reliable urinalysis is important in febrile patients in the emergency department. Current urine tests are moderately reliable and fast, or reliable but time consuming. Accurate diagnosis before starting with antibiotics is important to minimize resistance. The urine culture is worldwide accepted as the gold standard, but a time consuming and costly test, a large proportion of samples are negative. Flow cytometric counting of bacteria and leukocytes might be a good alternative. The aim of this study is to select an optimal strategy for urinalysis in febrile patients in the emergency department.
Methods:
Urine was obtained from 140 consecutive febrile patients in the emergency department. Dipstick, urine sediment, Gram stain and urine cultures were performed according to protocol. Flow cytometric analysis for bacteria and leukocytes was performed with the Accuri C6 flow cytometer. Diagnostic values were determined by using urine culture as the gold standard, a culture was considered positive with ≥105 CFU/mL.
Results:
1 in 3 febrile patients had a complicated urinary tract infection, 25% of the patients had a positive urine culture. The highest diagnostic accuracy for urinalysis was obtained with Gram stain and flow cytometric analysis, with AUCs of 0.953 and 0.957. The cutoff value for bacteria was 1.86 x 106 bacteria/mL, this resulted in a sensitivity of 94.7 % and a specificity of 88.2%. Pre-screening with the Accuri C6 would have resulted in a reduction of bacterial cultures by 56.4%. A cutoff value of 37 leukocytes/μL resulted in a sensitivity of 84.2% and a specificity of 67.6%.
Conclusions:
The Accuri C6 and Gram stain both have a high diagnostic value in urinalysis in febrile patients, but the Accuri C6 is much faster. Pre-screening urine samples with the Accuri C6 results in a reduction of urine cultures, workload and costs. Bacteriuria seems to be a better predictor for urinary tract infection than leukocyturia.

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De wetenschappelijke ontwikkelingen in de radiologie en radiotherapie binnen de geneeskunde in Nederland 1896-1922

No description abstract

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Clinical outcome of T1 colorectal carcinoma in pedunculated tumors, as compared to lateral spreading tumors: a retrospective multicenter study.

Introduction:
Although a lower incidence of lymph node metastasis (LNM) of T1 colorectal cancer (CRC) is suggested in pedunculated polyps compared to lateral spreading tumors (LSTs), no large cohort study has been performed comparing number of LNM, recurrence, and residual tissue. This study aimed to determine clinical outcomes of T1 CRC in pedunculated polyps and LSTs, and assess the risk-benefit balance of additional surgery in pedunculated T1 CRCs.
Method:
Patients diagnosed with a T1 CRC in 8 hospitals between January 2000 and July 2014 were extracted from the database of the Netherlands Cancer Registry. Patient characteristics, endoscopic and histological findings, treatment, and follow-up were collected of all patients. Recurrence was defined as the detection of metastasis or local recurrence during follow-up. Pedunculated T1 CRCs were at high risk if one or more of the following criteria were present: tumor at resection margin, poor differentiation, submucosal invasion into the stalk, lymphovascular invasion.
Results:
A total of 1026 patients with T1 CRC (410 pedunculated and 616 LSTs) were included. Polyps were treated with endoscopy only (pedunculated n=213 (52%) vs. LST n=156 (25%)), endoscopy followed by surgery (n=130 (32%) vs. n=123 (20%)) or primary surgery (n=67 (16%) vs. n=337 (55%)). Median follow-up was 41 months (IQR 18-74) in both groups. Pedunculated T1 CRCs had a more favorable 5-year disease free survival rate than LSTs (98% vs. 94%). Stratified to treatment, most survival benefit was observed for pedunculated T1 CRCs treated with endoscopy only (98% vs. 89%). However, after adjustment for follow-up with imaging and location in rectum this was no longer significant (adjusted HR 3.0 95%CI 0.9-10, p=0.08). In the primary surgery group, the rate of LNM was lower in pedunculated polyps (3% vs. 10%, p=0.06). Residual tissue was detected in 11.5% of pedunculated tumors versus 23.6% of LSTs. Piece-meal resection method was independently associated with residual tissue (OR 5.09; 95%CI 2.25-11.53; p<0.01). In high risk pedunculated T1 CRCs no difference in 5-year disease free survival was observed between endoscopic and surgical resection. Tumor at resection margin and lymphovascular invasion in the endoscopic resected tumor was associated with referral to surgeon, resulting in a higher rate of detected LNM as compared to the general population. Invasion into Haggitt level 4 was directly associated with LNM or/and recurrence. Cumulative risk of recurrence or/and LNM in pedunculated T1 CRCs was 7.0%. Morbidity and mortality after surgery was 20% and 2.5%, respectively. In a high risk population of patients with a higher age (>68) or with high comorbidity the mortality rate increased to 5.6%.
Conclusion:
Compared to LSTs, pedunculated T1 CRCs have a more favorable 5-year disease free survival and a lower risk of LNM. Effectiveness of surgical resection is comparable to endoscopic resection in pedunculated T1 CRCs with high risk features, suggesting the current risk factors are no efficient criteria for surgery in pedunculated T1 CRCs. In pedunculated T1 CRCs with tumor invasion deeply into the stalk, lymphovascular invasion or tumor at resection margin additional surgery seems of benefit in the current study. Further research with histological reevaluation of the resected specimens is needed to support these conclusions. Piece-meal resection method is an important risk factor for residual tissue and should be avoided. In patients of older age or with high comorbidity, the risk of mortality after surgery closely approaches the oncologic benefit, and surgery should therefore be carefully considered in these patients.

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