The effect of diffuse myocardial fibrosis in children with Tetralogy of Fallot on right and left ventricular function.

Background Diffuse myocardial fibrosis (or scarring) of the heart muscle is associated with heart failure and ventricular dysfunction in many diseases. The aim of this study was to study the presence of myocardial fibrosis by T1 mapping CMR in pediatric patients with repaired Tetralogy of Fallot (TOF), and to correlate the degree of fibrosis with the extent of ventricular dysfunction. Furthermore, regional myocardial function of the right and left ventricle (RV and LV) was assessed with feature tracking (FT) CMR. Methods In 31 patients (mean age 13.9±2.4 years, 19 male) after surgical repair of TOF, T1 measurements were performed at the mid and basal ventricular levels in short axis (SA) in the entire LV, RV, interventricular septum (IVS) and free wall as well as in each LV segment separately. The extracellular volume (ECV) was calculated from native and post-contrast T1 times of myocardium, blood and the hematocrit. Global and segmental circumferential (LV), longitudinal (LV and RV) strain as well as the standard deviation of time to peak strain were measured using CMR FT software (TomTec, Germany). Sixteen asymptomatic children (mean age 13.4±2.6, 7 male) who had a CMR screening test for arrhythmogenic right ventricular cardiomyopathy were used as controls. Differences in ECV and cardiac contractility were compared between patients and controls with an unpaired t-test, as well as gender differences. The correlation of native T1 times and ECV with strain parameters was tested using Pearson’s coefficient. Native T1 times and ECV were correlated to exercise test results and surgical information. Results The mean pulmonary regurgitation (PR) fraction in TOF patients was 33.4±16.1% and RV end-diastolic and LV end-diastolic volumes were enlarged (RV EDV 148±40 ml/m2; LV EDV 91±12 ml/m2) with near-normal ejection fraction (RVEF 49.9±5%; LVEF 55.1±5.8%). Most native T1 times and ECV did not differ significantly between patients and controls. However, patients with a transannular patch repair and higher PR had higher ECV in some parts of the LV as compared to patients with a valve sparing or valved conduit surgery (e.g. ECV entire LV base 26.0±3.0 versus 22.8±2.7%). Also, longer bypass- and cross-clamp times at surgery were associated with higher native T1 times and ECV. In addition, patients of female gender had higher native T1 times and ECV as compared to males (i.e. ECV entire LV mid 25.2±2.9 versus 22.7±3.3, p<0.05). Some cardiomechanical values as measured with FT were lower in patients as compared to controls: the average of 6 segments in mid SA for circumferential strain (-21.51±3.79 versus -24.07±3.27, p<0.05) and circumferential strain rate (-1.31±0.29 versus -1.59±0.31, p<0.05) as well as some segmental values. LV ejection fraction correlated negatively with mid and basal SA circumferential strain averaged from 6 segments (r= -0.515, p<0.001 and r= -0.522, p<0.05), and with mid and basal SA circumferential strain rate averaged from 6 segments (r= -0.513, p<0.001 and r= -0.505, p<0.005). LV 4 chamber longitudinal strain, averaged from 6 segments, correlated with native T1 times in mid SA entire LV (r=0.511, p<0.05), mid IVS (r=0.546, p<0.05), basal IVS (r=0.495, p<0.05). Conclusion Our study revealed subtle increases in LV fibrosis in juvenile patients after TOF repair. Overall, however, the LV myocardium of adolescents appears remarkably healthy. Similarly, the abnormalities in myocardial strain and torsion in TOF were relatively modest. Our data reveal, however, that increased myocardial fibrosis can be associated with abnormal strain as a sign of adverse morphological and anatomical remodeling. The clinical consequences of these findings need to be examined in the future. Also, further work is necessary to substantiate the findings and to develop more sophisticated approaches to RV tissue characteristics.

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QT Prolongation in Patients with Early Onset Psychosis

QT Prolongation in Patients with Early Onset Psychosis 2
Abstract
Background
Schizophrenia is a severe mental disorder, which is associated with loss of quality of life and shortened life expectancy. Within the increased risk of cardiovascular death, people with schizophrenia are more likely to have sudden cardiac death (SCD) compared with people in the general population. The QT-interval might potentiate the risk for lethal cardiac arrhythmias and SCD. Given that patients with schizophrenia often have more risk factors of QT-prolongation and there is little information about QT-interval in patients with early psychosis, this ECG-marker in this population is of interest. We aimed to determine whether QT-duration is prolonged in patients with early onset psychosis, and whether differences in QT-duration may be explained by use of QT-prolonging drugs and/or factors that influence QT-duration.
Materials and methods In a retrospectective cohort study, we analyzed ECGs of a cohort of 249 patients with early psychosis. We determined whether QT-prolongation was present, and assessed QT-duration. Patient demographics, as well as data about medications use and potential risk factors were recorded. Results were compared with a cohort of age-comparable healthy medical students.
Results QT-duration was significantly longer in the early psychosis cohort than in the control cohort (392.4 vs. 388.0 msec, p<0.05). QT-prolongation was more prevalent in patients (8.2%) than among controls (0.4%). Moreover, compared with patients without QT-prolonging drugs, patients with QT-prolonging drugs had a longer mean QT-duration (394.9 vs. 375.2 msec, p<0.05). All patients with QT-prolongation were within the patients group with QTc-prolonging medication. Female sex, potassium level, TC/HDL ratio, QTc-prolonging drugs and polytherapy were found to be associated with the QT-interval. Discussion and Conclusion Patients with early psychosis were found to have a longer mean QTc-interval compared with healthy controls. Moreover, prevalence of QTc-prolongation was significantly increased in patients. QTc-prolongation observed in patients with early psychosis appears primarily to be explained by use of QTc-prolonging medication. Apart from this, other non-medicamental risk factors and polytherapy are also associated with QTc-prolongation in patients with early onset psychosis.

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Exploring the neurobiological underpinnings of apathy: relationship between apathy and deactivation of the default mode network in schizophrenia patients

A critical component with regard to functional outcome in schizophrenia patients is apathy, characterized by lack of motivation and diminished goal-directed behavior. Since the default mode network (DMN) is involved in internally-directed cognitive function and attenuated during goal-directed activity, failure to suppress the DMN has been linked to several clinical features of schizophrenia. Here we suggest that apathy can be attributed to lack of DMN suppression. We hypothesized that schizophrenia patients with high apathy levels show less deactivation of the DMN during a task compared to patients scoring low on apathy.
We investigated the association between apathy and DMN deactivation using arterial spin labeling in 46 patients with schizophrenia or psychotic spectrum disorder and 11 healthy controls, while performing the tower of London task during fMRI scanning. We used independent component analysis to identify DMN regions and to extract mean time courses from these corresponding components for both patients and controls. The time courses for the DMN components were plotted with apathy score as coloring and a scatterplot was used as a visual representation of the correlation.
Our results demonstrated DMN deactivation during goal-directed activity. The DMN showed less activation during rest and less deactivation during the task in patients compared to controls during certain time points equally distributed between rest and task blocks. We were not able to detect a significant difference between patients and controls in modulating the DMN for most time points during the task, however. Moreover, we found no significant relationship between apathy and DMN deactivation.
These results suggest that schizophrenia patients may show abnormalities in DMN operation compared to controls. However, research repeating our study needs to be performed considering our limitations (e.g., small sample size of control group and use of ASL instead of BOLD fMRI).

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Preventie van chylothorax als complicatie bij oesofagusresecties.

Background.
Postesophagectomy chylothorax is a rare and potentially severe complication in patients diagnosed with oesophageal cancer. It is mostly caused by iatrogenic thoracic duct injury. This complication may be prevented by peroperative visualization of the thoracic duct. In this pilot study we evaluated the effects of peroperative enteral administration of methylene blue in visualizing the thoracic duct.
Methods.
From 15 October 2014 until 15 January 2015, all patients who underwent an esophagectomy according to the principles of the minimally invasive esophagectomy in our centre, received methylene blue through the jejunostomy in the abdominal phase of the operation. Blue discoloration of the thoracic duct was assessed during the thoracoscopic part of the operation.
Results.
There was no blue discoloration of the thoracic duct in any of the six patients. The primary outcome was 0%, with (95% CI 0-45%) and (99.9% CI 0-72%). The predetermined minimal required therapeutical effect was 90%, which was evidently outside the boundaries of the confidence intervals.
Conclusion.
Methylene blue does not give blue discoloration of the thoracic duct when administered enterally during esophagectomy. Therefore, methylene blue is not useful in the prevention of chylothorax.

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Kwaliteit van leven bij patiënten met de ziekte van Parkinson met voorspelbare en onvoorspelbare motorische complicaties

Objective
In this study we investigate the influence of motor complications on the quality of life in
patients with Parkinson Disease. These motor complications involve on-off fluctuations and
dyskinesias which can be predictable or unpredictable. The impact of these motor complications on
quality of life is not well understood. There have been little studies on this topic, and these studies
show conflicting results. The understanding of this association between motor complications and
quality of life can help medics to optimize the treatment strategies and thereby minimalize the negative
impact on the quality of life.
Methods
378 patients of the Medical Centre Leeuwarden with Parkinson Disease were included. A
total of 284 patients returned the completed questionnaire and could be used for data-analysis. The
disease specific quality of life was measured with the PDQ-39. (Parkinson disease questionnaire).
Data-analysis was done to determine the presence of 13 selected variables. After that, patients were
classified on the basis of the presence of the motor complications in three groups: 1: uncomplicated
phase, 2: complicated phase with predictable complications and 3: complicated phase with
unpredictable complications. The primary outcome is the PDQ-SI, our measure for quality of life..
Results
The mean PDQ-SI score in group 1 was 27.7, in group 2 36.7 and in group 3 37.1. This
difference between the three groups is significant (p<0.0001). Further analysis shows that the
difference in quality of life in PDQ-SI is present between group 1 and 2 and group 1 and 3, there is no
difference between group 2 and 3. The PDQ scores in group 2 and 3 are significantly higher, which
means a lower quality of life. In a multivariate analysis, we see that predictable complications are a
significant predictor of quality of life, this is not the case with unpredictable complications.
Conclusion
The quality of life in the group of Parkinson’s patients with motor complications is
significantly lower than the quality of life in the group without on-off fluctuations or dyskinesias. So
having motor complications is a significant predictor of a worse quality of life.

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Voorspelt transcutaan gemeten hypocapnie cerebrale hypoperfusie?

Background:
premature born children are very vulnerable. They often need respiratory care,
which is evaluated by measuring the blood gass value of CO2. These values are obtained by
bloodpuncturing, which causes a lot of stress and has several disadvantages. An alternative
non-invasive method would be desirable. In this study, we investigated the use of
transcutaneous measuring of CO2. It is known that hypocania measured by blood gasses
predicts cerebral hypoperfusion. It is not known whether transcutaneous measured
hypocapnia predicts the same.
Aim:
the aim of this study is to evaluate the relationship between tcCO2 and cerebral
bloodflow, measured using NIRS, on the third day postnatally in extreme premature born
children.
Methods:
we included preterm infants with a gestational age between 24+0/7 and 26+6/7
weeks, born between January 2011 and November 2014 who were admitted to the NICU of
the UMCG directly after birth. Data of rcSO2, tcCO2, SpO2 and pCO2 were collected from
different (online) databases and medical files at two moments (morning and evening). We
calculated the FTOE as a marker of hypoxia-ischemia. We used IBM SPSS Statistics 22 for
the statistical analyses.
Results:
51 children were included (mean gestation age 26.0 ± SD 0.76 weeks; median birth
weight 845 grams (525-1110 grams)). We found a negative correlation between tcCO2 and
FTOE (rho = -0.383; p = 0.06). The agreement between pCO2 and tcCO2 was moderate.
However, there was a strong correlation between pCO2 and tcCO2 (rho = 0.786; p = <0.001)
and between ΔpCO2 and ΔtcCO2 (rho=0,700; p=0,018). Negative trends were found for the
correlation between ΔpCO2 and ΔFTOE (rho=-0,544; p=0,065) and for the correlation
between ΔtcCO2 and ΔFTOE (rho=-0,265; p=0,054). Type of ventilation had a significant
influence on the FTOE when taking into account the tcCO2 and gestational age. tcCO2
increases with increasing postnatal age.
Conclusion:
transcutaneous measured hypocapnia predicts cerebral hypoperfusion. Despite a
difference with the golden standard pCO2, a relation between tcCO2 and cerebral bloodflow
has been found. This suggests that the tcCO2 can help to estimate whether cerebral bloodflow
is compromised as a result of low CO2.
Further research with a larger study population would be useful, as well as taking into
account the degree of illness, use of medication and perfusion of the skin.

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Predictors for distant metastases in patients with head and neck cancer.

Head and neck cancer (HNC) is the sixth most common solid malignancy in the world. Although HNC is considered to be a locoregional disease, in a significant number of patients, survival is highly influenced by the occurrence of distant metastases (DM). Data on risk factors of the presence of DM’s are controversial in the literature; however primary tumor site, T- and N-stage, histology grades and local disease control are considered to be the most important ones. Finding such predictors of DM’s in HNC patients can help clinicians in differentiating between high- and low-risk patients. The present study aimed to determine predictive patient and tumor characteristics, for the development of DM’s, in a cohort of HNC patients who developed DM within 60 months of primary diagnosis.
Methods
In our cross-sectional study one hundred and five HNC patients were included with in total 116 DM’s. HNC patients with DM were selected from a database acquired from the Dutch Comprehensive Cancer Center, regarding all HNC patients treated in the UMCG between 1999 and 2008, consisting of 2132 patients. Patient and tumor characteristics such as: gender, age, intoxication, height, length, body mass index, comorbidities, TNM-stage, histology, treatment and imaging modalities were extracted from the electronic patient’s dossiers. Descriptive statistics and Kaplan Meier survival analysis were performed.
Results
Of the 105 patients, there were 82 males (78%) and 23 females (22%). 67% of the included patients were active smokers and 57% were active drinkers. The median age at diagnosis was 61 years and median BMI was 23,2. Fifty-three percent of the population reported with none/mild comorbidity and 42 percent reported with moderate/severe comorbidity, classified according to the ACE-27 index. We found 73% Stage IV tumors, 49% T4 tumors and in 72% of the cases N+ nodal stage. Extracapsular spread, perineural growth and angioinvasion were found in respectively 18, 13 and 11 percent of the surgically treated cases, but were more often unknown (68, 73 and 70 percent of the cases). Post-operative resection margins were positive in 24% of the cases. The preferred location of the DM was the lung with 52%, followed by the bones with 32% and then the liver with 9%. The median metastasis-free survival time was 8 months. We did not find significant differences between the metastasis-free survival times of the different primary tumor sites, or DM sites. (p-values 0.280 and 0.882)
Conclusion
Male gender, smoking, drinking and BMI seems to play a role in the development of DM. N+, T4 and stage IV tumors were found in high percentage in the cohort of HNC patients with DM. The lungs and bones are the most prominent sites of DM; therefore these organs have to be screened for DM, especially within the first 8 months after diagnosis. This study can be an important first step towards the development of a clinically useable model; however, further and more extensive research is needed for such a model, analyzing a study population, containing HNC patients with and without DM in follow-up.

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Voorspellende factoren voor gecompliceerd beloop na hoofdtrauma in de huisartsenpopulatie.

Background:
In primary care, the care and policy for patients with a head injury are based on
guidelines of the Centraal Begeleiding Orgaan (Central Body for Guidance) from 2010. At the
present time there is no guideline, adapted to the population of patients with a head injury
seen by general practitioners, while it is plausible that there are differences in the severity and
seriousness of head injury seen in primary and secondary care.
Objective:
To describe clinical aspects of patients with a head injury referred by primary care
to an Emergency department and to determine the predictive factors for a complicated course
Methods:
In this retrospective, descriptive, observational study first all 661 patients with a
head injury (superficial injury included) referred by general practitioners (during the day and
during out-of-hours services) in 2011/2012 were screened and finally 282 patients were
included after excluding patients with solely superficial injury.
Patient characteristics (age, gender, use of anticoagulants), trauma characteristics ( cause and
nature) and clinical sign and symptoms were linked with clinical interventions like CT scan,
hospitalization and neurosurgery.
Results:
Anticoagulants were used by 18.4% of the patients: by far most in the eldest age
group of 75 years and older (70.2%).
A CT scan was performed in 52.8%, in the eldest group even in 89.4%. The use of AC and
receiving a CT scan is strongly related (88.5%). But with binary logistic regression, we
displayed that older than 75 years and use of AC independently increase the chance on
receiving a CT scan.
Of all CT scans, 26.8% display relevant (trauma related) abnormalities. The chance on
abnormality is largest in the patient group 40 years and older.
More CT scans were made in patients with a fracture: in this group more abnormalities were
found.
Not more abnormalities were found in patients with headache, nausea, amnesia, loss of
consciousness, neurological failure, hematoma, wound.
Of all referred patients 51,8% were admitted. Children below 6 years (64%) en the eldest
group (78,7%) were admitted most frequently. Patients using AC were also admitted
frequently (76,9%); even when corrected (binomiale logistic regression) for the high use of
AC by the eldest group, the admittance for AC (odds ratio 2,38) en the eldest group (odds
ratio 2,61) remained high.
From patients with alarm symptoms, only the group presenting retrograde amnesia was
admitted more frequently than the group without this symptom.
A neurosurgical intervention was done in 4 patients (1.4%); in 2 patients within 24 hours, in 2
after 24 hours. In both groups one patient died.
Conclusion:
It is desirable that the CBO guidelines about head injury in primary for adults will be adapted.
No difference in criteria is made in risk factors, while in this study we found a predictive
value for a complicated course for the following factors: use of AC, age of 75 years or older,
fracture of head and retrograde amnesia.

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Kinetic changes with fatigue and relationship to running related injuries(RRI) in female runners: a pilot study.

Objectives
The incidence of running related injuries (RRI) is fairly high in many recreational runners. Kinetic variables, like the vertical ground reaction force (vGRF), play a possible role in the development of RRI. The purpose of this study was to analyze how treadmill induced fatigue changed the vGRF and spatio-temporal variables of recreational female runners with and without previous RRI.
Design
Pilot study.
Methods
Nine recreational female runners with and nine without previous RRI were taking part in the treadmill induced fatigue protocol. Before and after fatigue the vGRF and spatio-temporal variables of all runners were measured at 9 km/h. The primary parameter was the loading rate of the vGRF. Secondary parameters were the impact- and active peak, step frequency, step length, contact time, duty factor, leg stiffness and arch height. A linear mixed model analysis and post-hoc bonferroni comparison (α=0,05) were performed. Results
Treadmill induced fatigue resulted in a significant decrease of the loading rate in the runners with and without RRI. The decrease was not significantly different between both groups. Only in the group with previous RRI the step frequency decreased. This was accompanied by an increase in step length, increase of the contact time, higher duty factor and a decrease in leg stiffness. Conclusion
Recreational female runners with and without RRI adapted their running style differently with treadmill induced fatigue, which resulted in changes of the vGRF and spatio-temporal variables.

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De Invloed van Ashy Dermatose / Lichen Planus Pigmentosus op de Gezondheidsgerelateerde Kwaliteit van Leven.

Background and objectives:
Ashy dermatosis (AD) is an uncommon skin pigmentary disorder characterized by ashy-gray macular discoloration of the skin. Some authors categorize AD as a pigmentary macular variant of lichen planus (lichen planus pigmentosus, LPP). However, the etiology is unknown and effective treatment options are not available. The impact of the skin lesions on (health related) quality of life (HRQoL) is unknown. The objective of this study is to assess the HRQoL of patients with AD/LPP. Secondary objective was to, retrospectively, identify a possible subgroup of patients who share a common clinical presentation, response to therapy and/or course of the disease. The identification of such a subgroup of patients could possibly support an improvement in the HRQoL.
Materials and methods:
32 patients diagnosed with AD/LPP filled out a validated questionnaire about quality of life (skindex-29) as well as questions about the course of their skin disorder and their response to therapy. An assessment of the clinical presentation was performed by an independent dermatologist who determined the morphology of the skin disorder based on photos made during the first consultation. The course of the skin disorder was investigated by comparing color, size, severity and difference in number of lesions based on the aforementioned photos and photos made during a single consultation for the purpose of this study. The results of this comparison are based on expert opinion (physician global assessment, PhGA). Patients also gave their opinion about the course of their disorder (patient global assessment, PtGA).
Results:
The mean scores (range: 0 – 100) of the different domains of HRQoL (‘scale scores’) were 26.0 (symptoms), 43.6 (emotions) and 22.7 (functioning). The mean total score was 30.7. The scale score for ‘emotions’ was significantly higher compared to the other domains (p<0.01). HRQoL was significantly more impaired for the emotional domain in patients who have had treatment in the past and in patients having hyperpigmentations located on the (ventral) chest (p<0.05).
Clinical presentation of the patients showed a high degree of variation. Most of the patients had undergone treatment in the past. The duration between the consultations ranged from 1 to 16 years. For most patients it was observed that the colour of the hyperpigmentations had become lighter (53.8%) or remained the same (30.8%). The size of the individual lesions remained the same (41.0%) or became smaller (41.0%). For 46.2% of the patients an increase in the number of lesions was observed. At clinical presentation, a moderate severity of the skin disorder was observed for most patients. For 47.7% of the patients the severity remained stable, for 38.5% an improvement was observed.
Conclusion:
AD/LPP has an adverse impact on HRQoL. Scores indicated that emotions were severely influenced and functioning was influenced mildly. Patients who had undergone treatment in the past and patients having hyperpigmented lesions on the ventral chest showed a higher impact on the emotional domain of HRQoL.
AD/LPP seems to be a dynamic disorder with a high degree of variation in clinical presentation. In many patients a change in colour, size or number of lesions was observed, however in the majority of the patients the severity of the skin disorder remained stable. No association between colour, size, severity or number of lesions and the duration of the skin disorder was found. No specific subgroup of patients who share a common clinical presentation, results to therapy and/or course of the disorder could be identified.

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Stratificatie van STEMI patiënten op basis van biomarkers.

Patients who have experienced a myocardial infarction could benefit greatly from custom preventive therapy based on their prognosis. In current practice the estimation of such a prognosis is primarily based on clinical parameters, despite clear indications in available literature that a strong relationship exists between cardiac biomarkers and outcome of cardiac function after an infarction.
This retrospective study focused on finding a biomarker driven predictive model for patient prognosis after enduring a ST-elevated myocardial infarction (STEMI) in an existing database. This model would subsequently be validated retrospectively in another large-scale database of STEMI patients. We looked for associations between a model based on left ventricular ejection fraction (LVEF) and 30-day mortality as well as major adverse cardiac events (MACE) in 1-year follow-up in the database. To this end patients were divided in groups of relative prognosis. Subsequent analysis was performed to calculate the odds ratio (OR) and hazard ratio (HR) between these groups. The resulting model used peak values for troponin T (TnT) and creatin kinase – myocardial band (CK-MB) to predict LVEF. All three groups that had a prognosis with worse LVEF than normal had a significantly raised OR in both follow-ups when compared to the normal group. In 30-day and 1-year follow-up we found an OR of respectively 1.93 (P=0.004) and 1.59 (P=0.001) was found for the group with a mild prognosis. An OR of 3.24 (P=0.006) and 2.28 (P=0.009) was found up for those with a moderate prognosis and an OR of 9.72 (P<0.001) and 3.72 (P=0.005) for those with a severe prognosis.
The predictive model found in this study is a valid tool for estimating the prognosis in STEMI patients for both 30-day all cause mortality and 1-year MACE.

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Early post-transplantation hypophosphatemia and the risk of graft failure and cardiovascular mortality after kidney transplantation.

Background and objectives
Post-transplantation hypophosphatemia, phosphate levels below 0.7 mmol/L, is common after kidney transplantation. Hypophosphatemia is probably the consequence of still elevated levels of fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH). Long-term exposure to FGF23 and PTH, have been associated with adverse patient and graft outcomes, but may also reflect good graft function. We therefore investigated whether post-transplant hypophosphatemia is associated with graft failure or mortality. Design, setting, participants & measurements
In a cohort of renal transplant recipients (n=957), the lowest serum phosphate during the first year post-transplantation was recorded. We analyzed the association between the lowest serum phosphate, either as a categorical (absent >0.7 mmol/L, mild 0.5-0.7 mmol/L, severe <0.5 mmol/L) or as a continuous variable (per halving), and the outcomes graft failure and mortality. This was done by multivariable Cox regression analyses adjusted for known risk factors for adverse patient and graft outcomes. Results 821 patients (86%) developed hypophosphatemia during the first year post-transplantation, of which 446 patients (47% of the total cohort) had severe hypophosphatemia. Lowest levels of serum phosphate were reached at 33 [21-51] days after transplantation. During follow-up for 9 [5-12] (median [IQR]) years, 181 (19%) patients developed graft failure and 295 (31%) patients died. The development of hypophosphatemia was significantly associated with a lower risk of graft failure (full model HR, severe vs no hypophosphatemia; 0.41 [0.22-0.73], P<0.01 mild vs no hypophosphatemia 0.41 [0.24-0.72], P<0.01). Furthermore, hypophosphatemia was associated with a reduced risk of cardiovascular mortality (severe vs no hypophosphatemia: 0.29 [95% CI 0.13-0.67], P<0.01 mild vs no hypophosphatemia: 0.25 [0.11-0.58], P<0.01). Hypophosphatemia was not associated with non-cardiovascular mortality.
Conclusions
The development of post-transplantation hypophosphatemia in the first year after kidney transplantation is associated with a lower risk of both graft failure and cardiovascular mortality. This indicates that an optimal renal phosphate excretion capacity after transplantation is beneficial for graft and patient outcomes.

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Het effect van neurolyse bij ramus infrapatellaris neuropathie.

Objective:
Entrapment neuropathy of the infrapatellar branch of the saphenous nerve is generally an unknown and unfrequently diagnosed cause of knee pain. The aim of this study was to evaluate the efficacy of surgery used by plastic surgeons to treat this neuropathy: neurolysis of the infrapatellar branch.
Methods:
A cohort of patiënts diagnosed with infrapatellar neuropathy was evaluated. Patiënts that received treatment were asked their pain scores (Numeral Rating Scale 0-10) before and after surgery, their global perceived effect, and the influence of this disease on their life in terms of working and sporting. Patients treated with neurolysis between September 2014 and Februari 2015 were also evaluated prospectively. Their pain score was evaluated using the visual analog scale (10-100mm). In addition, neural conduction was measured before and after surgery using somatosensory evoked potentials (SSEP).
Results:
A total of 55 patiënts with infrapatellar neuropathy were evaluated, of which 50 patiënts were treated by neurolysis. 74 percent of the treated patiënts (n = 32) demonstrated a numeral rating scale reduction of at least 50% in the first 6 months. On the long term, 96 percent (n = 48) showed a numeral rating scale reduction of on average 4 in 12 months after surgery. The reduction in pain score in treated patiënts differs significantly from that of untreated patients. Prospectively, 2 patiënt were evaluated. Both showed a visual analog scale reduction of at least 50% in 3 months after surgery. With the used SSEP technique described in literature no results could be reproduced that indicate neural conduction impairment.
Conclusion:
Surgical neurolysis as a treatment for infrapatellar neuropathy is effective in about two-thirds of the patiënts. In addition, almost all patiënts (96%) will retrieve a significant reduction in pain in a 12 months recovery period.

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Relationship between hyoid displacement on video fluoroscopic studies and swallowing impairment in head and neck cancer patients.

Background:
Concomitant chemo radiation therapy (CCRT) is nowadays the treatment of choice for advanced squamous cell carcinoma (SCC) of the head and neck. Each treatment option has undesirable functional side effects as does dysphagia, as does CCRT. Organ preservation does not necessarily preservation of function. Dysphagia can be serious health issue. For instance aspiration pneumonia can be potentially life threatening consequence of CCRT. Radiation-induced xerostomia may diminish patients’ swallowing disability. Due to this swallowing impairment is largely underappreciated and underreported.
Also from recent studies it is stated that a reduced anterior and superior movement of the hyoid bone, during swallowing, is contributing to this aspiration risk. The aim of this study is to determine to which degree reduced movement of the hyoid bone, as assessed with video fluoroscopy (VFS), is correlated with (both objective and subjective) swallowing impairment, and to assess to which degree reduced movement range can be a predictor of penetration-aspiration.
Patient’s perceived swallowing impairment will be scored using a questionnaire (subjective outcome measure). And objective swallowing impairment will be scored in two ways: by scores on the penetration-aspiration scale (PAS) and measures of the hyoid bone displacement on VFS images.
Methods:
This is a retrospective, single-blind study. All the data used in this study were obtained from a recent RCT: prevention of trismus, swallowing and speech problems in patients treated with CCRT for advanced head and neck cancer (H&NC.) 17 patients with advanced (stage III and IV) SCC of the head and neck treated at the Netherlands Cancer Institute (AvL-NKI) with CCRT participated in this study. We analyzed hyoid bone displacement using video fluoroscopy. We used a coordinate system to measure the anterior and superior hyoid displacement during swallowing. Due to poor image quality of VFS images, we had to exclude eight patients before analyzing.
Results:
our findings on hyoid bone displacement measurements were at the level of normal subjects, which was not what we expected. We found a significant increase in mean superior hyoid bone displacement (SHD) at ten weeks post CCRT for twee consistencies. For 5cc thin liquid boluses (P value 0,024. And for cake ( P value 0,012.)
At one year follow-up this increase in SHD had disappeared. For anterior hyoid displacement (AHD) no significant increase or decrease was measured. Furthermore 6 patients scored for penetration or aspiration on the PAS. At the same time three of them did not report any perceived swallowing problems. In general our subjects did not report much perceived problems at baseline. Ten weeks after CCRT an increase in scores on the questionnaires was witnessed. At one year follow-up most of those complaints diminished.
A correlation was found between one question at baseline assessment (swallow more than once while eating) with SHD in all four consistencies (P value 0,005.) At ten weeks follow up a significant correlation was found between SHD and the question difficulty with eating (P value 0,019).
Conclusion:
Ten weeks post CCRT a significant increase in mean SHD was measured in our study. Only in a few subjective outcome measures (questions) we could find a correlation with hyoid bone displacement. Discrepancies exist between the perception of the swallowing problems by the patient and the problems as identified by the doctor. Therefore it stresses once again that a thorough examination is of importance in the follow-up in patients who were treated with CCRT for cancer in the head neck region. Because the risk of silent aspiration, and therefore a potentially health issue will always exist.

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Predictoren van persisterende of veranderende ontwikkelingsproblemen bij matig prematuren op de kleuterleeftijd

Doel: Deze studie onderzoekt of er predictoren zijn voor het veranderen of persisteren van ontwikkelingsproblemen bij matig prematuren op kleuterleeftijd.
Materiaal & methoden: Er werd gebruik gemaakt van gegevens van de Pinkeltje studie, 641 matig prematuren werden geïncludeerd. Ontwikkelingsproblemen werden gemeten op 4- en 5-jarige leeftijd met de gevalideerde Ages and Stages Questionnaire(ASQ). De uitkomsten van de ASQ op leeftijd 4 en 5 jaar werden met elkaar vergeleken, waarna de deelnemers werden ingedeeld in ontwikkelingscategorieën: persisterend goede ontwikkeling, verbeterende ontwikkelingsproblemen, persisterende ontwikkelingsproblemen en verslechterende ontwikkelingsproblemen. Met multivariaat multinomiale logistische regressie analyse werd gekeken naar een associatie tussen de predictoren en de ontwikkelingscategorieën. Predictoren werden geselecteerd met univariaat multinomiale logistische regressie: bij p<0.20 werden ze meegenomen in het multivariaat model. De referentiegroep was persisterend goed.
Resultaten: De proporties kinderen per ontwikkelingscategorie waren: 64% persisterend goed, 10,9% verbetering, 12,3% persisterend slecht en 12,8% verslechtering. Predictoren met een significante associatie in alle ontwikkelingscategorieën: jongen in plaats van meisje (verbetering OR 2,69; persisterend slecht OR 3,07; verslechtering OR 2,97) en lage sociaal economische status (SES) ten opzichte van midden-hoge SES (verbetering OR 3,08; persisterend slecht OR 2,38; verslechtering OR 2,23). Tweeling (OR 2,70) en postnatale hypoglycemie (OR 2,97) waren geassocieerd met verbetering. Prematuur breken van de vliezen (PROM) (OR 1,82) was geassocieerd met verslechtering.
Conclusie: In dit onderzoek worden een aantal predictoren gevonden die relevant zijn voor veranderende en/of persisterende ontwikkelingsproblemen van matig prematuren op de kleuterleeftijd. Voor implementatie in de praktijk is verder onderzoek nodig met grotere aantallen per predictor.

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De voorspellende waarde van parameters gemeten met 3D speckle tracking echocardiografie voor cardiale events in patienten met chronisch hartfalen

Achtergrond: Linker ventrikel (LV) volumina en ejectie fractie (EF) zijn algemeen geaccepteerde prognostische variabelen in patiënten met hartfalen. Het accuraat meten van de LV volumina en de LVEF is van groot belang bij het identificeren van hoog-risico patiënten en bij het evalueren van hun behandeling. Cardiale magnetische resonantie imaging (CMR) is de referentie techniek gebleken voor de analyse van LVEF, CMR is echter niet overal beschikbaar en de analyse is tijdsintensief. Drie-dimensionale speckle tracking echocardiografie (3DSTE) is een relatief nieuwe techniek, waarbij door middel van snelle acquisitie en semi-automatische analyse van beelden in vier dimensies deze beperkingen overkomen kunnen worden. Met 3DSTE kunnen vervormingen, ook wel strain genoemd, van het myocard gedurende de hartcyclus gemeten worden. 3DSTE is een gevalideerd en betrouwbaar instrument gebleken voor het meten van volumina, LVEF en strain. Parameters gemeten met twee-dimensionale speckle tracking echocardiografie (2DSTE) hebben bewezen een voorspellende waarde te hebben voor patiënten met chronisch hartfalen, de voorspellende waarde van 3DSTE parameters is echter nog niet eerder onderzocht.
Doel van de studie: Het doel van deze studie was om te onderzoeken of LVEF en strain parameters, gemeten met 3DSTE, een voorspellende waarde hebben voor cardiale events bij patiënten met chronisch hartfalen.
Methode: Het betrof een retrospectieve studie van 113 patiënten met chronisch hartfalen die naar het VU medisch centrum (VUmc) werden verwezen voor CMR. De geïncludeerde patiënten kregen op dezelfde dag CMR en 3DSTE. Data werd verzameld over patiëntkarakteristieken en cardiovasculaire follow-up met behulp van patiëntendossiers. Patiënt-, CMR- en 3DSTE gegevens werden gerelateerd aan cardiale events. Cardiale events werden gedefinieerd als sterfte, hospitalisatie ten gevolge van hartfalen, myocardiale infarcering, revascularisatie, device implantatie en terechte device interventies. Deze cardiale events vormden samen het gecombineerd eindpunt. Regressie analyse is uitgevoerd om de correlatie tussen CMR- en 3DSTE parameters en cardiale events te onderzoeken.
Resultaten: Tijdens de follow-up periode (gemiddelde duur 41 ± 9 maanden) zijn er 44 patiënten (39%) die het gecombineerde eindpunt behaald hebben. In de groep die het eindpunt hadden behaald, kwam significant vaker hartfalen op basis van ischemische cardiomyopathie voor. Ook was er sprake van een significant lagere LVEF en een trend tot grotere LV volumina, gemeten met 3DSTE en CMR. Globale longitudinale strain (GLS), globale circumferentiële strain (GCS) en globale area strain (GAS) lieten significant lagere waarden zien in de groep die het eindpunt hadden behaald. Regressie analyse toonde aan dat LVEF, gemeten met CMR en 3DSTE, en strain parameters een voorspellende waarde hebben voor cardiale events. In deze studie was GLS de sterkste voorspeller. Bij een GLS ≥ -11,0% was het ruim vier maal zo waarschijnlijk dat een cardiaal event zou optreden. Strain parameters correleerden tevens sterk met elkaar en met LVEF.
Conclusie: LVEF en strain parameters, gemeten met 3DSTE, hebben een voorspellende waarde voor cardiale events in patiënten met chronisch hartfalen. De voorspellende waarde van deze parameters is non-inferieur aan die van LVEF met CMR. In deze studie blijkt dat een verminderde GLS het sterkst voorspellend is voor cardiale events. 3DSTE strain parameters kunnen in de toekomst mogelijk een additionele waarde kunnen hebben bovenop de klinische risicofactoren of zouden als prognostische variabele kunnen dienen in plaats van de LVEF.

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Nutrilon Nenatal Protein Fortifier bij extreme prematuren Het effect van NNPF op groei, tolerantie en (verdenking op) NEC

Nog altijd bestaat er veel onduidelijkheid over het voeden van prematuren met een extreem laag geboortegewicht. De onrijpheid van het gastro-intestinale stelsel van prematuren zorgt ervoor dat enterale voeding bemoeilijkt wordt. Vanwege de beschermende effecten is moedermelk de voedingsbron van eerste voorkeur voor zowel voldragen als premature neonaten. Echter schiet moedermelk tekort op het gebied van de eiwitbehoefte van een extreme prematuur. Eiwit is een zeer belangrijke voedingsstof als het gaat om groei en dient daarom extra gesuppleerd te worden bij prematuren, naast de standaardvoeding van moedermelk of kunstvoeding. Onbekend is echter wat de eventuele (schadelijke) effecten van deze extra eiwitten zijn op symptomen van voedingsintolerantie en op necrotiserende enterocolitis (NEC), omdat de exacte oorzaak van deze aandoening nog steeds onbekend is. Deze studie heeft door middel van een retrospectief cohortonderzoek een testgroep die gevoed is met extra eiwitten en een controlegroep met standaard voeding vergeleken. Alle prematuren hadden een geboortegewicht onder de 1000 gram en waren vanaf de eerste levensdag opgenomen op de NICU in het UMCG. De studiepopulatie is van geboorte tot ontslag gevolgd en er is ingezoomd op de weken vóór, tijdens en na het gebruik van het eiwitsupplement. De uitkomstparameters bestonden uit gemiddelde groei per week in gewicht, lengte en schedelomtrek, de aanwezigheid van symptomen van voedingsintolerantie en het optreden van (verdenking op) NEC. Afgezien van een bijna significant betere groei tijdens het gebruik van het supplement, is er qua groei geen significant verschil tussen de groepen gevonden op zowel korte als lange termijn. Bij de testgroep was vooraf aan de toediening van de eiwitten al vaker sprake van symptomen van voedingsintolerantie. Echter worden ook tijdens en na de NNPF-toediening vaker bolle buiken en gallige retentie geregistreerd bij de testgroep. Onduidelijk is welke rol het supplement exact gespeeld heeft bij het optreden van de intolerantieverschijnselen, onder andere omdat NEC vaker voorkomt in de testgroep dan in de controlegroep en NEC gepaard gaat met symptomen van voedingsintolerantie. Deze bevinding zou verder onderzocht kunnen worden, waarbij er echter rekening moet worden gehouden met de multifactoriële etiologie van NEC.

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TBX4 Mutations in Patients with Pulmonary Arterial Hypertension – Cause or Coincidence?

Introduction: A recent study found a relatively high incidence of TBX4 mutations in patients
diagnosed with Pulmonary Arterial Hypertension. This disease is characterized by endothelial
dysfunction leading to vascular remodelling, including endothelial-to-mesenchymal transition
(EndMT). It is hypothesized that loss of TBX4 causes a disruption in endothelial homeostasis,
(i) increasing the susceptibility to develop EndMT and (ii) disrupting the inhibitory pathways
activated by laminar shear stress (LSS) on EndMT.
Methods: Endothelial cells were treated with short hairpin RNAs directed at TBX4, and
exposed to EndMT inducers (TGFβ2 and IL1β) and laminar shear stress. The gene transcript
was analysed using RT-PCR and tested for significance using two-way ANOVA and post hoc
Bonferroni testing (α = 0.05).
Results: Laminar shear stress induces strong up-regulation of TBX4 compared to a rather low
expression under static conditions. Upon co-stimulation with TGFβ2 and IL1β, TBX4
deficient cells show tendencies consistent with EndMT, which are not significantly different
compared to healthy control cells. Absence of TBX4 causes a significant down-regulation of
KLF4 and ID1.
Conclusion: Although tendencies suggest that loss of TBX4 could possibly increase the cells
susceptibility to develop EndMT, significant changes are lacking. Interestingly however,
down-regulation of KLF4 and ID1 in the absence of TBX4, implicates that loss of TBX4
possibly interferes with EndMT inhibition exerted by LSS. Overall the results suggest that
TBX4 loss probably has the potential to play a causal role in EndMT development. Further
studies to investigate this complex connection are required.

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Patiënten met pijnklachten als gevolg van artrose van de heup of knie. Een inventarisatie van patiënteigenschappen en kenmerken van centrale sensitisatie

Artrose is wereldwijd de meest voorkomende gewrichtsaandoening en komt vooral bij
ouderen voor. Door de vergrijzing zal het aantal patiënten met artrose de komende jaren
aanzienlijk toenemen. Pijn is de hoofdreden voor patiënten om een arts te bezoeken. Recent
onderzoek heeft aangetoond dat pijn bij artrose zowel nociceptieve als neuropatische
kenmerken heeft. Studies hebben laten zien dat er in veel gevallen een discrepantie bestaat
tussen de radiologische afwijkingen en de ernst van de pijnklachten. Wanneer conservatieve
behandeling van de pijn niet afdoende is, wordt vaak overgegaan tot het plaatsen van een
gewrichtsprothese. Echter, een deel van de patiënten is ook na plaatsing hiervan niet pijnvrij.
Voorgaande studies hebben laten zien dat wellicht centrale sensitisatie een rol speelt bij de
pijnklachten die artrosepatiënten ervaren. Dit leidt tot een verhoogde gevoeligheid voor pijn
en uit zich in pijnklachten met neuropatische kenmerken. Het huidige onderzoek analyseert
met behulp van de modified PainDETECT-vragenlijst (mPDQ) hoe groot het aantal
artrosepatiënten met neuropatische pijnklachten is en hoe deze klachten zich verhouden tot
functie, kwaliteit van leven en centraal gemedieerde symptomen. Inzicht in deze problematiek
kan bijdragen aan de behandeling van pijnklachten bij patiënten met artrose.
Methode:
Met behulp van de mPDQ en een vooraf vastgestelde afkapscore werden 299 patiënten met
heup- of knieartrose onderverdeeld in een groep mét (NP+ groep) en zonder neuropatische
pijnklachten (NP- groep). Functie, kwaliteit van leven en pijn werden gescoord middels de
KOOS/HOOS, SF-36 en VAS. Mentale gezondheid en vitaliteit, subschalen van de SF-36, en
de Pittsburg Sleep Quality Index (PSQI) werden gebruikt op centraal gemedieerde klachten
(stemmingsklachten/vermoeidheid) te meten.
Resultaten:
Van de patiënten met artrose van de heup of knie scoorde 38,5 % >12 op de mPDQ, hetgeen
suggestief is voor de aanwezigheid van neuropatische pijnklachten. Patiënten in de NP+ groep
scoorden lager op alle KOOS/HOOS items en op de SF-36 subschalen fysiek functioneren en
pijn. Een hogere VAS-score en het ervaren van pijn in meerdere lichaamsdelen bleken
geassocieerd te zijn met een mPDQ-score >12.
Conclusie:
Een aanzienlijk deel van de patiënten met artrose van de heup of knie blijkt pijnklachten met
een neuropatische kenmerken te ervaren, mogelijk op basis van centrale sensitisatie. Patiënten
in de NP+ groep scoorden lager op functie en kwaliteit van leven. Mogelijk ondervinden
patiënten in de NP+ groep meer depressieve klachten en slaapproblemen. Meer onderzoek is
gewenst om een objectief meetinstrument voor centrale sensitisatie te ontwikkelen en de
behandeling voor artrosepatiënten met neuropatische pijnklachten te optimaliseren.

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Differences in donor site morbidity between the anterior iliac crest and the calvarium: a case-control study

Background: Due to bone resorption in patients with edentulous jaws, these patients often have problems wearing a denture. A solution is to fix the denture on dental implants, but most of the times there is an insufficient amount of bone left. Often, these patients require the har-vest of autologous bone which is then transplanted to the maxilla or mandible before dental implants can be placed. When a substantial amount of bone is needed, extra-orally harvested bone is required. Autologous bone harvesting is associated with the occurrence of donor site morbidity. The anterior iliac crest is currently in the Netherlands the mostly used location used for pre-prosthetic augmentation. For this location, the occurrence of morbidity includes nerve damage or short-term post-operative pain. Another harvesting site is the calvarium. Here morbidity includes dural exposures. The reported post-operative pain seems minimal.
Up to this date, the morbidity of these two donor sites it is not investigated in a comparative study. Therefore it was decided to assess morbidity (complications, post-operative pain, pa-tient satisfaction, and implant survival) of the anterior iliac crest and the calvarium.
Methods: In this case-control retrospective study, 27 edentulous patients, who had undergone a calvarial harvesting procedure, were matched with 27 edentulous patients, who had under-gone an iliac crest harvesting procedure during the same period. Patients were matched ac-cording to follow-up, age, and sex. Donor site morbidity was assessed by medical record as-sessment, patient questionnaires including pain and end result satisfaction scores, and physi-cal examination. To assess the success of the procedures, implant survival has been reported. Possible differences between harvesting groups were statistically tested.
Results: The per-operative and post-operative complications did not differ significantly be-tween the two donor sites. Per-operative complications were present in 11.1% in the calvarial group, and in 3.7% of the iliac crest group. In two patients of the calvarial group, a re-operation at the donor site was necessary, whereas none of the patients in the iliac group were re-operated. The post-operative pain (VAS) scores directly after harvesting, on recall, was significantly higher in the iliac crest group (Median: 4.7) than in the calvarial group (Median: 0.5) (p<0.001). The current pain scores was zero in both groups (Mean folow up: 2 years). End result satisfaction levels did not differ between both groups, iliac crest group (Mean: 89.5), calvarial group (Mean: 93.6). Implant survival, in the iliac group (94.4%), in the calvar-ial group (91.8%), did not differ significantly.
Conclusion: Low donor site morbidity, high patient satisfaction, and high implant survival were associated with both harvesting procedures. However, patients reported a higher pain level directly after iliac crest harvesting, than after calvarial harvesting.

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