Category Archives: Thesis

Master Theses UMCG 2017-03-15 11:15:31






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Pulmonary involvement in primary Sjögren’s syndrome






Background: In previous studies in primary Sjögren’s syndrome (pSS), the prevalence of
pulmonary involvement varied greatly depending on differences in inclusion criteria and
definitions of pulmonary involvement. The ESSDAI has been developed for standardized
assessment of the main organ involvements. Our aim was to evaluate the prevalence and types
of pulmonary involvement in pSS patients and to classify the manifestations using the
pulmonary domain of the ESSDAI.
Methods: This retrospective cohort study included all consecutive pSS patients, fulfilling the
AECG and/or ACR classification criteria, who visited the department of Rheumatology and
Clinical Immunology of the UMCG in 2015. Data were obtained from electronic patient records
of the first visit in 2015. In some cases, the difference between pulmonary manifestations
caused by pSS or coincidental factors remained unclear, resulting in a range of assumed to
possible pulmonary involvement in pSS.
Results: Of the 262 included pSS patients, 93% were female and mean age was 56 ± 15 years.
Pulmonary complaints were present in 88 (34%) patients. Additional pulmonary diagnostics
was performed in 225 (86%) patients. Pulmonary involvement was present in 25-39 (10-15%)
pSS patients. Overall, most common was interstitial lung disease (ILD), which was present in
15 patients; especially non-specific interstitial pneumonia (NSIP). In total, 16 (6%) patients had
a positive ESSDAI for the pulmonary domain; low activity (n=4), moderate activity (n=11) and
high activity (n=1).
Conclusion: In this cross-sectional study in daily clinical practice, pulmonary involvement was
present in 10-15% of pSS patients, most common ILD. Of all pSS patients, 6% were scored as
active on the pulmonary domain of the ESSDAI. Continue reading






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Protective Effects of Pharmacological TPRM2 Inhibition on Ischemia-reperfusion Injury of the liver






IBsachckemgrioa-urnepde rfusion injury (IRI) of the liver is a common clinical problem after liver surgery
and transplantation and new therapies are required to prevent it. Calcium overload in
hepatocytes plays a central role in the pathogenesis of IR… Continue reading






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Connective Fields (CF) in de vroege visuele cortex bij patienten met een psychotische aandoening






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The concept of micro-merging within professional services: a case study in the dutch healthcare industry






Although the literature on mergers and acquisitions (M&As) is quite advanced, analyses of micro-mergers—mergers of internal functional units within the same organization—remain limited. Clarification is needed regarding micro-mergers and their effects on performance. Therefore, this case study investigated micro-mergers within professional service firms (PSFs), specifically focusing on healthcare providers. Thereby, this study addresses the following research question: How do different types of micro-mergers affect the performance of PSFs?
Thus, it examined the various types of micro-mergers and the relationship between the type of micro-merger and PSF performance. In addition, it focused on the factors moderating the relationship between the type of micro-merger and PSF performance.
This study analyzed data on three cases within University Medical Center Groningen (UMCG). Twenty-one semi-structured interviews provided the bulk of this data. The results demonstrated that Napier’s (1989) typology of mergers also applies to micro-mergers, since all three types of micro-mergers (extension, collaborative, and redesign) were identifiable.
None of these micro-merger types led to a decline in the PSF’s performance. The collaborative and redesign micro-mergers led to an increase in the PSF’s performance. Furthermore, the results indicated that merging syndrome moderates the relationship between the type of micro-merger and PSF performance. Moreover, two factors affect the severity of the merging syndrome: equivalency and feelings of unity (social identity).
Regarding future research, researchers should explore whether these results hold true for other micro-mergers. Furthermore, the conceptual framework proposed should be further explored in a quantitative matter by measuring PSF performance. Regarding managerial implications, management should be aware that governance has significant effect on the micro-merging process. Thereby, communication is key to reduce uncertainty and stress, so as to create high levels of trust. Continue reading






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Connective Fields (CF) in de vroege visuele cortex bij paconnectiviteit in de visuele cortex, tussen enerzijds 11 patiënten met een psychotische connectiviteit in de visuele cortex, tussen enerzijds 11 patiënten met een psychotische connectiviteit in de v






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“Risk of hemorrhage after Gamma Knife radiosurgery versus natural history for hemorrhage in brain arteriovenous malformations: a retrospective descriptive study






Background: Gamma Knife Radiosurgery (GKRS) is frequently used for the treatment of brain arteriovenous malformations (BAVM). Patients with unruptured BAVM have a risk of 2.2% per year for intracranial hemorrhage with severe morbidity and mortality[16]. Patients with ruptured BAVM have 4.5% risk for a second haemorrhage[13]. Adverse radiation effects (ARE’s) are seen post treatment with variable incidence (1.8-22.9%)[39]. The latency period post GKRS is a crucial time frame for hemorrhage and ARE’s to occur. Timely follow-up and treatment are essential during this period.
Objective: The purpose of this report was to evaluate the risk of hemorrhage post GKRS for unruptured BAVM versus the natural history, in order to conclude that treatment in unruptured BAVMs with GKRS is a good approach in preventing hemorrhages. Secondly the goal was to evaluate the risk of a second hemorrhage post GKRS in ruptured BAVM versus the rebleeding risk. The incidence of ARE’s were evaluated to analyse the safety of GKRS treatment. Lastly, to evaluate the effect of treatment, obliteration rates for hemorrhage and non-hemorrhage BAVM were analysed.
Methods: The investigation was carried through a retrospective descriptive study of patients with BAVM who underwent GKRS between 2002 and 2015 at the Gamma Knife Center of the Elisabeth-Tweesteden hospital in Tilburg, the Netherlands. Patients were included based on the inclusion criteria ( age > 18 years, angiographically established BAVM and with a minimal follow-up of ≥ 3 years). Univariate and multivariate analyses were performed. The Chi square test was used to calculate the significance level (p Continue reading






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De relatie tussen de neonatale cerebrale oxygenatie en de vroeg neonatale neurologische uitkomst bij kinderen met ductusafhankelijke congenitale hartafwijkingen






Introductie: Ongeveer vijf tot elf per 1,000 levende pasgeborenen komen ter wereld met een congenitale hartafwijking (CHD). Dankzij verbeterde zorg bereikt tegenwoordig ongeveer 85% van deze kinderen de volwassen leeftijd. Kinderen met CHD hebben echter een hoger risico op neurologische ontwikkelingsstoornissen als gevolg van een complexe interactie tussen pre-operatieve, intra-operatieve en postoperatieve gebeurtenissen. Mogelijk ontstaat hersenschade ten gevolge van chronische foetale en vroeg neonatale hypoxie of ischemie van het brein. Een niet-invasieve en continue manier om de saturatie in het hersenweefsel te meten is door middel van near-infrared spectroscopy (NIRS). Neurologische uitkomst kan voorspeld worden door de beoordeling van general movements (GMs). Dit zijn spontane bewegingen die door het hele lichaam gemaakt worden en zeer voorspellend zijn voor latere neurologische uitkomst. In dit onderzoek wordt een correlatie gezocht tussen de kwaliteit van GMs op een leeftijd van 7 dagen en de cerebrale oxygenatie tijdens de eerste zeven dagen postnataal bij kinderen met CHD.
Methode: Kinderen met een antenataal bekende ductusafhankelijke CHD werden geïncludeerd en bij hen werd vervolgens gedurende de eerste zeven dagen de cerebrale oxygenatie door middel van NIRS gemeten. Op een leeftijd van 7 dagen werden de general movements gefilmd en vervolgens geanalyseerd.
Resultaten: Achttien kinderen in het Universitair Medisch Centrum Groningen (UMCG) werden geïncludeerd, waarvan er tien afwijkende GMs lieten zien. Er was geen relatie tussen de GMs bij zeven dagen en de cerebrale zuurstofsturatie in de eerste zeven dagen, ook niet na correctie voor de leeftijd waarop gefilmd werd.
Discussie: In een vervolgstudie zouden meer kinderen geïncludeerd moeten worden om de resultaten sterker te maken, daarnaast zouden kinderen ook bij drie maanden nog gefilmd moeten worden voor GMs, omdat dit een duidelijkere voorspeller is voor latere neurologische uitkomst. Continue reading






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Liver transplantation for cirrhosis secondary to non-alcoholic steatohepatitis is not performed at the expense of major postoperative morbidity






Background: Non-alcoholic steatohepatitis (NASH) is an emerging indication for liver transplantation due to the obesity pandemic. NASH frequently coexists with multiple comorbidities such as type 2 diabetes mellitus (T2DM), cardiovascular disease and the metabolic syndrome(MetS). Recent studies have shown that long-term patient and graft survival of patients transplanted for NASH cirrhosis are comparable to other indications. However, limited data exists about the short-term (procedure- related) complications after transplantation. Therefore, our aim was to investigate whether these patients are at an increased risk of short-term complications following transplantation.
Methods: This is a single centre retrospective cohort study including all adult patients (≥18 years) who underwent liver transplantation between January 2009 and December 2015 (N=224). Exclusion criteria were liver transplantation for acute hepatic failure or non-cirrhotic liver disease. Patients were censored at time of re-transplantation (n=17). Post-operative complications within 90 days were classified according to the Clavien-Dindo classification of surgical complications. NASH was defined by either: 1) histologic evidence of NASH on biopsy or explant; 2) imaging showing hepatic steatosis; 3) a phenotypic diagnosis consisting of BMI ≥ 30 kg/m2 and presence of T2DM (by either HbA1c ≥ 47 mmol/L or glucose lowering medication use) or the presence of at least 3 out of 5 diagnostic criteria for MetS as defined by the NCEP Adult Treatment Panel (ATP III). A p Continue reading






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Terminal cancer and suicide in older people; clinical characteristics and motives






Background: Terminally ill people represent a unique group where suicide may be considered as a rational and ethical act. Given their limited life expectancy and wish to reduce suffering, terminally ill people may exert their self-determination and autonomy by ending their life. Objectives: The aims of this study are to [i.] compare the socio-demographic and clinical variables of two groups of older people who completed suicide: those with advanced cancer and those without; and [ii] examine qualitatively whether the advanced cancer cases could be defined as rational suicide.
Methods: The New Zealand Coronial Services provided records of all suicide cases aged 65 years and over (n=225) between July 2007 and December 2012. We were able to determine whether there was an advanced cancer in 214 cases.
Findings: 23 (10.7%) older people who completed suicide were diagnosed with an advanced cancer. Bivariate analysis found that they were more likely to be male (91.3% versus 72.3%, p=0.048), married or in a defacto relationship (78.3% versus 46.1%, p=0.014); but less likely to have a diagnosis of depression (8.7% versus 46.6%, p=0.001), previous contact with psychiatric services (4.5% versus 35.0%, p=0.004) and past suicide attempt (9.1% versus 28.8%, p=0.048). Next to that the circumstances of 82.6 % of the advanced cancer patients who died by suicide were conceived as ‘understandable for uninvolved observers’.
Conclusions: With a growing elderly population and higher rates of suicide within the elderly, late-life suicide is becoming more prevalent. The diagnosis of terminal illness is higher amongst elderly. Further research is needed to delineate motives and suicide risks for terminally ill patients. More knowledge and understanding can offer the patient more targeted care and an earlier/better relieve of their mental and physical suffering. Continue reading






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Renal function more than twenty years after cisplatin-based chemotherapy fortesticular cancer






Background
The introduction of platinum-based chemotherapy for treatment of metastatic testicular cancer in the late 1970s has led to an increase in survival rates and a growing cohort of testicular cancer survivors. Consequently, attention for long-t… Continue reading






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Titration of oxygen therapy in critically ill emergency department patients: a feasibility study






Introduction- Oxygen is one of the most widely used drugs and is applied across the wide range of specialities. Liberal use of oxygen to reassure oxygen delivery has become standard treatment in resuscitation: in the ambulance, the emergency department (ED) and the intensive care unit (ICU). Today, most health care professionals do not adjust the amount of oxygen given when patients reach a saturation of 100% or a PaO2 which exceeds the normal range, resulting in hyperoxia. Because oxygen is a vital element, toxicity is not immediately obvious, but there is increasing evidence for the toxic effects of hyperoxia. Because of these potential harmful effects of hyperoxia it seems justified to aim for normoxia when giving oxygen therapy. Objective- This study aims to evaluate whether it is feasible to aim for normoxia when giving oxygen therapy to critically ill patients at the ED. Material and methods- This study was a prospective cohort study and was performed at the ED of the University Medical Center Groningen (UMCG). A protocol was developed, aiming for normoxia: PaO2 9,5-13,5 kPa or a corresponding oxygen saturation 94-98%. Hyperoxia was defined as PaO2 > 13.5 kPa or SaO2 > 98%, and hypoxia as PaO2 18 years admitted to the ED that were registered for cardiology, internal medicine, emergency medicine and pulmonology requiring oxygen therapy (according to the judgement of the ambulance nurse, ED nurse or ED physician) were included. Results- During the study period the protocol was followed and normoxia was obtained in 140 of the 162 study patients (86%). Patients in which the protocol was not successful were mostly severe COPD (GOLD III/IV) patients (P Continue reading






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Novel insights into pure and mixed clear cell carcinomas in endometrial cancer






background
Endometrial clear cell carcinoma (CCC) and mixed endometrioid carcinoma with a clear
cell component (EEC-CC) are rare forms of endometrial carcinoma (EC). Traditionally,
these tumors are classified and treated as high grade tumors. However, just a few studies
have identified clinical outcome for patients with pure CCCs and little is known
about the overall survival of the mixed carcinomas. Also, the predictive value of pipelle
in subtyping these tumors has not yet been determined. Lastly, determining an immunoprofile
of these tumors could bring new insights in the pathogenesis of these tumors
and be of potential diagnostic aid.
methods
We selected and revised 51 pure CCCs and 28 mixed EEC-CC cases diagnosed since 1980
in the UMCG and Isala Zwolle. Clinical outcome of these patients were compared to each
other. We also selected these patients for determining the positive predictive value of
pipelle compared to the definitive diagnosis on hysterectomy. Immunohistochemical
staining for ER, PR, PTEN, p53, HNF1-β, Napsin A, AMACR, p16 and MMR, which are
common markers used for CCC and endometrioid carcinoma, were performed on all
pure CCC and both components of the mixed carcinomas to obtain an immunoprofile of
these tumors.
results
We found an overall 5-year survival rate of 64% for CCC, compared to 68% for mixed
EEC-CC, which was not statistically significant. The positive predictive value of pipelle
for detecting a pure CCC is 100%, compared to 50% for a mixed EEC-CCC.
We found the immunophenotype of ER– and PR– (71.8-95.2% resp. 87.5-92.9%),
HNF1-β+ (61.9-91.7%) to be most common in all pure CCC cases. Loss of PTEN expression,
a p53 mutation and positive Napsin A was present in about 50% of all CCC and
AMACR immunoreactivity was present in 33%. For mixed carcinomas ER, PR and HNF1-
β expression significantly differed in expression between the endometrioid and clear
cell component. The clear cell component of the mixed tumor did show a significant
lower expression for HNF1-β and Napsin A compared to a pure CCC. Microsatellite instability
for MSH2/MSH6 was also significantly higher for mixed carcinomas compared to
pure CCC.
conclusion
The outcome of mixed carcinoma is not significantly different from a pure CCC, despite
the presence of a low-grade endometrioid component. Also, pipelle is highly predictive
for detecting a pure CCC, while correctly diagnosing just half of all mixed carcinomas.
An immunoprofile of loss of ER, PR and positive HNF1-β was most common in CCC of
our study. Furthermore, the immunoprofile of the CC component in mixed EEC-CC is
intermediate between pure CCC and EEC, suggesting a common pre-existing endometrioid
lesion from which the clear cell component originates. Continue reading






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Non-invasieve Cardiac Output Monitoring (NICOM®) als voorspeller van de respons op volumetherapie bij septische patiënten






Background: Sepsis is a major public health problem with a high level of mortality. The initial treatment of sepsis is based on the admission of intravenous fluid which significantly decreases the sepsis-related morbidity and mortality. However, only 50% of the patients are volume responders. When fluid therapy does not increase cardiac output (CO) or stroke volume (SV) it is useless and this overuse could be harmful, resulting in an increase of complications and mortality. This shows the importance of accurate admission of intravenous fluids to enhance the treatment of septic patients and minimalize the risks of excessive – or insufficient volume therapy. A method for noninvasive continue CO measurement is NICOM®, which uses bioreactance.
Objective: The purpose of this study is to evaluate the ability of the CO measured by NICOM® in combination with several standard measured clinical parameters to predict fluid responsiveness in septic patients. The use of clinical parameters appears to be insufficiently reliable for predicting fluid responsiveness.
Methods: During a period of 14 weeks, all patients admitted to the emergency department with suspected infection will be screened. If included, the first NICOM® measurements will be recorded 10 minutes after arrival (T0). Simultaneously, several hemodynamic – and metabolic parameters are registered. This process repeats for each admission of 500 ml fluids until discharge. A response to fluid therapy is defined as an increase in SV of at least 10% after fluid admission.
Results: In total, 38 septic patients who received fluid therapy were included, of which 66% were fluid responsive after infusion of 500 ml NaCl. After infusion of 1000 ml NaCl 81% of the study population were responder. Baseline characteristics including parameters measured by NICOM® and the clinical shockscore showed no differences between responders and non-responders and were not reliable for predicting fluid responsiveness in the total study population. However, the clinical shockscore was significantly higher in responders compared to non-responders in the severe septic patients. If patients were divided into responders/non-responders after 1000 ml fluid infusion, none of the non-responders showed a response after infusion of 1500 ml NaCl (NPV=100%, 95% CI=19,7-100).
Conclusion: Although NICOM® is able to monitor fluid responsiveness, it seems difficult to predict the response based on patient characteristics on baseline. For certain patients, infusion of 500 ml fluid therapy does not seem sufficient to induce an increase in SV. For this reason, the classification into responders and non-responders should be made after infusion of 1000 ml fluid therapy. If patients have not responded to fluid therapy at that time, the continuation of fluid infusion seems useless. The use of NICOM® could be beneficial in guiding fluid therapy, nevertheless further research is required to confirm this. Continue reading






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The effect of Deep Brain Stimulation on Corticomuscular Coherence in Parkinson’s Disease






Background: In advanced Parkinson’s disease (PD), deep brain stimulation (DBS) is considered as an ultimate treatment; however inefficacy and side-effects remain a challenge. A reliable, non-invasive neurophysiological biomarker could be valuable enabling the application of DBS in a highly selective way. Corticomuscular coherence (CMC) could be used as a potential biomarker. CMC is seen as a representation of the co-operation between brain areas and muscles in motor tasks and is present in PD symptoms of tremor (tremor frequency range) and akinesia-rigidity (beta range).
Aim: To test CMC, measured by electroencephalography (cortex) and electromyography (muscles), as a potential biomarker for improvement in tremor and akinesia-rigidity after DBS.
Methods: In this single center prospective cohort pilot study, five tremor-dominant and five akinetic-rigid PD DBS candidates of the University Medical Centre Groningen (UMCG) were included. In the akinetic-rigid PD group, beta CMC was measured during a flexion, pinching and resting task; symptoms were assessed by the MDS-UPDRS III upper body akinetic-rigid items. In the tremor-dominant PD group, tremor CMC was retrieved during a maximal tremor task; symptoms by use of a clinical tremor score and accelerometer. Change in CMC after DBS was tested and correlations were performed between CMC and symptom severity. Thereafter, correlations between change in CMC and improvement in symptoms; and pre-DBS CMC and improvement in symptoms were made.
Results: Tremor CMC decreased significantly after DBS (p=0.01) and significantly correlated with tremor severity (p Continue reading






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Imaging Characteristics and Recurrence Patterns of the Subventricular Zone in Glioblastoma






Glioblastomas (GBMs) are the commonest and most malignant primary brain tumour. It is suggested that GBMs can arise from neural stem cells within the subventricular zone (SVZ). However, evidence demonstrating these cancer stem cells in GBM is lacking…. Continue reading






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Neonatal sepsis incidence in preterm infants treated with standard care in an open bay in a level 2 Neonatal ward,2009-2012.






Background and objective Neonatal sepsis is a severe disease in preterm infants that can
result in significant morbidity in this vulnerable patient group. Our aim was to identify and
assess the risk factors and incidence of neonatal sepsis in two diff… Continue reading






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Local influence of rituximab and abatacept treatment on follicular helper T-lymphocytes in salivary glands of patients with primary Sjögren’s syndrome






The aim of this project was to investigate whether follicular helper T cells are present in the major salivary glands of primary Sjögren’s syndrome patients and to determine the effect of treatment with rituximab or abatacept on these cells. Furthermore, we analyzed local levels of IL21, a signature cytokine produced by Tfh-cells, before and after treatment. Tfh-cells defined by their expression of ICOS and CXCR5 were found in some, but not all patients analyzed. Also high numbers of IL21-positive cells were found in the parotid glands of all patients, and a decrease was seen in some patients after treatment with both rituximab and abatacept. Decreased expression of IL21 and CXCL13 was also seen at the mRNA level, suggesting a possible reduction in Tfh-cell activity and attraction of CXCR5+ cells into the salivary gland. Because of the small number of patients analyzed in this study, no statistically significant changes were yet detected. However, the results described here do suggest a possible local effect on Tfh-cells and other IL21-producing cells of both rituximab and abatacept in primary Sjögren’s syndrome. The presence of Tfh-cells and the high number of IL21-positive cells in the parotid glands also suggests that Tfh-cells are involved in the inflammatory process seen in pSS. Continue reading






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The Role of TLR4 / uPAR interaction in microvascular inflammation found in Diabetes Mellitus






Introduction Diabetes Mellitus is a systemic disease having many adverse long-term effects on multiple organs. The incidence of both Types of Diabetes is vastly rising, affecting patients particularly in the Western World.
Diabetic nephropathy (DN) is… Continue reading






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COMPARISON OF INVASIVELY AND NONINVASIVELY MEASURED RIGHT VENTRICULAR-VASCULAR COUPLING RATIO IN PEDIATRIC PULMONARY ARTERIAL HYPERTENSION: A MULTI-CENTER STUDY






Introduction: In pediatric pulmonary arterial hypertension (PAH), RV failure is the main cause of death. Right ventricular-vascular coupling ratio (VVCR) is gaining interest as it encloses both contractility and afterload. Conventional determination of VVCR by catheterization (VVCRs) is invasive and frequently requires anesthesia. Therefore, the goal of this study was to compare the usefulness of noninvasively determined VVCR by cardiac magnetic resonance (CMR) (VVCRm) to VVCRs in pediatric PAH.
Hypothesis: We assessed two hypotheses: 1) VVCRm is a good estimate of VVCRs; and 2) both serve as good measures of disease severity and outcome.
Methods: Retrospectively, PAH patients who had catheterization and CMR within 90 days were included from two specialized PH centers. VVCR was defined as the end-systolic elastance/effective arterial elastance ratio. VVCRm as stroke volume/end-systolic volume ratio and VVCRs by single-beat method were compared using regression analysis and Bland-Altman plots. Both were correlated to disease severity (PVRi, mRAP, CI) and adverse outcome (death, lung transplantation, atrial septostomy and intravenous medication). The area under the receiver operating characteristic curve (AU-ROC), Kaplan-Meier curves and hazard ratios (HR) from Cox regression determined their value in predicting adverse outcome.
Results: In the 31 patients included (17 from CHC and 14 from UMCG), median age was 14 years (0.3 – 23) and median PVRi was 7.6 WU × m2 (2.1 – 32). VVCRm and VVCRs were strongly correlated (r = 0.78, p Continue reading






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