Abstracts Wetenschapsdag - AAV-MUMC

in samenwerking met de Centrale OpleidingsCommissie
Abstracts
Wetenschapsdag
2014
“Kleine” studies
Naam (posternummer)
Pagina
Jurriaan Brekelmans, Oogheelkunde (1)
2
Mari Elshout, Oogheelkunde (2)
3
Cécile Kicken, Anaesthesie (3)
4
Lucas Ricker, Oogheelkunde (4)
5
Elleke Dresen, Radiologie (5)
6
Miriam van Heeswijk, Radiologie (6)
7
Soraya Jonker, Oogheelkunde (7)
8
Esther Martens, Klinische neurofysiologie, (8, 9)
9, 10
Milou Martens, Chirurgie (10)
11
Elwin Mommers, Chirurgie (11)
12
Givan Paulus, Chirurgie (12)
13
Hellen Römkens, Oogheelkunde (13)
14
Karin Sanders, Longziekten (14)
15
Koen Vermorgen, Oogheelkunde (15)
16
Eleana Zhang, Neurologie (16)
17
1
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Abstract
Jurriaan Brekelmans
WESP-student
Oogheelkunde
Nee
Precut Single Pass Ultradunne Preparatie van Endotheliale Lamellen met een Innovatieve
Microkeratoom
M.M. Dickman1, P. Steijger-Vermaat2, Y. Schuchard2, F.W.F. van Marion2, T. T.J.M. Berendschot1,
F.J.H.M. van den Biggelaar1, R.M.M.A. Nuijts1
1. Afdeling oogheelkunde, MUMC, Maastricht
2. Euro Cornea Bank, Beverwijk
Doel: De reproduceerbaarheid en endotheelcel overleving vaststellen van endotheliale lamellen
ultradun gesneden (<100μm) met de Gebauer SLc microkeratoom.
Methode: 22 gepaarde orgaanmedium gepreserveerde donorhoornvliezen (n=44) ongeschikt voor
transplantatie zijn gesneden met de Gebauer SLc microkeratoom met een beoogde lameldikte
<100μm. Hierna zijn ze gedurende 3 dagen in orgaanmedium bewaard. De dikte is gemeten via een
voorsegment OCT (Casia SS-1000;Tomey) en de endotheelcel overleving via trypaan blauw
kleuring.
Resultaten: De gemiddelde lameldikte bedroeg 65±13μm, significant kleiner dan 100μm (p<0.001).
Er is geen significant verschil gevonden in endotheelcelafname tussen gesneden en niet-gesneden
corneas op alle meetmomenten. Lineair-mixed-model-analyse liet alleen tijd van overlijden tot
koud preservatie en totale opslagtijd als significante voorspellers van endotheelcelafname zien.
Poster
Conclusie: De Gebauer SLc microkeratoom is een betrouwbare en veilige techniek voor het
oogsten van ultradunneendotheliale lamellen.
Liggende poster, nr 1
2
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Abstract
Mari Elshout
Arts-assistent in opleiding
Oogheelkunde
Nee
Kosteneffectiviteit van aflibercept voor de behandeling van leeftijdsgebonden
maculadegeneratie
M.I. van der Reis1, C.A.B. Webers1, J.S.A.G. Schouten1
1. Afdeling Oogheelkunde, MUMC, Maastricht
Doel: De kosteneffectiviteit bestuderen van aflibercept vergelijken met bevacizumab, ranibizumab
en geen behandeling, en de invloed van modelparameters.
Methode: Een 2-ogen model werd ontwikkeld. Effectiviteitsdata werd ontleend aan klinische trials.
Kosten waren gebaseerd op patient interviews en standaard kostprijzen. Tijdshorizon: 2 en 5 jaar.
Resultaten: Kosten en QALYs geassocieerd met aflibercept gedurende 5 jaren: €35,390; 2.171
QALYs. Bevacizumab, ABC study, CATT study (PRN en 1x/maand): respectievelijk €15,127; €18,469
en €27,210, met 2.172; 2.186 en 2.171 QALYs. Ranibizumab PRN en 1x/ maand: respectievelijk
€38,842 en €69,533, met 2.175 en 2.169 QALYs. ‘Geen behandeling’: €9,032 en 1.968 QALYs.
Resultaten waren sterk afhankelijk van of één of beide ogen werden geincludeerd, van de lengte
van de tijdshorizon, en of kosten van blindheid werden geincludeerd.
Poster
Conclusie: Aflibercept is kosteneffectief vergeleken met ranibizumab. Het is echter niet
kosteneffectief vergeleken met bevacizumab. Toepassing van correcte model parameters is mede
bepalend voor de uitkomsten.
Liggende poster, nr 2
3
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Abstract
Cécile Kicken
WESP-student
Anaesthesie
Nee
Pressured and warmed transfusion of platelet concentrates does not impair platelet function
M.D. Lancé1, R. Oerle2, H.M.S. Theunissen1, Y.M.C. Henskens3
1. Afdeling Anesthesiologie en Pijnbestrijding, MUMC, Maastricht
2. Laboratory for Clinical Thrombosis and Hemostasis, CARIM, Maastricht University, Maastricht
3. Centraal Diagnostisch Laboratorium, Cluster Speciële Hemostase en Transfusie, MUMC,
Maastricht
Rationale: In patients suffering from massive bleeding, platelet concentrate (PC) transfusion is an
important part of hemostatic resuscitation. For these patients it is of utmost importance that PCs
are delivered from the laboratory to the bloodstream in the fastest way possible. Ideally the PC
would also be warmed to 37 °C prior to transfusion because hypothermia compromises
hemostasis. A pneumatic tube transport system (PTS) connecting the laboratory with the OR,
combined with pressured and warmed transfusion offers such a fast delivery route. However
transfusion guidelines do not recommend it. This in vitro study investigated whether this fast
delivery route reduces platelet function.
Methods: In vitro platelet function was tested in 10 PCs, of which 5 were irradiated with 25 Gy.
PCs underwent a single PTS transport and were subsequently divided into smaller bags, which
were pressured to 300 mmHg or pressured to 300 mmHg and warmed in a Ranger™ blood warmer.
These conditions were tested on day 2 and 7 after donation. Platelet function was measured with
light transmission aggregometry (LTA) in terms of 10 μM ADP, 1 mM Na-arachidonic acid (Na-AA),
4 μg/ml collagen and 30 μM TRAP and multiple electrode aggregometry (MEA) in terms of 6.5 μM
ADPtest, 1 mM ASPItest, 3.2 μg/ml COLtest and 32 μM TRAPtest. Data were analyzed with nonparametric testing, p < 0.05 was considered statistically significant.
Poster
Results & conclusion: Single PTS transport reduces the ADP response markedly in fresh PCs.
However 7-day storage has an even more pronounced effect on ADP and collagen response. It
remains to be established whether this effect of PTS on ADP response is relevant in vivo. Other
platelet responses were overall well preserved. Subsequent application of pressure or pressure
and warming does not relevantly reduce platelet function in fresh and stored PCs.
For patients who greatly benefit from rapid PC delivery from the laboratory to the bloodstream,
transport by PTS and pressured plus warmed transfusion may be a feasible option.
Liggende poster, nr 3
4
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Abstract
Lukas Ricker
Arts-assistent in opleiding
Oogheelkunde
MHeNS
The immunocytological composition of subretinal fluid in patients with retinal detachment
E.C. La Heij1, A. Kijlstra2
1. Afdeling Oogheelkunde, Medisch Centrum Jan van Goyen, Amsterdam
2. Afdeling Oogheelkunde, MUMC, Maastricht
Purpose: A multitude of cytokines have been shown to be upregulated at the time of retinal
detachment surgery in patients who develop future proliferative vitreoretinopathy (PVR). Analysis
of cytologic specimens at this early stage may thus also provide insight into the cellular
composition of the pre-clinical stages of PVR. Since cytologic samples are difficult to handle and
cells are often identified using unreliable morphological criteria, data are scarce and often
inconclusive. We therefore performed an immunocytological study on cells in subretinal fluid to
expand the knowledge on the cellular basis of PVR.
Methods: Subretinal fluid samples of 33 consecutive cases with primary rhegmatogenous retinal
detachment were collected during scleral buckling surgery. Samples were immediately centrifuged
for 5 minutes at 700 rpm. Pellets from all samples were divided onto four slides per sample by
cytospin, air-dried, and stored at -80 degrees Celsius. A scale of cellular density was established for
each specimen: low cellularity for <100 cells per slide, intermediate cellularity for 100-200 cells per
slide, and high cellularity for > 200 cells per slide. Slides were immunostained for cytokeratin 8/18
and CD68 (double staining), CD3 and CD20 (double staining), pankeratin, and alpha-smooth muscle
actin (SMA).
Results: In the majority of samples only few cells were identified (low cellularity, 13/33 samples,
39%). Intermediate and high cellularity were seen in 12/33 (36%) and 8/33 samples (24%),
respectively. Pankeratin positive cells were identified in 33/33 (100%) samples investigated,
cytokeratin 8/18 positive cells in 19/33 samples (58%), and CD68 positive cells in 31/33 samples
(94%). CD3+ cells were seen in one sample (3%), whereas CD20 staining was negative in all samples
investigated. Staining for alpha-SMA was positive in 26 samples (79%). Of samples that stained
negative for alpha-SMA, 6/7 (86%) had low cellularity. In two samples, few cells double-stained for
both cytokeratin 8/18 and CD68.
Poster
Conclusions: These results underline the paradigm that retinal pigment epithelial cells and
infiltrating macrophages play a pivotal role in the sequelae resulting in PVR membrane formation
after retinal detachment. The discrepancy between the number of samples with pankeratin and
cytokeratin 8/18 positive cells may be explained by early dedifferentiation of pigment epithelial
cells. In line with this, alpha-SMA positivity in the majority of samples may be an early sign of
epithelial-mesenchymal transition. Lymphocytes are unlikely to play a role after retinal
detachment.
Liggende poster, nr 4
5
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Abstract
Elleke Dresen
Arts-assistent in opleiding
Radiologie
Nee
Kinetic parameters of DCE MRI selecting good responders after chemoradiation for rectal cancer
R.C. Dresen1, M.H. Martens2, S. Subhani2, L.A. Heijnen2, D.M.J. Lambregts1, M. Maas1, R.G. Riedl3, J.
Slenter1, G.L. Beets2, E. Kluza1, R.G.H. Beets-Tan1
1. Afdeling radiologie, MUMC, Maastricht
2. Afdeling chirurgie, MUMC, Maastricht
3. Afdeling pathologie, MUMC, Maastricht
Purpose: Response assessment after chemoradiation (CRT) in rectal cancer remains difficult. The
aim of this study was to investigate if kinetic analysis of dynamic contrast enhanced (DCE) MRI,
using the blood-pool contrast agent gadofosveset, can identify good responders after CRT.
Materials and Methods: Twenty-five patients with locally advanced rectal cancer received DCEMRI both before and 8 weeks after CRT. The kinetic parameters i.e., the initial slope, initial peak,
final slope, and area under the first 60, 90, and 120s of the enhancement curve (AUC60, AUC90,
AUC120) were determined from relative signal enhancement-time curves. Receiver operating
characteristics (ROC) curves were used to assess the diagnostic performance. Good responders
(n=11) were defined as patients with a tumor regression grade (TRG) of 1 or 2 at histopathologic
assessment after resection. Poor responders were defined as patients with a TRG of 3 to 5 (n=14).
Results: Post-CRT the initial peak, AUC90, and AUC120 were significantly lower in the good
responders compared with the poor responders (1.20 vs 1.53, 102 vs 128, 145 vs 181 and p=0.017,
0.028, 0.023 respectively). All parameters except the final slope changed significantly more postCRT in the good responders compared with the poor responders. Before neo-adjuvant CRT, the
final slope was significantly lower for the good responders (-1.61x10-3) compared with the poor
responders (5.18x10-3, p=0.004). ROC-curves ranged from 0.73 to 0.83.
Discussion: Differences in kinetic parameters could be used to distinguish good responders from
poor responders, which is still difficult with other imaging modalities.
Poster
Conclusion: Kinetic parameters of dynamic contrast enhanced MRI are a promising tool for
predicting response after chemoradiation in patients with rectal cancer, influencing further
treatment.
Staande poster, nr 5
6
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Abstract
Miriam van Heeswijk
WESP-student
Radiologie
Nee
Prospective validation of MR-volumetry for response after neoadjuvant therapy in rectal cancer.
M.H. Martens1,2, D.M.J. Lambregts1, R.F.A. Vliegen3, V. Vandecaveye4, M.N. Sosef5, G.L. Beets2,
R.G.H. Beets-Tan1
1. Afdeling Radiologie, MUMC, Maastricht
2. Afdeling Chirurgie, MUMC, Maastricht
3. Afdeling Radiologie, Atrium MC, Heerlen
4. Afdeling Radiologie, UZ Leuven, Leuven, België
5. Afdeling Chirurgie, Atrium MC, Heerlen
Introduction: Standard treatment for locally advanced rectal cancer is a long course of
chemoradiotherapy (CRT) followed by total mesorectal excision (TME). The assessment of tumor
response after CRT with standard MRI is difficult due to post-radiation fibrosis. There are several
retrospective studies that suggested that T2W MR volumetry can improve the accuracy the tumor
response post-CRT. In these studies cut-off values have been tested on a limited number of
patients and the golden standard remains pathology. The aim of this study is to prospectively
validate the diagnostic value of previously reported thresholds reported in literature for T2Wbased volumetry in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.
Material and Methods: Twenty-four patients with cT3-4 rectal tumor, with any N-stage, and no
metastasis were included. A standard T2W-MRI was performed both pre- and post-CRT. Tumor
volume was measured by free-hand regions of interest (ROI) delineating the tumor on each tumor
containing slice both before and after CRT. Tumor volume reduction rates (∆volume) were
calculated. The cut-off criteria were found by means of literature research.
Cut-off criteria tested for outcome were the following:
- Pre-CRT Volume of 15 cm3, 16.7 cm3 or 50 cm3;
- Post-CRT Volume of 1.6 cm3 and 5 cm3;
- Volume reduction cut-off criteria of 70%, 75%, 77%. 84.3% or 88.6%.
These criteria were compared between good and poor responders. Good response was defined as:
- Tumor downgrading (e.g. cT3 à ypT2)
- Tumor Regression Grade (TRG) by Mandard (1-2) or Dworak (3-4);
- Histopathologic complete response (pCR)
Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were
calculated.
Results: Pre-CRT volume thresholds resulted in sensitivities of 0-40%, specificities of 68-79%, PPV
0-71%, and NPV 39-89%. Post-CRT volume thresholds resulted in sensitivities of 0-60%, specificities
of 68-100%, PPV 0-100% and NPV 39-91%. The ∆volume thresholds resulted in sensitivities of 0100%, specificities of 71-100%, PPV of 0-100% and NPV of 41-100%.
Highest diagnostic accuracy was obtained with the thresholds of 75 and 77% for identifying a pCR,
resulting in a sensitivity of 100%, specificity of 82%, PPV 33% and NPV 100%.
Poster
Conclusion: The highest accuracy was obtained with the ∆volume cut-off value of 75 and 77%,
showing promising sensitivity of 100% and sensitivity of 82%. The validation results of the Pre- and
Post-CRT volume thresholds were not accurate enough for clinical application. The above
mentioned criteria will be tested on a larger, multi-center study population in the near future.
Staande poster, nr 6
7
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Abstract
Soraya Jonker
WESP-student
Oogheelkunde
Nee
Visuele functie na bilaterale implantatie van ReSTOR vs. Finevision multifocale IOLs
N.Y. Makhotkina1, N. J.C. Bauer1, T.T.J.M. Berendschot1, F.J.H.M. van den Biggelaar1, C. Pagnoulle2,
R.M.M.A. Nuijts1,
1. University Eye Clinic, MUMC, Maastricht
2. PhysIOL, Luik, België
Doel: Prospectieve evaluatie van visus en refractie uitkomsten in een gerandomiseerde
patiëntengroep met bilaterale IOL implantatie van twee verschillende multifocale IOLs.
Methode: 28 cataract patiënten met <1.0D corneaal astigmatisme werden gerandomiseerd voor
bilaterale implantatie van ofwel Finevision (micro F) trifocale IOLs ofwel Acrysof ReSTOR® IQ+3.0
IOLs.
Resultaten: Zes maanden postoperatief was de gemiddelde manifeste refractieve sferisch
equivalent +0.07+0.23 D voor de ReSTOR® en +0.12+0.59 D voor de FineVision groep. De
gemiddelde binoculaire ongecorrigeerde verte- (400cm), intermediaire- (70cm) en lees-visus
(40cm) was respectievelijk 0.00±0.09, 0.28±0.08 en 0.12±0.08 logMAR met de Restor, en
respectievelijk -0.01±0.11, 0.32±0.15 en 0.15±0.13 logMAR met de Finevision. Defocus curves,
contrast sensitiviteit en patiënt tevredenheid worden gepresenteerd.
Poster
Conclusie: Goede resultaten werden verkregen na bilaterale implantatie van zowel de Restor als
Finevision IOL, zonder significatie verschillen in visueel functioneren.
Staande poster, nr 7
8
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Abstract
Esther Martens
Klinisch fysicus in opleiding
Klinische neurofysiologie
Nee
Patiëntselectie en klepgrootte keuze voor transkatheter aortaklep implantatie (TAVI): CT vs. TTE
T. Jurençak1, W.R.M. Dassen2, M. Das1, L. van Garsse3, G.V.A. van Ommen2, B.L.J.H. Kietselaer2
1. Afdeling Radiologie, MUMC, Maastricht
2. Afdeling Cardiologie, MUMC, Maastricht
3. Afdeling Cardiothoracale Chirurgie, MUMC, Maastricht
Doel: Computer Tomografie (CT) is in opkomst als modaliteit voor het in kaart brengen van
aortaklep morfologie bij patiënten met een aortaklepstenose, die in aanmerking komen voor
transkatheter aortaklep implantatie (TAVI). Het doel van deze pilot-studie is om de gevolgtrekking
uit pre-TAVI CT data vs. transthoracale echocardiografie (TTE) data m.b.t. patiëntselectie (ernstige
vs. niet ernstige aortaklepstenose) en klepgrootte keuze (23 vs. 26 mm) te vergelijken.
Materialen en methoden: Van 29 patiënten die een TAVI hebben ondergaan zijn zowel CT als TTE
pre-TAVI data geanalyseerd. Ter vergelijking van CT en TTE, is stenose ernst puur gebaseerd op
aortaklepoppervlak (AVA) grootte: AVA < 1.0 cm2 is geclassificeerd als ernstig vs. AVA > 1.0 cm2 als
niet-ernstig.
Op CT is AVA bepaald door ROI intekening op een transversale oblique coupe genomen op 20%
van het RR-interval. De coupe is geselecteerd in het coronale vlak loodrecht op de aorta wortel op
dat niveau waarbij nog net de oorsprong van de klepbladen zichtbaar is. Op TTE is AVA bepaald uit
de continuïteitsvergelijking:
Vao* Aao = Vlvot* Alvot (1)
Met V de snelheid over en A het oppervlak van de aortaklep (index ao) of uitstroomopening van
het linkerventrikel (index lvot). Snelheden over aortaklep en LVOT zijn bepaald uit continuous
wave respectievelijk pulsed wave Doppler metingen. Alvot is berekend door LVOT diameter
intekening op de parasternale lange as opname onder aanname van een cirkelvorming oppervlak.
Uit vergelijking (1) volgt dan Aao ofwel AVA.
Klepgrootte keuze (23 vs. 26 mm) is gebaseerd op aorta annulus diameter (AAD) metingen. Op
zowel CT als TTE is deze bepaald door ROI intekening. Vooralsnog is uitgegaan van de Europese
richtlijnen die stellen dat een AAD gemeten op TTE tussen 18-21mm indicatief is voor een 23 mmklep en tussen 22-25mm voor een 26 mm-klep. Dezelfde richtlijnen zijn toegepast voor de kortste
as diameter gemeten op CT.
Resultaten: Voor 21 van de 29 patiënten (72%) kwamen CT en TTE patiëntclassificatie overeen. Bij
7 van de 8 tegenstrijdige bevindingen, wees TTE op ernstige stenose i.t.t. CT bevindingen. In van
deze 6 cases lag CT AVA dicht bij de afkapwaarde (1.0 of 1.1 cm2). TTE en CT klepmaat bevindingen
waren voor 12 patiënten (41%) in overeenstemming. In alle 17 tegenstrijdige bevindingen
indiceerde TTE de 23mm klep.
Poster
Conclusie: Om uitspraken te kunnen doen over de correctheid van zowel patiëntclassificatie als
klepgrootte keuze, is analyse van zowel pre- als post-TAVI data vereist. Op basis van grotendeels
overeenkomende CT-TTE bevindingen, kan voorlopig geconcludeerd worden dat TTE leidend zou
moeten zijn voor selectie, maar dat CT overwogen kan worden als er twijfel is over de ernst van
een aortaklepstenose. Wat betreft klepgrootte keuze, zijn de verschillen tussen TTE en CT erg
groot. Aangezien risico’s bij het plaatsen van een te grote klep minder ernstig zijn dan bij een te
kleine klep, lijkt CT een veiligere pre-TAVI indicator dan TTE.
Staande poster, nr 8
9
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Abstract
Esther Martens
Klinisch fysicus in opleiding
Klinische neurofysiologie
Nee
Centrifugal pump performance for application in low-flow extracorporeal CO2-removal
A.P. Simons 1, Y.G. Ganushchak1, P.W. Weerwind1
1. Department of Cardiothoracic Surgery, MUMC, Maastricht
Aim: Extracorporeal life support has been proven a successful technique to provide circulatory
and/or pulmonary assistance in acute heart and/or lung failure, thereby using pump flows of 3-6
l/min. More recently, this technique has been adapted to enable extracorporeal CO2 removal
using small catheters and decreased pump flows <0.5 l/min in patients suffering from COPD
exacerbation. Roller pumps are suitable for such low-flow applications, but the efficacy of modern
centrifugal pumps for this purpose has not yet been investigated. The aim of this study was to
examine hydrodynamic stability and gaseous micro-emboli (GME) activity to characterise the
performance of two centrifugal pump types for application in low-flow extracorporeal CO2
removal.
Materials & Methods: The performance of a RotAssist2.8 and a Rotaflow32 centrifugal pump
(Maquet Cardiopulmonary AG, Hirrlingen, Germany) was characterised in a mock circulation
consisting of a reservoir, the centrifugal pump, an oxygenator, and adjustable tube clamps at the
inlet and outlet of the pump. Pressure and gaseous micro-embolic activity was measured at both
the pump inlet and outlet using pressure transducers (Baxter International, Inc., Deerfield, IL, USA)
and bubble counters (BCC200, Gampt GmbH, Zappendorf, Germany). Flow was measured using
ultrasound flow probes (Transonic Systems, Inc., Ithaca, NY, USA). At pump speeds of 1000, 2000,
2500, 3000, 3500, 4000 and 5000 rpm, pressure-flow curves were acquired by stepwise closing the
pump inlet tube clamp in one pump speed series and the outlet tube clamp in another. Resulting
flow steps amounted to 1 l/min in the >1 l/min flow range, 0.25 l/min in the 1-0.5 l/min flow range,
and 0.1 l/min in the <0.5 l/min flow range.
Results: Minimum pump inlet and maximum pump outlet pressures were -593 mmHg and 754
mmHg for the RotAssist2.8 and -606 mmHg and 806 mmHg for the Rotaflow32. At flows ranging
from 8 to 0 l/min and regardless of which tube clamp, standard deviations of pump pressures and
flows for both pumps amounted to <3 mmHg [3.0 - 0.02 mmHg] and <0.03 l/min [0.03 - 0.002
l/min]. GME at the pump outlet were detectable at pump inlet pressures below -156 mmHg (first
measured at 2500 rpm and 0.2 l/min) for the RotAssist2.8 and below -224 mmHg (measured at
3000 rpm and 0.9 l/min) for the Rotaflow32.
Poster
Conclusion: Both RotAssist2.8 and Rotaflow32 centrifugal pumps remain hydro-dynamically stable
in the low flow area, however, GME formation with decreasing pump inlet pressures should be
taken into account to ensure safe low-flow extracorporeal CO2 removal.
Staande poster, nr 9
10
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Abstract
Milou Martens
PhD student
Chirurgie
GROW
Dynamic contrast enhanced MRI for response prediction before+after chemoradiation for rectal
cancer
S. Subhani1, L.A. Heijnen1,2, D.M.J. Lambregts1, J. Buijsen3, M. Maas1, R.G. Riedl4, C.R.L.P.N.
Jeukens1, G.L. Beets2, E. Kluza1, R.G.H. Beets-Tan1
1. Afdeling Radiologie, MUMC, Maastricht
2. Afdeling Chirurgie, MUMC, Maastricht
3. Afdeling Radiotherapie, Maastro Clinic, Maastricht
4. Afdeling Pathologie, MUMC, Maastricht
Introduction: Standard treatment for locally advanced rectal cancer is a long course of combined
radiation and chemotherapy. Response assessment is performed 8 weeks after the last radiation,
followed by surgical resection. Up to 20% of the patients obtain a histopathological complete
response, i.e. all tumors cells were destroyed by the chemoradiotherapy. The 5-year disease free
survival and overall survival of patients with a (near) complete response is high (83-87%).
Moreover, these patients may not need a surgical resection, if we are able to select the (near)
complete responders prior to surgery. However, response assessment after chemoradiotherapy
(CRT) in rectal cancer remains difficult due to post-radiation fibrosis. Using standard MRI, postradiation fibrotic thickening with or without residual tumor have similar imaging features and
cannot be reliably distinguished.
Currently it is not well understood why some tumors respond very well to CRT, while others show
no or very little response. If we were able to predict which tumors are likely going to respond to
CRT,
this
would
allow
for
more
individualized
treatment
options.
The aim of this study was to investigate if kinetic analysis of dynamic contrast enhanced(DCE) MRI,
using the blood-pool contrast agent gadofosveset, can predict tumor response both before and
after chemoradiation in patients with locally advanced rectal cancer.
Materials and Methods: Twenty-five patients with locally advanced rectal cancer received DCEMRI both before and 8 weeks after CRT. The kinetic parameters i.e., the initial slope, initial peak,
late slope, and area under the first 60, 90, and 120s of the enhancement curve (AUC60, AUC90,
AUC120) were determined from relative signal enhancement-time curves. Receiver operating
characteristics (ROC) curves were used to assess the diagnostic performance.
Good responders (n=11) were defined as patients with a tumor regression grade (TRG) of 1 or 2 at
histopathologic assessment after resection. Poor responders were defined as patients with a TRG
of 3 to 5 (n=14).
Results: Before neo-adjuvant CRT, the late slope was significantly lower for the good responders (1.61x10-3) compared with the poor responders (5.18x10-3, p=0.004). The area under the ROCcurve was 0.83.
Post-CRT the initial peak, AUC90, and AUC120 were significantly lower in the good responders
compared with the poor responders (1.20vs1.53, 102vs128, 145vs181 and p=0.017, 0.028, 0.023
respectively). ROC-curves ranged between 0.73-0.76.
All parameters except the late slope changed significantly more post-CRT in the good responders
compared with the poor responders. ROC-curves ranged from 0.77 to 0.81.
Poster
Conclusion: Kinetic parameters of dynamic contrast enhanced MRI are a promising tool for
predicting response both before and after chemoradiotherapy in patients with rectal cancer. This
would allow for a more personalized treatment, offering options for organ saving treatments.
Staande poster, nr 10
11
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Elwin Mommers
Student-assistent
Chirurgie
Nee
Results of Endoscopically assisted Component Separation Technique for large ventral hernias
J.A. Wegdam1, S.W. Nienhuijs2, T.S. de Vries Reilingh1
1. Afdeling Chirurgie, Elkerliek ziekenhuis, Helmond
2. Afdeling Chirurgie, Catharina ziekenhuis, Eindhoven
Background: Conventional Component Separation Technique (CST) is associated with a high
wound complication rate (up to 47%) due to large wound surface and dissection of peri-umbilical
perforating arteries to the abdominal skin. Endoscopically assisted Component Separation
Technique (ECST) reduces the wound surface and saves these arteries. This study evaluated the
results of ECST in terms of feasibility, wound complications and recurrence rate.
Methods: Since September 2012 complex ventral hernias were treated in a specialized regional
centre for abdominal wall reconstructions. Indications for ECST were medial abdominal wall
defects with a maximum transversal diameter of 12cm on pre-operative CT-scan and no previous
subcutaneous dissection. Enterostomy was no contra-indication. Follow-up consisted of 3-6
monthly visits to outpatient clinic.
Results: Sixteen patients (9 male) with median age of 62 years (range 46-77) underwent ECST. The
median defect size was 94.2cm2 (range 22-217). Thirteen patients received an intra-abdominal
mesh (Ventralight ST). Three patients did not receive any mesh because of simultaneous
extirpation of an infected mesh. The fascia could be closed in the midline in all patients. Eleven
patients received bilateral and 4 unilateral ECST. In 1 patient both open (left side) and endoscopic
(right side) component separation was performed due to a larger than expected defect (16cm
diameter).
Median operation time was 105 minutes (range 69-239). Duration of hospital stay was 5 days
[range 3-15]. Four patients (24%) had a wound complication within 30 days after surgery (seroma
(n=1), abscess (n=3)). Mean follow-up was 6 months (SD 4.4). Two patients had a recurrence
hernia cicatricalis after 6 and 7 months. Both were primary closures after extirpation of an infected
mesh during ECST.
Poster
Conclusion: This first experience showed closure of defects up to 12cm with endoscopically
assisted component separation was feasible with a modest complication rate of 24% and a
recurrence rate of 12%.
Staande poster, nr 11
12
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Givan Paulus
PhD student
Chirurgie
NUTRIM
Reduced caloric intake after plication of the stomach through altered ghrelin response
M. van Avesaat1, J.M. Conchillo1, A.A. Masclee1, N.D. Bouvy2
1. Afdeling Maag- Darm- Leverziekten, MUMC, Maastricht
2. Afdeling Heelkunde, MUMC, Maastricht
Bariatric surgery is the only long-term effective therapy for weight loss in morbidly obese patients.
With the rising number of procedures, research and development of minimal invasive procedures
also increases. Recently, our center started an endoscopic method to reduce the volume of the
stomach by creating plications.
The procedure starts with introducing an Articulating Circular Endoscopic (ACE) stapler device.
With the device, stomach tissue is acquired by vacuum and stapled to create eight to ten
permanent plications. Before and one month after the procedure patients underwent a
standardized meal test with blood sampling for gastrointestinal hormones, breath sampling for
gastric emptying (13C-octoanoic acid breath test) and visual analogue scale (VAS) for hunger and
satiety. Samples were obtained at several time points before and after a standardized breakfast.
Ten patients underwent the gastric plication procedure and were tested. Baseline weight was
119.3±3.5 kg, which had decreased to 111.6±3.4 kg (p<0.001) at the day of the standardized maeal
test. No changes were found in gastric emptying (GE) compared to baseline (GE half time
141.3±5.9 preoperative vs 138.7±12.3 minutes postoperative, p>0.05). Statistical analysis of
Ghrelin concentration in the first hour showed significantly different iAUC after the procedure
(6.7±9.1 vs. -33.3±12.0, p<0.05). Furthermore, iAUC of VAS for desire to eat significantly decreased
after the procedure (-21.2±7.1 vs. -41.7±7.4, p<0.05). After the procedure we found a significant
correlation between ghrelin levels and desire to eat in the first hour of the test day that did not
reach statistical significance before the procedure. We did not find any significant changes in the
anorexigenic hormones GLP-1 and PYY. One year after plicating the stomach mean weight loss was
19.0±2.4 kg.
Poster
Post-procedural plasma levels of the hunger hormone ghrelin, showed a significant decrease as a
response to the meal. This can be related to increased stretch on the plicated fundus. This effect
might explain part of the reduced caloric intake as desire to eat changes significantly after the
procedure and is positively correlated to plasma levels of Ghrelin. We emphasize that the changed
Ghrelin response is part of the explanation to why patients are more likely to reduce their caloric
intake and lose weight after plicating the stomach.
Staande poster, nr 12
13
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Hellen Römkens
PhD student
Oogheelkunde
Nee
Reproduceerbaarheid van voorste oogkamerhoek metingen met de SS-OCT
H.J.M. Beckers1, M. Frusch2, J.S.A.G. Schouten1, T.T.J.M. Berendschot1, J. de Brabander1, C.A.B.
Webers1
1. University Eye Clinic, Maastricht
2. Hogeschool Zuyd, Heerlen
Doel: Het onderzoeken van de reproduceerbaarheid van voorste oogkamerhoek metingen met de
Swept-source Optical Coherence Tomography (SS-OCT).
Methode: Eenendertig gezonde vrijwilligers met basale kennis van oogheelkunde (non-experts),
maakten 3 SS-OCT afbeeldingen van hun mede non-experts. Analyse van de beelden vond plaats
door experts en non-experts. De variatie tussen experts en non-experts, intra-observer variabiliteit
en variatiecoëfficiënt werden geanalyseerd.
Resultaten: Er werd een significant verschil gevonden tussen de nasale en temporale hoek in
AOD500 (p<0.01), AOD750 (p<0.01) en TISA750 (p<0.01). AOD500 (p=0.025), AOD750 (p=0.012) en
TISA500 (p=0.010) waren significant groter bij analyses verricht door non-experts. De
variatiecoëfficiënt was alleen significant groter voor AOD500 bij non-experts (11.1% versus 8.7%,
p<0.01).
Poster
Conclusie: Deze studie toont een hoge reproduceerbaarheid van SS-OCT voorste oogkamerhoek
metingen. Non-experts verkregen grotere AOD en TISA waarden vergeleken met experts.
Liggende poster, nr 13
14
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Karin Sanders
WESP-student
Longziekten
NUTRIM
Internalization and localization of silica in bronchial epithelial cells
P.M.P. Peeters1, N.L. Reynaert1
1. Department of Respiratory Medicine, MUMC, Maastricht University
Silicon dioxide (SiO2) or silica is one of the most common minerals in the earth’s crust and a major
component of sand and rock. Chronic inhalation due to occupational activities, such as agriculture
and construction, can cause persistent inflammation, fibrosis and breathing problems, which is
known as silicosis. Moreover, it is associated with the development of COPD, heart failure and
cancer. Treatment with immuunsuppressive agents is not effective and pneumoconiosis is
therefore an important health issue.
Exposure of macrophages to SiO2 causes the release of pro-inflammatory cytokines. Production of
these cytokines is regulated by the (NOD)-like receptor (NLR) family pyrin domain containing
protein 3 (NLRP3). NLRP3 is a multiprotein formed of innate immune receptors, which is also called
the inflammasome. NLRP3 is activated in several ways, which eventually results in proteolytic
maturation and secretion of inflammatory proteins, such as Il-1β and Il-18.
The topic of this research is silica-induced inflammasome activation in bronchial epithelial cells,
since epithelial cells are the primary barrier to environmental exposures. It is generally assumed
that epithelial lung cells are relatively inactive when exposed to silica. However, results of our
group have shown that certain stress-related genes such as Il-1, Il-6, Il-8 and thioredoxininteracting protein (TXNIP) are upregulated in epithelial cells when exposed to SiO2. Furthermore,
in vitro it is found that caspase-1, basic Fibroblast Growth Factor (bFGF) and High Mobility Group
Box 1 (HMGB1) are increasingly secreted by epithelial cells in response to silica exposure in an
NLRP3- and uptake-dependent manner. However, the mechanism of uptake, the localization of the
internalized silica particles and the mechanisms by which the inflammasome is activated is
unknown.
In order to analyze particle uptake, bronchial epithelial cells are exposed to fluorescently labelled
SiO2. Furthermore, to determine the intracellular localization cell organelles, such as lysosomes
and mitochondria are fluorescently labelled. Analysis will be performed by fluorescence and
confocal microscopy.
Poster
We have successfully fluorescently labelled SiO2 particles. Initial studies showed the labelled
particles have a similar toxicity towards the non-labelled particles. Furthermore, using confocal
optical sectioning, silica particles were shown to be present within the cytoplasm of the epithelial
cells. Further, results about the intracellular localization and molecular mechanism are pending.
Liggende poster, nr 14
15
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Koen Vermorgen
Arts-assistent in opleiding
Oogheelkunde
Nee
Visualisatie van filterblazen na trabeculectomie met SS-OCT Casia Tomey
C.A.B. Webers1, T.T.J.M. Berendschot1, H.J.M. Beckers1
1. Afdeling Oogheelkunde, MUMC, Maastricht
Doel: Het verkrijgen van 3D informatie over interne structuren van de filterblaas na
trabeculectomie.
Methode: Acht filterblazen werden 1 maand postoperatief onderzocht met de Casia OCT. De
kwalitatieve interne structuren (zichtbaarheid van: trabeculectomie-opening, interne ostium,
scleraflap, microcysten, hyporeflectief gebied) en kwantitatieve structuren (dikte scleraflap, aantal
microcysten, lengte, hoogte en volume van de interne holte, minimale en maximale dikte van de
filterblaaswand, totale filterblaashoogte) werden onderzocht en gecorreleerd met de oogdruk.
Resultaten: De trabeculectomie-opening, microcysten en een hyporeflectief gebied waren bij alle
filterblazen zichtbaar, het interne ostium en de sclerale flap bij 87,5% en een interne holte bij
62,5%. Er werd geen significante correlatie gevonden tussen de oogdruk en de onderzochte
structuren.
Poster
Conclusie: Middels de Casia OCT kunnen de interne structuren van een filterblaas goed
gevisualiseerd worden.
Liggende poster, nr 15
16
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Eleana Zhang
PhD student
Neurologie
CARIM
Blood-brain barrier permeability is quantitatively increased in lacunar stroke patients
S.M. Wong1, H.J. van de Haar1, J.E.A. Staals2, J.F.A. Jansen1, C.R.L.P.N. Jeukens1, P.A.M.
Hofman1,W.H. Backes1, R.J. van Oostenbrugge2
1. Department of Radiology, MUMC, Maastricht
2.Department of Neurology, MUMC, Maastricht
Background: Lacunar stroke (LS) is a major clinical consequence of cerebral small vessel disease
(cSVD). Increased blood-brain barrier (BBB) permeability is thought to play a pivotal role in the
pathophysiology of cSVD. Previous studies showed a qualitative increase of BBB permeability in
the entire cerebral white matter (WM), and in the normal appearing white matter (NAWM) in LS
patients compared to healthy controls. However, quantitative studies are lacking, hence no
reliable comparison can be made between studies and no quantitative reference points exist for
BBB permeability. We developed a new dynamic contrast enhanced MRI (DCE-MRI) protocol and
applied this to quantify BBB permeability in WM and NAWM, in LS patients and healthy controls.
Methods: We included 17 first ever LS patients and 8 age and gender matched healthy controls. All
received a DCE-MRI using a 3T scanner. Signal intensities were incorporated in the Patlak model to
determine the transfer constant Ki, a pharmacokinetic parameter for BBB permeability, in the WM
and NAWM. Mean Ki values were compared between the two groups. Here, only Ki values of >
0,002 min-1 were used, as we consider values above this cut off point to be indicative of an
abnormal permeability. In addition, risk factors such as hypertension and diabetes were compared.
Results: LS patients had a significantly higher mean Ki in WM (3.73∙10-3 vs 3.26∙10-3 min-1;
p=0.043) and NAWM (3.74∙10-3 vs 3.26∙10-3 min-1; p=0.043) compared to healthy controls. No
differences in risk factors were found between the groups.
Poster
Conclusion: BBB permeability in WM and NAWM was quantitatively higher in LS patients
compared to healthy controls, with negligible differences between NAWM and WM within each
group. This finding supports previous qualitative studies, reflecting the generalized white matter
pathology in cSVD. Moreover, this study provides quantitative BBB permeability data in LS
patients, which are essential for future data comparison and analysis.
Liggende poster, nr 16
17
“Originele”studies
Naam (posternummer)
Pagina
Sema Bektas, Cardiologie (17, 18)
19,20
Maikel Bakens, Chirurgie (19)
21
Dominique Disseldorp, Chirurgie (20, 21)
22, 23
Judith Hilderink, Interne Geneeskunde (22)
24
Inca Hundscheid, Chirurgie (23)
25
Monique de Jong, Keel-, Neus-, en Oorheelkunde (24)
26
Madeleine Kok, Radiologie (25)
27
Noreen van der Linden, Klinische Chemie (26)
28
Alma Mingels, Klinische Chemie (27)
29
Marjolein van der Poel, Interne Geneeskunde (28)
30
Roald Schnerr, Radiologie (29)
31
Ellen Schoorel, Interne Geneeskunde (30)
32
Jantien van der Heyden, Gynaecologie en Obstetrie (31)
33
Desiree Rutten, Cardiologie (32)
34
18
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Sema Bektas
PhD student
Cardiologie
CARIM
Heart Failure with preserved vs reduced ejection fraction: Do they really differ from each other?
S. Sanders -van Wijk1, D.J.M. Rutten1, M. Maeder2, W. Estlinbaum3, P. Erne4, H. Rickli2, M.E.
Pfisterer5, H.P. Brunner-La Rocca1
1.Department of Cardiology, MUMC, Maastricht
2. Department of Cardiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
3. Department of Cardiology, Cantonal Hospital Liestal, Liestal, Switzerland
4. Department of Cardiology, Lucerne Cantonal Hospital, Lucerne, Switzerland
5. Department of Cardiology, University Hospital Basel, Basel, Switzerland
Background: Several studies showed that patients with heart failure with preserved (HFPEF) versus
those with reduced EF (HFREF) are older, more often female and have higher body mass index
(BMI). It is unclear to what extent age, gender differences and BMI explain the other differences
between HFPEF and HFREF in regard to signs and symptoms, quality of life (QOL) and survival.
Methods: 97 HFPEF (EF ≥50%) and 97 HFREF (EF ≤40%) patients from TIME-CHF were included and
matched 1:1 for age (79±7 vs 80±7, P=0.65), gender (38% vs 38% male) and BMI >25 (64% vs 64%)
respectively. Follow-up period was 548 days.
Results: The most common cause of HF in HFREF and HFPEF patients are coronary artery disease
(55%) and hypertensive heart disease (HHD) (57%) respectively. The number of comorbidities
reflected by the Charlson score was similar in both groups. Severity of complaints reflected by New
York Heart Association class, angina, orthopnea, fatigue, exercise intolerance and edema were
similarly impaired. Laboratory findings, except haemoglobin and N-terminal brain natriuretic
peptide (P<0.01), where similar in both groups. QOL measured by Minnesota living with HF
questionnaire and Duke Activity Status Index (DASI) did not differ between the groups at baseline,
12 and 18 months. Hospital free survival in the HFPEF group is significantly lower (P=0.05).
Poster
Conclusion: After matching for age, gender and BMI, prevalence of comorbidities, severity of signs
and symptoms and QOL is strikingly similar in HFPEF and HFREF suggesting that age, gender or BMI
explain a large part of the differences between HF-groups. Despite these similarities, the
hospitalisation free survival is significantly worse in HFPEF. Suggesting that more research is
needed to understand the pathophysiology and optimize therapy for HFPEF.
Liggende poster, nr 17
19
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Sema Bektas
PhD student
Cardiologie
CARIM
INTERACT-in-HF:improving knowledge to efficaciously raise level of contemporary treatment in
HF
S. Sanders-van Wijk1, D.J.M. Rutten1, M. Spanjers1, J. Boyne1, C. Hausdorf2, V.M. Brandenburg2, L.
de Maesschalck3, C. Knackstedt1, H.P. Brunner-La Rocca1
1. Department of Cardiology, MUMC, Maastricht
2. RWTH University Hospital Aachen, Aachen, Germany
3. Thomas More Mobilab, Research, Geel, Belgium
Background: Heart failure (HF) remains to have a poor outcome. Recent advances in HF therapy
were identified to improve both morbidity and mortality, but improvement in outcome is much
less than expected based on large randomized trials. Various reasons may be responsible, such as
complexity of disease and comorbidities, inadequate diagnosis and inappropriate treatment.
Little attention was placed on patients seen in primary care and HF care mainly focuses on the
individual patient-doctor relationship. However, the increasing complexity prevents individual
physicians from covering all aspects of care. Thus, multiple stakeholders are involved in the care,
both primary and secondary. Still, the relative role, the interaction between them and the
processes included are hardly defined. These aspects may not only be relevant for patient care, but
also for the setup of health care systems. Whereas the multidisciplinary team should resemble a
seamless system across primary and hospital care, there is a scarcity of research considering how
these disease management programs perform, in what form they should be offered, and what care
and support patients and caregivers would benefit most.
Purpose: The INTERACT study is set up to determine and assess relevant factors of the quality of
HF care. The study investigates processes of HF care, relevant players and interactions between
them. It collects data from individual patients to assess characteristics and management of
contemporary HF patients in different countries (the Netherlands, Belgium and Germany) and to
evaluate decision making with respect to diagnostics and treatment.
Methods: Cross-sectional mixed-methods are used. Patients (n=30 per centre) and their caregivers
are interviewed. The patient is the central starting point. Then, the treating GP, cardiologist and HF
nurse are interviewed. In parallel, retrospective data based on records from these patients are
reviewed to verify data from interviews and to determine characteristics of them. Retrospective
data of additional patients (n=60 per centre) are collected to complete the picture of the current
situation.
Poster
Conclusion: These data will be used to define bottlenecks that prevent best clinical practice to be
used in daily care at all levels, comparing practice in different countries. Based on these results,
intelligent information and communication technology (ICT) will be developed to improve care.
Thus, the proposal aims to better understand HF care, which will lead to a better care and finally to
improved outcome.
Liggende poster, nr 18
20
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Maikel Bakens
WESP-student
Chirurgie
Nee
Sarcopenia patients undergoing surgery for pancreatic carcinoma, influences postoperative
outcomes?
M.M.E. Coolsen1,2, M.C. de Jong1,2, D. van Dijk1,2, R.M. van Dam1,2, C.H.C. Dejong1,2, S.W.M. Olde
Damink1,2,3
1. Department of Surgery, MUMC, Maastricht
2. Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht
3. Department of Surgery, Royal Free Hospital, and University College London, Division of Surgery
and Interventional Science, United Kingdom
Introduction: The influence of sarcopenia, defined as depletion of muscle mass, on postoperative
short-term outcomes following pancreatic surgery and its effects on postoperative infectious
complications remains undefined and is therefore the aim of the present study.
Methods: All patients scheduled to undergo a pancreaticoduodenectomy (PD) for malignancy
between July 2008-August 2012 were included. Sarcopenia was assessed using the pre-operative
CT-scan according to established methods; a cutoff value of 52.4 55.4 cm2/m2 in men and 38.5
38.9 cm2/m2 in women was used to define sarcopenia. Patient characteristics and postoperative
complications were prospectively collected and subsequently analysed.
Results: 154 patients were enrolled. 95 patients underwent a PD, 59 received a double bypass (DB)
because of irresectability. 91/154 patients (59.1%) were classified as sarcopenic. 90-day-mortality
was higher in sarcopenic patients (n=11 (7.1%) vs n=1 (0.6%); p=0.02). Infectious complications
occurred in 59/154 patients (38.1%) and overall complications in 79/154 patients (51.3%). Of the
total group, significantly more patients with sarcopenia developed infectious complications
(n=41(26.6%) vs n=18 (11.7%);p=0.04); while the occurrence of overall complications was
comparable (n=51 (33.1%) vs n=28(18.2%); p=0.15). Significantly more sarcopenic patients
developed infectious as well as overall complications after PD (n=31 (32.6%) vs n=11 (31.6%);
p=0.009 and n=37 (38.9%) vs n=17 (17.9%); p=0.03, respectively). No differences in complications
were observed in the DB group (all p>0.05). On univariate analysis but not on multivariate analysis,
sarcopenia was found to increase the risk of infectious complications (OR=2.1 [95%-CI 1.04.1];p=0.04), On multivariate analysis, obesity (OR=2.3 [95%-CI 1.2-4.7];p=0.01) and undergoing a
PD (vs DB: (OR=2.2 [95%-CI 1.0-4.6];p=0.04)) were associated with an increased risk of infectious
complications.
Poster
Conclusion: 90-day mortality seems higher in sarcopenic patients. However, due to low incidence
further analysis was not possible. Whereas sarcopenia might negatively impact short-term
outcomes, its real effects remain ill-defined. Conversely, obesity and undergoing a
pancreaticoduodenectomy were found to be independent predictors of postoperative morbidity
Staande poster, nr 19
21
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Dominique Disseldorp
Arts-assistent niet-in-opleiding
Chirurgie
Nee
Botplastiek bij correctie-osteotomie voor malunions van de distale radius is niet noodzakelijk
P.R.G. Brink1, M. Poeze1, P.F.W. Hannemann1
1. Afdeling Chirurgie, MUMC, Maastricht
Introductie: Malunion is één van de meest voorkomende complicaties van distale radius fracturen
na zowel conservatieve als operatieve behandeling. Malunions kunnen geassocieerd zijn met
pijnklachten, krachtsverlies en functiebeperking. Hiermee vormen ze een behoorlijke belemmering
in het dagelijks functioneren. Diverse chirurgische methoden kunnen gebruikt worden bij de
behandeling van malunions, maar open wig osteotomie met plaatfixatie en botplastiek wordt als
dé standaardprocedure beschouwd. Met deze techniek wordt de radius op lengte gebracht en de
stand gecorrigeerd. Het ontstane botdefect wordt opgevuld met autoloog corticospongieus of
spongieus bottransplantaat, of een allogene botspaan. Hierbij is de gedachte dat zowel de biologie
als de stabiliteit verbeterd. Er zijn ook nadelen aan het gebruik van botspanen zoals morbiditeit op
donorplaats, langere operatieduur, hogere kosten en mismatch tussen de botspaan en het defect.
Ondanks de nadelen zijn er talloze studies met deze standaardprocedure gepubliceerd, waarbij
diverse uitkomstmaten worden geëvalueerd. Het doel van dit onderzoek was om te kijken of
correctie-osteotomie zonder opvulling van het defect vergelijkbare resultaten laat zien.
Patiënten en methoden: Sinds 1993 zijn er 122 patiënten behandeld met een correctieosteotomie zonder opvulling van het defect. Alle patiënten zijn door dezelfde operateur
behandeld. De indicaties voor correctie-osteotomie waren pijn en bewegingsbeperking. Er is
gekeken naar het eventueel optreden van nonunion, standsverlies en complicaties met betrekking
tot de wekedelen.
Resultaten: Slechts 2 van de 122 correcties had een vertraagde botgenezing (6 en 15 maanden in
plaats van 4 maanden). Alle correcties zijn in dezelfde stand genezen welke tijdens de operatie was
bereikt. In totaal waren er 22 complicaties opgetreden ten gevolge van de gebruikte
fixatietechniek: tendinitis (7), CTS (3), peesruptuur (3), CRPS (4), tendovaginitis stenosans (1),
snapping tendon (1) en functiebeperking door overmatige callusvorming (1). Tevens had één
patiënt pijnklachten op basis van een te lange schroef. Bij een andere patiënt zat de schroef los in
de processus styloideus radii. Bij deze complicaties werden geen significante verschillen gevonden
tussen dorsale of volaire plaatfixatie. De radiologische uitkomsten waren postoperatief verbeterd
in vergelijking met preoperatieve uitkomsten en nagenoeg vergelijkbaar met de onaangedane
zijde. Deze onderzoeksresultaten zijn vergelijkbaar met in de literatuur beschreven studies, waarbij
de standaardprocedure van correctie-osteotomie met plaatfixatie en botplastiek is gebruikt.
Poster
Conclusie: Deze studie laat zien dat het opvullen van het defect bij correctie-osteotomie van de
distale radius niet noodzakelijk is voor botgenezing of het voorkomen van secundaire dislocatie.
Hiermee worden de nadelen van een botplastiek voorkomen.
Staande poster, nr 20
22
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Dominique Disseldorp
Arts-assistent niet-in-opleiding
Chirurgie
Nee
Geen verschil in uitkomstmaten tussen volaire en dorsale plaatfixatie bij distale radius fracturen
P.R.G. Brink1, M. Poeze1, P.F.W. Hannemann1
1. Afdeling Chirurgie, MUMC, Maastricht
Introductie: Diverse chirurgische methoden worden gebruikt voor de behandeling van distale
radius fracturen. In de afgelopen twee decennia heeft open repositie met interne fixatie middels
volaire of dorsale plaat aan populariteit gewonnen. In de praktijk wordt meestal de voorkeur
gegeven aan volaire plaatfixatie vanwege de angst voor complicaties die dorsale platen in het
verleden gaven. De nieuwere dorsale fragment specifieke platen met een kleiner profiel zouden
mogelijk minder complicaties geven. Momenteel bestaat er in de literatuur geen consensus over
welke plaatfixatie de beste behandeling is voor distale radius fracturen. Het doel van deze studie
was het vergelijken van complicaties, functionele en radiografische resultaten tussen volaire en
dorsale plaatfixatie. Dit onderzoek is de eerste Nederlandse studie die deze vergelijking maakt bij
een grote patiëntenpopulatie.
Patiënten en methode: In dit retrospectief cohort onderzoek zijn in totaal 147 volwassen
patiënten met een gedisloceerde distale radius fractuur of malunion geïncludeerd. Deze patiënten
zijn tussen januari 2003 en april 2010 behandeld met plaatosteosynthese. Alle patiënten hadden
een postoperatief follow-up van 2 jaar. Zestig patiënten zijn behandeld met volaire plaatfixatie en
87 patiënten met dorsale plaatfixatie. Complicaties werden middels dossieronderzoek vastgesteld.
Daarnaast zijn de patiënten benaderd om terug te komen naar het ziekenhuis voor het ondergaan
van diverse onderzoeken. Als eerste hebben de patiënten gevalideerde vragenlijsten ingevuld,
waaronder de Patient-Rated Wrist Evaluation (PRWE) en Disabilities of the Arm, Shoulder and
Hand questionnaire (DASH). Deze vragenlijsten gaan vooral over het uitoefenen van de dagelijkse
activiteiten en eventuele klachten na de operatie. Vervolgens zijn bij deze patiënten de functie en
de kracht van beide polsen getest. Als laatste zijn röntgenfoto’s van beide polsen gemaakt.
Resultaten: De demografische en baseline kernmerken waren vergelijkbaar tussen beide groepen.
De complicaties waren niet significant verschillend tussen beide groepen. Bij de verschillende
functionele en radiologische uitkomstmaten werden eveneens geen significante verschillen
gevonden tussen beide groepen behalve de palmaire flexie en radiale deviatie. De palmaire flexie
bleek significant beter te zijn bij de patiënten met een gedisloceerde distale radius fractuur die
behandeld waren met een volaire plaat. De radiale deviatie was significant beter bij de patiënten
met correctie van een malunion die een dorsale plaat hadden gekregen. Deze verschillen waren
mogelijk ten gevolge van de anatomische opbouw door de type plaatfixatie en hadden geen
invloed op het dagelijks functioneren.
Poster
Conclusie: Deze studie toont aan dat er geen voorkeur gegeven kan worden aan de type
plaatfixatie. De keuze van type plaat dient dus gebaseerd te zijn op fractuurtype en de ervaring van
de chirurg met de verschillende fixatietechnieken.
Staande poster, nr 21
23
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Judith Hilderink
Student-assistent
Interne Geneeskunde
Nee
Ontwikkeling van een smartphone-app voor de interpretatie van laboratoriumuitslagen
S. Meex1, R. Koopman2, R. Rennenberg2
Affiliaties
1. Afdeling Klinische chemie, MUMC, Maastricht
2. Afdeling Interne Geneeskunde, MUMC, Maastricht
Inleiding: Bij het vervolgen van patiënten in de tijd is het soms lastig om echte veranderingen in
laboratoriumuitslagen te onderscheiden van zogeheten ‘natuurlijke schommelingen’. Dit
onderscheid wordt door veel artsen gemaakt op basis van klinische ervaring en intuïtie. Er zijn
echter voorbeelden te bedenken waar een wetenschappelijk onderbouwde objectivering van deze
kansberekening een zinvolle aanvulling kan zijn op het klinisch gevoel. Wij beschrijven de
ontwikkeling van een smartphone-app waarmee de waarschijnlijkheid van een stijging of daling
van een laboratoriumuitslag ten opzichte van de vorige uitslag objectief kan worden vastgesteld,
gegeven de tijd tussen de metingen.
Abstract
Methoden: Een verandering in opeenvolgende uitslagen bij een individu kan pas met grote
waarschijnlijkheid als ‘echt’ worden beschouwd indien het verschil tussen de opeenvolgende
uitslagen groter is dan de totale intrinsieke variatie. De grootte van dit kritisch verschil is voor elke
bepaling verschillend, en wordt bepaald door twee componenten: de biologische binnenpersoonsvariatie (CVi), en de analytische variatie (CVa).
De waarschijnlijkheid dat de verandering echt is kan berekend worden met de volgende formule:
Z-score= procentuele verandering/ √(2* (CVa²) + (CVi²))
De belangrijkste parameter voor een goede functionaliteit van de app is een betrouwbare
schatting van de biologische binnen-persoonsvariatie over de tijd. Aan de hand van de
gepubliceerde literatuur over de biologische variatie hebben we statistische modellen opgesteld
die het effect van het tijdsinterval tussen twee metingen op de biologisch variatie beschrijven.
Voor het modelleren van deze gegevens is een log-lineair verband gebruikt.
Deze modellen zijn geïntegreerd in de smartphone-app.
Resultaten: Voor het ontwikkelen van de app hebben we uit de wetenschappelijke literatuur data
verzameld over de biologische variatie van 42 laboratoriumbepalingen. Bij 50% van de
bestudeerde analyten werd een tijdsrelatie gevonden in de biologische variatie, waarvan 12% een
verschil aantoont tussen binnendaagse- en tussendaagse biologische variatie en in 38% werd een
continue tijdsrelatie gevonden in de biologische variatie. Deze informatie hebben we statistisch
gemodelleerd en geïntegreerd in een smartphone-app die voor alle standaard
laboratoriumbepalingen de waarschijnlijkheid berekent dat een verandering tussen twee
laboratoriumuitslagen ‘echt’ is.
Poster
Conclusie: Deze smartphone-app kan als hulpmiddel dienen bij de interpretatie van
opeenvolgende laboratoriumuitslagen en is met name bedoeld voor beginnend arts-assistenten en
coassistenten om hun klinische gevoel te helpen ontwikkelen.
Staande poster, nr 22
24
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Inca Hundscheid
PhD student
Chirurgie
NUTRIM
Females are better protected from gut injury during ischemia-reperfusion than males: sex
matters
J. Grootjans3, D.H.S.M. Schellekens1,2, J. P.M. Derikx1,2, R. M. van Dam1,2, W.A. Buurman1,2, K.
Lenaerts1,2, C.H.C. Dejong1,2
1. Department of Surgery, MUMC, Maastricht
2. School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht
3. Department of Internal Medicine, Slotervaart ziekenhuis, Amsterdam
Introduction: Gender differences in the pathophysiological response to ischemia-reperfusion (IR)
have particularly been recognized in cardiovascular and cerebral systems. However, it is unknown
if sexual dimorphism exists in human intestinal IR, a frequent occurring and highly lethal disease.
Recognition of such differences and elucidation of the underlying pathophysiological mechanisms
could lead to more evidence-based medicine for females, and the development of novel
therapeutic strategies to reduce IR-associated morbidity and mortality. Therefore, we aimed to
investigate sex differences in human intestinal mucosal responses to IR.
Materials & Methods: Intestinal IR was studied using a human experimental model. In 16 patients
(M8:F8) undergoing pancreaticoduodenectomy, an isolated part of jejunum was subjected to 45
minutes of ischemia (45I) followed by 30 (30R) or 120 minutes of reperfusion (120R). Intestinal
tissue was collected at all time points to assess morphology (hematoxylin/eosin (HE)), neutrophil
influx (myeloperoxidase (MPO)) and Paneth cell apoptosis (Lysozyme/M30 double staining).
Endoplasmic reticulum (ER) stress was analyzed using an X-box binding protein-1 (XBP1) splicing
assay and XBP1-spliced/XBP1-unspliced (XBP1s/XBP1u) ratios were calculated. QPCR techniques
were used to determine inflammatory cytokine expression. Arteriovenous (V-A) concentration
differences of intestinal fatty acid binding protein (I-FABP) were measured using an enzyme-linked
immunosorbent assay (ELISA) to assess the level of enterocyte damage. Results were analyzed
using Mann-Whitney U tests. Data are presented as mean±SEM. A P-value <0.05 is considered
statistically significant.
Results: HE staining revealed more extensive small intestinal epithelial damage in male subjects
compared to females. In line, I-FABP V-A concentrations differences were higher in males
compared to females, both at 45I (233.9±73.3 ng/ml vs 55.5±18.3 ng/ml, P<.05) and at 45I30R
(79.2±19.4 ng/ml vs 24.4±6.6 ng/ml, P<.05). Furthermore, male small intestine showed higher
XBP1s/XBP1u ratios at 45I30R than female small intestine (4.3±0.8 vs 2.2±0.4, P<.05), indicating
enhanced ER stress in males. As expected, this was associated with a higher number of apoptotic
Paneth cells per crypt in male subjects compared to females at 45I (5.8±1.2 vs 1.7±0.4, P<.05) and
45I30R (18.3±2.9 vs 7.6±1.9, P<.05). Furthermore, males had a more pronounced influx of
neutrophils per villus at 45I30R (6.9±1.2 vs 3.6±0.6, P<.05) and a higher relative mRNA expression
of inflammatory cytokines TNF-a and IL-10 after 45I120R, compared to females (2.6 fold and 6.4
fold respectively, P<.05).
Poster
Conclusion: The human female small intestine is better protected from IR-induced epithelial
damage than the male small intestine, and correspondingly displayed notably less inflammatory
responses. Unravelling the molecular mechanisms underlying this effect could lead to new
therapeutic strategies for intestinal IR.
Staande poster, nr 23
25
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Monique de Jong
WESP-student
Keel-, Neus- en Oorheelkunde
Nee
DTI of the central auditory pathways in lambs after perinatal asphyxia
B. Kremer1, B. Kramer2, R.J. Stokroos1, J. Dudink2, S.M. Schaefer1
1. Afdeling KNO, MUMC, Maastricht
2. Afdeling Kindergeneeskunde, MUMC, Maastricht
Introduction: Each year 1-3 per 1000 newborns are diagnosed with congenital sensorineural
hearing loss (SNHL). In previous studies, severe perinatal hypoxic-ischemia was identified as one of
the main risk factors for auditory impairment, with affected newborns showing impaired
brainstem conduction in the post natal period.
To enable early detection of brain ischemia – and therefore the possibility for early intervention –
diffusion tensor magnetic resonance imaging (DTI) in the neonatal patient has become more
important in recent years. DTI can give an insight in white matter pathway integrity through for
example fractional anisotropy (FA). The additional value of this imaging modality has become
apparent for predicting patient outcome in the acute setting as well as for long-term follow-up.
The relation between abnormalities on DTI and functional outcome has also been subject of
investigation when it comes to SNHL. Several studies show a high radial diffusivity and
consequently low FA in multiple central auditory nuclei in patients with SNHL, which indicates a
demyelination of the auditory tract. Also, shorter latencies in electrophysiological auditory tests,
such as brainstem auditory evoked potentials (BAEP) and magneto encephalography (MEG), are
associated with a higher FA in the inferior colliculus and acoustic radiations, which indicate a
positive relation between white matter myelination on conduction velocity.
Smith et al. showed impaired brainstem conduction in a lamb model in subjects that underwent
severe asphyxia compared to controls. BAEP measurements of the intervention suggest retro
cochlear damage. The present study aims to identify the suggested retro cochlear damage in these
asphyxiated lambs by means of DTI.
Methods: The intervention group consists of 8 lambs with induced neonatal hypoxic-ischemia
according to the lamb model as described by Smit et al. The control group consists of 8 healthy
shams. DTI were obtained of the 16 lambs. The regions of interest (ROI) were determined
manually. ROI’s were the cochlear nuclei, the superior olive nucleus, the trapezoid body, the
lateral lemniscus, the inferior colliculus, the medial geniculate body and the auditory cortex
(superior temporal Heschl gyrus). The DWI was scored independently by two trained researchers.
A qualitative standardized scoring system was used for defining abnormalities in the ROI; 0 = no
abnormalities, 1= mild/possible abnormalities, 2= sever/definite abnormalities. Quantitative DTI
measurements as the apparent diffusion coefficient in the ROI, fractional anisotropy, axial
diffusivity, and radial diffusivity, were obtained for all subjects and compared among groups. All
measurements were achieved by two independent observers blinded for intervention with
determination of inter-rater reliability (for example intra-class correlation coefficient or Pearson’s
correlation coefficient).
Results: Pending.
Poster
Conclusion: Pending.
Staande poster, nr 24
26
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Madeleine Kok
PhD student
Radiologie
CARIM
Contrast media reduction using low kV settings in CT angiography: a phantom study
C. Mihl1,2, A. Seehofnerova1, S. Altintas1,2,3, B.L.J.H. Kietselaer1,2,3, J. Turek1, J.E. Wildberger1,2, M.
Das1,2
1. Department of Radiology, MUMC, Maastricht
2. CARIM school for Cardiovascular Diseases, MUMC, Maastricht
3. Department of Cardiology, MUMC, Maastricht
Purpose: Using lower kV settings will result in higher attenuation values for protocols with the
same iodine delivery rate (IDR) and total iodine load. This bares the potential to reduce contrast
media (CM), with potential benefit in terms of patient safety (contrast induced nephropathy: CIN)
and cost effectiveness. Thus, the purpose of this study was to investigate how to reduce IDR and
total iodine load in lower kV settings in CT angiography (CTA) while keeping attenuation values
diagnostically sufficient.
Methods and materials: CM with a concentration of 300 mg I/ml (Iopromide) was used and
injected in a circulation phantom with physiological parameters (BP 120/80mmHg, HR 60bpm).
Sequential serial CT (SOMATOM Definition Flash, Siemens) scans at the level of the aorta
ascendens (incl. coronaries) were performed with the following parameters: 128x0.6mm coll., mAs
142, cycletime 0.43s, gantry rot.time 0.28s, delay 10s. Images were reconstructed at 1 mm slice
thickness with an increment of 0.7 mm and a soft tissue kernel (B30f). Initially, the same injection
protocol (CM volume=40 ml, flow rate=5.3 ml/s, IDR=1.6 g I/s and total iodine load=12 g I) was
used for each kV setting (120, 100, 80 and 70 kV). Secondly, based on attenuation values of the
first scans IDR and total iodine load were chosen for each kV: 2.0 g I/s and 15 g (120 kV); 1.6 g I/s
and 12 g (100 kV); 1.2 g I/s and 9 g (80 kV) and 1.0 g I/s and 7.5 g (70 kV). After that, IDR was
decreased for each kV by steps of 0.2 g I/s until diagnostically insufficient attenuation values (<325
HU) were reached. Total iodine load was consecutively reduced to keep injection time constant
(7.5 s). Attenuation values were measured and compared in the ascending aorta (AA), descending
aorta (DA) and left main coronary artery (LM).
Results: Using the identical injection parameters for each kV, attenuation values (HU±SD) were as
follows: 326±2.1 (120 kV); 406±3.1 (100 kV); 524±3.0 (80 kV); 651±3.8 (70 kV). Attenuation values
>409 HU were found using the chosen IDR and total iodine load for each kV. After reducing IDR
with 0.2 g I/s, diagnostically sufficient attenuation values (>341<367 HU) were achieved. Minimal
IDR and iodine load for each kV were as follows: 1.8 g I/s and 13.5 g I (120 kV); 1.4 g I/s and 10.5 g I
(100 kV); 1.0 g I/s and 7.5 g I (80 kV); 0.8 g I/s and 6.0 g I (70 kV).
Poster
Conclusion: In lower kV settings (100, 80 and 70 kV) injection parameters such as total iodine load,
IDR and CM volume could be reduced by 22%, 44% and 56% respectively compared to 120 kV,
while keeping diagnostically sufficient attenuation values (>325 HU). This could play an important
role in terms of patient safety (CIN) and lowering costs.
Staande poster, nr 25
27
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Noreen van der Linden
PhD student
Klinische Chemie
CARIM
Effect of six-month resistance-type exercise training on cardiac troponin T in (pre)frail elderly
M. Tieland2,3, L.J.J. Klinkenberg1, L.B. Verdijk3,4, L.C.P.G.M. de Groot2,3, L.J.C. van Loon3,4, M.P. van
Dieijen-Visser1, S.J.R. Meex1
1. Department of Clinical Chemistry, Cardiovascular Research Institute Maastricht (CARIM),
MUMC, Maastricht
2. Division of Human Nutrition, Wageningen University , Wageningen
3. Top Institute Food and Nutrition, Wageningen University, Wageningen
4. Department of Human Movement Sciences, School for Nutrition, Toxicology and Metabolism
(NUTRIM), MUMC, Maastricht
Background: Cardiac troponin is the preferred biomarker for diagnosing non ST-segment elevation
myocardial infarction. With the introduction of high-sensitivity assays, cardiac troponin levels
became also detectable in apparently healthy subjects. This has expanded its role from acute
cardiac care to risk stratification and prognostic medicine. A previous, observational study showed
that higher physical activity in elderly subjects was associated with both a lower basal cardiac
troponin T (cTnT) and a lower probability of a significant increase of cTnT over time. However, a
causal relationship has not been demonstrated. The present trial was conducted to investigate the
hypothesis that a six-month resistance-type exercise training program can influence the basal
serum cardiac troponin T levels in (pre)frail elderly, a group with high vulnerability to adverse
cardiovascular outcomes and all-cause mortality.
Methods: Sixty-two (pre)frail elderly subjects (≥65 years) participated in a 24-week supervised
resistance-type exercise training program, or were followed up during a parallel non-interventional
control period. Training was scheduled twice per week and workload was gradually increased
during the study. Plasma cTnT was measured using the high-sensitive cTnT assay (Roche
Diagnostics) at 0, 12 and 24 weeks of intervention.
Results: All cTnT concentrations during the study (range 3.78–105.70ng/L) were above the
detection limit (3ng/L), and 40 subjects (65%) had at least one measurement above the 99th
percentile (14ng/L). Ten subjects withdrew from the study, leaving 52 subjects for follow-up
analyses. Using mixed linear model analyses, no differences between the intervention and the
control group on the course of cTnT levels during the six-month period were observed (intentionto-treat analysis p=0.38, per-protocol analysis p=0.16).
Poster
Discussion: Despite the elevated basal levels of cTnT and the fact that subjects had not previously
participated in any structured exercise program, we found no evidence for an effect of a 24-week
resistance-type exercise training program on the course of cTnT levels. Possible limitations of our
study are the type of exercise and the physical state of the subjects, which precluded a higher
training frequency. The biweekly schedule was however sufficient to induce substantial
improvements of muscle strength and physical performance in this group. Future studies will
reveal whether more intensive and more prolonged interventions can beneficially affect the course
of basal troponin levels over time.
Staande poster, nr 26
28
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Alma Mingels
Klinisch chemicus in opleidng
Klinisch chemie
CARIM
Cardiac troponins in patients with chest discomfort: strong contribution of the heart and kidneys
E.P.M Cardinaels1, S. Altintas2, M.O Versteylen2, I.A Joosen2, L.J Jellema3, J.E. Wildberger4, H.J
Crijns2, O. Bekers1, M.P van Dieijen-Visser1, B.L. Kietselaer2,4*, A.M.A Mingels1*
1. Central Diagnostic Laboratory, Department of Clinical Chemistry, CARIM, MUMC, Maastricht
2. Department of Cardiology, CARIM, MUMC
3. Department of Clinical Chemistry, Gelre Hospitals, Apeldoorn
4. Department of Radiology, CARIM, MUMC
(*) both authors contributed equally
Background: Highly sensitive cardiac troponin (hs-cTn) concentrations are strong predictors of
acute cardiovascular events in patients with coronary artery disease. Hs-cTn are also known to be
elevated in many other conditions such as renal dysfunction. This complicates the interpretation of
baseline hs-cTn levels in the individual patient and adds up to the current confusion regarding hscTn.
Aim: Hs-cTnT and hs-cTnI concentrations were investigated on their association with cardiac
imaging measures, renal function and the incidence of cardiovascular events in patients with chest
discomfort.
Materials and Methods: A cohort of 1864 patients with stable chest discomfort underwent cardiac
computed tomographic angiography and echocardiography. Serum samples were analyzed using
hs-cTnT and hs-cTnI assays. Renal function was assessed by the estimated glomerular filtration rate
(eGFR), established from serum creatinine and/or cystatin C.
Results: Hs-cTn concentrations were significantly associated with cardiac imaging parameters, such
as coronary calcium score (hs-cTnT: stβ=0.100; hs-cTnI: stβ=0.122) and left ventricular mass (hscTnT: stβ=0.179; hs-cTnI: stβ=0.267) and were also strongly associated with eGFR (hs-cTnT: stβ=0.289; hs-cTnI: stβ=-0.222)(all p<0.001 and after adjustment for traditional risk factors).
Interestingly, renal function exerted no confounding effects on the association of cardiac
parameters with hs-cTn concentrations. Moreover, the association between eGFR and hs-cTn
remained equally as strong among patients with no (hs-cTnT: stβeGFR:-0.295; hs-cTnI: stβeGFR:0.228), non-obstructive (hs-cTnT: stβeGFR:-0.290; hs-cTnI: stβeGFR:-0.176) and obstructive
plaques (hs-cTnT: stβeGFR:-0.293; hs-cTnI: stβeGFR:-0.249) (all p<0.001). Still, hs-cTn
concentrations remained significant and comparable predictors for cardiovascular events.
Poster
Conclusion: In patients with chest discomfort, we identified cardiac pathology and renal function
as two separate reasons leading to troponin accumulation. Even after consideration of these
influences, hs-cTn remained important for the prediction of cardiovascular events.
Staande poster, nr 27
29
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Marjolein van der Poel
Arts-assistent in opleiding
Interne Geneeskunde
GROW
Quality of life more impaired in younger than in older DLBCL survivors
M.W.M. van der Poel1, S. Oerlemans2,3, H.C. Schouten1, F. Mols2,3, J.F.M. Pruijt4, H. Maas5 and L.V.
van de Poll-Franse2,3
1. Department of Internal Medicine, MUMC, Maastricht
2. Comprehensive Cancer Centre South, Eindhoven
3. Center of Research on Psychology in Somatic Diseases (CoRPS), Tilburg University, Tilburg
4. Department of Internal Medicine, Jeroen Bosch hospital, ‘s Hertogenbosch
5. Department of Geriatric Medicine, TweeSteden hospital, Tilburg
Purpose: The objective of this study was to compare Health-Related Quality of Life (HRQOL)
between Diffuse Large B-Cell Lymphoma (DLBCL) survivors of different age categories (18-59
years/ 60-75 years/ 76-85 years) and to compare their HRQOL with an age- and sex-matched
normative population.
Methods: The population-based Eindhoven Cancer Registry was used to select all patients
diagnosed with DLBCL from 1999 to 2010. Patients (n=363) were invited to complete the EORTC
QLQ-C30 questionnaire and 307 survivors responded (85%). Data from an age-and sex-matched
normative population (n=596) were used for comparison.
Results: DLBCL survivors aged 18-59 years scored better on physical functioning, quality of life,
appetite loss and constipation than survivors of 76-85 years old (all p<.05). Financial problems
more often occurred in survivors aged 18-59 years compared to survivors of 76-85 years old
(p<.01). Compared to the normative population, DLBCL survivors aged 18-59 years showed worse
scores on cognitive and social functioning and on dyspnea and financial problems (p<.01, large and
medium size effects). In survivors of the other age categories only differences with trivial or small
size effects were found.
Poster
Conclusion: Although younger DLBCL survivors have better HRQOL than older survivors, the
differences found between younger survivors and the normative population were the largest. This
suggests that having DLBCL has a greater impact on younger than on older survivors and that the
worse HRQOL observed in older DLBCL survivors in comparison with younger survivors is caused
mostly by age itself and not by the disease.
Staande poster, nr 28
30
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Poster
Roald Schnerr
Klinisch fyiscus in opleiding
Radiologie
Nee
Angiography and pulsatility of small intracranial vessels at 7 Tesla
J.F. Jansen1,2, P.A. Hofman1,2, J.E. Wildberger1,2,5, K. Uludag3, R.J. van Oostenbrugge2,4,5, W.H.
Backes1,2,5
1. Department of Radiology, MUMC, Maastricht
2. Research School for Mental Health & Neurosciences (MHeNS), MUMC, Maastricht
3. Maastricht Brain Imaging Centre (M-BIC), Maastricht
4. Department of Neurology, MUMC, Maastricht
5. Cardiovascular Research Institute Maastricht (CARIM), MUMC, Maastricht
Cerebral small vessel disease (SVD) is a term that covers a large range of neuropathological
disorders and related clinical symptoms which are considered to be related. Observable features of
SVD on MRI are white matter lesions, microbleeds as well as lacunar infarcts. However, the direct
pathology of small cerebral blood vessels in terms of occlusions or increased vessel wall stiffness
has not yet been visualized.
Our goal is to directly image small (perforating) arteries of the brain and to characterize their
condition. To reach the required spatial resolution we use high field MRI imaging (7 Tesla
Magnetom MRI, Siemens Healthcare, Erlangen, Germany). We apply three-dimensional high
spatial resolution (0.2 mm) arteriography and velocity-sensitized (phase-contrast) MR angiography.
At 7-Tesla we identify the lenticulostriate arteries (LSAs) in healthy volunteers and determine their
pulsatility for the first time.
Staande poster, nr 29
31
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Ellen Schoorel
Arts-assistent in opleiding
Interne Geneeskunde
GROW
Probability of vaginal birth after caesarean: do not ask the obstetrician
D.R.M. Hünen1, S.M.J. van Kuijk2, B.C.C Augustijn1, A. Kwee3, B.W.J Mol4, J.G. Nijhuis1, L.J.M. Smits2,
R.P.M.G Hermens5, H.C.J. Scheepers1
1. GROW-School for Oncology and Developmental Biology, Department of Obstetrics, MUMC,
Maastricht
2. Department of Epidemiology, Caphri School for Public Health and Primary Care, MUMC,
Maastricht
3. Department of Obstetrics, University Medical Centre Utrecht, Utrecht
4. Department of Obstetrics, Academic Medical Centre, Amsterstam
5. Scientific Institute for Quality of Healthcare (IQ healthcare), Radboud University Nijmegen
Medical Centre, Nijmegen
Background: There is an increasing number of women with a prior caesarean section (CS) who
deliver by elective repeat CS (ERCS) instead of intended vaginal birth after caesarean (VBAC). The
probability of successful VBAC plays a central role within risk estimation for mode of birth. We
aimed to determine predictive performance of clinicians for successful VBAC compared to a
prediction model and used actual clinical outcomes as a benchmark.
Methods: Clinical vignettes were constructed from actual patients with known outcomes of
intended VBAC (successful or failed). We randomly drew 450 clinical cases in order to create
vignettes. For each vignette, the probability of successful VBAC was estimated both by a clinician
and prediction model, and compared to the actual outcome. Discriminative performance was
assessed by obtaining the areas under the curve (AUC) of the receiver operator characteristic;
predictive performance was assessed by calibration per-risk-quantile and Hosmer-Lemeshow (H-L)
statistics.
Findings: Four-hundred-and-six vignettes were completed. For clinicians, the AUC was 0.60 (CI 95%
0.54 – 0.67) while the AUC for the prediction model was 0.70 (CI 95% 0.64 – 0.76) (p-value for
difference P<0.003). Calibration-per-risk-quantile showed that clinicians generally underestimated
the probability of successful intended VBAC below 70.0%. Calibration-per-risk-quantile for the
prediction model was good in all probability ranges. The corresponding H-L statistic confirmed lack
of fit for clinicians (p = 0.024), no evidence was found for lack of fit for the prediction model (p =
0.42).
Interpretation: Compared to the model, clinicians performed poorly with regard to prediction of
successful intended VBAC whilst the majority counsels with a self-derived probability. Hence, in
comparison to clinical judgement, the use of the VBAC prediction model can be beneficial.
Poster
Funding: The Netherlands Organisation for Health Research and Development
Staande poster, nr 30
32
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Jantien van der Heyden
Arts-assistent in opleiding
Gynaecologie en Obstetrie
GROW
Ontwikkeling op 2-jarige leeftijd na vroegtijdig gebroken vliezen: Follow-up van de PPROMEXIL
studie
C. Willekes1, A.L. van Baar2, A.G. van Wassenaer3, E. Pajkrt3, M.A. Oudijk4, M.M. Porath5, J.J.
Duvekot6, K.W.M. Bloemenkamp7, M. Groenewout8, M. Woiski9, J. van ’t Hooft3, B. Nij Bijvank10,
C.J. Bax11, J.M. Sikkema12, A.L.M. Mulder1, J.G. Nijhuis1, B.W.J. Mol13, D.P. van der Ham14
1. Maastricht Universitair Medisch Centrum, Maastricht,
2. Universiteit Utrecht, Utrecht.
3. Academisch Medisch Centrum, Amsterdam.
4. Universitair Medisch Centrum Utrecht, Utrecht.
5. Máxima Medisch Centrum, Veldhoven.
6. Erasmus Medisch Centrum, Rotterdam.
7. Leids Universitair Medisch Centrum, Leiden.
8. Universitair Medisch Centrum Groningen, Groningen.
9. Universitair Medisch Centrum St. Radboud, Nijmegen.
10.Isala, Zwolle.
11.VU Medisch Centrum, Amsterdam.
12. Ziekenhuisgroep Twente, Almelo.
13. School of Paediatrics and Reproductive Health, University of Adelaide, Australia.
14. Martini ziekenhuis Groningen.
Introductie: De PPROMEXIL studie liet zien dat bij vrouwen met laat preterm gebroken vliezen
inleiding van de baring niet leidt tot een betere neonatale uitkomst. In deze studie analyseren we
de neurologische- en gedragsontwikkeling van deze kinderen op 2-jarige leeftijd.
Materiaal & methoden: De originele PPROMEXIL studie includeerde vrouwen met preterm
gebroken vliezen tussen 34 en 37 weken zwangerschapsduur, die 24 uur na het breken van de
vliezen niet in partu waren. Deelnemende vrouwen werden gerandomiseerd tussen inleiding van
de baring of afwachtend beleid. Vrouwen die niet wilden deelnemen, konden in een
observationale studie worden geïncludeerd. Op het moment dat de kinderen twee jaar oud
werden, kregen de ouders de ‘ages and stages questionnaire (ASQ)’, de ‘child behavioral checklist
(CBCL)’ en een algemene vragenlijst toegestuurd.
Resultaten: We benaderden 551 van de 739 geschikte vrouwen voor follow-up (75%). Complete
follow-up werd verkregen van 320 kinderen (responspercentage 58%). In de inleidgroep had 14%
(n=16) van de kinderen een abnormale score in ≥1 domeinen van de ASQ, versus 26% (n=27) in de
groep met afwachtend beleid (relatief risico (RR) 0.55, 95% betrouwbaarheidsinterval (BI) 0.320.96; p-waarde 0.033). Voor de CBCL, werd een abnormale score in ≥1 domeinen gevonden in 13%
(n=15) in de inleidgroep en in 15% (n=16) in de groep met afwachtend beleid (RR 0.96, 95% BI
0.45-1.65; p-waarde 0.645).
Poster
Conclusie: Hoewel inleiding van de baring niet leidt tot verbetering van de korte termijn neonatale
uitkomst, reduceert het mogelijk de kans op ontwikkelingsmoeilijkheden op de leeftijd van 2 jaar
vergeleken met een afwachtend beleid.
Liggende poster, nr 31
33
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Desiree Rutten
PhD student
Cardiologie
CARIM
The relationship between depression and heart failure: findings from TIME-CHF
S. Bektas1, S. van Wijk1, O. Pfister2, H. Rickli3, S. Kiencke4, M. Gutmann5, M. Peter6, R. Schindler2,
H.P. Brunner-La Rocca1,2
1. Department of Cardiology, MUMC, Maastricht
2. Department of Cardiology, University Hospital Basel, Basel, Switzerland
3. Department of Cardiology, Kantonsspital St.Gallen, St.Gallen, Switzerland
4. Department of Cardiology, University Hospital Bruderholz, Bruderholz, Switzerland
5. Department of Cardiology, University Hospital Liestal, Liestal, Switzerland
6. Department of Cardiology, Kantonales Spital Sursee-Wolhusen, Wolhusen, Switzerland
Purpose: There is an increased risk of depression in patients (pts) who suffer from heart failure
(HF). However, risk factors for depression and effects of HF on depression over time are not well
known. Thus, we examined prevalence and risk factors of depression in HF pts and analyzed the
impact of HF on depression over time.
Methods: A post-hoc analysis of the TIME-CHF data was done. The 15-item Geriatric Depression
Scale (GDS-15) was used to identify depression in HF pts.
Results: 593 pts (age 77±8y) completed the GDS-15 at baseline, 382 pts at 18 months. At baseline,
moderate depression (GDS-15 score 6-9) was found in 21% and severe depression (score≥10) in
8%, respectively. Little factors influenced depression. Thus, fatigue (p=0.001), exercise intolerance
(p=0.001) and orthopnea (p<0.03) were the only independent factors, but many other factors such
as age, gender, co-morbidities, aetiology of HF, NYHA-class, NT-proBNP and LVEF were not. In
patients with depression, mortality was higher (p<0.04) and quality of life (QoL) was lower
(Minnesota questionnaire) than in those without (median [IQR] 56 [41-67] vs 34 [22-47], p<0.001).
Over time, patients with decline in depression were older, had a higher BMI and Charlson score (all
p<0.05) than those with improvement of depression. Severity of HF and its changes had no
influence.
Poster
Conclusion: Depression is common in HF pts, affecting both outcome and QoL. HF itself and its
changes over time had little influence on depression in this elderly HF cohort.
Liggende poster, 32
34
“Veelbelovende” studies
Naam (posternummer)
Pagina
Mark Hazebroek, Cardiologie (33)
36
Caroline Jaarsma, Cardiologie (34)
37
Sophie Joosten, Oncologie (35)
38
Tim de Ruijter, Oncologie (36)
39
Siamack Sabrkhany, Fysiologie (37)
40
Gaston Duijsens, Chirurgie (38)
41
Lisa Hillen, Pathologie (39)
42
Marjolein Kleppe, Gynaecologie en Obstetrie (40)
43
Marjan Klinkert, Chirurgie (41)
44
Ruben Vogels, Chirurgie (42)
45
Michiel de Wolf, Anaesthesie (43)
46
Dirk Schellekens, Chirurgie (44)
47
Martijn Smulders, Cardiologie (45)
48
Mathijs Vaessen, Oogheelkunde (46)
49
Nienke Visser, Oogheelkunde (47)
50
Laura Wielders, Oogheelkunde (48)
51
35
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Mark Hazebroek
PhD student
Cardiologie
CARIM
Predictors of improved LVRR and long-term prognosis in idiopathic dilated cardiomyopathy
patients
R. Dennert1, J. Franssen1, J. Verdonschot1, S. Heymans1
1. Department of Cardiology, MUMC, Maastricht
Purpose: To determine the clinical and endomyocardial biopsy (EMB)-derived predictors of left
ventricular reverse remodeling (LVRR) in patients with idiopathic dilated cardiomyopathy (IDCM).
Methods: Between January 1st 2004 and April 31st 2013 we enrolled 223 consecutive patients
(131 males, mean age 53±12, baseline LVEF 29±10%, symptom duration 8.5 [3.7-25] months) who
underwent endomyocardial biopsy (EMB) because of IDCM. IDCM diagnosis is based on the WHOcriteria and is defined by left ventricular (LV) ejection fraction (EF) <50% and LV end-diastolic
dimension (LVEDD)>33mm/m2 without coronary artery disease, primary valvular disease or other
known diseases causing DCM. EMB was performed to evaluate viral presence and load, cardiac
inflammation, and/or fibrosis. LVRR was defined as a LVEF increase of ≥10 absolute units or a LVEF
≥50% together with a decrease of indexed LVEDD of ≥10% or ≤33mm/m2. Primary endpoint was
LVRR after 12 months (range 6–18 months). Secondary endpoint was the composite of mortality or
heart transplantation (HTx) after a mean follow-up of 3.5±2.0 years.
Results: Viral presence was found in 166 (74%), Parvovirus B19 (PVB19) presence in 152 (68%),
PVB19>500 c/mcg DNA in 46 (21%), cardiac inflammation in 94 (42%) and LVRR in 95 (43%)
patients. Baseline univariate positive predictors of LVRR were previous history or presence of
hypertension (P=0.02), higher heart rate (P=0.01), shorter symptom duration (P=0.005), and lower
baseline LVEF (P<0.001). Cardiac inflammation, viral presence, PVB19 presence or PVB19>500
c/mcg DNA did not significantly influence LVRR (P=0.59, P=0.93, P=0.87, P=0.40, resp.).
Multivariable analysis revealed hypertension (P=0.01), lower baseline LVEF (P<0.001), and shorter
symptom duration (P=0.01) as independent predictors of LVRR. Overall long-term survival was
relatively good (93%). Presence of LVRR was the only significant predictor of improved long-term
prognosis as compared to patients without LVRR (2 (2%) vs 14 (11%); Log-rank P=0.02).
Poster
Conclusion: Both clinical and echocardiographic parameters in patients with IDCM provide a better
prediction of LVRR after 12 months as compared to EMB results. Moreover, LVRR was the only
significant predictor of improved long-term outcome.
Liggende poster, nr 33
36
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Caroline Jaarsma
Arts-assistent niet-in-opleiding
Cardiologie
CARIM
Prognostic value of non-invasive cardiac imaging in suspected or known coronary artery disease
M.W. Smulders1,3 (gedeelte 1e auteur), P.J. Nelemans4, S.C.A.M. Bekkers1,3, J. Bucerius3,5,6, T.
Leiner7, H.J. Crijns1,3, J.E. Wildberger2,3, S. Schalla1,3
1. Afdeling Cardiologie, MUMC, Maastricht
2. Afdeling Radiologie, MUMC, Maastricht
3. CARIM, Universiteit Maastricht, Maastricht
4. Afdeling Epidemiologie, Universiteit Maastricht, Maastricht
5. Afdeling Nucleaire geneeskunde, MUMC, Maastricht
6. Afdeling Nucleaire geneeskunde, Aken
7. Afdeling Radiologie, UMC, Utrecht
Background: Non-invasive cardiac imaging plays a crucial role in the diagnosis and management of
patients with suspected or known coronary artery disease (CAD). However, the prognostic value of
these non-invasive tests is less well established.
Objective: The current study aimed to evaluate the prognostic value of commonly used noninvasive imaging modalities (coronary computed tomographic angiography [CCTA], cardiovascular
magnetic resonance [CMR], stress echocardiography [Echo], exercise electrocardiographic testing
[EET], positron emission tomography [PET], and single-photon emission tomography [SPECT]) in
patients with suspected or known CAD.
Data Sources: Studies published between 1990 and 2012 identified by a PubMed search and
citation tracking were evaluated.
Study Selection: A study was eligible for inclusion if 1) a (derivable) annual event rate (AER) of nonfatal myocardial infarction (MI) and cardiac death for a negative test result or 2) a hazard ratio (HR)
was reported.
Data Extraction and Synthesis: Pooled estimates of AERs and HRs were calculated for each
imaging modality.
Main Outcomes and Measures: Non-fatal MI and cardiac death.
Results: A total of 143 studies (108.627 patients) were included: 25 CCTA, 17 CMR (11 perfusion, 4
wall-motion, and 2 both), 38 Echo, 4 PET, 35 SPECT, and 24 EET studies. For all 7 modalities, a
negative test result was associated with an excellent prognosis with a pooled AER of ≤1.5% for
cardiac death and MI (ranging from 0.3% for CCTA to 1.5% for Echo) during a mean follow-up of
2.6 ± 1.8 years. Conversely, a positive test was associated with an increased risk of future cardiac
death and MI, with summarized HR estimates ranging from 1.48 (95% confidence interval [CI]
0.94–2.32) for SPECT to 10.93 (95% CI 6.75–17.70) for CMR-perfusion. Since considerable
differences exist in the investigated study populations, direct comparisons of the modalities are
not appropriate.
Poster
Conclusions: A negative non-invasive cardiac imaging test conveys an excellent prognosis for
patients with suspected or known CAD, whereas a positive test indicates a substantially higher risk
of cardiac death and MI. The current meta-analysis provides a higher level of evidence that noninvasive cardiac imaging allows appropriate risk-stratification in these patients.
Liggende poster, nr 34
37
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Sophie Joosten
PhD student
Oncologie
GROW
Epigenetic marker development for a decision support system in renal cancer treatment with
sunitinib
P.M.M.B. Soetekouw2, M.J. Aarts2, M. van Engeland1,3, V.C.G. Tjan-Heijnen2
1. GROW, Research school for Oncology and Developmental Biology, MUMC, Maastricht
2. Division of Medical Oncology, Department of Internal Medicine, MUMC, Maastricht
3. Department of Pathology, MUMC, Maastricht
Rationale: Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer,
accounting for 75-80% of all cases. ccRCC is often asymptomatic, and approximately 30% of the
patients have metastasized disease at time of diagnosis with a 5-year survival rate of less than
10%. The introduction of targeted agents, such as sunitinib, in the treatment of ccRCC has made a
significant impact on the survival of these patients. However, response rates to sunitinib lie around
30%, suggesting intrinsic resistance in a large group of patients. Furthermore, disease progression
usually occurs after 6-15 months despite continuous treatment, indicating the development of
acquired resistance. There is a need for predictive markers to select patients that will benefit from
treatment with sunitinib. At this time, the choice of therapy is based on the Motzer criteria that
include clinical factors such as performance status, disease-free interval and several laboratory
variables. No molecular markers reflecting the biological behavior of the tumor are available for
predictive purposes, resulting in overtreatment of patients without benefit of the treatment. In
other tumor types, epigenetic silencing of specific genes has been shown to be able to predict the
response to treatment. O6-methylguanine methyl transferase (O6-MGMT) promoter CpG island
hypermethylation in glioblastoma predicts response to treatment with temozolomide and Werner
gene (WRN) hypermethylation in colorectal cancer has been associated with response to
irinotecan.
Therefore, we hypothesize that promoter methylation of genes involved in the sunitinib pathways
predict the response to sunitinib, providing possible predictive markers that can be implemented
to guide treatment decisions for advanced RCC treatment, thereby avoiding overtreatment of
these patients.
Objective: To explore the methylome of sunitinib-resistant and sunitinib-sensitive ccRCC, and to
identify novel biomarkers that can predict response to sunitinib. We will combine molecular
analysis and patient parameters to develop a decision support tool to guide sunitinib treatment of
ccRCC patients.
Poster
Study design: A translational, retrospective study to identify methylation markers that predict
response to sunitinib in patients with metastasized ccRCC. We will analyse tumor samples of 60
patients, of which 30 responders and 30 non-responders to sunitinib. An epigenome-wide
methylation specific next generation sequencing approach, based on methyl-binding protein 2
(MBD2)-DNA interactions, will be performed to detect differences in the methylation patterns of
sunitinib-sensitive and sunitinib-resistant ccRCC. Genes of interest found by this approach will be
validated using methylation specific PCR (MSP).
Also, we will integrate the clinical patient data (e.g. the Motzer criteria, disease free survival, and
overall survival) and molecular data to obtain a decision support tool to guide sunitinib treatment
in ccRCC patients.
Liggende poster, nr 35
38
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Tim de Ruijter
PhD student
Oncologie
GROW
Personalising a targeted therapy for anti-endocrine breast cancer treatment: The transDATA
study
J.P. de Hoon1,2, B. de Vries2,3, L. van Neste2,3, P.M.M.B. Soetekouw1,2, M. van Engeland2,3, J. Veeck1,2,
V.C. Tjan-Heijnen1,2
1. Division of Medical Oncology, Department of Internal Medicine, MUMC, Maastricht
2. GROW, School for Oncology and Developmental Biology, MUMC, Maastricht
3. Department of Pathology, MUMC, Maastricht
Introduction: Systemic breast cancer treatments usually produce outcome benefits only in a
fraction of patients while others rapidly relapse. One reason for varying treatment response is the
intertumoural heterogeneity of breast tumours as reflected by their numerous molecular
differences. In about 70% of breast cancers growth depends on hormonal signalling, which is
therapeutically addressed by either blockade of tumoural hormone receptor (HR) or reducing
circulating oestradiol levels. Based on genomics HR positive tumours cluster in two clinical
phenotypes, luminal A and luminal B breast cancer. Interestingly, early relapses and nonresponsiveness to anti-endocrine treatment is highly enriched in the luminal B subtype, yet the
reasons for this remain unknown.
DNA methylation profiling studies have shown a distinct DNA methylation pattern in luminal B
cancers, suggesting a correlation between DNA methylation and poor outcome with antiendocrine treatment. This study assesses methylation differences between luminal A/B breast
cancer in a systematic way, identifying predictive biomarkers for anastrozole and potential novel
targets in anastrozole-unresponsive tumours.
Methods: A biospecimen and data registry is set-up derived of a phase III multicenter study
trialling the duration of anastrozole (3 vs. 6 years) in n=1895 post-menopausal women with HR
positive breast cancer (DATA study). Formalin-fixed, paraffin-embedded (FFPE) tissues and clinical
data are collected for n=1,000 cases. A tissue microarray (TMA) will be constructed allowing for
clinical phenotyping. From this cohort, n=120 specimens will be defined consisting of luminal A/B
breast cancers exhibiting un/favourable outcome. After optimisation of DNA processing methods,
tumor DNA of these patients will be subjected to Infinium 450K arrays. Identified biomarkers of
anastrozole response, potential targets of alternative treatment and discriminators between
luminal A/B breast cancer will then be validated by immunohistochemistry as well as methylationspecific PCR in the total cohort (n=1,000).
Results: So far, we have centrally collected clinical data for all n=1,895 cases, and FFPE tissues for
n=288 cases. For TMA construction a fully automated arrayer (GrandMaster, 3D Histech) has been
obtained and installed. The methods of FFPE DNA extraction have been optimised for DNA
integrity, yield and purity by using different extraction kits (Qiagen, Promega) and tissue sources
(cores, sections). In collaboration with a service partner, the integrity of extracted FFPE DNA has
been further improved to a quality necessary for processing on Infinium 450K arrays.
Poster
Discussion: Here we present a study design for translational research in large clinical trials. The
described DNA optimisation efforts facilitate the use of FFPE DNA on array-based tissue
epigenomics. Having established the infrastructural requirements for a registry set-up will
empower further studies of this kind.
Liggende poster, nr 36
39
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Siamack Sabrkhany
PhD student
Department of Physiology
CARIM
Is platelet count confounding results in cancer biomarker research?
M.J.E. Kuijpers1,2, A.W. Griffioen3, M.G.A. oude Egbrink1,4
1. Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht
2. Department of Biochemistry, Maastricht University, Maastricht
3. Angiogenesis Laboratory, Dept. of Medical Oncology, VU Medical Center, Amsterdam
4. Department of Physiology, Maastricht University, Maastricht
Introduction: Angiogenesis regulatory proteins may be the key to the early detection of cancer.
Since the discovery of tumor angiogenesis as a rate-limiting step in cancer progression, attempts to
identify clinically relevant biomarkers in plasma and/or serum have not been successful. The
recent discovery of platelets as transporters of tumor angiogenesis regulatory proteins may
provide the solution. Platelets may not only serve as transporters but the total platelet count could
also be abnormal in patients with an active malignancy. Hence, we hypothesize that platelet count
is a confounder in biomarker research. To quantify the total blood growth factor content, we
measured various angiogenic and angiostatic factors in platelets and in platelet free plasma (PFP)
of a healthy control group. To determine platelet count dynamics in patients with cancer we
recorded platelet count of patients before, during and after chemotherapy or surgery and
compared this to platelet count of healthy individuals.
Methods: Patients with confirmed lung cancer (stage I-IV; n=65) were included in our study.
Exclusion criteria contained the use of a platelet-modifying drug or a blood transfusion in the
previous two weeks, the presence of non-healing wounds/ulcers, an active inflammatory disease,
or major surgery within 28 days prior to this study. Healthy individuals (n=20) were included as
controls.
All blood samples were collected from the antecubital vein in 3.2% sodium. A Beckman Coulter
Counter was used to quantify platelet count in all subjects. Platelets and PFP were isolated from
healthy individuals, after which concentrations of VEGF, PDGF, PF4 and CTAPIII were measured by
ELISA.
Results: A cancer stage dependent increase in platelet count of patients was observed in
comparison to healthy individuals (P<0.001). Also chemotherapy and surgery showed to
significantly affect platelet count (p<0.001). Quantification of different pro- and antiangiogenic
factors revealed that the growth factors levels in platelets were much higher than those in platelet
free plasma by factors of: VEGF (726-fold); PDGF (3930-fold); PF-4 (3144-fold); and CTAPIII (5466fold). Calculation of the circulating concentrations of these growth factors showed that the net
platelet growth factor content in whole blood is also higher than in PFP by factors of: VEGF (3fold); PDGF (6-fold); PF-4 (4.5-fold); and CTAPIII (10-fold).
Poster
Conclusion: We confirmed that platelets are an important source of angiogenesis related growth
factors in blood and that platelet count is dynamic in patients with cancer during chemotherapy
and surgery. These findings indicate that biomarker researchers should look beyond traditional
fluid sources of growth factors such as plasma or serum.
In order to include the potential variations in platelet count, it is imperative to record platelet
count in whole blood, so that measured concentrations per platelet can be used to calculate the
circulating levels in whole blood.
Liggende poster, nr 37
40
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Gaston Duijsens
WESP-student
Chirurgie
Nee
De kans op uitgebreide lymfekliermetastasering na een negatieve echo axilla bij het
mammacarcinoom
L.M. van Roozendaal1, M. Moossdorff1,2, R.M. Pijnappel3, S. Siesling4, M.B.I. Lobbes5, M.L. Smidt1
1. Afdeling Chirurgie, MUMC, Maastricht
2. GROW School for Oncology & Developmental Biology
3. Afdeling Radiologie, UMC Utrecht, Utrecht
4. Intergraal Kankercentrum Nederland (IKNL)
5. Afdeling Radiologie, MUMC, Maastricht
In Nederland bestaat preoperatieve lymfeklierstadiëring van mammacarcinoompatiënten uit
lichamelijk onderzoek en echografie van de axilla. Indien er klinisch geen verdachte lymfeklieren
worden gedetecteerd (cN0), volgt een schildwachtklierprocedure. Bij een positieve
schildwachtklier werd voorheen bij iedere patiënt een completerende okselklierdissectie (cOKD)
verricht. De ACOSOG-Z0011 studie toonde aan dat een cOKD veilig achterwege gelaten kan
worden bij cN0 mammacarcinoompatiënten met 1 of 2 schildwachtkliermetastasen, behandeld
middels lumpectomie, adjuvante radiotherapie en systemische therapie. Dit resulteerde in twijfel
ten aanzien van de waarde van de schildwachtklierprocedure. Dit heeft geleid tot het opzetten van
de BOOG 2013-08 studie. In deze studie zullen vrouwen met een cT1-2N0 mammacarcinoom
behandeld middels lumpectomie en radiotherapie van de mamma, gerandomiseerd worden voor
wel versus geen schildwachtklierprocedure. Het doel van deze studie is om te onderzoeken of een
negatieve echografie van de axilla accuraat is in het uitsluiten van uitgebreide
lymfekliermetastasering (≥4 lymfeklieren, pN2-3) bij cT1-2N0 mammacarcinoompatiënten
behandeld middels lumpectomie, schildwachtklierprocedure en radiotherapie van de mamma in
een Nederlands cohort.
Vrouwen met cT1-2N0 mammacarcinoom, gediagnosticeerd tussen 2011 en 2012 en behandeld
middels lumpectomie, schildwachtklierprocedure en radiotherapie, werden geïncludeerd. De data
evenals de centra werden geanonimiseerd aangeleverd door IKNL uit de Nederlandse
Kankerregistratie. De negatief voorspellende waarde voor het echografisch uitsluiten van
uitgebreide lymfekliermetastasen werd berekend voor ieder centrum afzonderlijk en de voor alle
centra tezamen.
In totaal werden 10.806 patiënten geïncludeerd uit 85 centra. Na een negatieve echografie van de
axilla toonde de schildwachtklier en/of het cOKD in 812 (7,5%) van de patiënten een
micrometastase (pN1mi), in 1247 (11,5%) 1-3 macrometastasen (pN1) en in 193 (1,8%) 4 of meer
macrometastasen (pN2-3). Dit resulteert in een mediane negatief voorspellende waarde voor een
negatieve echografie van de axilla voor het uitsluiten van pN2-3 van 98,6%. De negatief
voorspellende waarde tussen de deelnemende centra onderling varieert tussen 86.7%-100%.
Poster
Concluderend, een negatieve echografie van de axilla mist slechts bij 1.8% van de patiënten
uitgebreide lymfekliermetastasen (pN2-3) bij patiënten met een cT1-2N0 mammacarcinoom
behandeld middels lumpectomie, schildwachtklierprocedure en radiotherapie van de mamma.
Deze Nederlandse cohortstudie laat zien dat de echografie een betrouwbaar instrument is voor
het aantonen van uitgebreide lymfekliermetastasen, en derhalve accuraat patiënten kan
selecteren die voldoen aan de inclusiecriteria van de BOOG 13-08 studie.
Staande poster, nr 38
41
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Poster
Lisa Hillen
Arts-assistent in opleiding
Pathologie
Nee
Antiviral drugs to target malignant melanoma
A. Haugg1, A. zur Hausen1, V. Winnepenninckx¹
1. Department of Pathology, MUMC, Maastricht
Skin cancer is the second most common cancer in the Netherlands with malignant melanoma
(MM) as the major cause of death. Every year 4.500 to 5.000 patients are diagnosed with MM in
the Netherlands (data from IKNL). Of importance, death rates and incidence are increasing in
contrast to neighbouring countries. This difference might be owed to the different international
treatment regimens.
Early detection and complete surgical resection remains the golden therapeutic standard to reduce
mortality. In advanced disease, treatment options are limited and rarely curative. Therapy is
applied according to stage of disease which is based on histomorphological and clinical criteria.
Molecular profiling of MM has recently led to the development of targeted therapies with BRAF
inhibitors and combinations with MEK inhibitors. Unfortunately, a multitude of critical issues have
arisen with these new therapy options: I) development of tumor resistance to BRAF inhibitors, II)
high rate of considerable adverse effects and III) unsolved economic issues reflecting the high costs
of these targeted therapies. Finally, adequate treatment options for the remaining 52% MM
patients harbouring of non-mutated BRAF are lacking.
In the framework of drug repositioning, establishment of new drug combinations and patient
stratification we have conducted an in-vitro investigation, assessing the tumour-sensitivity to
classically used immunotherapeutic drugs alone and in combination with off-use (antiviral) drugs
for the treatment of MM. We selected a panel of BRAF mutated and BRAF wildtype human
melanoma cell lines. Anticancer sensitivity of interferon alpha 2b (IFNa2b) - an internationally
widely used immunomodulator in advanced stages of melanoma - was assessed in these cell lines.
IFNa2b is also used in other therapeutic regimes, e.g. renal cell carcinomas and Hepatitis C and B
virus infection. In this setting the triad of IFNa2b together with the antiviral drugs Ribavirin and
Proteaseinhibitors such as Saquinavir has shown beneficial therapeutic outcome compared to
monotherapy. Here we successfully tested the response of melanoma cell lines to immunotherapy
with IFNa2b and repositioning of an antiviral therapeutic triad of IFNa2b, Ribavirin and Saquinavir
in an anti-melanoma setting. Our experiments showed heterogeneous sensitivity to these drugs
alone and in combinatory experimental designs. The different drug responsiveness yielded into
two groups of MM cells revealing a Ribavirin sensitive group and a Ribavirin less-sensitive group,
whereby a reciprocal trend was seen regarding responsiveness to IFNa2b in melanoma cells. In line
with these findings, cytomorphological observations, in vitro characteristics and with one
exception also the BRAF mutational status could also be clustered to the preliminary identified
drug-related groups.
Concluding we could show responsiveness of antiviral drugs in the investigated human melanoma
cell lines. Furthermore stratification based on drug responsiveness, morphology and proliferative
activity could be developed in this study. The underlying molecular biology of the drug-related
groups remains to be elucidated in future experiments. Cell line modelling might be a potential
tool for personalizing treatment strategies in MM patients by identifying BRAF-inhibitor
responders and those patients benefiting from combination therapy or alternative chemo- and
immunotherapeutic reagents.
Staande poster, nr 39
42
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Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Marjolein Kleppe
Arts-assistent in opleiding
Gynaecologie en Obstetrie
GROW
Should appendectomy be performed in mucinous borderline tumours of the ovary?
J. Bruls2, T. van Gorp1,3, L. Massuger2, B.F.M. Slangen1,3, K.K. van de Vijver3,4, A.J. Kruse1,3, R.F.P.M.
Kruitwagen1,3
1. Department of Obstetrics and Gynecology, MUMC, Maastricht
2. Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre,
Nijmegen
3. GROW - School for Oncology and Developmental Biology, Maastricht
4. Department of Pathology, MUMC, Maastricht
Objectives: Appendectomy is often recommended in patients with mucinous borderline ovarian
tumours (mBOTs) based on studies suggesting that metastatic disease from a primary appendiceal
tumour can mimic mBOT. The present study assessed the incidence of mucinous neoplasms in the
appendix associated with the presence of mBOT.
Methods: A retrospective cohort study was performed in two university hospitals in the
Netherlands between 1990 and 2011. All patients with mBOT and/or a mucinous appendiceal
tumour were included.
Results: Of 127 patients included, 98 had a primary mBOT and 29 had a primary mucinous
appendiceal tumour.
In patients with an mBOT, the appendix was either removed at prior surgery (4%), resected as part
of the staging procedure showing no pathological abnormalities (13%), described as normal and
not resected (58%), or not described and not resected (25%). During a median follow-up period of
5 years (range 2−23), two patients developed a recurrence in which the appendix was not
involved.
In all patients with a primary mucinous tumour of the appendix, the appendix appeared abnormal
at the time of surgery. Eight of these patients (28%) were diagnosed with invasive ovarian
metastases.
A review of the literature including the cases from this study identified 510 mucinous ovarian
tumours with borderline features and 214 associated appendectomies, of which 4 (1.9%)
contained a primary appendiceal malignancy.
Poster
Conclusions: A thorough inspection of the appendix should be performed in patients with a
mucinous ovarian tumour with borderline features. An appendectomy should only be performed
when the appendix is macroscopically abnormal.
Staande poster, nr 40
43
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School
Titel
Co-auteurs
Affiliaties
Abstract
Marjan Klinkert
WESP-student
Chirurgie
Nee
Schildwachtkliermetastasering bij patiënten met de preoperatieve diagnose ductaal carcinoma
in situ
L.M. van Roozendaal1, M. Moossdorff1, J. Wesseling2, B. de Vries3,M.L. Smidt1
1. Afdeling Chirurgie, MUMC, Maastricht
2. Afdeling Pathologie, Antoni van Leeuwenhoek, Amsterdam
3. Afdeling Pathologie, MUMC, Maastricht
Het ductaal carcinoma in situ (DCIS) is een pre-maligniteit van de mamma met toegenomen
signalering sinds de introductie van de borstkankerscreening. Na de diagnose DCIS op histologisch
biopt wordt bij circa 20% van de patiënten alsnog een invasief carcinoom gevonden in het
resectiepreparaat. In de richtlijn wordt bij DCIS op biopt een schildwachtklierprocedure
geadviseerd in geval van mastectomie, leeftijd <55 jaar, solide component op mammografie,
verdenking op invasie en matig of slechte gedifferentieerde DCIS. Bij het invasieve
mammacarcinoom bestaat de trend naar vermindering van de (chirurgische) behandeling van de
oksel, DCIS is tot dusver aan deze trend ontsnapt. Het doel van deze inventarisatie-studie was te
onderzoeken
hoeveel
patiënten
met
de
preoperatieve
diagnose
DCIS
een
schildwachtkliermetastase hadden.
Uit de lokale PALGA-database werden alle patiënten met alleen DCIS op biopt (periode 2008-2013)
verzameld. Patiënten met tevens een ipsilateraal invasief mammacarcinoom op biopt werden
geëxcludeerd. Klinische, radiologische en pathologische data van iedere patiënt werden
verzameld.
In totaal werden 161 patiënten geïncludeerd, waarvan 108 (67%) een schildwachtklierprocedure
ondergingen. De schildwachtklier(en) waren negatief (pN0) bij 95/108 patiënten, 11/108 hadden
geïsoleerde tumorcellen (pN0i+) en 2/108 hadden een micrometastase (pN1mi). Er werden geen
macrometastasen aangetroffen. In totaal werd bij 133/161 patiënten alleen DCIS in het
resectiepreparaat aangetroffen en bij 28/161 (17%) naast DCIS ook een invasief carcinoom. Een
schildwachtklierbiopsie was verricht bij 83/133 patiënten met alleen DCIS, resulterend in 75/83
pN0 en 8/83 pN0i+. Van de 28 patiënten met DCIS en een invasieve component hadden 25
patiënten een schildwachtklierbiopsie ondergaan. Pathologie toonde bij 20/25 patiënten pN0, bij
3/25 pN0i+ en bij 2/25 pN1mi. Eén van de twee patiënten met pN1mi had mammografisch een
kalkhoudend gebied van 90mm en de diagnose DCIS graad 2 na histologisch biopt. Het
mastectomiepreparaat toonde 105mm DCIS graad 3 waarin 90mm invasief ductaal carcinoom
(IDC) graad 3. Een completerende okselklierdissectie werd niet verricht. De tweede patiënt met
pN1mi had een niet-afwijkend mammogram, een massa op echografie en de diagnose DCIS graad
3 na histologisch biopt. Het lumpectomiepreparaat toonde 39mm DCIS graad 2 waarin 4mm IDC
graad 1. De completerende okselklierdissectie (18 lymfeklieren) toonde een tweede
micrometastase.
Poster
Concluderend blijkt uit deze inventarisatiestudie dat bij 17% van de patiënten met de
preoperatieve diagnose DCIS alsnog een invasieve component werd gevonden in het
resectiepreparaat, vergelijkbaar met beschikbare literatuur. Onafhankelijk van deze conversie
toont de schildwachtklierprocedure slechts in 1,5% een metastase. De schildwachtklierprocedure
lijkt derhalve meer overbehandeling dan goede zorg. Het aantal patiënten zal worden uitgebreid
met data uit meerdere Nederlandse centra.
Staande poster, nr 41
44
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Co-auteurs
Affiliaties
Abstract
Ruben Vogels
PhD student
Chirurgie
NUTRIM
Biocompatibility and mechanical analysis of a new elastic polyurethane suture
A. Lambertz1, P. Schuster3, S. Jockenhoevel3, N.D. Bouvy2, C. Disselhorst-Klug4, U.P. Neumann1, U.
Klinge1, C.D. Klink1
1. Department of General, Visceral and Transplantation Surgery, RWTH Aachen, Germany
2. Department of General Surgery, MUMC, Maastricht
3. Institut fuer Textiltechnik at RWTH Aachen University, Germany
4. Applied Medical Engineering, Helmholtz Institute, RWTH Aachen, Germany
Background: Current surgical threads are mostly made of non-elastic materials like polypropylene.
As a suture material these rigid treads can cause wound comlications due to compression of tissue
with subsequent tissue damage. Elastic materials could reduce these complications by adapting
the thread length and thus reduce tension. Aim of this study was to evaluate the biocompatibility
of an elastic Thermoplastic Polycarbonate Urethane (PCU) thread in a rat model and the
biomechanical characteristics of PCU sutures in vivo in a pig model.
Methods: PCU and polypropylene threads (2-0 USP size) were implanted subcutaneously in 48 rats
for 7 or 21 days; every rat received both suture types. The extent of inflammatory tissue response
was assessed and immunohistochemistry was performed for macrophages (CD68), apoptosis, and
proliferation (KI67).
Subsequently, tension experiments were performed in a pig. Suture tension of knotted
polypropylene and PCU sutures was measured during the first 30 minutes after implantation.
Results: In a rat model the extent of foreign body reaction between PCU and PP sutures was
comparable. Significantly less macrophages were found in the granuloma of PCU sutures after 21
days (p=0,015). The amount of apoptotic cells was significantly less in PCU groups at both
timepoints (p<0,05).
The tension experiments show a significantly reduced peak tension in the PCU group with a
significant reduction in tension loss in the first minute when compared to polypropylene (p<0,05).
After 30 minutes both materials have highly comparable residual suture tensions.
Poster
Conclusions: Elastic PCU sutures show excellent biocompatibility and the elastic nature of the
material leads to superior tension curves for knotted sutures. The use of this material in surgical
practice as suture material or as basis for other scaffolds requiring elasticity should be evaluated.
Staande poster, nr 42
45
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Abstract
Michiel de Wolf
Arts-assistent in opleiding
Anaesthesie
Nee
Emergency ventilation through an airway exchange catheter using Ventrain: an animal study
R. Gottschall1, N. Preussler1, B. Preussler1, D. Enk2
1. Afdeling Anaesthesie, Universitair Ziekenhuis Jena, Jena, Duitsland
2. Afdeling Anaesthesie, MUMC, Maastricht
The ‘at-risk’ algorithm of the DAS extubation guidelines includes an airway exchange catheter
(AEC)-assisted extubation [1]. Flow resistance of a small-bore AEC demands a high pressure oxygen
source, but injecting compressed oxygen through an AEC in an airway emergency bears the risks of
barotrauma, haemodynamic deterioration and even death. To minimize these hazards expiratory
times have to be prolonged leading to low minute volumes. The Ventrain (Dolphys Medical,
Eindhoven, The Netherlands) is a flow-regulated, manually operated ejector ventilator capable of
assisting expiration by jet-flow generated suction [2]. This device has been shown to achieve
minute volumes of about 7.5 L/min through a 100 cm long, 3 mm inner diameter (ID) AEC in-vitro
[3]. The goal of our study was to investigate the efficacy of Ventrain connected to this AEC on reoxygenation and ventilation in an acute hypoxic animal model with a simulated completely
obstructed airway.
Methods: With approval of the local animal welfare committee six pigs (26.5-29.8 kg) were
anaesthetised and pressure-controlled normoventilated (PCV) via a cuffed endotracheal tube with
an FiO2 of 0.4. After placement of monitoring lines and baseline recordings the ventilator was
disconnected. During apnoea the 100 cm long, 3 mm ID AEC was placed in the distal trachea
through a bronchoscopy adapter simulating complete upper airway obstruction. When peripheral
saturation reading revealed an oxygen saturation of 70 % (“0”), ventilation with Ventrain was
started at an oxygen flow of 15 L/min, a frequency of 30/min, and an inspiration/expiration ratio of
1 : 1 while continuously observing chest movements. Arterial blood samples were collected at
baseline, “0”, and during ten minutes after resumption of ventilation.
Results: The minute volume necessary for normoventilation during PCV was 5.1 [3.6-6.3] L/min. No
signs of barotrauma or haemodynamic deterioration were noted. The data are presented as
median [range].
Arterial bloodgass samling revealed oxygen saturations to have dropped to 47.3% [29.6-56.9]
during apnoea and pCO2 to have risen to 59.5 [51.7-63.3] mmHg. After commencement of
ventilation using Ventrain, oxygen saturations and pCO2 levels returned to baseline within one
minute.
Discussion: Ventilation with Ventrain through small-bore AEC’s ensures rapid re-oxygenation and
sufficient ventilation. As (almost completely) decompressed oxygen is insufflated and expiration
can be assisted, Ventrain overcomes the drawbacks of jet ventilation through an AEC when
managing airway obstruction after extubation.
Conflicts of interest: D. Enk is the inventor of the Ventrain and receives royalty payments from
Dolphys Medical.
Poster
References:
1. Popat M et al.. Anaesthesia 2012; 67: 318-40.
2. Hamaekers A, Borg P, Enk D. British Journal of Anaesthesia 2012; 108: 1017-21.
3. Dias EM et al.. European Journal of Anaesthesiology 2012; 29 (Suppl. 50): 239-40.
Staande poster, 43
46
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Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Dirk Schellekens
PhD student
Chirurgie
NUTRIM
SM22 in plasma and urine reflects transmural ischemic injury of the intestines
K. Reisinger1,2, J. Derikx1,2, K. Lenaerts1,2, M. Poeze1,2, W.Buurman2, K. Dejong1,2
1. Department of Surgery, MUMC, Maastricht
2. NUTRIM School for Nutrition, Toxicology and Metabolism, MUMC, Maastricht
Acute mesenteric ischemia is an abdominal emergency requiring rapid diagnosis and treatment
since the duration of ischemia is the most important determinant of outcome. Current biomarkers
only detect ischemic mucosal injury, whereas differentiation between mucosal and transmural
ischemic intestinal damage is imperative because only the later needs emergency surgery. A
previous study showed that SM22 (22-kDa protein exclusively expressed in visceral smooth muscle
tissue) is a potential biomarker for intestinal muscularis externa injury. Our aim is to study SM22
release test characteristics and its usefulness in differentiation between mucosal and transmural
damage in patients.
SM22 release was investigated in rats subjected to mesenteric ischemia by 0, 2, 4, 6, 8, 12, 24
hours jejunal blood supply ligation. One day after laparotomy blood, urine and tissue was sampled
and SM22 concentrations were measured using a newly build ELISA. Organ-specific SM22 release
and clearance was studied in blood drawn from portal, hepatic, renal vein and a (radial) artery in
rats and in 10 patients undergoing major upper abdominal surgery. SM22 and I-FABP (a sensitive
marker to study enterocyte damage) were quantified in plasma of 12 patients with proven
intestinal ischemia and 50 healthy volunteers. Tissue sections were stained with
haematoxylin/eosin (HE) and SM22.
In rats, histological assessment revealed degeneration of the mucosa and necrosis of the muscular
layers of the intestinal wall in jejunum exposed to 24h ischemia as compared to control. Staining
for SM22 revealed a decrease in staining intensity or even a total absence of SM22 protein in the
muscular layers after 24h ischemia. Baseline plasma SM22 levels were ≤0.1 ng/ml in all animals.
After ischemia, SM22 plasma levels continued to rise significantly for the 24h period compared to
control (p < 0.05). Urinary SM22 concentrations were significantly higher in rats with intestinal
ischemia compared to control (p < 0.05). Transorgan measurements showed that SM22 was
specifically released from the intestines and removed from circulation by the kidneys, resulting in a
plasma half-life of about 16 minutes in rats and 22 minutes in man. SM22 levels were significantly
higher in patients with histopathological proven transmural infarction compared to patients with
only ischemic mucosal injury and healthy controls (5.9 ng/ml vs 0.6 ng/ml and 0.4 ng/ml (p <
0.001), respectively).
Poster
In conclusion, SM22 is released into the circulation after severe intestinal ischemic injury and is
potentially useful as a marker for the detection of transmural injury during intestinal ischemia.
Liggende poster, nr 44
47
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Martijn Smulders
PhD student
Cardiologie
CARIM
Utility of CMR for Differentiating Acute From Chronic Myocardial Infarction
S.C.A.M. Bekkers1, H.W. Kim2,3, L.M.R.van Assche2,3, M.A. Parker2,3, R.J. Kim2,3,4
1. Department of Cardiology, MUMC, Maastricht
2. Duke Cardiovascular Magnetic Resonance Center, Duke University Medical Center, NC, USA
3. Division of Cardiology, Duke University Medical Center, NC, USA
4. Department of Radiology, Duke University Medical Center, NC, USA
Introduction: Published reports have concluded that T2-weighted CMR (T2W-CMR) is highly
accurate in differentiating acute from chronic MI. However, the majority of patients investigated
had infarcts <1-week-old or >6-months-old. Clinically, it would be vital to distinguish an infarct a
few days versus a few months old, however some studies suggest T2W-CMR edema may persist
for months [Heart 2001;85:639-42, AHJ 2007;154:929-36], possibly precluding this differentiation.
Purpose: The study primary aim was to assess the prevalence of T2W-CMR edema across a range
of infarct ages and to assess its accuracy with and without the inclusion of intermediate-aged
infarcts. Secondary aims were to evaluate other CMR markers of acute MI, and to compare image
quality of CMR techniques.
Methods: 221 CMR studies were performed at various time points post-MI in 117 first STelevation-MI patients enrolled prospectively and consecutively from two CMR centers.
Prespecified markers of "acute" MI were hyperintensity on T2W-CMR, microvascular obstruction
(MO) on delayed-enhancement-CMR (DE-CMR), and increased end-diastolic wall thickness
(Increased-EDWT, >150% of remote measured quantitatively) on cine-CMR. Images were scored
blinded to identity and all clinical information. Individual CMR techniques were interpreted
separately. Image quality and frequency/severity of artifacts were also evaluated.
Results: Mean age was 58±11 years; 84% were men. Prevalence of T2W-CMR hyperintensity
steadily decreased for older infarcts starting 1-month post-MI but was still substantial for 1-6
month-old infarcts (Panel A). Even after requiring T2W-hyperintensity to be in the correct infarctrelated-artery territory (to reduce false positives post-hoc) prevalence was 59% (1-3 months), 32%
(3-6 months), and 4% (>6-months). Individually, prevalence of MO (57%) and Increased-EDWT
(45%) was low for <1-week-old infarcts but substantially increased in combination (77%, p<0.001)
while retaining low prevalence for intermediate-aged infarcts (Panel B). Defining acute and chronic
MI as <1 and ≥1-month-old, T2W sensitivity and specificity were 88% and 66%. For combined
DE/Cine-CMR this was 74% and 97%. When removing patients with 1-6-month-old infarcts, T2WCMR specificity increased to 83% (p<0.01). One-third of T2W-images were graded poor, nearly 5fold higher than cine or DE-CMR (Panel C), as 52% and 92% of T2W-images had some myocardial
signal drop-out (2.4±1.8 segments of 17-segments) and/or slow flow (7±3.5 segments).
Poster
Conclusion: Sensitivity of T2W-CMR to detect <1-month-old infarcts is moderately high, but
because edema may persist, T2W-CMR is less specific when including intermediate-aged infarcts
(1-6 months). Although mildly less sensitive, the presence of MO or increased-EDWT on DE/cineCMR is very specific, and unlike T2W-CMR image quality is rarely poor.
Liggende poster, nr 45
48
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Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Mathijs Vaessen
Arts-assistent in opleiding
Oogheelkunde
Nee
Opsporing van glaucoom: onderzoek en verwijzing door extramurale optometristen
H.J.M Beckers1, A. Coops1,2, H.G. Lemij3, N.M. Jansonius4, C.A.B. Webers1
1. Afdeling Oogheelkunde, MUMC, Maastricht
2. Optometristen Vereniging Nederland
3. Afdeling Oogheelkunde, Oogziekenhuis Rotterdam
4. Afdeling Oogheelkunde, Universitair Medisch Centrum Groningen
Doel: Het vaststellen van de diagnostische accuratesse en uitvoerbaarheid van de OVN
glaucoomrichtlijn voor extramurale optometristen.
Methode: Alle opeenvolgende cliënten (≥45 jaar) van participerende optometriepraktijken komen
in aanmerking voor glaucoomonderzoek volgens een ‘intent to examine’ principe. Primaire
uitkomstmaten zijn het percentage (correct) uitgevoerde onderzoeken en het percentage
verwezen cliënten. Verwezen cliënten worden in de tweede lijn geclassificeerd als
glaucoompatiënt, glaucoom suspect of anderszins.
Voorlopige resultaten: 868 van de eerste 1379 cliënten (63%) werden onderzocht. De richtlijn
werd in 742 van de 868 gevallen (85%) correct opgevolgd. Zesenzestig cliënten werden verwezen
waarvan 43 (65%) geclassificeerd werden als glaucoompatiënt of glaucoom suspect.
Poster
Conclusie: De richtlijn heeft een positief voorspellende waarde van 65%. Voor een effectievere
opsporing van glaucoom zou het percentage onderzochte cliënten hoger moeten liggen.
Liggende poster, nr 46
49
Naam
Functie
Specialisme
School
Titel
Co-auteurs
Affiliaties
Abstract
Nienke Visser
Arts-assistent in opleiding
Oogheelkunde
MHeNS
Toric vs monofocal intraocular lens implantation in patients with cataract and corneal
astigmatism
H.J.M. Beckers1, N.J.C. Bauer1, S.T.J.M. Gast1, C.A.B. Webers1, R.M.M.A. Nuijts1
1. Afdeling Oogheelkunde, MUMC, Maastricht
Purpose: To compare toric and monofocal intraocular lens (IOL) implantation in patients with
cataract and corneal astigmatism.
Setting: University Eye Clinic Maastricht, the Netherlands.
Method: Eighty-six patients with bilateral cataract and at least 1.25 D of corneal astigmatism were
randomized for either bilateral toric or bilateral monofocal IOL implantation. Six months
postoperatively the uncorrected and best-corrected distance visual acuity (UDVA and BDVA),
refraction, misalignment, spectacle use for distance vision and complications were evaluated.
Results: Postoperatively, the UDVA in the toric and monofocal group was 0.06 ± 0.14 and 0.21 ±
0.16 LogMAR, respectively (P<0.001). The BDVA was comparable in both groups: 0.00 ± 0.11
LogMAR in the toric group and -0.01 ± 0.09 LogMAR in the monofocal group(P>0.05). Seventy
percent of patients with toric IOLs achieved a Snellen UDVA of at least 20/25, compared to 30% of
patients with monofocal IOLs (P< 0.001). A refractive cylinder of 1.0 D or less was achieved in 74%
of patients in the toric group and 30% of patients in the monofocal group (P<0.001). Seventy-eight
percent of patients with toric IOLs reported being spectacle independent for distance vision,
compared to 22% of patients with monofocal IOLs (P<0.001). Mean misalignment of toric IOLs was
3.6 ± 3.2 degrees and IOL repositioning was required in 1 patient.
Poster
Conclusion: Toric IOLs result in a better UDVA, a lower refractive astigmatism and a higher
spectacle independence for distance vision compared to monofocal IOLs.
Liggende poster, nr 47
50
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Titel
Co-auteurs
Affiliaties
Abstract
Laura Wielders
PhD student
Oogheelkunde
Nee
The ESCRS PREMED study: PREvention of Macular EDema after cataract surgery
L.H.P. Wielders1, J.S.A.G. Schouten1,2, F.J.H.M. van den Biggelaar1, B. Winkens3, R.M.M.A. Nuijts1,2
1. Universiteitskliniek voor Oogheelkunde, MUMC, Maastricht
2. Regiopraktijk Oogheelkunde, Atrium Medisch Centrum Parkstad, Heerlen
3. Afdeling Methodologie en Statistiek, Universiteit Maastricht, Maastricht
Introductie: Jaarlijks worden er in Nederland ongeveer 150.000 cataractoperaties uitgevoerd.
Cystoid maculaoedeem (CMO) is een van de meest voorkomende oorzaken van visusvermindering
na cataractchirurgie. Gebruik makend van Optical Coherence Tomography (OCT) kan de diagnose
CMO na een cataractoperatie worden gesteld bij 4-20% van de gezonde patiënten. 0-5,8% van de
patiënten ontwikkelt hierdoor ook daadwerkelijk een verminderde postoperatieve visus. Bij
patiënten met diabetes mellitus (DM) ligt deze incidentie veel hoger: tot wel 56% van deze
patiënten ontwikkelt klinisch significant CMO na een cataractoperatie.
Het ontstaan van CMO beïnvloedt in grote mate het herstel na een cataractoperatie. Daarom zijn
er de laatste jaren veel verschillende preventieve behandelingen voorgesteld om het ontstaan van
CMO na cataractchirurgie te voorkomen. Helaas is er tot op heden nog geen gerandomiseerde,
gecontroleerde studie uitgevoerd, waarin deze preventieve strategieën worden vergeleken.
Doel: Het evalueren van verschillende behandelingen ter preventie van CMO na cataractchirurgie
bij patiënten met en zonder DM.
Methoden: Aan deze Europese multicenterstudie zullen in totaal 1050 patiënten zonder DM en
300 patiënten met DM deelnemen. De studie wordt gecoördineerd door de Universiteitskliniek
voor Oogheelkunde Maastricht UMC en wordt gefinancierd door de European Society of Cataract
& Refractive Surgeons (ESCRS).
Patiënten ondergaan een reguliere cataractextractie met plaatsing van een intraoculaire lens.
Patiënten zonder DM worden behandeld met non-steroidal anti-inflammatory drug (NSAID)
oogdruppels (bromfenac), corticosteroïd oogdruppels (dexamethason) of een combinatie van
beide. Patiënten met DM worden behandeld met beide oogdruppels en worden vervolgens
gerandomiseerd over een aantal peroperatieve behandelingsstrategieën, namelijk een
subconjunctivale corticosteroïd injectie (triamcinolon acetonide), een intravitreale anti-vascular
endothelial growth factor (anti-VEGF) injectie (bevacizumab) of een combinatie van beide. Een
controlegroep zal enkel met bromfenac en dexamethason oogdruppels worden behandeld.
De primaire uitkomstmaat van deze studie is de verandering in maculadikte zes weken
postoperatief, in vergelijking met preoperatief. Verder zal het effect van deze behandelingen op de
best gecorrigeerde vertevisus (logMAR) en kwaliteit van leven worden beoordeeld.
Resultaten: Tot nu toe werden er 91 patiënten geïncludeerd in de studie. Definitieve resultaten
van de PREMED study worden verwacht in 2015.
Poster
Discussie & Conclusie: Aan de hand van de resultaten van deze studie hopen wij
wetenschappelijke aanbevelingen te kunnen doen, die zullen leiden tot een kosteneffectieve
preventieve behandeling van CMO na cataractchirurgie bij patiënten met en zonder DM.
Liggende poster, nr 48
51
Inhoudsopgave
Naam (posternummer)
Pagina
Maikel Bakens, Chirurgie (19)
21
Sema Bektas, Cardiologie (17, 18)
19,20
Jurriaan Brekelmans, Oogheelkunde (1)
2
Dominique Disseldorp, Chirurgie (20, 21)
22, 23
Elleke Dresen, Radiologie (5)
6
Gaston Duijsens, Chirurgie (38)
41
Mari Elshout, Oogheelkunde (2)
3
Mark Hazebroek, Cardiologie (33)
36
Miriam van Heeswijk, Radiologie (6)
7
Jantien van der Heyden, Gynaecologie en Obstetrie (31)
33
Judith Hilderink, Interne Geneeskunde (22)
24
Lisa Hillen, Pathologie (39)
42
Inca Hundscheid, Chirurgie (23)
25
Caroline Jaarsma, Cardiologie (34)
37
Monique de Jong, Keel-, Neus-, en Oorheelkunde (24)
26
Soraya Jonker, Oogheelkunde (7)
8
Sophie Joosten, Oncologie (35)
38
Cécile Kicken, Anaesthesie (3)
4
Marjolein Kleppe, Gynaecologie en Obstetrie (40)
43
Marjan Klinkert, Chirurgie (41)
44
Madeleine Kok, Radiologie (25)
27
Noreen van der Linden, Klinische Chemie (26)
28
Esther Martens, Klinische neurofysiologie (8, 9)
9, 10
Milou Martens, Chirurgie (10)
11
Alma Mingels, Klinische Chemie (27)
29
Elwin Mommers, Chirurgie (11)
12
Givan Paulus, Chirurgie (12)
13
Marjolein van der Poel, Interne Geneeskunde (28)
30
Lucas Ricker, Oogheelkunde (4)
5
Hellen Römkens, Oogheelkunde (13)
14
Tim de Ruijter, (36)
39
Desiree Rutten, Cardiologie (32)
34
Siamack Sabrkhany, Fysiologie (37)
40
52
Karin Sanders, Longziekten (14)
15
Dirk Schellekens, Chirurgie (44)
47
Roald Schnerr, Radiologie (29)
31
Ellen Schoorel, Interne Geneeskunde (30)
32
Martijn Smulders, Cardiologie (45)
48
Mathijs Vaessen, Oogheelkunde (46)
49
Koen Vermorgen, Oogheelkunde (15)
16
Nienke Visser, Oogheelkunde (47)
50
Ruben Vogels, Chirurgie (42)
45
Laura Wielders, Oogheelkunde (48)
51
Michiel de Wolf, Anaesthesie (43)
46
Eleana Zhang, Neurologie (16)
17
53