14 research outputs found
Single beat 3D echocardiography for the assessment of right ventricular dimension and function after endurance exercise: Intraindividual comparison with magnetic resonance imaging
<p>Abstract</p> <p>Background</p> <p>Our study compares new single beat 3D echocardiography (sb3DE) to cardiovascular magnetic resonance imaging (CMR) for the measurement of right ventricular (RV) dimension and function immediately after a 30 km run. This is to validate sb3DE against the "gold standard" CMR and to bring new insights into acute changes of RV dimension and function after endurance exercise.</p> <p>Methods</p> <p>21 non-elite male marathon runners were examined by sb3DE (Siemens ACUSON SC2000, matrix transducer 4Z1c, volume rates 10-29/s), CMR (Siemens Magnetom Avanto, 1,5 Tesla) and blood tests before and immediately after each athlete ran 30 km. The runners were not allowed to rehydrate after the race. The order of sb3DE and CMR examination was randomized.</p> <p>Results</p> <p>Sb3DE for the acquisition of RV dimension and function was feasible in all subjects. The decrease in mean body weight and the significant increase in hematocrit indicated dehydration. RV dimensions measured by CMR were consistently larger than measured by sb3DE.</p> <p>Neither sb3DE nor CMR showed a significant difference in the RV ejection fraction before and after exercise. CMR demonstrated a significant decrease in RV dimensions. Measured by sb3DE, this decrease of RV volumes was not significant.</p> <p>Conclusion</p> <p>First, both methods agree well in the acquisition of systolic RV function. The dimensions of the RV measured by CMR are larger than measured by sb3DE. After exercise, the RV volumes decrease significantly when measured by CMR compared to baseline.</p> <p>Second, endurance exercise seems not to induce acute RV dysfunction in athletes without rehydration.</p
Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries
Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely
Association studies of variants in ATG16L1 and Myosin IXb in patients with inflammatory bowel disease
In dieser Arbeit wurden fĂŒnf genetische VerĂ€nderungen an 910 CED-Patienten und
707 Kontrollen mittels Schmelzkurvenanalyse untersucht. Dabei wurde eine
Variante im ATG16L1-Gen (c.898G>A; p.T300A; rs2241880), die in zwei
genomweiten Studien als Risikofaktor beschrieben worden ist, und vier
Varianten im MYO9B (rs1545620 in Exon 20 [p.S1011A], rs1457092 in Intron 20,
rs2305764 in Intron 28 und rs2279002 in Intron 32), fĂŒr die eine signifikante
Assoziation mit der Zöliakie berichtet wurde, untersucht. Im Rahmen dieser
Arbeit konnte die signifikante Assoziation der ATG16L1-Variante mit dem MC fĂŒr
die deutsche Population bestĂ€tigt, und fĂŒr die ungarische, sowie
niederlĂ€ndsche erstmals nachgewiesen werden. DarĂŒber hinaus konnte gezeigt
werden, dass ATG16L1 einen unabhĂ€ngigen SuszeptibilitĂ€tsfaktor fĂŒr den MC
darstellt und keine Gen-Gen-Interaktionen mit bereits etablierten
CARD15-Varianten bestehen. CARD15 ist ein Bestandteil des angeborenen
Immunsystems. Das aktuelle pathogenetische Modell der Entstehung der CED geht
von einer unangemessen heftigen Reaktion des angeborenen Immunsystems auf
intraluminale Antigene im Gastrointestinaltrakt aus. ATG16L1 ist ein wichtiger
Bestandteil des Autophagosoms, das intrazellulÀre Zellbestandteile und
Krankheitserreger zersetzt. Die Fragmente werden durch Exozytose an
Immunzellen prÀsentiert. Eine beeintrÀchtigte Autophagozytose kann daher das
Gleichgewicht zwischen Immuntoleranz und Inflammation beeinflussen und damit
das derzeit gĂŒltige VerstĂ€ndnis ĂŒber die Entstehung der CED unterstĂŒtzen.
Unter den untersuchten vier MYO9B-Varianten konnte lediglich in der
niederlÀndischen Population eine Assoziation von rs2305764 in Intron 28
gezeigt werden. Da MYO9B als Bestandteil des Zytoskeletts Zell-Zell-
Verbindungen beeinflussen kann, wurden PermeabilitÀtsuntersuchungen von
Erkrankten und gesunden Kontrollen ausgewertet. Dabei konnte gezeigt werden,
dass drei genetische VerÀnderungen im MYO9B mit einer gesteigerten
gastroduodenalen und intestinalen PermeabilitÀt einhergehen. Eine gesteigerte
intestinale PermeabilitĂ€t könnte als Ursache fĂŒr einen vermehrten Kontakt der
intestinalen Immunzellen mit intraluminalen Antigenen ein weiterer Baustein
fĂŒr die inflammatorische Komponente in der Entstehung der CED bedeuten.In this study five genetic variants have been investigated in 910 inflammatory
bowel disease (IBD) patients and 707 healthy controls by melting curve
analysis using FRET-probes. The first variant in the ATG16L1-Gene (c.898G>A;
p.T300A; rs2241880), was previously identified as a risk factor for IBD in two
genome-wide studies. The other four genetic variants are located in the MYO9B-
Gene (rs1545620 in Exon 20 [p.S1011A], rs1457092 in Intron 20, rs2305764 in
Intron 28 and rs2279002 in Intron 32), and have been reported to show a
significant association with Celiac disease. In the course of this work the
predescribed significant association of the ATG16L1 variant with Crohnâs
disease could be confirmed in the German population. In addition, for the
first time a significant association could also be detected in the Dutch
population. Moreover, it could be shown that ATG16L1 resembles an independent
susceptibility factor for Crohnâs disease without interactions with already
established CARD15 variants. CARD15 is known to be a constituent of the innate
immune system. The current pathogenetic model for IBD-development discusses an
abnormal severe reaction of the innate immune system with intraluminal
antigens within the gastrointestinal tract. ATG16L-1 is an important component
of the autophagosome, that disintegrates intracellular particles and
pathogens. The fragments are then presented to immune cells by exocytosis. An
impaired process of autophagocytosis due to changes in ATG16L-1 activity may
thereby affect the balance between immunotolerance and inflammation, and thus
support the current concept about the development of IBD. Regarding the four
investigated MYO9B variants, only in the Dutch population an association of
rs2305764 in Intron 28 with IBD could be shown. As a part of the cytoskeleton
MYO9B may influence cell-to-cell junctions and intestinal permeability.
Permeability investigations of patients and controls were evaluated employing
a three sugar test. Hereby a trend towards an increased intestinal
permeability was shown for three genetic variants in MYO9B. A higher
intestinal permeability may enhance contact of intestinal immune cells with
intraluminal antigens and thus could be considered as another important
element for inflammation in IBD
Multiparametric MRI in detection and image-guided biopsy of prostate cancer
Mit groĂen Schritten etablierte sich die multiparametrische MRT (mpMRT) als
zuverlÀssige bildgebende Diagnostik zur Detektion des Prostatakarzinoms.
DarĂŒber hinaus weisen Arbeiten der letzten Jahre darauf hin, dass die mpMRT
durchaus auch ein bildgebendes âGradingâ erlauben kann. In der ersten Arbeit
dieser Habilitationsschrift (Prostatektomiekontrolliert n = 69) wurde geprĂŒft,
ob die Kombination der konventionellen MRT mit der diffusionsgewichteten
Bildgebung eine verbesserte AggressivitÀtseinschÀtzung von Prostatakarzinomen
erlaubt. Insbesondere die EinschÀtzung hinsichtlich der wichtigen Frage,
welches dominante Wachstumsmuster im Tumor vorliegt, wĂŒrde in der
Therapieentscheidung weiterhelfen und damit das Einsatzgebiet der MRT als
nichtinvasive diagnostische Methode erweitern. In Originalarbeit 1 konnte
gezeigt werden, dass eine genaue Aufarbeitung der diffusionsgewichteten
Bildgebung in der Tat mit dem primÀren Wachstumsmuster nach Gleason
korreliert. MR Verlaufskontrollen von bekannten Prostatakarzinomen z.B. im
Active Surveillance Setting mithilfe der DWI sind daher vielversprechend und
sollten weiter untersucht werden. Die Kombination mit der T2w SignalintensitÀt
erscheint jedoch hinsichtlich des nicht-invasiven âGradingsâ nicht zielfĂŒhrend
zu sein. Um unnötige Biopsien und radikale Therapien durch eine genauere,
nicht-invasive AggressivitÀtseinschÀtzung zu vermindern, sollte die
Kombinationen mit anderen innovativen Parametern (z.B. T2 Mapping) weiterhin
angestrebt werden. Eine weitere MR Technik im Rahmen der mpMRT zur Detektion
ist die Kontrastmitteldynamik (DCE) anhand paramagnetischer Kontrastmittel
(KM). Da in den letzten Jahren MR-KM durch ihre Assoziation mit der
nephrogenen systemischen Fibrose (NSF) Aufmerksamkeit erregten, wurde in
Originalarbeit 2 ein hinsichtlich der NSF sicheres makrozyklisches KM
(Gadobutrol) mit dem zu diesem Zitpunkt standardmĂ€Ăig verwendeten linearen KM
verglichen. Als Referenzstandard diente auch hier die Prostatektomie
(Karzinome in Gadobutrol-Gruppe n = 34 , Gd-DTPA Gruppe n = 42). Hierbei
konnte qualitativ kein signifikanter Unterschied festgestellt werden, wÀhrend
quantitativ zugunsten des KM mit höherer T1-RelaxivitÀt (Gadobutrol) eine
höhere SignalverstÀrkung sowohl im normalen Prostatagewebe, als auch im
Prostatakarzinomgewebe festgestellt werden konnte. Somit ist insgesamt
anzunehmen, dass es auch aus diagnostischem Gesichtspunkt her sicher ist,
makrozyklische KM in der MRT der Prostata zu verwenden. Insbesondere
T1-RelaxivitÀtsunterschiede können jedoch zu unterschiedlicher
SignalverstĂ€rkung fĂŒhren, so dass dies in der Bildinterpretation
berĂŒcksichtigt werden sollte. WĂ€hrend die Techniken hinsichtlich bildgebender
Detektion und AggressivitÀtseinschÀtzung voranschreiten, ist es aus
radiologischer Sicht enorm wichtig, diese Informationen auf eine
standardisierte Weise zu erheben und den mitbehandelnden Kollegen auf eine
möglichst einfache Art und Weise zu kommunizieren. HierfĂŒr sind von der ESUR
2012 Kriterien (MR PI-RADS) veröffentlicht worden, welche in Originalarbeit 3
an einem Kollektiv von 55 direkt MR-gestĂŒtzt biopsierten Patienten, evaluiert
wurden. Aus dieser Studie konnte schlussgefolgert werden, dass insgesamt die
MR PI-RADS Kriterien unter Verwendung der konventionellen MRT (T2w, T1w) und
der diffusionsgewichteten Bildgebung (DWI, ADC) eine hohe diagnostische
Genauigkeit erlauben. Die diagnostische Genauigkeit der evaluierten Kriterien
zur Beurteilung der DCE im Rahmen der mpMRT war jedoch statistisch signifikant
schlechter als die der T2w und DWI. Auch in Kombination konnte ein
inkrementaler diagnostischer Zugewinn nicht festgestellt werden, so dass
hieraus geschlossen wurde, dass die aktuellen PI-RADS Kriterien hinsichtlich
der DCE zumindest revisionsbedĂŒrftig erscheinen. Da die bildgebende Detektion
des Prostatakarzinoms einen histopathologischen Nachweis nicht ersetzen kann,
wird die Biopsie des Prostatakarzinoms weiterhin erforderlich sein. Durch den
rasanten Erfolg der mpMRT sind gezielte Biopsien in den letzten Jahren ins
Rampenlicht gerĂŒckt, welche direkt MR-gestĂŒtzt (Originalarbeit 4, 5) und
indirekt mit Hilfe von MR/Ultraschallfusionssystemen bewerkstelligt werden
können (Originalarbeit 6). SÀmtliche Leitlinien zur urologischen Diagnostik
und Therapie basieren auf ultraschallgestĂŒtzte systematische Biopsien. Durch
die gezielte Biopsie werden konventionelle Logiken, wie âmehr Gewebe ergibt
höhere Wahrscheinlichkeit zur Karzinomdetektionâ, egalisiert (Originalarbeit
4, 5). In Originalarbeit 4 (n= 87) konnte gezeigt werden, dass die
Karzinomdetektion im MR-gezielten Setting unabhÀngig davon wie oft ein Patient
vorher biopsiert wurde, konstante Detektionsraten aufweist. Insgesamt wurden
in dieser Studie im Median 3 Stanzen pro Patient entnommen, wobei die
Detektionsrate bei den verschiedenen Gruppen zwischen 29% und 67% lag. In
Originalarbeit 5 (Stanzen 16G n = 140; 18G n = 143) konnte ein signifikanter
Einfluss auf die diagnostische Genauigkeit durch unterschiedliche
Nadeldiameter ausgeschlossen werden (Originalarbeit 5), wie es im
vergleichbaren Setting bei systematischen TRUS-Biopsien der Fall ist: Auf
Stanzenbasis fand sich eine Karzinomdetektionsrate bei 16G Nadeln von 22,1%
und bei 18G 24,5% (p = 0,77). Diese ZusammenhÀnge deuten darauf hin, dass
Leitlinien, welche klinische SchlĂŒsse aufgrund der Anzahl positiver Stanzen
oder dem prozentualen Anteil von Karzinomgewebe im Stanzengewebe ziehen,
ĂŒberdacht werden mĂŒssen, wenn die Diagnose mittels gezielter Biopsie gestellt
wird. In Originalarbeit 6 wird prospektiv (n = 32) eine neue Technik zur
Fusion von MR-Bildern mit einer Echtzeit-Ultraschalluntersuchung wÀhrend der
transrektalen Prostatabiopsie evaluiert. Die ersten Ergebnisse dieser Arbeit
zeigen durch eine signifikant höhere Detektionsrate gezielter Fusionsstanzen
im Vergleich zur systematischen 10-12-fach Biopsie, dass eine Fusion der MR-
DatensÀtze mit der Echtzeit-Ultraschalluntersuchung möglich und sehr
vielversprechend ist. Diese Technik könnte es erlauben insbesondere
VerfĂŒgbarkeitslimitationen der direkten MR Biopsie aufzuheben, dabei jedoch
die Information der mpMRT in der Prostatabiopsie beizubehalten, so dass
gezielte Biopsien flÀchendeckend angeboten werden könnten.Multiparametric magnetic resonance imaging (mpMRI) has rapidly established
itself as a reliable imaging tool for detection of prostate cancer. In
addition, some recent studies suggest that mpMRI may also allow some degree of
prostate cancer grading. This habilitation thesis compiles 6 original studies
of prostate imaging. The first study included 69 patients with histologic
verification of diagnosis after prostatectomy and investigated whether the
combination of conventional MRI and diffusion-weighted imaging (DWI) improves
prediction of prostate cancer aggressiveness. Stratification of prostate
cancer aggressiveness by imaging would be highly desirable as this information
could help in guiding patient management, thereby expanding the use of MRI as
a noninvasive grading tool. The results of this study suggest that detailed
analysis of DWI does indeed correlate with Gleason scores. Therefore, DWI
appears to be a promising imaging approach for monitoring patients included in
active surveillance programs and merits further study. In contrast, analysis
of T2 signal intensity appears not to improve noninvasive grading. Combination
with other novel MRI parameters (e.g., T2 mapping) appears more promising and
should be pursued further to improve diagnostic accuracy and thus reduce
unnecessary biopsies and radical treatment. Original study 2 investigated
dynamic contrast-enhanced MRI (DCE-MRI), another technique included in mpMRI
of the prostate. Since MR contrast agents have raised concerns because of
their association with nephrogenic systemic fibrosis (NSF), this study 2
compared a macrocyclic contrast agent (gadobutrol), which is considered to be
safe with regard to NSF, with the standard linear MR contrast agent used at
that time. Again, prostatectomy was the standard of reference (n = 34 cancers
in the gadobutrol group and n =42 in the Gd-DTPA group). There was no
statistically significant difference in subjective image quality between the
two contrast agents, while quantitative analysis revealed more pronounced
signal enhancement of both normal prostate and cancer for gadobutrol, which
has higher T1-relaxivity. These results indicate that the macrocyclic contrast
agent is comparable to the standard contrast agent in terms of diagnostic
accuracy in prostate imaging while minimizing the risk of NSF. However, when
interpreting the images, the radiologist using gadobutrol must beaer in mind
that the higher T1 relaxivity may produce more marked enhancement. The rapid
development of imaging techniques for prostate cancer imaging make it
desirable to have a standardized tool for image interpretation, which would
also allow the radiologist to communicate imaging findings in a manner that is
easily understood by clinicians. In 2012, the ESUR published a standardized
system for reporting prostate MRI findings (MR PI-RADS). Original study 3
investigated the MR PI-RADS criteria in a population of 55 patients who
underwent directly MRI-guided prostate biopsy. The results of this study
suggest that the MR PI-RADS criteria have high diagnostic accuracy when used
for reporting conventional MRI (T2w, T1w) and diffusion-weighted imaging (DWI,
ADC), while their accuracy was significantly lower for assessment of the DCE-
MRI component of mpMRI. Even in combination, there was no incremental
diagnostic gain, suggesting that this first PI-RADS version might require
revision with regard to DCE-MRI. Since even the most advanced imaging
modalities cannot replace histopathologic confirmation of prostate cancer,
prostate biopsy will continue to be necessary in the future. The rapid
advancement of mpMRI has sparked an increased interest in targeted prostate
biopsy â either with direct MRI guidance (original studies 4 and 5) or with
use of MRI/ultrasound fusion (original study 6). All guidelines for urologic
diagnosis and treatment of prostate cancer are based on ultrasound-guided
systematic biopsy. However, when targeted biopsies are obtained, the
assumption that âmore tissue increases the likelihood of cancer detectionâ is
no longer valid (original studies 4 and 5). Study 4 (n = 87 patients) showed
that targeted biopsies yielded constant cancer detection rates irrespective of
the number of prior biopsies. In this study, a median of 3 tissue cores were
sampled per patient, with detection rates in the different subgroups ranging
from 29% to 67%. The results of original study 5 (n = 140 biopsies using 16G
needles and n = 143 using 18G needles) ruled out a significant effect of
different biopsy needle diameters on diagnostic accuracy, while there is such
an effect when systematic biopsies are obtained in a similar setting: the
cancer detection rate per tissue core was 22.1% when 16G needles were used and
24.5% for 18G needles (p = 0.77). These findings suggest that guidelines which
derive clinical conclusions based on the number of positive tissue cores or
the percentage of cancer tissue in the sampled tissue must be revised when
targeted biopsy is used. Original study 6 (n = 32) prospectively evaluated a
new technique of fusion of MR images with real-time ultrasound during
transrectal prostate biopsy. The results of this study show a significantly
higher detection rate of targeted fusion biopsy compared with systematic 10-
or 12-core biopsy, suggesting that fusion of MR imaging datasets with real-
time ultrasound is feasible and promising. With this technique, it might be
possible to overcome the limited availability of direct MR-guided biopsy,
while carrying over the diagnostic information of mpMRI to prostate biopsy,
thus allowing widespread use of targeted prostate biopsy
Quantification of aortic valve stenosis in patients with preexisting renal insufficiency: feasibility of contrast material volume reduction in computed tomography
Quantification of aortic valve stenosis in patients with preexisting renal insufficiency: feasibility of contrast material volume reduction in computed tomography
Assessment of Mitral Valve Stenosis by Helical MDCT: Comparison With Transthoracic Doppler Echocardiography and Cardiac Catheterization
Comparison of gadoteric acid and gadobutrol for detection as well as morphologic and dynamic characterization of lesions on breast dynamic contrast-enhanced magnetic resonance imaging
OBJECTIVE
In contrast to conventional breast imaging techniques, one major diagnostic benefit of breast magnetic resonance imaging (MRI) is the simultaneous acquisition of morphologic and dynamic enhancement characteristics, which are based on angiogenesis and therefore provide insights into tumor pathophysiology. The aim of this investigation was to intraindividually compare 2 macrocyclic MRI contrast agents, with low risk for nephrogenic systemic fibrosis, in the morphologic and dynamic characterization of histologically verified mass breast lesions, analyzed by blinded human evaluation and a fully automatic computer-assisted diagnosis (CAD) technique.
MATERIALS AND METHODS
Institutional review board approval and patient informed consent were obtained. In this prospective, single-center study, 45 women with 51 histopathologically verified (41 malignant, 10 benign) mass lesions underwent 2 identical examinations at 1.5 T (mean time interval, 2.1 days) with 0.1-mmol kg doses of gadoteric acid and gadobutrol. All magnetic resonance images were visually evaluated by 2 experienced, blinded breast radiologists in consensus and by an automatic CAD system, whereas the morphologic and dynamic characterization as well as the final human classification of lesions were performed based on the categories of the Breast imaging reporting and data system MRI atlas. Lesions were also classified by defining their probability of malignancy (morpho-dynamic index; 0%-100%) by the CAD system. Imaging results were correlated with histopathology as gold standard.
RESULTS
The CAD system coded 49 of 51 lesions with gadoteric acid and gadobutrol (detection rate, 96.1%); initial signal increase was significantly higher for gadobutrol than for gadoteric acid for all and the malignant coded lesions (P < 0.05). Gadoteric acid resulted in more postinitial washout curves and fewer continuous increases of all and the malignant lesions compared with gadobutrol (CAD hot spot regions, P < 0.05). Morphologically, the margins of the malignancies were different between the 2 agents, whereas gadobutrol demonstrated more spiculated and fewer smooth margins (P < 0.05). Lesion classifications by the human observers and by the morpho-dynamic index compared with the histopathologic results did not significantly differ between gadoteric acid and gadobutrol.
CONCLUSIONS
Macrocyclic contrast media can be reliably used for breast dynamic contrast-enhanced MRI. However, gadoteric acid and gadobutrol differed in some dynamic and morphologic characterization of histologically verified breast lesions in an intraindividual, comparison. Besides the standardization of technical parameters and imaging evaluation of breast MRI, the standardization of the applied contrast medium seems to be important to receive best comparable MRI interpretation
Myosin IXb variants and their pivotal role in maintaining the intestinal barrier: a study in Crohn's disease
Our data suggest a link between MYO9B variants to an increased intestinal permeability in CD patients. This supports the influence of Myosin IXb on the integrity of the epithelial barrier. The role of MYO9B variants in the overall susceptibility to IBD, however, remains to be elucidated