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Untersuchung eines neuartigen Konzepts für die Zukunft der Mitralklappenreparatur: Bildgestützte Vorhersage der Annuloplastie-Ringgröße
Get PDFObjectives: Annuloplasty rings are used in surgical mitral valve repair (MVr), to stabilize and reshape the MV annulus. Precise selection of the ring size is crucial in MVr to achieve a positive outcome. If the ring is selected too large or too small, it may cause unfavorable repair results. Moreover, the conventional sizing strategies highly depend on the surgeons´ experience. Considering the aforementioned information, our study examined the efficacy of 3D transesophageal echocardiography (3D-TEE) coupled with post-processing utilizing a specialized software package. The investigation specifically focuses on its feasibility in predicting annuloplasty ring sizes for MVr.
Methods: In this study, patients who underwent minimally invasive mitral valve repair (MI-MVr) using Physio-II (Edwards Lifesciences, Irvine, CA, USA) as ring annuloplasty between August 2018 and August 2021 were analyzed. Inclusion criteria for the study were limited to patients presenting Carpentier type II pathology and those who were discharged with either no residual mitral regurgitation (MR) or only trace amounts. A total of 150 patients who met these criteria were considered for the 3D-MV reconstruction analysis using a semi-automated software package to quantify MV geometry. The feasibility of 3D-MV reconstruction values in predicting ring size was examined using univariable and multivariable linear regression analyses.
Results: Our findings revealed correlations between the implanted ring size and 3D-MV reconstruction values. The highest correlation coefficients were observed for the CW with a coefficient of 0.839 (p<0.001), followed closely by the ITD (r=0.796; p<0.001), the annulus area (r=0.782 ;p<0.001), and the AML area (r=0.767; p<0.001). Within the context of the multivariable regression analysis, only CW and ITD emerged as independent predictors for ring size in MVr surgery. The highest level of agreement between predicted and implanted ring size was obtained with the model including CW and ITD (76.6%).
Conclusions: The study demonstrates that the use of the 4D-MV Assessment Tool may play a pivotal role in assisting surgeons during the decision-making process for ring sizing, especially in minimally invasive settings. This advancement is a crucial initial step towards achieving ring size predictions, potentially paving the way for future developments including multimodal machine learning decision support.Einleitung: Annuloplastieringe werden in der chirurgischen Mitralklappenrekonstruktion (MVr) verwendet, um den Mitralklappenring zu stabilisieren und neu zu formen. Die präzise Auswahl der Annuloplastieringgröße ist entscheidend für den Erfolg der MVr. Ein zu großer oder zu kleiner Annuloplastiering, kann zu einer Restundichtigkeit der Mitralklappe oder zu einem Einziehen des vorderen Segels in den Ausflusstrakt des linken Ventrikels in der Systole führen. Darüber hinaus sind herkömmliche Sizing-Strategien stark von der Erfahrung der Chirurgen und Chirurginnen abhängig. Vor diesem Hintergrund haben wir die Wertigkeit der 3D-TEE mit anschließender Verarbeitung mithilfe einer dezierten Software zur Vorhersage der Annuloplastieringgröße für die MVr untersucht.
Methodik: In dieser Studie wurden Patienten eingeschlossen, die zwischen August 2018 und August 2021 einer minimal-invasiven MVr mit einem CE Physio-II-Annuloplastiering (Edwards Lifesciences, Irvine, CA, USA) unterzogen wurden. Nur Patienten mit Carpentier-Typ-II-Pathologie, die ohne bzw. nur geringer Restinsuffizienz der Mitralklappe entlassen wurden, wurden in die Studie eingeschlossen. Insgesamt wurden 150 Patienten für die 3D-MV-Rekonstruktionsanalyse mithilfe einer halbautomatisierten Software zur Quantifizierung der MV-Geometrie untersucht. Zur Vorhersage der Ringgröße wurden univariable und multivariable lineare Regressionsanalysen durchgeführt.
Ergebnisse: Unsere Ergebnisse zeigten Korrelationen zwischen der implantierten Ringgröße und gewissen Werten der 3D-MV-Rekonstruktion. Die höchsten Korrelationskoeffizienten wurden für den interkommissuralen Abstand (CW) mit einem Koeffizienten von 0,839 (p<0,001) festgestellt, gefolgt von dem intertrigonalen Abstand (ITD) (r=0,796; p<0,001), der Fläche des Mitralklappenrings (r=0,782; p<0,001) und der Fläche des Mitralklappensegels (r=0,767; p<0,001). In der multivariablen Regressionsanalyse wurden nur die CW und die ITD als unabhängige Prädiktoren für die Ringgröße der Annuloplastie identifiziert. Das höchste Maß an Übereinstimmung zwischen vorhergesagter und implantierte Ringgröße wurde mit dem Modell erzielt, das die CW und ITD einschloss (76,6%).
Schlussfolgerung: Die vorliegende Studie zeigt einen eindeutigen Zusammenhang zwischen dem interkommissuralen und dem intertrigonalen Abstand, erhoben aus dem 4D-MV Assessment Tool, mit der Größe des Annuloplastieringes für Mitralklappenrekonstruktionen. Dieser Fortschritt stellt einen entscheidenden ersten Schritt zur präoperativen Vorhersage von Ringgrößen dar und ebnet potenziell den Weg für zukünftige Entwicklungen, einschließlich der Entscheidungsunterstützung durch multimodale maschinelle Lernverfahren
Mars Express: From the Launch Pad to a 20-Year Success Record at Mars
Get PDFMars Express was conceived and built by ESA as a successor of the unsuccessful Russian Mars-96 mission. It was planned from the onset as an orbiter and lander mission to be able to carry out long-term, remote sensing and in-situ scientific investigations of the planet Mars and its environment. As an exceptionally successful workhorse and a backbone of the Agency’s Science Programme in operation at Mars since end December 2003, Mars Express has proven to be a highly productive mission returning excellent scientific value for the investments made by ESA and its Member States. This paper is intended as the introduction to the series of papers that make this special collection. It briefly reviews the history of the mission, its science goals, its uniqueness while establishing its complementarity with other Mars missions in a collaborative context. It also lists the teams and operational aspects and innovations that made this mission a success. Then the paper highlights Mars Express’s scientific achievements throughout its 20-year lifetime. Mars Express results and discoveries continue playing an essential role in understanding the geological, atmospheric and climate evolution of the Red Planet and determining its potential past habitability. To conclude, a preview of the science and other topics covered by this collection is given. Mars Express, a pioneering mission for Europe at Mars, is currently continuing on its long scientific journey around the Red Planet
Utilization of Complementary and Integrative Medicine as exemplified by two different German cross-sectional studies
Get PDFHintergrund: Methoden aus dem Bereich Komplementäre und Integrative Medizin (KIM) werden in Deutschland von einem Großteil der Bevölkerung in Anspruch genommen. Diese Verfahren sind häufig zu wenig wissenschaftlich untersucht. Die Dissertation umfasst zwei Studien, die die Inanspruchnahme von KIM analysieren.
Methoden: Menschen mit einem Bezug zu KIM (Studie I) wurden in den Jahren 2020/21 zu gesundheitsfördernden Selbsthilfemaßnahmen aus dem KIM-Bereich und dem emotionalen Befinden während der COVID-19-Pandemie befragt. Im Jahr 2019 wurden Medizinstudierende (Studie II) zur Inanspruchnahme von und Einstellung zu KIM befragt. Die Daten der explorativen Querschnittserhebungen wurden deskriptiv ausgewertet und vergleichend dargestellt. Es wurden Fragebögen zur Inanspruchnahme und Wirksamkeit von KIM mit einer Auswahl von 17 (Studie I), beziehungsweise 16 (Studie II) KIM-Methoden entwickelt. In Studie I wurde das emotionale Befinden für neun Emotionen mittels numerischer Ratingskalen erfasst. In Studie II wurde eine deutsche Version des Complementary and Alternative Medicine Health Belief Questionnaire (CHBQ) für Medizinstudierende eingeführt (Range von 10 bis 70, höherer Wert ≙ positivere Einstellung zu KIM).
Ergebnisse: Insgesamt konnten über 2000 Teilnehmende (Studie I: n=1605; Studie II: n=349) eingeschlossen werden, mehrheitlich weibliche (Studie I: 80,6%; Studie II 69,0%). Die in Studie I am meisten genutzten KIM-Methoden zur Gesundheitsförderung waren Naturaufenthalte (85,6%), gesunde Ernährung (85,6%) sowie Bewegung (83,6%). Fast die Hälfte der Medizinstudierenden in Studie II hat bereits KIM angewandt, insbesondere pflanzliche Arzneimittel (34,3%), Yoga (27,4%) und Homöopathie (27,1%). Die Wirksamkeit wurde überwiegend als „stark“ oder „mittel“ (Studie I), beziehungsweise „gut“ oder „etwas“ (Studie II) eingeschätzt. Die Inanspruchnahme von acht Methoden wurde in den Studien ähnlich erfragt: Yoga, Nahrungsergänzungsmittel, Meditation, Anthroposophische Medizin, Heilpflanzen, Indische Medizin, Chinesische Medizin und Homöopathie. Bei Menschen mit KIM-Bezug sind negative Emotionen wie Angst geringer ausgeprägt als positive wie Wohlfühlen. Medizinstudierende befürworten mehr Forschung im Bereich KIM. Ihre Haltung zu KIM ist mit einem CHBQ-Score von 44,2±10,7 (Mittelwert±Standardabweichung) als eher neutral zu bewerten.
Fazit: Die Inanspruchnahme von KIM ist in den untersuchten Studienpopulationen relevant. Die mit Lebensstilmaßnahmen aus dem KIM-Bereich verbundenen Erwartungen hinsichtlich einer Gesundheitsförderung in Krisensituationen könnten einen Einfluss auf das emotionale Befinden haben. Das Interesse von Medizinstudierenden könnte durch die Randposition von KIM im Curriculum bedingt sein. Kausale Zusammenhänge lassen sich aufgrund des Querschnittsdesigns nicht zeigen. Künftige vergleichende Forschung im Bereich KIM benötigt klare Definitionen bei der Abfrage, um Vergleichbarkeit und Validität der Studienergebnisse zu gewährleisten.Background: Methods from the field of complementary and integrative medicine (CIM) are used by a large part of the population in Germany, but these procedures are often not or insufficiently scientifically studied. This thesis includes two studies that focus on the use of CIM in two different study populations.
Methods: People with a known connection to CIM (study I) were surveyed in 2020/21 about health-promoting self-help measures from the field of CIM and their emotional status during the COVID-19 pandemic. In 2019, medical students (study II) were surveyed about their use of CIM and attitudes toward CIM. Data from the exploratory cross-sectional surveys were analyzed descriptively and compared. The research group developed questionnaires on the use and estimated effectiveness of CIM with a selection of 17 (study I) or 16 (study II) CIM methods. In study I, the emotional status was assessed for nine emotions by using numerical rating scales. In study II, a German version of the Complementary and Alternative Medicine Health Belief Questionnaire (CHBQ) was introduced (range 10 to 70, higher score ≙ more positive attitude toward CIM).
Results: In total, more than 2000 participants were included (study I: n=1605; study II n=349) in both studies. The majority was female (study I: 80.6%; study II: 69.0%). In study I, frequently used CIM methods for health promotion were staying in nature (85.6%), healthy nutrition (85.6%) and physical activity (83.6%). In study II, almost half of the medical students have already used CIM, especially herbal remedies (34.3%), yoga (27.4%), and homeopathy (27.1%). Efficacy was predominantly rated as “strong” or “moderate” (study I), or “good” or “somewhat” (study II). The use of eight methods was surveyed similarly in both studies: yoga, nutritional supplements, meditation, Anthroposophic
Medicine, herbal medicine, Indian Medicine, Chinese Medicine, and homeopathy. In people with an affinity to CIM, negative emotions such as fear are less pronounced than positive emotions such as wellbeing. Medical students wish for more research on CIM. Their attitude towards CIM can be rated as rather neutral, with an average CHBQ score of 44.2±10.7 (mean±standard deviation).
Conclusion: The use of CIM is relevant in the study populations. Expectations associated with lifestyle measures from the CIM area regarding to health promotion in crisis situations could have an influence on the emotional wellbeing. The interest of medical students towards CIM could be influenced by the marginal position of CIM in the curriculum. Causality cannot be shown due to the cross-sectional design. Future comparative research in the field of CIM requires clear definitions in the survey to establish comparability and validity of the study results
Changes in Ruminal Fermentation and Growth Performance in Calves After Increasing Ruminal Undegradable Protein at Two Different Time Points Pre-Weaning
Get PDFThe cost-effective rearing of heifers depends on the provision of adequate nutrients at an appropriate age to meet nutrient requirements for growth and production. The objective of the present study was to investigate how the time of switching to a rumen-undegradable protein (RUP) source affects the ruminal fermentation and growth performance of Holstein dairy calves. A total of 36 Holstein female calves were randomly allocated to one of three dietary treatments on day 28 or 42 of life. In the first 28 days of life, they were on the same soybean meal (SBM)-based starter diet containing 22.2% crude protein with 37% RUP. The RUP content of the experimental diet was increased to 48% by a total replacement of the original SBM with xylose-treated soybean meal (XSBM). The following treatments were used: (1) starter diet containing SBM from d 28 (SBM28); (2) starter diet containing XSBM from d 28 (XSBM28); and (3) starter diet containing XSBM from d 42 (XSBM42). All the calves were fed a constant amount of milk (4 L/d), weaned on day 60, and then remained in the experiment until day 70 of life. The results showed that neither feed intake nor BW were influenced by the treatments in the pre-weaning period (days 28 to 60). The calves fed the XSBM28 and XSBM42 diets had greater daily gain and gain-to-feed ratio compared to those on the SBM28 diet post-weaning from day 61 to 70 (p < 0.05). The inclusion of XSBM in the starter diets from days 28 and 42 increased the calves’ height pre- and post-weaning (p < 0.05). The ruminal pH and concentrations of butyrate and iso-butyrate were higher at weaning when the calves were fed the XSBM diets. The calves fed the XSBM diets had less ammonia-N and total short-chain fatty acids at day 70 of life (p < 0.05) and a lower neutral detergent fiber digestibility in the post-weaning period (p < 0.05). The fecal scores and blood metabolites were not different among the treatments. The results showed that increasing the RUP content from 37% to 48% in the starter diets by a total replacement of SBM with XSBM during the pre-weaning period may improve the growth performance around weaning. A later replacement at 42 days of life appears equally effective compared to a replacement at 28 days of life
Specific Aspects of Day Clinic Psychiatric Care Using the Examples of Dialectical Behavior Therapy (DBT) and Acceptance and Commitment Therapy (ACT)
No full textThis habilitation thesis focuses on specific questions within psychiatric health services research, particularly regarding day clinic treatment offerings. It begins with the first survey conducted in the German-speaking world on disorder-specific, day clinic, and inpatient treatment options for individuals with borderline personality disorder (BPD). The findings reveal a significant undersupply of care, characterized by long waiting times and a very high patient-to-treatment-place ratio for DBT (Dialectical Behavior Therapy), clearly indicating that existing services do not meet actual demand.
Building on this, a specialized DBT day clinic in a Berlin psychiatric care region was evaluated. This clinic aimed to address the identified treatment gap. The evaluation showed, for the first time, statistically significant to highly significant improvements in BPD-specific symptoms. The study also systematically examined negative effects of the DBT treatment – a first for a day clinic setting – by identifying which negative effects patients subjectively experienced. Additionally, the research sought to identify patient-level predictors for poor treatment response, with the goal of informing future therapeutic developments for BPD.
Subsequent publications stemmed from this methodological evaluation approach, now applied to a different therapeutic concept: a transdiagnostic (i.e., not disorder-specific) treatment in a day clinic for a more heterogeneous psychiatric patient group. These studies also demonstrated high treatment effectiveness, not only in symptom reduction but also in improvements in patients’ subjective quality of life. Notably, the negative effects of the transdiagnostic ACT (Acceptance and Commitment Therapy) approach were found to be lower compared to other clinical populations.
The ACT day clinic study was conducted during the COVID-19 pandemic, thus reflecting the challenges of delivering mental health care during a particularly vulnerable period.
In summary, the thesis examines the real-world implementation of psychiatric care structures from a health services research perspective, with a focus on day clinics. It scientifically documents the benefits and possible downsides of selected therapeutic methods and their sometimes surprising treatment outcomes. The findings are based on real, unfiltered data from two Berlin psychiatric care regions and provide a representative snapshot of mental health service delivery at the time of study. These results may contribute to the ongoing development of day clinic models to improve mental health care delivery.
The two day clinics investigated serve as examples of different models within the evolving landscape of psychiatric care: one being a highly specialized, disorder-specific DBT program, the other a broad, transdiagnostic ACT approach. Both reflect recent trends toward more outpatient-oriented treatment structures in psychiatry
Effects of different concentrations of a white grape marc extract on broiler performance, apparent ileal digestibility, antioxidant capacity, intestinal barrier function and nutrient transport markers
Get PDFThe current study evaluated the effect of a white grape marc extract (GME) on growth performance, gut health, and intestinal function in broiler chickens at different dosages to determine a dose-related efficacy of the extract without inducing any adverse effects. Four hundred male broiler chickens received a basal diet without (CON) or with the GME at different levels, based on its polyphenolic concentration: 200 (LPP), 750 (MPP), and 1,500 (HPP) mg/kg, respectively. Growth performance parameters were recorded during the whole trial. At 35 days, apparent ileal digestibility (AID) of several nutrients was determined. Additionally, jejunal and cecal tissues were collected to assess tissue morphology. Jejunal tissue was also gathered for gene expression and Ussing chamber studies. Finally, breast muscle was collected for lipid oxidation assessment. Dietary supplementation of the GME did not significantly impact the growth performance of broiler chickens with the exception of the FCR that seemed to be increased by the GME supplementation (P = 0.083). The AID of most of the analyzed nutrients was also unaffected with the exception of the amino acid aspartic acid, which was higher in MPP and HPP compared to LPP (P = 0.006). No significant differences (P > 0.05) were found in villus length (VL), crypt depth (CD), villus-to-crypt ratio (V/C) in the jejunum, or in cecal CD. The number of goblet cells in jejunal villi and crypts was higher in MPP and HPP than in CON (P < 0.001). There were no effects on the mRNA abundance of some pro-inflammatory cytokines, mucins, or tight junction proteins measured in jejunal tissue nor on antioxidant capacity measured in breast muscle. In the Ussing chamber experiment, the GME decreased jejunal tissue conductance after glucose addition in MPP and HPP groups (P = 0.033). In conclusion, although the inclusion of a white GME in the diet of broiler chickens did not significantly enhance growth performance or nutrient absorption, it was confirmed that none of the tested concentrations induced adverse effects
Reading Mirtha Dermisache
Get PDFBeginning in the late 1960s, the Argentinian conceptual artist Mirtha Dermisache (1940–2012) produced publications that consist of asemic writing: marks that resemble language but lack semantic content. Her artist’s books, letters and postcards challenge habitual responses to both art and literature, leading us to re-evaluate how language works, how we perceive it, and how it might be distinguished from drawing. This publication brings together three academic essays and an artist’s tribute, each offering a distinct approach to “reading” Mirtha Dermisache
Threshold guided automated delineation of acute cerebral infarction based on apparent diffusion coefficient (ADC) thresholds
Get PDFZusammenfassung
Hintergrund: In der Diagnostik des ischämischen Schlaganfalls ist die automatisierte Quantifizierung des Infarktes von zunehmender Bedeutung. Zur Abgrenzung des Infarktkerns in der diffusionsgewichteten Bildgebung (DWI) verwenden etablierte Algorithmen generalisierte Grenzwerte des scheinbaren Diffusionskoeffizienten (ADC). Zugrundeliegende Annahmen wurden bisher nur unzureichend überprüft, auch bleiben Einflussfaktoren auf die automatisierte Methode unbekannt.
Methoden: Anhand von Bilddaten der von 2008 bis 2013 durchgeführten 1000Plus Studie (clinicaltrials.org NCT00715533) wurde eine experimentelle retrospektive Analyse von ADC-Grenzwert basierenden Läsionssegmentierungen durchgeführt. Ein eigens entwickelter Segmentierungsalgorithmus wurde an einer heterogenen Gruppe von 108 ischämischen Schlaganfallpatienten getestet, welcher einen üblichen ADC-Grenzwert von ≤620×10-6mm2/s anwendet. Als Ground Truth diente die manuelle Abgrenzung der DWI-Läsion durch erfahrene Neuroradiologen. In der vorliegenden Patientenkohorte wurden optimale ADC-Grenzwerte zur DWI-Läsionsabgrenzung in Grenzwertanalysen identifiziert. Einflussfaktoren auf ADC-Grenzwert-abhängige Segmentierungsmethoden wurden mittels Regressionsmodellen untersucht.
Ergebnisse: Automatisiert segmentierte DWI-Läsionen wiesen im Vergleich zur manuellen Standardmethode signifikant geringere Volumina (Mittlere Differenz: -4.9 ml) und ADC-Werte (Mittlere Differenz: -186 × 10−6mm2/s) auf (n = 108). Der Dice-Koeffizient betrug im Median 0.43 (IQR 0.20 – 0.64). Einflussfaktoren auf die räumliche Übereinstimmung des entwickelten Segmentierungsalgorithmus stellten die ADC-Werte innerhalb der DWI-Läsion (β = -0.65, p <.01) und des gesunden Hirnparenchyms (β = 0.17, p <.01) dar. Das Volumen der Läsion (β = 0.55, p <.01) korrelierte mit dem Dice-Koeffzienten. Der mittels gepoolter Grenzwertoptimierungskurve bestimmte optimale ADC-Grenzwert in vorliegender Kohorte betrug 693×10-6mm2/s (Sensitivität 63%, Spezifität 75%). Optimale individuelle Kurven zeigten ADC-Grenzwerte mit einem Interquartilenabstand von ≤634 – 735×10-6mm2/s auf. Signifikante Einflussfaktoren auf den diagnostischen Nutzen optimaler individueller ADC-Grenzwerte waren im Regressionsmodell die ADC-Werte innerhalb der DWI-Läsionen (β = -0.9, p <.01) und im übrigen Hirnparenchyms (β = 0.29, p <.01). Es zeigte sich kein relevanter Einfluss des Zeitintervalls (0 – 24 Stunden) auf die mittleren ADC-Werte innerhalb der DWI-Läsion oder die Leistungsfähigkeit von ADC-Grenzwerten. Ein ADC-Anstieg innerhalb der DWI-Läsion konnte zwischen Tag 3 und 7 nachgewiesen werden.
Konklusion: Die Anwendung von restriktiven ADC-Grenzwerten führt zu signifikant geringeren Läsionsvolumina im Vergleich zur Standardmethode. Läsionsspezifische und patientenspezifische Faktoren beeinflussen die Leistungsfähigkeit der angewandten ADC-Grenzwerte. Das Zeitintervall stellt innerhalb von 24 Stunden keinen Einflussfaktor dar.Abstract
Background: Automated infarct quantification methods are already established in ischemic stroke diagnostics. Algorithms use threshold values of the apparent diffusion coefficient (ADC) to delineate the infarct core in diffusion-weighted imaging (DWI). Only a few independent studies have examined differences to the previous standard method of examiner-dependent manual delineation. Factors influencing the supposedly more objective method remain unknown.
Methods: Using image data from the 1000Plus study conducted from 2008 to 2013 (clinicaltrials.org NCT00715533), an experimental retrospective analysis of ADC threshold-based lesion segmentation was performed. For this purpose, a segmentation algorithm was developed and tested on a heterogeneous group of 108 ischemic stroke patients using a standard ADC threshold of ≤620×10-6mm2/s. Manual delineation of the DWI lesion by experienced neuroradiologists served as ground truth. Resulting segmentations were analyzed. In receiver operating characteristics (ROC) analysis, optimal ADC thresholds for DWI lesion delineation were identified in the present patient cohort. Multiple linear regression models were used to analyze factors influencing the performance of the algorithm as well as the diagnostic capabilities of ADC thresholds identified in the ROC analysis. The time course of the ADC values within the DWI lesion was recorded.
Results: Automated segmented DWI lesions had significantly lower volumes (mean difference: -4.9 ml) and ADC values (mean difference: -186×10-6mm2/s) compared to the manual standard method. The median Dice coefficient was 0.43 (IQR 0.20 - 0.64). Factors influencing the spatial agreement of the developed segmentation algorithm were the ADC values within the DWI lesion (β = -0.65, p <.01) and the unaffected brain parenchyma (β = 0.17, p <.01). DWI lesion volume (β = 0.55, p <.01) correlated positively with the Dice coefficient. The optimal ADC threshold determined by pooled ROC analysis in the present cohort was 693×10-6mm2/s (sensitivity 63%, specificity 75%). Optimal individual curves showed ADC thresholds with an interquartile range of ≤634 - 735×10-6mm2/s. In the regression model, the ADC value within the DWI lesion (β = -0.9, p <.01) and the brain parenchyma (β = 0.29, p <.01) were influential factors on the diagnostic benefit of optimal individual ADC thresholds. There was no relevant influence of the time interval (0 - 24 hours) on the mean ADC values within the DWI lesion or the performance of ADC thresholds. An ADC increase within the DWI lesion was detected between day 3 and 7.
Conclusion: The application of restrictive ADC thresholds leads to significantly lower lesion volumes compared to the standard method. Lesion as well as patient specific factors influence the performance of the applied ADC thresholds. However, the time of symptom onset to imaging within 24 hours is not considered an influential factor
The Lung Clearance Index in Preschool Children with Primary Ciliary Dyskinesia Compared to Preschool Children with Cystic Fibrosis
Get PDFHintergrund: Die primäre ziliäre Dyskinesie (PCD) ist eine seltene angeborene Erkrankung, die mit einer gestörten Motilität der Zilien im Körper einhergeht. Klinisch manifestiert sie sich, aufgrund der gestörten mukoziliären Clearance, vor allem durch Erkrankungen der Atemwege. Eine andere Erkrankung, der eine Störung der mukoziliären Clearance zugrunde liegt ist die Mukoviszidose (CF). Verschiedene Studien konnten zeigen, dass die Lungenerkrankung bei Kindern mit Mukoviszidose (CF) bereits im Säuglingsalter existiert. Diese konnte bei Vorschulkindern mit CF durch den Lung Clearance Index (LCI), der durch Multiple-Breath Washout (MBW) bestimmt wird, sensitiv detektiert werden. Im Gegensatz dazu gibt es nur wenige Daten zu Beginn und Ausprägung der Lungenerkrankung bei Vorschulkindern mit primärer ziliärer Dyskinesie (PCD). Auch zur Eignung des LCI als sensitivem, quantitativem und nicht-invasivem Messwert liegen für die PCD bei Vorschulkindern kaum Daten vor.
Zielsetzung: Das Ziel dieser Studie war es, die Durchführbarkeit von MBW, sowie die Sensitivität von MBW zur Detektion von pulmonalen Ventilationsinhomogenitäten bei Vorschulkindern mit PCD zu untersuchen.
Methoden: Diese Studie war eine prospektive, multizentrische Querschnittsstudie. Per MBW mit Stickstoffauswaschung wurde bei Vorschulkindern mit PCD, Vorschulkindern mit CF und gesunden Kontrollen im gleichen Alter der LCI bestimmt und zwischen den Gruppen verglichen.
Ergebnisse: MBW wurde erfolgreich von 27 Vorschulkindern mit PCD, 34 Vorschulkindern mit CF und 30 gesunden Kontrollen durchgeführt (Altersdurchschnitt 4,8 Jahre, Spannweite 2,2-6,9 Jahre). Die Durchführbarkeit von MBW unterschied sich mit 93,1% in der PCD-Gruppe nicht von der in der CF-Gruppe (91,9%) und den gesunden Kontrollen (85,7%; P=0,55). Der LCI der Vorschulkinder mit PCD (Median, 9,1) war im Vergleich zu dem der gesunden Kontrollen (Median, 7,0) erhöht (P<0,0001). Er unterschied sich nicht vom LCI der Vorschulkinder mit CF (Median, 8,6; P=0,71).
Schlussfolgerungen: Diese Studie konnte zeigen, dass die Lungenerkrankung bereits bei Vorschulkindern mit PCD nachweisbar war und ähnlich zur frühen Lungenerkrankung bei CF ausgeprägt sein könnte. Aufgrund dessen sollten früh ein systematisches Monitoring und die Therapie bei Patienten mit PCD erfolgen. LCI könnte für Kinder mit PCD ein geeigneter diagnostischer Marker und ein potenzieller Endpunkt in klinischen Interventionsstudien sein.Background: Primary ciliary dyskinesia (PCD) is a rare congenital disorder associated with impaired motility of the cilia in the body. It manifests itself primarily through respiratory diseases due to impaired mucociliary clearance. Cystic fibrosis (CF) is another disease characterised by impaired mucociliary clearance. Previous studies demonstrated that lung disease in cystic fibrosis (CF) exists already in young infants. The lung clearance index (LCI) derived from multiple-breath washout (MBW) sensitively detects this early lung disease in preschool children with CF. In preschool children with primary ciliary dyskinesia (PCD), only limited data on the onset and severity of lung disease exist. Also LCI has not been investigated as a non-invasive quantitative endpoint to studies in this patients.
Objective: The objective of this study was to determine the feasibility and sensitivity of MBW to detect ventilation inhomogeneity in preschool children with PCD and to compare the LCI of preschool children with PCD to the LCI of age-matched healthy controls and children with CF.
Methods: In this prospective cross-sectional multicenter study, LCI was determined in clinically stable preschoolers with PCD, preschoolers with CF, and healthy control (HC) participants using nitrogen MBW. LCI was compared between the three groups.
Results: Twenty-seven children with PCD, 34 children with CF, and 30 HC participants (mean age, 4.8 years; range, 2.2-6.9 years) performed MBW successfully. The feasibility in preschoolers with PCD was 93.1% and did not differ from that in preschoolers with CF (91.9%) and in HC participants (85.7%; P=0.55). LCI was increased in preschool children with PCD (median, 9.1) compared to healthy controls (median, 6.9; P<0.0001), but did not differ from children with CF (median, 8.6; P=0.71).
Conclusion: This study demonstrated an early onset of lung disease in preschool children with PCD. It suggested that the severity of lung disease in PCD in the preschool years may be similar to early lung disease in CF. These data support the need for diagnostic monitoring and therapy early in life and support the LCI as a non-invasive diagnostic tool and as a potential endpoint in clinical trials testing early intervention strategies in children with PCD
