39 research outputs found
Toward a standardized multidisciplinary team approach in preterm infants at-risk for pulmonary hypertension
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Editorial: Management of Patent Ductus Arteriosus in Preterm Infants
Wearable cardioverter-defibrillator as bridging to ICD in pediatric hypertrophic cardiomyopathy with myocardial bridging - a case report
Background: There is only limited experience with wearable cardioverter-defibrillators (WCD) in pediatric patients. We report on the successful application of a WCD in an adolescent patient with hypertrophic cardiomyopathy and myocardial bridging.
Case presentation: A 15-year-old girl presented with a history of recurrent syncope, dyspnea, and vertigo with exercise. Diagnostic work-up revealed non-obstructive hypertrophic cardiomyopathy and signs of myocardial ischemia with exercise. Given this high-risk constellation, the patient was scheduled for prophylactic implantation of an implantable cardioverter-defibrillator (ICD). One month after initial presentation and days prior to the planned ICD implantation, the patient collapsed during an episode of sustained ventricular tachycardia (VT) while running. VT was terminated by WCD shock delivery. Following this event, computerized tomography scan revealed myocardial bridging of the left anterior descending coronary artery causing a 90% stenosis in systole. After coronary surgery, life threatening arrhythmias have not recurred, but due to progressive heart failure, the patient underwent successful heart transplantation after 2 years.
Conclusions: The reported case highlights the importance and applicability of WCDs and the potentially malign nature of myocardial bridging in pediatric high-risk patients
Soluble Receptor for Advanced Glycation End Products (sRAGE) Is a Sensitive Biomarker in Human Pulmonary Arterial Hypertension.
Pulmonary arterial hypertension (PAH) is a progressive condition with an unmet need for early diagnosis, better monitoring, and risk stratification. The receptor for advanced glycation end products (RAGE) is activated in response to hypoxia and vascular injury, and is associated with inflammation, cell proliferation and migration in PAH. For the adult cohort, we recruited 120 patients with PAH, 83 with idiopathic PAH (IPAH) and 37 with connective tissue disease-associated PAH (CTD-PAH), and 48 controls, and determined potential plasma biomarkers by enzyme-linked immunoassay. The established heart failure marker NTproBNP and IL-6 plasma levels were several-fold higher in both adult IPAH and CTD-PAH patients versus controls. Plasma soluble RAGE (sRAGE) was elevated in IPAH patients (3044 ± 215.2 pg/mL) and was even higher in CTD-PAH patients (3332 ± 321.6 pg/mL) versus controls (1766 ± 121.9 pg/mL; p < 0.01). All three markers were increased in WHO functional class II+III PAH versus controls (p < 0.001). Receiver-operating characteristic analysis revealed that sRAGE has diagnostic accuracy comparable to prognostic NTproBNP, and even outperforms NTproBNP in the distinction of PAH FC I from controls. Lung tissue RAGE expression was increased in IPAH versus controls (mRNA) and was located predominantly in the PA intima, media, and inflammatory cells in the perivascular space (immunohistochemistry). In the pediatric cohort, plasma sRAGE concentrations were higher than in adults, but were similar in PH (n = 10) and non-PH controls (n = 10). Taken together, in the largest adult sRAGE PAH study to date, we identify plasma sRAGE as a sensitive and accurate PAH biomarker with better performance than NTproBNP in the distinction of mild PAH from controls
Current Controversy on Platelets and Patent Ductus Arteriosus Closure in Preterm Infants.
Platelets are critically involved in murine patent ductus arteriosus (PDA) closure. To date, the clinical significance of these findings in human preterm infants with PDA is still controversial. We discuss the available study data on the role of platelets for PDA closure in preterm infants: Several mostly retrospective studies have yielded conflicting results on whether thrombocytopenia contributes to failed spontaneous ductal closure. The same applies to investigations on the role of thrombocytopenia as a risk factor for unsuccessful ductus arteriosus closure by pharmacological treatment with cyclooxygenase inhibitors. Nonetheless, recent meta-analyses have concluded that thrombocytopenia constitutes an independent risk factor for both failed spontaneous and pharmacological PDA closure in preterm infants. However, the available investigations differ in regard to patient characteristics, diagnostic strategies, and treatment protocols. Several studies suggest that impaired platelet function rather than platelet number is critically involved in failure of ductus arteriosus closure in the preterm infant. A recent randomized-controlled trial on platelet transfusions in preterm infants with PDA failed to show any benefit for liberal vs. restrictive transfusion thresholds on PDA closure rates. Importantly, liberal transfusions were associated with an increased rate of intraventricular hemorrhage, and thus should be avoided. In conclusion, the available evidence suggests that thrombocytopenia and platelet dysfunction contribute to failure of spontaneous and pharmacological PDA closure in preterm infants. However, these platelet effects on PDA seem to be of only moderate clinical significance. Furthermore, platelet transfusions in thrombocytopenic preterm infants in order to facilitate PDA closure appear to cause more harm than good
Independent effects of sham laparotomy and anesthesia on hepatic microRNA expression in rats
Background: Studies on liver regeneration following partial hepatectomy (PH) have identified several microRNAs (miRNAs) that show a regulated expression pattern. These studies involve major surgery to access the liver, which is known to have intrinsic effects on hepatic gene expression and may also affect miRNA screening results. We performed two-third PH or sham laparotomy (SL) in Wistar rats to investigate the effect of both procedures on miRNA expression in liver tissue and corresponding plasma samples by microarray and qRT-PCR analyses. As control groups, non-treated rats and rats undergoing anesthesia only were used. Results: We found that 49 out of 323 miRNAs (15%) were significantly deregulated after PH in liver tissue 12 to 48 hours postoperatively (>20% change), while 45 miRNAs (14%) were deregulated following SL. Out of these miRNAs, 10 miRNAs were similarly deregulated after PH and SL, while one miRNA showed opposite regulation. In plasma, miRNA upregulation was observed for miR-133a and miR-133b following PH and SL, whereas miR-100 and miR-466c were similarly downregulated following anesthesia and surgery. Conclusions: We show that miRNAs are indeed regulated by sham laparotomy and anesthesia in rats. These findings illustrate the critical need for finding appropriate control groups in experimental surgery
Challenges and special aspects of pulmonary hypertension in middle- to low-income regions: JACC state-of-the-art review
Challenges and special aspects related to the management and prognosis of pulmonary hypertension (PH) in middle- to low-income regions (MLIRs) range from late presentation to comorbidities, lack of resources and expertise, cost, and rare options of lung transplantation. Expert consensus recommendations addressing the specific challenges for prevention and therapy of PH in MLIRs with limited resources have been lacking. To date, 6 MLIR-PH registries containing mostly adult patients with PH exist. Importantly, the global prevalence of PH is much higher in MLIRs compared with high-income regions: group 2 PH (left heart disease), pulmonary arterial hypertension associated with unrepaired congenital heart disease, human immunodeficiency virus, or schistosomiasis are highly prevalent. This consensus statement provides selective, tailored modifications to the current PH guidelines to address the specific challenges faced in MLIRs, resulting in the first pragmatic and cost-effective consensus recommendations for PH care providers, patients, and their families
Large expert-curated database for benchmarking document similarity detection in biomedical literature search
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe
Microfluidics-based quantification of circulating endothelial cells in pulmonary arterial hypertension
Hintergrund: Die pulmonalarterielle Hypertonie (PAH) ist eine ätiologisch
heterogene, proliferative kardiovaskuläre Erkrankung, die mit einer hohen
Mortalität einhergeht. Zirkulierende Endothelzellen (circulating endothelial
cells, CECs) werden als potentielle Biomarker zur Diagnose und
Verlaufsbeurteilung bei PAH diskutiert. Die aktuell verfügbaren Methoden zur
Isolierung und Quantifizierung dieser Zellen sind aber zeit- und
arbeitsaufwendig. Fragestellung: Ziel dieser Studie war es, eine auf
Microfluidics-Technologie basierende Plattform zur Messung von CECs zu
entwickeln und diese bei PAH-Patienten zu validieren. Methoden: Basierend auf
einer aus Vorarbeiten verfügbaren polymerischen diagnostischen Plattform zur
Quantifizierung endothelialer Progenitorzellen (endothelial progenitor cells,
EPCs) wurde ein modifizierter Microfluidics-basierter Chip für die CEC
Messung entwickelt. Humanes Vollblut wurde gesammelt und in die Microfluidics-
Plattform injiziert. Hier erfolgte die Bindung der Zellen an anti-CD146
Antikörper-tragende Mikrosäulen. Nach Komplettierung der
immunfluoreszenzbasierten Färbungen wurden die Zellen ausgezählt. Ergebnisse:
Zuerst wurde der CEC Chip gegen konventionelle Durchflusszytometrie validiert
(r = 0.89, n=7). Danach wurden die CEC Zahlen von 66 weiblichen PAH-Patienten
mit denen von Kontrollpatienten ohne PAH verglichen. Es konnte eine
signifikante, drei- bis fünffache Erhöhung der CEC Zahlen bei PAH gezeigt
werden (p < 0.001). Diese war unabhängig von der Subgruppenzugehörigkeit der
PAH-Patienten (idiopathische/hereditäre PAH, Medikamenten-induzierte PAH und
Connective Tissue Disease-assoziierte PAH). Eine Korrelation zu den potentiell
den Krankheitsverlauf beeinflussenden Faktoren Alter und Body Mass Index
bestand nicht. Diskussion: Der Microfluidics CEC Chip ist zur schnellen und
verlässlichen Bestimmung der CEC Zahl geeignet. Der Chip benötigt 200-400 μl
Vollblut und bietet potentiell die Grundlage für ein bettseitiges Screening
von Patienten mit PAH oder anderen mit Gefäßschäden assoziierten Erkrankungen.Background: Pulmonary arterial hypertension (PAH) is a proliferative
cardiovascular disease of heterogeneous etiology. PAH is still associated with
a high mortality. Thus, methods allowing for a timely diagnosis and adequate
risk-stratification are highly warranted. Circulating endothelial cells (CECs)
have been discussed as potential biomarkers in patients with PAH. However,
current protocols for isolation and quantification of these cells are
laborious and time-consuming. Objective: The aim of this study was to develop
a disposable microfluidic chip platform capable of enumerating CECs and to
test whether CECs measured by this device may serve as useful biomarker in
patients with PAH. Methods: We previously developed a polymeric cell-affinity
microfluidic diagnostic platform for the enumeration of human endothelial
progenitor cells (EPC). Herein, we developed a modified chip for CEC
detection. Human whole blood was collected and injected into microfluidic
chips containing microcolumns pre-coated with anti-CD146 antibodies. Captured
cells were immunofluorescently stained for additional stem and endothelial
cell markers and enumerated by fluorescence microscopy. Results: The CEC
capture chip was initially validated against conventional flow cytometry (r =
0.89, n=7). In a cohort of 66 patients with three types of PAH
(idiopathic/heritable, drug-induced, and connective tissue disease), CEC
numbers were significantly increased 3-5 fold in PAH subjects vs. matched
controls (p < 0.001) and CEC numbers were comparable across PAH sub-classes.
However, they were not related to the potential disease modifiers age and body
mass index. Discussion: The CEC capture chip allows for a rapid and reliable
detection of CECs. The device requires 200-400 μL of whole blood and can
potentially be automated. Thus, it may serve as a bedside test for the
screening and monitoring of patients with PAH and other diseases related to
vascular injury
Patent ductus arteriosus in preterm infants - determinants of risk, treatment effects, and outcome
Im letzten Jahrzehnt konnte ein Paradigmenwandel im Management Frühgeborener mit persistierendem Ductus arteriosus (PDA) hin zu einer selteneren und weniger invasiven Therapie beobachtet werden. Dennoch legen mehrere Beobachtungen einen therapeutischen Benefit einer PDA-Therapie bei ausgewählten Frühgeborenen nahe. Die Kenntnis spezifischer Risikofaktoren stellt eine Voraussetzung für die Entwicklung einer individuell-adaptierten PDA-Therapie dar. Die vorliegende Arbeit ergänzt die verfügbaren Daten zur klinischen Bedeutung einer Thrombozytopenie als Riskofaktor für ein Ausbleiben des PDA-Verschlusses. So kann ein Einfluss der Thrombozytenzahl innerhalb der ersten Lebenswoche auf den pharmakologischen PDA-Verschluss gezeigt werden. Zudem ist eine niedrige Anzahl insbesondere reifer Thrombozyten mit einem Ausbleiben des PDA-Verschlusses in der ersten Lebenswoche assoziiert. Hingegen zeigte sich kein Einfluss des zusätzlich untersuchten VEGF Polymorphismus rs2010963 auf die PDA-Verschlussrate. In der Regel erfolgt eine PDA-Therapie primär pharmakologisch mittels Indometacin oder Ibuprofen. Paracetamol bietet eine neue zusätzliche Option auch in der späten „Rescue“-Therapie des PDA. Die vorliegende Arbeit präsentiert die diesbezüglichen Erfahrungen aus der eigenen Klinik. Immer häufiger werden Frühgeborene nach medikamentöser Therapie mit hämodynamisch nicht signifikantem PDA nach Hause entlassen. In der vorliegenden Arbeit wird gezeigt, dass dieses Vorgehen unter regelmäßiger kinderkardiologischer Kontrolle als sicher anzusehen ist. Für den definitiven Ductusverschluss stehen die chirurgische Ligatur und neuerdings auch katheterinterventionelle Verfahren zur Verfügung. Die PDA-Ligatur wird insbesondere im Hinblick auf mögliche respiratorische Langzeitfolgen kontrovers diskutiert. Daher wurden Lungenfunktionsanalysen bei Frühgeborenen nach erfolgreicher pharmakologischer Ductustherapie und nach sekundärer chirurgischer Ligatur durchgeführt. Die hier vorliegende Arbeit diskutiert die Ergebnisse der zusammengefassten Publikationen und ihre Implikationen für die PDA-Therapie sehr unreifer Frühgeborener und die weitere Forschung