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2.
J Heart Lung Transplant ; 39(12): 1435-1444, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33082079

RESUMO

The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO; <45% vs ≥45% predicted), smoking status, and presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). A hierarchical agglomerative clustering algorithm was performed using Ward's minimum variance method. The clusters were analyzed in terms of baseline characteristics; survival; and response to pulmonary arterial hypertension (PAH) therapy, expressed as changes from baseline to follow-up in functional class, 6-minute walking distance, cardiac biomarkers, and risk. Three clusters were identified: Cluster 1 (n = 106; 12.6%): median age 45 years, 76% females, no comorbidities, mostly never smokers, DLCO ≥45%; Cluster 2 (n = 301; 35.8%): median age 75 years, 98% females, frequent comorbidities, no smoking history, DLCO mostly ≥45%; and Cluster 3 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, and low DLCO. Patients in Cluster 1 had a better response to PAH treatment than patients in the 2 other clusters. Survival over 5 years was 84.6% in Cluster 1, 59.2% in Cluster 2, and 42.2% in Cluster 3 (unadjusted p < 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified distinct phenotypes, which differed in clinical presentation, response to therapy, and survival.

3.
EMBO Mol Med ; 12(9): e12104, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32755029

RESUMO

We aimed at identifying the developmental stage at which leukemic cells of pediatric T-ALLs are arrested and at defining leukemogenic mechanisms based on ATAC-Seq. Chromatin accessibility maps of seven developmental stages of human healthy T cells revealed progressive chromatin condensation during T-cell maturation. Developmental stages were distinguished by 2,823 signature chromatin regions with 95% accuracy. Open chromatin surrounding SAE1 was identified to best distinguish thymic developmental stages suggesting a potential role of SUMOylation in T-cell development. Deconvolution using signature regions revealed that T-ALLs, including those with mature immunophenotypes, resemble the most immature populations, which was confirmed by TF-binding motif profiles. We integrated ATAC-Seq and RNA-Seq and found DAB1, a gene not related to leukemia previously, to be overexpressed, abnormally spliced and hyper-accessible in T-ALLs. DAB1-negative patients formed a distinct subgroup with particularly immature chromatin profiles and hyper-accessible binding sites for SPI1 (PU.1), a TF crucial for normal T-cell maturation. In conclusion, our analyses of chromatin accessibility and TF-binding motifs showed that pediatric T-ALL cells are most similar to immature thymic precursors, indicating an early developmental arrest.

4.
Cytokine ; 133: 155153, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32554157

RESUMO

INTRODUCTION: Congenital heart surgery with cardiopulmonary bypass (CPB) initiates an immune response which frequently leads to organ dysfunction and a systemic inflammatory response. Complications associated with exacerbated immune responses may severely impact the postoperative recovery. The objective was to describe the characteristics of monocyte subpopulations and neutrophils at the level of pattern recognition receptors (PRR) and the cytokine response after CPB in infants. METHODS: An observational cohort study was conducted between June 2016 and June 2017 of infants < 2 years of age, electively admitted for surgical correction of acyanotic congenital heart defects using CPB. Fourteen blood samples were collected sequentially and processed immediately during and up to 48 h following cardiac surgery for each patient. Flow cytometry analysis comprised monocytic and granulocytic surface expression of CD14, CD16, CD64, TLR2, TLR4 and Dectin-1 (CLEC7A). Monocyte subpopulations were further defined as classical (CD14++/CD16-), intermediate (CD14++/CD16+) and nonclassical (CD14+/CD16++) monocytes. Plasma concentrations of 14 cytokines, including G-CSF, GM-CSF, IL-1ß, IL-1RA, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, TNF-α, IFN-γ, MIP-1ß (CCL4) and TGF-ß1, were measured using multiplex immunoassay for seven points in time. RESULTS: Samples from 21 infants (median age 7.4 months) were analyzed by flow cytometry and from 11 infants, cytokine concentrations were measured. Classical and intermediate monocytes showed first receptor upregulation with an increase in CD64 expression four hours post CPB. CD64-expression on intermediate monocytes almost tripled 48 h post CPB (p < 0.0001). TLR4 was only increased on intermediate monocytes, occurring 12 h post CPB (p = 0.0406) along with elevated TLR2 levels (p = 0.0002). TLR4 expression on intermediate monocytes correlated with vasoactive-inotropic score (rs = 0.642, p = 0.0017), duration of ventilation (rs = 0.485, p = 0.0259), highest serum creatinine (rs = 0.547, p = 0.0102), postsurgical transfusion (total volume per kg bodyweight) (rs = 0.469, p = 0.0321) and lowest mean arterial pressure (rs = -0.530, p = 0.0135). Concentrations of IL-10, MIP-1ß, IL-8, G-CSF and IL-6 increased one hour post CPB. Methylprednisolone administration in six patients had no significant influence on the studied surface receptors but led to lower IL-8 and higher IL-10 plasma concentrations. CONCLUSIONS: Congenital heart surgery with CPB induces a systemic inflammatory process including cytokine response and changes in PRR expression. Intermediate monocytes feature specific inflammatory characteristics in the 48 h after pediatric CPB and TLR4 correlates with poorer clinical course, which might provide a potential diagnostic or even therapeutic target.

5.
J Clin Med ; 9(5)2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32414075

RESUMO

INTRODUCTION: Pulmonary hypertension (PH) is a common complication in patients with congenital heart disease (CHD), aggravating the natural, post-operative, or post-interventional course of the underlying anomaly. The various CHDs differ substantially in characteristics, functionality, and clinical outcomes among each other and compared with other diseases with pulmonary hypertension. OBJECTIVE: To describe current management strategies and outcomes for adults with PH in relation to different types of CHD based on real-world data. METHODS AND RESULTS: COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) is a prospective, international PH registry comprising, at the time of data analysis, >8200 patients with various forms of PH. Here, we analyzed a subgroup of 680 patients with PH due to CHD, who were included between 2007 and 2018 in 49 specialized centers for PH and/or CHD located in 11 European countries. At enrollment, the patients´ median age was 44 years (67% female), and patients had either pre-tricuspid shunts, post-tricuspid shunts, complex CHD, congenital left heart or aortic disease, or miscellaneous other types of CHD. Upon inclusion, targeted therapies for pulmonary arterial hypertension (PAH) included endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, and soluble guanylate cyclase stimulators. Eighty patients with Eisenmenger syndrome were treatment-naïve. While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%. The use of oral anticoagulants or antiplatelets was dependent on the underlying diagnosis or comorbidities. In the entire COMPERA-CHD cohort, after follow-up and receiving targeted PAH therapy (n = 511), 91 patients died over the course of a 5-year follow up. The 5-year Kaplan-Meier survival estimate for CHD associated PH was significantly better than that for idiopathic PAH (76% vs. 54%; p < 0.001). Within the CHD associated PH group, survival estimates differed particularly depending on the underlying diagnosis and treatment status. CONCLUSIONS: In COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH. Nevertheless, overall survival of patients with PAH due to CHD was still markedly reduced compared with survival of patients with other types of CHD, despite an increasing number of patients on PAH-targeted combination therapy.

6.
Front Pediatr ; 8: 26, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32175290

RESUMO

Objectives: Empirical assessment of parental needs and affecting factors for counseling success after prenatal diagnosis of congenital heart disease (CHD). Methods:Counseling success after fetal diagnosis of CHD was assessed by a validated standardized questionnaire. The dependent variable "Effective Counseling" was measured in five created analytical dimensions (1. "Transfer of Medical Knowledge-ToMK"; 2. "Trust in Medical Staff-TiMS"; 3. "Transparency Regarding the Treatment Process-TrtTP"; 4. "Coping Resources-CR"; 5. "Perceived Situational Control-PSC"). Analyses were conducted with regard to influencing factors and correlations. Results: Sixty-one individuals (n = 40 females, n = 21 males) were interviewed in a tertiary medical care center. Median gestational age at first parental counseling was 28 + 6 weeks. Parental counseling was performed four times (median), mostly by pediatric cardiologists (83.6%). Overall counseling was successful in 46.3%, satisfying in 51.9%, and unsuccessful in 1.9%. Analyses of the analytical dimensions show that counseling was less successful for TOMK (38.3%) and PSC (39%); success rates were higher if additional written information or links to web sources were provided (60 and 70%, respectively). Length of consultation was positively correlated to counseling success for ToMK (r = 0.458), TrtTP (r = 0.636), PSC (r = 0.341), and TiMS (r = 0.501). Interruptions were negatively correlated to the dimensions TiMS (r = -0.263), and TrtTP (r = -0.210). In the presence of high-risk CHD (37.5%) overall counseling success was lower (26.1%). By cross table analysis and to a low degree of positive correlation in one dimension (ToMK; r = 0.202), counseling tends to be less successful for ToMK, TrtTP, and TiMS if parents have not been counseled by cardiologists. Analyses regarding premises show a parental need for a separate counseling room, which significantly impacts ToMK (r = -0,390) and overall counseling success (r = -0.333). A language barrier was associated with lower success rates for ToMK, TiMS, and CR (21.4, 42.9, and 30.8%). Conclusions: Data from this multidisciplinary study indicate that parents after fetal diagnosis of CHD need uninterrupted counseling of adequate duration and quality in a separate counseling room. Providing additional written information or links to adequate web sources after initial counseling seems necessary. High-risk CHD needs more attention for counseling. There is a trend towards more counseling success if provided by cardiologists.

7.
J Card Fail ; 26(7): 599-609, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32147520

RESUMO

BACKGROUND: Survival of patients with congenital heart defects including increased right ventricular pressure load (ie, tetralogy of Fallot) or pulmonary hypertension is dependent on the function of the right ventricle (RV). RV remodeling has several effects with progressive transition from compensated status to heart failure. Transient receptor potential melastatin 4 (TRPM4) forms cation channels expressed in myocardium, which was shown to modulate cardiac remodeling in the left ventricle of mice. Aim of this study was to identify the role of TRPM4 for contractile function and remodeling of the RV in a rat model of right ventricular pressure load. METHODS AND RESULTS: We performed experiments with untreated rats and under monocrotaline (MCT)-induced pressure load comparing wild-type (Trpm4+/+) and TRPM4-deficient (Trpm4-/-) rats. RV function was characterized by echocardiography and contractility measurements of isolated papillary muscles. RV hypertrophy was investigated by echocardiography and by determination of hypertrophy indices. Pulmonary arterial remodeling was evaluated by echocardiography and histology. TRPM4 protein expression in RV of human, rat and mouse was detected by Western blot and quantified in rat. TRPM4 proteins were detected in RV myocardium of rat and mouse, which were not detectable in TRPM4-deficient animals. Proteins of the same size were found in RV of a pediatric patient with tetralogy of Fallot. In untreated status, Trpm4+/+ and Trpm4-/- rats showed comparable RV contractile function and dimensions. Under pressure load (42 days after MCT injection), RV hypertrophy was significantly increased in Trpm4-/- rats compared with Trpm4+/+ controls, whereas MCT-mediated alterations in cardiac contractility and pulmonary arterial remodeling were not affected by TRPM4 inactivation in rats. Finally, TRPM4 protein expression in RV was drastically reduced in MCT-treated rats, whereas left ventricle of the same animals showed no alteration in TRPM4 expression. CONCLUSIONS: Right ventricular pressure load evoked by MCT treatment in rats leads to a prominent downregulation of TRPM4 protein expression in the RV and complete deletion of TRPM4 expression aggravates right ventricular hypertrophy. Thus, therapeutic modulation of TRPM4 expression and activity might represent a novel approach to target right ventricular remodeling in patients with pulmonary hypertension or otherwise loaded RV.

8.
J Clin Med ; 9(2)2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32046298

RESUMO

The objective of this study was to analyze parental counselling for fetal heart disease in an interdisciplinary and multicenter setting using a validated questionnaire covering medical, sociodemographic, and psychological aspects. n = 168 individuals were recruited from two pediatric heart centers and two obstetrics units. Overall, counselling was combined successful and satisfying in >99%; only 0.7% of parents were dissatisfied. "Perceived situational control" was impaired in 22.6%. Adequate duration of counselling leads to more overall counselling success (r = 0.368 ***), as well as providing written or online information (57.7% vs. 41.5%), which is also correlated to more "Transfer of Medical Knowledge" (r = 0.261 ***). Interruptions of consultation are negatively correlated to overall counselling success (r = -0.247 **) and to "Transparency regarding the Treatment Process" (r = -0.227 **). Lacking a separate counselling room is associated with lower counselling success for "Transfer of Medical Knowledge" (r = 0.210 ***). High-risk congenital heart disease (CHD) is correlated to lower counselling success (42.7% vs. 71.4% in low-risk CHD). A lack of parental language skills leads to less overall counselling success. There is a trend towards more counselling success for "Transfer of Medical Knowledge" after being counselled solely by cardiologists in one center (r = 0.208). Our results indicate that a structured approach may lead to more counselling success in selected dimensions. For complex cardiac malformations, counselling by cardiologists is essential. Parental "Perceived Situational Control" is often impaired, highlighting the need for further support throughout the pregnancy.

9.
Perfusion ; 35(5): 427-435, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31928325

RESUMO

BACKGROUND: Depth of anesthesia may be insufficient in pediatric cardiac anesthesia if a total intravenous anesthetic regimen with opioids and midazolam is used during cardiopulmonary bypass. The advantages of sevoflurane-based balanced anesthesia may be (1) a more graduated regulation of the depth of anesthesia during cardiopulmonary bypass and (2) a reduction in postoperative ventilation time for children in comparison with total intravenous anesthesia. AIM: To evaluate a possibly positive effect of sevoflurane-based balanced anesthesia in children undergoing cardiac surgery we analyzed whether this anesthetic regimen had a significant effect related to (1) depth of anesthesia, (2) the need for opioids during cardiopulmonary bypass as well as on postoperative characteristics such as (3) time of postoperative ventilation, and (4) duration of stay in the intensive care unit in comparison with total intravenous anesthesia. METHODS: In a retrospective analysis, data from heart-lung machine protocols from 2013 to 2016 were compared according to anesthetic regimen (sevoflurane-balanced anesthesia, n = 70 vs. total intravenous anesthesia, n = 65). Children (age: 8 weeks to 14 years) undergoing cardiac surgery with cardiopulmonary bypass were included. As a primary outcome measure, we compared Narcotrend® system-extracted data to detect insufficient phases of anesthetic depth during extracorporeal circulation under moderate hypothermia. Postoperatively, we measured the postoperative ventilation time and the number of days in the intensive care unit. Furthermore, we analyzed patients' specific characteristics such as opioid consumption during cardiopulmonary bypass. Regression analysis relating primary objectives was done using the following variables: anesthetic regimen, age, severity of illness/surgery, and cumulative dosage of opiates during cardiopulmonary bypass. RESULTS: No significant differences were observed in descriptive patient characteristics (age, body weight, height, and body temperature) between the two groups. Further, no significant differences were found in depth of anesthesia by analyzing phases of superficial B1-C2-electroencephalography Narcotrend® data. No marked difference between the groups was observed for the duration of postoperative intensive care unit stay. However, the postoperative ventilation time (median (95% CI, hours)) was significantly lower in the sevoflurane-based balanced anesthesia group (6.0 (2.0-15.0)) than in the total intravenous anesthesia group (13.5 (7.0-25)). A higher dosage of opioids and midazolam was required in the total intravenous anesthesia group to maintain adequate anesthesia during cardiopulmonary bypass. Regression analysis showed an additional, significant impact of the following factors: severity of illness and severity grade of cardiac surgery (according to Aristotle) on the primary endpoint. CONCLUSION: In children undergoing cardiac surgery in our department, the use of sevoflurane-balanced anesthesia during cardiopulmonary bypass showed no superiority of inhalational agents over total intravenous anesthesia with opioids and benzodiazepines preventing phases of superficial anesthesia, but a marked advantage for the postoperative ventilation time compared with total intravenous anesthesia.

10.
Ann Rheum Dis ; 79(3): 370-378, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31818805

RESUMO

BACKGROUND: In this study, we investigated the impact of the new haemodynamic definition of pulmonary arterial hypertension (PAH) as proposed by the 6th PH World Symposium on phenotypes and survival in patients with systemic sclerosis (SSc). METHODS: In SSc patients who were prospectively and consecutively screened for PAH including right heart catheterisation in Heidelberg or Zurich, haemodynamic and clinical variables have been reassessed according to the new PAH definition. Patients have been followed for 3.7±3.7 (median 3.4) years; Kaplan-Meier survival analysis was performed. Patients with significant lung or left heart disease were excluded from comparative analyses. RESULTS: The final dataset included 284 SSc patients, 146 patients (49.2%) had mean pulmonary arterial pressure (mPAP) ≤20 mm Hg, 19.3% had mPAP 21-24 mm Hg and 29.4% had mPAP ≥25 mm Hg. In the group of mildly elevated mPAP, only four patients (1.4% of the whole SSc cohort) had pulmonary vascular resistance (PVR) values ≥3 Wood Units (WU) and could be reclassified as manifest SSc-APAH. Twenty-eight (9.8%) patients with mPAP of 21-24 mm Hg and PVR ≥2 WU already presented with early pulmonary vascular disease with decreased 6 min walking distance (6MWD) (p<0.001), TAPSE (p=0.004) and pulmonary arterial compliance (p<0.001). A PVR ≥2 WU was associated with reduced long-term survival (p=0.002). PVR and 6MWD were independent prognostic predictors in multivariate analysis. CONCLUSION: The data of this study show that a PVR threshold ≥3 WU is too high to enable an early diagnosis of PAH. A PVR threshold ≥2 WU was already associated with pulmonary vascular disease, significantly reduced survival and would be more appropriate in SSc patients with mild PAH.


Assuntos
Hemodinâmica/genética , Hipertensão Arterial Pulmonar/mortalidade , Escleroderma Sistêmico/mortalidade , Idoso , Pressão Arterial/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fenótipo , Prognóstico , Estudos Prospectivos , Hipertensão Arterial Pulmonar/genética , Artéria Pulmonar/fisiopatologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/genética , Resistência Vascular/genética
11.
World J Pediatr Congenit Heart Surg ; 10(6): 803-805, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31701841

RESUMO

Anomalous connection of the superior vena cava to the morphologic left atrium is a rare congenital systemic venous abnormality. As opposed to pulmonary venous anomalies, the significant right-to-left shunt in these patients warrants a correction early in life. Optimal repair technique for combined pulmonary and systemic venous anomalies is not defined yet. Herein, we describe a neonate with such a diagnosis treated with cavoatrial anastomosis, known as Warden procedure with excellent results.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Átrios do Coração/cirurgia , Cardiopatias Congênitas/cirurgia , Veia Cava Superior/cirurgia , Anastomose Cirúrgica/métodos , Átrios do Coração/anormalidades , Humanos , Recém-Nascido , Masculino
12.
Pediatr Pulmonol ; 54(10): 1516-1526, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31313530

RESUMO

OBJECTIVE: While pulmonary arterial hypertension (PAH) is rare in infants and children, it results in substantial morbidity and mortality. In recent years, prognosis has improved, coinciding with the introduction of new PAH-targeted therapies, although much of their use in children is off-label. Evidence to guide the treatment of children with PAH is less extensive than for adults. The goal of this review is to discuss the treatment recommendations for children with PAH, as well as the evidence supporting the use of prostanoids, endothelin receptor antagonists (ERAs), and phosphodiesterase type 5 inhibitors (PDE5i) in this setting. DATA SOURCES: Nonsystematic PubMed literature search and authors' expertise. STUDY SELECTION: Articles were selected concentrating on the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway in PAH. The methodology of an ongoing study evaluating the sGC stimulator riociguat in children with PAH is also described. RESULTS: Despite recent medical advances, improved therapeutic strategies for pediatric PAH are needed. The efficacy and tolerability of riociguat in adults with PAH have been well trialed. CONCLUSION: The pooling of data across trials, supplemented by registry data, will help to confirm the safety and tolerability of prostanoids, ERAs, and PDE5i in children. Ongoing studies will clarify the place of sGC stimulators in the treatment strategy for pediatric PAH.


Assuntos
GMP Cíclico/metabolismo , Óxido Nítrico/metabolismo , Hipertensão Arterial Pulmonar , Guanilil Ciclase Solúvel/metabolismo , Animais , Criança , Humanos , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/epidemiologia , Hipertensão Arterial Pulmonar/metabolismo
13.
Orphanet J Rare Dis ; 14(1): 96, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053163

RESUMO

BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem disease with prominent neurologic manifestations such as epilepsy, cognitive impairment and autism spectrum disorder. mTOR inhibitors have successfully been used to treat TSC-related manifestations in older children and adults. However, data on their safety and efficacy in infants and young children are scarce. The objective of this study is to assess the utility and safety of mTOR inhibitor treatment in TSC patients under the age of 2 years. RESULTS: A total of 17 children (median age at study inclusion 2.4 years, range 0-6; 12 males, 5 females) with TSC who received early mTOR inhibitor therapy were studied. mTOR inhibitor treatment was started at a median age of 5 months (range 0-19 months). Reasons for initiation of treatment were cardiac rhabdomyomas (6 cases), subependymal giant cell astrocytomas (SEGA, 5 cases), combination of cardiac rhabdomyomas and SEGA (1 case), refractory epilepsy (4 cases) and disabling congenital focal lymphedema (1 case). In all cases everolimus was used. Everolimus therapy was overall well tolerated. Adverse events were classified according to the Common Terminology Criteria of Adverse Events (CTCAE, Version 5.0). Grade 1-2 adverse events occurred in 12 patients and included mild transient stomatitis (2 cases), worsening of infantile acne (1 case), increases of serum cholesterol and triglycerides (4 cases), changes in serum phosphate levels (2 cases), increase of cholinesterase (2 cases), transient neutropenia (2 cases), transient anemia (1 case), transient lymphopenia (1 case) and recurrent infections (7 cases). No grade 3-4 adverse events were reported. Treatment is currently continued in 13/17 patients. Benefits were reported in 14/17 patients and included decrease of cardiac rhabdomyoma size and improvement of arrhythmia, decrease of SEGA size, reduction of seizure frequency and regression of congenital focal lymphedema. Despite everolimus therapy, two patients treated for intractable epilepsy are still experiencing seizures and another one treated for SEGA showed no volume reduction. CONCLUSION: This retrospective multicenter study demonstrates that mTOR inhibitor treatment with everolimus is safe in TSC patients under the age of 2 years and shows beneficial effects on cardiac manifestations, SEGA size and early epilepsy.


Assuntos
Serina-Treonina Quinases TOR/antagonistas & inibidores , Esclerose Tuberosa/tratamento farmacológico , Transtorno do Espectro Autista/tratamento farmacológico , Criança , Pré-Escolar , Colesterol/sangue , Colinesterases/sangue , Epilepsia/tratamento farmacológico , Everolimo/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Masculino , Estudos Multicêntricos como Assunto , Fosfatos/sangue , Estudos Retrospectivos , Triglicerídeos/sangue
14.
Case Rep Oncol ; 12(1): 33-38, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30792643

RESUMO

While Wilms tumors (WT) typically present solely with an abdominally palpable mass, rare cases exhibiting vascular tumor growth can also present with circulatory problems. Here, we report the case of a 2.5-year-old girl presenting with upper venous congestion and arterial hypertension as the primary symptoms of intraventricular tumor growth exhibiting remarkable tubular and perfused morphology. Clinical situation stabilized after initiation of neoadjuvant chemotherapy (NAC) with actinomycin D and vincristine, followed by surgical resection via laparotomy and sternotomy supported by cardiopulmonary bypass and deep hypothermia. Our results highlight the previously reported feasibility of this approach, even in primarily unstable patients.

16.
Int J Cardiol ; 272S: 79-88, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30195841

RESUMO

In the summer of 2016, delegates from the German Respiratory Society (DGP), the German Society of Cardiology (DGK) and the German Society of Pediatric Cardiology (DGPK) met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary hypertension (PH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH in adults associated with congenital heart disease (CHD). As such patients are often complex and require special attention, and the general PAH treatment algorithm in the ESC/ERS guidelines appears too unspecific for CHD, the working group proposes an analogous algorithm for the management of PH-CHD which takes the special features of this patient group into consideration, and includes general measures, supportive therapy, targeted PAH drug therapy as well as interventional and surgical procedures. The detailed results and recommendations of the working group on PH in adults with CHD, which were last updated in the spring of 2018, are summarized in this article.


Assuntos
Conferências de Consenso como Assunto , Cardiopatias Congênitas/epidemiologia , Hipertensão Pulmonar/epidemiologia , Guias de Prática Clínica como Assunto/normas , Alemanha/epidemiologia , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/terapia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/terapia
17.
Klin Padiatr ; 230(5): 251-256, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30016810

RESUMO

BACKGROUND: Congenital heart disease is the most common cause of major congenital anomalies. After prenatal diagnosis effective counseling is crucial. However, little research has been undertaken in determining the most effective techniques. OBJECTIVES: To develop a questionnaire suitable to assess parental needs for counseling. MATERIAL AND METHODS: A questionnaire was developed by pediatric cardiologists, maternal-fetal-medicine specialists and sociologists. Likert scaled and open-ended questions are combined with socio-demographical data. The questionnaire was prospectively pilot-tested on 17 parents. We present first analyses of n=41 parents. RESULTS: Response rate was 89.5%. The dependent variable "effective counseling" was measured in 5 dimensions (transfer of medical information, trust in medical staff, transparency of treatment process, coping resources and perceived situational control). The questionnaire's internal consistency is high (Cronbach's alpha>0.7). First analyses show that 44.7% perceived counseling as successful. Transfer of medical information seems difficult (36.6% success rate). Trust in medical staff was high with 75%. CONCLUSIONS: This newly developed tool measures counseling success in five dimensions. A multidisciplinary approach is recommended as methodological expertise is essential for constructing adequate tests. Preliminary data indicate that transfer of medical information is not easily achieved. Further analyses are needed to identify factors that determine counseling success.


Assuntos
Aconselhamento/métodos , Cardiopatias Congênitas/diagnóstico , Pais/psicologia , Pediatria/organização & administração , Diagnóstico Pré-Natal/métodos , Inquéritos e Questionários , Criança , Feminino , Humanos , Pais/educação , Gravidez , Estudos Prospectivos
19.
Cardiol Young ; 27(8): 1504-1521, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28619123

RESUMO

BACKGROUND: Palivizumab is the standard immunoprophylaxis against serious disease due to respiratory syncytial virus infection. Current evidence-based prophylaxis guidelines may not address certain children with CHD within specific high-risk groups or clinical/management settings. METHODS: An international steering committee of clinicians with expertise in paediatric heart disease identified key questions concerning palivizumab administration; in collaboration with an additional international expert faculty, evidence-based recommendations were formulated using a quasi-Delphi consensus methodology. RESULTS: Palivizumab prophylaxis was recommended for children with the following conditions: <2 years with unoperated haemodynamically significant CHD, who are cyanotic, who have pulmonary hypertension, or symptomatic airway abnormalities; <1 year with cardiomyopathies requiring treatment; in the 1st year of life with surgically operated CHD with haemodynamically significant residual problems or aged 1-2 years up to 6 months postoperatively; and on heart transplant waiting lists or in their 1st year after heart transplant. Unanimous consensus was not reached for use of immunoprophylaxis in children with asymptomatic CHD and other co-morbid factors such as arrhythmias, Down syndrome, or immunodeficiency, or during a nosocomial outbreak. Challenges to effective immunoprophylaxis included the following: multidisciplinary variations in identifying candidates with CHD and prophylaxis compliance; limited awareness of severe disease risks/burden; and limited knowledge of respiratory syncytial virus seasonal patterns in subtropical/tropical regions. CONCLUSION: Evidence-based immunoprophylaxis recommendations were formulated for subgroups of children with CHD, but more data are needed to guide use in tropical/subtropical countries and in children with certain co-morbidities.


Assuntos
Consenso , Cardiopatias Congênitas/complicações , Palivizumab/administração & dosagem , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/virologia , Antivirais/administração & dosagem , Pré-Escolar , DNA Viral/genética , Relação Dose-Resposta a Droga , Feminino , Cardiopatias Congênitas/terapia , Humanos , Imunização/métodos , Lactente , Masculino , Infecções por Vírus Respiratório Sincicial/terapia , Vírus Sinciciais Respiratórios/genética
20.
Heart ; 102 Suppl 2: ii36-41, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27053696

RESUMO

Childhood-onset pulmonary arterial hypertension (PAH) is considered complex and multifactorial, with relatively poor estimates of the natural history of the disease. Strategies allowing earlier detection, establishment of disease aetiology together with more accurate and sensitive biomarkers could enable better estimates of prognosis and individualise therapeutic strategies. Evidence is accumulating that genetic defects play an important role in the pathogenesis of idiopathic and hereditary forms of PAH. Altogether nine genes have been reported so far to be associated with childhood onset PAH suggesting that comprehensive multigene diagnostics can be useful in the assessment. Identification of disease-causing mutations allows estimates of prognosis and forms the most effective way for risk stratification in the family. In addition to genetic determinants the analysis of blood biomarkers are increasingly used in clinical practice to evaluate disease severity and treatment responses. As in genetic diagnostics, a multiplex approach can be helpful, as a single biomarker for PAH is unlikely to meet all requirements. This consensus statement reviews the current evidence for the use of genetic diagnostics and use of blood biomarkers in the assessment of paediatric patients with PAH.


Assuntos
Biomarcadores/sangue , Hipertensão Pulmonar Primária Familiar/diagnóstico , Testes Genéticos , Receptores de Activinas Tipo II/genética , Adolescente , Antígenos CD/genética , Fator Natriurético Atrial/sangue , Receptores de Proteínas Morfogenéticas Ósseas/genética , Proteína C-Reativa/metabolismo , Caveolina 1/genética , Criança , Consenso , Gerenciamento Clínico , Endoglina , Células Endoteliais/citologia , Endotelinas/sangue , Hipertensão Pulmonar Primária Familiar/sangue , Hipertensão Pulmonar Primária Familiar/genética , Galectina 3/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/genética , Peptídeo Natriurético Encefálico/sangue , Proteínas do Tecido Nervoso/genética , Fragmentos de Peptídeos/sangue , Canais de Potássio de Domínios Poros em Tandem/genética , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Receptor Notch3 , Receptores de Superfície Celular/genética , Receptores Notch/genética , Proteína Smad8/genética , Troponina T/sangue , Ácido Úrico/sangue
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