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|Title of publication||publication_post_content||DOI||Journal||Disease area||Partner / Member||DZL site||Work Type||Year|
|Title of publication||publication_post_content||DOI||Journal||Disease area||Partner / Member||DZL site||Work Type||Year|
|Pregnancy and Infants' Outcome: Nutritional and Metabolic Implications||
Pregnancy is a complex period of human growth, development, and imprinting. Nutrition and metabolism play a crucial role for the health and well-being of both mother and fetus, as well as for the long-term health of the offspring. Nevertheless, several biological and physiological mechanisms related to nutritive requirements together with their transfer and utilization across the placenta are still poorly understood. In February 2009, the Child Health Foundation invited leading experts of this field to a workshop to critically review and discuss current knowledge, with the aim to highlight priorities for future research. This paper summarizes our main conclusions with regards to maternal preconceptional body mass index, gestational weight gain, placental and fetal requirements in relation to adverse pregnancy and long-term outcomes of the fetus (nutritional programming). We conclude that there is an urgent need to develop further human investigations aimed at better understanding of the basis of biochemical mechanisms and pathophysiological events related to maternal-fetal nutrition and offspring health. An improved knowledge would help to optimize nutritional recommendations for pregnancy.
|10.1080/10408398.2012.745477||Crit Rev Food Sci Nutr||AA||FZB||ARCN||Review||2016|
|Do not leave the heart arrested. Non-cardioplegic continuous myocardial perfusion during complex aortic arch repair improves cardiac outcome||
OBJECTIVES: Myocardial protection with cardioplegia alone may be inadequate during complex aortic arch surgery, potentially resulting in postoperative myocardial insufficiency. We hypothesized that non-cardioplegic continuous myocardial perfusion (CMP) is feasible and safe to protect the heart while operating on the aortic arch, and improves cardiac outcome. METHODS: Between April 2010 and April 2014, 144 patients (60% male, age: 60 +/- 13 years) underwent complex aortic arch repair in our institution using prefabricated, branched aortic arch grafts. In 36 patients, the hearts were protected with a combination of cardioplegic cardiac arrest during cardiac procedures and subsequent non-cardioplegic CMP group during aortic arch repair. In 108 patients, myocardial protection was achieved by cardioplegic arrest (CA group) only. RESULTS: Preoperative risk factors were comparable in both groups. Acute aortic dissection was the indication for surgery in 42% (CMP) and 44% (CA) of patients; 22% (CMP) and 29% (CA) of patients underwent reoperations. Concomitant cardiac procedures were similar. CMP patients received a frozen elephant trunk more frequently (89 vs 66%, P = 0.0096). Cardiopulmonary bypass time (242 +/- 50 vs 264 +/- 68 min; P = 0.046), and cardiac ischaemic time (49 +/- 32 vs 149 +/- 56 min, P < 0.0001) were significantly lower in the CMP group. There were no conversions to CA in the CMP group. Aortic arch repair was not prolonged by CMP. Low cardiac output syndrome occurred less frequently in the CMP group (3 vs 22%, P = 0.0052). Thirty-day mortality was significantly lower in the CMP group (6 vs 21%, P = 0.040). There were no cardiac deaths in the CMP group (0 vs 9%, P = 0.067). Neurological outcome was comparable. Blood loss was higher in the CA group (P < 0.001). CONCLUSIONS: Routinely protecting the heart during complex aortic arch repair with non-cardioplegic CMP is a valuable new concept. The CMP technique is feasible and safe, does not prolong aortic arch repair, reduces myocardial damage and improves cardiac outcome. Further evaluation in a larger patient cohort is warranted to establish this novel technique.
|10.1093/ejcts/ezv009||Eur J Cardiothorac Surg||ELD||MHH||BREATH||Original||2016|
|Comparison of C-arm Computed Tomography and Digital Subtraction Angiography in Patients with Chronic Thromboembolic Pulmonary Hypertension||
PURPOSE: To assess the feasibility and diagnostic performance of contrast-enhanced, C-arm computed tomography (CACT) of the pulmonary arteries compared to digital subtraction angiography (DSA) in patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH). MATERIALS: Fifty-two patients with CTEPH underwent ECG-gated DSA and contrast-enhanced CACT. Two readers (R1, R2) independently evaluated pulmonary artery segments and their sub-segmental branching using DSA and CACT for optimal image quality. Afterwards, the diagnostic findings, i.e., intraluminal filling defects, stenosis, and occlusion, were compared. Inter-modality and inter-observer agreement was calculated, and subsequently consensus reading was done and correlated to a reference standard representing the overall consensus of both modalities. Fisher's exact test and Cohen's Kappa were applied. RESULTS: A total of 1352 pulmonary segments were evaluated, of which 1255 (92.8 %) on DSA and 1256 (92.9 %) on CACT were rated to be fully diagnostic. The main causes of the non-diagnostic image quality were motion artifacts on CACT (R1:37, R2:78) and insufficient contrast enhancement on DSA (R1:59, R2:38). Inter-observer agreement was good for DSA (kappa = 0.74) and CACT (kappa = 0.75), while inter-modality agreement was moderate (R1: kappa = 0.46, R2: kappa = 0.47). Compared to the reference standard, the inter-modality agreement for CACT was excellent (kappa = 0.96), whereas it was inferior for DSA (kappa = 0.61) due to the higher number of abnormal consensus findings read as normal on DSA. CONCLUSION: CACT of the pulmonary arteries is feasible and provides additional information to DSA. CACT has the potential to improve the diagnostic work-up of patients with CTEPH and may be particularly useful prior to surgical or interventional treatment.
|10.1007/s00270-015-1090-7||Cardiovasc Intervent Radiol||PH||MHH||BREATH||Original||2016|
|Retrograde in situ versus antegrade pulmonary preservation in clinical lung transplantation: a single-centre experience||
OBJECTIVE: Experimental and clinical studies have indicated a beneficial effect of retrograde lung preservation on post-transplant results. Accordingly, we conducted a non-randomized trial. METHODS: A total of 209 consecutive recipients transplanted with low-potassium dextrane (LPD)-preserved lungs were eligible for analysis. Antegrade lung preservation (AP) was performed in 173 patients and retrograde in situ perfusion (RP) in 36 patients using low-potassium dextrane solution in all cases. The prostacycline was added to preservation solution. RESULTS: The main donor, graft and recipient characteristics did not differ significantly between groups. There was a beneficial trend toward improved oxygenation indices in the RP cohort within the initial 48 post-transplant hours. The incidence of severe primary graft dysfunction was comparable up to 48 h post-transplant and was significantly increased in the RP cohort 72 h post-transplant (2.2% AP vs 14.8% RP, P = 0.016). Fatal bronchial dehiscences occurred more often in RP recipients (5.6% RP vs 0.6% AP, P = 0.067). The occurrence of bronchial stenoses revealed a slightly improved trend in the RP group (24.9% AP vs 13.9% RP, P = 0.218). Survival (P = 0.927) and bronchiolitis obliterans syndrome-free survival (P = 0.337) were comparable between groups. CONCLUSION: In our clinical survey, this analysis does not confirm the beneficial results of retrograde lung preservation alone, as was previously observed in experimental studies.
|10.1093/ejcts/ezv108||Eur J Cardiothorac Surg||ELD||MHH||BREATH||Original||2016|
|Unchanged NADPH Oxidase Activity in Nox1-Nox2-Nox4 Triple Knockout Mice: What Do NADPH-Stimulated Chemiluminescence Assays Really Detect?||
NADPH oxidases of the Nox family are considered important sources of cellular reactive oxygen species (ROS) production. This conclusion is, in part, based on the ability of NADPH to elicit a chemiluminescence signal in tissue/cell homogenates or membrane preparations in the presence of enhancers such as lucigenin, luminol, or L012. However, the ability of these particular assays to specifically detect Nox activity and Nox-derived ROS has not been proven. In this study, we demonstrate that combined knockout of the three main Nox enzymes of the mouse (Nox1-Nox2-Nox4 triple knockout) had no impact on NADPH-stimulated chemiluminescence signals in the aorta, heart, and kidney homogenates. In the NADPH-stimulated membrane assays, no effect of in vivo angiotensin II pretreatment or deletion of Nox enzymes was observed. In in vitro studies in HEK293 cells, the overexpression of Nox5 or Nox4 markedly increased ROS production in intact cells, whereas overexpression of Nox5 or Nox4 had no influence on the signal in membrane assays. In contrast, overexpression of nitric oxide synthase or cytochrome P450 enzymes resulted in an increased chemiluminescence signal in isolated membranes. On the basis of these observations, we propose the hypothesis that NADPH-stimulated chemiluminescence-based membrane assays, as currently used, do not reflect Nox activity.
|10.1089/ars.2015.6314||Antioxid Redox Signal||General Lung and Other||JLU||UGMLC||Original||2016|
|Moisture damage in home associates with systemic inflammation in children||
This study investigated the association between confirmed moisture damage in homes and systemic subclinical inflammation in children. Home inspections were performed in homes of 291 children at the age of 6 years. Subclinical inflammation at the age of 6 years was assessed by measuring the circulating levels of C-reactive protein (CRP) and leukocytes in peripheral blood and fractional exhaled nitric oxide (FeNO). Proinflammatory cytokines interleukin (IL)-1beta and IL-6 and tumor necrosis factor (TNF)-alpha were measured in unstimulated, and in phorbol 12-myristate 13-acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG)-stimulated whole blood. Major moisture damage in the child's main living areas (living room, kitchen, or child's bedroom) and moisture damage with mold in the bathroom were associated with increased levels of CRP and stimulated production of several proinflammatory cytokines. There were no significant associations between moisture damage/visible mold and leukocyte or FeNO values. The results suggest that moisture damage or mold in home may be associated with increased systemic subclinical inflammation and proinflammatory cytokine responsiveness.
|10.1111/ina.12216||Indoor Air||General Lung and Other||LMU, UMR||CPC-M, UGMLC||Original||2016|
|[Minimally invasive chest surgery. Is palpation control still necessary with modern computed tomography?]||
BACKGROUND: A fundamental argument against minimally invasive oncological chest surgery is the risk of overlooking pulmonary nodules due to a lack of intraoperative palpation. In the literature this risk in the treatment of primary lung cancer is given as up to 8.4 % and as more than 15 % in the surgical treatment of pulmonary metastases. OBJECTIVE: The aim of this study was to evaluate if modern computed tomography (CT) is sensitive enough to replace intraoperative palpation and justify a minimally invasive approach. PATIENTS AND METHODS: The medical records from 92 patients who underwent 95 open lung resections due to pulmonary malignancies from April 2010 through September 2011 at the Medical School Hannover were retrospectively analysed. A comparison was carried out between the lesions detected preoperatively by CT and those removed during surgery and histologically confirmed as being malignant. Patients with more than five nodules suspected of being malignant in the preoperative CT scan were excluded. RESULTS: According to the final histopathological examination 125 malignant nodules were resected and 2 of these were not detected in the preoperative CT scan, which were performed in external hospitals with a slice thickness of 5 mm and 8 mm, respectively. This represents a sensitivity of 98 % for all CT scans in terms of detection of pulmonary nodules. With thin slice CT (slice thickness up to 1.5 mm) a sensitivity of 100 % was even achieved. CONCLUSION: The results demonstrate that a high sensitivity of thin slice CT for detection of lung nodules can be achieved. Based on these results the categorical reservation with respect to thoracoscopic resection of pulmonary metastases should be reconsidered in suitable patients where a minimally invasive resection is possible. The extent of lymph node dissection is not influenced by these data. Further studies with larger sample sizes are warranted to confirm these results.
|Peak weight velocity in infancy is negatively associated with lung function in adolescence||
BACKGROUND: Rapid weight gain during infancy increases childhood asthma risk, which might be related to impaired lung function. This study investigated associations between peak weight velocity (PWV) during the first two years of life and spirometric lung function indices at 15 years of age. METHODS: Data from 1842 children participating in the GINIplus German birth cohort who underwent spirometry at age 15 were analysed. PWV was calculated from weight measurements obtained between birth and two years of age. Generalised additive models were fitted after adjustment for potential confounding factors (birth weight, height, and age at lung function testing). Results are presented per interquartile range increase (3.5 kg/year) in PWV. RESULTS: PWV was negatively associated with pre-bronchodilation flow rates after extensive adjustment for potential confounders including asthma: forced expiratory flow at 50% of forced vital capacity (FEF50 ) decreased by 141 ml/s (95%CI = [-225;-57]), FEF75 by 84 ml/s [-144;-24] and FEF25-75 by 118 ml/s [-192;-44]. FEV1 /FVC was also negatively associated with PWV (-0.750% [-1.273;-0.226]) whereas forced expiratory volume in 1s (FEV1 ) and forced vital capacity (FVC) were not. Similar results were found for measurements post-bronchodilation. CONCLUSION: Early life weight gain was negatively associated with flow indices in adolescence, suggesting structural changes in peripheral lungs.
|10.1002/ppul.23216||Pediatr Pulmonol||General Lung and other||HMGU||CPC-M||Original||2016|
|Prevalence of meconium ileus marks the severity of mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene||
RATIONALE: Meconium ileus (MI) is a perinatal complication in cystic fibrosis (CF), which is only minimally influenced by environmental factors. We derived and examined MI prevalence (MIP) scores to assess CFTR phenotype-phenotype correlation for severe mutations. METHOD: MIP scores were established using a Canadian CF population (n = 2,492) as estimates of the proportion of patients with MI among all patients carrying the same CFTR mutation, focusing on patients with p.F508del as the second allele. Comparisons were made to the registries from the US CF Foundation (n = 43,432), Italy (Veneto/Trentino/Alto Adige regions) (n = 1,788), and Germany (n = 3,596). RESULTS: The prevalence of MI varied among the different registries (13-21%). MI was predominantly prevalent in patients with pancreatic insufficiency carrying "severe" CFTR mutations. In this severe spectrum MIP scores further distinguished between mutation types, for example, G542X (0.31) with a high, F508del (0.22) with a moderate, and G551D (0.08) with a low MIP score. Higher MIP scores were associated with more severe clinical phenotypes, such as a lower forced expiratory volume in 1 second (P = 0.01) and body mass index z score (P = 0.04). CONCLUSIONS: MIP scores can be used to rank CFTR mutations according to their clinical severity and provide a means to expand delineation of CF phenotypes.Genet Med 18 4, 333-340.
|Thoracic and abdominal aortic diameters in a general population: MRI-based reference values and association with age and cardiovascular risk factors||
OBJECTIVES: To generate reference values for thoracic and abdominal aortic diameters determined by magnetic resonance imaging (MRI) and analyse their association with cardiovascular risk factors in the general population. METHODS: Data from participants (n = 1759) of the Study of Health in Pomerania were used for analysis in this study. MRI measurement of thoracic and abdominal aortic diameters was performed. Parameters for calculation of reference values according to age and sex analysis were provided. Multivariable linear regression models were used for determination of aortic diameter-related risk factors, including smoking, blood pressure (BP), high-density lipoprotein cholesterol (HDL-C). RESULTS: For the ascending aorta (beta = -0.049, p < 0.001), the aortic arch (beta = -0.061, p < 0.001) and the subphrenic aorta (beta = -0.018, p = 0.004), the body surface area (BSA)-adjusted diameters were lower in men. Multivariable-adjusted models revealed significant increases in BSA-adjusted diameters with age for all six aortic segments (p < 0.001). Consistent results for all segments were observed for the positive associations of diastolic BP (beta = 0.001; 0.004) and HDL (beta = 0.035; 0.087) with BSA-adjusted aortic diameters and for an inverse association of systolic BP (beta = -0.001). CONCLUSIONS: Some BSA-adjusted median aortic diameters are smaller in men than in women. All diameters increase with age, diastolic blood pressure and HDL-C and decrease as systolic BP increases. KEY POINTS: * Median aortic diameter increases with age and diastolic blood pressure. * Median aortic diameter is larger in men than in women. * Some BSA-adjusted median aortic diameters are smaller in men than in women.
|10.1007/s00330-015-3926-6||Eur Radiol||General Lung and Other||UKSH (Kiel)||ARCN||Original||2016|
|4||Original||Originalarbeiten mit Peer Review (z. B. Research Paper, Meta-Analyse, Short Communication, Research Letter, Guideline)|
|6||Review||Originalarbeiten mit begrenztem Peer Review|
|8||Other||Sonstige Publikationen ohne Peer Review (z. B. Letter to the Editor, Reply, Response, Editorial)|
|10||Involved site partner(s)||1|
|12||CAU||Christian-Albrechts-Universität zu Kiel|
|14||UzL||Universität zu Lübeck|
|20||MHH||Medizinische Hochschule Hannover (Hannover Medical School)|