Pulmonary perfusion with oxygenated blood or custodiol HTK solution during cardiac surgery for postoperative pulmonary function in COPD patients: a trial protocol for the randomized, clinical, parallel group, assessor and data analyst blinded Pulmonary Protection Trial

BACKGROUND: Five to thirty percent of patients undergoing cardiac surgery present with chronic obstructive pulmonary disease (COPD) and have a 2- to 10-fold higher 30-day mortality risk. Cardiopulmonary bypass (CPB) creates a whole body systemic inflammatory response syndrome (SIRS) that could impair pulmonary function. Impaired pulmonary function can, however, be attenuated by pulmonary perfusion with oxygenated blood or custodiol HTK (histidine-tryptophan-ketoglutarate) solution. METHODS/DESIGN: The Pulmonary Protection Trial (PP-Trial) randomizes 90 patients undergoing CPB-dependent cardiac surgery to evaluate whether pulmonary perfusion with oxygenated blood or custodiol HTK solution reduces postoperative pulmonary dysfunction in COPD patients. Further, we aim for a non-randomized evaluation of postoperative pulmonary function after transcatheter aortic-valve implantation (TAVI). The primary outcome measure is the oxygenation index measured from anesthesia induction to the end of surgery and until 24 hours after anesthesia induction for a total of six evaluations. DISCUSSION: Patients with COPD may be impaired by hypoxemia and SIRS. Thus, prolonged recovery and even postoperative complications and death may be reflected by the degree of hypoxemia and SIRS. The limited sample size does not aim for confirmatory conclusions on mortality, cardiovascular complications or risk of pneumonia and sepsis, but the PP-Trial is considered an important feasibility trial paving the road for a multicenter confirmatory trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01614951

Large D-Dimer Fluctuation in Normal Pregnancy: A Longitudinal Cohort Study of 4,117 Samples from 714 Healthy Danish Women

Introduction. D-dimer levels increase throughout pregnancy, hampering the usefulness of the conventional threshold for dismissing thromboembolism. This study investigates the biological fluctuation of D-dimer in normal pregnancy. Methods. A total of 801 healthy women with expected normal pregnancies were recruited. D-dimer was repeatedly measured during pregnancy, at active labor, and on the first and second postpartum days. Percentiles for each gestational week were calculated. Each individual D-dimer was normalized by transformation into percentiles for the relevant gestational age or delivery group. The range in percentage points during the pregnancy and the delivery was calculated, and reference intervals were calculated for each pregnancy trimester, during vaginal delivery and scheduled and emergency cesarean section, and for the first and second day postpartum. Results. D-dimer increased during pregnancy; the maximal fluctuation was approximately 20 percentile points in approximately half of the women. In one out of ten women, the D-dimer values fluctuated by more than 50 percentile points. Conclusions. Due to the biological variation in D-dimer within each individual woman during normal pregnancy, repeated D-dimer measurements are of no clinical use in the evaluation of thromboembolic events during pregnancy

The prevalence of tumour markers in malignant pleural effusions associated with primary pulmonary adenocarcinoma:a retrospective study

BACKGROUND: Oncological treatment of primary pulmonary adenocarcinoma (AC) includes drugs targeting the pathways involving programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK). The aim of the study was to report the prevalence of these tumour markers in pleural fluid with cytology positive for pulmonary AC and the potential influence of volume pleural fluid tested. METHODS: We retrospectively reviewed all thoracenteses performed in a two-year period at our interventional unit at Department of Respiratory Medicine at Zealand University Hospital Naestved, Denmark. ALK and PD-L1 testing was done using immunohistochemistry and EGFR testing using next-generation sequencing. We included pleural fluid specimens containing malignant cells originating from primary pulmonary AC and with at least one tumour marker requested by the clinicians. RESULTS: When screening 927 pleural fluid specimens, we identified 57 in accordance with the inclusion criteria. PD-L1, ALK and EGFR were obtained in 35/55 (64%), 38/57 (67%) and 26/47 (55%), respectively. The prevalence did not increase when analysing volumes > 50 mL (p = 0.21–0.58) CONCLUSION: Tumour markers in pleural fluid specimens containing cells from pulmonary AC can be demonstrated in more than half of the cases. Therefore, supplementary invasive procedures than thoracentesis could potentially await these analyses

Pulmonary artery perfusion versus no pulmonary perfusion during cardiopulmonary bypass in patients with COPD:a randomised clinical trial

INTRODUCTION: Absence of pulmonary perfusion during cardiopulmonary bypass (CPB) may be associated with reduced postoperative oxygenation. Effects of active pulmonary artery perfusion were explored in patients with chronic obstructive pulmonary disease (COPD) undergoing cardiac surgery. METHODS: 90 patients were randomised to receive pulmonary artery perfusion during CPB with either oxygenated blood (n=30) or histidine-tryptophan-ketoglutarate (HTK) solution (n=29) compared with no pulmonary perfusion (n=31). The coprimary outcomes were the inverse oxygenation index compared at 21 hours after starting CPB and longitudinally in a mixed-effects model (MEM). Secondary outcomes were tracheal intubation time, serious adverse events, mortality, days alive outside the intensive care unit (ICU) and outside the hospital. RESULTS: 21 hours after starting CPB patients receiving pulmonary artery perfusion with normothermic oxygenated blood had a higher oxygenation index compared with no pulmonary perfusion (mean difference (MD) 0.94; 95% CI 0.05 to 1.83; p=0.04). The blood group had also a higher oxygenation index both longitudinally (MEM, p=0.009) and at 21 hours (MD 0.99; CI 0.29 to 1.69; p=0.007) compared with the HTK group. The latest result corresponds to a difference in the arterial partial pressure of oxygen of 23 mm Hg with a median fraction of inspired oxygen of 0.32. Yet the blood or HTK groups did not demonstrate a longitudinally higher oxygenation index compared with no pulmonary perfusion (MEM, p=0.57 and 0.17). Similarly, at 21 hours there was no difference in the oxygenation index between the HTK group and those no pulmonary perfusion (MD 0.06; 95% CI −0.73 to 0.86; p=0.87). There were no statistical significant differences between the groups for the secondary outcomes. DISCUSSION: Pulmonary artery perfusion with normothermic oxygenated blood during cardiopulmonary bypass appears to improve postoperative oxygenation in patients with COPD undergoing cardiac surgery. Pulmonary artery perfusion with hypothermic HTK solution does not seem to improve postoperative oxygenation. TRIAL REGISTRATION NUMBER: NCT01614951; Pre-results

Development of Dietary Patterns Spanning Infancy and Toddlerhood: Relation to Body Size, Composition and Metabolic Risk Markers at Three Years

Little is known about the development of dietary patterns during toddlerhood and the relation to growth and health. The study objective was to characterise the development of dietary patterns from 9-36 mo of age and investigate the association to body size, body composition and metabolic risk markers at 36 mo. Food records were filled out at 9, 18 and 36 mo of age (n = 229). Dietary patterns were identified by principal component analysis (PCA). Three dietary patterns were identified: Transition Food, Healthy Food and Traditional Food. The course of development in dietary patterns from 9-36 mo indicated tracking for a relatively large group of participants in the three patterns. Transition Food and Healthy Food were associated with some of the investigated outcomes. Children with lower adherence to the Transition Food pattern than average at 18 and 36 mo irrespectively of intake at 9 mo had higher BMI z-scores at 36 mo. Similar trend was identified for higher fat mass indices. Children with lower adherence to the Healthy Food pattern than average at all three ages compared to children with higher adherence to the Healthy Food pattern at the first two registrations, 9 and 18 mo had higher total cholesterol and LDL. Hence, this could represent undesirable development of dietary patterns in toddlers. In conclusion, development of dietary patterns can be exploratory characterised by PCA and related to potential cardiovascular risk markers in toddlers even within a relatively homogeneous population with a high socioeconomic status. The tracking of dietary patterns from 9 mo of age indicates a need for early and sustained promotion of healthy diets

Changed activation, oxygenation, and pain response of chronically painful muscles to repetitive work after training interventions: a randomized controlled trial

The aim of this randomized controlled trial was to assess changes in myalgic trapezius activation, muscle oxygenation, and pain intensity during repetitive and stressful work tasks in response to 10 weeks of training. In total, 39 women with a clinical diagnosis of trapezius myalgia were randomly assigned to: (1) general fitness training performed as leg-bicycling (GFT); (2) specific strength training of the neck/shoulder muscles (SST) or (3) reference intervention without physical exercise. Electromyographic activity (EMG), tissue oxygenation (near infrared spectroscopy), and pain intensity were measured in trapezius during pegboard and stress tasks before and after the intervention period. During the pegboard task, GFT improved trapezius oxygenation from a relative decrease of −0.83 ± 1.48 μM to an increase of 0.05 ± 1.32 μM, and decreased pain development by 43%, but did not affect resting levels of pain. SST lowered the relative EMG amplitude by 36%, and decreased pain during resting and working conditions by 52 and 38%, respectively, without affecting trapezius oxygenation. In conclusion, GFT performed as leg-bicycling decreased pain development during repetitive work tasks, possibly due to improved oxygenation of the painful muscles. SST lowered the overall level of pain both during rest and work, possibly due to a lowered relative exposure as evidenced by a lowered relative EMG. The results demonstrate differential adaptive mechanisms of contrasting physical exercise interventions on chronic muscle pain at rest and during repetitive work tasks

Distribution of cholinergic nerve terminals in the aged human brain measured with [18F]FEOBV PET and its correlation with histological data

Introduction: [18F]fluoroetoxybenzovesamicol ([18F]FEOBV) is a positron emission topography (PET) tracer for the vesicular acetylcholine transporter (VAChT), a protein located predominantly in synaptic vesicles in cholinergic nerve terminals. We aimed to use [18F]FEOBV PET to study the cholinergic topography of the healthy human brain. Materials and methods: [18F]FEOBV PET brain data volumes of healthy elderly humans were normalized to standard space and intensity-normalized to the white matter. Stereotactic atlases of regions of interest were superimposed to describe and quantify tracer distribution. The spatial distribution of [18F]FEOBV PET uptake was compared with histological and gene expression data. Results: Twenty participants of both sexes and a mean age of 73.9 ± 6.0 years, age-range [64; 86], were recruited. Highest tracer binding was present in the striatum, some thalamic nuclei, and the basal forebrain. Intermediate binding was found in most nuclei of the brainstem, thalamus, and hypothalamus; the vermis and flocculonodular lobe; and the hippocampus, amygdala, insula, cingulate, olfactory cortex, and Heschl's gyrus. Lowest binding was present in most areas of the cerebral cortex, and in the cerebellar nuclei and hemispheres. The spatial distribution of tracer correlated with immunohistochemical post-mortem data, as well as with regional expression levels of SLC18A3, the VAChT coding gene. Discussion: Our in vivo findings confirm the regional cholinergic distribution in specific brain structures as described post-mortem. A positive spatial correlation between tracer distribution and regional gene expression levels further corroborates [18F]FEOBV PET as a validated tool for in vivo cholinergic imaging. The study represents an advancement in the continued efforts to delineate the spatial topography of the human cholinergic system in vivo