42 research outputs found
Wrench-fault structures superimposed by glaciotectonic complexes, interpreted from high-resolution reflectionseismic sections and boreholes along the western bank of Esrum Sø, north-east Sjælland, Denmark
Logistic Organ Dysfunction Score (LODS): A reliable postoperative risk management score also in cardiac surgical patients?
<p>Abstract</p> <p>Background</p> <p>The original Logistic Organ Dysfunction Sore (LODS) excluded cardiac surgery<ul/>patients from its target population, and the suitability of this score in cardiac surgery patients has never been tested. We evaluated the accuracy of the LODS and the usefulness of its daily measurement in cardiac surgery patients. The LODS is not a true logistic scoring system, since it does not use β-coefficients.</p> <p>Methods</p> <p>This prospective study included all consecutive adult patients who were admitted to<ul/>the intensive care unit (ICU) after cardiac surgery between January 2007 and December 2008. The LODS was calculated daily from the first until the seventh postoperative day. Performance was assessed with Hosmer-Lemeshow (HL) goodness-of-fit test (calibration) and receiver operating characteristic (ROC) curves (discrimination) from ICU admission day until day 7. The outcome measure was ICU mortality.</p> <p>Results</p> <p>A total of 2801 patients (29.6% female) with a mean age of 66.4 ± 10.7 years were<ul/>included. The ICU mortality rate was 5.2% (n = 147). The mean stay on the ICU was 4.3 ± 6.8 days. Calibration of the LODS was good with no significant difference between expected and observed mortality rates on any day (p ≥ 0.05). The initial LODS had an area under the ROC curve (AUC) of 0.81. The AUC was best on ICU day 3 with a value of 0.93, and declined to 0.85 on ICU day 7.</p> <p>Conclusions</p> <p>Although the LODS has not previously been validated for cardiac surgery<ul/>patients it showed reasonable accuracy in prediction of ICU mortality in patients after cardiac surgery.</p
Anticoagulation Strategies in Venovenous Hemodialysis in Critically Ill Patients: A Five-Year Evaluation in a Surgical Intensive Care Unit
Effect of implantable cardioverter-defibrillators in patients with non-ischaemic systolic heart failure and concurrent coronary atherosclerosis
AIMS: Prophylactic implantable cardioverter‐defibrillators (ICD) reduce mortality in patients with ischaemic heart failure (HF), whereas the effect of ICD in patients with non‐ischaemic HF is less clear. We aimed to investigate the association between concomitant coronary atherosclerosis and mortality in patients with non‐ischaemic HF and the effect of ICD implantation in these patients. METHODS AND RESULTS: Patients were included from DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non‐Ischaemic Systolic Heart Failure on Mortality), randomizing patients to ICD or control. Study inclusion criteria for HF were left ventricular ejection fraction ≤ 35% and increased levels (>200 pg/mL) of N‐terminal pro‐brain natriuretic peptide. Of the 1116 patients from DANISH, 838 (75%) patients had available data from coronary angiogram and were included in this subgroup analysis. We used Cox regression to assess the relationship between coronary atherosclerosis and mortality and the effect of ICD implantation. Of the included patients, 266 (32%) had coronary atherosclerosis. Of these, 216 (81%) had atherosclerosis without significant stenoses, and 50 (19%) had significant stenosis. Patients with atherosclerosis were significantly older {67 [interquartile range (IQR) 61–73] vs. 61 [IQR 54–68] years; P < 0.0001}, and more were men (77% vs. 70%; P = 0.03). During a median follow‐up of 64.3 months (IQR 47–82), 174 (21%) of the patients died. The effect of ICD on all‐cause mortality was not modified by coronary atherosclerosis [hazard ratio (HR) 0.94; 0.58–1.52; P = 0.79 vs. HR 0.82; 0.56–1.20; P = 0.30], P for interaction = 0.67. In univariable analysis, coronary atherosclerosis was a significant predictor of all‐cause mortality [HR, 1.41; 95% confidence interval (CI), 1.04–1.91; P = 0.03]. However, this association disappeared when adjusting for cardiovascular risk factors (age, gender, diabetes, hypertension, smoking, and estimated glomerular filtration rate) (HR 1.05, 0.76–1.45, P = 0.76). CONCLUSIONS: In patients with non‐ischaemic systolic heart failure, ICD implantation did not reduce all‐cause mortality in patients either with or without concomitant coronary atherosclerosis. The concomitant presence of coronary atherosclerosis was associated with increased mortality. However, this association was explained by other risk factors
Evolution of male pregnancy associated with remodeling of canonical vertebrate immunity in seahorses and pipefishes
A fundamental problem for the evolution of pregnancy, the most specialized form of parental investment among vertebrates, is the rejection of the nonself-embryo. Mammals achieve immunological tolerance by down-regulating both major histocompatibility complex pathways (MHC I and II). Although pregnancy has evolved multiple times independently among vertebrates, knowledge of associated immune system adjustments is restricted to mammals. All of them (except monotremata) display full internal pregnancy, making evolutionary reconstructions within the class mammalia meaningless. Here, we study the seahorse and pipefish family (syngnathids) that have evolved male pregnancy across a gradient from external oviparity to internal gestation. We assess how immunological tolerance is achieved by reconstruction of the immune gene repertoire in a comprehensive sample of 12 seahorse and pipefish genomes along the “male pregnancy” gradient together with expression patterns of key immune and pregnancy genes in reproductive tissues. We found that the evolution of pregnancy coincided with a modification of the adaptive immune system. Divergent genomic rearrangements of the MHC II pathway among fully pregnant species were identified in both genera of the syngnathids: The pipefishes (Syngnathus) displayed loss of several genes of the MHC II pathway while seahorses (Hippocampus) featured a highly divergent invariant chain (CD74). Our findings suggest that a trade-off between immunological tolerance and embryo rejection accompanied the evolution of unique male pregnancy. That pipefishes survive in an ocean of microbes without one arm of the adaptive immune defense suggests a high degree of immunological flexibility among vertebrates, which may advance our understanding of immune-deficiency diseases
A comparative study of four intensive care outcome prediction models in cardiac surgery patients
<p>Abstract</p> <p>Background</p> <p>Outcome prediction scoring systems are increasingly used in intensive care medicine, but most were not developed for use in cardiac surgery patients. We compared the performance of four intensive care outcome prediction scoring systems (Acute Physiology and Chronic Health Evaluation II [APACHE II], Simplified Acute Physiology Score II [SAPS II], Sequential Organ Failure Assessment [SOFA], and Cardiac Surgery Score [CASUS]) in patients after open heart surgery.</p> <p>Methods</p> <p>We prospectively included all consecutive adult patients who underwent open heart surgery and were admitted to the intensive care unit (ICU) between January 1<sup>st </sup>2007 and December 31<sup>st </sup>2008. Scores were calculated daily from ICU admission until discharge. The outcome measure was ICU mortality. The performance of the four scores was assessed by calibration and discrimination statistics. Derived variables (Mean- and Max- scores) were also evaluated.</p> <p>Results</p> <p>During the study period, 2801 patients (29.6% female) were included. Mean age was 66.9 ± 10.7 years and the ICU mortality rate was 5.2%. Calibration tests for SOFA and CASUS were reliable throughout (p-value not < 0.05), but there were significant differences between predicted and observed outcome for SAPS II (days 1, 2, 3 and 5) and APACHE II (days 2 and 3). CASUS, and its mean- and maximum-derivatives, discriminated better between survivors and non-survivors than the other scores throughout the study (area under curve ≥ 0.90). In order of best discrimination, CASUS was followed by SOFA, then SAPS II, and finally APACHE II. SAPS II and APACHE II derivatives had discrimination results that were superior to those of the SOFA derivatives.</p> <p>Conclusions</p> <p>CASUS and SOFA are reliable ICU mortality risk stratification models for cardiac surgery patients. SAPS II and APACHE II did not perform well in terms of calibration and discrimination statistics.</p
Analysis of shared heritability in common disorders of the brain
ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues