Clinical significance and risk factors for new onset and recurring atrial fibrillation following cardiac surgery - a retrospective data analysis

Background

Although mortality after cardiac surgery has significantly decreased in the last decade, patients still experience clinically relevant postoperative complications. Among others, atrial fibrillation (AF) is a common consequence of cardiac surgery, which is associated with prolonged hospitalization and increased mortality.

Methods

We retrospectively analyzed data from patients who underwent coronary artery bypass grafting, valve surgery or a combination of both at the University Hospital Muenster between April 2014 and July 2015. We evaluated the incidence of new onset and intermittent/permanent AF (patients with pre- and postoperative AF). Furthermore, we investigated the impact of postoperative AF on clinical outcomes and evaluated potential risk factors.

Results

In total, 999 patients were included in the analysis. New onset AF occurred in 24.9% of the patients and the incidence of intermittent/permanent AF was 59.5%. Both types of postoperative AF were associated with prolonged ICU length of stay (median increase approx. 2 days) and duration of mechanical ventilation (median increase 1 h). Additionally, new onset AF patients had a higher rate of dialysis and hospital mortality and more positive fluid balance on the day of surgery and postoperative days 1 and 2. In a multiple logistic regression model, advanced age (odds ratio (OR)?=?1.448 per decade increase, p?<?0.0001), a combination of CABG and valve surgery (OR?=?1.711, p?=?0.047), higher C-reactive protein (OR?=?1.06 per unit increase, p?<?0.0001) and creatinine plasma concentration (OR?=?1.287 per unit increase, p?=?0.032) significantly predicted new onset AF. Higher Horowitz index values were associated with a reduced risk (OR?=?0.996 per unit increase, p?=?0.012). In a separate model, higher plasma creatinine concentration (OR?=?2.125 per unit increase, p?=?0.022) was a significant risk factor for intermittent/permanent AF whereas higher plasma phosphate concentration (OR?=?0.522 per unit increase, p?=?0.003) indicated reduced occurrence of this arrhythmia.

Conclusions

New onset and intermittent/permanent AF are associated with adverse clinical outcomes of elective cardiac surgery patients. Different risk factors implicated in postoperative AF suggest different mechanisms might be involved in its pathogenesis. Customized clinical management protocols seem to be warranted for a higher success rate of prevention and treatment of postoperative AF.

     

Two Southern Ocean diatoms are more sensitive to ocean acidification and changes in irradiance than the prymnesiophyte Phaeocystis antarctica

To better understand the impact of ocean acidification (OA) and changes in light availability on Southern Ocean phytoplankton physiology, we investigated the effects of pCO₂ (380 and 800 µatm) in combination with low and high irradiance (20 or 50 and 200 µmol photons m^?2 s^?1) on growth, particulate organic carbon (POC) fixation and photophysiology in the three ecologically relevant species Chaetoceros debilis, Fragilariopsis kerguelensis and Phaeocystis antarctica. Irrespective of the light scenario, neither growth nor POC per cell was stimulated by OA in any of the tested species and the two diatoms even displayed negative responses in growth (e.g. C. debilis) or POC content (e.g. F. kerguelensis) under OA in conjunction with high light. For both diatoms, also maximum quantum yields of photosystem II (F_v/F_m) were decreased under these conditions, indicating lowered photochemical efficiencies. To counteract the negative effects by OA and high light, the two diatoms showed diverging photoacclimation strategies. While cellular chlorophyll a (Chl a) and fucoxanthin contents were enhanced in C. debilis to potentially maximize light absorption, F. kerguelensis exhibited reduced Chl a per cell, increased disconnection of antennae from photosystem II reaction centers and strongly lowered absolute electron transport rates (ETR). The decline in ETRs in F. kerguelensis might be explained in terms of different species‐specific strategies for tuning the available flux of adenosine triphosphate and nicotinamide adenine dinucleotide phosphate. Overall, our results revealed that P. antarctica was more tolerant to OA and changes in irradiance than the two diatoms, which may have important implications for biogeochemical cycling.     

Expression of zebrafish aldh1a3 (raldh3) and absence of aldh1a1 in teleosts

The vitamin A-derived morphogen retinoic acid (RA) plays important roles during the development of chordate animals. The Aldh1a-family of RA-synthesizing enzymes consists of three members, Aldh1a1-3 (Raldh1-3), that are dynamically expressed throughout development. We have searched the known teleost genomes for the presence of Raldh family members and have found that teleost fish possess orthologs of Aldh1a2 and Aldh1a3 only. Here we describe the expression of aldh1a3 in the zebrafish, Danio rerio. Whole mount in situ hybridization shows that aldh1a3 is expressed during eye development in the retina flanking the optic stalks and later is expressed ventrally, opposite the expression domain of aldh1a2. During inner ear morphogenesis, aldh1a3 is expressed in developing sensory epithelia of the cristae and utricular macula and is specifically up-regulated in epithelial projections throughout the formation of the walls of the semicircular canals and endolymphatic duct. In contrast to the mouse inner ear, which expresses all three Raldhs, we find that only aldh1a3 is expressed in the zebrafish otocyst, while aldh1a2 is present in the periotic mesenchyme. During larval stages, additional expression domains of aldh1a3 appear in the anterior pituitary and the swim bladder. Our analyses provide a starting point for genetic studies to examine the role of RA in these organs and emphasize the suitability of the zebrafish inner ear in dissecting the contribution of RA signaling to the development of the vestibular system.     

Diverse roles of hnRNP L in mammalian mRNA processing: a combined microarray and RNAi analysis

Alternative mRNA splicing patterns are determined by the combinatorial control of regulator proteins and their target RNA sequences. We have recently characterized human hnRNP L as a global regulator of alternative splicing, binding to diverse C/A-rich elements. To systematically identify hnRNP L target genes on a genome-wide level, we have combined splice-sensitive microarray analysis and an RNAi-knockdown approach. As a result, we describe 11 target genes of hnRNP L that were validated by RT-PCR and that represent several new modes of hnRNP L-dependent splicing regulation, involving both activator and repressor functions: first, intron retention; second, inclusion or skipping of cassette-type exons; third, suppression of multiple exons; and fourth, alternative poly(A) site selection. In sum, this approach revealed a surprising diversity of splicing-regulatory processes as well as poly(A) site selection in which hnRNP L is involved.     

Different rates of telomere attrition in peripheral lymphocytes in a pair of dizygotic twins with hematopoietic chimerism

Hematopoietic chimerism in dizygotic twins is due to placental vascular anastomoses and arises when hematopoietic stem cells from one twin home to the bone marrow of the other. We report a case of hematopoietic chimerism in a pair of 27-year-old dizygotic twins who each had a mixture of 46,XX and 46,XY blood lymphocytes, both with 98% male (XY) lymphocytes and 2% female (XX) lymphocytes. Analysis of telomere length by T/C FISH revealed that the female twin generally had longer telomeres than the male twin. Moreover, in the male sibling, the telomeres within the female lymphocytes were shortened to 87% of their original length, while the telomeres within the male lymphocytes were 33% longer in the female sibling. Thus, telomere length attrition in peripheral lymphocytes is determined mainly by the environment of the cell and less by intracellular factors.     

bFGF induces S1P1 receptor expression and functionality in human pulmonary artery smooth muscle cells

Sphingosine-1-phosphate (S1P), acting through five closely related G-protein coupled receptors termed S1P1-5, has recently emerged as a possible regulator of smooth muscle cell (SMC) physiology with the potential to induce contraction, proliferation and stress fiber formation. In the present study, real-time quantitative PCR was used to determine the expression patterns of S1P receptor subtypes in human primary pulmonary artery smooth muscle cells (PASMC). We report here that subconfluent PASMC express predominantly S1P2 and S1P3 receptors and we show that S1P1 receptor mRNA levels are significantly up-regulated following basic fibroblast growth factor (bFGF) treatment. As a consequence, increased responsiveness, as measured by impedance and ERK1/2 phosphorylation, was observed upon stimulation with a specific S1P1 receptor agonist SEW2871. We therefore demonstrate, for the first time, that a growth factor that was previously shown to be involved in physiological and pathological changes of SMC function induced S1P1 receptor expression and we propose that S1P1 receptor up-regulation could contribute to vascular remodeling.     

Progressive restriction of otic fate: the role of FGF and Wnt in resolving inner ear potential

The development of the vertebrate inner ear is an emergent process. Its progression from a relatively simple disk of thickened epithelium within head ectoderm into a complex organ capable of sensing sound and balance is controlled by sequential molecular and cellular interactions. Fibroblast growth factor (FGF) and Wnt signals emanating from mesoderm and neural ectoderm have been shown to direct inner ear fate. However, the role of these multiple signals during inner ear induction is unclear. We demonstrate that the action of the FGFs and Wnts is sequential, and that their roles support a model of hierarchical fate decisions that progressively restrict the developmental potential of the ectoderm until otic commitment. We show that signalling by Fgf3 and Fgf19 is required to initiate a proliferative progenitor region that is a precursor to both the inner ear and the neurogenic epibranchial placodes. Significantly, we find that only after FGF action is attenuated can the subsequent action of Wnt signalling allow otic differentiation to proceed. In addition, gain and loss of function of Wnt-signalling components show a role for this signalling in repressing epibranchial fate. This interplay of signalling factors ensures the correct and ordered differentiation of both inner ear and epibranchial systems.     

Periplasmic chaperone FkpA is essential for imported colicin M toxicity

Chaperones facilitate correct folding of newly synthesized proteins. We show here that the periplasmic FkpA chaperone is required for killing Escherichia coli by colicin M entering cells from the outside. Highly active colicin M preparations were inactive against fkpA mutant cells; 10⁴-fold dilutions killed fkpA ⁺ cells. Three previously isolated spontaneous mutants tolerant to colicin M carried a stop codon or an IS 1 insertion in the peptidyl-prolyl- cis-trans -isomerase (PPIase) domain (C-domain) of FkpA, which resulted in deletion of the domain. A randomly generated mutant carried a G148D mutation in the C-domain. A temperature-sensitive mutant tolerant to colicin M carried a Y25N mutation in the FkpA N-domain. Mutants transformed with wild-type fkpA were colicin M-sensitive. Isolated FkpA-His reduced colicin M-His cleavage by proteinase K and renatured denatured colicin M-His in vitro ; renaturation was prevented by the PPIase inhibitor FK506. In both assays, periplasmic SurA-His had no effect. No other tested periplasmic chaperone could activate colicin M. Among the tested colicins, only colicin M required FkpA for activity. Colicin M bound to cells via FhuA was inactivated by trypsin; unbound colicin M retained activity. We propose that colicin M unfolds during import across the outer membrane, FkpA specifically assists in folding colicin M into an active toxin in the periplasm and PPIase is essential for colicin M activity. Colicin M is a suitable tool for the isolation of FkpA mutants used to elucidate the functions of the FkpA N- and C-domains.