Incidence of stroke and acute renal failure in patients of postoperative atrial fibrillation after myocardial revascularization

Introduction

Postoperative atrial fibrillation is the most common arrhythmia in cardiac surgery, its incidence range between 20% and 40%.

Objective

Quantify the occurrence of stroke and acute renal insufficiency after myocardial revascularization surgery in patients who had atrial fibrillation postoperatively.

Methods

Cohort longitudinal bidirectional study, performed at Portuguese Beneficent Hospital (SP), with medical chart survey of patients undergoing myocardial revascularization surgery between June 2009 to July 2010. From a total of 3010 patients were weaned 382 patients that presented atrial fibrillation preoperatively and/or associated surgeries. The study was conducted in accordance with national and international following resolutions: ICH Harmonized Tripartite Guidelines for Good Clinical Practice - 1996; CNS196/96 Resolution, and Declaration of Helsinki.

Results

The 2628 patients included in this study were divided into two groups: Group I, who didn''t show postoperative atrial fibrillation, with 2302 (87.6%) patients; and group II, with 326 (12.4%) who developed postoperative atrial fibrillation. The incidence of stroke in patients was 1.1% without postoperative atrial fibrillation vs. 4% with postoperative atrial fibrillation (P<0.001). Postoperative acute renal failure was observed in 12% of patients with postoperative atrial fibrillation and 2.4% in the group without postoperative atrial fibrillation (P<0.001), that is a relation 5 times greater.

Conclusion

In this study there was a high incidence of stroke and acute renal failure in patients with postoperative atrial fibrillation, with rates higher than those reported in the literature.     

Pharmacokinetics of oral vs. intravenous dexamethasone in patients hospitalized with community-acquired pneumonia

Aim

The use of corticosteroids as adjunctive therapy might be effective in patients with community-acquired pneumonia (CAP). Oral administration of dexamethasone is a practical and safer alternative to the intravenous route. Since patients hospitalized with pneumonia might have delayed gastric emptying, this study explored systemic exposure in terms of area under the concentration–time curve (AUC) of oral dexamethasone in patients hospitalized with CAP.

Methods

In this randomized, open label study, 30 patients admitted with CAP were randomized to receive either 4 mg intravenous or 6 mg oral dexamethasone for 4 consecutive days. Serial blood samples were obtained before and after drug administration.

Results

Median AUC to infinity was 626 μg l⁻¹ h (IQR 401–1161) for the intravenous group and 774 μg l⁻¹ h (IQR 618–1146) for the oral group. The AUC ratio of 6 mg oral and 4 mg intravenous dexamethasone was 1.22 (95% confidence interval (CI) 0.81, 1.82)_, which represents a bioavailability of 81% (95% CI 54, 121) after correction for differences in dexamethasone dose.

Conclusions

Bioavailability of oral dexamethasone in patients hospitalized with pneumonia is sufficient. This makes oral dexamethasone an appropriate alternative for intravenous administration in these patients.     

Aversive Learning in Adolescents: Modulation by Amygdala–Prefrontal and Amygdala–Hippocampal Connectivity and Neuroticism

Neuroticism involves a tendency for enhanced emotional and cognitive processing of negative affective stimuli and a propensity to worry and be anxious. It is known that this trait modulates fear learning and the activation of brain regions involved in it such as the amygdala, hippocampus, and prefrontal cortex and their connectivity. Thirty-nine (21 female) 14-year-old healthy adolescents participated in functional magnetic resonance imaging (fMRI) of aversive pavlovian differential delay conditioning. An unpleasant sound served as unconditioned stimulus (US) and pictures of neutral male faces as conditioned stimuli (CS+ followed by the US in 50% of the cases; CS− never followed by the US). During acquisition (CS+/− differentiation), higher levels of neuroticism were associated with a stronger interaction between the right amygdala and the right hippocampus as well as the right amygdala and prefrontal cortical regions, specifically ventromedial prefrontal cortex, dorsolateral prefrontal cortex, and anterior cingulate cortex. The association of stronger conditionability of fear and connectivity of brain regions related to consolidation of fear associations and neuroticism points to underlying mechanisms of the enhanced propensity for anxiety disorders in highly neurotic participants. This is especially important in adolescence, a vulnerable time for the onset of mental disorders such as anxiety disorders.     

A 15-minute [13C]-urea breath test for the diagnosis of Helicobacter pylori infection in patients with non-ulcer dyspepsia

BACKGROUND: Non-ulcer dyspepsia (NUD) accounts for the majority of dyspeptic patients and studies on the epidemiology of Helicobacter pylori infection in NUD depend on a non-invasive and rapid diagnostic test. This study was performed to determine the sensitivity and specificity of a 15-min simplified protocol of the [13C]-urea breath test ([13C]-UBT) for the diagnosis of H. pylori infection in patients with NUD. METHODS: One hundred and thirty-six patients with a clinical and endoscopic diagnosis of NUD were included. The [13C]-UBT was modified from the European standard protocol. The baseline breath sample was collected 5 min after the patient took a test meal and the 13CO2 was collected 15 min after the patient drank 100 mg [13C]-urea. The gold standard used for comparison was either a positive culture or positive histology + positive rapid urease test sampled on upper gastrointestinal endoscopy. RESULTS: The prevalence of H. pylori infection in NUD by the gold standard was 59.6%, whereas that calculated by the [13C]-UBT was 60.3%. The sensitivity and specificity of [13C]-UBT was 93.8 and 89.1% compared with the gold standard. The shortened collection time and simplification of the procedure may have led to a decline in specificity. CONCLUSION: The 15-min [13C]-UBT is a rapid but less specific protocol for detecting the presence of H. pylori infection in patients with NUD.     

Reappraisal of Left Ventricular to Right Atrial (LV-RA) Shunt in Pediatric Patients With Isolated Perimembranous Ventricular Septal Defect

Background The purpose of this study was to investigate the follow-up results of perimembranous ventricular septal defect (VSD) with left ventricular to right atrial (LV-RA) shunt since infancy and to analyze the morphologic variations of this shunt. Methods and Results The study group comprised 232 consecutive pediatric patients with isolated perimembranous VSD and aneurysm, of whom 134 (58%) had LV-RA shunts. Follow-up echocardiography was performed to assess for the size of both the VSD and LV-RA shunt. There were no significant differences between groups in terms of sex, age at the initial echocardiography, follow-up period, number of patients with tricuspid regurgitation, and initial VSD size. There was a significant difference between groups in spontaneous closure (p=0.039). The event-free probability (no surgical repair of the defect) was not significantly different between the groups (p=0.129). Conclusions Perimembranous VSD with LV-RA shunt in infancy is common and associated with less chance of spontaneous closure. Color Doppler echocardiography can greatly improves the diagnostic efficacy and assist in understanding the mechanisms leading to this particular anomaly. (Circ J 2008; 72: 1487 - 1491).     

Size and speed of the working stroke of cardiac myosin in situ

The power in the myocardium sarcomere is generated by two bipolar arrays of the motor protein cardiac myosin II extending from the thick filament and pulling the thin, actin-containing filaments from the opposite sides of the sarcomere. Despite the interest in the definition of myosin-based cardiomyopathies, no study has yet been able to determine the mechanokinetic properties of this motor protein in situ. Sarcomere-level mechanics recorded by a striation follower is used in electrically stimulated intact ventricular trabeculae from the rat heart to determine the isotonic velocity transient following a stepwise reduction in force from the isometric peak force T_P to a value T (0.8–0.2 T_P). The size and the speed of the early rapid shortening (the isotonic working stroke) increase by reducing T from ∼3 nm per half-sarcomere (hs) and 1,000 s⁻¹ at high load to ∼8 nm⋅hs⁻¹ and 6,000 s⁻¹ at low load. Increases in sarcomere length (1.9–2.2 μm) and external [Ca²⁺]_o (1–2.5 mM), which produce an increase of T_P, do not affect the dependence on T, normalized for T_P, of the size and speed of the working stroke. Thus, length- and Ca²⁺-dependent increase of T_P and power in the heart can solely be explained by modulation of the number of myosin motors, an emergent property of their array arrangement. The motor working stroke is similar to that of skeletal muscle myosin, whereas its speed is about three times slower. A new powerful tool for investigations and therapies of myosin-based cardiomyopathies is now within our reach.The performance of heart depends on the power developed by the myocardium, which in turn is strongly dependent on the end-diastolic volume modulating the systolic pressure development (Frank–Starling law of the heart). At the level of the sarcomere, the structural unit of striated muscle, the Frank–Starling law originates from the increase in the force of contraction with an increase in sarcomere length (length-dependent activation). Mutations of sarcomere proteins affect power output and are considered responsible for various forms of cardiomyopathy (1, 2). Over 250 mutations in cardiac myosin II have been reported as the cause of cardiomyopathies (1, 3, 4). Defining the mechanokinetic properties of the cardiac myosin in situ is therefore fundamental to understand the pathomechanisms of these cardiomyopathies and to provide previously unidentified therapeutic opportunities.In the sarcomere, the myosin motors are organized in two bipolar arrays extending from the thick filament and pulling the thin actin-containing filaments from the opposite sides of the sarcomere toward its center. In each array, the myosin motors are connected in parallel via their attachments to the thick filament and the resulting collective motor provides steady force and shortening by cyclic asynchronous ATP-driven actin–myosin interactions. Thus, the performance of the heart relies on the integration of the mechanokinetic properties of the myosin motor and the properties emerging from its array arrangement in the half-sarcomere (hs). Using sarcomere-level mechanics in intact cells from the skeletal muscle, it has been shown that the isotonic velocity transient following stepwise changes in force imposed on the otherwise isometric contraction contains information on both the working stroke of the myosin motor and the steady-state force–velocity (T–V) relation resulting from the cyclic actin–myosin interactions and accounting for the power output (5–9).Here, this approach is applied for the first time (to our knowledge) to a multicellular cardiac preparation like the intact trabecula dissected from the right ventricle of the rat heart. A striation follower (10) proved to be a reliable tool for measurement of sarcomere length changes with nanometer–microsecond resolution owing to optical averaging of the image of the sarcomeres that reduces the background noise originating from intracellular and intercellular components of the trabecula. Following the original idea by ter Keurs et al. (11), the sarcomere shortening recorded during the force development in a fixed-end twitch is used as a feedforward signal to maintain sarcomere length constant during the next twitch. By switching from length control to force control, a stepwise drop in force was imposed at the peak of force (T_P) to record the isotonic velocity transient. In this way, the amplitude and speed of the rapid phase of the transient (phase 2), which is the mechanical manifestation of the myosin working stroke, could be determined. Increases in sarcomere length (SL) from 1.9 to 2.2 μm and in the external Ca²⁺ concentration ([Ca²⁺]_o) from 1 to 2.5 mM, which produce an increase in T_P, do not affect the myosin working stroke. This indicates that length-dependent potentiation of cardiac contractility is fully accounted for by an increase in the number of attached myosin motors. These experiments demonstrate that our sarcomere-level mechanical methods have the full potential for the in situ investigation of cardiomyopathy-causing mutations in cardiac myosin.     

Correlation between the course of the medial plantar artery and the morphology of the abductor hallucis muscle

The abductor hallucis muscle flap is commonly used as a proximally-based flap in the management of ankle, heel, and midfoot lesions, where it is ideally suited for closing defects. This study investigates the anatomical details of this muscle in 13 fresh male cadavers. The medial plantar artery (MPA) was studied by dissection and macroscopic analyses to document the relationship of its superficial and deep branches with respect to the abductor hallucis muscle (AHM). Three main patterns could be described. In Pattern A (54%) the MPA divides into two branches. The deep branch reaches the deep surface of the AHM, supplying its proximal part, and the superficial branch courses between the AHM and the flexor digitorum brevis, to end as the first plantar metatarsal artery. The latter supplies two to three small branches to the distal part of the AHM. The fibers of the AHM end symmetrically on the two sides of the tendon and the muscle presents an arciform shape. The MPA, in Pattern B (38%), lacks a deep branch and continues along the lateral border of the AHM as a superficial branch that supplies proximal and distal collaterals to the muscle. The muscle fibers of the AHM end mainly on the medial side of the tendon. The muscle belly presents an arciform shape and is located on the medial margin of the foot superomedially with respect to Pattern A. In Pattern C (8%) the MPA continues as a large deep branch on the deep surface of the AHM and ends as the medial collateral artery of the big toe. A smaller superficial branch of the MPA provides a few collaterals to the AHM from its proximal part and to the flexor digitorum brevis in its distal part. The AHM fibers end mainly on the lateral side of the tendon and morphologically the muscle presents a straight line on the sole of the foot compared to Pattern A. Although Patterns B and C, from a surgical point of view, necessitate interruption of the main trunk of the MPA, Pattern A may permit the vascularization of the muscles of the medial side of the sole of the foot by the superficial trunk of the MPA. Because preoperative radiological study of the plantar vessels correlate with the morphological characteristics of the AHM observed during surgery, such imaging may be useful in determining the appropriate flap design based on the patient's unique pattern of MPA branching.     

Mapping translocation breakpoints by next-generation sequencing

Balanced chromosome rearrangements (BCRs) can cause genetic diseases by disrupting or inactivating specific genes, and the characterization of breakpoints in disease-associated BCRs has been instrumental in the molecular elucidation of a wide variety of genetic disorders. However, mapping chromosome breakpoints using traditional methods, such as in situ hybridization with fluorescent dye-labeled bacterial artificial chromosome clones (BAC-FISH), is rather laborious and time-consuming. In addition, the resolution of BAC-FISH is often insufficient to unequivocally identify the disrupted gene. To overcome these limitations, we have performed shotgun sequencing of flow-sorted derivative chromosomes using "next-generation" (Illumina/Solexa) multiplex sequencing-by-synthesis technology. As shown here for three different disease-associated BCRs, the coverage attained by this platform is sufficient to bridge the breakpoints by PCR amplification, and this procedure allows the determination of their exact nucleotide positions within a few weeks. Its implementation will greatly facilitate large-scale breakpoint mapping and gene finding in patients with disease-associated balanced translocations.