Gastritis staging: interobserver agreement by applying OLGA and OLGIM systems

Atrophic gastritis remains a difficult histopathological diagnosis with low interobserver agreement. The aim of our study was to compare gastritis staging and interobserver agreement between general and expert gastrointestinal (GI) pathologists using Operative Link for Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia (OLGIM). We enrolled 835 patients undergoing upper endoscopy in the study. Two general and two expert gastrointestinal pathologists graded biopsy specimens according to the Sydney classification, and the stage of gastritis was assessed by OLGA and OLGIM system. Using OLGA, 280 (33.4 %) patients had gastritis (stage I–IV), whereas with OLGIM this was 167 (19.9 %). OLGA stage III– IV gastritis was observed in 25 patients, whereas by OLGIM stage III–IV was found in 23 patients. Interobserver agreement between expert GI pathologists for atrophy in the antrum, incisura angularis, and corpus was moderate (kappa?=?0.53, 0.57 and 0.41, respectively, p?<?0.0001), but almost perfect for intestinal metaplasia (kappa?=?0.82, 0.80 and 0.81, respectively, p?<?0.0001). However, interobserver agreement between general pathologists was poor for atrophy, but moderate for intestinal metaplasia. OLGIM staging provided the highest interobserver agreement, but a substantial proportion of potentially high-risk individuals would be missed if only OLGIM staging is applied. Therefore, we recommend to use a combination of OLGA and OLGIM for staging of chronic gastritis.     

Transient repolarization alterations dominate the initial phase of an acute anterior infarction — a vectorcardiography study

Objective

To study effects of ischemia-reperfusion on ventricular electrophysiology in humans by three-dimensional electrocardiography.

Methods

Fifty-seven patients with first-time acute anterior ST elevation myocardial infarction were monitored from admission and > 24 h after symptom onset with continuous vectorcardiography (VCG; modified Frank orthogonal leads). Global ventricular depolarization and repolarization (VR) measures were compared at maximum vs. minimum ST vector magnitude (STVM) (median 208; 111–303 vs. 362; 165–1359 min after symptom onset).

Results

At maximum vs. minimum STVM the Tarea (overall VR dispersion) almost tripled (118 vs. 41 μVs; p < 0.0001), the T-loop bulginess was 90% greater (Tavplan 0.91 vs 0.48 μV; p < 0.0001), and Tpeak-end/QT was 39% larger (0.32 vs 0.23; p < 0.0001). QRSarea (overall dispersion of depolarization) was 12% larger at maximum STVM, while QRS duration was 10% longer at minimum STVM.

Conclusions

Ischemia-reperfusion was accompanied by profound and transient alterations of VR dispersion, while changes in depolarization were modest and delayed.     

A Polymorphism in leuS Confers Reduced Susceptibility to GSK2251052 in a Clinical Isolate of Staphylococcus aureus

GSK2251052 is a broad-spectrum antibacterial inhibitor of leucyl tRNA-synthetase (LeuRS) that has been evaluated in phase II clinical trials. Here, we report the identification of a clinical isolate of Staphylococcus aureus that exhibits reduced susceptibility to GSK2251052 without prior exposure to the compound and demonstrate that this phenotype is attributable to a single amino acid polymorphism (P₃₂₉) within the editing domain of LeuRS.     

Right ventricular pacing–induced electrophysiological remodeling in the human heart and its relationship to cardiac memory

BACKGROUND: Right ventricular apical (RVA) pacing induces electrophysiological and structural remodeling. Cardiac memory (CM) evolves during the course of pacing and is readily apparent on electrocardiography (ECG) or vectorcardiography (VCG) when normal ventricular activation resumes. OBJECTIVE: This study sought to assess ventricular repolarization (VR) changes during pacing and intermittent normal ventricular conduction by ECG and VCG and to determine the temporal and conformational evolution of CM. METHODS: Twenty sick sinus patients received a dual-chamber rate-adaptive (DDD-R) pacemaker and were paced from the RVA endocardium. The pacemakers were programmed to a short AV delay to maximize ventricular preexcitation. The ECG and VCG were recorded before and 1 day after implantation, and then daily for the first week (n=6) or weekly for 5 to 8 weeks (n=14), with the pacemakers temporarily programmed to AAI (normal ventricular activation). RESULTS: The first parameters to change were T-vector amplitude, T(area), and T(peak)-T(end) (T(p-e)), which decreased within 1 day after initiating pacing. CM became apparent between day 1 and day 3, was fully established after 1 week, and then remained stable. Signs of increased VR heterogeneity were observed as the T loop became more circular (decreased T(egenv)) and distorted (increased T(avplan)), which have previously been observed in conditions with increased risk for arrhythmias. Over weeks, VR duration was prolonged (increased QTc). In contrast, during ventricular pacing, a gradual shortening of the repolarization time was observed, suggesting a stabilizing adaptive process. CONCLUSION: In sick sinus syndrome patients in whom ventricular pacing is indicated, switching between normal AV conduction and ventricular pacing should be minimized to avoid periods of repolarization instability.     

Effects of NAAG peptidase inhibitor 2-PMPA in model chronic pain - relation to brain concentration

N-acetylated-alpha-linked-acidic peptidase (NAAG peptidase) converts N-acetyl-aspartyl-glutamate (NAAG, mGluR3 agonist) into N-acetyl-aspartate and glutamate. The NAAG peptidase inhibitor 2-PMPA (2-(phosphonomethyl)pentanedioic acid) had neuroprotective activity in an animal model of stroke and anti-allodynic activity in CCI model despite its uncertain ability to penetrate the blood–brain barrier. The NAAG concentration in brain ECF under basal conditions and its alteration in relation to the brain ECF concentration of 2-PMPA is unclear. We therefore assessed those brain concentrations after i.p. administration of 2-PMPA, using in vivo microdialysis combined with LC/MS/MS analysis. Administration of 2-PMPA (50 mg/kg) produced a mean peak concentration of 2-PMPA of 29.66 ± 8.1 μM. This concentration is about 100,000 fold more than is needed for inhibition of NAAG peptidase, and indicates very good penetration to the brain. Application of 2-PMPA was followed by a linear increase of NAAG-concentration reaching a maximum of 2.89 ± 0.42 μM at the end of microdialysis. However, during the time the anti-allodynic effects of 2-PMPA were observed, the NAAG concentration in the ECF did not reach levels which are likely to have an impact on any known target. It appears therefore that the observed behavioural effects of 2-PMPA may not be mediated by NAAG nor, in turn, by mGluR3 receptors.     

Ischemia-induced repolarization response in relation to the size and location of the ischemic myocardium during short-lasting coronary occlusion in humans

Background

The ventricular repolarization (VR) response to short-lasting coronary occlusion has been characterized by 3-dimensional vectorcardiography (VCG) in humans; the T vector loop becomes distorted and more circular. The purpose of this study was to relate these changes to the size of the myocardium at risk (MAR) and its location.

Methods

Continuous VCG was applied during transient coronary occlusion in 35 elective angioplasty patients, and the size of the MAR was estimated by single-photon emission computed tomography. Three VR aspects were assessed at baseline vs maximum ischemia: the ST segment, the T vector angles, and the T vector loop morphology.

Results

The T loop morphology changes were significantly associated with MAR size, but also dependent of its location. In contrast, the early phase of VR reflected by the ST segment responded to acute ischemia in relation to the MAR size independent of location.

Conclusion

The VR changes were related both to the size and the location of the MAR and most pronounced during occlusion of the left anterior descending artery.     

Distorted T-vector loop and increased heart rate are associated with ventricular fibrillation in a porcine ischemia-reperfusion model

Background

The ventricular repolarization (VR) response to short-lasting coronary occlusion has been characterized by 3-dimensional vectorcardiography during angioplasty in humans; the T-vector loop becomes distorted (increased T_avplan) and more circular (decreased T_eigenvalue), but these changes have not been related to ventricular arrhythmias.

Purpose

The VR response was therefore explored in a porcine ischemia-reperfusion model and compared in pigs with (n = 16) vs without (n = 17) ventricular fibrillation (VF).

Methods

Different aspects of VR were evaluated at baseline, at maximum ischemia, before reperfusion and at the subsequent ST maximum, after 1 hour of reperfusion, and before VF. Three aspects of the VR response were assessed: the ST-segment, the T-vector angles, and the T-vector loop morphology.

Results

All parameters changed significantly from baseline during ischemia and/or reperfusion. The early changes were similar to those previously observed in humans during angioplasty. The VF episodes were preceded by a significantly exaggerated T-loop distortion (increased T_avplan) and increased heart rate.

Conclusion

Aggravated T-loop distortion might, in this porcine ischemia-reperfusion model, reflect aspects of VR relevant to arrhythmogenesis.     

The application of PGT-A for carriers of balanced structural chromosomal rearrangements

Abstract

The aim of this study was to analyze differences in chromosomal aberrations and euploidy in embryos of each translocation type and gender of carrier in the case series of 10 couples with balanced translocations who underwent IVF with embryos trophectoderm (TE) biopsy and PGT-A to detect chromosomal aberrations. This is a Case Series (Retrospective study). In each case, controlled ovarian hyperstimulation, oocyte insemination with intracytoplasmic sperm injection (ICSI) and cultivation gave multiple blastocysts, that underwent trophectoderm (TE) biopsy with PGT-A analysis using aCGH and NGS. Number of total unbalanced translocations compared to the number of sporadic aneuploid embryos was 39.6% to 39.6% (50% to 50% of all 37 aneuploid embryos). The highest euploidy rate was in male carrier group – 26.7% and the lowest in the Robertsonian translocation carrier group – 18.2%. Sporadic aneuploidy – 68.2% was highest in Robertsonian translocation carrier group and lowest in female group – 11.1%. Chromosomal aberrations related to translocation were highest in female carrier group – 77.8% and lowest in Robertsonian translocation carrier group – 13.6%. Our study showed that expectancy of total embryo aneuploidy rates will be higher in carriers, than in people with normal karyotype. The prevalence of chromosomal aberrations related to translocation was 4.5 times higher in Reciprocal carrier group than in Robertsonian translocation carrier group. Among maternal and paternal carrier groups, the embryos from female carriers had the lowest euploidy rate, unbalanced translocation rate 4.7 times higher than in the male carrier group and higher total aneuploidy rates.     

Breath testing as potential colorectal cancer screening tool

Although colorectal cancer (CRC) screening is included in organized programs of many countries worldwide, there is still a place for better screening tools. In this study, 418 breath samples were collected from 65 patients with CRC, 22 with advanced or nonadvanced adenomas, and 122 control cases. All patients, including the controls, had undergone colonoscopy. The samples were analysed with two different techniques. The first technique relied on gas chromatography coupled with mass spectrometry (GC‐MS) for identification and quantification of volatile organic compounds (VOCs). The T‐test was used to identify significant VOCs (p values < 0.017). The second technique relied on sensor analysis with a pattern recognition method for building a breath pattern to identify different groups. Blind analysis or leave‐one‐out cross validation was conducted for validation. The GC‐MS analysis revealed four significant VOCs that identified the tested groups; these were acetone and ethyl acetate (higher in CRC), ethanol and 4‐methyl octane (lower in CRC). The sensor‐analysis distinguished CRC from the control group with 85% sensitivity, 94% specificity and 91% accuracy. The performance of the sensors in identifying the advanced adenoma group from the non‐advanced adenomas was 88% sensitivity, 100% specificity, and 94% accuracy. The performance of the sensors in identifying the advanced adenoma group was distinguished from the control group was 100% sensitivity, 88% specificity, and 94% accuracy. For summary, volatile marker testing by using sensor analysis is a promising noninvasive approach for CRC screening.