Predictors of left ventricular function after acute myocardial infarction: effects of time to treatment, patency, and body mass index: the GUSTO-I angiographic experience.

BACKGROUND: Despite the significant survival benefit associated with successful reperfusion therapy for acute myocardial infarction, global indices of outcome left ventricular function, such as ejection fraction, have often demonstrated little or no improvement. Although these measurements are confounded by numerous clinical, physiologic, and angiographic variables, no comprehensive analysis of this issue in a large series of patients is available. We used the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) database to better understand this phenomenon by determining independent predictors of left ventricular function and their interplay with regard to outcome ventricular function and improvement in function during the initial postinfarction week. METHODS: Ninety-minute and 5- to 7-day posttreatment global and regional indices derived from left ventriculograms were analyzed from a population of 676 patients. These observations were combined with clinical data to describe independent determinants of ventricular function outcome. RESULTS: Clinical factors predictive of global and regional ventricular function as well as improvement in function between 90 minutes and 5 to 7 days included time to treatment, early infarct-related artery flow grade, and body mass index. These same factors contribute significantly to compensatory hyperkinesis of the noninfarct zone, which is critical to maintenance of global ventricular function during this time period. CONCLUSIONS: The ventricular function benefits of early complete reperfusion after myocardial infarction are readily demonstrable after adjustment for multiple covariables and include (1) maintenance of global ventricular function and (2) prevention or delay in ventricular dilatation.     

Cost of outpatient care in patients with inflammatory bowel disease in a German University Hospital

BACKGROUND AND AIM: Because of its long duration, inflammatory bowel disease (IBD) causes high use of health services and high lifetime costs for medical care. The aim of the present study was to measure the costs of outpatient care in patients with IBD in a German University Hospital and to identify potentially relevant determinants of costs. METHODS: The use of resources of 599 outpatient patients treated at a German University Hospital (65% Crohn's disease [CD] and 26% ulcerative colitis [UC]) was measured using a routine database. Costs of medical services (diagnostics and treatment) were considered as well as costs of medication. Resource use was valued using fee schedules for hospital services and pharmacy prices for drugs. RESULTS: The mean cost of one outpatient visit was Euros 162, including physician costs, laboratory costs, and costs of diagnostic procedures following the visit. For a subgroup of 272 patients, the mean annual cost for outpatient care was Euros 3171. Medication accounted for 85% of the total annual costs. Potential determinants, such as main diagnosis (CD or UC), sex, age, localization of disease, and occurrence of anemia, had no influence on costs, whereas complications of IBD and use of corticosteroids showed an impact on annual costs. CONCLUSIONS: This is the first time that the structure and range of outpatient treatment costs for IBD have been demonstrated for a German hospital.     

Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma

Comparative genomic hybridization studies have shown gains in chromosome region 2p as the most common imbalance in classical Hodgkin lymphoma (cHL). The minimal region of gain contained 2 candidate oncogenes, REL and BCL11A. This study examined the involvement of REL and BCL11A loci in 44 primary cases of cHL by combined immunophenotyping and interphase cytogenetics (FICTION). A median 2p13 copy number above the tetraploid range was detected in 24 (55%) cases. Adjustment for centromere 2 copy number indicated gains of 2p13 in 11 of 31 cHLs (35%) with 8 (26%) high-level amplifications. One cHL displayed selective amplification of the REL locus not affecting BCL11A; another case studied by FICTION and a cHL with cytogenetic 2p change investigated by fluorescence in situ hybridization showed signal patterns suggesting breakpoints in the region spanned by the REL probe. These data indicate that REL rather than BCL11A may be the target of the 2p13 alterations in cHL.     

Studies on tumor-cell-induced platelet aggregation in human lung cancer cell lines

We investigated the ability of human lung cancer cells of different histological subtypes to cause platelet aggregation. Tumor-cell-induced platelet aggregation (TCIPA) was studied in vitro in 13 human lung cancer cell lines [small-cell lung cancer (SCLC), squamous-cell lung cancer, large-cell lung cancer, adenocarcinoma and alveolar-cell lung cancer]. Three tumor cell lines failed to aggregate platelets in plateletrich plasma, whereas platelet aggregation was induced by 12 cell lines when added to washed platelets and minimal amounts of platelet-poor plasma (0.5% v/v). The thrombin antagonist hirudin inhibited TCIPA in non-small-cell lung cancer cell lines (NSCLC). In SCLC, TCIPA was fully abolished only when the ADP scavenger apyrase was added to hirudin. Thus ADP and thrombin generation by these tumor cell lines are responsible for platelet aggregation. The ability to activate platelets independently of coagulation factors VII and X was demonstrated for 8 cell lines. Electronmiicroscopically, direct tumor-cell/platelet contact was found to be the initiating mechanism of TCIPA in SCLC, whereas tumor-cell/platelet contacts in NSCLC could only be observed at the peak of the aggregation curve. Lung cancer cells activate platelets in vitro by generation of thrombin and/or ADP.Abbreviations TCIPA tumor-cell-induced platelet aggregation - SCLC small-cell lung cancer - NSCLC non-small-cell lung cancer     

Identification and validation of selective upregulation of ventricular myosin light chain type 2 mRNA in idiopathic dilated cardiomyopathy.

BACKGROUND AND AIMS: the etiology of idiopathic dilated cardiomyopathy (IDCM) is unknown, methods such as suppression subtractive hybridization (SSH) and DNA microarray technology can help to identify genes which might be involved in the pathogenesis of this disease. METHODS AND RESULTS: we used SSH which compared mRNA populations extracted from the left ventricular tissue of IDCM hearts and from the control tissue to identify sequences which correspond to genes up-regulated in IDCM. We identified ventricular myosin light chain type 2 (MLC2V), skeletal alpha-actin, long-chain-acyl-CoA-synthetase and mRNA for the protein KIAA0465 as differentially up-regulated genes. Expression of MLC2V mRNA was determined by RT-PCR in patients with end-stage heart failure caused by IDCM (n=11) or coronary artery disease (CAD, n=9) who underwent heart transplantation as well as the controls (n=6). MLC2V/GAPDH ratios were 2.95+/-0.32, 0.69+/-0.03 and 0.28+/-0.08 (arbitrary unit) for the IDCM group, the CAD group and controls, respectively (P<0.05). DNA microarray analysis confirmed the finding of MLC2V upregulation in IDCM (3.7- and 1.8-fold increase in MLC2V mRNA). CONCLUSIONS: we have demonstrated that SSH is a useful method to identify differential myocardial upregulation of genes. Upregulation of MLC2V can be judged as a specific IDCM related feature, which might be clinically helpful.     

Experimental Investigations of Micro-Meso Damage Evolution for a Co/WC-Type Tool Material with Application of Digital Image Correlation and Machine Learning

Commercial Co/WC/diamond composites are hard metals and very useful as a kind of tool material, for which both ductile and quasi-brittle behaviors are possible. This work experimentally investigates their damage evolution dependence on microstructural features. The current study investigates a different type of Co/WC-type tool material which contains 90 vol.% Co instead of the usual <50 vol.%. The studied composites showed quasi-brittle behavior. An in-house-designed testing machine realizes the in-situ micro-computed tomography (μCT) under loading. This advanced equipment can record local damage in 3D during the loading. The digital image correlation technique delivers local displacement/strain maps in 2D and 3D based on tomographic images. As shown by nanoindentation tests, matrix regions near diamond particles do not possess higher hardness values than other regions. Since local positions with high stress are often coincident with those with high strain, diamonds, which aim to achieve composites with high hardnesses, contribute to the strength less than the WC phase. Samples that illustrated quasi-brittle behavior possess about 100–130 MPa higher tensile strengths than those with ductile behavior. Voids and their connections (forming mini/small cracks) dominant the detected damages, which means void initiation, growth, and coalescence should be the damage mechanisms. The void appears in the form of debonding. Still, it is uncovered that debonding between Co-diamonds plays a major role in provoking fatal fractures for composites with quasi-brittle behavior. An optimized microstructure should avoid diamond clusters and their local volume concentrations. To improve the time efficiency and the object-identification accuracy in μCT image segmentation, machine learning (ML), U-Net in the convolutional neural network (deep learning), is applied. This method takes only about 40 min to segment more than 700 images, i.e., a great improvement of the time efficiency compared to the manual work and the accuracy maintained. The results mentioned above demonstrate knowledge about the strengthening and damage mechanisms for Co/WC/diamond composites with >50 vol.% Co. The material properties for such tool materials (>50 vol.% Co) is rarely published until now. Efforts made in the ML part contribute to the realization of autonomous processing procedures in big-data-driven science applied in materials science.     

Secretoneurin as a marker for hypoxic brain injury after cardiopulmonary resuscitation

Purpose

The neuropeptide secretoneurin (SN) shows widespread distribution in the brain. We evaluated whether SN is elevated after cardiopulmonary resuscitation (CPR) and could serve as a potential new biomarker for hypoxic brain injury after CPR.

Methods

This was a prospective observational clinical study. All patients admitted to a tertiary medical intensive care unit after successful CPR with expected survival of at least 24 h were consecutively enrolled from September 2008 to April 2013. Serum SN and neuron-specific enolase were determined in 24 h intervals starting with the day of CPR for 7 days. Neurological outcome was assessed with the Cerebral Performance Categories Scale (CPC) at hospital discharge.

Results

A total of 134 patients were included with 49 % surviving to good neurological outcome (CPC 1–2). SN serum levels peaked within the first 24 h showing on average a sixfold increase above normal. SN levels were significantly higher in patients with poor (CPC 3–5) than in patients with good neurological outcome [0–24 h: 75 (43–111) vs. 38 (23–68) fmol/ml, p < 0.001; 24–48 h: 45 (24–77) vs. 23 (16–39) fmol/ml, p < 0.001]. SN determined within the first 48 h showed a receiver operating characteristic (ROC) area under the curve (AUC) of 0.753 (0.665–0.841). NSE in the first 72 h had a ROC-AUC of 0.881 (0.815–0.946). When combining the two biomarkers an AUC of 0.925 (0.878–0.972) for outcome prediction could be reached.

Conclusions

SN is a promising early biomarker for hypoxic brain injury. Further studies will be required for confirmation of these results.