Cancer-associated thrombosis - treatment and prevention with direct oral factor Xa inhibitors.

BACKGROUND: Venous thromboembolism (VTE) is a frequent cause of morbidity and mortality in patients with cancer. Moreover, management of VTE is frequently connected with complications, namely risk of recurrent VTE and bleeding. Low molecular weight heparins (LMWH) therapy administrated for 3-6 months is currently considered a standard for the treatment of cancer-associated VTE (CA-VTE). Direct oral factor Xa inhibitors (FXaI) apixaban, edoxaban and rivaroxaban have emerged as a new possibility for long-term antithrombotic therapy for VTE. These agents expose several advantages in individuals with cancer, and might overcome several disadvantages connected with LMWH therapy. PURPOSE: First clinical studies with oral FXaI for the treatment of CA-VTE with very promising results were recently published. The article summarizes current data regarding the use of oral FXaI in the treatment of CA-VTE.

NMR plasma metabolomics study of patients overcoming acute myocardial infarction: in the first 12 h after onset of chest pain with statistical discrimination towards metabolomic biomarkers.

Acute myocardial infarction (AMI) is one of the leading causes of death among adults in older age. Understanding mechanisms how organism responds to ischemia is essential for the ischemic patient's prevention and treatment. Despite the great prevalence and incidence only a small number of studies utilize a metabolomic approach to describe AMI condition. Recent studies have shown the impact of metabolites on epigenetic changes, in these studies plasma metabolites were related to neurological outcome of the patients making metabolomic studies increasingly interesting. The aim of this study was to describe metabolomic response of an organism to ischemic stress through the changes in energetic metabolites and aminoacids in blood plasma in patients overcoming acute myocardial infarction. Blood plasma from patients in the first 12 h after onset of chest pain was collected and compared with volunteers without any history of ischemic diseases via NMR spectroscopy. Lowered plasma levels of pyruvate, alanine, glutamine and neurotransmitter precursors tyrosine and tryptophan were found. Further, we observed increased plasma levels of 3-hydroxybutyrate and acetoacetate in balance with decreased level of lipoproteins fraction, suggesting the ongoing ketonic state of an organism. Discriminatory analysis showed very promising performance where compounds: lipoproteins, alanine, pyruvate, glutamine, tryptophan and 3-hydroxybutyrate were of the highest discriminatory power with feasibility of successful statistical discrimination.

MicroRNA and hyperaggregability of platelets in women with sticky platelet syndrome and pregnancy complications.

AIMS: We aimed to characterize relationship between the expression profiles of platelet miR-96, miR-126 and miR-223 and platelet function examination in patients with sticky platelet syndrome (SPS) and in healthy controls. BACKGROUND: MicroRNAs (miRNA, miR) are a group of small and non-coding RNAs involved in many mechanisms as regulators of post-transcriptional protein expression in platelets. SPS is defined as platelet hyperaggregability after administration of low doses of adenosine diphosphate and/or epinephrine. Clear genetic abnormality of this syndrome is not known yet. METHODS: We examined 45 patients with SPS and 30 healthy volunteers. For functional platelet examination we used light transmission aggregometry, and qRT-PCR was used to determine the expression of the miRNAs. RESULTS: We observed no relationship of the platelet miRNA expression with functional platelet examination in the entire cohort of patients with SPS. However, in a group of patients with SPS and pregnancy complications, we found that the expression of platelet miR-96 (p = 0.009) was up-regulated. CONCLUSION: In spite of the multiple limitations of the study, it can be considered that the increased expression of platelet miR-96 found in a group of patients with SPS and pregnancy complications could be related to the hyperaggregability in these selected patients (Tab. 2, Ref. 31).

Hyaluronic acid application vs arthroscopy in treatment of internal temporomandibular joint disorders.

AIMS: The goal of this study was to compare the treatment outcome after two different treatment modalities in cases of disc displacement of the temporomandibular joint diagnosed via magnetic resonance technique, namely surgical procedure in form of arthroscopic lysis and lavage vs. hyaluronic acid superior joint space application. MATERIALS AND METHODS: Magnetic resonance imaging was performed before and one year after treatment. Simultaneously, pre- and post-treatment visual analogue scales and maximal mouth opening distance were documented. RESULTS: In our study, out of the total of 145 patients who were initially diagnosed with magnetic resonance imaging to have internal derangements and treated with arthroscopic lysis and lavage or hyaluronic acid application, we observed progression of internal derangement in 27 cases (18.6 %), improvement in 37 cases (25.5 %) and stationary state in 81 patients (55.9 %). Both treatment methods significantly improved the followed maximal mouth opening distance and visual analogue scale, as confirmed upon the 12­month follow-up examination. Maximal mouth opening was 4.7mm for hyaluronic acid application and 12.2mm for arthroscopic lysis and lavage (p<0.005). The mean visual analogue scale values decreased from 6.2 to 2.1 for hyaluronic acid application and from 6.9 to 1.2 for arthroscopic lysis and lavage (p<0.005). CONCLUSION: Our study shows that both arthroscopic lysis and lavage and hyaluronic acid injections are effective and safe in the treatment of disc displacement in the temporomandibular joint (Tab. 3, Ref. 30).

Therapeutic effects of arthrocentesis in treatment of temporomandibular joint disorders.

OBJECTIVE: Analyse, compare and evaluate the effects of the treatment arthrocentesis with a control group of non-steroid drugs treated patients. MATERIAL AND METHODS: 1752 out-patients (1293 females, 459 males) were examined within the years 2013-2017. We evaluated the following criteria: gender, age, visual analog scale for pain (VAS), inter-incisal distance and reducing intake of orally administered analgesics. RESULTS: The pain level of the group of patients with arthrocentesis had stabilized at mark 2.5 on the pain scale, unlike in the control group after treatment with non-steroidal anti-inflammatory drugs, pain had stabilized at mark 9 on the pain scale. The inter incisal distance amongst the first group was 37 mm and in the control group only 27 mm, after completed treatment. The amount of applied analgesics in the group with arthrocentesis decreased to 100 mg daily, while in the control group, the dose was adjusted to 700 mg daily. CONCLUSION: In the observed study, arthrocentesis was effective in reducing pain, amount of analgesics per day and improving the mobility of temporomandibular joint (TMJ). The results of this study we use in the ongoing project, that focuses on progressive and innovative methodology of endoscopically assisted arthrocentesis. (Tab. 4, Fig. 5, Ref. 39).

Disruption of rcsB by a duplicated sequence in a curli-producing Escherichia coli O157:H7 results in differential gene expression in relation to biofilm formation, stress responses and metabolism.

BACKGROUND: Escherichia coli O157:H7 (O157) strain 86-24, linked to a 1986 disease outbreak, displays curli- and biofilm-negative phenotypes that are correlated with the lack of Congo red (CR) binding and formation of white colonies (CR-) on a CR-containing medium. However, on a CR medium this strain produces red isolates (CR+) capable of producing curli fimbriae and biofilms. RESULTS: To identify genes controlling differential expression of curli fimbriae and biofilm formation, the RNA-Seq profile of a CR+ isolate was compared to the CR- parental isolate. Of the 242 genes expressed differentially in the CR+ isolate, 201 genes encoded proteins of known functions while the remaining 41 encoded hypothetical proteins. Among the genes with known functions, 149 were down- and 52 were up-regulated. Some of the upregulated genes were linked to biofilm formation through biosynthesis of curli fimbriae and flagella. The genes encoding transcriptional regulators, such as CsgD, QseB, YkgK, YdeH, Bdm, CspD, BssR and FlhDC, which modulate biofilm formation, were significantly altered in their expression. Several genes of the envelope stress (cpxP), heat shock (rpoH, htpX, degP), oxidative stress (ahpC, katE), nutrient limitation stress (phoB-phoR and pst) response pathways, and amino acid metabolism were downregulated in the CR+ isolate. Many genes mediating acid resistance and colanic acid biosynthesis, which influence biofilm formation directly or indirectly, were also down-regulated. Comparative genomics of CR+ and CR- isolates revealed the presence of a short duplicated sequence in the rcsB gene of the CR+ isolate. The alignment of the amino acid sequences of RcsB of the two isolates showed truncation of RcsB in the CR+ isolate at the insertion site of the duplicated sequence. Complementation of CR+ isolate with rcsB of the CR- parent restored parental phenotypes to the CR+ isolate. CONCLUSIONS: The results of this study indicate that RcsB is a global regulator affecting bacterial survival in growth-restrictive environments through upregulation of genes promoting biofilm formation while downregulating certain metabolic functions. Understanding whether rcsB inactivation enhances persistence and survival of O157 in carrier animals and the environment would be important in developing strategies for controlling this bacterial pathogen in these niches.

Activity of coagulation factor XI in patients with spontaneous miscarriage: the presence of risk alleles.

The aim of this study was to compare the activity of coagulation factor XI (FXI) between patients with spontaneous miscarriage versus control group with no history of miscarriage and thrombosis, and then we evaluated the occurrence of risk alleles in the relation to miscarriage. FXI activity was determined using a coagulometer (Sysmex, CA 1500, Japan). Single nucleotide polymorphisms (SNPs) of F11 and CYP4V2 genes were evaluated. We examined 55 patients versus 31 control subjects. We found significantly higher activity of FXI (p = 0.04) in patients versus control subjects. The occurrence of two SNPs (rs2289252 and rs2036914) of the F11 gene and SNP (rs13146272) of CYP4V2 gene was not significantly different between both groups. Increased activity of FXI may be a potential risk factor for miscarriage. High activity of FXI diagnosed in women with history of miscarriage is not probably caused by the presence of studied SNPs.

Monitoring the efficacy of ADP inhibitor treatment in patients with acute STEMI post-PCI by VASP-P flow cytometry assay.

INTRODUCTION: Dual antiplatelet treatment (DAPT) with clopidogrel and aspirin represents common approach in prevention of thromboembolic events in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). The drawback of clopidogrel treatment is large interindividual variability in response. AIM: Our article aims to suggesting the most convenient method in monitoring the DAPT of post-PCI patients. METHODS: We analyzed the on-treatment platelet reactivity by light transmission aggregometry and vasodilator-stimulated phosphoprotein (VASP) flow cytometric assay. Samples were obtained in 3 intervals: first prior to PCI, then 1, and 30 days after PCI. RESULTS: Based on VASP-platelet reactivity index (PRI), we observed 100% response rate in prasugrel-treated patients and 62% to 73 % in the clopidogrel group. Overall, only 2 (7%) patients with the VASP-PRI value in therapeutic range had major adverse cardiovascular events. CONCLUSION: Our results hint VASP-phosphorylation assay as a relevant method for guiding and tailoring DAPT.

Techniques in electron microscopy of animal tissue.

Technical improvements in electron microscopy, both instrumental and preparative, permit increasingly accurate analyses. Digital images for transmission electron microscopy (TEM) can be processed by software programs that automate tasks and create custom tools that allow for image enhancement for brightness, contrast and coloration; for creation of rectangular, ellipsoidal or irregular area selections; and for measurement of mean area and standard deviation. Sample preparation remains a source of error since organelles and spatial arrangements of macromolecules rapidly change after anoxia. Guidelines for maintaining consistency in preparation, examination and interpretation are presented for different electron microscopy (EM) modalities.

SnapShot: Visualization to Propel Ice Hockey Analytics.

Sports analysts live in a world of dynamic games flattened into tables of numbers, divorced from the rinks, pitches, and courts where they were generated. Currently, these professional analysts use R, Stata, SAS, and other statistical software packages for uncovering insights from game data. Quantitative sports consultants seek a competitive advantage both for their clients and for themselves as analytics becomes increasingly valued by teams, clubs, and squads. In order for the information visualization community to support the members of this blossoming industry, it must recognize where and how visualization can enhance the existing analytical workflow. In this paper, we identify three primary stages of today's sports analyst's routine where visualization can be beneficially integrated: 1) exploring a dataspace; 2) sharing hypotheses with internal colleagues; and 3) communicating findings to stakeholders.Working closely with professional ice hockey analysts, we designed and built SnapShot, a system to integrate visualization into the hockey intelligence gathering process. SnapShot employs a variety of information visualization techniques to display shot data, yet given the importance of a specific hockey statistic, shot length, we introduce a technique, the radial heat map. Through a user study, we received encouraging feedback from several professional analysts, both independent consultants and professional team personnel.

Examining the Use of a Visual Analytics System for Sensemaking Tasks: Case Studies with Domain Experts.

While the formal evaluation of systems in visual analytics is still relatively uncommon, particularly rare are case studies of prolonged system use by domain analysts working with their own data. Conducting case studies can be challenging, but it can be a particularly effective way to examine whether visual analytics systems are truly helping expert users to accomplish their goals. We studied the use of a visual analytics system for sensemaking tasks on documents by six analysts from a variety of domains. We describe their application of the system along with the benefits, issues, and problems that we uncovered. Findings from the studies identify features that visual analytics systems should emphasize as well as missing capabilities that should be addressed. These findings inform design implications for future systems.

Malignant tumours of colon and rectum from the blood clotting view.

OBJECTIVES: The relationship between malignant tumours and blood coagulation disorders is generally well known. BACKGROUND: The authors notice blood coagulation in patients with colorectal cancer and evaluate prothrombotic markers. METHODS: The authors analyzed a group of 137 patients with malignant tumour of colon and rectum, drew attention to the relationship between level of D-dimer, PAI-1, F 1+2, Protein C and the progress of malignant tumour, its localization, clinical stage, histopathology type, method of surgery considering the stapling use. RESULTS: Very aggressive and advance tumours have high level of D dimer, plasminogen activator inhibitor I (PAI-1). Prothrombotic fragments 1+2 were significantly higher by anastomotic dehiscence. Protein C level was lower by age from sixty to seventy and in advanced clinical stage. CONCLUSION: Pre-operative surveys of D dimer, PAI-1, prothrombotic fragments and Protein C give informations abaout risk of thrombosis, far gone of malignant diseases, they clinical stage and histological type. D dimer and PAI-1 have the most clinical value (Fig. 5, Ref. 11).

D-dimer, plasminogen activator inhibitor-1, prothrombin fragments and protein C - role in prothrombotic state of colorectal cancer.

The relationship between malignant tumors and blood coagulation disorders is generally well known. The authors studied blood coagulation in patients with colorectal cancer and evaluated some prothrombotic markers. The authors analyzed by latex-aglutination method, ProC Global test, Asserachrom PAI-1 test and Enzygnost F 1+2 test the group of 137 patients with malignant tumor of colon and rectum, drew attention to the relationship between level of D-dimer, PAI-1, F 1+2, Protein C and the progress of malignant tumor, its localization, clinical stage, histopathology type, method of surgery considering the stapling use. Very aggressive and advanced tumors have significantly higher level of D-dimer, plasminogen activator inhibitor I (PAI-1). Prothrombotic fragments 1+2 were significantly higher by anastomosis dehiscence. Protein C level was lower in the age from sixty to seventy and in advanced clinical stage. Pre-operative surveys of D-dimer, PAI-1, prothrombotic fragments and Protein C give informations about risk of thrombosis of malignant diseases, their clinical stage and histological type. D-dimer and PAI-1 have a real clinical value and can be reliable prothrombotic marker.

Graph analytics-lessons learned and challenges ahead.

Lessons learned from developing four graph analytics applications reveal good research practices and grand challenges for future research. The application domains include electric-power-grid analytics, social-network and citation analytics, text and document analytics, and knowledge domain analytics.

[The value of baroreflex sensitivity for cardiovascular risk stratification in hypertensives]. / Význam senzitivity baroreflexu pre stratifikáciu kardievaskulárneho rizika u hypertonikov.

Impaired baroreflex sensitivity (BRS) is a marker of autonomous dysfunction, which may play an important role in the long-term development of arterial hypertension, disease progression as well as complications related to global cardiovascular risk. The aim of the study was to evaluate the clinical significance of baroreflex sensitivity in hypertensives with/without major cardiovascular events. We found out that essential hypertension is associated with decreased BRS, and that grade of hypertension is inversely related to BRS values. Spontaneous BRS values in hypertensives with major cardiovascular event (stroke, myocardial infarction) were significantly lower even 6 months and more after myocardial infarction and stroke onset compared to remaining patients (p < 0.05). BRS is a clinically applicable, noninvasive method for assessing early dysfunction of autonomic nervous system, which seems to be an additive emerging marker of cardiovascular risk stratification in hypertensive patients.

The significance of baroreflex sensitivity in hypertensive subjects with stroke.

The relationship between baroreflex sensitivity expressed in ms/mm Hg (BRS) or in Hz/mm Hg (BRSf) in hypertensives with stroke in comparison with a group of stroke-free patients was evaluated. Twenty-six patients (aged 66+/-10 years, 11 females/ 15 males) with a history of the first ever ischemic stroke (6 months and more after stroke onset), which was neuroradiologically confirmed, were studied. These were compared to 30 hypertensive patients without history of any cardiovascular event, being of similar age and sex. BRS and BRSf were determined by the sequence and spectral methods (five-minute non-invasive beat-to-beat recording of blood pressure and inter-beat interval, controlled breathing at a frequency of 0.1 Hz). A significant negative correlation between spontaneous BRS and blood pressure (BP) represented by the grade of hypertension was present (r = -0.52, p<0.001). Differences between hypertensives with and without stroke were detected in BRS obtained by the spectral method (BRS spect p=0.0237, BRSf spect p=0.0285) or BRS obtained by sequence method (BRS seq p=0.0532, BRSf seq p=0.0273). The greatest decline in BRS values was in hypertensive stroke patients with metabolic syndrome, who had BRS values below 3 ms/mm Hg. We found out that BRS and BRSf were more impaired in stroke patients with essential hypertension even 6 months and more after stroke onset than in stroke-free hypertensive patients. This finding was independent of age-dependent decrease of BRS. Examination of baroreflex sensitivity as a marker of autonomic dysfunction along with global cardiovascular risk stratification of individuals seems to be a method for identifying patients at high residual cardiovascular risk.

Spontaneous idiopathic arteritis of the testicular artery in raccoons (Procyon lotor).

The testes and the spermatic cord of raccoons (Procyon lotor, kits to adult breeders; n = 48) were examined. Segmental arteritis confined to the extratesticular portions of the testicular artery was present in raccoons of all ages. The arterial changes were seen in laboratory-confined experimental and control animals as well as in wild-caught raccoons. The lesions consisted of proliferative endarteritis with presence of inflammatory cells within the intima, media, and the adventitial regions of most affected vessels. Some aspects of the proliferative arterial lesions were reminiscent of systemic necrotizing vasculitis (polyarteritis nodosa), an immunologically mediated condition of animals and humans. Etiologic agents were not identified at the affected sites. Arteritis was not attributed to the administration of infectious agents because it was present in raccoons of all age and origin. To our knowledge multifocal arteritis confined to the testicular artery has not previously been documented in raccoons.

[Colorectal malignancies with respect to hemocoagulation]. / Malignómy kólonu a rekta z pohl'adu hemokoagulácie.

AIM: Relationship between malignants tumors and damage of hemocoagulation is known. The aim is analyse this damage and evaluate the thrombotic markers. MATERIAL AND METHODICS: Authors analyses group of 137 patients with colorectal malignants tumors. They notifyes to relationship between plasmatic preoperative D dimer, PAI-1, F 1+2, Protein C level with controll group. RESULTS: Especially aggressive forms of colorectal tumours have increased levels of D dimer and PAI-1. Protrombin fragments 1+2 were enhanced in the course of anastomotic dehiscence. Protein C level was reduced in 6.-7. decade and in advanced clinical stage. CONCLUSION: Praeoperative thrombotic markers assays inform about risk of thrombosis and clinical diseases stage. They prefere mini-invasive operations procedures. The maximall validity provides D dimer and PAI-1.

Health care risks and access within the community of Michigan over-the-road truckers.

This mixed methods study explored health care access problems faced by long-distance truck drivers. Thirty trucking professionals were interviewed at truck-stops in Michigan about health status and health care access. Thirty of the 88 drivers approached participated. The most common illnesses they reported concerned the eye, back, excessive stress at work and painful joints or arthritis. Most respondents had a family doctor; for those who did not, cost was a major contributing factor. More than one third stated their health is "not excellent" because of poor accessibility to healthcare on the road. Almost unanimously, drivers desired to have access to health care clinics in truck-stop areas and described particular access problems; the solution may be as simple as making the existing health care system more amenable to those driving large truck rigs.