Optimization of intravascular volume determination in patients with acute decompensated heart failure

Acute decompensated heart failure (ADHF) is based on multilevel pathological pathways, which include hemodynamic overload and venous stasis. Determination of the volemic status is one of the most important tasks in managing such patients. Despite the availability of modern diagnostic markers (physical examination, chest x-ray, and brain natriuretic peptide (BNP) assessment), they do not accurately assess the degree of fluid overload, and therefore there remains a need to find a new, accurate and simple technology for assessing pulmonary congestion. The urgency of this problem has led to the development of a novel non-invasive remote dielectric sensing (ReDS) technology, which is a quantitative method for measuring the total volume of lung fluid by determining the tissue dielectric properties. The use of this technology makes it possible to quickly, non-invasively and quantitatively measure the fluid content in the lungs, makes it possible to optimize the treatment regimen and reduces the number of readmissions. This article presents the results of studies on the efficacy, safety and prospects for using a ReDS technology for the quantitative measurement of total lung fluid in patients with ADHF

Гены детоксикации ксенобиотиков и их роль в развитии пневмонии

Objective: to analyze DNA polymorphism in inpatients with pneumonia. Subjects and methods. Group 1 consisted of 99 patients with acute community-acquired pneumonia (CAP). Group 2 included 95 patients with severe concomitant injury, including wounds (n=63) and generalized peritonitis (n=32). Among Group 2 patients, the authors singled out two subgroups: 2A comprising 57 patients with nosocomial pneumonia (NP) and 2B including 38 patients without NP. A control group was composed of 160 apparently healthy individuals. Polymerase chain reaction genotyping was carried out for the polymorphic genes controlling xenobiotic detoxification (such as GSTM1, GSTT1, GSTP1, and CYP1A1) and the MTHFR gene that is responsible for DNA synthesis and methylation. Results. Predisposition to acute CAP has been shown for the carriers of a minor allele (4889G) at the CYP1A1 locus: 12.7% versus 5.4% in the controls (p=0.034; OR=2.6); In Group 1 patients, the development of complications (toxic myocarditis, pleuritis, pleural empyema, toxic nephropathy) is most probable for a combination of GSTT1 + GSTM1 0/0 genotypes (OR=3.2; p=0.010 versus the control group). It has been established that in severe injury, peritonitis (2B), NP does not develop statistically significantly in 61.1% of cases with the GSTM1 + GSTT1 + genotype versus 38.8% in the controls (p=0.022) or versus 37.5% in subgroup 2A (p=0.045; OR=2.6). Key words: acute community-acquired pneumonia, nosocomial pneumonia, gene polymorphism.Цель — анализ полиморфизма ДНК у больных пневмонией, находившихся на стационарном лечении. Материал и методы: первую группу (I) составили 99 человек с острой внебольничной пневмонией (ВП), вторую группу (II) — 95 человек (тяжелая сочетанная травма, включая ранения — 63, общий перитонит — 32). Среди больных II группы были выделены две подгруппы: ПА — 57 человек с нозокомиальной пневмонией (НП) и 38 человек (ИВ) — без НП. Группу сравнения (К) составили 160 относительно здоровых людей. ПЦР-генотипирование проводили для полиморфных генов, контролирующих детоксикацию ксенобиотиков (GSTM1, GSTT1, GSTP1, CYP1A1) и MTHFR-гена, ответственного за синтез и метилирование ДНК. Результаты. Показана предрасположенность к заболеванию острой ВП для носителей минорного аллеля (4889G) в локусе CYP1A1 : 12,7% против 5,4% в контроле (p=0,034; OR=2,6); развитие осложнений у больных I группы (токсический миокардит, плеврит, эмпиема плевры, токсическая нефропатия) наиболее вероятно для комбинации генотипов GSTT1 + GSTM1 0/0 (OR=3,2; p=0,010 относительно группы контроля). Выявлено, что при тяжелой травме, перитоните (ИВ) статистически достоверно в 61,1% случаев не развивается НП при генотипе GSTM1 + GSTT1 + против 38,8% в контроле (p=0,022) или против 37,5% во НА подгруппе (p=0,045; OR=2,6). Ключевые слова: внебольничная пневмония, нозокомиальная пневмония, полиморфизм генов

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases