Effect of hemodialysis session on acute changes in inflammatory and cardiovascular risk biomarkers

Background: Inflammation is associated with enhanced cardiovascular risk profile and increased cardiovascular mortality in end-stage kidney disease patients undergoing hemodialysis. Mechanisms of activated acute phase reaction in patients on chronic hemodialysis remain to be identified. As successful treatment of the inflammatory condition in these patients may improve long-term survival, we studied potential changes in different inflammatory biomarkers of cardiovascular risk in end-stage kidney disease patients after a mid-week hemodialysis session. Methods: Inflammatory biomarkers of cardiovascular risk (cystatin-C, homocysteine, C-reactive protein, procalcitonin, pentraxin-3, serum amyloid-A) and atherogenic plasma lipoproteins (Lipoprotein(a), cholesterol low and high density lipoproteins) were studied in 21 end-stage kidney disease patients previously and after a mid-week hemodialysis session. Results: We found a significant reduction in serum levels of low molecular weight molecules: cystatin-C (5.56 to 1.85 mg/L, 66.73%, p < 0.001), homocysteine (22.85 to 13.25 µmol/L, 42.01%, p < 0.001) and procalcitonin (0.788 to 0.457 ng/mL, 42.01%, p < 0.001). Large molecules as C-reactive protein (9.70 to 9.90 mg/L, 2.06%, p = 0.022) and pentraxin-3 (1.67 to 4.28 ng/mL, 156%, p < 0.001) increased, but serum amyloid-A decreased (15.90 to 12.70 mg/L, 20.13%, p < 0.05). There was no change in Lipoprotein (a) levels. Conclusion: Pentraxin-3 was a more specific inflammatory vascular marker than C-reactive protein, and the best inflammatory marker associated with hemodialysis. Homocysteine, procalcitonin and the other small proteins could be released and removed during hemodialysis session. Further studies are needed to understand the behavior and significance of these markers after successive hemodialysis

Gestión del conocimiento. Perspectiva multidisciplinaria. Volumen 17

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, Volumen 17 de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro es una publicación internacional, seriada, continua, arbitrada, de acceso abierto a todas las áreas del conocimiento, orientada a contribuir con procesos de gestión del conocimiento científico, tecnológico y humanístico. Con esta colección, se aspira contribuir con el cultivo, la comprensión, la recopilación y la apropiación social del conocimiento en cuanto a patrimonio intangible de la humanidad, con el propósito de hacer aportes con la transformación de las relaciones socioculturales que sustentan la construcción social de los saberes y su reconocimiento como bien público

TNF inhibitors exert a "hidden" beneficial effect in the cardiovascular lipoprotein profile of RA patients

Purpose: A high cardiovascular risk has been described in patients with rheumatoid arthritis (RA); the effects of different biological agents have also been described in these patients. The aim of the present study is to examine the effects of tumor necrosis factor inhibitors (TNFi) in the lipoprotein profile of RA patients using a broad laboratory assessment including a large number of non-routine tests. Patients and Methods: RA patients treated with and without TNFi (70 patients in each group) were cross-sectionally compared regarding a broad spectrum of lipoprotein parameters including serum levels of total and HDL, LDL and VLDL cholesterol triglycerides, lipoprotein A (LpA), apolipoprotein A1 (Apo A), B100 (Apo B) and paroxonase. For each lipoprotein subfraction (HDL, LDL and VLDL), we assess specific concentrations of cholesterol, triglycerides, phospholipids and proteins and total mass of each one. Additionally, HDL Apo A, LDL and VLDL Apo B concentrations and number of particles of LDL and VLDL were also determined. Exploratory univariate and multivariate analyses of the different variables were performed. Results: Seventy patients in each subset were enrolled. Patients on treatment with TNFi showed a trend to be younger and to have a longer disease duration. Regarding the lipoprotein analyses, borderline significant higher levels of serum Apo A were detected and an independent association with lower HDL mass, LDL triglyceride, VLDL cholesterol, VLDL Apo B, VLDL mass, number of VLDL cholesterol molecules and number of particles of VLDL was clearly observed. Conclusion: TNFi treatment was associated with beneficial atherogenic effects at the lipoprotein level especially centered in the VLDL-related parameters consistent with a reduction of the atherogenic risk.Funding: This study was carried out with the support of Instituto de Salud Carlos III (ISCIII) (grant number PI0810119)

Measurement and clinical usefulness of bilirubin in liver disease

Elevated plasma bilirubin levels are a frequent clinical finding. It can be secondary to alterations in any stage of its metabolism: (a) excess bilirubin production (i.e., pathologic hemolysis); (b) impaired liver uptake, with elevation of indirect bilirubin; (c) impaired conjugation, prompted by a defect in the UDP-glucuronosyltransferase; and (d) bile clearance defect, with elevation of direct bilirubin secondary to defects in clearance proteins, or inability of the bile to reach the small bowel through bile ducts. A liver lesion of any cause reduces hepatocyte cell number and may impair the uptake of indirect bilirubin from plasma and diminish direct bilirubin transport and clearance through the bile ducts. Various analytical methods are currently available for measuring bilirubin and its metabolites in serum, urine and feces. Serum bilirubin is determined by (1) diazo transfer reaction, currently, the gold-standard; (2) high-performance liquid chromatography (HPLC); (3) oxidative, enzymatic, and chemical methods; (4) direct spectrophotometry; and (5) transcutaneous methods. Although bilirubin is a well-established marker of liver function, it does not always identify a lesion in this organ. Therefore, for accurate diagnosis, alterations in bilirubin concentrations should be assessed in relation to patient anamnesis, the degree of the alteration, and the pattern of concurrent biochemical alterations

Bilirrubina: Medición y utilidad clínica en la enfermedad hepática

Un aumento en los niveles plasmáticos de bilirrubina es una alteración frecuente. Puede deberse a cualquier causa que altere alguna de las fases de su metabolismo: a) producción excesiva de bilirrubina (ej. hemólisis patológica); b) defecto en la captación hepática, con aumento de bilirrubina indirecta); c) defecto de conjugación, por alteración del enzima encargada (UDP-glucuronosiltransferasa); y d) defecto de excreción biliar, con aumento de bilirrubina directa, por defectos en las proteínas encargadas de la excreción, o bien por la imposibilidad del paso de la bilis a través de los conductos biliares hasta el intestino. Una lesión hepática de cualquier causa, al disminuir el número de hepatocitos, puede producir una disminución de la captación de bilirrubina indirecta desde el plasma y una disminución del transporte y excreción de la bilirrubina directa hacia los conductillos biliares. Se pueden usar diferentes técnicas analíticas para medir la bilirrubina y sus metabolitos en el suero, la orina y las heces. La bilirrubina sérica se mide mediante (1) la "reacción diazo", actualmente el método de referencia; (2) cromatografía líquida de alta resolución (HPLC); (3) métodos oxidativos, enzimáticos y químicos; (4) espectrofotometría directa; y (5) métodos transcutáneos. Aunque la bilirrubina es un marcador clásico de disfunción hepática, no siempre indica una lesión de este órgano. Por tanto, para obtener un diagnóstico preciso, el significado de las alteraciones de este parámetro biológico ha de valorarse en conjunción con la anamnesis del paciente, la magnitud de la alteración, y el patrón de las alteraciones bioquímicas. acompañantes

Circulating levels of mitochondrial oxidative stress-related peptides MOTS-c and Romo1 in stable COPD: a cross-sectional study

Background: MOTS-c and Romo1 are mitochondrial peptides that are modulated by oxidative stress. No previous studies have explored circulating levels of MOTS-c in patients with chronic obstructive pulmonary disease (COPD). Methods: We enrolled 142 patients with stable COPD and 47 smokers with normal lung function in an observational cross-sectional study. We assessed serum levels of both MOTS-c and Romo1 and associated these findings with clinical characteristics of COPD. Results: Compared with smokers with normal lung function, patients with COPD had lower levels of MOTS-c (p = 0.02) and higher levels of Romo1 (p = 0.01). A multivariate logistic regression analysis revealed that above-median MOTS-c levels were positively associated with Romo1 levels (OR 1.075, 95% CI 1.005–1.150, p = 0.036), but no association was found with other COPD characteristics. Below-median levels of circulating MOTS-c were associated with oxygen desaturation (OR 3.25 95% CI 1.456–8.522, p = 0.005) and walking <350 meters (OR 3.246 95% CI 1.229–8.577, p = 0.018) in six-minute walk test. Above-median levels of Romo1 were positively associated with current smoking (OR 2.756, 95% CI 1.133–6.704, p = 0.025) and negatively associated with baseline oxygen saturation (OR 0.776 95% CI 0.641–0.939, p = 0.009). Conclusions: Reduced levels of circulating MOTS-c and increased levels of Romo1 were detected in patients diagnosed with COPD. Low levels of MOTS-c were associated with oxygen desaturation and poorer exercise capacity using 6 min walk test. Romo1 was associated with current smoking and baseline oxygen saturationFunding: This study was funded by Instituto de Investigación Sanitaria of Cantabria (IDIVAL): NextVAL grant: NVAL19/01. This study received funding from GSK (NCT04449419). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decisión to submit it for publication. GSK was provided the opportunity to review a preliminary version of this manuscript for factual accuracy, but the authors are solely responsible for final content and interpretation. Acknowledgments: We want to particularly acknowledge the patients and the Biobank Valdecilla (PT17/0015/0019) integrated in the Spanish Biobank Network for its collaboration

Accuracy of plasma Abeta40, Abeta42, and p-tau181 to detect CSF Alzheimer's pathological changes in cognitively unimpaired subjects using the Lumipulse automated platform

Background The arrival of new disease-modifying treatments for Alzheimer’s disease (AD) requires the identifca tion of subjects at risk in a simple, inexpensive, and non-invasive way. With tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is neces sary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fuid or PET imaging. With this research, we want to evaluate the performance of plasma Aβ40, Aβ42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform. Methods Both plasma and CSF Aβ40, Aβ42, and p-tau181 have been evaluated in a group of 208 cognitively unim paired subjects with a 30.3% of ApoE4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the diferences in plasma marker values according to amyloid status (A−/+), AD status (consider ing AD+subjects to those A+plus Tau+), and ATN group defned by CSF. Finally, ROC curves have been performed, and the area under the curve has been measured using amyloid status and AD status as an outcome and diferent combinations of plasma markers as predictors. Results Aβ42, amyloid ratio, p-tau181, and p-tau181/Aβ42 ratio correlated signifcantly between plasma and CSF. For these markers, the levels were signifcantly diferent in the A+/−, AD+/−, and ATN groups. Amyloid ratio pre dicts amyloid and AD pathology in CSF with an AUC of 0.89. Conclusions Plasma biomarkers of AD using the automated Lumipulse platform show good diagnostic performance in detecting Alzheimer’s pathology in cognitively unimpaired subjects

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p &lt; 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p &lt; 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p &lt; 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

non present