Proteína C reactiva, aspectos cardiovasculares de una proteína de fase aguda: una actualización para el médico / C-reactive protein, cardiovascular issues of an acute-phase protein: an update for the clinician

Resumen La inflamación es un factor patogénico importante para el desarrollo de la enfermedad cardiovascular aterosclerótica. Actualmente, el biomarcador utilizado con mayor frecuencia que refleja la inflamación sistémica es la proteína C reactiva (PCR), una proteína de fase aguda producida principalmente por los hepatocitos bajo la influencia de la interleucina 6, la interleucina 1 beta y el factor de necrosis tumoral. La evidencia proveniente de estudios epidemiológicos ha demostrado una fuerte asociación entre las concentraciones elevadas de PCR en suero o plasma y la incidencia de un primer evento cardiovascular (incluido infarto agudo de miocardio, accidente vascular cerebral isquémico y muerte cardíaca súbita) en la población general, así como la recurrencia de eventos cardiovasculares adversos en los pacientes con enfermedad establecida. El valor aditivo que la medición de la PCR otorga a los factores de riesgo tradicionales se refleja en novedosas calculadoras de riesgo cardiovascular y en los actuales regímenes de intervención, que ya consideran a la PCR como objetivo terapéutico. Sin embargo, las variaciones en los niveles de PCR, que dependen del sexo, la etnia, el estado hormonal y algunas peculiaridades de los ensayos de medición, deben tenerse en cuenta al decidir implementar la PCR como un biomarcador útil en el estudio y el tratamiento de la enfermedad cardiovascular aterosclerótica. Esta revisión pretende ofrecer una visión actualizada de la importancia de medir la PCR como biomarcador de riesgo cardiovascular más allá de los factores tradicionales que estiman el riesgo de enfermedad aterosclerótica.

Abstract Inflammation is an important pathogenic factor for the development of atherosclerotic cardiovascular disease. Currently, the most frequently used biomarker reflecting systemic inflammation is C-reactive protein (CRP), an acute-phase protein produced primarily by hepatocytes under the influence of interleukin-6, interleukin-1 beta, and tumor necrosis factor. Growing evidence from epidemiological studies has shown a robust association between elevated serum or plasma CRP concentrations and the incidence of a first cardiovascular adverse event (including acute myocardial infarction, ischemic stroke, and sudden cardiac death) in the general population, as well as recurrence of major adverse cardiovascular events among patients with established disease. The additive value that CRP measurement gives to traditional risk factors is reflected in novel cardiovascular risk calculators and in current intervention regimens, which already consider CRP as a target therapeutic. However, the variations in CRP levels, that depend on sex, ethnicity, hormonal status, and some peculiarities of the measurement assays, must be taken into consideration when deciding to implement CRP as a useful biomarker in the study and treatment of atherosclerotic cardiovascular disease. This review aims to offer an updated vision of the importance of measuring CRP levels as a biomarker of cardiovascular risk beyond the traditional factors that estimate the risk of atherosclerotic disease.

O Índice de Imuno Inflamação Sistêmica Prevê Mortalidade Hospitalar em Pacientes Submetidos à Cirurgia Cardíaca com Circulação Extracorpórea / The Systemic Immune-Inflammation Index Predicts In-Hospital Mortality in Patients Who Underwent On-Pump Cardiac Surgery

Resumo Fundamento: O índice de imuno-inflamação sistêmica (SII), um novo índice inflamatório calculado usando contagens de plaquetas, neutrófilos e linfócitos, demonstrou ser um fator de risco independente para a identificação de doença arterial coronariana de alto risco em pacientes submetidos a intervenção coronária percutânea e cardiovascular e cirurgia com circulação extracorpórea (CEC). A relação entre as taxas de mortalidade relacionadas ao SII e à CEC permanece obscura. Objetivo: Esta pesquisa foi desenhada para investigar o uso do SII para prever mortalidade hospitalar em pacientes submetidos à cirurgia cardíaca com CEC. Métodos: Quatrocentos e oitenta pacientes submetidos a procedimento cardíaco envolvendo CEC durante 3 anos foram coletados do banco de dados do hospital. Foram comparados os dados demográficos, comorbidades, perfis hematológicos e bioquímico e dados operatórios dos grupos. Análises múltiplas de regressão logística foram feitas para determinar preditores independentes de mortalidade. Os fatores prognósticos foram avaliados por análise multivariada e os valores preditivos de SII, relação neutrófilo-linfócito (NLR) e razão plaqueta-linfócito (PLR) para mortalidade foram comparados. Um valor de p <0,05 foi considerado significativo. Resultados: Dos 480 pacientes, 78 desenvolveram mortalidade hospitalar após cirurgia cardíaca. O SII foi um preditor independente de mortalidade hospitalar (odds ratio: 1,003, intervalo de confiança de 95%: 1,001-1,005, p<0,001). O valor de corte do SII foi >811,93 com sensibilidade de 65% e especificidade de 65% (área sob a curva: 0,690). Os valores preditivos de SII, PLR e NLR foram próximos entre si. Conclusão: Altos escores pré-operatórios do SII podem ser usados para determinação precoce de tratamentos apropriados, o que pode melhorar os resultados cirúrgicos de cirurgia cardíaca no futuro.

Abstract Background: Systemic immune-inflammation index (SII), a new inflammatory index calculated using platelet, neutrophil, and lymphocyte counts, has been demonstrated to be an independent risk factor for the identification of high-risk coronary artery disease in patients undergoing percutaneous coronary intervention and cardiovascular surgery with cardiopulmonary bypass (CPB). The relationship between SII and CPB-related mortality rates remains unclear. Objective: This research was designed to investigate the use of SII to predict in-hospital mortality in patients undergoing cardiac surgery with CPB. Methods: Four hundred eighty patients who underwent a cardiac procedure involving CPB over 3 years, were obtained from the hospital's database. The demographic data, comorbidities, hematological and biochemical profiles, and operative data of the groups were compared. Multiple logistic regression analyses were done to determine independent predictors of mortality. Prognostic factors were assessed by multivariate analysis, and the predictive values of SII, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) for mortality were compared. A p-value <0.05 was considered significant. Results: Of 480 patients, 78 developed in-hospital mortality after cardiac surgery. SII was an independent predictor of in-hospital mortality (Odds ratio: 1.003, 95% confidence interval: 1.001-1.005, p<0.001). The cut-off value of the SII was >811.93 with 65% sensitivity and 65% specificity (area under the curve: 0.690). The predictive values of SII, PLR, and NLR were close to each other. Conclusion: High preoperative SII scores can be used for early determination of appropriate treatments, which may improve surgical outcomes of cardiac surgery in the future.

Effective Inhibition of TNF-α/mTOR Axis-Mediated Liver Inflammation and Fibrosis Induced by TAA Using a Combination of Metformin and Resveratrol in Association with the Inhibition of the Profibrotic Gene and Protein Expression

SUMMARY: The response of the immune system to harmful stimuli leads to inflammation, and the adverse effects of the toxic hepatitis chemical, thioacetamide (TAA) on the human body are well documented. This article investigated the degree of protection provided by the combined pleotropic drug, metformin (Met) and the plant polyphenolic and the antiinflammatory compound, resveratrol (Res) on liver tissue exposed to TAA possibly via the inhibition of the inflammatory cytokine, tumor necrosis factor-α (TNF-α) / mammalian target of rapamycin (mTOR) axis-mediated liver fibrosis, as well as amelioration of profibrotic gene and protein expression. Rats were either given TAA (200 mg/kg via intraperitoneal injection) for 8 weeks beginning at the third week (experimental group) or received during the first two weeks of the experiment combined doses of metformin (200 mg/kg) and resveratrol (20 mg/kg) and continued receiving these agents and TAA until experiment completion at week 10 (treated group). A considerable damage to hepatic tissue in the experimental rats was observed as revealed by tissue collagen deposition in the portal area of the liver and a substantial increase (p<0.0001) in hepatic levels of the inflammatory marker, tumor necrosis factor-α (TNF-α), as well as blood levels of hepatocellular injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TAA also augmented hepatic tissue levels of the signalling molecule that promotes liver fibrosis (mTOR), and profibrogenic markers; alpha-smooth muscle actin (α-SMA) protein, tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, and matrix metalloproteinase-9 (MMP-9) mRNA. All these parameters were protected (p≤0.0016) by Met+Res. In addition, a significant correlation was detected between liver fibrosis score and inflammation, liver injury enzymes, mTOR, and profibrogenesis markers. Thus, these findings suggest that Met+Res effectively protect the liver against damage induced by thioacetamide in association with the downregulation of the TNF-α/mTOR/fibrosis axis.

La respuesta del sistema inmunológico a estímulos dañinos conduce a la inflamación y los efectos adversos de la tioacetamida (TAA), una sustancia química tóxica para el hígado, están bien documentadas. Este artículo investigó el grado de protección proporcionado por el fármaco pleotrópico combinado metformina (Met), el polifenólico vegetal y el compuesto antiinflamatorio resveratrol (Res) en el tejido hepático expuesto a TAA, posiblemente a través de la inhibición de la citoquina inflamatoria, factor de necrosis tumoral α (TNF-α)/objetivo de la fibrosis hepática mediada por el eje de rapamicina (mTOR), así como mejora de la expresión de genes y proteínas profibróticas. Las ratas recibieron TAA (200 mg/kg mediante inyección intraperitoneal) durante 8 semanas a partir de la tercera semana (grupo experimental) o recibieron durante las dos primeras semanas del experimento dosis combinadas de metformina (200 mg/kg) y resveratrol (20 mg/kg) y continuaron recibiendo estos agentes y TAA hasta completar el experimento en la semana 10 (grupo tratado). Se observó un daño considerable al tejido hepático en las ratas experimentales, como lo revela el depósito de colágeno tisular en el área portal del hígado y un aumento sustancial (p<0,0001) en los niveles hepáticos del marcador inflamatorio, el factor de necrosis tumoral-α (TNF- α), así como los niveles sanguíneos de biomarcadores de lesión hepatocelular, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). TAA también aumentó los niveles en el tejido hepático de la molécula de señalización que promueve la fibrosis hepática (mTOR) y marcadores profibrogénicos; proteína actina del músculo liso alfa (α- SMA), inhibidor tisular de las metaloproteinasas-1 (TIMP-1) mRNA y matriz metaloproteinasa-9 (MMP-9) mRNA. Todos estos parámetros fueron protegidos (p≤0.0016) por Met+Res. Además, se detectó una correlación significativa entre la puntuación de fibrosis hepática y la inflamación, las enzimas de lesión hepática, mTOR y los marcadores de profibrogénesis. Por lo tanto, estos hallazgos sugieren que Met+Res protege eficazmente el hígado contra el daño inducido por la tioacetamida en asociación con la regulación negativa del eje TNF-α/mTOR/fibrosis.

Value of precision nutrition in the inflammatory control of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies directed against endogenous antigens causing various clinical manifestations, chronic inflammation and tissue damage. Although the pathophysiology of SLE remains unknown, it is recognized that genetic, epigenetic, environmental and neuroendocrine factors are involved in the development of the disease and its complications. A notable proportion of patients with SLE also present obesity, and this dysmetabolic profile can cause renal, musculoskeletal and/or respiratory deterioration, fatigue, various pathophysiological alterations and functional deterioration. In this context, precision nutrition emerges as a promising tool in the inflammatory control of SLE, especially in patients with associated obesity. Various studies demonstrate the beneficial influence of balanced dietary patterns in macronutrients with foods rich in fiber, vitamins, minerals, antioxidants and polyphenols on the inflammatory control of SLE and the most diverse pathologies, highlighting the Mediterranean diet and plant-based diets. Finally, the intestinal microbiota may play a relevant role in this clinical scenario, since dysbiosis is associated with inflammatory processes and immune deregulation. It is believed that precision nutrition can modulate inflammatory profiles and immune dysfunctions to ensure better quality of life and metabolic well-being of SLE patients with the support of precision omics technologies.

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune caracterizada por la producción de autoanticuerpos dirigidos contra antígenos endógenos causando diversas manifestaciones clínicas, inflamación crónica y daño tisular. Aunque la fisiopatología del LES sigue siendo desconocida, se reconoce que factores genéticos, epigenéticos, ambientales y neuroendocrinos están implicados en el desarrollo de la enfermedad y sus complicaciones. Una proporción notable de pacientes con LES presenta también obesidad, y este perfil dismetabólico puede producir deterioro renal, musculoesquelético y/o respiratorio, fatiga, diversas alteraciones fisiopatológicas y deterioro funcional. En este contexto, la nutrición de precisión emerge como una herramienta prometedora en el control inflamatorio del LES, especialmente en pacientes con obesidad asociada. Diversos estudios demuestran la influencia beneficiosa de patrones dietéticos equilibrados en macronutrientes con alimentos ricos en fibra, vitaminas, minerales, antioxidantes y polifenoles en el control inflamatorio del LES y de las más diversas patologías, destacando la dieta Mediterránea y las dietas basadas en plantas/vegetales. Por último, la microbiota intestinal puede tener un papel relevante en este escenario clínico, ya que la disbiosis se asocia con procesos inflamatorios y desregulación inmune. Se cree que con la nutrición de precisión se pueden modular los perfiles inflamatorios y las disfunciones inmunitarias para garantizar una mejor calidad de vida y el bienestar metabólico de los pacientes con LES con el apoyo de las tecnologías de precisión ómicas.

Hemograms and serial hemogram-derived ratios in survivors and non-survivors of COVID-19 in Campinas, Brazil

Introduction The hemogram and hemogram-derivative ratios (HDRs) are becoming markers of the severity and mortality of COVID-19. We evaluated the hemograms and serial weekly HDRs [neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), neutrophil-platelet ratio (NPR) and systemic immune-inflammatory index (SII)] in the survivors and non-survivors of COVID-19. Methods We retrospectively reviewed the medical notes and serial hemograms of real-time reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 adults hospitalized from April 2020 to March 2021 from the time of diagnosis to the 3rd week of diagnosis. Results Of the 320 adults, 257 (80.3%) were survivors and had a lower mean age than the non-survivors (57.73 vs. 64.65 years, p < 0.001). At diagnosis, the non-survivors had lower hematocrit (p = 0.021), and lymphocyte (p = 0.002) and basophil (p = 0.049) counts and the hematocrit showed a p-value (Is this what you meant???) of 0.021); higher NLR (p < 0.001), PLR (p = 0.047), NPR (p = 0.022) and SII (p = 0.022). Using general linear models, the survivors and non-survivors showed significant variations with weekly lymphocyte count (p < 0.001), neutrophil count (p = 0.005), NLR (p = 0.009), MLR (p = 0.010) and PLR (p = 0.035). All HDRs remained higher in the non-survivors in the 2nd week and 3rd week of diagnosis and the HDRs were higher in the intubated patients than in the non-intubated patients. The NLR and SII were more efficient predictors of mortality in COVID-19 patients. Conclusions This study shows that serial lymphocyte and neutrophil counts, NLR, PLR, MLR, NPR and SII could serve as good and easily accessible markers of severity and predictors of outcomes in COVID-19 patients and should be used for the monitoring of treatment response.

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

Mucositis oral como efecto adverso al uso del metotrexato en el tratamiento de la artritis reumatoide: una revisión sistematizada de casos / Oral mucositis as an adverse effect of the use of methotrexate in the treatment of rheumatoid arthritis: a systematized review of cases

Introducción: el metotrexato se usa ampliamente para el tratamiento de una variedad de enfermedades neoplásicas y autoinmunes. Sin embargo, como todo fármaco, su eficacia viene marcada por cierto grado de toxicidad debido a la farmacocinética del medicamento. El metotrexato se creó como un fármaco anticancerígeno; sin embargo, se ha convertido en el tratamiento de elección contra la artritis reumatoide. Principalmente, el metotrexato causa inflamación de las mucosas epiteliales. La mayoría de los efectos secundarios del metotrexato se pueden detectar de forma temprana y son reversibles. La mucositis del tracto alimentario es el principal efecto secundario de la quimioterapia contra el cáncer. Se le conoce colectivamente como lesión de la mucosa inducida por quimioterapia, afecta todo el canal alimentario desde la boca hasta el ano, ocasionando la mucositis oral y la mucositis intestinal. Material y métodos: se buscaron casos clínicos en los que se reporte mucositis causada por metotrexato en tratamiento de artritis reumatoide. Se empleó un diagrama de flujo, PRISMA modificado para la búsqueda de artículos. Finalmente, se cotejó que los casos clínicos cumplieran con los fundamentos de la CARE guide, para manejar una correcta estructura y bajo riesgo a sesgo. Conclusiones: una correcta anamnesis y exploración clínica oral es lo más importante de la medicina oral. Es relevante indagar sobre las enfermedades que presentan los pacientes, así como la historia de medicamentos que se administren, especialmente en pacientes mayores, con mayores padecimientos de enfermedades sistémicas (AU)

Introduction: methotrexate is widely used for the treatment of a variety of neoplastic and autoimmune diseases. However, like all drugs its efficacy is marked by a certain degree of toxicity due to the pharmacokinetics of the drug. Methotrexate was developed as an anticancer drug, however, it has become the treatment of choice for rheumatoid arthritis. Methotrexate primarily causes inflammation of the epithelial mucous membranes. Most of the side effects of methotrexate can be detected early and are reversible. Mucositis of the alimentary tract is the main side effect of cancer chemotherapy. It is collectively known as chemotherapy-induced mucosal injury, affecting the entire alimentary canal from the mouth to the anus, where oral mucositis and intestinal mucositis are both common. Material and methods: we searched for clinical cases reporting mucositis caused by methotrexate in the treatment of rheumatoid arthritis, using a modified PRISMA flowchart to search for articles. Finally, the clinical cases were checked for compliance with the fundamentals of the CARE guide, in order to manage a correct approach to oral medicine. It is important to inquire about the diseases the patients present, as well as the history of medications administered, especially in older patients, with more systemic disease conditions, structure, and low risk of bias. Conclusion: a correct anamnesis and oral clinical examination is the most important aspect of oral medicine. It is important to inquire about the diseases that the patients present, as well as the history of medications that are administered, especially in older patients with major systemic diseases (AU)

Effect of whole-body vibration stimulation on plasma soluble TNF receptors in elderly with sarcopenia: a randomized controlled trial

Abstract Sarcopenia is a pathology resulting from a progressive and severe loss of muscle mass, strength, and function in the course of aging, which has deleterious consequences on quality of life. Among the most widespread studies on the issue are those focused on the effect of different types of physical exercise on patients with sarcopenia. This randomized controlled study aimed to compare the effects of a whole-body vibration exercise (WBV) session on the inflammatory parameters of non-sarcopenic (NSG, n=22) and sarcopenic elderly (SG, n=22). NSG and SG participants were randomly divided into two protocols: intervention (squat with WBV) and control (squat without WBV). After a one-week washout period, participants switched protocols, so that everyone performed both protocols. Body composition was assessed by dual-energy radiological absorptiometry (DXA) and function through the six-minute walk test (6MWD) and Short Physical Performance Battery (SPPB). Plasma soluble tumor necrosis factor receptors (sTNFR) were determined by enzyme-linked immunosorbent assay (ELISA) and measured before and immediately after each protocol. After exercise with WBV, there was an increase in sTNFR2 levels in the NSG (P<0.01; d=-0.69 (-1.30; -0.08) and SG (P<0.01, d=-0.95 (-1.57; -0.32) groups. In conclusion, an acute session of WBV influenced sTNFr2 levels, with sarcopenic individuals showing a greater effect. This suggested that WBV had a more pronounced impact on sTNFr2 in those with loss of muscle strength and/or physical performance. Additionally, WBV is gaining recognition as an efficient strategy for those with persistent health issues.

Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression

Abstract Background: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA.

Albúmina en cirrosis: perspectiva inflamatoria / Albumin in cirrhosis: inflammatory perspective

La albúmina sérica humana es la proteína más abundante en el plasma, su estructura molecular le confiere estabilidad, pero también flexibilidad para ligar y transportar un amplio rango de moléculas. Su función oncótica es la propiedad más reconocida que la lleva a introducirse en la terapéutica médica como un expansor de volumen. Sin embargo, en los últimos años se le han adicionado funciones con carácter antioxidante, inmunomodulador y de estabilización endotelial, que hacen presumir que su impacto terapéutico está más allá de sus funciones volumétricas. En los últimos años, específicamente en la cirrosis y la falla hepática aguda sobre crónica, se ha tenido un cambio en el paradigma fisiológico, desde una perspectiva netamente hemodinámica hacia una perspectiva inflamatoria, en donde las funciones oncóticas y no oncóticas de la albúmina están alteradas y tienen un carácter pronóstico en estas entidades. Este conocimiento creciente, desde una perspectiva inflamatoria, hace que se fortalezca el uso terapéutico de la albúmina sérica humana desde las indicaciones tradicionales como prevención de la disfunción circulatoria posparacentesis, prevención y tratamiento de lesión renal aguda, hasta las discusiones para administración a largo plazo en pacientes cirróticos con ascitis.

Human serum albumin is the most abundant protein in plasma, with a molecular structure that provides stability while also allowing flexibility to bind and transport a wide range of molecules. Its oncotic function is the most recognized property, leading to its introduction in medical therapy as a volume expander. However, in recent years, additional functions with antioxidant, immunomodulatory, and endothelial stabilization properties have been identified, suggesting that its therapeutic impact extends beyond its volumetric functions. Specifically, in cirrhosis and acute-on-chronic liver failure, there has been a shift in the pathophysiological paradigm from a purely hemodynamic perspective to an inflammatory perspective, where both oncotic and non-oncotic functions of albumin are altered and have prognostic significance in these conditions. This growing understanding from an inflammatory perspective strengthens the therapeutic use of human serum albumin, not only for traditional indications such as the prevention of post-paracentesis circulatory disfunction, prevention and treatment of acute kidney injury, but also for discussions regarding long-term administration in cirrhotic patients with ascites.

Systemic and local antiinflammatory effect of magnesium chloride in experimental arthritis

Abstract Objective Despite some knowledge gaps in scientific evidence, MgCl2 is largely used for pain relief in musculoskeletal diseases. Mg salts were shown to provide analgesia postoperatively in orthopedic surgery and low Mg levels were linked to arthritis development and severity. We determined the anti-inflammatory activity of MgCl2 in an acute arthritis model. Methods Mice received 0.1 mg/25μL Zymosan (Zy) or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, and interleukin (IL)-1 level were assessed in joint lavage at 6 h. Synovia were excised for histopathology and analysis of immunoexpression of nuclear factor kappa B (NFκB) and tumor necrosis factor (TNF)-α. Groups (n = 6/group) received either 90 mg/kg MgCl2/100 μL or saline per os (systemic) or 500 μg/25 μL MgCl2 or saline intra-articularly (i.a.) 30 min prior to Zy. Results MgCl2 given either systemically or locally significantly reduced cell influx (p = 0.0012 and p = 0.0269, respectively), pain (p = 0.0005 and p = 0.0038, respectively), and intra-articular IL-1 level (p = 0.0391), as compared to saline. Systemic MgCl2 significantly decreased NFκB (p < 0.05) immmunoexpression, as compared to saline. Conclusion MgCl2 given systemically or locally displayed anti-inflammatory activity in a severe acute arthritis model reducing cell influx, pain, and cytokine release. MgCl2 operates at least partially via inhibiting NFκB activation. This is the first in vivo demonstration that MgCl2 decreases cytokine release in arthritis, prompting reduction of inflammation and pain relief.

Avaliação da lactoferrina e da calprotectina como marcadores de inflamação intestinal na pancreatite crônica / Evaluating lactoferrin and calprotectin as markers of intestinal inflammation inchronic pancreatitis

ABSTRACT Background: The treatment of chronic pancreatitis does not consistently solve intestinal abnormalities, and despite the implementation of various therapeutic measures, patients often continue to experience persistent diarrhea. Therefore, it is imperative to recognize that diarrhea may stem from factors beyond pancreatic insufficiency, and intestinal inflammation emerges as a potential contributing factor. Objective: The aim of this study was to assess fecal lactoferrin and calprotectin levels as indicators of intestinal inflammation in patients with chronic pancreatitis experiencing persistent diarrhea. Methods: In this study, 23 male patients with chronic pancreatitis primarily attributed to alcohol consumption and presenting with diarrhea (classified as Bristol stool scale type 6 or 7), underwent a comprehensive evaluation of their clinical and nutritional status. Fecal lactoferrin and calprotectin levels were mea­sured utilizing immunoassay techniques. Results: The average age of the participants was 54.8 years, 43.5% had diabetes, and 73.9% were smokers. Despite receiving enzyme replacement therapy and refraining from alcohol for over 4 years, all participants exhibited persistent diarrhea, accompanied by elevated calprotectin and lactoferrin levels indicative of ongoing intestinal inflammation. Conclusion: The findings of this study underscore that intestinal inflammation, as evidenced by elevated fecal biomarkers calprotectin and lactoferrin, may contribute to explaining the persistence of diarrhea in patients with chronic pancreatitis.

RESUMO Contexto: O tratamento da pancreatite crônica não resolve de forma consistente as anomalias intestinais e, apesar da implementação de várias medidas terapêuticas, os pacientes muitas vezes continuam a apresentar diarreia persistente. Portanto, é imperativo reconhecer que a diarreia pode resultar de fatores além da insuficiência pancreática, e a inflamação intestinal surge como um potencial fator contribuinte. Objetivo: O objetivo deste estudo foi avaliar os níveis fecais de lactoferrina e calprotectina como indicadores de inflamação intestinal em pacientes com pancreatite crônica com diarreia persistente. Métodos: Neste estudo, 23 pacientes do sexo masculino com pancreatite crônica atribuída principalmente ao consumo de álcool e apresentando diarreia (classificada na escala de fezes de Bristol tipo 6 ou 7), foram submetidos a uma avaliação abrangente de seu estado clínico e nutricional. Os níveis fecais de lactoferrina e calprotectina foram medidos utilizando técnicas de imunoensaio. Resultados: A idade média dos participantes foi de 54,8 anos, 43,5% tinham diabetes e 73,9% eram fumantes. Apesar de receber terapia de reposição enzimática e abster-se de álcool por mais de 4 anos, todos os participantes apresentaram diarreia persistente, acompanhada por níveis elevados de calprotectina e lactoferrina, indicativos de inflamação intestinal contínua. Conclusão: Os achados deste estudo ressaltam que a inflamação intestinal, evidenciada pelos biomarcadores fecais elevados calprotectina e lactoferrina, pode contribuir para explicar a persistência da diarreia em pacientes com pancreatite crônica.

Evaluation of pathogen from the FilmArray meningitis/encephalitis panel and recommendations on atypical findings / Avaliação do patógeno do painel de meningite/encefalite FilmArray e recomendações sobre achados atípicos

Abstract Background Infectious meningoencephalitis is a potentially fatal clinical condition that causes inflammation of the central nervous system secondary to the installation of different microorganisms. The FilmArray meningitis/encephalitis panel allows the simultaneous detection of 14 pathogens with results in about one hour. Objective This study is based on retrospectively evaluating the implementation of the FilmArray meningitis/encephalitis panel in a hospital environment, highlighting the general results and, especially, analyzing the consistency of the test results against the clinical and laboratory conditions of the patients. Methods Data were collected through the results reported by the BioFire FilmArray system software from the meningitis/encephalitis panel. The correlated laboratory tests used in our analysis, when available, included biochemical, cytological, direct and indirect microbiological tests. Results In the analyzed period, there were 496 samples with released results. Of the total of 496 samples analyzed, 88 (17.75%) were considered positive, and 90 pathogens were detected, and in 2 of these (2.27%) there was co-detection of pathogens. Viruses were the agents most frequently found within the total number of pathogens detected. Of the 496 proven samples, 20 (4.03%) were repeated, 5 of which were repeated due to invalid results, 6 due to the detection of multiple pathogens and 9 due to disagreement between the panel results and the other laboratory tests and/or divergence of the clinical-epidemiological picture. Of these 20 repeated samples, only 4 of them (20%) maintained the original result after repeating the test, with 16 (80%) being non-reproducible. The main factor related to the disagreement of these 16 samples during retesting was the detection of bacterial agents without any relationship with other laboratory tests or with the patients' clinical condition. Conclusion In our study, simply reproducing tests with atypical results from the FilmArray meningitis/encephalitis panel proved, in most cases, effective and sufficient for interpreting these results.

Resumo Antecedentes A meningoencefalite infecciosa é uma condição clínica potencialmente fatal que causa inflamação do sistema nervoso central secundária à instalação de diversos microrganismos. O painel de meningite/encefalite FilmArray permite a detecção simultânea de 14 patógenos, com resultados em cerca de uma hora. Objetivo Este estudo baseia-se em avaliar retrospectivamente a implementação do painel de meningite/encefalite FilmArray em ambiente hospitalar, destacando os resultados gerais e, principalmente, analisando a consistência dos resultados do teste frente às condições clínicas e laboratoriais dos pacientes. Métodos Os dados foram coletados por meio dos resultados relatados pelo software do sistema BioFire FilmArray do painel de meningite/encefalite. Os exames laboratoriais correlacionados utilizados em nossa análise, quando disponíveis, incluíram exames bioquímicos, citológicos, microbiológicos diretos e indiretos. Resultados No período analisado, foram 496 amostras com resultados divulgados. Do total de 496 amostras analisadas, 88 (17,75%) foram consideradas positivas e 90 patógenos foram detectados, sendo que em duas destas (2,27%) houve codetecção de patógenos. Os vírus foram os agentes mais frequentemente encontrados dentro do total de patógenos detectados. Das 496 amostras analisadas, 20 (4,03%) foram repetidas, sendo 5 repetidas por resultado inválido, 6 pela detecção de múltiplos patógenos e 9 por discordância dos resultados do painel com os demais exames laboratoriais e/ou divergência do quadro clínico-epidemiológico. Destas 20 amostras repetidas, apenas 4 delas (20%) mantiveram o resultado original após a repetição do teste, sendo 16 (80%) não reprodutíveis. O principal fator relacionado à discordância destas 16 amostras na retestagem foi a detecção de agentes bacterianos sem qualquer relação com os demais exames laboratoriais ou com o quadro clínico dos pacientes. Conclusão Em nosso estudo, a simples repetição dos testes com resultados atípicos do painel de meningite/encefalite FilmArray mostrou-se, na maior dos casos, efetiva e suficiente para a interpretação destes achados.

Increased Circulating Fetuin-A Levels in Patients with Atrial Fibrillation

Abstract Background Biomarkers related to the pathogenesis of atrial fibrillation (AF) have attracted the attention of experts. One of these recently studied biomarkers is Fetuin-A. Objectives This study aimed to evaluate the relationship between serum Fetuin-A levels and AF. Methods This study used the convenience sampling method, based on inclusion criteria and consent to participate in the study. The Shapiro-Wilk test was used to confirm the normal distribution of all continuous variables. Categorical variables were presented using absolute and relative frequencies. Both groups (48 patients with AF and 47 controls) were compared in terms of biochemical, hematological, and echocardiographic findings and Fetuin-A. the Chi-square or Fisher's exact test were used to compare groups concerning categorical variables. Continuous variables were compared using the independent samples t-test. P<0.05 was considered statistically significant. Results Serum Fetuin-A values increased in AF patients when compared to the controls (544±49 μg/mL versus 484±46 μg/mL, p=0.001). Moreover, Fetuin-A level was independently associated with AF — AOR = 0.978, 95%; confidence interval (CI) 0.969-988, p < 0.001. The cut-off values in Fetuin-A levels in patients with AF were >511.80 μg/mL with a sensitivity of 75% and a specificity of 73% — area under the curve (AUC) = 0.804, 95% CI = 0.715 - 0.892. Conclusions According to this study, there was a relationship between serum Fetuin-A levels and AF, regardless of conventional cardiovascular risk factors. Therefore, Fetuin-A may play a role in the pathophysiology of AF. Prospectively designed cohort studies are necessary to assess whether or not the results can be generalized for other populations.

Didymin protects against polystyrene nanoplastic-induced hepatic damage in male albino rats by modulation of Nrf-2/Keap-1 pathway

Polystyrene nanoplastics (PS-NPs) are ubiquitous environmental pollutants that can cause oxidative stress in various organs, including the liver. Didymin is a dietary flavanone that displays multiple pharmacological activities. Therefore, the present study evaluated the palliative role of didymin against PS-NPs-induced hepatic damage in rats. Albino rats (n=48) were randomly distributed into 4 groups: control, PS-NPs treated group, PS-NPs + didymin co-administered group, and didymin supplemented group. After 30 days, PS-NPs intoxication lowered the expression of Nrf-2 and anti-oxidant genes [catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione-S-transferase (GST), and heme oxygenase-1 (HO-1)], whereas the expression of KEAP1 kelch like ECH associated protein 1 (Keap-1) was increased. PS-NPs exposure also reduced the activities of anti-oxidants enzymes (CAT, SOD, GPx, GSR, GST, GSH, and OH-1), while malondialdehyde (MDA) and reactive oxygen species (ROS) levels were increased. The levels of alanine transaminase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were increased in PS-NPs-exposed rats. Moreover, inflammatory indices [interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), nuclear factor-kappa B (NF-κB), and cyclooxygenase-2 (COX-2)] were increased in PS-NPs-exposed rats. Furthermore, PS-NPs intoxication increased the expressions of apoptotic markers including Bax and Caspase-3, as well as reducing Bcl-2 expression. The histopathological analysis showed significant damage in PS-NPs-treated rats. However, didymin supplementation ameliorated all the PS-NPs-induced damage in the liver of rats. Therefore, it was concluded that didymin can act as a remedy against PS-NPs-induced liver toxicity due to its anti-apoptotic, anti-oxidant, and anti-inflammatory activities.

Could a reduced hemoglobin, albumin, lymphocyte, and platelet (HALP) score predict autoimmune hepatitis and degree of liver fibrosis?

SUMMARY OBJECTIVE: Autoimmune hepatitis is a rare inflammatory disease of the liver that is characterized by elevated liver enzymes. The hemoglobin, albumin, lymphocyte, and platelet score, which is derived from hemoglobin, serum albumin, circulating lymphocyte count, and platelet count, is also associated with inflammatory conditions. The aim was to examine the hemoglobin, albumin, lymphocyte, and platelet score of patients with autoimmune hepatitis and to compare it to that of healthy individuals in this retrospective analysis. METHODS: Subjects diagnosed with autoimmune hepatitis were enrolled in the study, and healthy individuals were enrolled as controls. Moreover, autoimmune hepatitis subjects were grouped into mild or moderate/advanced fibrosis. Furthermore, aspartate to platelet ratio index, Fibrosis-4, and hemoglobin, albumin, lymphocyte, and platelet scores of the autoimmune hepatitis patients and controls were compared. In addition, the hemoglobin, albumin, lymphocyte, and platelet score of the autoimmune hepatitis patients with mild fibrosis is compared to that of those with moderate/advanced fibrosis. RESULTS: The mean hemoglobin, albumin, lymphocyte, and platelet score of the autoimmune hepatitis patients was 44.2±14.5 while this value was 76.8±15.5 in control subjects. The hemoglobin, albumin, lymphocyte, and platelet score was significantly reduced in autoimmune hepatitis patients than healthy controls (p<0.001). The hemoglobin, albumin, lymphocyte, and platelet score was significantly and negatively correlated with C-reactive protein, aspartate, alanine transaminase, gamma glutamyl transferase, aspartate to platelet ratio index, and Fibrosis-4 values. A hemoglobin, albumin, lymphocyte, and platelet score that was lower than 52.3 had 83% sensitivity and 73% specificity in predicting autoimmune hepatitis. The sensitivity and specificity of the hemoglobin, albumin, lymphocyte, and platelet score were higher than the Fibrosis-4 score in predicting moderate/advanced fibrosis in autoimmune hepatitis. CONCLUSION: We suggest that the hemoglobin, albumin, lymphocyte, and platelet score be used as an additional noninvasive diagnostic tool for autoimmune hepatitis and to predict moderate/advanced liver fibrosis in patients with autoimmune hepatitis.

Role of Interleukin-17 family cytokines in disease severity of patients with knee osteoarthritis

Abstract Background Interleukin-17 (IL-17) family plays a role in the pathogenesis of knee osteoarthritis (KOA) by contributing to the inflammatory and destructive processes in the affected joint. This study aimed to measure levels of IL-17 A and IL-25 (IL-17E) in serum of KOA patients and determine their roles in the disease severity of patients. Methods In this, 34 patients with KOA and 30 age and sex-matched healthy subjects (HS) were enrolled. Patients were categorized based on their Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS), and Body Mass Index (BMI) scores. The enzyme-linked immunosorbent assay (ELISA) technique was employed to measure serum levels of IL-17 A and IL-25. Results Level of IL-25 was significantly higher (P < 0.0001) in the KOA subjects than HS. IL-17 A level was significantly higher in KOA cases with WOMAC < 40 (P < 0.0001) in comparison to HS. IL-25 level was significantly higher in the KOA cases with WOMAC < 40 (P < 0.0001) and with WOMAC ≥ 40 (P < 0.0001) compared to HS. IL-17 A concentration was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) compared to HS. IL-25 level was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) and with VAS ≥ 5 (P < 0.0001) in comparison to HS. KOA patients with BMI ≥ 30 had significantly higher IL-17 A and IL-25 concentration in comparison to HS. Conclusions The serum level of IL-25 in KOA patients is increased probably due to negative controlling feedback on inflammatory responses, which can be associated with obesity and disease activity.

Is Trimethylamine N-oxide (TMAO) Associated with NF-κB mRNA Expression in Patients with Coronary Artery Disease?

Abstract Background: Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, is associated with cardiovascular disease (CVD) development. TMAO can trigger an inflammatory response by inducing the nuclear factor-kappa B (NF-κB) signaling cascade and increasing the expression of pro-inflammatory cytokines, contributing to the worsening of CVD. This study aimed to evaluate the association between TMAO plasma levels and inflammation in patients with coronary artery disease (CAD). Methods: A cross-sectional study was carried out including 29 patients with CAD. Peripheral blood mononuclear cells (PBMC) were isolated from fasting blood samples, and NF-κB and vascular cell adhesion protein 1 (VCAM1) mRNA expression were estimated using real-time quantitative PCR. We determined TMAO plasma levels by LC-MS/MS and TNF-α by ELISA. Routine biochemical parameters were evaluated using an automatic biochemical analyzer. Correlations were estimated by Spearman or Pearson test. Statistical significance was set at the level of p < 0.05. Results: All patients presented TMAO levels within the normal range according to EUTox (normal range: 2.83 ± 1.53 mg/L; CAD patients: 0.2 [0.1 to 0.2] ng/μL). TMAO plasma levels were positively correlated with NF-κB mRNA expression (0.555; p = 0.002). Conclusion: TMAO plasma levels may be associated with NF-κB mRNA expression in patients with CAD and may contribute to the pathogenesis of this disease.

Hemoglobin/Red Cell Distribution Width Ratio is Associated With Poor Prognosis in Patients With Acute Coronary Syndrome in Long-Term Follow-Up

Abstract Background Acute coronary syndrome (ACS) is the most common subtype of coronary artery disease (CAD). It is one of the main reasons affecting the expected life expectancy and quality of life. Objetives In this study, we aimed to investigate the relationship between major adverse cardiac events (MACE) and Hemoglobin (Hb)/Red cell distribution width (RDW) in long-term follow-up after ACS. Methods A total of 1,146 ACS patients were included in the study, being classified according to the type of myocordial infarction (MI). MACE were recorded in long-term follow-up. The relationship between Hb/RDW and MACE was investigated. The statistical analyses of Mann-Whitney U test for comparison of two independent groups and chi-square test for categorical variables were used. In order to determine the diagnostic feature of the HB/RDW ratio, the diagnostic ratios were calculated by applying Receiver Operating Characteristic Curve (ROC) analysis. A p < 0.05 value was considered statistically significant in all analyses. Results: When the patients were analyzed according to MI types — ST segment elevation myocardial infarction (STEMI)/Non-ST segment elevation myocardial infarction (NSTEMI) —, it was observed that Hb/RDW (p = 0.038) was significantly higher in the STEMI group. The Hb/RDW ratio was statistically significant in predicting mortality. As a result of ROC analysis, Area Under the Curve (AUC) = 0.654 (p < 0.001) was found. The cut-off value for the Hb/RDW ratio was calculated as 0.947. The sensitivity and specificity of 76.9% and 48.4% for the diagnostic rates obtained were moderately acceptable. Conclusion The Hb/RDW-long-term mortality relationship was found to be significant in ROC analysis. It can be used in clinical practice as it is cheap, easy to apply, and reduces possible bias in post-ACS follow-up.