Increased TNF-α production in response to IL-6 in patients with systemic inflammation without infection.

Acute systemic inflammation can lead to life-threatening organ dysfunction. In patients with sepsis, systemic inflammation is triggered in response to infection, but in other patients, a systemic inflammatory response syndrome (SIRS) is triggered by non-infectious events. IL-6 is a major mediator of inflammation, including systemic inflammatory responses. In homeostatic conditions, when IL-6 engages its membrane-bound receptor on myeloid cells, it promotes pro-inflammatory cytokine production, phagocytosis, and cell migration. However, under non-physiologic conditions, such as SIRS and sepsis, leucocyte dysfunction could modify the response of these cells to IL-6. So, our aim was to evaluate the response to IL-6 of monocytes from patients diagnosed with SIRS or sepsis. We observed that monocytes from patients with SIRS, but not from patients with sepsis, produced significantly more TNF-α than monocytes from healthy volunteers, after stimulation with IL-6. Monocytes from SIRS patients had a significantly increased baseline phosphorylation of the p65 subunit of NF-κB, with no differences in STAT3 phosphorylation or SOCS3 levels, compared with monocytes from septic patients, and this increased phosphorylation was maintained during the IL-6 activation. We found no significant differences in the expression levels of the membrane-bound IL-6 receptor, or the serum levels of IL-6, soluble IL-6 receptor, or soluble gp130, between patients with SIRS and patients with sepsis. Our results suggest that, during systemic inflammation in the absence of infection, IL-6 promotes TNF-α production by activating NF-κB, and not the canonical STAT3 pathway.

Medical Theatre as an Innovative Pedagogical Strategy in Medical Simulation.

Medical education has overshadowed the importance for interpersonal abilities in modern medicine practice. In this work, we report an innovative strategy to teach, practice, and evaluate communication and empathy abilities, based on medical theater. This approach was based on interdisciplinary effort between Medicine, Performing Arts, and Bioethics Faculty. Development and first pilot experience results are here reported. A multidisciplinary team was established with the objective to structure the methodology where simulated clinical consultations were performed: two interviews took place, each with one medical student as physician and one performing arts student as simulated patient. Thirty students and 7 Faculty members participated as spectators. Students received immediate feedback and they qualitatively evaluated the global experience. We conclude that medical theater methodology is a developmental strategy that could promote integral acquisition of communication competences. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01551-8.

Accurate diagnosis of sepsis using a neural network: Pilot study using routine clinical variables.

BACKGROUND AND OBJECTIVES: Sepsis is a severe infection that increases mortality risk and is one if the main causes of death in intensive care units. Accurate detection is key to successful interventions, but diagnosis of sepsis is complicated because the initial signs and symptoms are not specific. Biomarkers that have been proposed have low specificity and sensitivity, are expensive, and not available in every hospital. In this study, we propose the use of artificial intelligence in the form of a neural network to diagnose sepsis using only common laboratory tests and vital signs that are routine and widely available. METHODS: A retrospective, cross sectional cohort of 113 patients from an intensive care unit, each with 48 routinely evaluated vital signs and biochemical parameters was used to train, validate and test a neural network with 48 inputs, 10 neurons in a single hidden layer and one output. The sensitivity and specificity of the neural network as a point sampled diagnostic test was calculated. RESULTS: All but one case were correctly diagnosed by the neural network, with 91% sensitivity and 100% specificity in the validation data set, and 100% sensitivity and specificity in the test data set. CONCLUSIONS: The designed neural network system can identify patients with sepsis, with minimal resources using standard laboratory tests widely available in most health care facilities. This should reduce the burden on the medical staff of a difficult diagnosis and should improve outcomes for patients with sepsis.

Impact of Metabolic Syndrome in the Clinical Outcome of Disease by SARS-COV-2.

BACKGROUND: It has been observed that subjects with comorbidities related to metabolic syndrome (MetS) as hypertension, obesity, cardiovascular disease (CVD), and diabetes mellitus (DM2) show severe cases and a higher mortality by COVID-19. To date, there is little information available on the impact of the interaction between these comorbidities in the risk of death by COVID-19. AIM OF THE STUDY: To evaluate the impact of the combinations of MetS components in overall survival (OS) and risk of death among COVID-19 patients. METHODS: Using public data of the Ministry of Health, suspected, and confirmed COVID-19 cases from February 25-June 6, 2020 was analyzed. Mortality odds ratio (OR) was calculated with a univariate analysis (95% CI) and attributable risk. Interactions between components and survival curves were analyzed and a multivariate logistics regression analysis was conducted. RESULTS: The analysis included 528,651 cases out of which 202,951 were confirmed for COVID-19. Probabilities of OS among confirmed patients were 0.93, 0.89, 0.87, 0.86, and 0.83 while the OR of multivariate analysis was 1.83 (1.77-1.89), 2.58 (2.48-2.69), 2.83 (2.66-3.01), and 3.36 (2.83-3.99) for zero, one, two, three, and four MetS components, respectively. The combination with the highest risk was DM2 + hypertension at 2.22 (2.15-2.28), and the attributable risk for any component was 9.35% (9.21-9.49). Only the combination obesity + CVD showed no significant interaction. CONCLUSION: The presence of one MetS component doubles the risk of death by COVID-19, which was higher among patients with DM2 + hypertension. Only obesity and CVD do not interact significantly.

Metabolic Syndrome and Cardiovascular Disease: A Health Challenge.

Metabolic Syndrome (MetS) is a cluster of risk factors that, taken alone or synergically, are independent predictors of type 2 diabetes and cardiovascular disease (CVD), which are both major public health problems that requires urgent containment actions. Current controversies regarding MetS are focused on ascertain the unifying explanation of molecular and pathophysiological mechanisms originating the syndrome, involving insulin resistance and low-grade chronic inflammation. This review aims to present the clinical relevance of MetS and its complications, as well as the hypotheses addressing its etiopathogenic relation with CVD. We conclude that health policies should emphasize basic research promotion, timely detection and early treatment of MetS, which will help to reduce the risk of CVD and their impact on public health and health-care related costs.

Relationship of hyperuricemia with low density lipoprotein , liver function tests and markers of systemic inflammation in patients with morbid obesity. / Relación de la hiperuricemia con las lipoproteínas de baja densidad, las pruebas de funcionamiento hepático y los marcadores de inflamación sistémica en pacientes con obesidad mórbida.

Objective: To examine the relationship of uric acid levels with parameters of systemic inflammation, metabolic dysfunction as well as anthropometric parameters and liver function tests in subjects with morbid obesity. Methods: C-reactive protein (CRP), tumour necrosis factor-alpha, and interleukin 10 (IL-10) were analyzed in 49 women and men with morbid obesity, relating these markers with uric acid, hepatic function tests, anthropometric and metabolic parameters. Metabolic parameters as serum glucose level, glycosylated hemoglobin, total cholesterol, triglycerides, high density lipoprotein and low density lipoprotein (c-LDL) as well as hepatic function parameters were measured in all subjects. Results: -Comparing subjects with morbid obesity without hyperuricemia versus subjects with morbid obesity and hyperuricemia, an increase of total bilirubin values and gamma glutamil trans peptidase (GGT) was observed, suggesting hyperuricemia as associated with alteration of hepatic metabolism. Serum uric acid levels were statistically correlated with c-LDL, total bilirubin, albumin, GGT and CRP suggesting hyperuricemia could be associated with a dyslipidemic state, hepatic damage and increase in acute pro-inflammatory phase markers. In addition, a multiple linear regression analysis revealed that GGT and IL-10 were better predictors of the behavior of uric acid in the study population. Conclusion: These results suggest an -interdependent relationship among serum uric acid, CRP and IL-10 levels, which could be related to early hepatic -damage.

[Good's syndrome. Report of case]. / Síndrome de Good. Reporte de un caso.

BACKGROUND: Good's syndrome is an association of thymoma and immunodeficiency. The symptoms are recurrent sinopulmonary infections in addition to the compressive side of thymoma. A laboratory finding is notable for the absence or decrease of B lymphocytes, hypogammaglobulinemia, inversion ratio CD4/CD8 and abnormal proliferative response to mitogens. CASE REPORT: Female, 49-year-old started five months earlier with lower limb edema, postprandial vomiting, dysphagia, chronic diarrhea and weight loss. A second endoscopy ruled gastric neoplasia. Chest radiography with mediastinal widening, Thoraco-abdominal CT with bilateral pleural effusion and a mass in the anterior mediastinum, histopathological report of the tumor: B1 thymoma. Laboratory findings: IgG 349 mg/dL, IgA 70.3 mg/dL, 37.1 IgM mg/dL, Ca125 631 UI/mL, leukocytes 7890 mm3, hemoglobin 13.2 g/dL, lymphocytes 2060 mm3, CD16+CD56+ 122 cells/µL, CD19 77 cells/µL, CD3 2052 cells/µL, CD4 977 cells/µL, CD8 998 cells/µL; ratio CD4/CD8 0.98, hepatitis C, B and HIV negative. They requested valuation to Clinical Immunology and Allergy due to hypogammaglobulinemia, the diagnosis of Good's syndrome was confirmed and initiated with intravenous gamma globulin replacement to immunomodulatory dose of 1 g/kg, she reached replacement goal in the third dose of immunoglobulin intravenous, with clinical improvement. She died four months later from cardiac complications. CONCLUSIONS: Despite the variability of presentation, Good's syndrome should be suspected as part of the paraneoplastic manifestations of thymoma.

Introducción: El síndrome de Good es una asociación de timoma e inmunodeficiencia. Los síntomas son infecciones sinopulmonares recurrentes, además de los provocados por la compresión del timoma. Los exámenes paraclínicos se caracterizan por ausencia o disminución de linfocitos B, hipogammaglobulinemia, inversión de la relación CD4/CD8 y respuesta proliferativa anormal a mitógenos. Caso clínico: Mujer de 49 años de edad con edema de miembros inferiores, vómito posprandial, disfagia, diarrea crónica y pérdida ponderal. Con una segunda endoscopia se descartó cáncer gástrico. En la placa de tórax se observó ensanchamiento de mediastino y en la tomografía toracoabdominal, derrame pleural bilateral y tumor en mediastino anterior. El reporte histopatológico fue timoma B1. Exámenes paraclínicos: IgG, IgA e IgM de 349, 70.3 y 37.1 mg/dL, respectivamente; Ca125 631 UI/mL, leucocitos 7890 mm3, hemoglobina 13.2 g/dL, linfocitos 2060 mm3; CD16+CD56+, CD19, CD3, CD4 y CD8 de 122, 77, 2052, 977 y 998 cel/µL, respectivamente; relación CD4/CD8 0.98; panel viral para hepatitis C, B y VIH negativo. La hipogammaglobulinemia confirmó síndrome de Good; se inició con 1 g/kg de gammaglobulina intravenosa, alcanzando meta de reemplazo a la tercera dosis, con mejoría clínica. La paciente falleció a los 4 meses por complicaciones cardiacas. Conclusiones: A pesar de la variabilidad de la presentación del síndrome de Good, debe sospecharse como parte de las manifestaciones paraneoplásicas del timoma.

[Low-grade systemic inflammation and the development of metabolic diseases: from the molecular evidence to the clinical practice]. / Inflamación sistémica de grado bajo y su relación con el desarrollo de enfermedades metabólicas: de la evidencia molecular a la aplicación clínica.

BACKGROUND: Systemic inflammation is characterised by high circulating levels of inflammatory cytokines and increased macrophage infiltration in peripheral tissues. Most importantly, this inflammatory state does not involve damage or loss of function of the infiltrated tissue, which is a distinctive feature of the low-grade systemic inflammation. The term "meta-inflammation" has also been used to refer to the low-grade systemic inflammation due to its strong relationship with the development of cardio-metabolic diseases in obesity. OBJECTIVE: A review is presented on the recent clinical and experimental evidence concerning the role of adipose tissue inflammation as a key mediator of low-grade systemic inflammation. Furthermore, the main molecular mechanisms involved in the inflammatory polarization of macrophages with the ability to infiltrate both the adipose tissue and the vascular endothelium via activation of toll-like receptors by metabolic damage-associated molecular patterns, such as advanced glycation-end products and oxidized lipoproteins, is discussed. Finally, a review is made of the pathogenic mechanisms through which the low-grade systemic inflammation contributes to develop insulin resistance, dyslipidaemia, atherogenesis, type 2 diabetes, and hypertension in obese individuals. CONCLUSIONS: A better understanding of the molecular mechanisms of low-grade systemic inflammation in promoting cardio-metabolic diseases is necessary, in order to further design novel anti-inflammatory therapies that take into consideration clinical data, as well as the circulating levels of cytokines, immune cells, and metabolic damage-associated molecular patterns in each patient.

Pathophysiological implications between chronic inflammation and the development of diabetes and obesity.

The different theories about the mechanisms involved in the development of metabolic disease and its complications converge in the presence of an etiologic chronic proinflammatory state. Chronic inflammation is, at present, the central pathophysiological mechanism involved in the genesis of metabolic diseases. The multiple interactions between the immune system, adipose tissue, the vascular wall and the pancreas are the issues addressed in this review, focusing on specific intracellular and molecular aspects that may become new therapeutic targets. These lead to a proinflammatory, prothrombotic state as well as to proapoptotic endothelial damage that allows the development of atherosclerosis and, consequently, cardiovascular disease. The multiple immunopathological processes associated with the etiology and pathophysiology of different chronic diseases is still in the process of being fully elucidated, allowing the development of new therapeutic targets.