Notable correlation between serum epidermal growth factor values and inflammatory status in patients with COVID-19.

INTRODUCTION: Despite its crucial role in Epidermal Growth Factor Receptor (EGFR) activation, and the resulting impact on the health-disease process, epidermal growth factor (EGF) is an underexplored molecule in relation to how its serum concentrations relate to other analytes and clinical variables in pathological contexts. OBJECTIVE: To clarify the possible correlation between EGF and clinical and analytical variables in the context of COVID-19. METHODS: Cross-sectional observational and analytical study, in patients with virological and clinical diagnosis of COVID-19, selected by simple random sampling, admitted between August and September 2021. UMELISA-EGF commercial kits were used. RESULTS: Differences in overall EGF values were observed between groups (566.04 vs. 910.53 pg/ml, p = .0430). In COVID-19 patients, no notable correlations were observed for neutrophil, platelet, triglyceride or liver enzyme values (p > .05). Significant correlations were observed with the neutrophil-lymphocyte indicator (r = 0.4711, p = .0128) as well as with the platelet-lymphocyte index (r = 0.4553, p = .0155). Statistical results of multivariate regression analysis suggest NLR (ß = .2232, p = .0353) and PLR (ß = .2117, p = .0411) are predictors of inflammation in patients with COVID-19. CONCLUSIONS: Serum EGF concentrations in COVID-19 correlate positively with prognostic inflammatory markers of severity and could presumably act as an independent risk factor for the development of inflammation in response to new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Inflammation and all-cause mortality in patients undergoing peritoneal dialysis.

OBJECTIVE: This study aimed to evaluate inflammatory biomarkers in patients undergoing peritoneal dialysis and investigate their association with all-cause mortality or transfer to hemodialysis. METHODS: This prospective cohort study included 43 patients undergoing peritoneal dialysis. Plasma levels of cytokines were measured using flow cytometry and capture enzyme-linked immunosorbent assay. Biomarkers were categorized based on their respective median values. Survival analysis was conducted using the Kaplan-Meier estimator, considering two outcomes: all-cause mortality and transfer to hemodialysis. RESULTS: After adjusting for confounding factors, plasma levels above the median of the levels of CCL2 and plasma, as well as below the median of TNF-α, and the median of dialysate IL-17 levels, were associated with an increased risk of experiencing the specified outcomes after approximately 16 months of follow-up. CONCLUSION: These findings suggest that inflammatory biomarkers may be a valuable tool for predicting all-cause mortality and transfer to hemodialysis in patients undergoing peritoneal dialysis.

Assessment of Biochemical, Inflammatory Biomarkers and Ultra-Processed Food Consumption in Children with Small Intestinal Bacterial Overgrowth: A Cross-Sectional Study.

OBJECTIVE: This study evaluated anthropometric, biochemical, and inflammatory biomarkers, as well as dietary intake in Brazilian children diagnosed with small intestinal bacterial overgrowth (SIBO) and compared them with their counterparts without SIBO. METHODS: This was a cross-sectional study with 106 children aged 7 to 10 years. A glucose-hydrogen breath test was performed to diagnose small intestinal bacterial overgrowth (SIBO). Anthropometric and dietary characteristics were assessed. Blood samples were collected and serum biochemical parameters and cytokines were measured. RESULTS: The occurrence of SIBO was 13.2%. Age, BMI, BMI/age WC, BFP, sex and biochemical markers were similar between SIBO-positive and SIBO-negative children (p > 0.05). High consumption of ultra-processed foods tended to be higher in SIBO-positive compared to SIBO-negative children (47.8 ± 8.2 vs. 42.6 ± 9.5, p = 0.06). Serum levels of IL-17 were higher in SIBO-positive than in SIBO-negative children [69.5 (5.4-125.7) vs. 53.4 (2.3-157.7), p = 0.03], while serum levels of IL-10 were lower in SIBO-positive than in SIBO-negative children [2.3 (0.6-7.2) vs. 5.7 (0.5-30.8), p = 0.04]. Finally, in a logistic regression adjusted for sex, BMI and age, consumption of ultra-processed foods (p = 0.03) and IL-6 levels (p = 0.003) were found to contribute to the occurrence of SIBO. CONCLUSION: this study identified for the first time an occurrence of 13% of SIBO in children living in the northeastern region of Brazil and showed that consumption of ultra-processed foods and serum levels of IL-6 may influence the occurrence of the SIBO in the pediatrics population.

Unraveling the Interaction between Inflammation and the Cardiometabolic Index in Older Men: A Pilot Study.

Both cardiometabolic and chronic inflammatory diseases pose a significant challenge to global public health, particularly among older adults. Here, we investigated the interplay between systemic inflammatory status and the cardiometabolic index (CMI) in older men with adequate weight or obesity. In this observational cross-sectional study, older men (71.79 ± 7.35 years) were separated into groups with normal weight (NW, n = 34) and obesity (O, n = 32) to assess circulating levels of pro- and anti-inflammatory cytokines and CMI. Overall, the O group showed not only a higher inflammatory status but also increased CMI (p < 0.0001) compared with the NW group. Interestingly, only positive correlations were found between pro- and anti-inflammatory cytokines in both groups. Through multivariate regression analysis, IL-6 (ß = -0.2276, p = 0.0003) and IL-10 (ß = 0.2023, p = 0.0030) significantly influenced CMI in the NW group. No significant results were found in the O group. Our findings reinforce the effects of obesity in inflammaging, as well as suggesting that the influence of cytokines in CMI occurs in older men with normal weight, since the elevated pro-inflammatory profile observed in older men with obesity can interfere in this effect.

The effectiveness of early systemic inflammatory indices in predicting advanced intraventricular hemorrhage in preterm infants.

Some systemic inflammatory indices have been reported to be associated with intracerebral hemorrhage in adults. However, the relationship between systemic inflammatory indices and intraventricular hemorrhage (IVH) in premature neonates is still not completely understood. OBJECTIVE: To evaluate the relationship between systemic inflammatory indices obtained on the first day of life in premature infants and the development of severe IVH. PATIENTS AND METHOD: Premature newborns < 32 weeks of gestational age were included. Eligible patients were divided into 2 groups: Group 1: without IVH or grade I and II hemorrhage, and Group 2: grade III and IV HIV. Demographic characteristics, clinical outcomes, monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), pan-immune inflammation value (PIV), and Systemic inflammation response index (SIRI) were compared between groups. RESULTS: A total of 1176 newborns were included in the study, 1074 in Group 1 and 102 premature babies in Group 2. There was no difference between the groups in terms of the count of leukocytes, neutrophils, monocytes, lymphocytes and platelets (p > 0.05). The values of NLR, MLR, PLR, PIV, SII and SIRI were similar in both groups (p > 0.05). CONCLUSION: While the relationship between inflammation, hemodynamics and IVH is still under discussion, our results show that systemic inflammatory indices have no predictive value for IVH.

Brazil Nut (Bertholletia excelsa H.B.K.) Consumption in Energy-Restricted Intervention Decreases Proinflammatory Markers and Intestinal Permeability of Women with Overweight/Obesity: A Controlled Trial (Brazilian Nuts Study).

BACKGROUND: Obesity is associated with low-grade inflammation and increased intestinal permeability (IP). The Brazil nut (BN) (Bertholletia excelsa H.B.K.) appears to be a promising dietary intervention to control inflammation by enhancing antioxidant defenses. OBJECTIVES: We aimed to assess the effect of daily BN consumption on inflammatory biomarkers and IP in the context of an energy-restricted intervention. Furthermore, we evaluated the correlation between the changes in these inflammatory markers and the changes in serum selenium and IP. METHODS: In this 8-wk nonrandomized controlled trial, 56 women with overweight or obesity were allocated into 2 groups, both following an energy-restricted diet (-500 kcal/d). The control group (CO) consumed a nut-free diet, while the BN group consumed 8 g BN/d, providing 347.2 µg selenium (Se). Inflammatory cytokines were analyzed in plasma and Se in serum. IP was assessed using the lactulose/mannitol test (LM ratio). RESULTS: Forty-six women completed the intervention. Both groups achieved similar energy restriction (CO Δ= -253.7 ± 169.4 kcal/d; BN Δ= -265.8 ± 141.8 kcal/d) and weight loss (CO Δ= -2.5 ± 0.5 kg; BN Δ= -3.5 ± 0.5 kg). The BN group showed lower values of C-reactive protein, tumor necrosis factor, interleukin (IL)1-ß, IL-8, percentage lactulose excretion, and LM ratio than the CO group. Additionally, changes in serum Se concentration were predictive of changes in IL-8 concentration (ß: -0.054; adjusted R2: 0.100; 95% confidence interval [CI]: -0.100; -0.007; P = 0.025), and changes in IL-8 were predictive of changes in the LM ratio (ß: 0.006; adjusted R2: 0.101; 95% CI: 0.001, 0.011; P = 0.024). CONCLUSIONS: Regular intake of BNs can be a promising complementary dietary strategy for controlling low-grade inflammation and improving IP in women with overweight/obesity undergoing energy-restricted treatment. However, the effects of BNs seem to be Se status-dependent. This trial was registered at the Brazilian Registry of Clinical Trials (ReBEC: https://ensaiosclinicos.gov.br/rg/RBR-3ntxrm/.

Inflammation Burden and Atrial Fibrillation Burden: A Bidirectional Relationship. / Carga Inflamatória e Carga de Fibrilação Atrial: Uma Relação Bidirecional.

BACKGROUND: Atrial fibrillation (AF) burden is defined as the proportion of time the patient remains in AF over a given period of time; thus, it is theoretically highest in permanent AF and lowest in paroxysmal AF. Inflammation is associated with the initiation and maintenance of AF. However, the relationship between systemic immune-inflammation index (SII) and AF burden is unknown. OBJECTIVE: In the present study, we investigated the relationship between SII and AF burden. METHODS: The present study is a cross-sectional analysis of 453 patients (252 females and 201 males, aged 44 to 94 years) with AF (138 with paroxysmal AF and 315 with permanent AF) who visited the cardiology outpatient clinic between October 2022 and June 2023. SII was calculated as (neutrophils × platelets/lymphocytes). The predictive role of SII and other inflammatory markers in the likelihood of AF pattern was evaluated by logistic regression analyses, and p value < 0.05 was considered statistically significant. RESULTS: Age, diastolic blood pressure, heart rate, diabetes mellitus, neutrophil, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, SII, C-reactive protein, red blood cell distribution width, hemoglobin A1c, and left atrial diameter were significantly higher in the permanent AF group. According to the logistic regression analysis, age (p = 0.038), diabetes mellitus (p = 0.024), red blood cell distribution width (p = 0.023), C-reactive protein (p = 0.010), SII (p = 0.001), and left atrial diameter (p < 0.001) significantly contributed to the prediction of the likelihood of permanent AF. CONCLUSION: SII is independently associated with the AF burden. Prospective studies are needed to determine whether SII may be useful in identifying patients at high risk for AF progression.

FUNDAMENTO: A carga de fibrilação atrial (FA) é definida como a proporção de tempo que o paciente permanece em FA durante um determinado período de tempo; portanto, é teoricamente mais elevado na FA permanente e mais baixo na FA paroxística. A inflamação está associada ao início e à manutenção da FA. No entanto, a relação entre o índice de inflamação imune sistêmica (SII, do inglês systemic immune-inflammation index) e a carga de FA é desconhecida. OBJETIVO: No presente estudo, investigamos a relação entre o SII e a carga de FA. MÉTODOS: O presente estudo é uma análise transversal de 453 pacientes (252 do sexo feminino e 201 do sexo masculino, com idade entre 44 e 94 anos) com FA (138 com FA paroxística e 315 com FA permanente) atendidos no ambulatório de cardiologia entre outubro de 2022 e junho de 2023. O SII foi calculado como (neutrófilos × plaquetas/linfócitos). O papel preditivo do SII e de outros marcadores inflamatórios na probabilidade do padrão de FA foi avaliado por análises de regressão logística, sendo considerado estatisticamente significativo o valor de p < 0,05. RESULTADOS: Idade, pressão arterial diastólica, frequência cardíaca, diabetes mellitus, neutrófilos, relação plaquetas-linfócitos, relação neutrófilos-linfócitos, SII, proteína C reativa, largura de distribuição de glóbulos vermelhos, hemoglobina A1c e diâmetro do átrio esquerdo foram significativamente maiores no grupo com FA permanente. De acordo com a análise de regressão logística, idade (p = 0,038), diabetes mellitus (p = 0,024), largura de distribuição de glóbulos vermelhos (p = 0,023), proteína C reativa (p = 0,010), SII (p = 0,001) e o diâmetro do átrio esquerdo (p < 0,001) contribuíram significativamente para a predição da probabilidade de FA permanente. CONCLUSÃO: O SII está independentemente associado à carga de FA. Estudos prospectivos são necessários para determinar se o SII pode ser útil na identificação de pacientes com alto risco de progressão da FA.

Nutritional and Inflammatory Markers Associated with SARS-CoV-2 Infection in the Elderly.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has posed unprecedented challenges to global health systems, particularly among vulnerable populations such as the elderly. Understanding the interplay between anthropometric markers, molecular profiles, and disease severity is crucial for effective clinical management and intervention strategies. We conducted a cohort study comprising 43 elderly COVID-19 patients admitted to São Lucas Hospital, PUCRS, Brazil. Anthropometric measurements, including calf circumference (CC) and abdominal circumference (AC), were assessed alongside molecular analyses of peripheral blood samples obtained within 48 h of hospital admission. Sociodemographic data were collected from electronic medical records for comprehensive analysis. Our findings revealed a possible relationship between overweight status, increased abdominal adiposity, and prolonged hospitalization duration, alongside heightened disease severity. We also found no significant correlations between BMI, vitamin D levels, and clinical outcomes. Elevated oxygen requirements were observed in both normal and overweight individuals, with the latter necessitating prolonged oxygen therapy. Molecular analyses revealed changes in the inflammatory profile regarding the outcome of the patients. Our study highlights the critical importance of both anthropometric and molecular markers in predicting disease severity and clinical outcomes in elderly individuals with COVID-19.

A preliminary study on the association between prognostic nutritional index and neutrophil-to-lymphocyte ratio with nutritional status and inflammation in febrile children's susceptibility to seizures.

OBJECTIVE: The aim of this study was to evaluate the association between nutritional status, inflammation, and susceptibility to seizures in febrile children. METHODS: This observational single-center study was carried out from January 2020 to December 2023 with 324 children aged 6 months and 6 years; 106 were diagnosed with febrile seizure, 108 were febrile children, and 110 were healthy controls. The prognostic nutritional index and neutrophil-to-lymphocyte ratio were calculated, and the cutoff threshold was established through receiver operating characteristics. The study utilized correlation and univariate-multivariate logistic regression analysis. The comparison between simple and complex febrile seizure was conducted to analyze differences. RESULTS: The optimal cutoff values were identified as 61.25 for prognostic nutritional index and 1.04 for neutrophil-to-lymphocyte ratio. Our findings showed a significant negative association between febrile seizure and platelet count, high C-reactive protein, and high ferritin levels. Additionally, the febrile seizure group showed a significant positive correlation with high neutrophil-to-lymphocyte ratio values (≥1.04) and body temperature (≥38). Our findings revealed that high neutrophil-to-lymphocyte ratio, high C-reactive protein, and age less than 18 months were independently associated with seizure susceptibility in febrile children. CONCLUSION: High neutrophil-to-lymphocyte ratio values and low prognostic nutritional index scores may serve as novel surrogate independent factors for seizure susceptibility in febrile children. Febrile children who are less than 18 months old are more prone to experience seizures than older febrile children. Moreover, there was a correlation between febrile seizures and elevated C-reactive protein levels and neutrophil-to-lymphocyte ratio values.

Vitamin D supplementation does not alter inflammatory markers in overweight and obese individuals: A systematic review and meta-analysis of randomized controlled trials.

Chronic low-grade inflammation is a common feature of obesity and plays a crucial role in the progression of its complications. Vitamin D (VitD) plays an important role in modulating the immune response and regulating inflammation. Thus, this systematic review and meta-analysis aimed to evaluate the effects of isolated VitD supplementation on main inflammatory markers in overweight and obese individuals with no comorbidities and with VitD deficiency. We hypothesized that the increase in serum VitD concentrations after supplementation would significantly reduce the concentrations of inflammatory markers. The search was conducted in Medline/PubMed, SCOPUS, EMBASE, and Web of Science. Eleven randomized placebo-controlled studies were included in the final analysis, with a total of 504 participants and daily (1000-7000 international units) or bolus (100,000-200,000 international units) doses of VitD lasting from 2 to 26 weeks. The VitD supplementation did not influence C-reactive protein (mean difference [MD]: 0.01; 95% confidence interval [CI] -0.37, 0.39; P = .97), interleukin-6 (MD: -0.34; 95% CI -1.09, 0.42; P = .38), and tumor necrosis factor concentrations (MD: -0.02; 95% CI -0.23, 0.19; P = .85). In the analysis considering the studies with a significant increase in serum VitD concentrations, VitD supplementation also did not influence C-reactive protein (MD: -0.17; 95% CI -0.88, 0.54; P = .64), interleukin-6 (MD: -0.47; 95% CI -1.31, 0.37; P = .27), and tumor necrosis factor concentrations (MD: 0.01; 95% CI -1.34, 1.37; P = .98). This meta-analysis suggests that VitD supplementation does not significantly alter inflammatory markers in overweight and obese individuals.

Myeloproliferative Neoplasms Transcriptome Reveals Pro-Inflammatory Signature and Enrichment in Peripheral Blood Monocyte-Related Genes.

Myeloproliferative neoplasms (MPN) are hematological diseases associated with genetic driver mutations in the JAK2, CALR, and MPL genes and exacerbated oncoinflammatory status. Analyzing public microarray data from polycythemia vera (n = 41), essential thrombocythemia (n = 21), and primary myelofibrosis (n = 9) patients' peripheral blood by in silico approaches, we found that pro-inflammatory and monocyte-related genes were differentially expressed in MPN patients' transcriptome. Genes related to cell activation, secretion of pro-inflammatory and pro-angiogenic mediators, activation of neutrophils and platelets, coagulation, and interferon pathway were upregulated in monocytes compared to controls. Together, our results suggest that molecular alterations in monocytes may contribute to oncoinflammation in MPN.

Decreased Hepatic and Serum Levels of IL-10 Concur with Increased Lobular Inflammation in Morbidly Obese Patients.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Accumulating evidence in animal models suggests that loss of interleukin-10 (IL-10) anti-inflammatory actions might contribute to lobular inflammation, considered one of the first steps toward NASH development. However, the role of IL-10 in lobular inflammation remains poorly explored in humans. We examined mRNA and protein levels of IL-10 in liver biopsies and serum samples from morbidly obese patients, investigating the relationship between IL-10 and lobular inflammation degree. Materials and Methods: We prospectively enrolled morbidly obese patients of both sexes, assessing the lobular inflammation grade by the Brunt scoring system to categorize participants into mild (n = 7), moderate (n = 19), or severe (n = 13) lobular inflammation groups. We quantified the hepatic mRNA expression of IL-10 by quantitative polymerase chain reaction and protein IL-10 levels in liver and serum samples by Luminex Assay. We estimated statistical differences by one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Results: The hepatic expression of IL-10 significantly diminished in patients with severe lobular inflammation compared with the moderate lobular inflammation group (p = 0.01). The hepatic IL-10 protein levels decreased in patients with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.008 and p = 0.0008, respectively). In circulation, IL-10 also significantly decreased in subjects with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.005 and p < 0.0001, respectively). Conclusions: In liver biopsies and serum samples of morbidly obese patients, the protein levels of IL-10 progressively decrease as lobular inflammation increases, supporting the hypothesis that lobular inflammation develops because of the loss of the IL-10-mediated anti-inflammatory counterbalance.

Assessment of inflammatory parameters as predictive markers for malignancy in thyroid nodules: a study on the correlation with Bethesda classification.

OBJECTIVE: The study aimed to assess the predictive significance of inflammatory parameters as potential markers for malignancy in individuals with thyroid nodules. METHOD: Nine hundred and ninety-one patients with thyroid nodules who had undergone thyroid fine-needle aspiration biopsy were included and classified according to the Bethesda system. Neutrophil lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) values obtained from hemogram parameters were determined for each patient. The study examined the correlation between the Bethesda classification and NLR/SII levels. In addition, a comparison was made between the inflammatory parameters of the benign and malignant Bethesda groups. RESULTS: Five hundred and seventy-three patients were classified as Bethesda 2 (benign), 34 as Bethesda 6 (malignant). A correlation was observed between the Bethesda classification and NLR and SII levels (r: 0.230, p < 0.001; r: 0.207 p < 0.001, respectively). NLR and SII values were significantly higher in the malignant group (p < 0.001). The cutoff value for SII in predicting benign and malignant thyroid nodules was 489.86 × 103/mm3 with a sensitivity of 88.2% and a specificity of 63.7%. The cutoff value for NLR for the same prediction was 2.06 with a sensitivity of 82.4% and a specificity of 83.4%. CONCLUSIONS: The findings of this study indicate that SII and NLR may be valuable prognostic markers for predicting the malignancy of thyroid nodules.

OBJETIVO: Evaluar parámetros inflamatorios como posibles marcadores de malignidad en individuos con nódulos tiroideos. MÉTODO: Se incluyeron 991 pacientes con nódulos tiroideos que se sometieron a biopsia por aspiración con aguja fina y se clasificaron según el sistema de Bethesda. Se determinaron los valores de la relación neutrófilo-linfocito (NLR) y el índice de inflamación inmunitaria sistémica (SII). El estudio exploró la correlación entre la clasificación de Bethesda y los valores de NLR/SII, y comparó los parámetros inflamatorios de los grupos benignos y malignos de Bethesda. RESULTADOS: Se clasificaron 573 pacientes como Bethesda 2 (benigno) y 34 como Bethesda 6 (maligno). Se observó una correlación entre la clasificación de Bethesda y los valores de NLR y SII (r: 0.230; r: 0.207). Los valores de NLR y SII fueron mayores en el grupo maligno (p < 0.001). El valor de corte para SII en la predicción de nódulos tiroideos benignos y malignos fue de 489.86 × 103/mm3, con una sensibilidad del 88.2% y una especificidad del 63.7%; para NLR fue de 2.06, con una sensibilidad del 82.4% y una especificidad del 83.4%. CONCLUSIONES: El SII y el NLR pueden ser valiosos marcadores pronósticos para predecir la malignidad de los nódulos tiroideos.

Decoding the inflammatory signature of the major depressive episode: insights from peripheral immunophenotyping in active and remitted condition, a case-control study.

Depression is a prevalent and incapacitating condition with a significant impact on global morbidity and mortality. Although the immune system's role in its pathogenesis is increasingly recognized, there is a lack of comprehensive understanding regarding the involvement of innate and adaptive immune cells. To address this gap, we conducted a multicenter case-control study involving 121 participants matched for sex and age. These participants had either an active (or current) major depressive episode (MDE) (39 cases) or a remitted MDE (40 cases), including individuals with major depressive disorder or bipolar disorder. We compared these 79 patients to 42 healthy controls (HC), analyzing their immunological profiles. In blood samples, we determined the complete cell count and the monocyte subtypes and lymphocyte T-cell populations using flow cytometry. Additionally, we measured a panel of cytokines, chemokines, and neurotrophic factors in the plasma. Compared with HC, people endorsing a current MDE showed monocytosis (p = 0.001), increased high-sensitivity C-reactive protein (p = 0.002), and erythrocyte sedimentation rate (p = 0.003), and an altered proportion of specific monocyte subsets. CD4 lymphocytes presented increased median percentages of activation markers CD69+ (p = 0.007) and exhaustion markers PD1+ (p = 0.013) and LAG3+ (p = 0.014), as well as a higher frequency of CD4+CD25+FOXP3+ regulatory T cells (p = 0.003). Additionally, patients showed increased plasma levels of sTREM2 (p = 0.0089). These changes are more likely state markers, indicating the presence of an ongoing inflammatory response during an active MDE. The Random Forest model achieved remarkable classification accuracies of 83.8% for MDE vs. HC and 70% for differentiating active and remitted MDE. Interestingly, the cluster analysis identified three distinct immunological profiles among MDE patients. Cluster 1 has the highest number of leukocytes, mainly given by the increment in lymphocyte count and the lowest proinflammatory cytokine levels. Cluster 3 displayed the most robust inflammatory pattern, with high levels of TNFα, CX3CL1, IL-12p70, IL-17A, IL-23, and IL-33, associated with the highest level of IL-10, as well as ß-NGF and the lowest level for BDNF. This profile is also associated with the highest absolute number and percentage of circulating monocytes and the lowest absolute number and percentage of circulating lymphocytes, denoting an active inflammatory process. Cluster 2 has some cardinal signs of more acute inflammation, such as elevated levels of CCL2 and increased levels of proinflammatory cytokines such as IL-1ß, IFNγ, and CXCL8. Similarly, the absolute number of monocytes is closer to a HC value, as well as the percentage of lymphocytes, suggesting a possible initiation of the inflammatory process. The study provides new insights into the immune system's role in MDE, paving the ground for replication prospective studies targeting the development of diagnostic and prognostic tools and new therapeutic targets.

Prognostic risk stratification using C-reactive protein, albumin, and associated inflammatory biomarkers in patients with advanced cancer in palliative care.

PURPOSE: To evaluate the prognostic value of C-reactive protein (CRP), albumin, CRP/albumin ratio (CAR), and modified Glasgow Prognostic Score (mGPS) at different thresholds in patients with advanced cancer in palliative care. METHODS: Prospective cohort study with patients evaluated at a palliative care unit in Brazil between July 2016 and March 2020. We included patients ≥ 20 years old, both sexes, able to provide the necessary information or accompanied by someone able to do so, and Karnofsky Performance Status ≥ 30 %. The exclusion criteria were the absence of laboratory data and previous diagnosis of autoimmune and infectious diseases. The thresholds analyzed were: CRP < 5 vs. 5-10 vs. > 10 mg/L, albumin < 2.4 vs. 2.4-2.9 vs. 3.0-3.5 vs. > 3.5 g/dL; CAR <1.2 vs. 1.2-2.0 vs. > 2.0, and mGPS equal to 0 vs. 1 vs. 2. Kaplan-Meier curves and Cox regression models (with hazard ratios [HR] and 95% confidence interval [CI]) were used to evaluate prognostic value, and the concordance statistic (C-statistic) was used to evaluate the predictive accuracy of these thresholds to predict death within 90 days. RESULTS: A total of 1,877 patients were included. Median overall survival was 51 (19;124) days and decreased in line with the deterioration of the inflammatory biomarkers. According to the Cox regression models, HR increased as the thresholds worsened (CRP: 1.74 [95% CI, 1.50-2.02] to 2.30 [95% CI, 2.00-2.64]; albumin: 1.77 [95% CI, 1.52-2.07] to 2.60 [95% CI, 2.15-3.14]; CAR: 1.47 [95% CI, 1.21-1.77] to 2.35 [95% CI, 2.05-2.69]; mGPS: 1.78 [95% CI, 1.40-2.23] to 1.89 [95% CI, 1.65-2.15]). All the inflammatory biomarkers evaluated showed discriminatory accuracy for predicting death (C-statistic >0.70), with CAR as the best parameter (C-statistic: 0.80). CONCLUSION: Our results suggest that CRP, albumin, CAR, and mGPS can be used as clinically meaningful biomarkers to stratify patients with advanced cancer in palliative care according to the severity of these indicators.

Prevalence of body composition phenotypes and their associations with glycemic, lipidic, and inflammatory biomarkers: a population-based study.

We aimed to verify the prevalence of body composition phenotypes and the association of glycemic, lipidic, and inflammatory biomarkers with such phenotypes. This is a cross-sectional, population-based study, with 720 participants aged 20 to 59 years. Body composition was assessed by dual-energy X-ray absorptiometry. Obesity was defined as body fat percentage ≥ 25% in males and ≥ 32% in females and sarcopenia by appendicular muscle mass index < 7.0kg/m2 in males and < 5.5kg/m2 in females. Sarcopenic obesity (SO) was defined as the presence of both sarcopenia and obesity. The prevalence of obesity, sarcopenia, and SO were 62.5%, 4.5%, and 6.2%, respectively. The association between biomarkers and phenotypes was verified using multinomial logistic regression models adjusted for confounding factors. The models showed that increased glycemia (OR = 3.39; 95%CI: 1.83-6.27), total cholesterol (TC) (OR = 2.24; 95%CI: 1.35-3.70), LDL-c (OR = 1.01; 95%CI: 1.00-1.02), VLDL-c (OR = 1.04; 95%CI: 1.02-1.06), non-HDL-c (OR = 1.02; 95%CI: 1.01-1.03), triglycerides (Tg) (OR = 3.66; 95%CI: 2.20-6.06), and decreased HDL-c (OR = 0.97; 95%CI: 0.95-0.98) were significantly associated with the obesity phenotype. Increased HOMA-IR (OR = 3.94; 95%CI: 1.69-9.21), LDL-c (OR = 1.01; 95%CI: 1.00-1.02), non-HDL-c (OR = 1.01; 95%CI: 1.00-1.02), and hs-CRP (OR = 2.42; 95%CI: 1.04-5.66) were independently associated with SO phenotype. Our findings indicate that increased glycemia, TC, Tg, LDL-c, VLDL-c, non-HDL-c, and decreased HDL-c may be indicators of the obesity phenotype and that increased hs-CRP, HOMA-IR, LDL-c, and non-HDL-c appear to be indicators of the SO phenotype. Those parameters may be used as additional markers for screening.

Inflammation and immune system pathways as biological signatures of adolescent depression-the IDEA-RiSCo study.

The biological mechanisms underlying the onset of major depressive disorder (MDD) have predominantly been studied in adult populations from high-income countries, despite the onset of depression typically occurring in adolescence and the majority of the world's adolescents living in low- and middle-income countries (LMIC). Taking advantage of a unique adolescent sample in an LMIC (Brazil), this study aimed to identify biological pathways characterizing the presence and increased risk of depression in adolescence, and sex-specific differences in such biological signatures. We collected blood samples from a risk-stratified cohort of 150 Brazilian adolescents (aged 14-16 years old) comprising 50 adolescents with MDD, 50 adolescents at high risk of developing MDD but without current MDD, and 50 adolescents at low risk of developing MDD and without MDD (25 females and 25 males in each group). We conducted RNA-Seq and pathway analysis on whole blood. Inflammatory-related biological pathways, such as role of hypercytokinemia/hyperchemokinemia in the pathogenesis of influenza (z-score = 3.464, p < 0.001), interferon signaling (z-score = 2.464, p < 0.001), interferon alpha/beta signaling (z-score = 3.873, p < 0.001), and complement signaling (z-score = 2, p = 0.002) were upregulated in adolescents with MDD compared with adolescents without MDD independently from their level of risk. The up-regulation of such inflammation-related pathways was observed in females but not in males. Inflammatory-related pathways involved in the production of cytokines and in interferon and complement signaling were identified as key indicators of adolescent depression, and this effect was present only in females.

Diabetes and hypertension in elderly women: interactions between severity and failure to control inflammation.

Elderly women are more susceptible to the development of chronic non-communicable diseases. Among these, diabetes mellitus (DM) and systemic arterial hypertension (SAH) stand out. This work aimed to carry out an expanded study on the interactions of anthropometric, biochemical and inflammatory parameters associated with the risk of severity in elderly women with hypertension and diabetes. The study involved the evaluation of 126 elderly women with hypertension and diabetes mellitus. The women were divided according disease severity (low, moderate, high and very high). Anthropometric data were collected by bioimpedance analysis. The inflammatory and biochemical data were obtained from volunteer blood samples. Waist circumference, waist circumference/height ratio, and systolic and diastolic pressures increased with severity. Biochemical marker levels increased with risk of severity, except HDLc. In the very high risk group, there was a higher IL-1ß, IFN-γ and TNF-α production, however, lower IL-10 levels were observed. The very high risk group showed change values for the IL-10/IL-1ß, IL-10/IL-17 and IL-10/TNF-α ratios. The results showed to be extensively altered in the very high risk group, where the inflammatory profile loses its responsiveness. This is the first study that shows an expanded view of the different parameters evaluated in elderly women with hypertension and diabetes.

Does physical activity and inflammation mediate the job stress-headache relationship? A sequential mediation analysis in the ELSA-Brasil study.

BACKGROUND: Evidence indicates that physical activity reduces stress and promote a myriad of health-enhancing effects through anti-inflammatory mechanisms. However, it is unknown whether these mechanisms interfere in the association between psychosocial job stress and headache disorders. OBJECTIVE: To test whether physical activity and its interplay with the systemic inflammation biomarkers high-sensitivity C-reactive protein (hs-CRP) and acute phase glycoproteins (GlycA) would mediate the associations between job stress and headache disorders. METHODS: We cross-sectionally evaluated the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) regarding job stress (higher demand and lower control and support subscales), migraine and tension-type headache (ICHD-2 criteria), self-reported leisure-time physical activity, and plasma hs-CRP and GlycA levels. Conditional process analyses with a sequential mediation approach were employed to compute path coefficients and 95 % confidence intervals (CI) around the indirect effects of physical activity and biomarkers on the job stress-headache relationship. Separate models were adjusted for sex, age, and depression and anxiety. Further adjustments added BMI smoking status, and socioeconomic factors. RESULTS: In total, 7,644 people were included in the study. The 1-year prevalence of migraine and tension-type headache were 13.1 % and 49.4 %, respectively. In models adjusted for sex, age, anxiety, and depression, the association between job stress (lower job control) and migraine was mediated by physical activity [effect = -0.039 (95 %CI: -0.074, -0.010)] but not hs-CRP or GlycA. TTH was associated with higher job control and lower job demand, which was mediated by the inverse associations between physical activity and GlycA [Job Control: effect = 0.0005 (95 %CI: 0.0001, 0.0010); Job Demand: effect = 0.0003 (95 %CI: 0.0001, 0.0007]. Only the mediating effect of physical activity in the job stress-migraine link remained after further adjustments including socioeconomic factors, BMI, smoking, and the exclusion of major chronic diseases. CONCLUSION: In the ELSA-Brasil study, physical activity reversed the link between job stress and migraine independently of systemic inflammation, while the LTPA-mediated downregulation of GlycA was associated with lower job stress-related TTH.

The Predictive Value of the Inflammatory Prognostic Index for Detecting No-Reflow in ST-Elevation Myocardial Infarction Patients. / O Valor Preditivo do Índice Prognóstico Inflamatório para Detecção de No-Reflow em Pacientes com Infarto do Miocárdio com Supradesnivelamento do Segmento ST.

BACKGROUND: No-reflow (NR) is characterized by an acute reduction in coronary flow that is not accompanied by coronary spasm, thrombosis, or dissection. Inflammatory prognostic index (IPI) is a novel marker that was reported to have a prognostic role in cancer patients and is calculated by neutrophil/lymphocyte ratio (NLR) multiplied by C-reactive protein/albumin ratio. OBJECTIVE: We aimed to investigate the relationship between IPI and NR in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI). METHODS: A total of 1541 patients were enrolled in this study (178 with NR and 1363 with reflow). Lasso panelized shrinkage was used for variable selection. A nomogram was created based on IPI for detecting the risk of NR development. Internal validation with Bootstrap resampling was used for model reproducibility. A two-sided p-value <0.05 was accepted as a significance level for statistical analyses. RESULTS: IPI was higher in patients with NR than in patients with reflow. IPI was non-linearly associated with NR. IPI had a higher discriminative ability than the systemic immune-inflammation index, NLR, and CRP/albumin ratio. Adding IPI to the baseline multivariable logistic regression model improved the discrimination and net-clinical benefit effect of the model for detecting NR patients, and IPI was the most prominent variable in the full model. A nomogram was created based on IPI to predict the risk of NR. Bootstrap internal validation of nomogram showed a good calibration and discrimination ability. CONCLUSION: This is the first study that shows the association of IPI with NR in STEMI patients who undergo pPCI.

FUNDAMENTO: O no-reflow (NR) é caracterizado por uma redução aguda no fluxo coronário que não é acompanhada por espasmo coronário, trombose ou dissecção. O índice prognóstico inflamatório (IPI) é um novo marcador que foi relatado como tendo um papel prognóstico em pacientes com câncer e é calculado pela razão neutrófilos/linfócitos (NLR) multiplicada pela razão proteína C reativa/albumina. OBJETIVO: Nosso objetivo foi investigar a relação entre IPI e NR em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST) submetidos a intervenção coronária percutânea primária (ICPp). MÉTODOS: Um total de 1.541 pacientes foram incluídos neste estudo (178 com NR e 1.363 com refluxo). A regressão penalizada LASSO (Least Absolute Shrinkage and Select Operator) foi usada para seleção de variáveis. Foi criado um nomograma baseado no IPI para detecção do risco de desenvolvimento de NR. A validação interna com reamostragem Bootstrap foi utilizada para reprodutibilidade do modelo. Um valor de p bilateral <0,05 foi aceito como nível de significância para análises estatísticas. RESULTADOS: O IPI foi maior em pacientes com NR do que em pacientes com refluxo. O IPI esteve associado de forma não linear com a NR. O IPI apresentou maior capacidade discriminativa do que o índice de imunoinflamação sistêmica, NLR e relação PCR/albumina. A adição do IPI ao modelo de regressão logística multivariável de base melhorou a discriminação e o efeito do benefício clínico líquido do modelo para detecção de pacientes com NR, e o IPI foi a variável mais proeminente no modelo completo. Foi criado um nomograma baseado no IPI para prever o risco de NR. A validação interna do nomograma Bootstrap mostrou uma boa capacidade de calibração e discriminação. CONCLUSÃO: Este é o primeiro estudo que mostra a associação de IPI com NR em pacientes com IAMCSST submetidos a ICPp.