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The present study aimed to evaluate the performance of plasma immune mediators in classifying leprosy patients [L(PB) and L(MB), paucibacillary and multibacillary leprosy, respectively], leprosy reaction patients (T1LR and T2LR, type 1 and type 2 leprosy reaction, respectively), household contacts (HHC), and non-infected (NI) controls. Quantitative measurements of these immune mediators were carried out using high-throughput multiplex microbead array. The results demonstrated that most of the plasma immune mediators were increased in all clinical groups compared with NI controls. Higher frequencies but lower maximum magnitudes of increase (fold change according to NI) were observed for T1LR (63%, 6.1×) and T2LR (63%, 9.7×) compared with HHC (48%, 68.5×), L(PB) (56%, 8.5×), and L(MB) (48%, 37.9×). The bi-dimensional scattering profiles (magnitude order vs. significance) identified a higher number of immune mediators in T2LR (12/27) compared with HHC (8/27), L(PB) (7/27), L(MB) (5/27), and T1LR (5/27). CXCL8 was selected as the parameter with the highest accuracy and significance [area under the receiver operating characteristic curve (AUC) = 0.98, p = 0.0002] in classifying NI vs. HHC. CCL3 (C–C motif chemokine ligand 3) was the single analyte with moderate accuracy and significance (AUC = 0.74, p = 0.0422) in classifying L(PB) vs. L(MB). IL-9 was selected as an attribute with moderate accuracy and significance (AUC = 0.77, p = 0.0041) in classifying T1LR vs. T2LR. Decision tree algorithms confirmed the high accuracy (96%) of CXCL8 in classifying NI vs. HHC. The use of CCL3 followed by IFN-γ classified L(MB) vs. L(PB) with high accuracy (93%). Moreover, the analysis of IL-9 followed by IL-6 and CXCL10 classified T1RL vs. T2RL with high accuracy (96%). In general, combined stepwise algorithms showed enhanced classification accuracy compared with single-attribute analysis. Together, our findings supported the potential use of plasma immune mediators as complementary laboratory biomarkers for the identification of HHC and the classification of distinct clinical forms of leprosy and leprosy reactions.

ObjectiveTo characterize the clinical manifestations of yellow fever disease and identify risk factors for mortality.MethodsA retrospective study was conducted in the referral center for infectious diseases (Hospital Eduardo de Menezes-HEM) in Belo Horizonte, Minas Gerais, Brazil. Analysis included data from 283 patients with confirmed YF infection older than 13 years old who presented to HEM between January 2017 and June 2018. In-hospital mortality (hypothesis formulated after data collection), demographic factors and clinical and laboratory assessments were used.ResultsStudy patients were mainly men (87.6%), with a median age of 46.0 (IQR 36.5, 57.0). 131 (46.3%) patients were admitted to the ICU, and 62 (22.0%) used invasive mechanical ventilation for a median of 2 days (IQR 1, 3). The median (IQR) total length of stay (LOS) in the ICU was 6 days (IQR 4, 8). The in-hospital mortality rate was 24.0%. Age was significantly higher in fatal (median 49.5, IQR 41.0, 61.0]) than in non-fatal cases [46 (36, 55)] (p < 0.01). Male sex was associated with an increased risk of death (RR 4.66, 95% CI 1.19, 18.2; p < 0.01). Most common symptoms and signs on admission to HEM were fever (31.9%), myalgia (27.8%), jaundice (24.3%), headache (23.9%), abdominal pain (16.1%), vomiting (12.2%), weakness (10.4%), and arthralgias (10.0%). Initial viral load above the cutoff of 4.45 log10 copies/mL was significantly associated with death prior to discharge (OR 12.2; CI 2.83, 92.3). Five factors were significantly related to increased odds of death prior to discharge: log-transformed AST (OR 3.65; CI 2.02, 7.81; p < 0.001), log-transformed INR (OR 7.40; CI 1.31, 33.0; p = 0.010), log-transformed lactate (OR 4.57; CI 1.48, 17.1; p = 0.013), log-transformed WBC (OR 4.33; CI 1.19, 18.5; p = 0.034), and age (OR 1.06; CI 1.01, 1.12; p = 0.026).Conclusions and relevanceAST, INR, lactate, WBC, and age are statistically associated with death prior to discharge in YF patients. These clinical markers should be applied to improve patient screening and management during future YF epidemics.

Aging is associated with several physiological changes, including a remarkable remodeling of the immune system. Herein, the rhythms and shifts in serum immune mediators were characterized in a decade lifespan as a longitudinal community-based prospective investigation from Bambuí Health and Aging Study. The study population included paired samples from 713 subjects survivors from the original BHAS cohort and at 10-years Follow-up, categorized into 5-years age range intervals (60-64Yrs towards 90 + Yrs). Quantification of soluble mediators were carried out by Cytometric Bead Array. The results demonstrated a rhythmic increase in serum immune mediators, especially CXCL9, CXCL10, IL-1β, IL-6 and TNF following the aging process, particularly at age intervals 70-74Yrs and 85-89Yrs. More prominent fold change magnitudes were observed for TNF (27.64×), CXCL9 (2.40×), IL-1β (2.20×), IL-6 (1.47×), and CXCL10 (1.26×). On the other hand, analysis of integrative networks showed a waning in the correlation numbers between immune mediators in a decade lifespan and a shift of connectivity from chemokines at Enrollment towards cytokines at 10-years Follow-up. Cross-correlation approaches revealed that CXCL9, CXCL10, IL-1β, IL-6, and IL-10 were placed in the innermost position, underscoring the higher contribution of these mediators along aging. Overall, these findings re-emphasize the impact of aging in the dynamic profile of serum immune mediators, highlighting the shift of selective mediators and their rhythmic signatures across chronological aging.

The present study aimed at investigating whether the hydroxychloroquine (HCQ) treatment would impact the neutralizing antibody production, viremia levels and the kinetics of serum soluble mediators upon planned 17DD-Yellow Fever (YF) primovaccination (Bio-Manguinhos-FIOCRUZ) of primary Sjögren’s syndrome (pSS). A total of 34 pSS patients and 23 healthy controls (HC) were enrolled. The pSS group was further categorized according to the use of HCQ (HCQ and Non-HCQ). The YF-plaque reduction neutralization test (PRNT ≥1:50), YF viremia (RNAnemia) and serum biomarkers analyses were performed at baseline and subsequent time-points (Day0/Day3–4/Day5–6/Day7/Day14-D28). The pSS group showed PRNT titers and seropositivity rates similar to those observed for HC (GeoMean = 238 vs 440, p = .11; 82% vs 96%, p = .13). However, the HCQ subgroup exhibited lower seroconversion rates as compared to HC (GeoMean = 161 vs 440, p = .04; 69% vs 96%, p = .02) and Non-HQC (GeoMean = 161 vs 337, p = .582; 69% vs 94%, p = .049). No differences in YF viremia were observed amongst subgroups. Serum biomarkers analyses demonstrated that HCQ subgroup exhibited increased levels of CCL2, CXL10, IL-6, IFN-γ, IL1-Ra, IL-9, IL-10, and IL-2 at baseline and displayed a consistent increase of several biomarkers along the kinetics timeline up to D14–28. These results indicated that HCQ subgroup exhibited a deficiency in assembling YF-specific immune response elicited by 17DD-YF primovaccination as compared to Non-HCQ subgroup. Our findings suggested that hydroxychloroquine is associated with a decrease in the humoral immune response after 17DD-YF primovaccination.

The aim of this study was to assess the impact of administering an energy-protein supplement with fibrolytic enzymes, either singly or in a blend, on the intake, digestibility, ruminal, and metabolic parameters in grazing beef cattle. Five rumen-cannulated Nellore steers, averaging 36 months of age and a body weight of 559.57 ± 35 kg were evaluated using a 5 x 5 Latin Square design. The treatments included a protein-energy supplement (2 g/kg BW) without additives (Control), or supplemented with 4 g β-glucanase/animal (BGLU); 4 g xylanase/animal (XYLA); 4 g β-glucanase and 1 g xylanase/animal (BGLU+XYLA); and 4 g xylanase and 1 g β-glucanase/animal (XYLA+BGLU). The administration of either single fibrolytic enzymes or the enzyme blend did not significantly influence (P > 0.05) the intakes of forage dry matter (DM), total DM, crude protein (CP), neutral detergent fiber (NDF), organic matter (OM), digestible OM, or the digestibility coefficients of DM, NDF, CP, and OM. Similarly, the use of these enzymes individually or combined did not impact (P > 0.05) the levels of rumen pH, volatile fatty acids, ruminal ammonia nitrogen, microbial nitrogen, serum urea nitrogen, or urinary nitrogen excretion. Providing fibrolytic enzymes, individually or in blends, does not modify the nutrient intake, digestibility, or metabolism in beef cattle on tropical pastures receiving low levels of protein-energy supplements.

This investigation elucidated the differences in humoral and H1N1 HA-specific memory B-cells response in participants exhibiting distinct immune response patterns prior to and after vaccination with Fluzone, the quadrivalent split-inactivated seasonal influenza virus vaccine. Participants were categorized into persistent non-responders and persistent responders based on their hemagglutination-inhibition (HAI) antibody titers to the H1N1 component from each vaccine administered between the 2019-2020 to 2023-2024 seasons. Persistent responders had higher fold change in H1N1 HA-specific CD21 expressing B-cells, plasmablasts, and plasma cells. A significant increase in H1N1 HA-specific transitional B-cells in persistent non-responders was observed. The frequency and fold change of H1N1-specific IgM-expressing memory B-cells was higher in persistent non-responders. Dimensionality reduction analysis also demonstrated higher IgM expression for persistent non-responders than persistent responders. Furthermore, persistent non-responders had a significant fold change increase in IgA tissue-like memory, IgG exhausted tissue-like memory, and double negative (DN) activated memory cells. In contrast, persistent responders had increased frequency of IgG-activated memory B-cells, IgG resting B-cells and DN resting B-cells. Correlation analysis revealed a positive correlation between HAI titers and DN memory B-cells and a negative correlation between HAI titers and IgG-expressing memory B-cells in persistent non-responders. Conversely, persistent responders had a positive correlation between HAI titers and IgA resting memory B-cells and a negative correlation between IgG memory B-cells and DN memory B-cells. Overall, this study provided valuable insights into the differential immune memory B-cell responses following influenza virus vaccination and paves the way for future research to further unravel the complexities of vaccine-induced memory B-cells and ultimately improve vaccination strategies against influenza virus infection.

Objetivou-se avaliar o efeito da inclusão de nitrogênio não proteico (NNP) no suplemento e a influência de diferentes tempos de maturação sobre características físico-químicas no músculo de bovinos de corte (½ Angus + ½ Nelore) em pastejo. Foram utilizados 108 bifes do músculo Longissimus dorsi, retirados de 36 bovinos não castrados, com aproximadamente 20 meses de idade e peso corporal inicial de 400,33 ± 40,87 kg, em delineamento experimental inteiramente casualizado e esquema fatorial, com doze tratamentos, constituídos pela combinação de quatro dietas pré-abate e três tempos de maturação da carne, sendo um bife por unidade experimental totalizando nove repetições. As dietas pré-abate foram compostas por pasto e suplementação concentrada com baixo, médio e alto teor de NNP e controle (não suplementado). Não houve interação (p > 0,05) entre dietas e tempos de maturação (TM) sobre a luminosidade, teor de vermelho e intensidade de amarelo, pH e força de cisalhamento da carne. Independente dos TM, animais não suplementados apresentaram menor (p < 0,05) perda de água por cocção (5,92%) e carnes mais duras (3,32 kgf cm-3) que bovinos que receberam dieta com média concentração de NNP (2,62 kgf cm-3). Os animais que receberam dietas com baixa suplementação de NNP apresentaram carnes com maior (p < 0,05) pigmentação vermelha, além de bifes mais leves (p < 0,05) no pós-cocção do que bovinos não suplementados e aqueles alimentados com dieta contendo média suplementação de NNP. Independente das classes de NNP, a maturação realizada até o 9º dia é eficaz para aumentar a maciez da carne dos bovinos. Bovinos cruzados (½ Angus + ½ Nelore) que consomem dietas com baixa ou média suplementação de nitrogênio não proteico apresentam bifes com melhores condições de intensidade de cor vermelha e de maciez, respectivamente.

Objective: To evaluate the humoral response to and impact of SARS-CoV-2 vaccination in patients with systemic lupus erythematosus in a multicenter cohort design. Methods: Data for this analysis were obtained from the Study of Safety, Effectiveness and Duration of Immunity after Vaccination against SARS-CoV-2 in Patients with Immune-Mediated Inflammatory Diseases (SAFER), a prospective, multicenter, phase IV, real-world study conducted across different regions of Brazil from June/2021 to March/2024. Patients aged >18 years with systemic lupus erythematosus (SLE) who received any one of the SARS-CoV-2 vaccines approved by the Brazilian health regulatory agency (CoronaVac [inactivated SARS-CoV-2 vaccine], ChAdOx-1 [AstraZeneca], or BNT162b2 [Pfizer-BioNTech]) were included. Immunogenicity was assessed in pre- and post-vaccination blood samples, and patients were monitored in person and remotely for the occurrence and severity of COVID-19. Results: Two hundred and thirty-five patients with SLE who had completed their vaccination schedules (two doses + booster dose) were included in this study. Most patients were female (89.3%) and had low disease activity or were in remission (72.4%); the majority were also on some form of immunosuppressive therapy (58.1%). One hundred and sixteen patients received two doses of CoronaVac followed by one dose of BNT162b2 (Pfizer-BioNTech) vaccine, eighty-seven received two doses of ChAdOx1-S (AstraZeneca) followed by one dose of BNT162b2 (Pfizer-BioNTech) vaccine, and thirty-two received three doses of BNT162b2 (Pfizer-BioNTech) vaccine. Twenty-eight cases of COVID-19, none meeting criteria for severe COVID-19, were recorded in patients with respiratory symptoms after the second dose of a SARS-CoV-2 vaccine. Regarding immunogenicity, an increase in seroconversion rate was observed following consecutive vaccine doses, with no difference between vaccination schedules, reaching 97.57% seropositivity after a booster dose. The geometric mean IgG titers differed between the different vaccination schedules after the first and the second vaccine dose, being lowest for the CoronaVac-based schedule, but titers were similar after the administration of a booster dose. Conclusion: In patients with SLE, SARS-CoV-2 vaccines are immunogenic, inducing a robust humoral response. No severe outcomes associated with death or hospitalization were found in the evaluated patient sample. Complete vaccination schedules including a booster dose induced higher humoral responses than incomplete schedules, especially in patients initially immunized with an inactivated virus vaccine schedule and those with a suboptimal humoral response.

The present study aimed to verify the impact of etiological treatment on the genotype-specific serological diagnosis of chronic Chagas disease patients (CH), using the Chagas-Flow ATE IgG1 methodology. For this purpose, a total of 92 serum samples from CH, categorized as Not Treated (NT, n = 32) and Benznidazole-Treated (Bz-T, n = 60), were tested at Study Baseline and 5Years Follow-up. At Study Baseline, all patients have the diagnosis of Chagas disease confirmed by Chagas-Flow ATE IgG1, using the set of attributes ("antigen/serum dilution/cut-off"; "EVI/250/30%"). The genotype-specific serodiagnosis at Study Baseline demonstrated that 96% of patients (44/46) presented a serological profile compatible with TcII genotype infection. At 5Years Follow-up monitoring, NT and Bz-T presented no changes in anti-EVI IgG1 reactivity. However, significant differences were detected in the genotype-specific IgG1 reactivity for Bz-T. The most outstanding shift comprised the anti-amastigote TcVI/(AVI), anti-amastigote TcII/(AII) and anti-epimastigote TcVI/(EVI) reactivities. Regardless no changes in the genotype-specific serology of NT (TcI = 6%; TcII = 94%), distinct T. cruzi genotype-specific sero-classification was detected for Bz-T samples at 5Years Follow-up (TcII = 100%) as compared to Baseline (TcII = 97%; TcVI = 3%). The anti-trypomastigote TcI/(TI) was the attribute accountable for the change in genotype-specific sero-classification. In conclusion, our findings of dissimilar T. cruzi genotype-specific serology upon Bz-treatment re-emphasize the relevance of accomplishing the genotype-specific serodiagnosis during clinical pos-therapeutic management of chronic Chagas disease patients.

IntroductionVisceral leishmaniasis (VL) is an important tropical and neglected disease and represents a serious global health problem. The initial interaction between the phagocytes and the parasite is crucial to determine the pathogen’s capacity to initiate infection and it shapes the subsequent immune response that will develop. While type-1 T-cells induce IL-6, IL-1β, TNF-α, and IL-12 production by monocytes/macrophages to fight the infection, type-2 T-cells are associated with a regulatory phenotype (IL-10 and TGF-β) and successful infection establishment. Recently, our group demonstrated the role of an important Th1/Th17 T-cell population, the mucosal-associated invariant T (MAIT) cells, in VL. MAIT cells can respond to L. infantum by producing TNF-α and IFN-γ upon MR1-dependent activation.Objective and methodsHere, we describe the impact of the MR1-blockage on L. infantum internalization on the functional profile of circulating neutrophils and monocytes as well as the impact of the MR1-blockage on the soluble mediator signatures of in vitro whole blood cultures.ResultsOverall, our data showed that VL patients presents higher percentage of activated neutrophils than asymptomatic and non-infected controls. In addition, MR1 blockade led to lower TNF-α and TGF-β production by non-activated neutrophils from asymptomatic individuals. Moreover, TNF-α and IL-10 production by monocytes was higher in VL patients. In the analysis of soluble mediators produced in vitro, MR1-blockade induced a decrease of IFN-γ and an increase of IL-10, IL-27 and IL-33 in the cell cultures of AS group, a cytokine pattern associated with type 2 deleterious response.Discussion and conclusionThese data corroborate the hypothesis that MR1-restricted responses are associated to a protective role during Leishmania infection.

Extracellular vesicles (EVs) are heterogeneous, phospholipid membrane enclosed particles that are secreted by healthy and cancerous cells. EVs are present in diverse biological fluids and have been associated with the severity of diseases, which indicates their potential as biomarkers for diagnosis, prognosis and as therapeutic targets. This study investigated the phenotypic characteristics of EVs derived from peripheral blood (PB) and bone marrow (BM) in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) during different treatment stages. PB and BM plasma were collected from 20 B-ALL patients at three time points during induction therapy, referred to as: diagnosis baseline (D0), day 15 of induction therapy (D15) and the end of the induction therapy (D35). In addition, PB samples were collected from 10 healthy children at a single time point. The EVs were measured using CytoFLEX S flow cytometer. Calibration beads were employed to ensure accurate size analysis. The following, fluorescent-labeled specific cellular markers were used to label the EVs: Annexin V (phosphatidylserine), CD235a (erythrocyte), CD41a (platelet), CD51 (endothelial cell), CD45 (leukocyte), CD66b (neutrophil), CD14 (monocyte), CD3 (T lymphocyte), CD19, CD34 and CD10 (B lymphoblast/leukemic blast). Our results demonstrate that B-ALL patients had a marked production of EV-CD51/61+, EV-CD10+, EV-CD19+ and EV-CD10+CD19+ (double-positive) with a decrease in EV-CD41a+ on D0. However, the kinetics and signature of production during induction therapy revealed a clear decline in EV-CD10+ and EV-CD19+, with an increase of EV-CD41a+ on D35. Furthermore, B-ALL patients showed a complex biological network, exhibiting distinct profiles on D0 and D35. Interestingly, fold change and ROC curve analysis demonstrated that EV-CD10+CD19+ were associated with B-ALL patients, exhibited excellent clinical performance and standing out as a potential diagnostic biomarker. In conclusion, our data indicate that EVs represent a promising field of investigation in B-ALL, offering the possibility of identifying potential biomarkers and therapeutic targets.

ABSTRACT This study was conducted to assess prediction models for production indexes in batches of growing pigs using performance regressors (period of the year and farm size). A database containing 663 records on the performance of pig batches (18.83 ± 4.37 to 111.26 ± 10.59 kg body weight (BW) at housing and finisher, respectively) from a private company was used to assess the following average animal characteristics: initial number of animals (INA), initial BW (IBW), initial age (IA), final BW (FBW), final age (FA), daily feed intake (DFI) and feed conversion ratio (FCR). Data were categorized by period (P) of the year (P1 = Nov to Apr and P2 = May to Oct), and farm size (FS): 0 ≤ INA ≤ 1,000, FS1; 1,001 ≤ INA ≤ 2,000, FS2; 2,001 ≤ INA ≤ 3,000, FS3; and INA > 3,000, FS4. The analysis resulted in representing 58 % of the variance of FCR data. The INA impaired FCR, and having larger pig batches improves FCR and profitability. The FBW prediction errors ranged from 2.47 to 3.38 %. Feed conversion ratio prediction errors ranged from 3.27 to 4.47 %. Based on the joint criteria of non-bias and accuracy, the models for predicting the FBW of growing pig batches have practical value in animal science on account of their accuracy. In addition, increasing the initial number of housed pigs in batches affects the FCR regardless of the period of the year.

Abstract The re-emergence of yellow fever (YF) urged new mass vaccination campaigns and, in 2017, the World Health Organization approved the use of the fractional dose (FD) of the YF vaccine due to stock shortage. In an observational cross-sectional investigation, we have assessed viremia, antibodies, soluble mediators and effector and memory T and B-cells induced by primary vaccination of volunteers with FD and standard dose (SD). Similar viremia and levels of antibodies and soluble markers were induced early after immunization. However, a faster decrease in the latter was observed after SD. The FD led to a sustained expansion of helper T-cells and an increased expression of activation markers on T-cells early after vaccination. Although with different kinetics, expansion of plasma cells was induced upon SD and FD immunization. Integrative analysis reveals that FD induces a more complex network involving follicular helper T cells and B-cells than SD. Our findings substantiate that FD can replace SD inducing robust correlates of protective immune response against YF.

Background/Objectives: The effectiveness of COVID-19 vaccine in patients with immune-mediated inflammatory diseases (IMID) depends on the underlying disease, immunosuppression degree and the vaccine regimens. We evaluate the safety and immunogenicity of different COVID-19 vaccine schedules. Methods: The SAFER study: “Safety and effectiveness of the COVID-19 Vaccine in Rheumatic Disease”, is a Brazilian multicentric prospective observational phase IV study in the real-life. Data were analyzed after 2 or 3 doses of COVID-19 vaccines: adenoviral vectored vaccine (ChAdOx1 nCoV-19, Astrazeneca), mRNA vaccine (BNT162b2, Pfizer–BioNTech) or inactivated SARS-COV-2 vaccine (CoronaVac, Sinovac Biotech). IgG antibody against SARS-CoV-2 spike (IgG-S) receptor-binding domain level were quantified at baseline (T1) and 28 days after the first (T2), 2nd (T3) and 3rd (T4) doses by chemiluminescence (SARS-CoV-2-IgG-II Quant-assay, Abbott-Laboratories). Results: 721 patients with IMID were included in the analysis. The median titers of IgG-S (BAU/mL) increased progressively over the times: at baseline was 6.26 (5.41–7.24), T2: 73.01 (61.53–86.62), T3: 200.0 (174.36–229.41) and T4: 904.92 (800.49–1022.97). The multivariate linear regression showed that greater IgG-S titers were associated with pre-exposure to COVID-19 (p < 0.001) and BNT162b2 booster vaccine (p < 0.001). Rituximab and immunosuppressant drugs were independent factors for low titers (p = 0.002, p < 0.001, respectively). No serious adverse event was reported. Conclusions: All platforms were safe and induced an increase in IgG-S antibodies. COVID-19 pre-exposure and BNT162b2 booster regimens were predictors of higher humoral immune responses, which is relevant in immunosuppressed populations. Immunosuppressants (mainly rituximab) predicted the lowest antibodies.

The present study aimed to evaluate the kinetics of the phenotypic profile and integrative networks of T/B-cells in severe COVID-19 patients, categorized according to disease outcome, during the circulation of the B.1.1.28 and B.1.1.33 SARS-CoV-2 strains in Brazil. Peripheral blood obtained at distinct time points (baseline/D0; D7; D14-28) was used for ex vivo flow cytometry immunophenotyping. The data demonstrated a decrease at D0 in the frequency of CD3+ T-cells and CD4+ T-cells and an increase in B-cells with mixed activation/exhaustion profiles. Higher changes in B-cell and CD4+ T-cells at D7 were associated with discharge/death outcomes, respectively. Regardless of the lower T/B-cell connectivity at D0, distinct profiles from D7/D14-28 revealed that, while discharge was associated with increasing connectivity for B-cells, CD4+ and CD8+ T-cells death was related to increased connectivity involving B-cells, but with lower connections mediated by CD4+ T-cells. The CD4+CD38+ and CD8+CD69+ subsets accurately classified COVID-19 vs. healthy controls throughout the kinetic analysis. Binary logistic regression identified CD4+CD107a+, CD4+T-bet+, CD8+CD69+, and CD8+T-bet+ at D0 and CD4+CD45RO+CD27+ at D7 as subsets associated with disease outcomes. Results showed that distinct phenotypic timeline kinetics and integrative networks of T/B-cells are associated with COVID-19 outcomes that may subsidize the establishment of applicable biomarkers for clinical/therapeutic monitoring.

This study was conducted to assess the effects of dietary monoglycerides and tributyrin on performance, blood metabolites, and intestinal health function in nursery piglets. A total of 96 crossbred entire male piglets (7.70 ± 0.49 kg) were allotted for 35 d in a complete block design to one of four treatments: (1) negative control (NC): no feed additive, (2) positive control (PC) containing 60 mg halquinol/kg diet, (3) diet containing 2 g monoglyceride blend/kg diet (MGD), and (4) diet containing 2 g tributyrin/kg diet (TBT). The growth phases were defined as pre-starter (day 0–20), and starter (day 20–35). No treatment effect on performance was observed. Pre-starter piglets fed NC showed higher diarrhoea occurrence (DO) than those fed PC and TBT (p

Abstract Immunobiography describes the life-long effects of exogenous or endogenous stimuli on remodeling of immune cell biology, including the development of memory T and B-cells. The present study aimed at investigating the rhythms of changes in phenotypic features of memory T and B-cells along childhood and adolescence. A descriptive-observational investigation was conducted including 812 healthy volunteers, clustered into six consecutive age groups (9Mths–1Yr; 2Yrs; 3–4Yrs; 5–7Yrs; 8–10Yrs; 11–18Yrs). Immunophenotypic analysis of memory T-cell (CD4+ and CD8+) and B-cell subsets were performed by flow cytometry. The results pointed out that memory-related biomarkers of T and B-cells displayed a bimodal profile along healthy childhood and adolescence, regardless of sex. The first stage of changes occurs around 2Yrs, with predominance of naive cells, while the second and more prominent wave occurs around the age 8–10Yrs, with the prevalence of memory phenotypes. The neighborhood connectivity profile analysis demonstrated that the number of correlations reaches a peak at 11–18Yrs and lower values along the childhood. Males presented higher and conserved number of correlations when compared to females. Altogether, our results provide new insights into immunobiography and a better understanding of interactions among the cellular subsets studied here during childhood and adolescence.

The objective of the current study was to compare the rumen inoculum of slaughtered cattle with the ruminal inoculum of cannulated cattle; additionally, determine its reliability in the in vitro analysis of ruminant feeds throughout a multivariate approach. Five male bovines (weight 320 ± 9.4 kg; mean ± standard deviation) provided with ruminal cannula and between five and seven bovines slaughtered in slaughterhouse were used. The evaluations were carried out following a completely randomized design. The data obtained were subjected to different multivariate analyzes to determine the reliability of the ruminal inoculum of animals slaughtered in commercial slaughterhouses compared to that obtained from cannulated animals. The relative contribution indicated that the in vitro dry matter digestibility (IVDMD, 50.75%) and in vitro neutral detergent fiber digestibility (IVNDFD, 29.83%) analysis influence 80.13% of the results to determine the reliability of the ruminal inoculum from slaughtered cattle. Furthermore, it was determined that the first two principal components (IVNDFD and acetic acid production) are the ones that influence the results by 89.87%. The grouping of diets using the Tocher optimization method and the dendrogram shows the formation of six groups and two groups, respectively. The grouping shows that the ruminal inoculum source was not the limiting parameter in the evaluation. Rumen inoculum from cattle slaughtered in a commercial slaughterhouse (with unknown diet) has potential as an alternative for the in vitro analysis of cattle feed, provided that the lignin concentration in the diet is less than 35.5 g/kg DM.

Immunosenescence is a phenomenon caused by changes in the immune system, and part of these changes involves an increase in circulating immunological biomarkers, a process known as “Inflammaging.” Inflammaging can be associated with many diseases related to older people. As the older population continues to grow, understanding changes in the immune system becomes essential. While prior studies assessing these alterations have been conducted in countries with Caucasian populations, this investigation marks a pioneering effort. The object of the study is to describe for the first time that the distribution of cytokines, chemokines, and growth factors serum levels, assessed by Luminex platform, has been examined in a Brazilian population-based study of older adult females and males by age. Blood samples from 2111 participants (≥50 years old) were analyzed at the baseline (2015/2016) of the ELSI-Brazil study. The exploratory variables considered in the study were age, sex, educational level, residence area, geographic region, alcohol and smoking consumption, physical activity, and self-reported medical diagnoses of hypertension, diabetes, asthma, arthritis, and cancer. The association between serum biomarker levels and age was assessed by a quantile regression model adjusted in the total population and stratified by sex. The significance level considered in the analysis was 0.05. The mean age of the participants was 62.9 years, with a slight majority of female (52.7 %). Differences were found between the sexes in the median circulating levels of the CCL11, CXCL10, and FGF biomarkers. Eight biomarkers showed significant associations with age, including the pro-inflammatory CXCL10, TNF-α, IL-6, IL-17, and IL-2; and type 2/regulatory CCL11 and IL-4, showing positive associations, and anti-inflammatory IL-1Ra showing a negative association. The results suggest similar associations between the sexes, revealing an inflammatory profile characterized by types 1 and 2. Remarkably, these findings reinforce the concept of the Inflammaging process in Brazilian population. These findings add novel insights to about the immunosenescence aspects in middle-income countries and help define biomarkers capable of monitoring inflammation in older adults.

ABSTRACTBetween 2016 and 2018, Brazil experienced major sylvatic yellow fever (YF) outbreaks that caused hundreds of casualties, with Minas Gerais (MG) being the most affected state. These outbreaks provided a unique opportunity to assess the immune response triggered by the wild-type (WT) yellow fever virus (YFV) in humans. The plaque reduction neutralization test (PRNT) is currently the standard method to assess the humoral immune response to YFV by measuring neutralizing antibodies (nAbs). The present study aimed to evaluate the humoral immune response of patients from the 2017–2018 sylvatic YF outbreak in MG with different disease outcomes by using PRNTs with a WT YFV strain, isolated from the 2017–2018 outbreak, and a vaccine YFV strain. Samples from naturally infected YF patients were tested, in comparison with healthy vaccinees. Results showed that both groups presented different levels of nAb against the WT and vaccine strains, and the levels of neutralization against the strains varied homotypically and heterotypically. Results based on the geometric mean titers (GMTs) suggest that the humoral immune response after a natural infection of YFV can reach higher levels than that induced by vaccination (GMT of patients against WT YFV compared to GMT of vaccinees, P < 0.0001). These findings suggest that the humoral immune responses triggered by the vaccine and WT strains of YFV are different, possibly due to genetic and antigenic differences between these viruses. Therefore, current means of assessing the immune response in naturally infected YF individuals and immunological surveillance methods in areas with intense viral circulation may need to be updated.IMPORTANCEYellow fever is a deadly febrile disease caused by the YFV. Despite the existence of effective vaccines, this disease still represents a public health concern worldwide. Much is known about the immune response against the vaccine strains of the YFV, but recent studies have shown that it differs from that induced by WT strains. The extent of this difference and the mechanisms behind it are still unclear. Thus, studies aimed to better understand the immune response against this virus are relevant and necessary. The present study evaluated levels of neutralizing antibodies of yellow fever patients from recent outbreaks in Brazil, in comparison with healthy vaccinees, using plaque reduction neutralization tests with WT and vaccine YFV strains. Results showed that the humoral immune response in naturally infected patients was higher than that induced by vaccination, thus providing new insights into the immune response triggered against these viruses.

Chagas disease, caused by Trypanosoma cruzi, remains a serious public health problem worldwide. The parasite was subdivided into six distinct genetic groups, called “discrete typing units” (DTUs), from TcI to TcVI. Several studies have indicated that the heterogeneity of T. cruzi species directly affects the diversity of clinical manifestations of Chagas disease, control, diagnosis performance, and susceptibility to treatment. Thus, this review aims to describe how T. cruzi genetic diversity influences the biology of the parasite and/or clinical parameters in humans. Regarding the geographic dispersion of T. cruzi, evident differences were observed in the distribution of DTUs in distinct areas. For example, TcII is the main DTU detected in Brazilian patients from the central and southeastern regions, where there are also registers of TcVI as a secondary T. cruzi DTU. An important aspect observed in previous studies is that the genetic variability of T. cruzi can impact parasite infectivity, reproduction, and differentiation in the vectors. It has been proposed that T. cruzi DTU influences the host immune response and affects disease progression. Genetic aspects of the parasite play an important role in determining which host tissues will be infected, thus heavily influencing Chagas disease’s pathogenesis. Several teams have investigated the correlation between T. cruzi DTU and the reactivation of Chagas disease. In agreement with these data, it is reasonable to suppose that the immunological condition of the patient, whether or not associated with the reactivation of the T. cruzi infection and the parasite strain, may have an important role in the pathogenesis of Chagas disease. In this context, understanding the genetics of T. cruzi and its biological and clinical implications will provide new knowledge that may contribute to additional strategies in the diagnosis and clinical outcome follow-up of patients with Chagas disease, in addition to the reactivation of immunocompromised patients infected with T. cruzi.

IntroductionChagas disease is a neglected parasitic disease caused by Trypanosoma cruzi. While most patients are asymptomatic, around 30% develop Chronic Chagasic Cardiomyopathy (CCC).MethodsHere, we employed high-dimensional flow cytometry to analyze CD4+ T and B cell compartments in patients during the chronic phase of Chagas disease, presenting the asymptomatic and mild or moderate/severe cardiac clinical forms.ResultsEffector CD27-CD4+ T cells were expanded in both CCC groups, and only mild CCC patients showed higher frequencies of effector memory and T follicular helper (Tfh) cells than healthy donors (CTL) and asymptomatic patients. Unsupervised analysis confirmed these findings and further revealed the expansion of a specific subpopulation composed of Tfh, transitional, and central memory CD4+ T cells bearing a phenotype associated with strong activation, differentiation, and exhaustion in patients with mild but not moderate/severe CCC. In contrast, patients with mild and moderate/severe CCC had lower frequencies of CD4+ T cells expressing lower levels of activation markers, suggesting resting status, than CTL. Regarding the B cell compartment, no alterations were found in naïve CD21-, memory cells expressing IgM or IgD, marginal zone, and plasma cells in patients with Chagas disease. However, expansion of class-switched activated and atypical memory B cells was observed in all clinical forms, and more substantially in mild CCC patients.DiscussionTaken together, our results showed that T. cruzi infection triggers changes in CD4+ T and B cell compartments that are more pronounced in the mild CCC clinical form, suggesting an orchestrated cellular communication during Chagas disease.ConclusionOverall, these findings reinforce the heterogeneity and complexity of the immune response in patients with chronic Chagas disease and may provide new insights into disease pathology and potential markers to guide clinical decisions.

Abstract The effects of β-mannanase supplementation in metabolizable energy (ME)-reduced diets containing xylanase-phytase were investigated on growth performance, fecal score, ultra-sounded backfat thickness and loin depth, blood profile, apparent total tract digestibility (ATTD), digesta passage rate, and fecal microbiome in grower pigs (n = 40, 26.09 ± 0.96 kg) randomly assigned within 4 treatments: a control diet containing isolated phytase and xylanase valued at 40 kcal of ME/kg (CD0), CD0 + β-mannanase (0.3 g/kg valued at 30 kcal of ME/kg) (CD70), CD0 + β-mannanase (0.3 g/kg valued at 45 kcal of ME/kg) (CD85), and CD0 + β-mannanase (0.3 g/kg valued at 60 kcal of ME/kg) (CD100). Growth performance was not affected in pigs fed ME-reduced diets containing β-mannanase. Pigs with CD100 had lower serum IL-1β concentration, and higher IL-10 was observed in pigs on CD0 than those fed β-mannanase. Coefficients of ATTD, and ATTD of DM and CP were higher in animals fed CD85 or CD100. Pigs with CD85 had higher alpha diversity richness but lower Firmicutes:Bacteroidota ratio. Acidaminococcaceae and Ruminococcaceae were more abundant in pigs fed CD0, but lower for Christensenellaceae NSJ-63 and NSJ-63 sp014384805. Pigs in CD85 showed higher Bacteroidaceae and Prevotella abundance, and lower for Streptococcaceae and Streptococcus. In conclusion, supplementation of β-mannanase in diets containing xylanase-phytase saved 85 to 100 kcal of ME/kg by supporting growth performance and improving nutrient digestibility in grower pigs.

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune-mediated rheumatic disease (IMRD) patients are scarce. This study describes breakthrough COVID-19 occurring in IMRD patients participating in the SAFER-study, a Brazilian multicentric cohort evaluating the safety, effectiveness, and immunogenicity of SARS-CoV-2 vaccines in patients with autoimmune diseases. A descriptive analysis of the population and a binary logistic regression model were performed to evaluate the predictors of COVID-19-related hospitalization. A p-value < 0.05 was significant. The included 160 patients were predominantly females (83.1%), with a mean (SD) age of 40.23 (13.19) years. The patients received two (19%), three (70%), or four (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n = 150) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n = 112) was with BNT162b2 (40%) or ChAdOx1 (26%). The COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84; CI: 1.9–18.5; p = 0.002) and treatment with corticosteroids (OR: 2.94; CI: 1.02–8.49; p = 0.0043) were associated with higher odds of hospitalization, while increasing the number of vaccine doses was protective (OR: 0.37; CI: 0.15–0.9; p = 0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favor of booster vaccination in IMRD patients.

ABSTRACT This study aimed to assess an alkaline protease supplemented in diets with and without crude protein (CP) reduction on performance, apparent total tract digestibility (ATTD), blood parameters, and carcass and meat traits in growing-finishing pigs. Forty male pigs (26.2±1.2 kg) were randomly allocated into one of five treatments: negative control (NC, 2% and 1% reduction of CP in grower and finisher phases, respectively, no protease); NC150: NC + 150 mg protease kg−1 diet; NC300: NC + 300 mg protease kg−1 diet; PC: positive control (no CP reduction and protease); and PC300: PC + 300 mg protease kg−1 diet, with eight replicates of one pig/pen. Pigs fed NC showed greater average daily feed intake (ADFI) than pigs fed NC300 or PC and lower ADFI compared to pigs fed NC150. Pigs fed PC had lower ADFI than those fed PC300. Greater average daily gain and gain to feed ratio (G:F) were observed in pigs on NC compared with those on NC300 or NC150 and NC300, respectively. Pigs fed PC showed better G:F than pigs fed PC300. Lower coefficients of ATTD (CTTAD) of dry and organic matter (OM), digestible dry matter (DDM), digestible organic matter (DOM), and digestible protein were observed in growing II pigs fed NC compared with pigs fed NC150 or NC300. Pigs fed NC showed a lower DP compared with PC or NC150. Positive control group showed increased digestible protein compared with NC. Finishing II pigs fed NC showed lower DDM, DOM, CTTAD of OM, and gross energy than pigs fed NC150 or NC300. Pigs fed PC showed greater albumin concentration compared with pigs fed PC300 in finishing II. Pigs fed NC and PC300 showed greater luminosity in the l. thoracis muscle than pigs fed PC. A greater color score was evidenced in the l. thoracis in pigs fed PC compared with pigs fed PC300. The dietary supplementation of isolated alkaline protease and CP-reduced diets improves ATTD without supporting pig performance.

IntroductionUnderstanding compartmentalized immune responses in target organs is crucial for elucidating the pathogenesis of various diseases. However, obtaining samples from affected vital organs often poses safety challenges. In this study, we aimed to investigate potential correlations between the levels of disease-associated immune molecules in the bloodstream with their gene expression profiles in the hearts of patients suffering from Chagas Cardiomyopathy (CCC). This debilitating and often fatal condition is caused by infection with the protozoan Trypanosoma cruzi.MethodsBlood samples were analyzed using the Bio-Plex platform. Gene Expression Omnibus (GEO) database was used to determine gene expression profile in heart tissue from CCC and non-Chagas controls (CTRL).ResultsElevated levels of inflammatory cytokines were detected in the plasma of CCC patients, and these levels correlated with clinical indicators of deteriorating cardiac function. Notably, 75% of the soluble factors assessed in the plasma exhibited a consistent relationship with their gene expression levels in the cardiac tissue of CCC patients. Analysis of interactions and signaling pathways related to these molecules revealed an overrepresentation of inflammatory pathways in both blood and heart compartments. Moreover, we identified that differentially expressed genes in CCC cardiac tissue were primarily associated with T-cell signaling pathways and correlated with the presence of CD8+ T cells in the myocardium.DiscussionOur findings establish a strong correlation between relevant immune molecules and their signaling pathways in both the blood and heart tissue in CCC. This validates the use of blood as a non-invasive medium for understanding immunopathology and identifying markers for cardiac dysfunction in Chagas disease.

Este estudo foi composto por dois experimentos conduzidos para avaliar os efeitos de dietas com baixo e alto teor de proteína bruta suplementadas até o quarto aminoácido essencial e dois cruzamentos comerciais sobre o desempenho zootécnico, concentração de ureia plasmática (CUP), viabilidade econômica, digestibilidade aparente de nutrientes, e balanço de nitrogênio em leitões iniciantes. No Exp. I, um total de 128 leitões (14,02 ± 1,96 kg de peso corporal inicial e 48 dias de idade) foram distribuídos baseado no peso corporal inicial em um delineamento de blocos casualizados com arranjo fatorial 2 × 2. Foram avaliados dois cruzamentos comerciais (DB e PIC) e duas dietas de proteína bruta (baixa proteína bruta, BPB, e alta proteína bruta, APB). Foram utilizados quatro tratamentos, oito repetições e quatro leitões por unidade experimental. Exp. II foi conduzido utilizando 24 leitões machos inteiros (20,00 ± 1,41 kg de peso corporal inicial) alojados em gaiolas metabólicas por 12 dias e distribuídos no mesmo desenho experimental do Expt. I (seis repetições). Os resultados do Exp. I sugerem que os leitões alimentados com APB apresentaram melhor desempenho zootécnico. Foi observado um aumento de 25,2% na CUP em leitões alimentados com APB. Houve aumento de 18,2% no índice de eficiência econômica quando os leitões foram alimentados com APB, e também foi observada redução no custo por kg de ganho de peso corporal. No Exp. II, os leitões alimentados com APB apresentaram maiores coeficientes de digestibilidade aparente dos nutrientes, proteína e energia digestíveis, consumo e absorção de N. Não houve efeito dos cruzamentos comerciais sobre as variáveis de desempenho e metabolismo. Conclui-se que as dietas APB, independente da genética, promoveram melhorias no desempenho e no índice de viabilidade econômica, mas aumentaram a CUP nos leitões. Além disso, as dietas APB influenciaram positivamente a digestibilidade aparente dos nutrientes e a ingestão e absorção de N.

IntroductionChagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi. Although endemic mainly in Latin America, CD has become a global public health problem due to migration of infected individuals to non-endemic regions. Despite progress made in drug development, preclinical assays for drug discovery are required to accelerate the development of new drugs with reduced side effects, which are much needed for human treatment.MethodsWe used a cure model of infected mice treated with Fexinidazole (FZ) to further validate a novel Enzyme Linked Aptamer (ELA) assay that detects parasite biomarkers circulating in the blood of infected animals.ResultsThe ELA assay showed cure by FZ in ~71% and ~77% of mice infected with the VL-10 and Colombiana strains of T. cruzi, respectively. The ELA assay also revealed superior treatment efficacy of FZ compared to Benznidazole prior to immunosuppression treatment.DiscussionOur study supports the use of ELA assay as an alternative to traditional serology or blood PCR to assess the efficacy of antichagasic drugs during their preclinical phase of development. Further, the combination of high sensitivity and ease of use make this parasite antigen detection assay an attractive new tool to facilitate the development of much needed new therapies for CD.

The present study compares the ability of distinct immunological assays (chemiluminescence immunoassay-CLIA, western blot-WB and flow cytometry-FC-Simplex and Duplex) to detect anti-HTLV (human T-lymphotropic virus) antibodies in candidates for blood donations at the Amazonas State Blood Center (Brazil) between January 2018 and December 2022. Overall, 257,942 samples from candidates for blood donations were screened using CLIA, which led to 0.15% seropositivity for HTLV (409 samples). A total of 151 candidates for blood donations were enrolled for retesting with CLIA followed by additional testing using WB and FC-Simplex and Duplex analysis. Our results demonstrated that 62% (93/151), 20% (30/151) and 17% (26/151) of the samples presented positive results with retesting using CLIA, WB and FC-Simplex analysis, respectively. Additional analysis of the CLIA, WB and FC-Simplex results revealed an overall agreement of 56% for CLIA and WB (22 co-negative; 30 co-positive samples), 48% for CLIA and FC-Simplex (21 co-negative; 24 co-positive samples) and 80% for WB and FC-Simplex (51 co-negative; 23 co-positive samples). Considering the WB as the reference standard for the diagnosis of infection with HTLV-1/2, we observed that the CLIA results of ≤3.0 RLU and >10.0 RLU in the retest can be used define a negative or positive result, respectively, and could be used as new specific cut-off values. The overall agreement between WB and FC-Duplex for accomplishing the differential diagnosis was evaluated and demonstrated 100% correspondence for the diagnosis of HTLV-1 (15/15) and HTLV-2 (7/7). Our findings demonstrate that gaps in the diagnosis of infection with HTLV-1/2 could be overcome by the simultaneous use of distinct immunological assays during retesting of candidates for blood donations.

Objective This study was to assess the effects of different doses of an essential oil blend (EOB) on growth performance, diarrhea occurrence (DO), hematological and blood biochemical profile, intestinal morphometry, morphology and microbiology, relative weight and length of organs, digestive content pH, and liver antioxidant status in weaning piglets. Methods A total of 135 barrows (7.09±0.29 kg body weight) were allotted randomly in a randomized complete block design based on body weight with nine replications and three animals per pen. Dietary treatments were a negative control (NC): basal diet; positive control (PC): NC plus 125 mg performance-enhancing antibiotic (enramycin 8%)/kg diet; NC plus 100 mg EOB/kg diet (EO100); NC plus 200 mg EOB/kg diet (EO200); and NC plus 400 mg EOB/kg diet (EO400). Diarrhea occurrence was monitored daily, and performance at the end of each phase. Results Gain to feed ratio was greater (p

BackgroundChildren with B-cell acute lymphoblastic leukemia (B-ALL) have an immune imbalance that is marked by remodeling of the hematopoietic compartment, with effects on peripheral blood (PB). Although the bone marrow (BM) is the main maintenance site of malignancy, the frequency with which immune cells and molecules can be monitored is limited, thus the identification of biomarkers in PB becomes an alternative for monitoring the evolution of the disease.MethodsHere, we characterize the systemic immunological profile in children undergoing treatment for B-ALL, and evaluate the performance of cell populations, chemokines and cytokines as potential biomarkers during clinical follow-up. For this purpose, PB samples from 20 patients with B-ALL were collected on diagnosis (D0) and during induction therapy (days 8, 15 and 35). In addition, samples from 28 children were used as a control group (CG). The cellular profile (NK and NKT-cells, Treg, CD3+ T, CD4+ T and CD8+ T cells) and soluble immunological mediators (CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-6, TNF, IFN-γ, IL-17A, IL- 4, IL-10 and IL-2) were evaluated via flow cytometry immunophenotyping and cytometric bead array assay.ResultsOn D0, B-ALL patients showed reduction in the frequency of cell populations, except for CD4+ T and CD8+ T cells, which together with CCL2, CXCL9, CXCL10, IL-6 and IL-10 were elevated in relation to the patients of the CG. On D8 and D15, the patients presented a transition in the immunological profile. While, on D35, they already presented an opposite profile to D0, with an increase in NKT, CD3+ T, CD4+ T and Treg cells, along with CCL5, and a decrease in the levels of CXCL9, CXCL10 and IL-10, thus demonstrating that B-ALL patients present a complex and dynamic immune network during induction therapy. Furthermore, we identified that many immunological mediators could be used to classify the therapeutic response based on currently used parameters.ConclusionFinally, it is noted that the systemic immunological profile after remission induction still differs significantly when compared to the GC and that multiple immunological mediators performed well as serum biomarkers.

Neurological complications are frequent during the active course of infective endocarditis (IE), and they are associated with high in-hospital mortality rates. However, limited data exist on the prognostic value of these complications for late outcomes. This study aimed to assess the long-term impact of neurological complications in patients surviving an IE episode. A total of 263 consecutive IE patients admitted to a tertiary care center between 2007 and 2022 were prospectively included. Neurological complications at admission included transient ischemic attack (TIA), ischemic stroke, hemorrhagic stroke, intracerebral abscess, and meningitis. The primary outcome was a composite of overall mortality or heart valve surgery. Of the patients, 34.2% died in the hospital, leaving 173 survivors for long-term follow-up. Over a median of 3.5 years, 29 patients died, and 13 (9%) underwent cardiac surgery, resulting in an overall adverse event rate of 30%. Neurological complications independently predicted long-term adverse outcomes (hazard ratio (HR) 2.237; 95% CI 1.006–4.976), after adjusting for age, chronic kidney disease (CKD), and heart failure (HF) development. In an IE patient cohort, neurological complications at admission, which is a complication directly related to the IE process, were independent predictors of long-term outcomes.