Rapid identification of early infections in febrile patients after CD19 target CAR-T cell therapy for B-cell malignancies.

BACKGROUND: CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy stands out as a revolutionary intervention, exhibiting remarkable remission rates in patients with refractory/relapsed (R/R) B-cell malignancies. However, the potential side effects of therapy, particularly cytokine release syndrome (CRS) and infections, pose significant challenges due to their overlapping clinical features. Promptly distinguishing between CRS and infection post CD19 target CAR-T cell infusion (CTI) remains a clinical dilemma. Our study aimed to analyze the incidence of infections and identify key indicators for early infection detection in febrile patients within 30 days post-CTI for B-cell malignancies. METHODS: In this retrospective cohort study, a cohort of 104 consecutive patients with R/R B-cell malignancies who underwent CAR-T therapy was reviewed. Clinical data including age, gender, CRS, ICANS, treatment history, infection incidence, and treatment responses were collected. Serum biomarkers procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were analyzed using chemiluminescent assays. Statistical analyses employed Pearson's Chi-square test, t-test, Mann-Whitney U-test, Kaplan-Meier survival analysis, Cox proportional hazards regression model, Spearman rank correlation, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic accuracy and develop predictive models through multivariate logistic regression. RESULTS: In this study, 38 patients (36.5%) experienced infections (30 bacterial, 5 fungal, and 3 viral) within the first 30 days of CAR T-cell infusion. In general, bacterial, fungal, and viral infections were detected at a median of 7, 8, and 9 days, respectively, after CAR T-cell infusion. Prior allogeneic hematopoietic cell transplantation (HCT) was an independent risk factor for infection (Hazard Ratio [HR]: 4.432 [1.262-15.565], P = 0.020). Furthermore, CRS was an independent risk factor for both infection ((HR: 2.903 [1.577-5.345], P < 0.001) and severe infection (9.040 [2.256-36.232], P < 0.001). Serum PCT, IL-6, and CRP were valuable in early infection prediction post-CAR-T therapy, particularly PCT with the highest area under the ROC curve (AUC) of 0.897. A diagnostic model incorporating PCT and CRP demonstrated an AUC of 0.903 with sensitivity and specificity above 83%. For severe infections, a model including CRS severity and PCT showed an exceptional AUC of 0.991 with perfect sensitivity and high specificity. Based on the aforementioned analysis, we proposed a workflow for the rapid identification of early infection during CAR-T cell therapy. CONCLUSIONS: CRS and prior allogeneic HCT are independent infection risk factors post-CTI in febrile B-cell malignancy patients. Our identification of novel models using PCT and CRP for predicting infection, and PCT and CRS for predicting severe infection, offers potential to guide therapeutic decisions and enhance the efficacy of CAR-T cell therapy in the future.

The time-dependent changes in serum immunoglobulin after kidney transplantation and its association with infection.

Introduction: Kidney transplant recipients often experience significant alterations in their immune system, which can lead to increased susceptibility to infections. This study aimed to analyze time-dependent changes in serum immunoglobulin and complement levels and determine the risk factors associated with infection. Methods: A retrospective analysis of serum samples from 192 kidney transplant recipients who received transplantations between August 2016 and December 2019 was conducted. The serum samples were obtained at preoperative baseline (T0), postoperative 2 weeks (T1), 3 months (T2), and 1 year (T3). The levels of serum C3, C4, IgG, IgA, and IgM were measured to evaluate immune status over time. Results: The analysis revealed significant decreases in IgG and IgA levels at T1. This period was associated with the highest occurrence of hypogammaglobulinemia (HGG) and hypocomplementemia (HCC), as well as an increased incidence of severe infection requiring hospitalization and graft-related viral infections. Using a time-dependent Cox proportional hazards model adjusted for time-varying confounders, HGG was significantly associated with an increased risk of infection requiring hospitalization (HR, 1.895; 95% CI: 1.871-1.920, P-value<0.001) and graft-related viral infection (HR, 1.152; 95% CI: 1.144-1.160, P-value<0.001). Discussion: The findings suggest that monitoring serum immunoglobulin levels post-transplant provides valuable insights into the degree of immunosuppression. Hypogammaglobulinemia during the early post-transplant period emerges as a critical risk factor for infection, indicating that serum immunoglobulins could serve as feasible biomarkers for assessing infection risk in kidney transplant recipients.

Procalcitonin, brain natriuretic peptide and albumin as markers to predict prognosis in hospitalized older Japanese patients with a risk of infection.

AIM: Whether serum concentration of procalcitonin (PCT), brain natriuretic peptide (BNP) and albumin (Alb) have an association with the outcome of hospitalized older patients is unclear. We investigated clinical outcomes and any predictive factors in hospitalized Japanese older patients with a risk of infection. METHODS: In the retrospective study, 820 Japanese patients were followed up for 30 days or until death. During the observation period, 656 patients survived and 164 patients died. The predictive factors of death were analyzed according to demographic and clinical variables. RESULTS: The survival rate was decreased as the serum PCT increased from <0.5 to ≥10 ng/mL, as was also the case with BNP from <300 to ≥300 pg./mL, whereas low Alb (<2.5 g/dL) showed a lower survival rate than high Alb (≥2.5 g/dL; P < 0.01). Using the Cox regression model, the multivariable-adjusted hazard ratios (95% confidence interval) were as follows: PCT 0.5-2 versus <0.5 ng/mL: 1.61(1.04-2.49), PCT 2-10 versus <0.5 ng/mL: 1.91(1.15-3.16), PCT ≥10 versus <0.5 ng/mL: 2.90(1.84-4.59), high BNP 1.26 (0.89-1.76) and low Alb 0.68 (0.52-0.87). The mortality rate increased as the number of scores (PCT + BNP + Alb) increased. CONCLUSIONS: Concentration-dependent high PCT, high BNP and low Alb were positive risk factors associated with poor prognosis in hospitalized older patients with a risk of infection. Geriatr Gerontol Int 2024; 24: 571-576.

Detection and Analysis of Commonly Used Infection Indicators in Patients with Acute Urticaria.

INTRODUCTION: In this study, we investigated the correlation and clinical significance of peripheral blood leukocytes, neutrophils, C-reactive protein (CRP), and procalcitonin (PCT) in patients with acute urticaria. METHODS: Complete blood count with differential, CRP, and PCT tests were conducted on patients with acute urticaria. A total of 614 patients with acute urticaria were divided into three groups: the first group consisted of patients with elevated leukocyte and neutrophil count, the second group consisted of patients with normal leukocyte and neutrophil count, and the third group consisted of patients with abnormal leukocyte and neutrophil count. A correlation analysis was conducted to investigate the levels of leukocytes, neutrophils, CRP, and PCT in the three groups. RESULTS: The results of Kruskal-Wallis' nonparametric test revealed statistically significant variations in leukocytes, neutrophils, CRP, and PCT among the three groups (p < 0.001). However, CRP and PCT showed no statistically significant differences between the second and third groups (p < 0.001, p = 0.0041, p = 0.0032). Additional multiple comparisons in Spearman correlation analysis indicated statistically significant differences (p = 0.55). Across all groups, there was a statistically significant difference in the correlation between CRP-PCT and leukocytes-neutrophils (p = 0.53). CONCLUSION: Leukocytes and neutrophils are sensitive to the impact of medications and stress on the body. Combining CRP and PCT, as well as routine blood test, may be a comprehensive assessment of infection presence and severity in patients, providing guidance for antibiotic treatment.

Serum procalcitonin improves diagnosis of infectious complications after CRS/HIPEC.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve the survival of selected patients with peritoneal metastasis. A major cause of treatment-related morbidity after CRS/HIPEC is infection and sepsis. HIPEC alters the diagnostic sensitivity and specificity of blood and serum markers and therefore has an impact on early diagnosis of postoperative complications. This study aimed to assess the sensitivity and specificity of blood and serum markers after CRS/HIPEC. METHODS: Patients from two centers, operated between 2009 and 2017, were enrolled in this study. Perioperative blood samples were analyzed for white blood cells (WBC), C-reactive protein (CRP), and procalcitonin (PCT); postoperative complications were graded according to Clavien-Dindo and infectious complications according to CDC criteria. RESULTS: Overall, n=248 patients were included with peritoneal metastasis from different primary tumors treated by CRS/HIPEC. Depending on the applied HIPEC protocol, patients presented a suppressed WBC response to infection. In addition, a secondary and unspecific CRP elevation in absence of an underlining infection, and pronounced after prolonged perfusion for more than 60 min. PCT was identified as a highly specific - although less sensitive - marker to diagnose infectious complications after CRS/HIPEC. DISCUSSION/CONCLUSION: Sensitivity and specificity of WBC counts and CRP values to diagnose postoperative infection are limited in the context of HIPEC. PCT is helpful to specify suspected infection. Overall, diagnosis of postoperative complications remains a clinical diagnosis, requiring surgical expertise and experience.

Characterization of acquired anemia in children by iron metabolism parameters.

Inflammatory states are associated with anemia of chronic disease and acute infection. Hepcidin, a regulator of iron metabolism, is involved in iron pathophysiology during inflammation. We investigated biochemical characteristics in children with anemia from different causes. Four patient groups (n = 38; mean age: 12.44 ± 4.35 years) were studied: (1) inflammatory bowel disease (IBD, 10 patients); (2) iron deficiency anemia (IDA, 12); (3) celiac disease (CD, 8); (4) acute infection (AI, 8). Laboratory measurements were evaluated at diagnosis: blood count, serum iron, transferrin, ferritin, vitamin B12, folic acid, CRP, erythropoietin, hepcidin and soluble transferrin receptor (sTfR). IDA patients had the lowest Hgb (6.9 ± 1.7 g/dL), MCV (63.2 ± 7.2 fL), iron (16.8 ± 13.5 µg/dL), ferritin (4.5 ± 4.5 ng/mL) and hepcidin (3.1 ± 0.8 ng/mL) values, and the highest transferrin and sTfR values. AI patients had the highest ferritin (156.2 ± 124.5 ng/mL), CRP (144.6 ± 94 mg/L) and hepcidin (74.67 ± 12.3 ng/ml) values. Overall, hepcidin levels correlated with CRP and with ferritin (r = 0.83 and 0.85, respectively). Elucidating specific etiology-related biochemical profiles in pediatric patients with anemia from different causes using a combination of laboratory biomarkers, including hepcidin, can help physicians treat the anemia.

Hypogammaglobulinemia and Infections in Patients With Multiple Sclerosis Treated With Rituximab.

BACKGROUND AND OBJECTIVES: To determine the frequency of hypogammaglobulinemia and infections in patients with multiple sclerosis (PwMS) receiving rituximab (RTX). METHODS: This prospective observational study included all consecutive PwMS receiving RTX at the university hospital of Marseille, France, between 2015 and 2020. Patient visits occurred at least every 6 months. RESULTS: We included 188 patients (151 with relapsing-remitting MS; the mean age was 43.4 years [SD 12.9], median disease duration 10 years [range 0-36], median Expanded Disability Status Scale 5 [range 0-8], median follow-up 3.5 years [range 1-5.8], and median number of RTX infusions 5 [range 1-9]). Overall, 317 symptomatic infections and 13 severe infections occurred in 133 of 188 (70.7%) and 11 of 188 (5.9%) patients, respectively. After 4 years, 24.4% of patients (95% CI 18.0-33.1) were free of any infection and 92.0% (95% CI 87.1-97.1) had not experienced a severe infection. At RTX onset, the immunoglobulin G (IgG) level was abnormal in 32 of 188 (17%) patients. After RTX, IgG level was <7, <6, <4 and <2 g/L for 83 (44%), 44 (23.4%), 8 (4.2%) and 1 (0.53%) patients, respectively. The risk of infection was associated with reduced IgG levels (multivariate Cox proportional hazards hazard ratio [HR] = 0.86, 95% CI 0.75-0.98, p = 0.03). The risk of reduced IgG level <6 g/L increased with age (HR = 1.36, 95% CI 1.05-1.75, p = 0.01). DISCUSSION: In PwMS receiving RTX, reduced IgG level was frequent and interacted with the risk of infection.

A systematic review of maternal TORCH serology as a screen for suspected fetal infection.

BACKGROUND: The acronym 'TORCH' refers to well-recognised causes of perinatal infections: toxoplasmosis, rubella, cytomegalovirus (CMV) and herpes simplex virus (HSV). A TORCH serology panel is often used to test for maternal primary infection following detection of ultrasound abnormalities in pregnancy. AIM: This review aims to estimate the diagnostic yield of maternal TORCH serology in pregnancy following fetal ultrasound abnormalities. MATERIALS AND METHODS: Primary studies published since 2000 that assessed maternal TORCH serology for suspected fetal infection and included information on indications for testing, definition of positive TORCH serology results, and perinatal outcomes were included. RESULTS: Eight studies with a total of 2538 pregnancies were included. The main indications for testing were polyhydramnios, fetal growth restriction and hyperechogenic bowel. There were 26 confirmed cases of congenital CMV, of which 15 had multiple ultrasound abnormalities. There were no cases of congenital toxoplasmosis, rubella or HSV confirmed in any of the eight studies. CONCLUSIONS: The clinical utility of TORCH serology for non-specific ultrasound abnormalities such as isolated fetal growth restriction or isolated polyhydramnios is low. It is time to retire the TORCH acronym and the reflex ordering of 'TORCH' panels, as their continued use obscures, rather than illuminates, appropriate investigation for fetal ultrasound abnormalities.

Secondary Immunodeficiency and Risk of Infection Following Immune Therapies in Neurology.

Secondary immunodeficiencies (SIDs) are acquired conditions that may occur as sequelae of immune therapy. In recent years a number of disease-modifying therapies (DMTs) has been approved for multiple sclerosis and related disorders such as neuromyelitis optica spectrum disorders, some of which are frequently also used in- or off-label to treat conditions such as chronic inflammatory demyelinating polyneuropathy (CIDP), myasthenia gravis, myositis, and encephalitis. In this review, we focus on currently available immune therapeutics in neurology to explore their specific modes of action that might contribute to SID, with particular emphasis on their potential to induce secondary antibody deficiency. Considering evidence from clinical trials as well as long-term observational studies related to the patients' immune status and risks of severe infections, we delineate long-term anti-CD20 therapy, with the greatest data availability for rituximab, as a major risk factor for the development of SID, particularly through secondary antibody deficiency. Alemtuzumab and cladribine have relevant effects on circulating B-cell counts; however, evidence for SID mediated by antibody deficiency appears limited and urgently warrants further systematic evaluation. To date, there has been no evidence suggesting that treatment with fingolimod, dimethyl fumarate, or natalizumab leads to antibody deficiency. Risk factors predisposing to development of SID include duration of therapy, increasing age, and pre-existing low immunoglobulin (Ig) levels. Prevention strategies of SID comprise awareness of risk factors, individualized treatment protocols, and vaccination concepts. Immune supplementation employing Ig replacement therapy might reduce morbidity and mortality associated with SIDs in neurological conditions. In light of the broad range of existing and emerging therapies, the potential for SID warrants urgent consideration among neurologists and other healthcare professionals.

Measurable Residual Disease Monitoring of SPAG6, ST18, PRAME, and XAGE1A Expression in Peripheral Blood May Detect Imminent Relapse in Childhood Acute Myeloid Leukemia.

Overexpressed genes may be useful for monitoring of measurable residual disease (MRD) in patients with childhood acute myeloid leukemia (AML) without a leukemia-specific target. The normal expression of five leukemia-associated genes (SPAG6, ST18, MSLN, PRAME, XAGE1A) was defined in children without hematologic disease (n = 53) and children with suspected infection (n = 90). Gene expression at AML diagnosis (n=50) and during follow-up (n = 21) was compared with child-specific reference values. At diagnosis, 34/50 children (68%) had high expression of at least one of the five genes, and so did 16/31 children (52%) without a leukemia-specific target. Gene expression was quantified in 110 peripheral blood (PB) samples (median, five samples/patient; range, 1 to 10) during follow-up in 21 patients with high expression at diagnosis. All nine patients with PB sampling performed within 100 days of disease recurrence displayed overexpression of SPAG6, ST18, PRAME, or XAGE1A at a median of 2 months (range, 0.6 to 9.6 months) before hematologic relapse, whereas MSLN did not reach expression above normal prior to hematologic relapse. Only 1 of 130 (0.8%) follow-up analyses performed in 10 patients in continuous complete remission had transient expression above normal. SPAG6, ST18, PRAME, and XAGE1A expression in PB may predict relapse in childhood AML patients and facilitate MRD monitoring in most patients without a leukemia-specific target.

UPLC-MS/MS Determination of Linezolid and Heme in Plasma of Infected Patients and Correlation Analysis.

Linezolid can cause serious haematological toxicity, such as thrombocytopenia and aneamia. Heme, composed of iron and porphyrin, is an important component of hemoglobin. In order to investigate the relationship between the concentration of linezolid and heme in the plasma of infected patients, a UPLC-MS/MS method that can determine the concentrations of linezolid and heme simultaneously was developed and validated. A total of 96 healthy subjects and 81 infected patients, who received blood routine blood tests, were included and determined by the UPLC-MS/MS method. The results showed that the concentration of linezolid was 5.08 ± 3.46 µg/mL in infected patients who were treated with linezolid. The heme in healthy subjects was 7.05 ± 8.68 µg/mL, and it was significantly decreased to 0.88 ± 0.79 µg/mL in infected patients (P < 0.01). Spearman correlation analysis showed that linezolid had a high negative correlation with platelet (PLT) (R = -0.309). Heme had a high positive correlation with hemoglobin (Hb) (R = 0.249) in healthy subjects and infected patients. The ROC analysis showed that heme had diagnostic value to distinguish low Hb (110 g/L). In conclusion, there was a positive correlation between heme and Hb, and this correlation was also observed in infected patients. A high concentration of linezolid was inclined to decrease PLT. Monitoring of heme and linezolid helps in the early diagnose of low Hb and PLT.

Extra cellular vesicles in blood circulation as biomarkers and messengers of patho-hysiological activity and alterations.

There is an increasing interest in Extracellular Vesicles released by many cells through membrane shedding. In addition to cell signaling, these particles are true messenger cargos, which can carry cell surface proteins, miRNAs and non-coding RNAs to other and distant cells. They are part of the inter-cellular crosstalk and they contribute to transferring biological messages far away from the triggering event. EVs are biomarkers of many diseases, including thrombo-embolic pathology, infections, neurological or metabolic disorders, and malignancy. Their role and significance are presented and discussed in this short review, as consequences of disease and causes of its progression. But they can also be beneficial for tissue healing or repair, and they can be prepared in vitro to be used for cell- targeted treatments. Many identification and measurement methods for EV's are sophisticated, which restricts their use to research studies, but they have, nevertheless, a high laboratory potential for diagnosis, prognosis and evolution as follow-up of many pathologies. New emerging laboratory tools offer more friendly and easy applications for characterizing EVs and testing their associated activity, especially for the procoagulant ones.

The Assessment of Pentraxin 3: A Novel Biomarker in Early Detection of Infection in Newborns.

INTRODUCTION: As the clinical manifestation of neonatal infection is nonspecific and characterised by varied clinical features, it is highly problematic to establish an early diagnosis. Recently, hopes have been raised by the new acute-phase protein-pentraxin 3 (PTX3). PTX3 belongs to the family of long pentraxins, which is synthesized in numerous cells like endothelial cells, macrophages, and monocytes infiltrating sites of inflammation. Material and Methods. In our research, we have enrolled 29 newborns with infection as the study group and 47 healthy ones as the control group, as well as their mothers. The C-reactive protein (CRP), procalcitonin (PCT), and PTX3 levels were determined in venous blood samples from all investigated neonates and their mothers. Moreover, PTX3 concentrations were assessed in the umbilical cord. RESULTS: There were statistically significant differences in PTX3 levels between healthy and sick newborns both in the umbilical cord (p = 0.02) and venous blood (p = 0.01). The highest PTX3 concentrations were observed in children with infection in the presence of premature rupture of membranes (PROM). PTX3 concentrations in this group were significantly higher compared to those in healthy children without PROM. We observed elevated PCT levels in newborns with infection. No differences in CRP levels in 12 hours of life were noticed between the investigated groups. A comparison of ROC curves for PTX3 and PCT concentrations revealed similar sensitivity and specificity in the prediction of infection in neonates. CONCLUSIONS: Serum PTX3 is an important and specific biomarker of early infection. It is already elevated in the umbilical cord, so measuring PTX3 concentration might be useful in the early prediction of infection in newborns.

Long-term mortality due to infection associated with elevated liver enzymes: a population-based cohort study.

We aimed to investigate whether elevated liver enzymes in the adult population were associated with mortality due to infection. As a population-based cohort study, data from the National Health Insurance Service Health Screening Cohort were used. Adult individuals (aged ≥ 40 years) who underwent standardized medical examination between 2002 and 2003 were included, and infectious mortality was defined as mortality due to infection between 2004 and 2015. Aspartate transaminase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), AST/ALT ratio, and dynamic AST/ALT ratio (dAAR) were included in multivariable Cox modeling. A total of 512,746 individuals were included in this study. Infectious mortality occurred in 2444 individuals (0.5%). In the multivariable model, moderate and severe elevation in AST was associated with 1.94-fold [hazard ratio (HR):1.94, 95% confidence interval (CI) 1.71-2.19; P < 0.001] and 3.93-fold (HR: 3.93, 95% CI 3.05-5.07; P < 0.001) higher infectious mortality respectively, compared with the normal AST group. Similar results were observed for moderate and severe elevation in ALT and mild, moderate, and severe elevation in γ-GTP. Additionally, a 1-point increase in the AST/ALT ratio and dAAR was associated with higher infection mortality. Elevated liver enzymes (AST, ALT, AST/ALT ratio, γ-GTP, and dAAR) were associated with increased infectious mortality.

Editor's Choice - Validation of the Management of Aortic Graft Infection Collaboration (MAGIC) Criteria for the Diagnosis of Vascular Graft/Endograft Infection: Results from the Prospective Vascular Graft Cohort Study.

OBJECTIVE: The timely management of vascular graft/endograft infection (VGEI) is crucial to a favourable outcome, yet can be challenging as there is no validated gold standard diagnostic test. Recently, a new case definition has been proposed by the Management of Aortic Graft Infection Collaboration (MAGIC) to close the diagnostic gap. The aim of this study was to validate the MAGIC criteria as a suggested diagnostic standard for the diagnosis of suspected VGEI in the prospective Vascular Graft Cohort study (VASGRA). METHODS: VASGRA is an open, prospective, observational cohort study. Prospective participants in VASGRA between 2013 and 2019 were included (257 patients; 137 with VGEI). The accuracy of the MAGIC criteria for a diagnosis of VGEI was evaluated retrospectively by calculating the sensitivity and specificity vs. the consensually adjudicated VASGRA infection status. RESULTS: The VASGRA cohort categorised 137 (53.3%) patients as "diseased" and 120 patients as "not diseased"; using the MAGIC criteria, 183/257 (71.2%) patients were considered to be "diseased". Thus, for the MAGIC criteria, a sensitivity of 99% (95% confidence interval [CI] 96-100) and a specificity of 61% (95% CI 52-70) were calculated. Considering suspected VGEI according to the MAGIC criteria as "not diseased" achieved congruent assessments of the VASGRA team and the MAGIC criteria, with a sensitivity of 93% and a specificity of 93%. The accuracy of the MAGIC criteria for the different graft locations were also compared. If the suspected VGEIs were assigned to the "not diseased" group, VGEIs of the thoracic aorta seemed to have a poorer sensitivity (86%; 95% CI 73-95) than the other graft locations. CONCLUSION: The current MAGIC criteria offer good sensitivity and specificity in the context of true infections but a reduced specificity for a possible VGEI.

Prehospital troponin as a predictor of early clinical deterioration.

BACKGROUND AND OBJECTIVES: Elevated troponin T (cTnT) values are associated with comorbidities and early mortality, in both cardiovascular and noncardiovascular diseases. The objective of this study is to evaluate the prognostic accuracy of the sole utilization of prehospital point-of-care cardiac troponin T to identify the risk of early in-hospital deterioration, including mortality within 28 days. METHODS: We conducted a prospective, multicentric, controlled, ambulance-based, observational study in adults with acute diseases transferred with high priority by ambulance to emergency departments, between 1 January and 30 September 2020. Patients with hospital diagnosis of acute coronary syndrome were excluded. The discriminative power of the predictive cTnT was assessed through a discrimination model trained using a derivation cohort and evaluated by the area under the curve of the receiver operating characteristic on a validation cohort. RESULTS: A total of 848 patients were included in our study. The median age was 68 years (25th-75th percentiles: 50-81 years), and 385 (45.4%) were women. The mortality rate within 28 days was 12.4% (156 cases). The predictive ability of cTnT to predict mortality presented an area under the curve of 0.903 (95% CI: 0.85-0.954; P < .001). Risk stratification was performed, resulting in three categories with the following optimal cTnT cut-off points: high risk greater than or equal to 100, intermediate risk 40-100 and low risk less than 40 ng/L. In the high-risk group, the mortality rate was 61.7%, and on the contrary, the low-risk group presented a mortality of 2.3%. CONCLUSIONS: The implementation of a routine determination of cTnT on the ambulance in patients transferred with high priority to the emergency department can help to stratify the risk of these patients and to detect unknown early clinical deterioration.

Decreased Peripheral Naïve T Cell Number and Its Role in Predicting Cardiovascular and Infection Events in Hemodialysis Patients.

Patients with end-stage renal disease (ESRD) are at high risk of morbidity and mortality from cardiovascular and infectious diseases, which have been found to be associated with a disturbed immune response. Accelerated T-cell senescence is prevalent in these patients and considered a significant factor contributing to increased risk of various morbidities. Nevertheless, few studies have explicated the relevance of T-cell senescence to these fatal morbidities in ESRD patients. In this study, we designed a longitudinal prospective study to evaluate the influence of T-cell senescence on cardiovascular events (CVEs) and infections in hemodialysis (HD) patients. Clinical outcomes of 404 patients who had been on HD treatment for at least 6 months were evaluated with respect to T-cell senescence determined using flow cytometry. We found that T-cell senescence was associated with systemic inflammation. High-sensitivity C-reactive protein was positively associated with decreased naïve T cell levels. Elevated tumor necrosis factor-α and interleukin 6 levels were significantly associated with lower central memory T cell and higher T effector memory CD45RA cell levels. Decreased CD4+ naïve T cell count was independently associated with CVEs, whereas decreased CD8+ naïve T cell count was independently associated with infection episodes in HD patients. In conclusion, HD patients exhibited accelerated T-cell senescence, which was positively related to inflammation. A reduction of naïve T cell could be a strong predictor of CVEs and infection episodes in HD patients.

Transcriptome and IgH Repertoire Analyses Show That CD11chi B Cells Are a Distinct Population With Similarity to B Cells Arising in Autoimmunity and Infection.

A distinct B cell population marked by elevated CD11c expression is found in patients with systemic lupus erythematosus (SLE). Cells with a similar phenotype have been described during chronic infection, but variable gating strategies and nomenclature have led to uncertainty of their relationship to each other. We isolated CD11chi cells from peripheral blood and characterized them using transcriptome and IgH repertoire analyses. Gene expression data revealed the CD11chi IgD+ and IgD- subsets were highly similar to each other, but distinct from naive, memory, and plasma cell subsets. Although CD11chi B cells were enriched in some germinal center (GC) transcripts and expressed numerous negative regulators of B cell receptor (BCR) activation, they were distinct from GC B cells. Gene expression patterns from SLE CD11chi B cells were shared with other human diseases, but not with mouse age-associated B cells. IgH V-gene sequencing analysis showed IgD+ and IgD- CD11chi B cells had somatic hypermutation and were clonally related to each other and to conventional memory and plasma cells. However, the IgH repertoires expressed by the different subsets suggested that defects in negative selection during GC transit could contribute to autoimmunity. The results portray a pervasive B cell population that accumulates during autoimmunity and chronic infection and is refractory to BCR signaling.