Influence of Pathogen Type on Neonatal Sepsis Biomarkers

Understanding immunoregulation in newborns can help to determine the pathophysiology of neonatal sepsis and will contribute to improve the diagnosis, prognosis, and treatment and remains an urgent and unmet medical need to understand hyperinflammation or hypoinflammation associated with sepsis in newborns. This study included infants (up to 4 days old). The “sepsis” criteria was a positive blood culture. C-reactive protein demonstrates a strong dependence on the pathogen etiology. Therefore, its diagnostic odds ratio in Gram-positive bacteremia was 2.7 and the sensitivity was 45%, while Gram-negative was 15.0 and 81.8%, respectively. A neutrophil-lymphocyte ratio above 1 and thrombocytopenia below 50 ∗ 109 cells/L generally do not depend on the type of pathogen and have a specificity of 95%; however, the sensitivity of these markers is low. nCD64 demonstrated good analytical performance and was equally discriminated in both Gram (+) and Gram (−) cultures. The sensitivity was 87.5–89%, and the specificity was 65%. The HLA-DR and programmed cell death protein study found that activation-deactivation processes in systemic infection is different at points of application depending on the type of pathogen: Gram-positive infections showed various ways of activation of monocytes (by reducing suppressive signals) and lymphocytes (an increase in activation signals), and Gram-negative pathogens were most commonly involved in suppressing monocytic activation. Thus, the difference in the bacteremia model can partially explain the problems with the high variability of immunologic markers in neonatal sepsis.

Association between immunologic markers and cirrhosis in individuals with chronic hepatitis B

Host immune response and chronic inflammation associated with chronic hepatitis B virus (HBV) infection play a key role in the pathogenesis of liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). We sampled 175 HCC, 117 cirrhotic and 165 non-cirrhotic controls from a prospective cohort study of chronically HBV-infected individuals. Multivariable polytomous logistic regression and canonical discriminant analysis (CDA) were used to compare baseline plasma levels for 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. Leave-one-out cross validation was used to generate receiver operating characteristic curves to compare the predictive ability of marker groups. After multivariable adjustment, HGF (Q4v1OR: 3.74; p-trend = 0.0001), SLAMF1 (Q4v1OR: 4.07; p-trend = 0.0001), CSF1 (Q4v1OR: 3.00; p-trend = 0.002), uPA (Q4v1OR: 3.36; p-trend = 0.002), IL-8 (Q4v1OR: 2.83; p-trend = 0.004), and OPG (Q4v1OR: 2.44; p-trend = 0.005) were all found to be associated with cirrhosis development compared to controls; these markers predicted cirrhosis with 69% accuracy. CDA analysis identified a nine marker model capable of predicting cirrhosis development with 79% accuracy. No markers were significantly different between HCC and cirrhotic participants. In this study, we assessed immunologic markers in relation to liver disease in chronically-HBV infected individuals. While validation in required, these findings highlight the importance of immunologic processes in HBV-related cirrhosis.

Plasma markers of neurologic injury and systemic inflammation in individuals with self-reported neurologic post-acute sequelae of SARS-CoV-2 infection (PASC)

Background: The biologic mechanisms underlying neurologic post-acute-sequelae of SARS-CoV-2 infection (PASC) are incompletely understood. Methods: We measured markers of neuronal injury (glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) and soluble markers of inflammation among a cohort of people with prior confirmed SARS-CoV-2 infection at early and late recovery following the initial illness (defined as less than and greater than 90 days, respectively). The primary clinical outcome was the presence of self-reported central nervous system (CNS) PASC symptoms during the late recovery timepoint. We compared fold-changes in marker values between those with and without CNS PASC symptoms using linear mixed effects models and examined relationships between neurologic and immunologic markers using rank linear correlations. Results: Of 121 individuals, 52 reported CNS PASC symptoms. During early recovery, those who went on to report CNS PASC symptoms had elevations in GFAP (1.3-fold higher mean ratio, 95% CI 1.04-1.63, p=0.02), but not NfL (1.06-fold higher mean ratio, 95% CI 0.89-1.26, p=0.54). During late recovery, neither GFAP nor NfL levels were elevated among those with CNS PASC symptoms. Although absolute levels of NfL did not differ, those who reported CNS PASC symptoms demonstrated a stronger downward trend over time in comparison to those who did not report CNS PASC symptoms (p=0.041). Those who went on to report CNS PASC also exhibited elevations in IL-6 (48% higher during early recovery and 38% higher during late recovery), MCP-1 (19% higher during early recovery), and TNF-alpha (19% higher during early recovery and 13% higher during late recovery). GFAP and NfL correlated with levels of several immune activation markers during early recovery; these correlations were attenuated during late recovery. Conclusions: Self-reported neurologic symptoms present >90 days following SARS-CoV-2 infection are associated with elevations in markers of neurologic injury and inflammation at early recovery timepoints, suggesting that early injury can result in long-term disease. The correlation of GFAP and NfL with markers of systemic immune activation suggests one possible mechanism that might contribute to these symptoms. Additional work is needed to better characterize these processes and to identify interventions to prevent or treat this condition.

Evaluation of GATA4 Gene Expression in Ventricular Septal Defects Patients with Pneumonia

Background: GATA-binding protein 4 (GATA4) can regulate vital genes, such as troponin C, and play an important role in cardiac formation and immune response maturation. Objectives: In this study, GATA4 gene expression was evaluated in two groups of ventricular septal defect (VSD) patients with pneumonia and healthy cases. Methods: This case-control study evaluated GATA4 gene expression by real-time polymerase chain reaction in 80 participants and statically estimated the association between GATA4 expression and immunologic markers, such as immunoglobulin M, immunoglobulin A, mean corpuscular hemoglobin, white blood cell neutrophil, lymphocyte, and number of abortions in mothers of VSD patients with pneumonia. Results: According to the results, there was a significant relationship between mean birth weight and neutrophil-to-lymphocyte ratio with GATA4 gene expression in the case group (P < 0.05). Conclusions: It can be concluded that GATA4 gene expression, especially in patients with VSD, can indicate their susceptibility to pneumonia.

Association Between Immunologic Markers And Cirrhosis In Individuals With Chronic Hepatitis B

Background: Host immune response and chronic inflammation associated with chronic hepatitis B virus (HBV) infection play a key role in the pathogenesis of liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Methods: We sampled 175 HCC, 117 cirrhotic and 165 non-cirrhotic controls from a prospective cohort study of chronically HBV-infected individuals. Multivariable polytomous logistic regression and canonical discriminant analysis (CDA) were used to compare baseline plasma levels for 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. Leave-one-out cross validation was used to generate receiver operating characteristic curves to compare the predictive ability of marker groups. Results: After multivariable adjustment, HGF (Q4v1OR:3.74;p-trend=0.0001), SLAMF1 (Q4v1OR:4.07;p-trend=0.0001), CSF1 (Q4v1OR:3.00;p-trend=0.002), uPA (Q4v1OR:3.36;p-trend=0.002), IL-8 (Q4v1OR:2.83;p-trend=0.004), and OPG (Q4v1OR:2.44;p-trend=0.005) were all found to be associated with cirrhosis development compared to controls; these markers predicted cirrhosis with 69% accuracy. CDA analysis identified a nine marker model capable of predicting cirrhosis development with 79% accuracy. No markers were significantly different between HCC and cirrhotic participants. Conclusion: This is the first prospective study to assess immunologic markers in relation to liver disease in chronically-HBV infected individuals. While validation in required, these findings highlight the importance of immunologic processes in HBV-related cirrhosis.

Immune Response to SARS-CoV-2 in an Asymptomatic Pediatric Allergic Cohort

Disease-specific COVID-19 pediatric comorbidity has not been studied effectively to date. Atopy and food anaphylaxis disease states require improved characterization of SARS-CoV-2 infection risk. To provide the first such characterization, we assessed serum samples of a highly atopic, food anaphylactic, asymptomatic pediatric cohort from across the US during the height of the pandemic. From our biobank, 172 pediatric patient serum samples were characterized specific to atopic, food anaphylactic, and immunologic markers in the US at the beginning of the pandemic, from 1 February to 20 April 2020. Clinical and demographic data were further analyzed in addition to sample analysis for SARS-CoV-2 IgM and IgG ELISA. SARS-CoV-2 antibody results were positive in six patients (4%). Nearly half of the pediatric patients had a history of asthma (49%). Total IgE, total IgG, and IgG1-3 were similar in those positive and negative to SARS-CoV-2. Median total IgG4 in the SARS-CoV-2 positive group was nearly three times (p-value = 0.02) that of the negative group. Atopy controller medications did not confer additional benefit. Our data suggest that food anaphylaxis and highly atopic children are not at increased risk for SARS-CoV-2 seropositivity. This specific population appears either at equal or potentially less risk than the general population. Total and specific IgG4 may be a novel predictor of SARS-CoV-2 infection risk specific to the allergic pediatric population.

Primary synchronous ipsilateral renal fibrosarcoma and renal pelvic carcinoma: a case report and literature review

BackgroundRenal fibrosarcoma is a rare tumor, with only a few cases reported so far, and simultaneous occurrence of ipsilateral renal fibrosarcoma and renal pelvic carcinoma in a patient is extraordinarily rare.Case presentationA 66-year-old man admitted to our hospital with right renal percutaneous nephrostomy and recurrent fever. And the patient underwent laparoendoscopic nephrectomy and partial ureterectomy for pyonephrotic nonfunctioning kidneys. Postoperative pathology showed fibrosarcoma of right kidney and carcinoma of the renal pelvis.ConclusionsThis is the first case of simultaneous occurrence of ipsilateral renal fibrosarcoma and renal pelvic carcinoma in a patient. The diagnosis of fibrosarcoma is one of ultimate immunohistologic exclusion, because there are no specific immunologic markers for fibroblasts. The most common primary treatment for localized disease is radical surgery plus adjuvant chemotherapy.