Elevated plasma interleukin-8 as a risk factor for mortality in children presenting with cerebral malaria.

BACKGROUND: Cerebral malaria (CM) is a neuropathology which remains one of the deadliest forms of malaria among African children. The kinetics of the pathophysiological mechanisms leading to neuroinflammation and the death or survival of patients during CM are still poorly understood. The increasing production of cytokines, chemokines and other actors of the inflammatory and oxidative response by various local actors in response to neuroinflammation plays a major role during CM, participating in both the amplification of the neuroinflammation phenomenon and its resolution. In this study, we aimed to identify risk factors for CM death among specific variables of inflammatory and oxidative responses to improve our understanding of CM pathogenesis. METHODS: Children presenting with CM (n = 70) due to P. falciparum infection were included in southern Benin and divided according to the clinical outcome into 50 children who survived and 20 who died. Clinical examination was complemented by fundoscopic examination and extensive blood biochemical analysis associated with molecular diagnosis by multiplex PCR targeting 14 pathogens in the patients' cerebrospinal fluid to rule out coinfections. Luminex technology and enzyme immunoassay kits were used to measure 17 plasma and 7 urinary biomarker levels, respectively. Data were analysed by univariate analysis using the nonparametric Mann‒Whitney U test and Pearson's Chi2 test. Adjusted and multivariate analyses were conducted separately for plasma and urinary biomarkers to identify CM mortality risk factors. RESULTS: Univariate analysis revealed higher plasma levels of tumour necrosis factor (TNF), interleukin-1beta (IL-1ß), IL-10, IL-8, C-X-C motif chemokine ligand 9 (CXCL9), granzyme B, and angiopoietin-2 and lower urinary levels of prostanglandine E2 metabolite (PGEM) in children who died compared to those who survived CM (Mann-Whitney U-test, P-values between 0.03 and < 0.0001). The multivariate logistic analysis highlighted elevated plasma levels of IL-8 as the main risk factor for death during CM (adjusted odd ratio = 14.2, P-value = 0.002). Values obtained during follow-up at D3 and D30 revealed immune factors associated with disease resolution, including plasma CXCL5, C-C motif chemokine ligand 17 (CCL17), CCL22, and urinary 15-F2t-isoprostane. CONCLUSIONS: The main risk factor of death during CM was thus elevated plasma levels of IL-8 at inclusion. Follow-up of patients until D30 revealed marker profiles of disease aggravation and resolution for markers implicated in neutrophil activation, endothelium activation and damage, inflammatory and oxidative response. These results provide important insight into our understanding of CM pathogenesis and clinical outcome and may have important therapeutic implications.

Prognostic Biomarkers in Melanoma: Tailoring Treatments to the Patient.

BACKGROUND: It is often difficult to accurately predict how a melanoma will progress because melanomas can be so diverse in their genetic and histological makeup. OBJECTIVE: We sought to characterize the current state and progression of biomedical markers towards their utilization as prognostic indicators for patients with melanoma. METHODS: A literature search of the research repository databases PubMed and GoogleScholar was conducted using the following inclusion criteria: (1) published within the last 10 years, and (2) use of overall survival, disease progression, or clinical outcome as primary endpoints. Search terms included various permutations of "biomarkers," "prognostic," "immunologic," "serologic," "visual," and "melanoma." Results were evaluated for statistical power, results significance, and experimental design integrity. RESULTS: The prognostic capabilities of clinical tests for malignant melanoma have made great strides in the last few years, with several serologic and immunohistochemical biomarkers being preliminarily linked to various measures of clinical prognosis. While clinical feasibility of a single sensitive and specific biomarker remains unfeasible, use of select combinations of tested biomarkers remain viable. CONCLUSION: Diagnostic and prognostic genetic assays have begun to cross over from research to commercial application, giving physicians additional tools during the early stages of diagnosis to optimize and individualize treatments.

Presence of multiple abnormal immunologic markers is an independent prognostic factor of diffuse large B-cell lymphoma.

Autoimmune diseases (ADs) increase the risk of non-Hodgkin's lymphoma and contribute to poor prognosis of patients. However, the association between immunologic markers and clinical outcome has rarely been investigated. This study aims to analyze the prognostic value of pretreatment immunologic markers in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed the data on 502 patients with DLBCL treated in our institution from January 2013 to March 2018. Survival functions were estimated using Kaplan-Meier method and Cox regression model. The 3-year progression free survival (PFS) and overall survival (OS) rates were 70.2% and 80.9%, respectively, and the complete remission (CR) rate was 78.1%. Among the patients, those with multiple ( ⩾ 3) abnormal immunologic markers had significantly shorter 3-year PFS (52.7% vs. 77.3%, P < 0.001) and OS (68.5% vs. 85.8%, P = 0.001) than those without multiple abnormal immunologic markers. Multivariate analysis revealed that the presence of multiple abnormal immunologic markers and the elevated serum levels of lactate dehydrogenase were the independent adverse prognostic factors for PFS (P = 0.008, P < 0.001) and OS (P = 0.003, P < 0.001). Meanwhile, advanced Ann Arbor stage was an independent adverse prognostic factor for PFS (P = 0.001) and age > 60 years for OS (P = 0.014). In conclusion, the immunologic status was closely related to lymphoma progression, and this study provides new insights into the risk stratification of patients with DLBCL.

Presence of multiple abnormal immunologic markers is an independent prognostic factor of diffuse large B-cell lymphoma / 医学前沿

Autoimmune diseases (ADs) increase the risk of non-Hodgkin's lymphoma and contribute to poor prognosis of patients. However, the association between immunologic markers and clinical outcome has rarely been investigated. This study aims to analyze the prognostic value of pretreatment immunologic markers in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed the data on 502 patients with DLBCL treated in our institution from January 2013 to March 2018. Survival functions were estimated using Kaplan-Meier method and Cox regression model. The 3-year progression free survival (PFS) and overall survival (OS) rates were 70.2% and 80.9%, respectively, and the complete remission (CR) rate was 78.1%. Among the patients, those with multiple ( ⩾ 3) abnormal immunologic markers had significantly shorter 3-year PFS (52.7% vs. 77.3%, P 60 years for OS (P = 0.014). In conclusion, the immunologic status was closely related to lymphoma progression, and this study provides new insights into the risk stratification of patients with DLBCL.

Procalcitonin: The marker of pediatric bacterial infection.

Timely recognition of systemic bacterial infections in pediatric care setting is the basis for effective treatment and control. This review provides an overview of procalcitonin (PCT) as an early marker for the detection of severe, invasive bacterial infection in children. Almost all articles on biochemical property and clinical studies in PubMed and Scopus databases regarding their use in pediatric infections and the use of PCT as a marker of bacterial infections were examined. Various methods and analyzers are currently available for the evaluation of PCT. Employment of PCT in the identification of neonatal bacterial infection is a complex process in some conditions. Age specific cut-off, underlying syndrome, and maternal antibiotics usage should be considered when PCT is to be applied in neonates. PCT might be false-negative in these conditions. However, if used appropriately, it can lead to a higher specificity than other immunologic markers. Due to its correlation with the severity of infection, PCT can consequently be used as a prognostic indicator especially for sepsis and urinary tract infection. It is, therefore, a practical supplementary means for the identification of bacterial infections in pediatric health settings.

The Utility of Immunological Markers and Pulmonary Function Test in the Early Diagnosis of Pulmonary Involvement in the Patients with Rheumatoid Arthritis / 결핵

BACKGROUND: It is reported that frequency of pulmonary involvement in the patients with rheumatoid arthritis reaches 10 to 50% and pulmonary involvement is a principal cause of death. As immunology and radiology has developed, interest for the early diagnosis of pulmonary involvement is increasing. METHOD: Among the patients at Hanyang University Hospital from March, 1990 to July, 1995, we compared the 29 patients having pulmonary involvement with the 18 patients controls in clinical and chest high resolution computed tomography(HRCT) findings by immunological markers and findings of pulmonary function test. We sought useful markers for early diagnosis of pulmonary involvement with noninvasive investigations. RESULTS: The ratio of males to females was 14: 15 in the group of pulmonary involvement, and all of the 18 patients were females in the control group. Smoking history was 31%(9/29) in the former group and none in the latter group. Rheumatoid factor(RF) was positive in 96.5%(28/29) of the pulmonary involvement group and in 100%(18/18) of the control group(p=0.12). Antiperinuclear factor(APF) showed a significant difference: 86.9%(20/23, average value: 2.0) was positive in the pulmonary involvement group and 50%(8/16, average value: 1.1) in the control group(p=0.04). Antinuclear antibody(ANA) was positive in 60.7%(17/28) of the pulmonary involvement group and in 72.2%(13/18) of the control group(p=0.33). Cryoglobulin, also showed a significant difference: 72%(18/25) in the pulmonary involvement group was positive and 56.2% (9/16) in the control group was positive(p=0.02). Bony erosion was positive in 61.5%(16/26) of the pulmonary involvement group and in 77.7%(14/18) of the control group(p=0.8). On the pulmonary function test, the average value of alveolar volume corrected diffusion capacity and residual volume in the pulmonary involvement group and in the control group were 1.07mmol/min/KPa(predicted value: 64.2%), 1.32L(predicted value: 70%)and 1.44mmol/min/KPa, 3.75L(predicted value: 86.6%), respectively(p=0.003, p=0.004), showing a significant difference. CONCLUSION: APF or cryoglobulin on the serological test, the measurement of residual volume and alveolar volume corrected diffusion capacity may be used as effective markers in the diagnosis of pulmonary involvement of the patients with rheumatoid arthritis.