scholarly journals IL-16 and BCA-1 Serum Levels Are Associated with Disease Severity of C. difficile Infection

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 631
Author(s):  
Dor Gotshal ◽  
Maya Azrad ◽  
Zohar Hamo ◽  
Orna Nitzan ◽  
Avi Peretz

Clostridioides difficile infection (CDI) is associated with a high risk for complications and death, which requires identifying severe patients and treating them accordingly. We examined the serum level of six cytokines and chemokines (IL-16, IL-21, IL-23, IL-33, BCA-1, TRAIL) and investigated the association between them and patients’ disease severity. Concentrations of six cytokines and chemokines were measured using the MILLIPLEX®MAP kit (Billerica, MA, USA) in serum samples attained from CDI patients within 24–48 h after laboratory confirmation of C. difficile presence. Demographic and clinical data were collected from medical records. The disease severity score was determined according to guidelines of the “Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America” (SHEA-IDSA). Out of 54 patients, 20 (37%) had mild to moderate disease and 34 (63%) had severe disease. IL-16 (p = 0.005) and BCA-1 (p = 0.012) were associated with a more severe disease. In conclusion, IL-16 and BCA-1, along with other cytokines and chemokines, may serve as biomarkers for the early prediction of CDI severity in the future. An improved and more accessible assessment of CDI severity will contribute to the adjustment of the medical treatment, which will lead to a better patient outcome.

2020 ◽  
Author(s):  
Dor Gotshal ◽  
Maya Azrad ◽  
Zohar Hamo ◽  
Orna Nitzan ◽  
Avi Peretz

Abstract Background: Clostridioides difficile infection (CDI) have a high risk for complications up to death which requires identifying patients with severe disease and treating them accordingly. We examined the serum level of 6 cytokines and chemokines (IL-6, IL-21, IL-23, IL-33, BCA-1, TRAIL) and we checked the correlation between them to the patients' clinical characteristics and the bacterial strain.Methods: Concentrations of 6 cytokines and chemokines were measured using the MILLIPLEX®MAP kit (Billerica, USA) based on the Luminex xMAP® technology, in serum samples, attained from 54 CDI patients within a median time of 24-48 hours after laboratory confirmation of C. difficile presence. The demographic and clinical data were retrospectively collected from medical records. Disease severity score was determined according to the guidelines of the "Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America" (SHEA-IDSA).Results: Out of 54 patients (mean age, 76.6 years, 61.1% female), 20 (37%) had mild to moderate disease and 34 (63%) had severe disease. Two immunological markers were associated with a more severe disease: IL-16 (p = 0.005) and BCA-1 (p = 0.012). The study didn’t show a correlation between the immunological markers to the gender, the type of toxin which produced by the bacteria, in hospital mortality and infection acquisition.Conclusions: cytokines and chemokines may serve as a biomarker for early prediction of CDI severity in the future. Improved and more accessible assessment of CDI severity will contribute to adjustment of the medical treatment which will lead to a better patient outcome and hopefully will reduce the patient's mortality.


2019 ◽  
Vol 7 (10) ◽  
pp. 435 ◽  
Author(s):  
Hamo ◽  
Azrad ◽  
Nitzan ◽  
Peretz

The high risk of complications and death following Clostridioides difficile infection (CDI) requires identifying patients with severe disease and treating them accordingly. We characterized the immune response of CDI patients in relation to infection severity. Concentrations of 28 cytokines and chemokines were measured in serum samples, obtained from 54 CDI patients within a median timeframe of 24–48 h after laboratory confirmation of C. difficile infection. Demographic and clinical data were retrospectively collected from medical records. Disease severity score was determined by “Score indices for Clostridioides difficile infection severity”. Of 54 patients (mean age, 76.6 years, 61.1% female), 38 (70.4%) had mild disease and 16 (29.6%) had moderate disease. Seven cytokines were associated with a more severe CDI: granulocyte-macrophage colony-stimulating factor (p = 0.0106), interleukin (IL)-1β (p = 0.004), IL-8 (p = 0.0098), IL-12p70 (p = 0.0118), interferon-α (p = 0.0282), IL-15 (p = 0.0015), and IL-2 (p = 0.0031). Additionally, there was an increased T-helper 1 response in more severe cases of CDI. Cytokines may serve as biomarkers for early prediction of CDI severity. Better and earlier assessment of illness severity will contribute to the adjustment of medical treatment, including monitoring and follow-up.


2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S50-S50
Author(s):  
Abhishek Verma ◽  
Sanskriti Varma ◽  
Daniel Freedberg ◽  
David Hudesman ◽  
Shannon Chang ◽  
...  

Abstract Background Guidelines recommend testing inflammatory bowel disease (IBD) patients hospitalized with flare for Clostridioides difficile infection (CDI), though little is known about whether a delay in testing for CDI is related to adverse outcomes. We examined the relationship between time-to-C. difficile PCR test order, collection, and result with adverse IBD outcomes. Methods We performed a retrospective cohort study of IBD patients hospitalized with flare through the emergency department (ED) between 2013 and 2020 at an urban academic medical center. The time from ED presentation to C. difficile test order (time-to-order), sample collection (time-to-collection), and test result (time-to-result) were collected. Time-to-result was stratified by within 6 hours, 6–24 hours, and 24 hours or longer. The primary outcome was length of stay (LOS). Secondary outcomes were inpatient anti-TNF administration and surgery. We used hemodynamic and laboratory values at presentation to evaluate disease severity as a confounding variable between length of stay and time-dependent variables. Results We identified 122 IBD patients hospitalized with flare. There were no significant differences in baseline characteristics among time-to-result groups. Despite a shorter time-to-result, the average LOS in the 6 hours group was 7.3 days, longer compared to the 6–24 hours group (4.3 days, p=0.018) and the 24 hours group (4.2 days, p=0.035; Table 1). There were no differences in inpatient anti-TNF administration (p=0.10) or surgery (p=0.08) among time-to-result groups. The markers of disease severity that correlated with longer LOS were C-reactive protein (CRP) (0.28 days, p=0.003), heart rate (0.478 days, p<0.001), diastolic hypotension (0.228 days, p=0.01), and hypoalbuminemia (0.215 days, p=0.02). Higher CRP correlated with earlier time-to-result (-0.218 hours, p=0.02). Patients with more markers of disease severity had earlier times-to-result (12.8 hours vs. 32.2 hours, p=0.014) and had a longer LOS (7.9 vs. 3.4 days, p=0.007) (Table 2). Patients with more severe disease had an earlier time-to-order (4.48 hours) compared to those with less severe disease (17.4 hours), though this difference did not meet statistical significance (p=0.09; Table 2). Conclusion Earlier time-to-result for CDI is associated with longer LOS in IBD patients hospitalized with flare. This inverse relationship is confounded by disease severity at presentation: patients with more severe disease have a shorter time-to-result and a longer LOS. It may be that these patients produce a stool sample more readily; however, the near significance of differences in time-to-order among severity groups suggest a role for provider bias, which must be studied further. Delay in testing was not associated with higher rates of inpatient anti-TNF administration or surgery.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S811-S812 ◽  
Author(s):  
Johanna Sandlund ◽  
Joel Estis ◽  
Phoebe Katzenbach ◽  
Niamh Nolan ◽  
Kirstie Hinson ◽  
...  

Abstract Background Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections, resulting in significant morbidity, mortality, and economic burden. Diagnosis of CDI relies on the assessment of clinical presentation and laboratory tests. We have evaluated the clinical performance of ultrasensitive Single Molecule Counting technology for detection of C. difficile toxins A and B. Methods Stool specimens from 298 patients with suspected CDI were tested with nucleic acid amplification test (NAAT; BD MAX™ Cdiff assay or Xpert® C. difficile assay) and Singulex Clarity® C. difficile toxins A/B assay. Specimens with discordant results were tested with cell cytotoxicity neutralization assay (CCNA), and results were correlated with disease severity and outcome. Results There were 64 NAAT-positive and 234 NAAT-negative samples. Of the 32 NAAT+/Clarity− and 4 NAAT-/Clarity+ samples, there were 26 CCNA− and 4 CCNA- samples, respectively. CDI relapse or overall death was more common in NAAT+/toxin+ patients than in NAAT+/toxin− and NAAT−/toxin− patients, and NAAT+/toxin+ patients were 3.7 times more likely to experience relapse or death (Figure 1). The clinical specificity of Clarity and NAAT was 97.4% and 89.0%, respectively, and overdiagnosis was over three times more common in NAAT+/toxin− than in NAAT+/toxin+ patients (Figure 2). Negative percent agreement between NAAT and Clarity was 98.3%, and positive percent agreement increased from 50.0% to effective 84.2% and 94.1% after CCNA testing and clinical assessment. Conclusion The Clarity assay was superior to NAATs in diagnosis of CDI, by reducing overdiagnosis and thereby increasing clinical specificity, and presence of toxins was associated with disease severity and outcome. Disclosures All authors: No reported disclosures.


Dermatology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Jesper Grønlund Holm ◽  
Guillem Hurault ◽  
Tove Agner ◽  
Maja Lisa Clausen ◽  
Sanja Kezic ◽  
...  

Background: A growing body of evidence links various biomarkers to atopic dermatitis (AD). Still, little is known about the association of specific biomarkers to disease characteristics and severity in AD. Objective: To explore the relationship between various immunological markers in the serum and disease severity in a hospital cohort of AD patients. Methods: Outpatients with AD referred to the Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark, were divided into groups based on disease severity (SCORAD). Serum levels of a preselected panel of immunoinflammatory biomarkers were tested for association with disease characteristics. Two machine learning models were developed to predict SCORAD from the measured biomarkers. Results: A total of 160 patients with AD were included; 53 (33.1%) with mild, 73 (45.6%) with moderate, and 34 (21.3%) with severe disease. Mean age was 29.2 years (range 6–70 years) and 84 (52.5%) were females. Numerous biomarkers showed a statistically significant correlation with SCORAD, with the strongest correlations seen for CCL17/thymus and activation-regulated chemokine (chemokine ligand-17/TARC) and CCL27/cutaneous T cell-attracting-chemokine (CTACK; Spearman R of 0.50 and 0.43, respectively, p < 0.001). Extrinsic AD patients were more likely to have higher mean SCORAD (p < 0.001), CCL17 (p < 0.001), CCL26/eotaxin-3 (p < 0.001), and eosinophil count (p < 0.001) than intrinsic AD patients. Predictive models for SCORAD identified CCL17, CCL27, serum total IgE, IL-33, and IL-5 as the most important predictors for SCORAD, but with weaker associations than single cytokines. Conclusions: Specific immunoinflammatory biomarkers in the serum, mainly of the Th2 pathway, are correlated with disease severity in patients with AD. Predictive models identified biomarkers associated with disease severity but this finding warrants further investigation.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Maria Abreu ◽  
Marta Miranda ◽  
Mafalda Castro ◽  
Iolanda Fernandes ◽  
Renata Cabral ◽  
...  

The itch associated with cutaneous T-cell lymphoma (CTCL), including Mycosis Fungoides (MF) and Sézary syndrome (SS), is often severe and poorly responsive to treatment with antihistamines. Recent studies have highlighted the possible role of interleukins in nonhistaminergic itch. We investigated the role of IL-31 and IL-8 in CTCL, concerning disease severity and associated itch. Serum samples of 27 patients with CTCL (17 MF and 10 SS) and 29 controls (blood donors) were analyzed for interleukin- (IL-) 31 and IL-8; correlations with disease and itch severity were evaluated. IL-31 serum levels were higher in CTCL patients than in controls and higher in SS than in MF. Also, serum IL-31 levels were higher in patients with advanced disease compared to those with early disease, and they correlated positively with lactate dehydrogenase and beta 2-microglobulin levels, as well as with the Sézary cell count. Itch affected 67% of CTCL patients (MF: 47%; SS: 100%). Serum IL-31 levels were higher in itching patients than in controls and in patients without itching. There was no association between serum IL-8 and disease severity, nor with itching. Serum IL-8 levels correlated positively with peripheral blood leukocyte and neutrophil counts in CTCL patients. Our study suggests a role for IL-31 in CTCL-associated itch, especially in advanced disease and SS, offering a rational target for new therapeutic approaches. Increased serum IL-8 observed in some patients may be related to concomitant infections, and its role in exacerbating itch by recruiting neutrophils and promoting the release of neutrophil proteases deserves further investigation.


2021 ◽  
Author(s):  
Tsogtsaikhan Sandag ◽  
Enkhsaikhan Lkhagvasuren ◽  
Munkhundrakh Batmunkh ◽  
Oyungerel Ravjir

SARS-CoV-2 disturbs the normal immune responses causing an uncontrolled inflammatory response in patients with severe COVID-19. The pattern of the immune response to the SARS-CoV-2 in individuals may fluctuate. Some have a virus-dependent protective immune response resulting in asymptomatic or mild disease with elimination of the virus within 7-10 days after onset of infection. Others develop virus non-dependent uncontrolled hyper-inflammation in the later period, leading to severe disease with cytokine storm, acute respiratory distress syndrome, disseminated intravascular coagulation and multi-organ failure. Methods: The serum of 72 patients was investigated for titers of 15 cytokines and chemokines using Enzyme-linked immunosorbent assay (ELISA) kits in the serum of peripheral blood samples. The means of groups were compared using ANOVA followed by Tukey multiple post hoc comparisons if the ANOVA p-value was <0.05. Results: Patients with pulmonary infiltrates on CT demonstrated a lower percentage of eosinophils (1.38±1.46%) and elevated level of serum CRP (8.57±19.10 mg/dL) compared to patients without pulmonary infiltrates (2.52±1.47% and 1.96±3.02 mg/dL respectively; p<0.05). ROC analysis for patients aged ≥35 years showed patients with mild disease (n=3) had a significantly higher titer of IL-1α and MCP-1 (AUC, 0.958 and 0.917 respectively, p<0.05) compared to patients with moderate disease (n=7).


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Antonio Aceti ◽  
Lory Marika Margarucci ◽  
Elena Scaramucci ◽  
Massimiliano Orsini ◽  
Gerardo Salerno ◽  
...  

Abstract SARS-CoV-2 infection shows a wide-ranging clinical severity, requiring prognostic markers. We focused on S100B, a calcium-binding protein present in biological fluids, being a reliable biomarker in disorders having inflammatory processes as common basis and RAGE as main receptor. Since Covid-19 is characterized by a potent inflammatory response also involving RAGE, we tested if S100B serum levels were related to disease severity. Serum samples (n = 74) were collected from hospitalized SARS-CoV-2 positive patients admitted to Covid center. Illness severity was established by admission clinical criteria and Covid risk score. Treatment protocols followed WHO guidelines available at the time. Circulating S100B was determined by ELISA assay. Statistical analysis used Pearson’s χ2 test, t-Test, and ANOVA, ANCOVA, Linear Regression. S100B was detected in serum from Covid-19 patients, significantly correlating with disease severity as shown both by the level of intensity of care (p < 0.006) as well by the value of Covid score (Multiple R-squared: 0.3751); the correlation between Covid-Score and S100B was 0.61 (p < 0.01). S100B concentration was associated with inflammation markers (Ferritin, C-Reactive Protein, Procalcitonin), and organ damage markers (Alanine Aminotransferase, Creatinine). Serum S100B plays a role in Covid-19 and can represent a marker of clinical severity in Sars-CoV-2 infected patients.


2021 ◽  
Author(s):  
Poorandokht Afshari ◽  
Mehrnoosh Zakerkish ◽  
Parvin Abedi ◽  
Maryam Beheshtinasab ◽  
Elham Maraghi ◽  
...  

Abstract Background: There is some evidence about alteration of sex hormones in patients with COVID-19 infection. This study aimed to evaluate the levels of sex hormones in female and male patients with COVID-19 during hospitalization and one month after discharge. Methods: The levels of sex hormones including estradiol, progesterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone, and free testosterone were measured in 162 female and male patients with COVID-19 infection during hospitalization and one month after discharge. A demographic questionnaire and a checklist were used to collect the data. The ANCOVA test was used to compare the level of hormones in patients with severe and moderate disease. Results: In the primary assessment, 162 patients were assessed for serum levels of sex hormones, while a month after discharge, only 69 patients provided consent for assessment, and nine had passed away. During hospitalization, female patients with severe disease had an elevated level of estradiol (407.70±623.37 pg/mL) in comparison to those with a moderate disease (213.78±407.17 pg/mL). The levels of progesterone and LH were high during hospitalization, but there was a decrease in these levels after discharge. The reduction in the level of FSH in patients with severe disease was greater than in patients with moderate disease, which increased after discharge. While the level of testosterone decreased during hospitalization, the alteration of free testosterone was negligible in male patients.Conclusion: In this study, we observed alteration in sex hormones (increased level of estrogen, progesterone, LH and reduction in the level of FSH and total testosterone) in female and male patients, with the alteration being greater in the latter. Due to the attrition of patients in follow-up period, more studies are needed to confirm these results.


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