scholarly journals Binary toxin expression by Clostridioides difficile is associated with worse disease

2022 ◽  
Author(s):  
Mary K Young ◽  
Jhansi L Leslie ◽  
Gregory R Madden ◽  
David M Lyerly ◽  
Robert J Carman ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Disease Severity ◽  
Severe Disease ◽  
Fecal Microbiota ◽  
Binary Toxin ◽  
Enzyme Linked Immunosorbent Assay ◽  
Rrna Gene ◽  
Clostridioides Difficile ◽  
Cell Counts ◽  
Significant Difference

Abstract Background The incidence of Clostridioides difficile infection (CDI) has increased over the past two decades and is considered an urgent threat by the Centers for Disease Control. Hypervirulent strains such as ribotype 027, that possess genes for the additional toxin C. difficile binary toxin (CDT), are contributing to increased morbidity and mortality. Methods We retrospectively tested stool from 215 CDI patients for CDT by enzyme-linked immunosorbent assay (ELISA). Stratifying patients by CDT status, we assessed if disease severity and clinical outcomes correlated with CDT positivity. Additionally, we completed qPCR DNA extracted from patient stool to detect cdtB gene. Lastly, we performed 16 S rRNA gene sequencing to examine if CDT positive samples had an altered fecal microbiota. Results We found that patients with CdtB, the pore forming component of CDT, detected in their stool by ELISA were more likely to have severe disease with a higher 90-day mortality. CDT positive patients also had higher C. difficile bacterial burden and white blood cell counts. There was no significant difference in gut microbiome diversity between CDT positive and negative patients. Conclusions Patients with fecal samples that were positive for CDT had increased disease severity and worse clinical outcomes. Utilization of PCR and C. difficile Toxins A and B testing may not reveal the entire picture when diagnosing CDI, with the detection of CDT-expressing strains valuable in identifying patients at risk of more severe disease.

scholarly journals Binary toxin expression by Clostridioides difficile is associated with worse disease

2021 ◽  
Author(s):  
Mary K Young ◽  
Jhansi L Leslie ◽  
Gregory R Madden ◽  
David M Lyerly ◽  
Robert J Carman ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Disease Severity ◽  
Severe Disease ◽  
Patient Treatment ◽  
Binary Toxin ◽  
Enzyme Linked Immunosorbent Assay ◽  
Rrna Gene ◽  
Clostridioides Difficile ◽  
Cell Counts ◽  
Significant Difference

Background. The incidence of Clostridioides difficile infection (CDI) has increased over the past two decades and is considered an urgent threat by the Centers for Disease Control. Hypervirulent strains such as ribotype 027, that possess genes for an additional toxin C. difficile binary toxin (CDT) are contributing to increased morbidity and mortality. In the mouse model, CDT activates Toll-like receptor 2 resulting in suppression of a protective type 2 innate immune response mediated by eosinophils. Methods. We retrospectively tested stool from 215 CDI patients for CDT by enzyme-linked immunosorbent assay (ELISA). Stratifying patients by CDT status, we assessed if disease severity and clinical outcomes correlated with CDT positivity. Additionally, we performed 16 S rRNA gene sequencing to examine if CDT positive samples had an altered fecal microbiota. Results. We found that patients with CdtB, the pore forming component of CDT, detected in their stool were more likely to have severe disease and had higher 90-day mortality compared to CDT negative patients. CDT positive patients also had higher C. difficile bacterial burden and white blood cell counts. There was no significant difference in gut microbiome diversity between CDT positive and negative patients. Conclusions. Patients with fecal samples that were positive for CDT had increased disease severity and worse clinical outcomes. Utilization of PCR and C. difficile Toxins A and B testing may not reveal the entire picture when diagnosing CDI and the detection of CDT-expressing strains may be valuable during patient treatment.

scholarly journals Association Between SARS-CoV-2 Cycle Threshold Values and Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis

2021 ◽  
Vol 8 (9) ◽  
Author(s):  
Vishal P Shah ◽  
Wigdan H Farah ◽  
James C Hill ◽  
Leslie C Hassett ◽  
Matthew J Binnicker ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Outcomes ◽  
Disease Severity ◽  
Meta Analysis ◽  
Severe Disease ◽  
Sample Type ◽  
Sample Collection ◽  
Cycle Threshold ◽  
Significant Difference ◽  
Polymerase Chain

Abstract Cycle threshold (CT) values are correlated with the amount of viral nucleic acid in a sample and may be obtained from some qualitative real-time polymerase chain reaction tests used for diagnosis of most patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, CT values cannot be directly compared across assays, and they must be interpreted with caution as they are influenced by sample type, timing of sample collection, and assay design. Presently, the correlation between CT values and clinical outcomes is not well understood. We conducted a systematic review and meta-analysis of published studies through April 19, 2021, that reported an association between CT values and hospitalization, disease severity, and mortality in patients ≥18 years old with SARS-CoV-2. A meta-analysis of 7 studies showed no significant difference in mean CT values between hospitalized and nonhospitalized patients. Among hospitalized patients, those with CT values <25 had a high risk of more severe disease and mortality than patients with CT values >30 (odds ratio [OR], 2.31; 95% CI, 1.70 to 3.13; and OR, 2.95; 95% CI, 2.19 to 3.96; respectively). The odds of increased disease severity and mortality were less pronounced in patients with CT values of 25–30 compared with >30.

Evaluation of Platelet Activity Markers in Prognostic Value of Children with Crimean-Congo Hemorrhagic Fever

2020 ◽  
Vol 15 (03) ◽  
pp. 123-128
Author(s):  
Ahmet Sami Güven ◽  
Fatma Duksal ◽  
Özge Metin Akcan ◽  
Utku Aygüneş ◽  
Mehmet Burhan Oflaz
Keyword(s):  
Disease Severity ◽  
Prognostic Value ◽  
Severe Disease ◽  
Multivariate Logistic Regression Analysis ◽  
Prognostic Index ◽  
Hemorrhagic Fever ◽  
Healthy Children ◽  
Distribution Width ◽  
Crimean Congo Hemorrhagic Fever ◽  
Significant Difference

Abstract Objective The aim of this study is to investigate the prognostic value of platelet (PLT) activity markers in children with Crimean-Congo hemorrhagic fever (CCHF) and compare results with healthy controls. Materials and Methods A total of 135 patients with CCHF and 100 healthy children were included in this retrospective study. Mean age was 12.4 ± 3.3 years in CCHF group, and 92 patients were male. We measured PLT count, mean platelet volume (MPV), platelet distribution width (PDW), and mean platelet mass (MPM) as PLT activity markers. Results A statistically significant decrease in MPM and PLT, and significantly higher levels of PDW and activated partial thromboplastin time (aPTT) and no significant difference in MPV were observed in patients with CCHF compared with controls. Although there were no significant differences between the severe and nonsevere CCHF groups in term of MPV and PDW, the MPM value was significantly decreased in severe patients (p < 0.001). Furthermore, MPM values were inversely correlated with aPTT (r = −0.617, p = 0.015), and positively correlated with PLT (r = 0.703, p < 0.001) which are considered likely to be indicators of disease severity. Multivariate logistic regression analysis revealed MPM as an independent risk factor for severe disease. Conclusion Our study demonstrated that MPM values were decreased in severe cases compared with nonsevere in children with CCHF. The MPM as an indicator of PLT activation at the time of diagnosis in children with CCHF can be used as a prognostic index for disease severity.

scholarly journals 2402. Clinical Outcomes Associated with an Emerging Clostridioides difficile Ribotype 255 in Texas

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S829-S829
Author(s):  
Anne J Gonzales-Luna ◽  
Travis J Carlson ◽  
Chris Lancaster ◽  
Julie M Miranda ◽  
Kevin W Garey
Keyword(s):  
Clinical Outcomes ◽  
Severe Disease ◽  
Tertiary Care ◽  
Albumin Level ◽  
Multivariable Logistic Regression Analysis ◽  
Relative Reduction ◽  
Contributing Factors ◽  
Clostridioides Difficile ◽  
Pcr Ribotyping ◽  
Tertiary Care Centers

Abstract Background PCR ribotyping of Clostridioides difficile strains is commonly used to describe the epidemiology of C. difficile infection (CDI). Certain ribotypes (RT) have been associated with more severe disease and clinical outcomes, such as RT 027, while others are considered less virulent, such as RT 014-020. Texas statewide surveillance identified the emergence of a rarely-described RT 255 beginning in 2015, which now represents the fifth most common ribotype across the state. Here we describe clinical outcomes associated with an emergent RT 255 in Texas. Methods A retrospective cohort study was conducted including patients from two tertiary care centers in Houston, Texas. Patients infected with C. difficile strains of either RT 255, 014-020, or 027 between 2016–18 were included. The primary outcome was disease severity as classified by the 2017 IDSA guidelines. Multivariable logistic regression analysis was done to control for other patient factors. Results were significant at P < 0.05, and all statistical analyses were completed using SPSS, version 25. Results A total of 150 patients were included (50 patients infected with each RT). Overall, 53% of the patients had severe or fulminant disease most commonly due to RT 027 (80%) followed by RT 014-020 (40%) and RT 255 (38%). Patients infected with RT 255 or 014-020 had a 75% relative reduction in the odds of severe disease compared with RT 027 after controlling for patient age and serum albumin level (OR, 0.25; 95% CI, 0.86–0.74; P = 0.12;). No differences were seen in the rates of 30- or 90-day recurrence between RTs. Conclusion Although RT 255 is becoming increasingly common across Texas, it does not appear to be associated with more severe disease when compared with other common ribotypes. Further studies are warranted to determine contributing factors for its increasing prevalence. Disclosures All authors: No reported disclosures.

scholarly journals Salivary Levels of IL-6 and IL-17 Could Be an Indicator of Disease Severity in Patients with Calculus Associated Chronic Periodontitis

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Husniah Batool ◽  
Ahmed Nadeem ◽  
Muhammad Kashif ◽  
Faheem Shahzad ◽  
Romeeza Tahir ◽  
...  
Keyword(s):  
Chronic Periodontitis ◽  
Alveolar Bone ◽  
Gingival Crevicular Fluid ◽  
Severe Disease ◽  
Cross Sectional Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Significant Difference ◽  
Crevicular Fluid

Background/Purpose. Chronic periodontitis is an inflammatory disease of gums that causes loss of supporting structures of teeth, that is, gingiva, periodontal ligament, cementum, and alveolar bone. Levels of various cytokines in the serum, gingival tissues, and gingival crevicular fluid in patients with chronic periodontitis have been studied, but limited data are available on the level of cytokines in saliva. Therefore, a study was designed to determine levels of salivary IL-6 and IL-17 in patients with calculus associated chronic periodontitis. Materials and Methods. It was a comparative, cross-sectional study that is comprised of 41 healthy controls and 41 calculus associated chronic periodontitis patients (CP patients). According to the degree of attachment loss, CP patients were subcategorized as mild (CAL 1-2 mm), moderate (CAL 3-4 mm), and severe (CAL > 5 mm) forms of periodontitis. Salivary levels of IL-6 and IL-17 were determined using enzyme-linked immunosorbent assay (ELISA) technique. Data was analyzed using SPSS 20.0. Results. Between healthy controls and CP patients (moderate and severe disease), a statistically significant difference was observed in the concentrations of IL-6 and IL-17. In CP patients, the highest mean ± SD of salivary IL-6 and IL-17 was observed in severe CP, followed by moderate and mild CP. Regarding level of IL-6, a statistically significant difference was observed between mild and severe disease and between moderate and severe subcategories of CP patients. Similarly, statistically significant difference was observed in the level of IL-17 between mild and moderate, mild and severe disease, and moderate and severe disease. Conclusion. The levels of salivary IL-6 and IL-17 were increased significantly in calculus associated CP patients as compared to healthy controls and these levels increased with the progression of CP. Clinical Significance. Salivary levels of IL-6 and IL-17 may help in the subcategorization of CP.

scholarly journals ANTIBODY RESPONSE TO COVID-19 INFECTION- CLINICAL VARIABLES AT PLAY

2020 ◽  
Author(s):  
Anuj Parkash ◽  
Parul Singla ◽  
Meenu Bhatia
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Disease Severity ◽  
Statistical Significance ◽  
Severe Disease ◽  
Initial Symptom ◽  
Igg Antibody ◽  
Duration Of Symptoms ◽  
Clinical Variables ◽  
Significant Difference

ABSTRACTBackgroundThe current COVID19 pandemic began in December 2019 and rapidly expanded to become a global pandemic. The COVID 19 presents multitude of clinical disorders, ranges from asymptomatic infection to severe disease, which can accompanied by multisystem failure leading to death. The immune response to SARS CoV 2 is understood to involve all the components of the system that together causes viral elimination and recovery from the infection. However, such immune responses implicated in the disease has varied presentation ranging from mild to a severe form, which appears to hinge on the loss of the immune regulation between protective and altered responses. In this study, we want to unravel this association of immune responses to various clinical variables, which might have a major role to play, while generating the immune response. The objective was to test this hypothesis in our settings and comparing the results of serologic tests from a group of COVID 19 patients and will analyzed the disease severity in comparison.MethodsTesting for SARS COV2 IgG Antibody was done with chemiluminescent assay on the Ortho Clinical Diagnostic’s (OCD) Vitros 5600 platform.ResultsA total of 106 COVID 19 patients were included in this study, of whom 61 were male and 45 were female. Their mean age was 43.7 years (range 17–83) and the median interval between initial symptom onset and sample collection was 12.33 days. Eighty patients (82%) had mild or moderate symptoms and twenty-six patients (18%) had severe symptoms. The antibody titers were positive in 99 patients (93%) and were found negative in 7 patients (7%). When comparing patients with mild/moderate symptoms and patients with severe/critical diseases, no statistically significant difference was observed between their gender ratios (P = 0.373) and age composition (P = 0.224).ConclusionsThe data presented in this research study did not find any statistical significance between SARS CoV 2 IgG antibody levels with COVID 19 disease severity, duration of symptoms, age, gender, and length of convalescence.

scholarly journals The Cytopathic Effect of Different Toxin Concentrations From Different Clostridioides difficile Sequence Types Strains in Vero Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Zohar Hamo ◽  
Maya Azrad ◽  
Boris Fichtman ◽  
Avi Peretz
Keyword(s):  
Disease Severity ◽  
Cytopathic Effect ◽  
Vero Cells ◽  
Bacterial Strains ◽  
Host Immune Responses ◽  
Clostridioides Difficile ◽  
Cell Counts ◽  
Healthcare Associated ◽  
Sequence Types

Clostridioides difficile is one of the leading causes of healthcare-associated diarrhea, with severity ranging from mild, self-limiting disease, to life-threatening toxic megacolon. C. difficile infection (CDI) pathogenesis is mediated by the TcdA and TcdB toxins. This work aimed to draw correlations between toxin levels, bacterial strains, and disease severity in 63 CDI patients. C. difficile typing was performed by multi-locus sequence types (MLST). Toxin concentrations were measured using the TOX A/B test. In addition, cell cytotoxicity assay was performed following Vero cell exposure to stool extracts (24 h). The most prevalent sequence types (ST) were ST2, ST4, ST6, ST13, ST37, ST42, and ST104, with highest toxin levels produced by ST42 and ST104 (302.5 and 297.1 ng/ml, respectively). These strains had a stronger cytopathic effect (CPE) on Vero cells as compared to strains with lower toxin concentrations (p &lt; 0.001), as manifested by lower cell counts and higher percentages of cell rounding and adhesion loss. Although no association was found between ST, toxin concentrations, and disease severity, a diverse in vitro effect of different STs on the viability and activity of Vero cells was observed. These findings suggest that disease severity is affected by both host immune responses and by bacterial characteristics.

scholarly journals Effects of Giardia lamblia Colonization and Fenbendazole Treatment on Canine Fecal Microbiota

2020 ◽  
Author(s):  
Naomi N Lee ◽  
Willie A Bidot ◽  
Aaron C Ericsson ◽  
Craig L Franklin
Keyword(s):  
Giardia Lamblia ◽  
16S Rrna Gene Sequencing ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Limited Information ◽  
Sample Collection ◽  
Minimal Impact ◽  
Clinically Normal ◽  
Significant Difference ◽  
Rrna Gene Sequencing

The gut microbiota (GM) is the sum of hundreds of distinct microbial species that can equal or outnumber their host’ssomatic cells. The GM influences a multitude of physiologic and immunologic processes in the host, and changes in the GM have been shown to alter the phenotypes of animal models. Previous studies using rodents have also shown that the composition of the GM is affected by many factors, including diet, husbandry, housing, and the genetic background of the animals. However, limited information exists about factors that may modulate GM in other laboratory species, such as dogs. We sought to eliminate sporadic Giardia colonization of dogs using fenbendazole (FBZ), an antiprotozoal widely used in biomedical research dog colonies. Concerns that FBZ could have inadvertent effects on the canine GM led us to assess GM over the course of treatment. FBZ (50 mg/kg) was given orally to all dogs in 3 different facilities (n = 19 to 25) for 10 consecutive days. Fecal samples were obtained 2 d before the initiation of treatment, on the last day of treatment, and 2 wk after the completion of treatment. Targeted 16S rRNA gene sequencing was used to analyze fecal microbiota. All dogs were clinically normal throughout the sample collection period. Statistical analyses of data showed significant differences between dogs housed in the 3 different facilities, further emphasizing the effect of housing and husbandry factors on the GM. However,negligible differences were seen between time points, indicating that FBZ did not significantly alter the canine GM. Comparison of the GM of Giardia lamblia positive and negative dogs revealed no significant difference between the 2 groups. These findings suggest that FBZ can be used therapeutically in dogs with minimal impact on the GM. Furthermore, the presence ofG. lamblia in clinically normal animals may not be sufficient to influence the normal canine microbiota.

scholarly journals Cardiovascular drugs and COVID-19 clinical outcomes: a living systematic review and meta-analysis

2020 ◽  
Author(s):  
Innocent G Asiimwe ◽  
Sudeep Pushpakom ◽  
Richard M Turner ◽  
Ruwanthi Kolamunnage-Dona ◽  
Andrea Jorgensen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Outcomes ◽  
Disease Severity ◽  
Meta Analysis ◽  
Severe Disease ◽  
Cardiovascular Drugs ◽  
Susceptibility To Infection ◽  
Drug Classes ◽  
All Cause Mortality ◽  
Length Of Hospitalization

ABSTRACTOBJECTIVETo continually evaluate the rapidly evolving evidence base on the role of cardiovascular drugs in COVID-19 clinical outcomes (susceptibility to infection, hospitalization, hospitalization length, disease severity, and all-cause mortality).DESIGNLiving systematic review and meta-analysis.DATA SOURCESEligible publications identified from >500 databases indexed through 31st July 2020 and additional studies from reference lists, with planned continual surveillance for at least two years.STUDY SELECTIONObservational and interventional studies that report on the association between cardiovascular drugs and COVID-19 clinical outcomes.DATA EXTRACTIONSingle-reviewer extraction and quality evaluation (using ROBINS-I), with half the records independently extracted and evaluated by a second reviewer.RESULTSOf 23,427 titles screened, 175 studies were included in the quantitative synthesis. The most reported drug classes were angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) with ACEI/ARB exposure being associated with higher odds of testing positive for COVID-19 (pooled unadjusted OR 1.15, 95% CI 1.02 to 1.30). Among patients with COVID-19, unadjusted estimates showed that ACEI/ARB exposure was associated with being hospitalized (OR 2.25, 1.70 to 2.98) and having severe disease (OR 1.50, 1.27 to 1.77) but not with the length of hospitalization (mean difference −0.45, −1.33 to 0.43 days) or all-cause mortality (OR 1.25, CI 0.98 to 1.58). However, after adjustment, ACEI/ARB exposure was not associated with testing positive for COVID-19 (pooled adjusted OR 1.01, 0.93 to 1.10), being hospitalized (OR 1.16, 0.80 to 1.68), having severe disease (1.04, 0.76 to 1.42), or all-cause mortality (0.86, 0.64 to 1.15). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with being hospitalized (OR 0.84, 0.58 to 1.22), disease severity (OR 0.88, 0.68 to 1.14) or all-cause mortality (OR 0.77, 0.54 to 1.12) while it decreased the length of hospitalization (mean difference −0.71, −1.11 to −0.30 days). After adjusting for relevant covariates, other cardiovascular drug classes were mostly not found to be associated with poor COVID-19 clinical outcomes. However, the validity of these findings is limited by a high level of heterogeneity in terms of effect sizes and a serious risk of bias, mainly due to confounding in the included studies.CONCLUSIONOur comprehensive review shows that ACEI/ARB exposure is associated with COVID-19 outcomes such as susceptibility to infection, severity, and hospitalization in unadjusted analyses. However, after adjusting for potential confounding factors, this association is not evident. Patients on cardiovascular drugs should continue taking their medications as currently recommended. Higher quality evidence in the form of randomized controlled trials will be needed to determine any adverse or beneficial effects of cardiovascular drugs.PRIMARY FUNDING SOURCENoneSYSTEMATIC REVIEW REGISTRATIONPROSPERO (CRD42020191283)

scholarly journals Soluble Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Helena Enocsson ◽  
Cornelia Idoff ◽  
Annette Gustafsson ◽  
Melissa Govender ◽  
Francis Hopkins ◽  
...  
Keyword(s):  
Hospital Stay ◽  
Plasminogen Activator ◽  
Disease Severity ◽  
Length Of Hospital Stay ◽  
Urokinase Plasminogen Activator ◽  
Enzyme Linked Immunosorbent Assay ◽  
Urokinase Plasminogen Activator Receptor ◽  
Cell Counts ◽  
Hospitalised Patients ◽  
Plasminogen Activator Receptor

Background: Efficient healthcare based on prognostic variables in hospitalised patients with COVID-19 could reduce the risk of complications and death. Recently, soluble urokinase Plasminogen Activator Receptor (suPAR) was shown to predict respiratory failure, kidney injury, and clinical outcome in patients with SARS-CoV-2 infection. The aim of this study was to investigate the value of suPAR as a prognostic tool, in comparison with other variables, regarding disease severity and length of hospital stay in patients with COVID-19.Patients and Methods: Individuals hospitalised with COVID-19 (40 males, 20 females; median age 57.5 years) with a median symptom duration of 10 days and matched, healthy controls (n = 30) were included. Admission levels of suPAR were measured in serum by enzyme-linked immunosorbent assay. Blood cell counts, C-reactive protein (CRP) levels, lactate dehydrogenase (LDH), plasma creatinine and estimated glomerular filtration rates were analysed and oxygen demand, level of care and length of hospitalisation recorded.Results: Patients had significantly higher suPAR levels compared to controls (P &lt; 0.001). Levels were higher in severely/critically (median 6.6 ng/mL) compared with moderately ill patients (median 5.0 ng/mL; P = 0.002). In addition, suPAR levels correlated with length of hospitalisation (rho = 0.35; P = 0.006). Besides suPAR, LDH, CRP, neutrophil count, neutrophil-to-monocyte and neutrophil-to-lymphocyte ratio, body mass index and chronic renal failure were discriminators of COVID-19 severity and/or predictors of length of hospitalisation.Conclusion: Admission levels of suPAR were higher in patients who developed severe/critical COVID-19 and associated with length of hospital stay. In addition, we showed that suPAR functioned as an independent predictor of COVID-19 disease severity.

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