Diagnostic SARS-CoV-2 Cycle Threshold Value Predicts Disease Severity, Survival, and Six-Month Sequelae in COVID-19 Symptomatic Patients.
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ABSTRACT:
SUBMITTER: Trunfio M
PROVIDER: S-EPMC7917896 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There is no stand-alone Clostridium difficile diagnostic that can sensitively and rapidly detect fecal free toxins. We investigated the performance of the C. difficile PCR cycle threshold (CT ) for predicting free toxin status. Consecutive stool samples (n = 312) positive for toxigenic C. difficile by the GeneXpert C. difficile/Epi tcdB PCR assay were tested with the rapid membrane C. Diff Quik Chek Complete immunoassay (RMEIA). RMEIA toxin-negative samples were tested with the cell cytotoxicity neutralization assay (CCNA) and tgcBIOMICS enzyme-linked immunosorbent assay (ELISA). Using RMEIA alone or in combination with CCNA and/or ELISA as the reference method, the accuracy of CT was measured at different CT cutoffs. Using RMEIA as the reference method, a CT cutoff of 26.35 detected toxin-positive samples with a sensitivity, specificity, positive predictive value, and negative predictive value of 96.0% (95% confidence interval [CI], 90.2% to 98.9%), 65.9% (95% CI, 59.0% to 72.2%), 57.4% (95% CI, 52.7% to 62%), and 97.1% (95% CI, 92.8% to 98.9), respectively. Inclusion of CCNA in the reference method improved CT specificity to 78.0% (95% CI, 70.7% to 84.2%). Intercartridge lot CT variability measured as the average coefficient of variation was 2.8% (95% CI, 1.2% to 3.2%). Standardizing the input stool volume did not improve CT toxin specificity. The median CT values were not significantly different between stool samples with Bristol scores of 5, 6, and 7, between pediatric and adult samples, or between presumptive 027 and non-027 strains. In addition to sensitively detecting toxigenic C. difficile in stool, on-demand PCR may also be used to accurately predict toxin-negative stool samples, thus providing additional results in PCR-positive stool samples to guide therapy.
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Project description:Vaccination has proven effective against infection with SARS-CoV-2, as well as death and hospitalisation following COVID-19 illness. However, little is known about the effect of vaccination on other acute and post-acute outcomes of COVID-19. Data were obtained from the TriNetX electronic health records network (over 81 million patients mostly in the USA). Using a retrospective cohort study and time-to-event analysis, we compared the incidences of COVID-19 outcomes between individuals who received a COVID-19 vaccine (approved for use in the USA) at least 2 weeks before SARS-CoV-2 infection and propensity score-matched individuals unvaccinated for COVID-19 but who had received an influenza vaccine. Outcomes were ICD-10 codes representing documented COVID-19 sequelae in the 6 months after a confirmed SARS-CoV-2 infection (recorded between January 1 and August 31, 2021, i.e. before the emergence of the Omicron variant). Associations with the number of vaccine doses (1 vs. 2) and age (<60 vs. ≥ 60 years-old) were assessed. Among 10,024 vaccinated individuals with SARS-CoV-2 infection, 9479 were matched to unvaccinated controls. Receiving at least one COVID-19 vaccine dose was associated with a significantly lower risk of respiratory failure, ICU admission, intubation/ventilation, hypoxaemia, oxygen requirement, hypercoagulopathy/venous thromboembolism, seizures, psychotic disorder, and hair loss (each as composite endpoints with death to account for competing risks; HR 0.70-0.83, Bonferroni-corrected p < 0.05), but not other outcomes, including long-COVID features, renal disease, mood, anxiety, and sleep disorders. Receiving 2 vaccine doses was associated with lower risks for most outcomes. Associations between prior vaccination and outcomes of SARS-CoV-2 infection were marked in those <60 years-old, whereas no robust associations were observed in those ≥60 years-old. In summary, COVID-19 vaccination is associated with lower risk of several, but not all, COVID-19 sequelae in those with breakthrough SARS-CoV-2 infection. The findings may inform service planning, contribute to forecasting public health impacts of vaccination programmes, and highlight the need to identify additional interventions for COVID-19 sequelae.
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Project description:Bordetella pertussis testing performed using real-time polymerase chain reaction (RT-PCR) is interpreted based on a cycle threshold (Ct) value. At Public Health Ontario Laboratories (PHOL), a Ct value <36 is reported as positive, and Ct values ≥36 and <40 are reported as indeterminate. PHOL reported indeterminate results to physicians and public health units until May 2012, after which these results were only reported to physicians. We investigated the association between Ct value and disease symptom and severity to examine the significance of indeterminate results clinically, epidemiologically and for public health reporting. B. pertussis positive and indeterminate RT-PCR results were linked to pertussis cases reported in the provincial Integrated Public Health Information System (iPHIS), using deterministic linkage. Patients with positive RT-PCR results had a lower median age of 10.8 years compared to 12.0 years for patients with indeterminate results (p = 0.24). Hospitalized patients had significantly lower Ct values than non-hospitalized patients (median Ct values of 20.7 vs. 31.6, p<0.001). The proportion of patients reporting the most indicative symptoms of pertussis did not differ between patients with positive vs. indeterminate RT-PCR results. Taking the most indicative symptoms of pertussis as the gold-standard, the positive predictive value of the RT-PCR test was 68.1%. RT-PCR test results should be interpreted in the context of the clinical symptoms, age, vaccination status, prevalence, and other factors. Further information on interpretation of indeterminate RT-PCR results may be needed, and the utility of reporting to public health practitioners should be re-evaluated.
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Project description:Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Ample data have been reported to unravel the carcinogenesis over the past decades. Although pinpointing the cause of the HCC is challenging, this in and of itself may not be an insuperable problem. Indeed, the emergence of novel molecular targets has given rise to targeted therapy for HCC. Compared to traditional treatments, drugs with molecularly targeted agents are considered an optimal way to treat HCC. However, targeted approaches are currently limited among HCC patients. In our work, we explored more potential genes for targeted treatment of HCC. Initially, differentially expressed genes (DEGs) were identified in gene expression profiling interactive analysis (GEPIA) and NetworkAnalyst. Subsequently, 10 key genes were selected through enrichment analysis and PPI network construction. Based on the GEPIA and Oncomine databases, six upregulated genes were selected. High protein expression of these six genes were confirmed through the Human Protein Atlas database. In addition, these six genes were associated with unfavorable overall survival and progression-free survival based on Kaplan-Meier plotter bioinformatics. Moreover, gene expression was closely related to the tumor stages and pathological grades, as determined with UALCAN. More importantly, PTTG1, UBE2C, and ZWINT were identified as potential targets of anti-cancer drugs using cBioPortal. qPCR and western blot assays were used to show the high expression levels of the latter three genes in HCC cell lines. Collectively, these findings are expected to provide a theoretical basis for and give novel insights into clinical research of HCC.
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Project description:Previous studies have investigated differences in the volumes of subcortical structures (e.g., caudate nucleus, putamen, thalamus, amygdala, and hippocampus) between individuals with and without Tourette syndrome (TS), as well as the relationships between these volumes and tic symptom severity. These volumes may also predict clinical outcome in Provisional Tic Disorder (PTD), but that hypothesis has never been tested. This study aimed to examine whether the volumes of subcortical structures measured shortly after tic onset can predict tic symptom severity at one-year post-tic onset, when TS can first be diagnosed. We obtained T1-weighted structural MRI scans from 41 children with PTD (25 with prospective motion correction (vNavs)) whose tics had begun less than 9 months (mean 4.04 months) prior to the first study visit (baseline). We re-examined them at the 12-month anniversary of their first tic (follow-up), assessing tic severity using the Yale Global Tic Severity Scale. We quantified the volumes of subcortical structures using volBrain software. Baseline hippocampal volume was correlated with tic severity at the 12-month follow-up, with a larger hippocampus at baseline predicting worse tic severity at follow-up. The volumes of other subcortical structures did not significantly predict tic severity at follow-up. Hippocampal volume may be an important marker in predicting prognosis in Provisional Tic Disorder.
| S-EPMC7355974 | biostudies-literature
Project description:BackgroundThe World Health Organization recommends GeneXpert MTB/RIF Ultra (Xpert Ultra), a fully automated polymerase chain reaction (PCR) assay, as the initial tuberculous meningitis (TBM) diagnostic test. The assay's PCR cycle threshold (Ct) values represent the number of PCR cycles required for probe signal to be detected (low Ct value = high bacillary load) and may approximate tuberculosis (TB) bacillary load. We measured the relationship between cerebrospinal fluid (CSF) TB bacillary load with mortality.MethodsWe prospectively enrolled 102 human immunodeficiency virus (HIV)-positive Ugandans with probable or definite TBM from April 2015 to August 2019. Xpert Ultra Ct tertiles and semi-quantitative categories were separately analyzed as predictors of 2-week mortality. We investigated associations between Ct and baseline clinical and CSF parameters.ResultsSubjects with Ct values in the low tertile (ie, high bacillary load) had 57% 2-week mortality-worse than the intermediate (17%) and high (25%) Ct tertiles and Xpert Ultra-negative (30%) probable TBM cases (P = .01). In contrast, the reported semi-quantitative Xpert Ultra categorization was less precise; with the medium to low category trending toward worse 2-week survival (42%) compared with very low (28%), trace (26%), and negative (30%) categories (P = .48). Ct tertile was significantly associated with baseline CSF lactate (P = .03).ConclusionsHigh CSF TB bacillary load, as measured by Xpert Ultra Ct tertile, is associated with an almost 2-fold higher 2-week mortality in HIV-associated TBM and is a better predictor than the reported Xpert Ultra semi-quantitative category. Xpert Ultra Ct values could identify TBM patients at increased risk of death who may benefit from enhanced supportive care.
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Project description:INTRODUCTION: The aim of this study was to evaluate the usefulness of the APACHE II (Acute Physiology and Chronic Health Evaluation II), SAPS II (Simplified Acute Physiology Score II) and SOFA (Sequential Organ Failure Assessment) scores compared to simpler models based on age and Glasgow Coma Scale (GCS) in predicting long-term outcome of patients with moderate-to-severe traumatic brain injury (TBI) treated in the intensive care unit (ICU). METHODS: A national ICU database was screened for eligible TBI patients (age over 15 years, GCS 3-13) admitted in 2003-2012. Logistic regression was used for customization of APACHE II, SAPS II and SOFA score-based models for six-month mortality prediction. These models were compared to an adjusted SOFA-based model (including age) and a reference model (age and GCS). Internal validation was performed by a randomized split-sample technique. Prognostic performance was determined by assessing discrimination, calibration and precision. RESULTS: In total, 1,625 patients were included. The overall six-month mortality was 33%. The APACHE II and SAPS II-based models showed good discrimination (area under the curve (AUC) 0.79, 95% confidence interval (CI) 0.75 to 0.82; and 0.80, 95% CI 0.77 to 0.83, respectively), calibration (P?>?0.05) and precision (Brier score 0.166 to 0.167). The SOFA-based model showed poor discrimination (AUC 0.68, 95% CI 0.64 to 0.72) and precision (Brier score 0.201) but good calibration (P?>?0.05). The AUC of the SOFA-based model was significantly improved after the insertion of age and GCS (?AUC +0.11, P?<?0.001). The performance of the reference model was comparable to the APACHE II and SAPS II in terms of discrimination (AUC 0.77; compared to APACHE II, ?AUC -0.02, P?=?0.425; compared to SAPS II, ?AUC -0.03, P?=?0.218), calibration (P?>?0.05) and precision (Brier score 0.181). CONCLUSIONS: A simple prognostic model, based only on age and GCS, displayed a fairly good prognostic performance in predicting six-month mortality of ICU-treated patients with TBI. The use of the more complex scoring systems APACHE II, SAPS II and SOFA added little to the prognostic performance.
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Project description:ObjectiveThe objective of this study was to assess the clinical significance of increased fluorine-18-fluorodeoxyglucose (F-FDG) uptake on PET/CT in joints for evaluation of symptomatic osteoarthritis (OA) and prediction of progression.Patients and methodsIn this prospective study, shoulder, hip, and knee joints were imaged in 65 patients undergoing routine F-FDG PET/CT imaging. Patients completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire to assess joint pain, stiffness, and physical function. Standardized uptake values (SUVs) were measured in hip, knee, acromioclavicular (AC), and glenohumeral (GH) joints. Scout PET/CT images were evaluated for OA using the Kellgren and Lawrence (K/L) system. Patients were followed-up for 5 years to determine the progression of OA on the basis of follow-up imaging or surgical intervention.ResultsSUV of knee (r=0.309, P=0.0003), hip (r=0.260, P=0.0027), AC (r=0.186, P=0.0313), and GH (r=0.191, P=0.0271) joints correlated with WOMAC overall scores. Furthermore, SUV of knee (r=0.410, P<0.0001), hip (r=0.203, P=0.0199), and AC (r=0.364, P<0.0001) joints correlated with K/L scores. The area under the receiver operating characteristic curves for SUV were 0.734 (knee), 0.678 (hip), 0.661 (AC), and 0.544 (GH) for symptomatic OA detection based on WOMAC overall z-score greater or equal to 2. Compared with K/L score [hazard ratio (HR)=0.798, P=0.5324], age (HR=0.992, P=0.8978), and WOMAC overall score (HR=1.089, P=0.1265), only SUV (HR=5.653, P=0.0229) was an independent predictor of OA progression in the knees.ConclusionF-FDG PET/CT may be helpful with localization of painful abnormalities in the inflamed regions of the joints, which could potentially be used to direct individualized treatment in moderate and severe OA. Furthermore, SUV measurement on F-FDG PET/CT could serve as an inflammation activity index in the knees that may be predictive of outcomes and progression rate of OA.
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Project description:Monitoring the emergence of new SARS-CoV-2 variants is important to detect potential risks of increased transmission or disease severity. We investigated the identification of SARS-CoV-2 variants from real-time reverse transcriptase polymerase chain reaction (RT-PCR) routine diagnostics data. Cycle threshold (Ct) values of positive samples were collected from April 2021 to January 2022 in the Northern Metropolitan Area of Barcelona (n = 15,254). Viral lineage identification from whole genome sequencing (WGS) was available for 4618 (30.3%) of these samples. Pairwise differences in the Ct values between gene targets (ΔCt) were analyzed for variants of concern or interest circulating in our area. A specific delay in the Ct of the N-gene compared to the RdRp-gene (ΔCtNR) was observed for Alpha, Delta, Eta and Omicron. Temporal differences in ΔCtNR correlated with the dynamics of viral replacement of Alpha by Delta and of Delta by Omicron according to WGS results. Using ΔCtNR, prediction of new variants of concern at early stages of circulation was achieved with high sensitivity and specificity (91.1% and 97.8% for Delta; 98.5% and 90.8% for Omicron). Thus, tracking population-wide trends in ΔCt values obtained from routine diagnostics testing in combination with WGS could be useful for real-time management and response to local epidemics.
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Project description:Understanding viral kinetics of SARS-CoV-2 is important to assess risk of transmission, manage treatment, and determine the need for isolation and protective equipment. The impact of viral load in asymptomatic infected children is important to understand transmission potential. We sought to determine whether children deemed to be asymptomatic had a difference in the PCR cycle threshold (Ct) value of respiratory samples from symptomatic children with SARS-CoV-2 infection. This was a retrospective cross-sectional study to compare PCR Ct values of children who tested positive for SARS-CoV-2 by respiratory samples collected over a 4-month period at a large tertiary care children's hospital. We analyzed 728 children who tested positive for SARS-CoV-2 by RT-PCR from a respiratory sample over a 4-month period and for whom data was available in the electronic medical record. Overall, 71.2% of infected children were symptomatic. The mean Ct value for symptomatic patients (Ct mean 19.9, SD 6.3) was significantly lower than asymptomatic patients (Ct mean 23.5, SD 6.5) (P value < 0.001, CI 95th 2.6 - 4.6). The mean PCR Ct value was lowest in children less than 5 years of age. In this retrospective review of children who tested positive by RT-PCR for SARS CoV-2, the mean Ct was significantly lower in symptomatic children and was lowest in children under 5 years of age, indicating that symptomatic children and younger children infected with SARS-CoV-2 may have a higher viral load in the nasopharynx compared to asymptomatic children. Further studies are needed to assess the transmission potential from asymptomatic children.
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