scholarly journals Detection of Neoplasms by Metagenomic Sequencing of Cerebrospinal Fluid

Author(s):  
Wei Gu ◽  
Andreas M. Rauschecker ◽  
Elaine Hsu ◽  
Kelsey C Zorn ◽  
Yasemin Sucu ◽  
...  

Importance: Malignant neoplasms of the central nervous system (CNS) are frequently not detected by cerebrospinal fluid (CSF) flow cytometry or cytology, and clinical phenotypes can overlap with inflammatory meningoencephalitis. Objective: To determine whether an existing CSF metagenomic next-generation sequencing (mNGS) assay can identify a hallmark of malignant neoplasms -aneuploidy - in difficult-to-diagnose cases of CNS malignancy. Design: Two retrospective, case-control studies included a total of 155 samples from patients with an eventual diagnosis of a CNS malignancy (n=59 patients) and controls with other CNS diseases (n=73 patients). The first study was used to evaluate test performance in positive and negative controls. The second study was used to assess the potential utility of aneuploidy detection in patients whose CSF was sent for mNGS because of suspected neuroinflammatory disease who were ultimately found to have a CNS malignancy. Setting: This is a single site study at a large tertiary care center, University of California San Francisco, that enrolled from 2014 to 2019. Participants: The test performance case-control study enrolled positive control patients with a CNS malignancy (n=47 patients) and negative controls with other neurologic diseases (n=56 patients) who had had CSF flow cytometry and/or cytology performed. The second case-control study enrolled patients with suspected neuroinflammatory disease who were ultimately diagnosed with a CNS malignancy (n=12) and other neurologic disease controls (n=17). Main Outcome(s) and Measure(s): The primary outcome measures were the performance characteristics of detecting aneuploidy in CSF by a cell-free DNA mNGS assay compared to cytology and/or flow cytometry and the tumor fraction in CSF from patients with CNS malignancies. Results: Across the two case-control studies, the overall sensitivity of the CSF mNGS assay for detecting aneuploidy in patients ultimately diagnosed with a CNS malignancy was 75% (63-96%, 95% CI), and specificity was 100% (96-100%, 95% CI). Notably, CSF mNGS detected aneuploidy in 64% of the non-diagnostic cytology and flow cytometry cases in the test performance study and in 55% of the cases with suspected neuroinflammatory disease who were ultimately diagnosed with a CNS malignancy. Of the cases in whom aneuploidy was detected, 90% had multiple chromosomal copy number variants with tumor fractions ranging from 31% to 49%. Conclusions and Relevance: Metagenomic NGS of CSF, originally designed to diagnose neurologic infections, detects evidence of CNS malignancies (i.e., aneuploidy) in cases where CSF flow cytometry and/or cytology were negative with a low risk of false positive results.

2019 ◽  
Vol 29 (8) ◽  
pp. 282-287 ◽  
Author(s):  
Kaoru Araki ◽  
Megumi Hara ◽  
Chisato Shimanoe ◽  
Yuichiro Nishida ◽  
Muneaki Matsuo ◽  
...  

2012 ◽  
Vol 54 (5) ◽  
pp. 239-244 ◽  
Author(s):  
Claudio Cesar Jaguaribe Ekman ◽  
Maria Fernanda do Valle Chiossi ◽  
Luciana Regina Meireles ◽  
Heitor Franco de Andrade Júnior ◽  
Walter Manso Figueiredo ◽  
...  

Foodborne diseases represent operational risks in industrial restaurants. We described an outbreak of nine clustered cases of acute illness resembling acute toxoplasmosis in an industrial plant with 2300 employees. These patients and another 36 similar asymptomatic employees were diagnosed with anti-T. gondii IgG titer and avidity by ELISA. We excluded 14 patients based on high IgG avidity and chronic toxoplasmosis: 13 from controls and one from acute disease other than T. gondii infection. We also identified another three asymptomatic employees with T.gondii acute infection and also anti-T. gondii IgM positive as remaining acute cases. Case control study was conducted by interview in 11 acute infections and 20 negative controls. The ingestion of green vegetables, but not meat or water, was observed to be associated with the incidence of acute disease. These data reinforce the importance of sanitation control in industrial restaurants and also demonstrate the need for improvement in quality control regarding vegetables at risk for T. gondii oocyst contamination. We emphasized the accurate diagnosis of indexed cases and the detection of asymptomatic infections to determine the extent of the toxoplasmosis outbreak.


2021 ◽  
Author(s):  
Thiago Cerqueira-Silva ◽  
Jason R Andrews ◽  
Viviane S Boaventura ◽  
Otavio T Ranzani ◽  
Vinicius de Araujo Oliveira ◽  
...  

Background. COVID-19 vaccines have proven highly effective among SARS-CoV-2 naive individuals, but their effectiveness in preventing symptomatic infection and severe outcomes among individuals with prior infection is less clear. Methods. Utilizing national COVID-19 notification, hospitalization, and vaccination datasets from Brazil, we performed a case-control study using a test-negative design to assess the effectiveness of four vaccines (CoronaVac, ChAdOx1, Ad26.COV2.S and BNT162b2) among individuals with laboratory-confirmed prior SARS-CoV-2 infection. We matched RT-PCR positive, symptomatic COVID-19 cases with RT-PCR-negative controls presenting with symptomatic illnesses, restricting both groups to tests performed at least 90 days after an initial infection. We used multivariable conditional logistic regression to compare the odds of test positivity, and the odds of hospitalization or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines. Findings. Among individuals with prior SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection ≥ 14 days from vaccine series completion was 39.4% (95% CI 36.1-42.6) for CoronaVac, 56.0% (95% CI 51.4-60.2) for ChAdOx1, 44.0% (95% CI 31.5-54.2) for Ad26.COV2.S, and 64.8% (95% CI 54.9-72.4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose compared with the first dose. Effectiveness against hospitalization or death ≥ 14 days from vaccine series completion was 81.3% (95% CI 75.3-85.8) for CoronaVac, 89.9% (95% CI 83.5-93.8) for ChAdOx1, 57.7% (95% CI -2.6-82.5) for Ad26.COV2.S, and 89.7% (95% CI 54.3-97.7) for BNT162b2.


2019 ◽  
Vol 96 (4) ◽  
pp. 306-311 ◽  
Author(s):  
Stephen J Jordan ◽  
Evelyn Toh ◽  
James A Williams ◽  
Lora Fortenberry ◽  
Michelle L LaPradd ◽  
...  

ObjectivesChlamydia trachomatis (CT) and Mycoplasma genitalium (MG) cause the majority of non-gonococcal urethritis (NGU). The role of Ureaplasma urealyticum (UU) in NGU is unclear. Prior case–control studies that examined the association of UU and NGU may have been confounded by mixed infections and less stringent criteria for controls. The objective of this case–control study was to determine the prevalence and aetiology of mixed infections in men and assess if UU monoinfection is associated with NGU.MethodsWe identified 155 men with NGU and 103 controls. Behavioural and clinical information was obtained and men were tested for Neisseria gonorrhoeae and CT, MG, UU and Trichomonas vaginalis (TV). Men who were five-pathogen negative were classified as idiopathic urethritis (IU).ResultsTwelve per cent of NGU cases in which a pathogen was identified had mixed infections, mostly UU coinfections with MG or CT; 27% had IU. In monoinfected NGU cases, 34% had CT, 17% had MG, 11% had UU and 2% had TV. In controls, pathogens were rarely identified, except for UU, which was present in 20%. Comparing cases and controls, NGU was associated with CT and MG monoinfections and mixed infections. UU monoinfection was not associated with NGU and was almost twice as prevalent in controls. Men in both the case and control groups who were younger and who reported no prior NGU diagnosis were more likely to have UU (OR 0.97 per year of age, 95% CI 0.94 to 0.998 and OR 6.3, 95% CI 1.4 to 28.5, respectively).ConclusionsMixed infections are common in men with NGU and most of these are UU coinfections with other pathogens that are well-established causes of NGU. UU monoinfections are not associated with NGU and are common in younger men and men who have never previously had NGU. Almost half of NGU cases are idiopathic.


2020 ◽  
Vol 9 (8) ◽  
pp. 2369 ◽  
Author(s):  
Diego O. Andrey ◽  
Patrick Cohen ◽  
Benjamin Meyer ◽  
Giulia Torriani ◽  
Sabine Yerly ◽  
...  

Background: Comparative data of SARS-CoV-2 IgM/IgG serology rapid diagnostic tests (RDTs) is scarce. We thus performed a head-to-head comparison of three RDTs. Methods: In this unmatched case-control study, blood samples from 41 RT-PCR-confirmed COVID-19 cases and 50 negative controls were studied. The diagnostic accuracy of three commercially available COVID-19 RDTs: NTBIO (RDT-A), Orient-Gene (RDT-B), and MEDsan (RDT-C), against both a recombinant spike-expressing immunofluorescence assay (rIFA) and Euroimmun IgG ELISA, was assessed. RDT results concordant with the reference methods, and between whole blood and plasma, were established by the Kendall coefficient. Results: COVID-19 cases’ median time from RT-PCR to serology was 22 days (interquartile range (IQR) 13–31 days). Whole-blood IgG detection with RDT-A, -B, and -C showed 0.93, 0.83, and 0.98 concordance with rIFA. Against rIFA, RDT-A sensitivity (SN) was 92% (95% CI: 78–98) and specificity (SP) 100% (95% CI: 91–100), RDT-B showed 87% SN (95% CI: 72–95) and 98% SP (95% CI: 88–100), and RDT-C 100% SN (95% CI: 88–100) and 98% SP (95% CI: 88–100). Against ELISA, SN and SP were above 90% for all three RDTs. Conclusions: RDT-A and RDT-C displayed IgG detection SN and SP above 90% in whole blood. These RDTs could be considered in the absence of routine diagnostic serology facilities.


1997 ◽  
Vol 119 (2) ◽  
pp. 127-134 ◽  
Author(s):  
T. H. ROELS ◽  
P. A. FRAZAK ◽  
J. J. KAZMIERCZAK ◽  
W. R. MACKENZIE ◽  
M. E. PROCTOR ◽  
...  

Consumers in the United States continue to eat raw or undercooked foods of animal origin despite public health warnings following several well-publicized outbreaks. We investigated an outbreak of Salmonella serotype Typhimurium infection in 158 patients in Wisconsin during the 1994 Christmas holiday period. To determine the vehicle and source of the outbreak, we conducted cohort and case-control studies, and environmental investigations in butcher shop A. Eating raw ground beef purchased from butcher shop A was the only item significantly associated with illness [cohort study: relative risk=5·8, 95% confidence interval (CI)=1·5–21·8; case control study: odds ratio=46·2, 95% CI=3·8–2751]. Inadequate cleaning and sanitization of the meat grinder in butcher shop A likely resulted in sustained contamination of ground beef during an 8-day interval. Consumer education, coupled with hazard reduction efforts at multiple stages in the food processing chain, will continue to play an important role in the control of foodborne illness.


2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Mackenzie M. Herzog ◽  
Jessica C. Young ◽  
Jennifer L. Lund ◽  
Virginia Pate ◽  
Christina D. Mack ◽  
...  

Abstract Background This study further investigates a protective association between oral contraceptive (OC) use and anterior cruciate ligament (ACL) injury noted in prior case-control studies. Methods Active comparator new user cohort analysis of women aged 13–45 years in the United States from the IBM MarketScan Commercial Claims and Encounters database who newly-initiated low-dose OCs (exposed) or underwent intrauterine device (IUD) insertion (comparison group) from 2000 to 2014. Women were followed for ACL injury starting 90 days after OC initiation or IUD insertion until OC or IUD discontinuation or end of continuous enrollment. Adjusted hazard ratios (adjHR) and 95% confidence intervals (CI) were estimated controlling for age. Secondary analysis replicated previously-published case-control studies assessing “ever” versus “never” OC use over 1- and 5-year periods among women who underwent ACL reconstruction compared to age-matched controls. Results In the cohort analysis, 2,370,286 women initiated OCs and 621,798 underwent IUD insertion. There were 3571 (0.15%) ACL injuries during an average 370.6 days of continuous OC use and 1620 (0.26%) during an average 590.5 days of IUD use. No difference in risk of ACL injury was observed between OC initiators and IUD users (adjHR = 0.95; 95%CI 0.89, 1.01). The case-control analysis replicated the slight protective association observed in prior studies over a 5-year period (OR = 0.90; 95%CI 0.85, 0.94). Conclusions This cohort study suggests no association between OC use and ACL injury, while the case-control study suggested bias from uncontrolled confounding and selection factors may have influenced previous findings that suggested a protective association between OC use and ACL injury.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S248-S249
Author(s):  
Wan-Ting Huang ◽  
TienYu Owen Yang

Abstract Background In Taiwan, H1N1 vaccination began on November 1, 2009 and coincided with peak H1N1 pandemic activity. Nationwide ecological and case–control studies have identified no substantial association between the use of H1N1 vaccines and narcolepsy; however, wild-type H1N1 virus infection might have triggered narcolepsy onset, or potentially confounded the findings. Methods Data collected in the nationwide case–control study was reanalyzed. Confirmed narcolepsy cases (Brighton levels 1–2 for ages 0–15 years and 1–4a for ages at least 16 years) with onset during November 1, 2009–September 30, 2010 were included and ascertained receipt of H1N1 vaccines. We compared incidence of narcolepsy between the H1N1 vaccinated and unvaccinated population and assessed daily cumulative risk throughout the study period, with adjustment for age. We applied population estimates (census data, 2009) and daily doses of H1N1 vaccines administered (Influenza Vaccine Information System) to calculate the number of persons and person-time for each group. Results There were 22 narcolepsy cases; five (23%) occurred after H1N1 vaccination. The vaccinated population had higher incidence (1.2 vs. 1.0 per million person-years, P = 0.711) (incidence rate ratio 1.24, 95% confidence interval [CI] 0.40–3.83), and higher cumulative risk (1.1 vs. 0.9 per million persons, P = 0.772) (risk ratio 1.16, 95% CI 0.43–3.14) of narcolepsy (figure). These differences, however, were not significant. Conclusion We found comparable average and cumulative risk of narcolepsy between the H1N1 vaccinated and unvaccinated Taiwanese population during the 2009–2010 pandemic. Disclosures All authors: No reported disclosures.


1996 ◽  
Vol 17 (4) ◽  
pp. 249-255
Author(s):  
Jonathan Freeman

AbstractWe provide guidance for new practitioners in the vocabulary of modern epidemiology and the application of quantitative methods. Most hospital epidemiology involves surveillance (observational) data that were not part of a planned experiment, so the rubric and logic of controlled experimental studies cannot be applied. Forms of incidence and prevalence often are confused. The names “cohort study” and “case-control study” are unfortunate, as cohort studies rarely involve cohorts and case-control studies allow no active control by the investigator. Either type of study can be prospective or retrospective. Results of studies with discrete outcomes (infected or not, lived or died) often are represented best by a form of the risk ratio with 95% confidence intervals. The potential distorting effects of selection bias, misclassification, and confounding need to be considered.


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