Quick cell-free DNA testing for the prediction of postconcussion syndrome: a single-center prospective pilot trial

2021 ◽  
pp. 1-7
Author(s):  
Ido Ben Zvi ◽  
Oren Shaia Harel ◽  
Amos Douvdevani ◽  
Penina Weiss ◽  
Chen Cohen ◽  
...  
Keyword(s):  
Large Scale ◽  
Characteristic Curve ◽  
Performance Status ◽  
Pilot Trial ◽  
Normal Function ◽  
Control Group ◽  
Single Center ◽  
Postconcussion Syndrome ◽  
Cell Free Dna ◽  
Free Dna

OBJECTIVE Mild traumatic brain injury (mTBI) is a major cause of emergency room (ER) admission. Thirty percent of mTBI patients have postconcussion syndrome (PCS), and 15% have symptoms for over a year. This population is underdiagnosed and does not receive appropriate care. The authors proposed a fast and inexpensive fluorometric measurement of circulating cell-free DNA (cfDNA) as a biomarker for PCS. cfDNA is a proven, useful marker of a variety of acute pathological conditions such as trauma and acute illness. METHODS Thirty mTBI patients were recruited for this prospective single-center trial. At admission, patients completed questionnaires and blood was drawn to obtain cfDNA. At 3–4 months after injury, 18 patients returned for cognitive assessments with questionnaires and the Color Trails Test (CTT). The fast SYBR Gold assay was used to measure cfDNA. RESULTS Seventeen men and 13 women participated in this trial. The mean ± SD age was 50.9 ± 13.9 years. Of the 18 patients who returned for cognitive assessment, one-third reported working fewer hours, 4 (22.2%) changed their driving patterns, and 5 (27.7%) reduced or stopped performing physical activity. The median cfDNA level of the mTBI group was greater than that of the matched healthy control group (730.5 vs 521.5 ng/ml, p = 0.0395). Admission cfDNA concentration was negatively correlated with performance on the CTT1 and CTT2 standardized tests (r = −0.559 and −0.599), meaning that greater cfDNA level was correlated with decreased cognitive performance status. The performance of the patients with normal cfDNA level included in the mTBI group was similar to that of the healthy participants. In contrast, the increased cfDNA group (> 800 ng/ml) had lower scores on the CTT tests than the normal cfDNA group (p < 0.001). Furthermore, patients with moderate/severe cognitive impairment according to CTT1 results had a greater median cfDNA level than the patients with scores indicating mild impairment or normal function (1186 vs 473.5 ng/ml, p = 0.0441, area under the receiver operating characteristic curve = 0.8393). CONCLUSIONS The data from this pilot study show the potential to use cfDNA, as measured with a fast test, as a biomarker to screen for PCS in the ER. A large-scale study is required to establish the value of cfDNA as an early predictor of PCS.

scholarly journals The use of plasma donor-derived, cell-free DNA to monitor acute rejection after kidney transplantation

2019 ◽  
Vol 35 (4) ◽  
pp. 714-721 ◽  
Author(s):  
Els M Gielis ◽  
Kristien J Ledeganck ◽  
Amélie Dendooven ◽  
Pieter Meysman ◽  
Charlie Beirnaert ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Serum Creatinine ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Threshold Value ◽  
Nucleotide Polymorphisms ◽  
Kidney Transplant Recipients ◽  
Cell Free Dna ◽  
Free Dna ◽  
Set Up

Abstract Background After transplantation, cell-free deoxyribonucleic acid (DNA) derived from the donor organ (ddcfDNA) can be detected in the recipient’s circulation. We aimed to investigate the role of plasma ddcfDNA as biomarker for acute kidney rejection. Methods From 107 kidney transplant recipients, plasma samples were collected longitudinally after transplantation (Day 1 to 3 months) within a multicentre set-up. Cell-free DNA from the donor was quantified in plasma as a fraction of the total cell-free DNA by next generation sequencing using a targeted, multiplex polymerase chain reaction-based method for the analysis of single nucleotide polymorphisms. Results Increases of the ddcfDNA% above a threshold value of 0.88% were significantly associated with the occurrence of episodes of acute rejection (P = 0.017), acute tubular necrosis (P = 0.011) and acute pyelonephritis (P = 0.032). A receiver operating characteristic curve analysis revealed an equal area under the curve of the ddcfDNA% and serum creatinine of 0.64 for the diagnosis of acute rejection. Conclusions Although increases in plasma ddcfDNA% are associated with graft injury, plasma ddcfDNA does not outperform the diagnostic capacity of the serum creatinine in the diagnosis of acute rejection.

Circulating microbial cell-free DNA is associated with inflammatory host-responses in severe pneumonia

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-216013
Author(s):  
Haopu Yang ◽  
Ghady Haidar ◽  
Nameer S Al-Yousif ◽  
Haris Zia ◽  
Daniel Kotok ◽  
...  
Keyword(s):  
Large Scale ◽  
Inflammatory Responses ◽  
Severe Pneumonia ◽  
Systemic Circulation ◽  
Microbial Cell ◽  
Metagenomic Sequencing ◽  
Cell Free Dna ◽  
Free Dna ◽  
Culture Positive ◽  
Culture Negative

Host inflammatory responses predict worse outcome in severe pneumonia, yet little is known about what drives dysregulated inflammation. We performed metagenomic sequencing of microbial cell-free DNA (mcfDNA) in 83 mechanically ventilated patients (26 culture-positive, 41 culture-negative pneumonia, 16 uninfected controls). Culture-positive patients had higher levels of mcfDNA than those with culture-negative pneumonia and uninfected controls (p<0.005). Plasma levels of inflammatory biomarkers (fractalkine, procalcitonin, pentraxin-3 and suppression of tumorigenicity-2) were independently associated with mcfDNA levels (adjusted p<0.05) among all patients with pneumonia. Such host–microbe interactions in the systemic circulation of patients with severe pneumonia warrant further large-scale clinical and mechanistic investigations.

scholarly journals Sauna Yoga Superiorly Improves Flexibility, Strength, and Balance: A Two-Armed Randomized Controlled Trial in Healthy Older Adults

2019 ◽  
Vol 16 (19) ◽  
pp. 3721 ◽  
Author(s):  
Bucht ◽  
Donath
Keyword(s):  
Large Scale ◽  
Controlled Trial ◽  
Pilot Trial ◽  
Intervention Group ◽  
Control Group ◽  
Minimization Method ◽  
Important Indicator ◽  
Randomized Controlled ◽  
Eyes Closed ◽  
Healthy Elderly

Besides strength and balance, flexibility is an important indicator of health-related physical fitness. Thus, the aim of this two-armed randomized controlled pilot trial was to investigate whether sauna yoga at a moderate temperature (50 °C) beneficially affects flexibility, strength, balance, and quality of life (QOL) in healthy elderly community dwellers. Participants were randomly assigned to an intervention group (INT, n = 11, age: 68.7 ± 5.9) or control group (CON, n = 12, age: 69.3 ± 4.9), using the minimization method. Age, physical activity, gender, and the primary outcome flexibility were used as strata for group allocation. Both groups completed similar exercises in the sauna over eight weeks. Only the INT group was exposed to moderate temperatures of 50 °C. Large and statistically significant improvement in favor of the sauna group (INT) was observed for the chair sit-and-reach test (INT: +83%, CON +3%, p = 0.028, nр² = 0.24). The shoulder and lateral spine flexibility were not relevantly affected. Strength in the lower extremities merely showed a tendency to significant changes (INT: 16%, CON: 3%, p = 0.061, nр² = 0.181). Additionally, balance abilities, with eyes closed, improved (INT: 187%, CON +58%, p = 0.056, nр² = 0.189) in favor of the INT group. QOL only improved in favor of the INT for environmental dimension (INT: +7%, CON: 0%, p = 0.034, nр² = 0.227). These first but preliminary findings indicate that sauna yoga may serve as a promising and feasible means to improve flexibility in elderly people. Strength and balance do not meaningfully benefit from a sauna environment, although strength improved to a slightly higher extent in the sauna group. Future large-scale research is needed to elucidate underlying mechanisms and corroborate these findings

scholarly journals Targeted fetal cell‐free DNA screening for aneuploidies in 4,594 pregnancies: Single center study

2019 ◽  
Vol 7 (7) ◽  
Author(s):  
Altug Koc ◽  
Ozge Ozer Kaya ◽  
Berk Ozyilmaz ◽  
Yasar B. Kutbay ◽  
Ozgur Kirbiyik ◽  
...  
Keyword(s):  
Fetal Cell ◽  
Single Center ◽  
Cell Free Dna ◽  
Free Dna ◽  
Single Center Study ◽  
Center Study

scholarly journals Evaluation of five cell-free DNA isolation kits for plasma

2019 ◽  
Author(s):  
Zhongzhen Liu ◽  
Xi Yang ◽  
Haixiao Chen ◽  
Sujun Zhu ◽  
Juan Zeng ◽  
...  
Keyword(s):  
Clinical Application ◽  
Large Scale ◽  
Circulating Dna ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Prenatal Test ◽  
Wide Scale ◽  
The Cost ◽  
Pooled Samples

AbstractCell-free DNA (cfDNA) has been widely used in prenatal test and cancer diagnosis nowadays. The cost- and time-effective isolation kits are needed especially in large-scale clinical application. Here, we compared three domestic kits: VAHTS Serum/Plasma Circulating DNA kit (VZ), MagPure Gel Pure DNA mini kit (MG) and Serum/Plasma Circulating DNA Kit (TG), together with QIAamp Circulating Nucleic Acid Kit (QC) and QIAamp DNA Blood Mini Kit (QD) in cfDNA isolation. cfDNA was isolated from the pooled samples with spike-in fragments, qPCR was conducted to quantify the spike-in fragments recovery. The results indicated that all of the five kits could isolate cfDNA with different efficiency. The VZ kit had an efficiency as high as 90 percent, which is comparable to QC kit. The libraries were constructed using the isolated cfDNAs, quantified by Qubit and analyzed by 2100 bioanalyzer. Both showed the libraries were qualified. Finally, cffDNAs were detected by qPCR targeting SRY gene using libraries from pregnant women bearing male fetuses. All five kits could isolate cffDNAs that could be detected by qPCR. Our results provided more choices in wide-scale clinical application of cfDNA-based non-invasive genetic tests.

scholarly journals Targeting of cell-free DNA by DNase I diminishes endothelial dysfunction and inflammation in a rat model of cardiopulmonary bypass

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Carolyn Weber ◽  
Alexander Jenke ◽  
Vasilena Chobanova ◽  
Mariam Yazdanyar ◽  
Agunda Chekhoeva ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Endothelial Dysfunction ◽  
Adhesion Molecules ◽  
Therapeutic Strategy ◽  
Dnase I ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Cell Free Dna ◽  
Free Dna ◽  
Group 3

AbstractThe use of cardiopulmonary bypass (CPB) results in the activation of leukocytes, release of neutrophil extracellular traps (NETs) and severe inflammation. We hypothesize that targeting of circulating cell-free DNA (cfDNA) by DNases might represent a feasible therapeutic strategy to limit CPB-associated side effects. Male Wistar rats (n = 24) underwent CPB with deep hypothermic circulatory arrest (DHCA) and were divided into 3 groups: control (group 1), one i.v. bolus DNase I before CPB start (group 2) and a second DNase I dose before reperfusion (group 3). We found a positive correlation between plasma cfDNA/NETs levels and compromised endothelial vasorelaxation after CPB. DNase I administration significantly diminished plasma cfDNA/NETs levels. Further, a dose-dependent improvement in endothelial function accompanied by significant reduction of circulating intercellular adhesion molecule (ICAM)-1 was observed. Rats of group 3 had significantly reduced plasma IL-6 levels and downregulated expression of adhesion molecules resulting in impaired leukocyte extravasation and reduced MPO activity in lungs. Mechanistically, digestion of NETs by DNase I significantly diminished NETs-dependent upregulation of adhesion molecules in human endothelial cells. Altogether, systemic DNase I administration during CPB efficiently reduced cfDNA/NETs-mediated endothelial dysfunction and inflammation and might represents a promising therapeutic strategy for clinical practice.

Single‐center utilization of donor‐derived cell‐free DNA testing in the management of heart transplant patients

2021 ◽  
Author(s):  
Keerthi T. Gondi ◽  
Andrew Kao ◽  
Jodie Linard ◽  
Bethany A. Austin ◽  
Mark P. Everley ◽  
...  
Keyword(s):  
Heart Transplant ◽  
Single Center ◽  
Dna Testing ◽  
Cell Free Dna ◽  
Transplant Patients ◽  
Free Dna

scholarly journals Circulating cell free DNA and miRNA Amount in Congenital Hearing Loss

Acta Medica ◽  
2018 ◽  
Vol 49 (3) ◽  
pp. 19
Author(s):  
Ozge Caglar ◽  
Akin Cayir ◽  
Begum Cilgin ◽  
Sefa Derekoy
Keyword(s):  
Hearing Loss ◽  
Private School ◽  
Deaf Children ◽  
Control Group ◽  
Congenital Hearing Loss ◽  
Healthy Individuals ◽  
Cell Free Dna ◽  
Free Dna ◽  
Group 5 ◽  
Circulating Cell Free Dna

Objective: Our aim is to detect the amount of miRNA and free DNA in the peripheral blood of young people with congenital hearing loss and compare this with control group. Materials and Methods: In our study, 16 patients who have congenital hearing loss and  go to the private school for deaf children and 16 healthy individuals  were selected in the same age group.  5 cc blood was taken from peripheral vessels of   each individual. We compared the circulating cell-free DNA and miRNA amount with the results of the control group. Results: The ccfDNA amount of the patients with hearing loss was lower than the control group and  It was  statistically significant. On the contrary, we found the higher amount of ccfmiRNA in plasma samples of the patients with hearing loss. The statistical analysis showed that ccfmiRNA amount in congenital loss is consistently significantly higher than the control group. Conclusion: The miRNA and freeDNA can be used early in the diagnosis of congenital hearing loss.

scholarly journals Lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsis

2019 ◽  
Author(s):  
Axel Nyberg ◽  
Alexander Larsson ◽  
Juulia Jylhävä ◽  
Mikko Hurme ◽  
Jesper Sperber ◽  
...  
Keyword(s):  
Tidal Volume ◽  
Hepatic Vein ◽  
Venous Blood ◽  
Jugular Bulb ◽  
Protective Ventilation ◽  
Lung Protective Ventilation ◽  
Control Group ◽  
Cell Free Dna ◽  
Free Dna ◽  
Organ Specific

Abstract Background: Plasma levels of cell-free DNA (cf-DNA) are known to be elevated in sepsis and high levels are associated with a poor prognosis. Mechanical ventilation affects systemic inflammation in which lung-protective ventilation attenuates the inflammatory response. Aim: To study the effect of tidal volume and PEEP on arterial and organ-specific venous blood as well as on trans-organ differences in cf-DNA levels in a porcine post-operative sepsis model. Method: One group of anaesthetised, domestic-breed, 9-12 weeks old, pigs were ventilated with protective ventilation (VT 6mL x kg-1, PEEP 10 cmH2O) n=20. Another group, ventilated with a medium high tidal volume and lower PEEP, served as a control group (VT 10 mL x kg-1, PEEP 5 cm H2O) n=10. Blood samples were taken from four sources: artery, hepatic vein, portal vein and, jugular bulb. A continuous endotoxin infusion at 0.25 µg x kg-1 x h-1 for 5 h was started following 2 h of laparotomy, which simulated a surgical procedure. Inflammatory cytokines and cf-DNA in plasma were analysed and trans-organ differences calculated. Results: The protective ventilation group had lower levels of cf-DNA in arterial (p=0.02) and hepatic venous blood (p=0.03) compared with the controls. Transhepatic differences in cf-DNA were lower in the protective group, compared with the controls (p=0.03). No differences between the groups were noted as regards the transcerebral, transsplanchnic or the transpulmonary cf-DNA differences. Conclusions: Protective ventilation suppresses arterial levels of cf-DNA. The liver seems to be a net contributor to the systemic cf-DNA levels, but this effect is attenuated by protective ventilation.

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