Exploring free pregnancy associated plasma protein a (fPAPP-A) as a biomarker in early pregnancy.

Objectives: In combined first trimester screening for Down syndrome, Pregnancy-Associated Plasma Protein A (PAPP-A) is pivotal. PAPP-A tests evaluate total PAPP-A, consisting of the biologically active free PAPP-A (fPAPP-A) and PAPP-A complexed with eosinophil major basic protein's proform (proMBP). While PAPP-A is well-researched, limited understanding persists regarding fPAPP-A's first trimester concentrations and diagnostic utility. Design: and methods: PAPP-A and fPAPP-A levels were gauged in 602 serum samples at 2-week intervals (gestational weeks 4-14) from 159 women with delivery of a healthy neonate and 80 samples from 37 miscarriages. The final sample at the time of diagnosis from women who miscarried was included in analyses. Results: During the first trimester, PAPP-A and fPAPP-A levels displayed significant and strong correlation (r = 0.94), with median values doubling weekly. Free PAPP-A constituted only 3.0 % of PAPP-A over gestational weeks. Low fPAPP-A linked to miscarriage (p < 0.001), maternal weight (p < 0.001), and smoking (p = 0.02). For miscarriage prediction fPAPP-A was equal to PAPP-A (area under the receiver operating characteristics curve 0.79 vs. 0.81, p = 0.44). Conclusions: Investigating fPAPP-A presence and concentration directly in first trimester serum has not been done previously. This study report lower fPAPP-A values than anticipated from prior enzymatic studies of fPAPP-A. fPAPP-A was not superior to PAPP-A as a first trimester biomarker in this dataset.

Tenascin-C in patients with central nervous system infections.

BACKGROUND: The extracellular matrix protein tenascin-C has been discovered to be an important regulator of the response to tissue injury and repair in cerebrovascular diseases. This study investigated if tenascin-C is released in response to infections in the central nervous system (CNS). METHODS: Tenascin-C concentration in the cerebrospinal fluid (CSF) was measured in patients, (>18 years) with and without CNS infections, admitted to a department of infectious diseases in Denmark. CSF tenascin-C was measured on the Meso-scale platform. RESULTS: 174 patients were included of which 140 were diagnosed with a CNS infection and 34 where this was ruled out (control group). Median CSF tenascin-C levels were significantly higher among patients with bacterial meningitis (147 pg/mL), viral meningitis (33 mg/mL), viral encephalitis (39 pg/mL) and Lyme neuroborreliosis (45 pg/mL) when compared to controls (21 pg/mL). Correlations between tenascin-C and CSF markers of inflammation and age were only moderate. CONCLUSION: Levels of CSF tenascin-C are higher among patients with bacterial and viral neuroinfections, already on admission, but exhibit only a modest correlation with baseline indices of neuroinflammation. CSF tenascin-C is highest among patients with bacterial meningitis compared to the other CNS infections. Patients with unfavorable outcomes presented with higher median CSF tenascin-C than their counterparts.

A Novel Approach to Predicting Early Pregnancy Outcomes Dynamically in a Prospective Cohort Using Repeated Ultrasound and Serum Biomarkers.

This study aimed to develop a dynamic model for predicting outcome during the first trimester of pregnancy using baseline demographic data and serially collected blood samples and transvaginal sonographies. A prospective cohort of 203 unselected women with an assumed healthy pregnancy of < 8 weeks' gestation was followed fortnightly from 4-14 weeks' gestation until either miscarriage or confirmed first trimester viability. The main outcome was development of a model to predict outcome from gestational age-dependent hazard ratios using both baseline and updated serial data from each visit. Secondary outcomes were descriptions of risk factors for miscarriage. The results showed that 18% of the women experienced miscarriages. A fetal heart rate detected before 8 weeks' gestation indicated a 90% (95% CI 85-95%) chance of subsequent delivery. Maternal age (≥ 35 years), insufficient crown-rump-length (CRL) and mean gestational sac diameter (MSD) development, and presence of bleeding increased the risk of miscarriage. Serum biomarkers, including hCG, progesterone, and estradiol, were found to impact the risk of miscarriage with estradiol as the most important. The best model to predict miscarriage was a combination of maternal age, vaginal bleeding, CRL, and hCG. The second-best model was the sonography-absent model of maternal age, bleeding, hCG, and estradiol. This study suggests that combining maternal age, and evolving data from hCG, estradiol, CRL, and bleeding could be used to predict fetal outcome during the first trimester of pregnancy.Trial registration ClinicalTrials.gov identifier: NCT02761772.

Pentraxin 3 in the cerebrospinal fluid during central nervous system infections: A retrospective cohort study.

The present study describes diagnostic and prognostic abilities of Cerebrospinal fluid (CSF) Pentraxin 3 (PTX3) in central nervous system (CNS) infections. CSF PTX3 was measured retrospectively from 174 patients admitted under suspicion of CNS infection. Medians, ROC curves and Youdens index was calculated. CSF PTX3 was significantly higher among all CNS infections and undetectable in most of the patients in the control group, and significantly higher in bacterial infections compared to viral and Lyme infections. No association was found between CSF PTX3 and Glasgow Outcome Score. PTX3 in the CSF can distinguish bacterial infection from viral and Lyme infections and non-CNS infections. Highest levels were found in bacterial meningitis. No prognostic abilities were found.

A non-enzymatic, isothermal strand displacement and amplification assay for rapid detection of SARS-CoV-2 RNA.

The current nucleic acid signal amplification methods for SARS-CoV-2 RNA detection heavily rely on the functions of biological enzymes which imposes stringent transportation and storage conditions, high cost and global supply shortages. Here, a non-enzymatic whole genome detection method based on a simple isothermal signal amplification approach is developed for rapid detection of SARS-CoV-2 RNA and potentially any types of nucleic acids regardless of their size. The assay, termed non-enzymatic isothermal strand displacement and amplification (NISDA), is able to quantify 10 RNA copies.µL-1. In 164 clinical oropharyngeal RNA samples, NISDA assay is 100 % specific, and it is 96.77% and 100% sensitive when setting up in the laboratory and hospital, respectively. The NISDA assay does not require RNA reverse-transcription step and is fast (<30 min), affordable, highly robust at room temperature (>1 month), isothermal (42 °C) and user-friendly, making it an excellent assay for broad-based testing.

Triage Strategies Based on C-Reactive Protein Levels and SARS-CoV-2 Tests among Individuals Referred with Suspected COVID-19: A Prospective Cohort Study.

C-reactive protein (CRP) has prognostic value in hospitalized patients with COVID-19; the importance of CRP in pre-hospitalized patients remains to be tested. Methods: Individuals with symptoms of COVID-19 had a SARS-CoV-2 PCR oropharyngeal swab test, and a measurement of CRP was performed at baseline, with an upper reference range of 10 mg/L. After 28 days, information about possible admissions, oxygen treatments, transfers to the ICU, or deaths was obtained from the patient files. Using logistic regression, the prognostic value of the CRP and SARS-CoV-2 test results was evaluated. Results: Among the 1006 patients included, the SARS-CoV-2 PCR test was positive in 59, and the CRP level was elevated (>10 mg/L) in 131. In total, 59 patients were hospitalized, only 3 of whom were SARS-CoV-2 positive, with elevated CRP (n = 2) and normal CRP (n = 1). The probability of being hospitalized with elevated CRP was 4.21 (95%CI 2.38-7.43, p < 0.0001), while the probability of being hospitalized with SARS-CoV-2 positivity alone was 0.85 (95%CI 0.26-2.81, p = 0.79). Conclusions: CRP is not a reliable predictor for the course of SARS-CoV-2 infection in pre-hospitalized patients. CRP, while not a SARS-CoV-2 positive test, had prognostic value in the total population of patients presenting with COVID-19-related symptoms.

Validity of data in the Danish Colorectal Cancer Screening Database.

BACKGROUND: In Denmark, a nationwide screening program for colorectal cancer was implemented in March 2014. Along with this, a clinical database for program monitoring and research purposes was established. OBJECTIVE: The aim of this study was to estimate the agreement and validity of diagnosis and procedure codes in the Danish Colorectal Cancer Screening Database (DCCSD). METHODS: All individuals with a positive immunochemical fecal occult blood test (iFOBT) result who were invited to screening in the first 3 months since program initiation were identified. From these, a sample of 150 individuals was selected using stratified random sampling by age, gender and region of residence. Data from the DCCSD were compared with data from hospital records, which were used as the reference. Agreement, sensitivity, specificity and positive and negative predictive values were estimated for categories of codes "clean colon", "colonoscopy performed", "overall completeness of colonoscopy", "incomplete colonoscopy", "polypectomy", "tumor tissue left behind", "number of polyps", "lost polyps", "risk group of polyps" and "colorectal cancer and polyps/benign tumor". RESULTS: Hospital records were available for 136 individuals. Agreement was highest for "colorectal cancer" (97.1%) and lowest for "lost polyps" (88.2%). Sensitivity varied between moderate and high, with 60.0% for "incomplete colonoscopy" and 98.5% for "colonoscopy performed". Specificity was 92.7% or above, except for the categories "colonoscopy performed" and "overall completeness of colonoscopy", where the specificity was low; however, the estimates were imprecise. CONCLUSION: A high level of agreement between categories of codes in DCCSD and hospital records indicates that DCCSD reflects the hospital records well. Further, the validity of the categories of codes varied from moderate to high. Thus, the DCCSD may be a valuable data source for future research on colorectal cancer screening.

[Beta-thalassemia in a Danish family]. / Beta-thalassaemia hos en dansk familie.

We report a case of beta-thalassaemia in a family of Danish origin, owing to a C to T substitution in codon 39 of the beta-globin gene.