Blood amyloid β oligomerization as a biomarker of Alzheimer’s disease: a blinded validation study

2020 ◽  
Author(s):  
Young Chul Youn ◽  
Byoung Sub Lee ◽  
Gwang Je Kim ◽  
Ji Sun Ryu ◽  
Kuntaek Lim ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Sensitivity And Specificity ◽  
Detection System ◽  
Amyloid Β ◽  
High Sensitivity ◽  
Community Based ◽  
Clinical Sensitivity ◽  
Aβ Oligomerization ◽  
Normal Cognition

Abstract INTRODUCTION: Oligomeric amyloid ß (Aß) is one of the major contributors to the pathomechanism of AD; Aß oligomerization in plasma can be measured using a Multimer Detection System-Oligomeric Aß (MDS-OAß) after incubation with spiked synthetic Aß. METHODS: We evaluated the clinical sensitivity and specificity of the MDS-OAß values by inBlood TM OAß test using heparin-treated plasma samples from 52 AD patients in comparison with 52 community-based subjects with normal cognition (NC). The inclusion criterion was proposed by the NINCDS-ADRDA and additionally required for the least 6 months of follow-up from the initial clinical diagnosis in the course of AD. RESULTS: The MDS-OAβ values were 1.43 ± 0.30 ng/ml in AD and 0.45 ± 0.19 ( p <0.001) in NC, respectively. Using a cut-off value of 0.78 ng/ml, the results revealed that 100% sensitivity 92.31% specificity. DISCUSSION: MDS-OAß to measure plasma Aβ oligomerization is a valuable blood-based biomarker for clinical diagnosis of AD, with high sensitivity and specificity.

scholarly journals Novel Blood Biomarkers for an Earlier Diagnosis of Alzheimer’s Disease: A Literature Review

2020 ◽  
Author(s):  
Shiavax Rao ◽  
Andrew J. Boileau
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Literature Review ◽  
Clinical Diagnosis ◽  
Sensitivity And Specificity ◽  
Memory Loss ◽  
High Sensitivity ◽  
Diagnostic Techniques ◽  
Pubmed Database ◽  
Diagnostic Approaches

Alzheimer’s disease is a neurodegenerative condition associated with neurofibrillary tangles and cortical deposition of amyloid plaques. Clinical presentation of the disease involves manifestations such as memory loss, cognitive decline and dementia with some of the earliest reported deficits being episodic memory impairment and olfactory dysfunction. Current diagnostic approaches rely on autopsy characterization of gross brain pathology, or brain imaging of biomarkers late in the disease course. The aim of this literature review is to identify and compare newly emerging and novel CSF, serum and mucosal biomarkers, with the potential of making an earlier clinical diagnosis of Alzheimer’s disease. Utilizing such techniques may allow for earlier therapeutic intervention, reduction of disability and enhancement of quality of life. Literature review and analysis was performed by screening the PubMed database for relevant studies within the past 5 years. All studies showed statistically significant (P < 0.05) differences in testing between AD patients and controls. Two categories of serum biomarkers (redox-reactive antiphospholipid antibodies and microRNAs) and an olfactory mucosal marker (microRNA-206) could discriminate between early AD patients and controls with high sensitivity and specificity. In conclusion, certain studies have shown promising results with high sensitivity and specificity, high discriminative potential for Alzheimer’s disease early in its progression, and statistically significant results in larger study samples. Utilization of such diagnostic techniques should increase the efficacy of making an earlier clinical diagnosis of Alzheimer’s disease.

scholarly journals Peripheral Inflammatory Biomarkers for Myocardial Infarction Risk: A Prospective Community-Based Study

2017 ◽  
Vol 63 (3) ◽  
pp. 663-672 ◽  
Author(s):  
Zhijun Wu ◽  
Zhe Huang ◽  
Wei Jin ◽  
Eric B Rimm ◽  
Alice H Lichtenstein ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Repeated Measures ◽  
High Sensitivity ◽  
Community Based ◽  
Reactive Protein ◽  
Inflammatory Status ◽  
Increased Risk ◽  
Hs Crp ◽  
Wbc Count

Abstract BACKGROUND Most previous studies regarding chronic inflammation and risk of myocardial infarction (MI) have lacked repeated measures of high-sensitivity C-reactive protein (hs-CRP) and/or white blood cell (WBC) count over time. We examined whether cumulative average and longitudinal changes in these biomarkers were associated with subsequent MI risk. METHODS In this prospective, community-based study, we included 82544 Chinese participants [66796 men and 15748 women; mean (SD) age 55.1 (9.86) y] without prior cardiovascular diseases or cancer at baseline (2006–2007). hs-CRP, WBC and other clinical covariates were assessed at baseline and every 2 years during follow-up. RESULTS During 6 years of follow-up (2006–2012), we documented 714 incident MI cases. Higher baseline and cumulative average concentrations of hs-CRP and/or WBC were consistently associated with increased risk of MI (Ptrend &lt;0.001 for both). Longitudinal increase in hs-CRP (Ptrend &lt;0.001), but not WBC, was also associated with a higher future risk of MI, after adjustment for their baseline values and other covariates. Each 1-mg/L increment per year in hs-CRP was associated with a 9.3% increase in risk for future MI [hazard ratio (HR) = 1.09, 95% CI, 1.03; 1.17]. Participants with high-grade inflammatory status (hs-CRP ≥10 mg/L and WBC ≥10 × 109/L) had a higher risk of MI occurring &lt;3 months after hs-CRP/WBC assessments vs those with hs-CRP &lt;0.5 mg/L and WBC &lt;5 × 109/L (HR = 6.64; 95% CI, 1.49–29.6), as compared with MI occurring ≥4 years (HR = 2.95; 95% CI, 0.90, 9.65). CONCLUSIONS Plasma hs-CRP concentration and WBC predicted MI risk. Longitudinal increase in hs-CRP was also associated with a higher risk of MI.

Objectification of vocal folds mucosal wave

2018 ◽  
Vol 72 (5) ◽  
pp. 24-30
Author(s):  
Paulina Krasnodębska ◽  
Wiktor Krasnodębski ◽  
Agata Szkiełkowska
Keyword(s):  
Clinical Diagnosis ◽  
Sensitivity And Specificity ◽  
Clinical Utility ◽  
Voice Disorders ◽  
High Sensitivity ◽  
Vocal Folds ◽  
Wave Measurement ◽  
Voice Pathologies

The work assessed the clinical utility of open quotients measured during laryngovideostroboscopy and electroglottography. Values of the parameters were analyzed according to clinical diagnosis. An algorithm based on direct and indirect mucosal wave measurement is presented, which allows for differentiation of voice disorders. The method developed for the objectification of glottal functions in various voice pathologies is characterized by high sensitivity and specificity.

scholarly journals Canine Leishmaniasis in Brazil: Serological Follow-Up of a Dog Population in an Endemic Area of American Visceral Leishmaniasis

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Alba Valéria Machado da Silva ◽  
Adelzon Assis de Paula ◽  
Daniela de Pita Pereira ◽  
Reginaldo Peçanha Brazil ◽  
João Carlos Araujo Carreira
Keyword(s):  
Visceral Leishmaniasis ◽  
Western Blot ◽  
Sensitivity And Specificity ◽  
Endemic Area ◽  
High Sensitivity ◽  
Control Measures ◽  
Canine Leishmaniasis ◽  
Indirect Immunofluorescent Assay ◽  
Indirect Immunofluorescent

We performed a serological, clinical, and parasitological follow-up of a dog population in an endemic area of American Visceral Leishmaniasis estimated by indirect immunofluorescent assay (IFA) and western blot (WB). After twelve months, the results obtained from IFA demonstrated that 50% were seropositive and two serological profiles were observed: the first one ranging from 1/40 to 1/80 and the second≥1/160. By WB, it was observed that the same percentage and sera from positive dogs presented the recognition of the peptides of 29 and 32 kDa up to 8 months before IFA serum conversion. Among the positive dogs, all the sera from symptomatic ones with tissue parasitism recognized the peptide of 68.5 kDa. Our results suggest the need of modifications in the control measures regarding the elimination of the dogs. They also corroborate the high sensitivity and specificity of western blot in the diagnosis of canine leishmaniasis, suggesting the possibility of its association with IFA.

scholarly journals Is transcranial sonography useful for diagnosing Parkinson’s disease in clinical practice?

2018 ◽  
Vol 76 (7) ◽  
pp. 459-466 ◽  
Author(s):  
Talyta Cortez Grippe ◽  
Nasser Allam ◽  
Pedro Renato de Paula Brandão ◽  
Danilo Assis Pereira ◽  
Francisco Eduardo Costa Cardoso ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Diagnosis ◽  
Positive Likelihood Ratio ◽  
High Sensitivity ◽  
Transcranial Sonography ◽  
Substantia Nigra Hyperechogenicity ◽  
Practical Usefulness ◽  
Alternative Condition

ABSTRACT Transcranial sonography (TCS) is an emerging ancillary examination for diagnosing Parkinson’s disease (PD). Objective To evaluate TCS features in patients with PD and its mimics, and establish their accuracy in predicting the final clinical diagnosis after follow-up. Methods We retrospectively studied 85 patients with an initial clinical suspicion of PD, atypical parkinsonism or essential tremor, all of whom underwent TCS. Two specialists reviewed the follow-up clinical visit records and determined the final clinical diagnosis. The accuracy analysis of the TCS was determined using Bayesian statistical methods. Results The finding of substantia nigra hyperechogenicity (> 20 mm2) showed high sensitivity (93.4%) and specificity (86.6%). The positive likelihood ratio showed 6.93-fold greater odds for diagnosing PD than an alternative condition when this finding was present. Conclusions This study revealed the practical usefulness of TCS in differentiating PD from its prevalent mimics when the clinical diagnosis was initially unclear.

scholarly journals Sensitive detection of multiple islet autoantibodies in type 1 diabetes using small sample volumes by agglutination-PCR

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242049
Author(s):  
Felipe de Jesus Cortez ◽  
David Gebhart ◽  
Peter V. Robinson ◽  
David Seftel ◽  
Narges Pourmandi ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Sensitivity And Specificity ◽  
High Sensitivity ◽  
Small Sample ◽  
Insulin Autoantibodies ◽  
Islet Autoantibodies ◽  
Antibody Detection ◽  
Clinical Sensitivity ◽  
Analysis Platform

Islet autoantibodies are predominantly measured by radioassay to facilitate risk assessment and diagnosis of type 1 diabetes. However, the reliance on radioactive components, large sample volumes and limited throughput renders radioassay testing costly and challenging. We developed a multiplex analysis platform based on antibody detection by agglutination-PCR (ADAP) for the sample-sparing measurement of GAD, IA-2 and insulin autoantibodies/antibodies in 1 μL serum. The assay was developed and validated in 7 distinct cohorts (n = 858) with the majority of the cohorts blinded prior to analysis. Measurements from the ADAP assay were compared to radioassay to determine correlation, concordance, agreement, clinical sensitivity and specificity. The average overall agreement between ADAP and radioassay was above 91%. The average clinical sensitivity and specificity were 96% and 97%. In the IASP 2018 workshop, ADAP achieved the highest sensitivity of all assays tested at 95% specificity (AS95) rating for GAD and IA-2 autoantibodies and top-tier performance for insulin autoantibodies. Furthermore, ADAP correctly identified 95% high-risk individuals with two or more autoantibodies by radioassay amongst 39 relatives of T1D patients tested. In conclusion, the new ADAP assay can reliably detect the three cardinal islet autoantibodies/antibodies in 1μL serum with high sensitivity. This novel assay may improve pediatric testing compliance and facilitate easier community-wide screening for islet autoantibodies.

scholarly journals Will Fluoroscopic Follow-up after Stent-Assisted Coiling of Cerebral Aneurysms Provide Information on Recanalization?

2014 ◽  
Vol 20 (6) ◽  
pp. 693-703 ◽  
Author(s):  
Hyun Ho Oh ◽  
Cheolkyu Jung ◽  
Tae Hong Lee ◽  
Bae Ju Kwon ◽  
Young Kim ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Imaging Modality ◽  
False Negative ◽  
Cerebral Aneurysms ◽  
High Sensitivity ◽  
Outpatient Basis ◽  
Good Imaging ◽  
Sensitivity Specificity ◽  
Interreader Agreement

Fluoroscopic images for comparison (FICs) can be easily obtained for follow-up on an outpatient basis. This study retrospectively assessed the diagnostic performance of a set of FICs for evaluation of recanalization after stent-assisted coiling, with digital subtraction angiography (DSA) as the reference standard. A total of 124 patients harboring 144 stent-assisted coiled aneurysms were included. At least one month postembolization they underwent follow-up angiograms comprising a routine frontal and lateral DSA and a working-angle DSA. For analysis, FICs should be compared with the mask images of postprocedural DSAs to find recanalization. Instead of FIC acquisition, the mask images of follow-up DSAs were taken as a substitute because of the same view-making processes as FICs, full availability, and perfect coincidence with follow-up DSAs. Two independent readers evaluated a set of 169 FICs and DSA images for the presence of recanalization one month apart. Sensitivity, specificity, and interreader agreement were determined. Recanalization occurred in 24 (14.2%) cases. Of these, nine (5.3%) cases were found to have significant recanalization in need of retreatment. Sensitivity and specificity rates were 79.2% (19 of 24) and 95.9% (139 of 145) respectively for reader 1, and 66.7% (16 of 24) and 97.9% (142 of 145) for reader 2. Minimal recanalization was identified in seven out of all eight false negative cases. Excluding minimally recanalized cases in no need for retreatment from the recanalization group, calculation resulted in high sensitivity and specificity of over 94% for both readers. Interreader agreement between the two readers was excellent (96.4%; κ = 0.84). FICs may be a good imaging modality to detect significant recanalization of stent-assisted coiled aneurysms.

Transient adverse events positively associated with patent foramen ovale after ultrasound-guided foam sclerotherapy

2009 ◽  
Vol 24 (3) ◽  
pp. 114-119 ◽  
Author(s):  
Pauline Raymond-Martimbeau
Keyword(s):  
Adverse Events ◽  
Sensitivity And Specificity ◽  
Patent Foramen Ovale ◽  
Varicose Veins ◽  
High Sensitivity ◽  
Foramen Ovale ◽  
Ultrasound Guided ◽  
Foam Sclerotherapy ◽  
Phone Calls

Objectives To prospectively study the association between patent foramen ovale (PFO) detected by contrast transcranial Doppler (cTCD) and adverse events (AEs) reported by patients after ultrasound-guided foam sclerotherapy (UGFS) for the treatment of varicose veins. Methods All patients reporting AEs after UGFS were studied using cTCD directed at the middle cerebral artery to determine the Spencer grading score by counting high-intensity transient signals. Agitated saline was used as the contrast medium. The Spencer grading score determined the presence or absence of PFO. All patients undergoing UGFS received follow-up phone calls within 24 hours and again two weeks after the procedure. Results Of the 3259 patients who underwent UGFS, AEs were reported by seven (0.21%) patients at their first session. These included visual disturbance, migraine and chest discomfort. Five (71.4%) of these seven patients tested positive for PFO by cTCD. The two-week follow-up confirmed no permanent symptoms. Published studies show high sensitivity and specificity for cTCD when compared with contrast transesophageal echocardiography (cTEE). Conclusions The overall rate of AEs reported is consistent with published results. The presence of a PFO was detected in most patients reporting AEs after undergoing UGFS. While PFO screening with high sensitivity and specificity can be performed efficiently in the clinic setting, based on the literature, further investigation is warranted.

scholarly journals Clinical Validation of Novel Chip-Based Digital PCR Platform for Fetal Aneuploidies Screening

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1131
Author(s):  
Anna Nykel ◽  
Rafał Woźniak ◽  
Agnieszka Gach
Keyword(s):  
Sensitivity And Specificity ◽  
Clinical Performance ◽  
High Sensitivity ◽  
Digital Pcr ◽  
Trisomy 13 ◽  
Prenatal Diagnostics ◽  
Aneuploidy Screening ◽  
Clinical Sensitivity ◽  
Fetal Aneuploidy ◽  
Increased Risk

Fetal aneuploidy is routinely diagnosed by karyotyping. The development of techniques for rapid aneuploidy detection based on the amplification reaction allows cheaper and rapid diagnosis. However, the currently available solutions have limitations. We tested a novel approach as a diagnostic tool in clinical practice. The objective of this study was to provide a clinical performance of the sensitivity and specificity of a novel chip-based digital PCR approach for fetal aneuploidy screening. The study was conducted in 505 pregnant women with increased risk for fetal aneuploidy undergoing invasive prenatal diagnostics. DNA extracted from amniotic fluid or CVS was analyzed for the copy number of chromosomes 13, 18, 21, X, and Y using a new chip-based solution. Performance was assessed by comparing results with findings from karyotyping. Aneuploidy was confirmed in 65/505 cases positive for trisomy 21, 30/505 cases positive for trisomy 18, 14/505 cases positive for trisomy 13 and 21/505 with SCAs. Moreover, 2 cases with triploidy and 2 cases with confirmed mosaicisms of 21 and X chromosomes were detected. Clinical sensitivity and specificity within this study was determined at 100% for T21 (95% CI, 99.26–100%), T18 (95% CI, 99.26–100%), and T13 (95% CI, 99.26–100%). Chip-based digital PCR provides equally high sensitivity and specificity in rapid aneuploidy screening and can be implemented into routine prenatal diagnostics.

scholarly journals Software for the Diagnosis of Sarcopenia in Community-Dwelling Older Adults: Design and Validation Study

10.2196/13657 ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. e13657 ◽  
Author(s):  
Lydia Lera ◽  
Bárbara Angel ◽  
Carlos Márquez ◽  
Rodrigo Saguez ◽  
Cecilia Albala
Keyword(s):  
Sensitivity And Specificity ◽  
Latin American ◽  
Daily Living ◽  
Diagnostic Algorithm ◽  
High Sensitivity ◽  
Community Dwelling ◽  
Incidence Density ◽  
Mobility Limitations ◽  
European Working

Background The usual diagnosis of sarcopenia requires a dual-energy x-ray absorptiometry (DXA) exam, which has low accessibility in primary care for Latin American countries. Objective The aim of this study is to design and validate software for mobile devices (Android, IOS) and computers, based on an adapted version of the diagnostic algorithm of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). Methods Follow-up exams were conducted on 430 community-dwelling Chileans 60 years and older (mean 68.2 years, SD 4.9) participating in the IsaMayor and Alexandros cohorts designed to study sarcopenia and disability associated with obesity, respectively. All the participants from the cohorts were randomly selected from the registries of primary health care centers and, for this study, must have a DXA scan at baseline. The software (HTSMayor) was designed according to an adapted version of the algorithm proposed by the EWGSOP and was divided into four phases: longitudinal validation of diagnostic algorithm of sarcopenia, alpha version, beta version, and release version. The software estimates appendicular skeletal muscle mass (ASM) using an anthropometric equation or DXA measurements with Chilean cut-off points. The predictive validation of the algorithm was estimated, comparing functional limitations (at least one activity of daily living, two instrumental activities of daily living, or three mobility limitations), falls, and osteoporosis at follow-ups in patients with and without sarcopenia at baseline, using adjusted logistic models. Results After a median follow-up of 4.8 years (2078.4 person-years), 37 (9.9%) new cases of sarcopenia, out of the 374 patients without sarcopenia at baseline, were identified (incidence density rate=1.78 per 100 person-years). ASM estimated with the anthropometric equation showed both a high sensitivity and specificity as compared with those estimated by DXA measurements, yielding a concordance of 0.96. The diagnostic algorithm of sarcopenia considered in the software with the equation showed both a high sensitivity (82.1%) and specificity (94.9%) when compared with DXA (reference standard). Adults without sarcopenia (at baseline) showed better physical performance (after approximately 5 years) than adults with sarcopenia. Loss of functionality was greater in adults with sarcopenia (OR 5.0, 95% CI 2.2-11.4) than in adults without sarcopenia. In addition, the risks of falls (OR 2.2, 95% CI 1.1-4.3) and osteoporosis (OR 2.8, 95% CI 1.2-6.6) were higher in older persons with sarcopenia than those without sarcopenia. The measurements and results were completed for the beta and release tests with a mean time of 10 minutes and 11 minutes, respectively. Conclusions We developed and validated a software for the diagnosis of sarcopenia in older Chilean adults that can be used on a mobile device or a computer with good sensitivity and specificity, thus allowing for the development of programs for the prevention, delay, or reversal of this disease. To our knowledge, HTSMayor is the first software to diagnose sarcopenia. International Registered Report Identifier (IRRID) RR2-10.2196/13657

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