diagnostic power
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Author(s):  
Ben Kirk ◽  
Nicky Lieu ◽  
Sara Vogrin ◽  
Myrla Sales ◽  
Julie A Pasco ◽  
...  

Abstract Background Markers of bone metabolism have been associated with muscle mass and function. Whether serum cross-linked C-terminal telopeptides of type I collagen (CTX) is also associated with these measures in older adults remains unknown. Methods In community-dwelling older adults at high risk of falls and fractures, serum CTX (biochemical immunoassays) was used as the exposure, while appendicular lean mass (dual-energy x-ray absorptiometry) and muscle function (grip strength [hydraulic dynamometer], short physical performance battery [SPPB], gait speed, sit to stand, balance, Timed Up and Go [TUG]) were used as outcomes. Potential covariates including demographic, lifestyle and clinical factors were considered in statistical models. Areas under the ROC curves were calculated for significant outcomes. Results 299 older adults (median age: 79 years, IQR: 73, 84; 75.6% women) were included. In multivariable models, CTX was negatively associated with SPPB (β = 0.95, 95% CI: 0.92, 0.98) and balance (β = 0.92, 0.86, 0.99) scores, and positively associated with sit to stand (β = 1.02, 95% CI: 1.00, 1.05) and TUG (β = 1.03, 95% CI: 1.00, 1.05). Trend line for gait speed (β = 0.99, 95% CI: 0.98, 1.01) was in the hypothesized direction but did not reach significance. AUC curves showed low diagnostic power (<0.7) of CTX in identifying poor muscle function (SPPB: 0.63; sit to stand: 0.64; TUG: 0.61). Conclusion In older adults, higher CTX levels were associated with poorer lower-limb muscle function (but showed poor diagnostic power for these measures). These clinical data build on the biomedical link between bone and muscle.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Wellington F. Rodrigues ◽  
Camila B. Miguel ◽  
Ferdinando Agostinho ◽  
Gabriela V. da Silva ◽  
Javier E. Lazo-Chica ◽  
...  

Periodontal disease is an infectious inflammatory disease related to the destruction of supporting tissues of the teeth, leading to a functional loss of the teeth. Inflammatory molecules present in the exudate are catalyzed and form different metabolites that can be identified and quantified. Thus, we evaluated the inflammatory exudate present in crevicular fluid to identify metabolic biological markers for diagnosing chronic periodontal disease in older adults. Research participants were selected from long-term institutions in Brazil. Participants were individuals aged 65 years or older, healthy, or with chronic periodontal disease. Gas chromatography/mass spectrometry was used to evaluate potential biomarkers in 120 crevicular fluid samples. We identified 969 metabolites in the individuals. Of these, 15 metabolites showed a variable importance with projection   score > 1 and were associated with periodontal disease. Further analysis showed that among the 15 metabolites, two (5-aminovaleric acid and serine, 3TMS derivative) were found at higher concentrations in the crevicular fluid, indicating their potential diagnostic power for periodontal disease in older adults. Our findings indicated that some metabolites are present at high concentrations in the crevicular fluid in older adults with periodontal disease and can be used as biomarkers of periodontal disease.


Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2120
Author(s):  
Takashi Kojima ◽  
Naoki Isogai ◽  
Tomoya Nishida ◽  
Tomoaki Nakamura ◽  
Kazuo Ichikawa

The keratometer keratoconus index (KKI) is a diagnostic index for the risk of keratoconus calculated from autokeratometer test values. We partially modified the KKI equation and assessed it without limiting the target age and severity of keratoconus. This retrospective study included 179 eyes of 99 patients with keratoconus and 468 eyes from 235 normal controls. In the modified KKI, oblique astigmatism or against-the-rule astigmatism was defined as ≥1D astigmatism. KKI diagnostic power was analyzed in subgroups of <50 and ≥50-year-old patients, and at different keratoconus stages. Although the sensitivity of modified KKI was comparable with that of original KKI (92.7% vs. 95.5%), modified KKI specificity was significantly higher (79.7% vs. 68.6%) (p = 0.0001). Using the modified KKI, sensitivity reached 100% (4/4) and specificity, 63.5% (33/52), in ≥50-year-old patients, while overall sensitivity in keratoconus ≥stage 2 was 100% (30/30). In conclusion, the modified KKI proved to be effective in keratoconus screening at all stages. However, it should be noted that false-positive frequency is higher in ≥50-year-old patients.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Ashwin V. Venkataraman ◽  
Wenjia Bai ◽  
Alex Whittington ◽  
James F. Myers ◽  
Eugenii A. Rabiner ◽  
...  

Abstract Background Amyloid-β (Aβ) PET has emerged as clinically useful for more accurate diagnosis of patients with cognitive decline. Aβ deposition is a necessary cause or response to the cellular pathology of Alzheimer’s disease (AD). Usual clinical and research interpretation of amyloid PET does not fully utilise all information regarding the spatial distribution of signal. We present a data-driven, spatially informed classifier to boost the diagnostic power of amyloid PET in AD. Methods Voxel-wise k-means clustering of amyloid-positive voxels was performed; clusters were mapped to brain anatomy and tested for their associations by diagnostic category and disease severity with 758 amyloid PET scans from volunteers in the AD continuum from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). A machine learning approach based on this spatially constrained model using an optimised quadratic support vector machine was developed for automatic classification of scans for AD vs non-AD pathology. Results This classifier boosted the accuracy of classification of AD scans to 81% using the amyloid PET alone with an area under the curve (AUC) of 0.91 compared to other spatial methods. This increased sensitivity to detect AD by 15% and the AUC by 9% compared to the use of a composite region of interest SUVr. Conclusions The diagnostic classification accuracy of amyloid PET was improved using an automated data-driven spatial classifier. Our classifier highlights the importance of considering the spatial variation in Aβ PET signal for optimal interpretation of scans. The algorithm now is available to be evaluated prospectively as a tool for automated clinical decision support in research settings.


2021 ◽  
Vol 10 (21) ◽  
pp. 4903
Author(s):  
Emilia Czyżewska ◽  
Olga Ciepiela

There is a possibility that renal dysfunction may potentially reduce the diagnostic power of the laboratory parameters Tn, NT-proBNP and sFLC levels, used in the current prognostic classification of AL amyloidosis and the diagnosis of heart involvement by amyloid. In this study, the impact of lowering the eGFR value on the usefulness of these parameters in the prognosis and diagnosis of the presence of amyloid in the myocardium was assessed in a group of 71 patients with newly diagnosed primary amyloidosis. The assessment of diagnostic power of laboratory parameters was performed on the entire study group, and in the ranges of eGFR ≥ 60 and < 60 mL/min/1.73 m2. It has been proven that, with a decrease in the eGFR value, the concentrations of NT-proBNP and the κ uninvolved light chains increase significantly (p < 0.001). To assess the diagnostic power of laboratory parameters used in the diagnosis of myocardial involvement in patients with AL amyloidosis, an ROC analysis was performed. The highest values of AUC were obtained for the NT-proBNP concentration (AUC = 0.906). The lowest values of the AUC and Youden’s index were obtained for the dFLC values (AUC = 0.723), and involved κ FLC concentration (AUC = 0.613). For all compared parameters, the smallest values of the AUC were obtained for eGFR (<60 mL/min/1.73 m2). It seems that the most suitable cardiac parameter used in the prognostic classification of AL amyloidosis, independent of renal function, is TnI. It should be noted that a concentration of involved λ chains hada higher diagnostic power to assess the heart involvement, compared to the routinely used “cardiac parameters”, TnI and NT-proBNP. It can therefore be an additional parameter used to assess the presence of amyloid in the myocardium. A decrease in eGFR value influenced the change in the diagnostic cut-off points of the most analyzed laboratory parameters. Finally, it is concluded that lowering the eGFR value reduces the utility of laboratory parameters used in the prognostic classification of AL amyloidosis.


Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1940
Author(s):  
Huang-Chen Chang ◽  
Yen-Ching Wu ◽  
Jun-Peng Chen ◽  
Yi-Da Wu ◽  
Wen-Nan Huang ◽  
...  

This study aimed to compare the test results of anti-double-stranded DNA (anti-dsDNA) antibodies obtained using chemiluminescent immunoassay (CIA) and enzyme-linked immunosorbent assay (ELISA), and investigate predictors of inconsistent results. This retrospective study included 502 patients who underwent CIA and ELISA to determine their anti-dsDNA antibody values within a year. We compared the diagnostic power for SLE, disease activity, and predictive power for lupus nephritis (LN). A multivariate analysis was performed to determine the predictors of inconsistencies. CIA and ELISA were moderately correlated in terms of their consistency (Cronbach’s α = 0.571), and yielded comparably favorable results in terms of SLE diagnostic power and SLE disease activity. However, if the patient had LN, CIA displayed higher predictive power than ELISA (0.620 vs. 0.555, p = 0.026). Compared with the CIA/ELISA double-positive group, the inconsistent group had lower anti-C1q circulating immune complexes (CIC) antibody values (OR: 0.42, 95% CI: 0.18–0.94, p = 0.036), and lower SLEDAI scores (≥4) (OR: 0.33, 95% CI: 0.14–0.79, p = 0.013). Anti-dsDNA antibody detection with CIA exhibited higher predictability for diagnosing LN than did ELISA. In the event of inconsistencies between anti-dsDNA methods, SLE disease activity and CIC test values should be considered simultaneously.


2021 ◽  
pp. 106689692110522
Author(s):  
Altan Kavuncuoglu ◽  
Ceren Damla Durmaz ◽  
Ozay Gokoz ◽  
Aysegul Uner ◽  
Kemal Kosemehmetoglu

Melanomas presenting in primary or metastatic sites with a poorly differentiated histology comprise dedifferentiated (DM) and undifferentiated melanomas (UM), the latter consisting purely of undifferentiated cells and totally lacking immunophenotypic features of melanoma. These entities have a wide morphological spectrum including round cell sarcoma-like features which pose a significant diagnostic challenge. Here we present a case of UM with morphological and immunohistochemical features resembling undifferentiated round cell sarcoma, whose diagnosis could only be established after proper integration of clinical and molecular data. This diagnostically challenging case, fulfilling the previously proposed diagnostic criteria by Agaimy et al, expands the clinicopathological spectrum of DM/UM, highlights the essence of molecular signature, and further emphasizes the importance of patient’s history in any morphological setting.


2021 ◽  
Vol 14 ◽  
Author(s):  
Kasra Honarmand Tamizkar ◽  
Elham Badrlou ◽  
Termeh Aslani ◽  
Serge Brand ◽  
Shahram Arsang-Jang ◽  
...  

Autism spectrum disorder (ASD) is a long-standing neurodevelopmental condition with prominent effects on social behavior of affected children. This disorder has been linked with neuroinflammatory responses. NF-κB has been shown to affect these responses in the orbitofrontal cortex of patients with ASD, thus being implicated in the pathogenesis of ASD. We measured expression of some NF-κB-associated lncRNAs and mRNAs (DILC, ANRIL, PACER, CHAST, ADINR, DICER1-AS1, HNF1A-AS1, NKILA, ATG5 and CEBPA) in the peripheral blood of ASD kids vs. healthy children. Expression quantities of ADINR, ANRIL, DILC, NKILA and CHAST were meaningfully higher in ASD cases compared with healthy kids (Posterior Beta = 1.402, P value &lt; 0.0001; Posterior Beta = 2.959, P value &lt; 0.0001; Posterior Beta = 0.882, P value = 0.012; Posterior Beta = 1.461, P value &lt; 0.0001; Posterior Beta = 0.541, P value = 0.043, respectively). The Bonferroni corrected P values for these lncRNAs remained significant except for CHAST and DILC. Expression levels of other genes were not considerably different between cases and controls. Expressions of ATG5, DICER-AS1 and DILC were correlated with age of ASD patients (P &lt; 0.0001). Among ASD cases, the most robust correlation has been detected between ADINR and NKILA (r = 0.87, P &lt; 0.0001). Expression of none of genes has been correlated with age of healthy children. Among this group of children, expression levels of ADINR and CHAST were robustly correlated (r = 0.83, P &lt; 0.0001). ANRIL had the greatest AUC value (AUC = 0.857), thus the best diagnostic power among the assessed genes. NKILA ranked the second position in this regard (AUC = 0.757). Thus, NF-κB-associated lncRNAs might partake in the pathogenesis of ASD.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xianyu Zhang ◽  
Dezhi Zhao ◽  
Yanling Yin ◽  
Ting Yang ◽  
Zilong You ◽  
...  

AbstractMammography is used to detect breast cancer (BC), but its sensitivity is limited, especially for dense breasts. Circulating cell-free DNA (cfDNA) methylation tests is expected to compensate for the deficiency of mammography. We derived a specific panel of markers based on computational analysis of the DNA methylation profiles from The Cancer Genome Atlas (TCGA). Through training (n = 160) and validation set (n = 69), we developed a diagnostic prediction model with 26 markers, which yielded a sensitivity of 89.37% and a specificity of 100% for differentiating malignant disease from normal lesions [AUROC = 0.9816 (95% CI: 96.09-100%), and AUPRC = 0.9704 (95% CI: 94.54–99.46%)]. A simplified 4-marker model including cg23035715, cg16304215, cg20072171, and cg21501525 had a similar diagnostic power [AUROC = 0.9796 (95% CI: 95.56–100%), and AUPRC = 0.9220 (95% CI: 91.02–94.37%)]. We found that a single cfDNA methylation marker, cg23035715, has a high diagnostic power [AUROC = 0.9395 (95% CI: 89.72–99.27%), and AUPRC = 0.9111 (95% CI: 88.45–93.76%)], with a sensitivity of 84.90% and a specificity of 93.88%. In an independent testing dataset (n = 104), the obtained diagnostic prediction model discriminated BC patients from normal controls with high accuracy [AUROC = 0.9449 (95% CI: 90.07–98.91%), and AUPRC = 0.8640 (95% CI: 82.82–89.98%)]. We compared the diagnostic power of cfDNA methylation and mammography. Our model yielded a sensitivity of 94.79% (95% CI: 78.72–97.87%) and a specificity of 98.70% (95% CI: 86.36–100%) for differentiating malignant disease from normal lesions [AUROC = 0.9815 (95% CI: 96.75–99.55%), and AUPRC = 0.9800 (95% CI: 96.6–99.4%)], with better diagnostic power and had better diagnostic power than that of using mammography [AUROC = 0.9315 (95% CI: 89.95–96.34%), and AUPRC = 0.9490 (95% CI: 91.7–98.1%)]. In addition, hypermethylation profiling provided insights into lymph node metastasis stratifications (p < 0.05). In conclusion, we developed and tested a cfDNA methylation model for BC diagnosis with better performance than mammography.


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