Magnetic resonance T1-mapping evaluates the degree of thyroid destruction in patients with autoimmune thyroiditis

Objective Autoimmune thyroiditis (AIT) is the most common autoimmune thyroid disease. Longitudinal relaxation time mapping (T1-mapping) measured by MRI is a new technique for assessing interstitial fibrosis of some organs, such as heart and liver. This study aimed to evaluate the relationship between T1-mapping value and thyroid function and determine the usefulness of T1-mapping in identifying thyroid destruction in AIT patients. Methods This case–control study recruited 57 drug-naïve AIT patients and 17 healthy controls. All participants were given thyroid MRI, and T1-mapping values were measured using a modified look-locker inversion-recovery sequence. Results AIT patients had significantly higher thyroid T1-mapping values than the healthy controls (1.077 ± 177 vs 778 ± 82.9 ms; P < 0.01). A significant increase in thyroid T1-mapping values was presented along with the increased severity of thyroid dysfunction (P < 0.01). Correlation analyses showed that increased thyroid T1-mapping values were associated with higher TSH and lower FT3 and FT4 levels (TSH: r = 0.75; FT3: r = −0.47; FT4: r = −0.72; all P < 0.01). Receiver-operating characteristic curve analysis revealed a high diagnostic value of T1-mapping values for the degree of thyroid destruction (area under the curve was 0.95, 95% CI: 0.90–0.99, P < 0.01). Conclusions AIT patients have higher thyroid T1-mapping values than the healthy controls, and the T1-mapping values increased with the progression of thyroid dysfunction. Thyroid T1-mapping value might be a new index to quantitatively evaluate the degree of thyroid destruction in AIT patients.

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Optimal Utility of H-Reflex RDD as a Biomarker of Spinal Disinhibition in Painful and Painless Diabetic Neuropathy

Diagnostics ◽

10.3390/diagnostics11071247 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1247

Author(s):

Anne Worthington ◽

Alise Kalteniece ◽

Maryam Ferdousi ◽

Luca Donofrio ◽

Shaishav Dhage ◽

...

Keyword(s):

Diabetic Neuropathy ◽

Characteristic Curve ◽

Area Under The Curve ◽

Initial Response ◽

Healthy Controls ◽

Painful Diabetic Neuropathy ◽

Stimulus Response ◽

Rate Dependent ◽

Potential Biomarker ◽

Spinal Inhibition

Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2–4 and 2–5 at 1 Hz, AUC = 0.84 (95%CI 0.76–0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.

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Adrenomedullin Is a Diagnostic and Prognostic Biomarker for Acute Intracerebral Hemorrhage

Current Issues in Molecular Biology ◽

10.3390/cimb43010027 ◽

2021 ◽

Vol 43 (1) ◽

pp. 324-334

Author(s):

Francisco J. Julián-Villaverde ◽

Laura Ochoa-Callejero ◽

Eva Siles ◽

Esther Martínez-Lara ◽

Alfredo Martínez

Keyword(s):

Hemorrhagic Stroke ◽

Prognostic Biomarker ◽

Characteristic Curve ◽

Area Under The Curve ◽

Nitroso Compounds ◽

Healthy Controls ◽

Stroke Patients ◽

Important Health ◽

Acute Intracerebral Hemorrhage ◽

Changes Over Time

Hemorrhagic stroke remains an important health challenge. Adrenomedullin (AM) is a vasoactive peptide with an important role in cardiovascular diseases, including stroke. Serum AM and nitrate–nitrite and S-nitroso compounds (NOx) levels were measured and compared between healthy volunteers (n = 50) and acute hemorrhagic stroke patients (n = 64). Blood samples were taken at admission (d0), 24 h later (d1), and after 7 days or at the time of hospital discharge (d7). Neurological severity (NIHSS) and functional prognosis (mRankin) were measured as clinical outcomes. AM levels were higher in stroke patients at all times when compared with healthy controls (p < 0.0001). A receiving operating characteristic curve analysis identified that AM levels at admission > 69.0 pg/mL had a great value as a diagnostic biomarker (area under the curve = 0.89, sensitivity = 80.0%, specificity = 100%). Furthermore, patients with a favorable outcome (NIHSS ≤ 3; mRankin ≤ 2) experienced an increase in AM levels from d0 to d1, and a decrease from d1 to d7, whereas patients with unfavorable outcome had no significant changes over time. NOx levels were lower in patients at d0 (p = 0.04) and d1 (p < 0.001) than in healthy controls. In conclusion, AM levels may constitute a new diagnostic and prognostic biomarker for this disease, and identify AM as a positive mediator for hemorrhagic stroke resolution.

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Urine β-2-glycoprotein 1 as a biomarker for diagnosis of systemic lupus erythematosus

Lupus ◽

10.1177/09612033211014268 ◽

2021 ◽

pp. 096120332110142

Author(s):

Jung Sun Lee ◽

Eun-Ju Lee ◽

Jeonghun Yeom ◽

Ji Seon Oh ◽

Seokchan Hong ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Medical Center ◽

Characteristic Curve ◽

Area Under The Curve ◽

Diagnostic Value ◽

Urine Samples ◽

Enzyme Linked Immunosorbent Assay ◽

Systemic Lupus ◽

Asan Medical

Objective The need for a biomarker with robust sensitivity and specificity in diagnosing systemic lupus erythematosus (SLE) remains unmet. Compared with blood samples, urine samples are more easily collected; thus, we aimed to identify such a biomarker based on urinary proteomics which could distinguish patients with SLE from healthy controls (HCs). Methods Urine samples were collected from 76 SLE patients who visited rheumatology clinic in 2019 at Asan medical center and from 25 HCs. Urine proteins were analyzed using sequential windowed acquisition of all theoretical fragment ion spectra-mass spectrometry, and the candidate marker was confirmed by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic curve analysis was used to determine the diagnostic value of the candidate biomarker. Results Of 1157 proteins quantified, 153 were differentially expressed in urine samples from HCs. Among them were previously known markers including α-1-acid glycoprotein 1, α-2-HS-glycoprotein, ceruloplasmin, and prostaglandin-H2 D-isomerase. Moreover, the amount of β-2 glycoprotein (APOH) was increased in the urine of patients with SLE. The ELISA results also showed the level of urine APOH was higher in patients with SLE than in HCs and patients with rheumatoid arthritis. Moreover, the level was not different between SLE patients with and without nephritis. The urine APOH had an area under the curve value of 0.946 at a cut-off value of 228.53 ng/mg (sensitivity 91.5%, specificity 92.0%) for the diagnosis of SLE. Conclusion The results indicate that the urine APOH level can be an appropriate screening tool in a clinical setting when SLE is suspected.

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Value of Fibrinogen to Discriminate Appendicitis from Nonspecific Abdominal Pain in Preschool Children

European Journal of Pediatric Surgery ◽

10.1055/s-0039-1692166 ◽

2019 ◽

Vol 30 (04) ◽

pp. 357-363

Author(s):

Javier Gómez-Veiras ◽

Ángel Salgado-Barreira ◽

José Luis Vázquez ◽

Margarita Montero-Sánchez ◽

José Ramón Fernández-Lorenzo ◽

...

Keyword(s):

Abdominal Pain ◽

Preschool Children ◽

Diagnostic Accuracy ◽

Prothrombin Time ◽

Characteristic Curve ◽

Area Under The Curve ◽

Diagnostic Value ◽

Suspected Appendicitis ◽

Uncomplicated Appendicitis ◽

Good Diagnostic Accuracy

Introduction The aim of this study was to assess the diagnostic value of the biomarker fibrinogen (FB), along with the markers white blood cell (WBC) count, absolute neutrophil count (ANC), and C-reactive protein (CRP), to discriminate appendicitis from nonspecific abdominal pain (NSAP) in preschool children. Materials and Methods We prospectively evaluated all children aged <5 years admitted for suspected appendicitis at an academic pediatric emergency department during 5 years. Diagnostic accuracy of FB (prothrombin time–derived method), WBC, ANC, and CRP were assessed by the area under the curve (AUC) of the receiver-operating characteristic curve. Results A total of 82 patients were enrolled in the study (27 NSAP, 17 uncomplicated, and 38 complicated appendicitides). WBC and ANC had moderate diagnostic accuracy for appendicitis versus NSAP (WBC: AUC 0.66, ANC: AUC 0.67). CRP and FB had good diagnostic accuracy for appendicitis versus NSAP (CRP: AUC 0.78, FB: AUC 0.77). WBC and ANC are not useful to discriminate complicated versus uncomplicated appendicitis (WBC: AUC 0.43, ANC: AUC 0.45). CPR and FB had good diagnostic accuracy for complicated versus uncomplicated appendicitis (CRP: AUC 0.80, FB: AUC 0.73). Conclusion CRP and FB are more useful than WBC and ANC to discriminate appendicitis from NSAP in preschool children. CRP and FB are especially useful to discriminate complicated from uncomplicated appendicitis and NSAP. In a child with suspected appendicitis, a plasma FB level (prothrombin time–derived method) >540 mg/dL is associated with an increased likelihood of complicated appendicitis.

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Diagnostic efficacy of serum and urinary netrin-1 in the early detection of diabetic nephropathy

Journal of Investigative Medicine ◽

10.1136/jim-2021-001785 ◽

2021 ◽

pp. jim-2021-001785

Author(s):

Rasha A Elkholy ◽

Reham L Younis ◽

Alzahraa A Allam ◽

Rasha Youssef Hagag ◽

Muhammad Tarek Abdel Ghafar

Keyword(s):

Diabetic Nephropathy ◽

Early Detection ◽

Characteristic Curve ◽

Fasting Blood Glucose ◽

Area Under The Curve ◽

Diagnostic Value ◽

Control Group ◽

Diagnostic Efficacy ◽

Significant Difference ◽

Patients With Diabetes

This study aimed to assess the diagnostic value of serum and urinary netrin-1 in patients with type 2 diabetes mellitus (T2DM) at different stages of diabetic nephropathy (DN) and to compare its efficacy of estimation in serum with that in the urine. This study was carried out on 135 patients with T2DM and 45 healthy subjects. The patients with diabetes were divided according to urinary albumin creatinine ratio (UACR) into: T2DM with normoalbuminuria, incipient DN with microalbuminuria, and overt DN with macroalbuminuria groups. Serum and urinary levels of netrin-1 were measured by ELISA. The mean levels of serum and urinary netrin-1 were significantly higher in the microalbuminuric and macroalbuminuric patients with DN than those in the normoalbuminuric patients with T2DM, with the highest values detected in macroalbuminuric patients with DN. Urinary netrin-1 level was significantly higher in the normoalbuminuric T2DM group than control group, whereas no significant difference existed regarding serum netrin-1 level. In T2DM groups, the urinary and serum netrin-1 correlated with each other and were independently related to fasting blood glucose, UACR, and estimated glomerular filtration rate. Receiver operating characteristic curve analysis showed that the area under the curve of urinary netrin-1 was 0.916 which is significantly higher than that of serum netrin-1 (0.812) for the detection of incipient DN and reached 0.938 on coestimation of both urinary and serum netrin-1. In conclusion, netrin-1 is a potential diagnostic marker for early detection of DN with its estimation in urine has higher accuracy than that of serum.

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Clinical suspicion of spondylodiscitis with equivocal MRI findings: does diffusion-weighted imaging prove helpful here?

Acta Radiologica ◽

10.1177/0284185120927905 ◽

2020 ◽

pp. 028418512092790

Author(s):

Jeanette Henkelmann ◽

Kristina Bremicker ◽

Timm Denecke ◽

Karl-Titus Hoffmann ◽

Ralf Henkelmann ◽

...

Keyword(s):

Diffusion Weighted Imaging ◽

Characteristic Curve ◽

Area Under The Curve ◽

Region Of Interest ◽

High Sensitivity ◽

Diagnostic Value ◽

Mri Findings ◽

Adc Value ◽

Diffusion Weighted ◽

Adc Values

Background Despite the high sensitivity of magnetic resonance imaging (MRI), early detection of spondylodiscitis (SpD) remains challenging due to its low specificity. Purpose To assess the diagnostic value of diffusion-weighted imaging (DWI) in suspected cases of SpD with ambiguous early MRI findings in the differentiation of degenerative disorders (DD). Material and Methods In this prospective study, 52 patients suspected of having SpD underwent a whole-spine 3-T MRI scan comprising sagittal DWI. Of 58 conspicuous, T2-weighted, signal increased discs, 39 were successfully evaluated using DWI. Apparent diffusion coefficient (ADC) values and ADC maps were blindly analyzed using the region of interest of the conspicuous disc and a normal adjacent reference disc. Intraindividual ratios (conspicuous disc: reference disc) were calculated. Results All conspicuous discs showed increased absolute ADC values, which did not differ significantly between SpD (n = 22) and DD (n = 17). However, ADC ratio was significantly higher in SpD vs. DD ( P < 0.05). In receiver operating characteristic curve analysis, an ADC ratio threshold of 1.6 resulted in 45% sensitivity and 88% specificity (area under the curve = 0.69) for SpD diagnosis. Conclusion The absolute ADC value does not provide a reliable diagnosis of SpD. Increased diffusivity can be an indication of infection but should always be discussed in the context of existing disc degeneration.

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Association and diagnostic value of serum SPINK4 in colorectal cancer

PeerJ ◽

10.7717/peerj.6679 ◽

2019 ◽

Vol 7 ◽

pp. e6679 ◽

Cited By ~ 1

Author(s):

Mingzhi Xie ◽

Kezhi Li ◽

Jilin Li ◽

Dongcheng Lu ◽

Bangli Hu

Keyword(s):

Colorectal Cancer ◽

Gastric Cancer ◽

Cancer Patients ◽

Characteristic Curve ◽

Disease Free Survival ◽

Diagnostic Value ◽

Healthy Controls ◽

Significant Difference ◽

Peptidase Inhibitor ◽

Gastric Cancer Patients

The role of serum serine peptidase inhibitor, Kazal type 4 (SPINK4), in colorectal cancer (CRC) is largely unknown. This study aimed to explore the association and diagnostic value of serum SPINK4 in CRC. A total of 70 preoperative CRC patients, 30 postoperative CRC patients, 30 gastric cancer patients, and 30 healthy controls were enrolled. Using enzyme-linked immunosorbent assays, we found that the serum SPINK4 level was significantly increased in preoperative CRC compared with postoperative CRC patients, gastric cancer patients, and healthy controls (p < 0.05). The serum SPINK4 level was remarkably elevated in colon cancer compared with rectal cancer and was enhanced in the M1 stage compared with the M0 stage (p < 0.05). The area under the receiver operating characteristic curve of serum SPINK4 level in the diagnosis of CRC was 0.9186, with a sensitivity and specificity of 0.886 and 0.900, respectively, and a cut-off value of 2.065. There was no significant difference between high and low expression of serum SPINK4 regarding the overall survival time and disease-free survival (p > 0.05). This study demonstrated that the serum SPINK4 level increased in CRC and was associated with the location and distant metastasis of CRC. It had a high diagnostic value in CRC but was not associated with the survival of CRC patients.

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Identification and Validation of Novel Serum Autoantibodies Biomarkers for Staging Liver Fibrosis in Patients With Chronic Hepatitis B

Frontiers in Medicine ◽

10.3389/fmed.2021.807087 ◽

2022 ◽

Vol 8 ◽

Author(s):

Saiping Qi ◽

Jing Li ◽

Xiaomin He ◽

Jialing Zhou ◽

Zhibin Chen ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Fibrosis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Microarray Analysis ◽

Characteristic Curve ◽

Area Under The Curve ◽

Diagnostic Value ◽

Diagnostic Methods ◽

Pre Treatment

Aim: Liver fibrosis monitoring is essential in patients with chronic hepatitis B (CHB). However, less robust, noninvasive diagnostic methods for staging liver fibrosis, other than liver biopsy, are available. Our previous study demonstrated a panel of cellular proteins recognized by autoantibodies that may have potential value in discrimination of CHB and liver cirrhosis. We aim to assess the diagnostic value of these serum autoantibodies for staging liver fibrosis.Methods: Candidate autoantigens were screened and assessed by microarray analysis in 96 healthy controls and 227 CHB patients with pre-treatment biopsy-proven METAVIR fibrosis score, comprising 69, 115, and 43 cases with S0-1, S2-3, and S4 stages, respectively. Autoantibodies with potential diagnostic value for staging liver fibrosis were verified by enzyme-linked immunosorbent assays (ELISA). Receiver operating characteristic curve was conducted to evaluate autoantibody performance.Results: Microarray analysis identified autoantigens CENPF, ACY1, HSPA6, and ENO1 with potential diagnostic value for liver fibrosis staging, among which CENPF and ACY1 were validated using ELISA. CENPF and ACY1 autoantibodies had area under the curve values of 0.746 and 0.685, 58.14 and 74.42% sensitivity, and 88.41 and 60.87% specificity, respectively, for discriminating liver fibrosis stages S4 and S0-1. The prevalence of CENPF and ACY1 autoantibodies was not correlated with age, sex or level of inflammation.Conclusions: Autoimmune responses may be elicited during progression of liver fibrosis, and serum autoantibodies may be a valuable biomarker for staging liver fibrosis deserving of further study.

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Pre-analytical and analytical confounders of serum calprotectin as a biomarker in rheumatoid arthritis

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-0508 ◽

2019 ◽

Vol 58 (1) ◽

pp. 40-49

Author(s):

Lieve Van Hoovels ◽

Bert Vander Cruyssen ◽

Laura Bogaert ◽

Stefanie Van den Bremt ◽

Xavier Bossuyt

Keyword(s):

Rheumatoid Arthritis ◽

Infectious Disease ◽

Disease Activity ◽

Clinical Performance ◽

Area Under The Curve ◽

Diagnostic Value ◽

Healthy Controls ◽

Reactive Protein ◽

Diagnosis And Prognosis ◽

Edta Plasma

Abstract Background There is a need for additional biomarkers to assist in the diagnosis and prognosis of rheumatoid arthritis (RA). The aim of our study was to evaluate the (pre-analytical, analytical and clinical) performance of serum calprotectin as a marker of inflammation in RA. Methods The study population included 463 rheumatologic patients (including 111 RA patients and 352 controls) who for the first time consulted a rheumatologist, 20 healthy controls and 27 patients with an infectious disease. Calprotectin was measured (using four different assays) in serum or in serum and EDTA plasma (healthy controls and infectious disease group). For rheumatologic patients, results for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were available. Results Results for blood calprotectin were assay- and matrix-dependent, with higher values found in serum than in plasma. Serum calprotectin was higher in RA patients than in rheumatologic diseased controls and in healthy controls. Serum calprotectin was lower in RA patients than in patients with an infectious disease. Serum calprotectin was associated with disease activity (DAS score). The area under the curve (AUC) to discriminate RA from controls was 0.756 for CRP, 0.714 for ESR and 0.726–0.783 for calprotectin. Conclusions Our data document that calprotectin measurement is assay- and matrix-dependent. Serum calprotectin is associated with disease activity. Additional (prospective) studies are warranted to further evaluate the prognostic and diagnostic value of blood calprotectin measurements.

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Serum Lysyl Oxidase Is a Potential Diagnostic Biomarker for Kidney Fibrosis

American Journal of Nephrology ◽

10.1159/000509381 ◽

2020 ◽

Vol 51 (11) ◽

pp. 907-918

Author(s):

Xiao-qin Zhang ◽

Xin Li ◽

Wen-qian Zhou ◽

Xi Liu ◽

Jie-li Huang ◽

...

Keyword(s):

Kidney Disease ◽

Interstitial Fibrosis ◽

Lysyl Oxidase ◽

Characteristic Curve ◽

Area Under The Curve ◽

Renal Tissue ◽

Diagnostic Biomarker ◽

Kidney Fibrosis

Background: Kidney fibrosis is the ultimate consequence of advanced stages of chronic kidney disease (CKD); however, there are currently no reliable biomarkers or noninvasive diagnostic tests available for the detection of kidney fibrosis. Lysyl oxidase (LOX) promotes collagen cross-linking, and serum LOX levels have been shown to be elevated in patients with fibrosis of the heart, lungs, and liver. However, serum LOX levels have not been reported in patients with kidney fibrosis. We explored whether serum LOX levels are associated with kidney fibrosis. Method: Overall, 202 patients with kidney disease underwent renal biopsy, scoring of kidney fibrosis, and determination of the area of kidney fibrosis. LOX levels were measured in serum and in kidney tissues. We analyzed the association of circulating LOX and tissue LOX levels with the scores and areas of kidney fibrosis. LOX expression was also investigated with in vitro and in vivo kidney fibrosis models. Results: Serum LOX levels were higher in patients with kidney fibrosis than in those without kidney fibrosis (p < 0.001) and higher in patients with moderate-severe kidney fibrosis than in patients with mild kidney fibrosis (p < 0.001). Both serum LOX and renal tissue LOX levels correlated with the area of kidney fibrosis (r = 0.748, p < 0.001; r = 0.899, p < 0.001, respectively). Receiver operating characteristic curve analysis of serum LOX levels showed an area under the curve of 0.80 (95% CI: 0.74–0.86). The optimal serum LOX level cutoff point was 253.34 pg/mL for the prediction of kidney fibrosis and 306.56 pg/mL for the prediction of moderate-severe kidney fibrosis. LOX expression levels were significantly upregulated (2.3–2.6 and 6-fold, respectively) in in vitro and in vivo interstitial fibrosis models. Conclusions: Both serum LOX and tissue LOX levels correlated with the presence and degree of kidney fibrosis in patients with CKD. These results suggest that serum LOX levels could potentially serve as a noninvasive diagnostic biomarker for kidney fibrosis and may further potentially serve as a stratified biomarker for the identification of mild and moderate-severe kidney fibrosis.

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