scholarly journals Plasma Gelsolin Reinforces the Diagnostic Value of FGF-21 and GDF-15 for Mitochondrial Disorders

2021 ◽  
Vol 22 (12) ◽  
pp. 6396
Author(s):  
Ana Peñas ◽  
Miguel Fernández-De la Torre ◽  
Sara Laine-Menéndez ◽  
David Lora ◽  
María Illescas ◽  
...  

Mitochondrial disorders (MD) comprise a group of heterogeneous clinical disorders for which non-invasive diagnosis remains a challenge. Two protein biomarkers have so far emerged for MD detection, FGF-21 and GDF-15, but the identification of additional biomarkers capable of improving their diagnostic accuracy is highly relevant. Previous studies identified Gelsolin as a regulator of cell survival adaptations triggered by mitochondrial defects. Gelsolin presents a circulating plasma isoform (pGSN), whose altered levels could be a hallmark of mitochondrial dysfunction. Therefore, we investigated the diagnostic performance of pGSN for MD relative to FGF-21 and GDF-15. Using ELISA assays, we quantified plasma levels of pGSN, FGF-21, and GDF-15 in three age- and gender-matched adult cohorts: 60 genetically diagnosed MD patients, 56 healthy donors, and 41 patients with unrelated neuromuscular pathologies (non-MD). Clinical variables and biomarkers’ plasma levels were compared between groups. Discrimination ability was calculated using the area under the ROC curve (AUC). Optimal cut-offs and the following diagnostic parameters were determined: sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and efficiency. Comprehensive statistical analyses revealed significant discrimination ability for the three biomarkers to classify between MD and healthy individuals, with the best diagnostic performance for the GDF-15/pGSN combination. pGSN and GDF-15 preferentially discriminated between MD and non-MD patients under 50 years, whereas FGF-21 best classified older subjects. Conclusion: pGSN improves the diagnosis accuracy for MD provided by FGF-21 and GDF-15.

2016 ◽  
Vol 50 (1) ◽  
pp. 42 ◽  
Author(s):  
Dwi Fachri Harahap ◽  
Damayanti Rusli Sjarif ◽  
Soedjatmiko Soedjatmiko ◽  
Dwi Putro Widodo ◽  
Mayke Sugianto Tedjasaputra

Background Obesity can result in emotional and behavior problems in school-age children. Child Behavior Checklist (CBCL) is a standard instrument for evaluating behavior problems, however it is considered not practical. The 17-item Pediatric Symptom Checklist (PSC-17) is a more simple instrument but its diagnostic value has never been evaluated in obese children.Objectives To evaluate the diagnostic value of PSC-17 compared to CBCL as the gold standard.Methods This cross-sectional study was done in May - June 2009. Children aged 6-12 years with obesity were included. Parents filled the CBCL and PSC-17 questionnaires. Sensitivity, specificity, predictive values, and likelihood ratios were calculated for PSC-17.Results Most subjects aged 6-9 years (83%). Boys out numbered girls. Emotional and behavior problems detected by CBCL and PSC-17 were identified in 28% and 22% subjects, respectively. The most common problem was internalization (withdrawal, somatic complaints, anxiety/depression). The PSC-17 had sensitivity and specificity of 69.2% and 95.6% respectively. Positive and negative predictive values were 85.7% and 89%, whereas positive and negative likelihood ratios were 15.7 and 0.32.Conclusions The prevalence of emotional and behavior problems detected using CBCL and PSC-17 in obese children was 28% and 22%, respectively. The PSC-17 has moderate sensitivity to screen emotional and behavior problem in obese children.[Paediatr Indones. 2010;50:42-8].


2019 ◽  
Vol 9 (3-4) ◽  
pp. 155-162
Author(s):  
Boonsak Hanterdsith

Although the arcus corneae (AC) has long been used as an age indicator for forensic purposes, its diagnostic value has not been evaluated. To evaluate the AC as a predictor of chronological age, the author has studied the correlation of AC with respect to age of the deceased. A cross-sectional study was conducted of 342 Thai corpses at the Maharat Nakhon Ratchasima Hospital, Thailand. AC was graded into three levels: no AC, incomplete ring, and complete ring. One-way analysis of variance, chi-square test, binomial logistic regression, sensitivity, specificity, predictive values, and likelihood ratios were used for analysis. The Cohen’s kappa was used to determine the intraobserver and interobserver reliability. The prevalence of AC and the probability of complete AC were significant higher in corpses aged 60 years and above than in those under 60 years. Consequently, this study confirmed that the prevalence of AC was significantly correlated with the age of Thai individuals. If the complete AC is used as an indicator of age of 60 years and above, complete AC has high sensitivity (92.56%) but low specificity (72.85%), low positive predictive value (65.12%), but high negative predictive value (94.71%). For diagnostic value, the presence of AC can be used for age screening but not for absolute confirmation. The absence of AC indicates young age, incomplete AC indicates middle age, and complete AC indicates old age. The high intraobserver and interobserver reliability provides assurance of the value of AC as a means to estimate personal age.


2020 ◽  
Vol 12 ◽  
pp. 1759720X2097590
Author(s):  
Angelika Lackner ◽  
Viktoria Tiefenthaler ◽  
Jalia Mirzayeva ◽  
Florian Posch ◽  
Christopher Rossmann ◽  
...  

Aims: Line immune-assays (LIA) for the detection of myositis-specific antibodies (MSA) are used widely for characterization of idiopathic inflammatory myopathies (IIM). Their current use and significance for the diagnosis of IIM remains unclear. Methods: In this retrospective analysis, we retrieved clinical diagnoses of patients tested for MSA and myositis-associated antibodies (MAA) Jo-1, Mi-2α, Mi-2β, TIF1γ, SRP, MDA-5, NXP-2, SAE, PL-7, PL-12, EJ, OJ, PM-Scl100, PM-Scl75 and Ku. We calculated clinical specificity, clinical sensitivity, negative- and positive predictive values (PPV) as well as positive and negative likelihood ratios. Results: In total, we analyzed 3167 samples. After exclusion of repeated measurements and patients with insufficient clinical information, data of 1118 patients were available for analysis. A total of 242 patients tested positive for at least one antibody, of which 45 patients had a diagnosis of IIM; 25 IIM patients were negative for all MSA/MAA. Clinical specificity of MSA/MAA for the diagnosis of IIM ranged between 94.2% and 99.9%. Clinical sensitivity and PPV across all antibodies tested ranged from 0.0% to 12.9% and 0.0% to 72.7%, respectively. Conclusion: In clinical practice MSA/MAA are used widely for diagnostic work-up of IIM, resulting in a low pre-test probability. Clinicians should be aware that PPVs for most MSA/MAA are low.


2021 ◽  
pp. 155005942110467
Author(s):  
Xavier Merchán-del-Hierro ◽  
Gabriel Persi ◽  
María C. Vulycher ◽  
Carla Chicco ◽  
Emilia M. Gatto ◽  
...  

Introduction. In clinical practice, it is difficult to define the prognosis of patients with acute encephalopathy; a syndrome characterized by cognitive dysfunction and altered sensorium. Discharges with triphasic morphology (DTM) are an electroencephalographic pattern that might be useful to establish the risk of death. The aim of this study was to define the prognostic value of DTM regarding mortality in patients with acute encephalopathy. Methods. We conducted an observational retrospective cohort study including patients with acute encephalopathy with and without DTM paired by age and gender in a 1:2 ratio. We calculated the odds ratio (OR) to determine the association between DTM and mortality. In addition, we calculated sensibility, specificity, and predictive values. Results. We included 72 patients, 24 with DTM and 48 without DTM. Mortality was higher in patients with DTM (41.6% vs 14.5%, P  =  .01). Factors associated with a higher risk of death were DTM (OR  =  4.1, 95% confidence interval [CI] 1.3-13, P  =  .01) and sequential organ failure assessment score (OR  =  1.3, 95% CI 1.04-1.67, P  =  .02). A higher Glasgow coma scale score was associated with a lower risk of death (OR  =  0.65, 95% CI 0.51-0.83, P  =  .001). The sensibility and specificity of DTM were 59% and 75%, respectively. Positive and negative likelihood ratios were 2.36 and 0.55. Discussion. Our results revealed high mortality in patients with acute encephalopathy and DTM. This electroencephalographic pattern was associated with 4 times higher risk of death. However, its usefulness for predicting death was limited.


Author(s):  
Stephen L. Millar ◽  
Kristin M. Zersen

Abstract OBJECTIVE To assess the diagnostic value of the ultrasonographic description of a splenic mass or nodule as cavitated in dogs with nontraumatic hemoabdomen. ANIMALS 106 dogs with a nontraumatic hemoabdomen that underwent abdominal ultrasonography and splenectomy with histologic examination of splenic lesions between 2005 and 2018. PROCEDURES Medical records were reviewed for abdominal ultrasonographic and histologic findings. Diagnostic performance of ultrasonographic description of a splenic mass or nodule as cavitated as evidence of hemangiosarcoma or any malignancy was evaluated. RESULTS Ultrasonographic description of splenic lesions as cavitated had poor diagnostic utility in predicting presence of hemangiosarcoma or malignancy. Sensitivity and specificity of this test were 41.9% (95% CI, 30.5% to 54.3%) and 51.2% (95% CI, 36.8% to 65.4%), respectively, for detecting hemangiosarcoma, with positive and negative predictive values of 55.3% (95% CI, 41.2% to 68.6%) and 37.9% (95% CI, 26.6% to 50.8%), respectively. Results were similar for detecting malignancy. Cavitated lesions outside of the spleen were too rare for statistical analysis to be of value. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that relying on ultrasonographic description of cavitation to diagnose splenic lesions as malignant in dogs with nontraumatic hemoabdomen is unfounded. Other preoperative diagnostic tests may be more valuable in determining short- and long-term prognoses.


2020 ◽  
Vol 59 (1) ◽  
pp. e02162-20 ◽  
Author(s):  
Amanda J. Meyer ◽  
Emmanuel Ochom ◽  
Patricia Turimumahoro ◽  
Patrick Byanyima ◽  
Ingvar Sanyu ◽  
...  

ABSTRACTThe objective of this prospective cross-sectional study, conducted at a national referral hospital in Kampala, Uganda, was to determine diagnostic performance of serum C-reactive protein (CRP) as a triage test for tuberculosis (TB) among HIV-seronegative inpatients. We calculated the sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values to determine the diagnostic performance of a CRP enzyme-linked immunosorbent assay (ELISA) (Eurolyser) in comparison to that of a reference standard of Mycobacterium tuberculosis culture on two sputum samples. We constructed receiver operating curves and reported performance in reference to the manufacturer’s cutoff and also to a threshold chosen to achieve sensitivity of >90%, in accordance with the WHO’s target-product profile for a triage test. Among 119 HIV-seronegative inpatients, 46 (39%) had culture-positive pulmonary TB. In reference to M. tuberculosis culture, CRP had a sensitivity of 78% (95% confidence interval [CI], 64 to 89%) and a specificity of 52% (95% CI, 40 to 64%) at the manufacturer’s threshold of 10 mg/liter. At a threshold of 1.5 mg/liter, the sensitivity was 91% (95% CI, 79 to 98%) but the specificity was only 21% (95% CI, 12 to 32%). Performance did not differ when stratified by illness severity at either threshold. In conclusion, among HIV-seronegative inpatients, CRP testing performed substantially below targets for a TB triage test. Additional studies among HIV-seronegative individuals in clinics and community settings are needed to assess the utility of CRP for TB screening.


1991 ◽  
Vol 65 (01) ◽  
pp. 028-032 ◽  
Author(s):  
B Boneu ◽  
G Bes ◽  
H Pelzer ◽  
P Sié ◽  
H Boccalon

SummaryThis study was performed to determine the accuracy of D-Dimer fibrin derivatives, thrombin-antithrombin III (TAT) complexes and prothrombin fragments 1 + 2 (F 1 + 2) determinations for the diagnosis of deep vein thrombosis (DVT). One hundred and sixteen consecutive patients referred to the angiology unit of our hospital for a clinically suspected DVT were investigated. They were submitted to mercury strain gauge plethysmography and to ultrasonic duplex scanning examination; in cases of inconclusive results or of proximal DVT (n = 35), an ascending phlebography was performed. After these investigations were completed, the diagnosis of DVT was confirmed in 34 and excluded in 82. One half of the patients were already under anticoagulant therapy at the time of investigation. The 3 biological markers were assayed using commercially available ELISA techniques and the D-Dimer was also assayed with a fast latex method. The normal distribution of these markers was established in 40 healthy blood donors. The most accurate assay for the diagnosis of DVT was the D-Dimer ELISA which had both a high sensitivity (94%) and a high negative predictive value (95%). The D-Dirner latex, TAT complexes and F 1 + 2 were far less sensitive and provided negative predictive values which ranged between 78 and 85%. In spite of positive and significant correlations between the levels of ihe 3 markers, their association did not improve their overall accuracy for detecting D\/L Therefore, with the exception of the D-Dimer ELISA, these markers were of little value for the diagnosis of DVT in this specific population.


2020 ◽  
Vol 71 (Supplement_3) ◽  
pp. S257-S265 ◽  
Author(s):  
Kristen Aiemjoy ◽  
Dipesh Tamrakar ◽  
Shampa Saha ◽  
Shiva R Naga ◽  
Alexander T Yu ◽  
...  

Abstract Background Enteric fever, a bacterial infection caused by Salmonella enterica serotypes Typhi and Paratyphi A, frequently presents as a nonlocalizing febrile illness that is difficult to distinguish from other infectious causes of fever. Blood culture is not widely available in endemic settings and, even when available, results can take up to 5 days. We evaluated the diagnostic performance of clinical features, including both reported symptoms and clinical signs, of enteric fever among patients participating in the Surveillance for Enteric Fever in Asia Project (SEAP), a 3-year surveillance study in Bangladesh, Nepal, and Pakistan. Methods Outpatients presenting with ≥3 consecutive days of reported fever and inpatients with clinically suspected enteric fever from all 6 SEAP study hospitals were eligible to participate. We evaluated the diagnostic performance of select clinical features against blood culture results among outpatients using mixed-effect regression models with a random effect for study site hospital. We also compared the clinical features of S. Typhi to S. Paratyphi A among both outpatients and inpatients. Results We enrolled 20 899 outpatients, of whom 2116 (10.1%) had positive blood cultures for S. Typhi and 297 (1.4%) had positive cultures for S. Paratyphi A. The sensitivity of absence of cough was the highest among all evaluated features, at 65.5% (95% confidence interval [CI], 55.0–74.7), followed by measured fever at presentation at 59.0% (95% CI, 51.6–65.9) and being unable to complete normal activities for 3 or more days at 51.0% (95% CI, 23.8–77.6). A combined case definition of 3 or more consecutive days of reported fever and 1 or more of the following (a) either the absence of cough, (b) fever at presentation, or (c) 3 or more consecutive days of being unable to conduct usual activity--yielded a sensitivity of 94.6% (95% CI, 93.4–95.5) and specificity of 13.6% (95% CI, 9.8–17.5). Conclusions Clinical features do not accurately distinguish blood culture–confirmed enteric fever from other febrile syndromes. Rapid, affordable, and accurate diagnostics are urgently needed, particularly in settings with limited or no blood culture capacity.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1273.2-1274
Author(s):  
C. Lukas ◽  
G. Khoury ◽  
M. A. D’agostino ◽  
B. Combe ◽  
J. Morel

Background:The diagnostic process in a patient with early inflammatory back pain suggestive of axial spondyloarthritis (ax-SpA) requires assessment and integration of multiple aspects, including clinical examination, biological measurements and radiologic assessments. Among the physical examination features, alteration of spinal mobility is often observed in ax-SpA. However, whether mobility impairment might really increase diagnostic likelihood, and which of the measurements made have relevant diagnostic value remains unknown.Objectives:To describe the frequency and severity of mobility impairment in multiple traditional measurements in patients suspect of early ax-SpA at initial assessment time, and to analyze their individual diagnostic performances in reference to usual classification criteria applied after 2 years of follow-up.Methods:Data from the DESIR cohort, which included patients aged 18-50 with inflammatory back pain lasting for 3 months to 3 years and a clinical suspicion of ax-SpA diagnosis were used. Baseline measurements of Schober’s test (Schober), chest expansion (CEx), lateral spinal flexion (LatSpiFlex), cervical rotation (CervRot) and intermalleolar distance (IntMalDist) collected at baseline were classified according to reference data from the general population adjusted for age and -when appropriate- for height. Cutoffs were defined as above 2.5th, 5th, 10th and 25th percentiles. With ASAS classification for ax-SpA applied at 2 years follow-up visit as external reference, diagnostic performances (Sensitivity [Se], Specificity [Sp], Positive [PPV] and Negative [NPV] Predictive Values) were calculated.Results:Complete data were available for 575 patients (of whom 377 (66%) fulfilled the ASAS criteria at 2 years). Schober, CEx, LatSpiFlex, CervRot and IntMalDist were above 5th percentile in respectively 278 (48%), 82 (14%), 220 (38%) and 93 (16%) patients. None of the measurements showed a clinically relevant compromise between both Se and Sp, but Sp was highest for CEx-most impaired cutoffs (Figure 1). The highest PPV (73.6%) and NPV (39.4%) were observed for LatSpiFlex.Conclusion:Measures of mobility and their levels of impairment do not show sufficient individual diagnostic value for ax-SpA among patients with early inflammatory back pain. However, highest degrees of impairment when compared to general population are more specifically observed in patients finally classified with ax-SpA for CEx, which was –consistently- 1 of the 2 mobility measures that was retained in the modified New York criteria for ankylosing spondylitis.Disclosure of Interests:Cédric Lukas Speakers bureau: AbbVie; Lilly; Merck; Novartis; Pfizer; Roche-Chugai;, Consultant of: AbbVie; Bristol-Myers Squibb; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; UCB; Sanofi;, Grant/research support from: Pfizer: Novartis, Gisèle Khoury Grant/research support from: Pfizer, Maria-Antonietta d’Agostino: None declared., Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche-Chugai, Jacques Morel Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche-Chugai.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
J. A. M. C. Dirks ◽  
K. Janssen ◽  
C. J. P. A. Hoebe ◽  
T. H. B. Geelen ◽  
M. Lucchesi ◽  
...  

AbstractChlamydia trachomatis (CT) increases its plasmid numbers when stressed, as occurs in clinical trachoma samples. Most CT tests target the plasmid to increase the test sensitivity, but some only target the chromosome. We investigated clinical urogenital samples for total plasmid copy numbers to assess its diagnostic value and intra-bacterial plasmid copy numbers to assess its natural variation. Both plasmid and chromosome copies were quantified using qPCR, and the plasmid:chromosome ratio (PCr) calculated in two cohorts: (1) 383 urogenital samples for the total PCR (tPCr), and (2) 42 vaginal swabs, with one half treated with propium-monoazide (PMA) to prevent the quantification of extracellular DNA and the other half untreated to allow for both tPCr and intra-bacterial PCr (iPCr) quantification. Mann–Whitney U tests compared PCr between samples, in relation to age and gender. Cohort 1: tPCr varied greatly (1–677, median 16). Median tPCr was significantly higher in urines than vaginal swabs (32 vs. 11, p < 0.001). Cohort 2: iPCr was more stable than tPCr (range 0.1–3 vs. 1–11). To conclude, tPCr in urogenital samples was much more variable than previously described. Transport time and temperature influences DNA degradation, impacting chromosomal DNA more than plasmids and urine more than vaginal samples. Data supports a plasmid target in CT screening assays to increase clinical sensitivity.


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