scholarly journals Optimisation and usefulness of quantitative analysis of18F-florbetapir PET

2019 ◽  
Vol 92 (1101) ◽  
pp. 20181020 ◽  
Author(s):  
Daniel Fakhry-Darian ◽  
Neva Hiten Patel ◽  
Sairah Khan ◽  
Tara Barwick ◽  
William Svensson ◽  
...  

Objectives:This study investigates the usefulness of quantitative SUVR thresholds on sub types of typical (type A) and atypical (non-type A) positive (Aβ+) and negative (Aβ-)18F-florbetapir scans and aims to optimise the thresholds.Methods:Clinical18F-florbetapir scans (n = 100) were categorised by sub type and visual reads were performed independently by three trained readers. Inter-reader agreement and reader-to-reference agreement were measured. Optimal SUVR thresholds were derived by ROC analysis and were compared with thresholds derived from a healthy control group and values from published literature.Results:Sub type division of18F-florbetapir PET scans improves accuracy and agreement of visual reads for type A: accuracy 90%, 96% and 70% and agreement κ > 0.7, κ ≥ 0.85 and −0.1 < κ < 0.9 for all data, type A and non-type A respectively. Sub type division also improves quantitative classification accuracy of type A: optimum mcSUVR thresholds were found to be 1.32, 1.18 and 1.48 with accuracy 86%, 92% and 76% for all data, type A and non-type A respectively.Conclusions:Aβ+/Aβ- mcSUVR threshold of 1.18 is suitable for classification of type A studies (sensitivity = 97%, specificity = 88%). Region-wise SUVR thresholds may improve classification accuracy in non-type A studies. Amyloid PET scans should be divided by sub type before quantification.Advances in knowledge:We have derived and validated mcSUVR thresholds for Aβ+/Aβ-18F-florbetapir studies. This work demonstrates that division into sub types improves reader accuracy and agreement and quantification accuracy in scans with typical presentation and highlights the atypical presentations not suited to global SUVR quantification.

Neurology ◽  
2020 ◽  
Vol 94 (15) ◽  
pp. e1580-e1591 ◽  
Author(s):  
James D. Doecke ◽  
Virginia Pérez-Grijalba ◽  
Noelia Fandos ◽  
Christopher Fowler ◽  
Victor L. Villemagne ◽  
...  

ObjectiveTo explore whether the plasma total β-amyloid (Aβ) Aβ42/Aβ40 ratio is a reliable predictor of the amyloid-PET status by exploring the association between these 2 variables in a subset of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging cohort.MethodsTaking plasma samples at 3 separate time points, month 18 (n = 176), month 36 (n = 169), and month 54 (n = 135), we assessed the total Aβ42/Aβ40 ratio in plasma (TP42/40) with regard to neocortical Aβ burden via PET standardized uptake value ratio (SUVR) and investigated both association with Aβ-PET status and correlation (and agreement) with SUVR.ResultsThe TP42/40 plasma ratio was significantly reduced in amyloid-PET–positive participants at all time points (p < 0.0001). Adjusting for covariates age, gender, APOE ε4 allele status, and clinical classification clearly affects the significance, with p values reduced and only comparisons at 54 months retaining significance (p = 0.006). Correlations with SUVR were similar across each time point, with Spearman ρ reaching −0.64 (p < 0.0001). Area under the curve values were highly reproducible over time points, with values ranging from 0.880 at 36 months to 0.913 at 54 months. In assessments of the healthy control group only, the same relationships were found.ConclusionsThe current study demonstrates reproducibility of the plasma assay to discriminate between amyloid-PET positive and negative over 3 time points, which can help to substantially reducing the screening rate of failure for clinical trials targeting preclinical or prodromal disease.Classification of evidenceThis study provides Class II evidence that plasma total Aβ42/Aβ40 ratio is associated with neocortical amyloid burden as measured by PET SUVR.


2016 ◽  
Vol 86 (1-2) ◽  
pp. 9-17 ◽  
Author(s):  
Bekir Ucan ◽  
Mustafa Sahin ◽  
Muyesser Sayki Arslan ◽  
Nujen Colak Bozkurt ◽  
Muhammed Kizilgul ◽  
...  

Abstract.The relationship between Hashimoto’s thyroiditis and vitamin D has been demonstrated in several studies. The aim of the present study was to evaluate vitamin D concentrations in patients with Hashimoto’s thyroiditis, the effect of vitamin D therapy on the course of disease, and to determine changes in thyroid autoantibody status and cardiovascular risk after vitamin D therapy. We included 75 patients with Hashimoto’s thyroiditis and 43 healthy individuals. Vitamin D deficiency is defined as a 25-hydroxy vitamin D (25(OH)D3) concentration less than 20ng/mL. Vitamin D deficient patients were given 50.000 units of 25(OH)D3 weekly for eight weeks in accordance with the Endocrine Society guidelines. All evaluations were repeated after 2 months of treatment. Patients with Hashimoto’s thyroiditis had significantly lower vitamin D concentrations compared with the controls (9.37±0.69 ng/mL vs 11.95±1.01 ng/mL, p < 0.05, respectively). Thyroid autoantibodies were significantly decreased by vitamin D replacement treatment in patients with euthyroid Hashimoto’s thyroiditis. Also, HDL cholesterol concentrations improved in the euthyroid Hashimoto group after treatment. The mean free thyroxine (fT4) concentrations were 0.89±0.02 ng/dL in patients with Hashimoto’s thyroiditis and 1.07±0.03 ng/dL in the healthy control group (p < 0.001). The mean thyroid volumes were 7.71±0.44 mL in patients with Hashimoto’s thyroiditis and 5.46±0.63 mL in the healthy control group (p < 0.01). Vitamin D deficiency is frequent in Hashimoto’s thyroiditis and treatment of patients with this condition with Vitamin D may slow down the course of development of hypothyroidism and also decrease cardiovascular risks in these patients. Vitamin D measurement and replacement may be critical in these patients.


1997 ◽  
Vol 78 (03) ◽  
pp. 0990-0992 ◽  
Author(s):  
Andreas Hillarp ◽  
Bengt Zӧller ◽  
Peter J Svensson ◽  
Bjӧrn Dahlbäck

SummaryA dimorphism in the 3’-untranslated region of the prothrombin gene (G to A transition at position 20210) has recently been reported to be associated with increases in plasma prothrombin levels and in the risk of venous thrombosis (1). We have examined the prothrombin dimorphism among 99 unselected outpatients with phlebography verified deep venous thrombosis, and in 282 healthy controls. The prevalence of the 20210 A allele was 7.1% (7/99) in the patient group, and 1.8% (5/282) in the healthy control group (p = 0.0095). The relative risk of venous thrombosis was calculated to be 4.2 (95% Cl, 1.3 to 13.6), and was still significant when adjustment was made for age, sex and the factor V:R506Q mutation causing APC resistance [odds ratio 3.8 (95% Cl, 1.1 13.2)]. As previously reported, 28% of the patients were carriers of the factor V:R506Q mutation. Thus, 34% (one patient carried both traits) of unselected patients with deep venous thrombosis were carriers of an inherited prothrombotic disorder. To sum up, our results confirm the 20210 A allele of the prothrombin gene to be an important risk factor for venous thrombosis.


2020 ◽  
Vol 26 (27) ◽  
pp. 3341-3348 ◽  
Author(s):  
Marek Femlak ◽  
Anna Gluba-Brzozka ◽  
Beata Franczyk ◽  
Jacek Rysz

Introduction: Diabetes mellitus (DM) due to its increasing prevalence and associated morbidity and mortality has become a serious public health problem. In DM, HDL may lose its beneficial features and become proatherogenic due to its altered biological activity thus increasing cardiovascular risk. The aim of this study was to assess the influence of the presence of diabetes mellitus type 2 and its duration on the distribution of HDL subfractions. Moreover, the effect of statin treatment on HDL subfraction share was analysed in this study. Methods: The study group consisted of 50 patients with newly diagnosed DM and 50 persons with DM for longer than 10 years while the control group consisted of 50 healthy volunteers. HDL subfractions were analysed with the use of Lipoprint. Results: We demonstrated progressive worsening of heart functioning and impairment of its structure in the course of diabetes mellitus. Moreover, we observed that HDL-6 subfraction and intermediate HDL fraction are lowest in the group with advanced DMt2 compared to the group with newly diagnosed DM and a healthy control group. Finally, the results of our study indicated the effect of statin treatment on HDL subfractions that seems not to be advantageous. Conclusion: It seems that in patients with diabetes mellitus compromised antiatherogenic properties of HDL, as a result of oxidative modification and glycation of the HDL protein as well as the transformation of the HDL proteome into a proinflammatory protein, increase cardiovascular risk.


2020 ◽  
Vol 22 (9) ◽  
pp. 657-662 ◽  
Author(s):  
Mustafa Celik ◽  
Alper Şen ◽  
İsmail Koyuncu ◽  
Ataman Gönel

Aim and Objective:: To determine the mechanisms present in the etiopathogenesis of nasal polyposis. It is not clear whether amino acids contribute in a causal way to the development of the disease. Therefore, the aim of this study was to determine the plasma-free amino acid profile in patients with nasal polyposis and to compare the results with a healthy control group. Materials and Methods:: This was a prospective controlled study that took place in the Otolaryngology Department at the Harran University Faculty of Medicine between April 2017 and April 2018. Plasmafree amino acid profile levels were studied in serum samples taken from a patient group and a healthy control group. Patients who were diagnosed with bilateral diffuse nasal polyposis and were scheduled for surgical interventions were included in this study. Individuals whose age, gender, and body mass index values were compatible with that of the patient group and who did not have any health problems were included in the control group. All the participants whose levels of plasma-free amino acid were thought to be affected by one or more of the following factors were excluded from the study: smoking and alcohol use, allergic rhinitis presence, the presence of acute or chronic sinusitis, a history of endoscopic sinus surgery, unilateral nasal masses, a history of chronic drug use, systemic or topical steroid use in the last three months for any reason, and liver, kidney, hematological, cardiovascular, metabolic, neurological, or psychiatric disorders or malignancies. Results: In patients with nasal polyposis, 3-methyl histidine (3-MHIS: nasal polyposis group (ng) = 3.22 (1.92 – 6.07); control group (cg) = 1.21 (0.77 – 1.68); p = 0.001); arginine (arg: ng = 98.95 (70.81 – 117.75); cg = 75.10 (54.49 – 79.88); p = 0.005); asparagine (asn: ng = 79.84 (57.50 – 101.44); cg = 60.66 (46.39 – 74.62); p = 0.021); citrulline (cit: ng = 51.83 (43.81 – 59.78); cg = 38.33 (27.81 – 53.73); p = 0.038); cystine (cys: ng = 4.29 (2.43 – 6.66); cg = 2.41 (1.51 – 4.16); p = 0.019); glutamic acid (glu: ng = 234.86 (128.75 – 286.66); cg = 152.37 (122.51 – 188.34); p = 0.045); histidine (his: ng = 94.19 (79.34 – 113.99); cg = 74.80 (62.76 – 98.91); p = 0.018); lysine (lys: ng = 297.22 (206.55 – 371.25); cg = 179.50 (151.58 – 238.02); p = 0.001); ornithine (ng = 160.62 (128.36 – 189.32); cg = 115.91 (97.03 – 159.91); p = 0.019); serine (ser: ng = 195.15 (151.58 – 253.07); cg = 83.07 (67.44 – 92.44); p = 0.001); taurine (tau: ng = 74.69 (47.00 – 112.13); cg = 53.14 (33.57 – 67.31); p = 0.006); tryptophan (trp: ng = 52.31 (33.81 – 80.11); cg = 34.44 (25.94 – 43.07); p = 0.005), homocitrulline (ng = 1.75 (1.27 – 2.59); cg = 0.00 (0.00 – 0.53); p = 0.001); norvaline (ng = 6.90 (5.61 – 9.18); cg = 4.93 (3.74 – 7.13); p = 0.021); argininosuccinic acid (ng = 14.33 (10.06 – 25.65); cg = 12.22 (5.77 – 16.87) p = 0.046); and plasma concentrations were significantly higher than in the healthy control group (p <0.05). However, the gamma-aminobutyric acid (gaba: ng = 0.16 (0.10 – 0.24); cg = 0.21 (0.19 – 0.29); p = 0.010) plasma concentration was significantly lower in the nasal polyposis group than in the healthy control group. Conclusion: In this study, plasma levels of 15 free amino acids were significantly higher in the nasal polyposis group than in the healthy control group. A plasma level of 1 free amino acid was found to be significantly lower in the nasal polyposis group compared to the healthy control group. Therefore, it is important to determine the possibility of using the information obtained to prevent the recurrence of the condition and to develop effective treatment strategies. This study may be a milestone for studies of this subject. However, this study needs to be confirmed by further studies conducted in a larger series.


2020 ◽  
Vol 18 (3) ◽  
pp. 194-200
Author(s):  
Maryam Moradi ◽  
Alireza Tabibzadeh ◽  
Davod Javanmard ◽  
Saied Ghorbani ◽  
Farah Bokharaei-Salim ◽  
...  

Background: Coinfection of Hepatitis C virus (HCV) with human immunodeficiency virus (HIV) has a higher risk of mortality than HCV or HIV monoinfection. HCV and HIV infections are specified by systemic inflammation, but the inflammation process in HCV/HIV coinfection is much complicated and is not well characterized. Objective: The aim of this study was to analyze the expression of TLR-3, TLR-7, IL-10, IFN-1 (IFN-α, IFN-β), and TNF-α in HIV, HCV and HIV/HCV co-infected patients. Methods: Forty-five patients including HIV group (n=15), HCV group (n=15), HIV/HCV coinfection group (n=15) and healthy control group (n=15) participated. Peripheral blood mononuclear cells (PBMCs) were obtained. PBMC-RNA, HCV and HIV RNA were extracted from all subjects and cDNA was synthesized. The viral load analyzed by reverse transcription-quantitative PCR (RT-qPCR), and the expression levels of IFN-α, IFN-β, TLR-3, TLR-7, TNF, and IL-10 mRNA were quantified in PBMCs. Results: The levels of IFN-I, IL-10, and TNF-α were overexpressed in all patients’ groups (P<0.05), TLR-7 was upregulated in all groups, but this upregulation was not statistically significant (p>0.05). TLR-3 showed a decrease in all patient groups (P<0.05). The statistical analysis demonstrated that TLR-3 has a negative correlation with HIV load, whereas other genes positively correlated with HIV load. In addition, TLR-3, TNF-α, and IFN-I were negatively correlated with HCV load, whereas TLR-7 and IL-10 s were positively correlated with HCV load. Conclusion: Our results showed a significant relationship between the expression level of innate immunity genes and inflammation in HCV, HIV, and HIV/HCV coinfected patients.


2019 ◽  
Vol 16 (1) ◽  
pp. 113-119 ◽  
Author(s):  
Mohammad Aminianfar ◽  
Siavash Parvardeh ◽  
Mohsen Soleimani

Background: Clostridium botulinum causes botulism, a serious paralytic illness that results from the ingestion of a botulinum toxin. Because silver nanoparticle products exhibit strong antimicrobial activity, applications for silver nanoparticles in healthcare have expanded. Therefore, the objective of the current study was to assess a therapeutic strategy for the treatment of botulism toxicity using silver nanoparticles. Methods: A preliminary test was conducted using doses that produce illness in laboratory animals to determine the absolute lethal dose (LD100) of botulinum toxin type A (BoNT/A) in mice. Next, the test animals were divided into six groups containing six mice each. Groups I, II and III were the negative control (botulinum toxin only), positive control-1 (nano-silver only) and positive control-2 (no treatment), respectively. The remaining groups were allocated to the toxin that was supplemented with three nano-silver treatments. Results: The mortality rates of mice caused by BoNT/A significantly reduced in the treatment groups with different doses and injection intervals of nano-silver when compared to the negative control group. BoNT/A toxicity induced by intraperitoneal injection of the toxin of Clostridium botulinum causes rapid death while when coupled with nano-osilver results in delayed death in mice. Conclusion: These results, while open to future improvement, represent a preliminary step towards the satisfactory control of BoNT/A with the use of silver nanoparticles for human protection against this bioterrorism threat. Further study in this area can elucidate the underlying mechanism for detoxifying BoNT/A by silver nanoparticles.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuan-Yuan Gong ◽  
Hai-Ying Peng

Abstract Background To investigate the correlation between the thickness of epicardial adipose tissue (EAT), C-reactive protein (CRP), interleukin (IL) -6, visfatin, juxtaposed with another zinc finger protein 1 (JAZF1) and type 2 diabetic mellitus (T2DM) macroangiopathy. Methods The study enrolled 82 patients with T2DM with macroangiopathy (the Complication Group), and 85 patients with T2DM (the Diabetes Group) who were admitted to Shandong Provincial Third Hospital from February 2018 to February 2020. In addition, 90 healthy people who underwent physical examination at the same hospital during the same period were enrolled (the Healthy Control Group). Age, gender, height, weight, waist circumference (WC), hip circumference (HC), diabetic course and therapeutic drugs, waist hip ratio (WHR), and body mass index (BMI) were recorded and calculated. Results The baseline characteristics of the three groups were comparable, and the diabetic course of the Complication Group and the Diabetes Group was not significantly different (P > 0.05). The WHR of the Complication Group was higher than that of the Diabetes Group and the Healthy Control Group, with statistical significance (P < 0.05). The FPG, 2hPG, HbA1C, CRP, IL-6, Visfatin, JAZF1, HOMA-IR, EAT thickness, and baPWV of the Complication Group were all higher than those of the Diabetes Group and the Healthy Control Group (P < 0.05, respectively). The JAZF1 and FIns of the Complication Group and Diabetes Group were lower than those of the Healthy Control Group, and JAZF1 of the Complication Group was lower than the Diabetes Group with statistical significance (P<0.05, respectively). Pearson correlation analysis showed that the EAT thickness was positively correlated with CRP, IL-6, visfatin, and JAZF1 (r = 0.387, 0.451, 0.283, 0.301, respectively, all P<0.001). Pearson correlation analysis showed that baPWV was positively correlated with EAT thickness, CRP, IL-6, visfatin, and JAZF1 (r = 0.293, 0.382, 0.473, 0.286, respectively, all P < 0.001). Multivariate stepwise regression analysis showed that FPG, 2hPG, HbA1C, CRP, IL-6, visfatin, JAZF1, and EAT thickness were independent risk factors that affected T2DM macroangiopathy. Conclusions Clinical monitoring and treatment of T2DM macroangiopathy can use CRP, IL-6, Visfatin, JAZF1, and EAT thickness as new targets to delay the progression of the disease. Further research on the relationship between the above factors and the pathogenesis of T2DM macroangiopathy may be helpful provide new treatment strategies.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jae Hwa Kim ◽  
Go-Tak Kim ◽  
Siyeoung Yoon ◽  
Hyun Il Lee ◽  
Kyung Rae Ko ◽  
...  

Abstract Background Vitamin B12 (Vit B12) deficiency results in elevated homocysteine levels and interference with collagen cross-linking, which may affect tendon integrity. The purpose of this study was to investigate whether serum Vit B12 levels were correlated with degenerative rotator cuff (RC) tear. Methods Eighty-seven consecutive patients with or without degenerative RC tear were enrolled as study participants. Possible risk factors (age, sex, medical history, bone mineral density, and serum chemistries including glucose, magnesium, calcium, phosphorus, zinc, homocysteine, Vitamin D, Vit B12, homocysteine, and folate) were assessed. Significant variables were selected based on the results of univariate analyses, and a logistic regression model (backward elimination) was constructed to predict the presence of degenerative RC tear. Results In the univariate analysis, the group of patients with degenerative RC tear had a mean concentration of 528.4 pg/mL Vit B12, which was significantly lower than the healthy control group (627.1 pg/mL). Logistic regression analysis using Vit B12 as an independent variable revealed that Vit B12 concentrations were significantly correlated with degenerative RC tear (p = 0.044). However, Vit B12 levels were not associated with tear size. Conclusion Low serum levels of Vit B12 were independently related to degenerative RC tear. Further investigations are warranted to determine if Vit B12 supplementation can decrease the risk of this condition.


2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199296
Author(s):  
Juan Wang ◽  
Liu Yang ◽  
Yanjun Diao ◽  
Jiayun Liu ◽  
Jinjie Li ◽  
...  

Objective To evaluate the performance of a DNA methylation-based digital droplet polymerase chain reaction (ddPCR) assay to detect aberrant DNA methylation in cell-free DNA (cfDNA) and to determine its application in the detection of hepatocellular carcinoma (HCC). Methods The present study recruited patients with liver-related diseases and healthy control subjects. Blood samples were used for the extraction of cfDNA, which was then bisulfite converted and the extent of DNA methylation quantified using a ddPCR platform. Results A total of 97 patients with HCC, 80 healthy control subjects and 46 patients with chronic hepatitis B/C virus infection were enrolled in the study. The level of cfDNA in the HCC group was significantly higher than that in the healthy control group. For the detection of HCC, based on a cut-off value of 15.7% for the cfDNA methylation ratio, the sensitivity and specificity were 78.57% and 89.38%, respectively. The diagnostic accuracy was 85.27%, the positive predictive value was 81.91% and the negative predictive value was 87.20%. The positive likelihood ratio of 15.7% in HCC diagnosis was 7.40, while the negative likelihood ratio was 0.24. Conclusions A sensitive methylation-based assay might serve as a liquid biopsy test for diagnosing HCC.


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