scholarly journals Species-Specific Immunoassay for Diagnosis and Tracking Treatment Response in Foot and Ankle Infection

2020 ◽  
Vol 5 (4) ◽  
pp. 2473011420S0037
Author(s):  
Irvin Oh ◽  
Stephanie Hao ◽  
Olivia Waldman ◽  
Amanda H. Holleran ◽  
John L. Daiss

Category: Basic Sciences/Biologics; Diabetes Introduction/Purpose: Staphylococcus aureus is the major pathogen foot and ankle infections and osteomyelitis (>50%). There are currently no sensitive and specific diagnostic tools for monitoring a pathogen’s ongoing infection or providing prognostic measures. We have developed a novel immunoassay for S. aureus, and have applied this to diagnose and monitor its infectivity. We hypothesize that: 1) the species-specific immunoassay can serve as a reliable diagnostic tool for S. aureus foot and ankle infections and 2) the immunoassay provides a measure of treatment response and prognosis of clinical outcome to antibiotics therapy for S. aureus foot and ankle infections. Methods: From July 2015 to July 2019, 83 infected diabetic foot ulcer (DFU) patients undertaking surgical treatment were recruited. Blood were drawn from subjects at initial, 4-week, 8-week, and 12-week after surgery. Clinical wound healing status was determined by a fellowship-trained orthopaedic foot and ankle surgeon. Serum antibodies and plasmablast cultured antibodies (newly synthesized antibodies: NSA) were harvested. Eight unique S. aureusantigens from distinct functional classes were used for the immunoassay. All serum and NSA samples were run on a flow cytometer (Bio-Plex 200; Bio-Rad, Life Sciences Research) in duplicates and assessed for predictive ability in discriminating infection status and healing status using receiver operating characteristic (ROC) curve analysis, with accuracy summarized by the area under the ROC curve (AUC). Nonparametric estimates and 95% confidence intervals for the AUC were computed for each predictor along with p-values for testing the significance of each AUC. Results: Analysis of serum immunoassay showed significant difference in three anti-S. aureus antigens titers (IsdH (p = 0.037; AUC = 0.638), ClfB (p = 0.025; AUC = 0.644), and SCIN (p = 0.005; AUC = 0.677)) between S. aureus infected versus non- S. aureus infected DFU patients at initial presentation. NSA immunoassay showed elevation of two different S. aureus specific antigens, IsdH and LukS-PV, for S. aureus infected versus non- S. aureus infected DFU patients in ratios of approximately five and four, respectively. Changes of NSA based anti-S. aureus antibody titers over 12 weeks period, as single antigen or in combination, significantly correlated with clinical resolution of infection and wound healing status. Four anti-S. aureus antigen combinations achieved the highest AUC (Figure 1). Conclusion: Our results demonstrate that both the serum and NSA immunoassay can diagnose S. aureus infected DFUs. Furthermore, changes in NSA titers over a period of time against various S. aureus specific antigens significantly correlated with clinical representation of infection and wound healing status. The novel species-specific immunoassay can serve as a promising diagnostic system, tracking tool and prognostic potential in management of S. aureus associated foot and ankle infection.

2019 ◽  
Vol 185 (2) ◽  
pp. 52-52 ◽  
Author(s):  
Francesca Perondi ◽  
Ilaria Lippi ◽  
Gianila Ceccherini ◽  
Veronica Marchetti ◽  
Grazia Guidi

Urinary and blood biomarkers for diagnosis of acute kidney injury (AKI) in hospitalised dogs were evalueted. This prospective study included 97 dogs, classified according to the International Renal Interest Society classification into no AKI and AKI grade 1 (48-hour increase in serum creatinine≥0.3 mg/dl and/or urinary production <1 ml/kg/hour for at least six hours). A total of 62 of 97 dogs (64 per cent) were classified as AKI 1. A statistically significant difference was found between no AKI and AKI 1 in urine protein to creatinine ratio, urinary γ-glutamyl transferase (uGGT) and uGGT/cu (P<0.0001). Thirteen of 97 dogs (13.4 per cent) that developed increased creatinine and change in AKI grade showed high mortality (n=9/13; 69.2 per cent). The receiver operating characteristic (ROC) curve analysis of uGGT/cu index as a marker for AKI grade 1 had an area under the ROC curve of 0.78; optimal cut-off point was 57.50 u/g, with sensitivity and specificity of 75.4 per cent and 75.6 per cent, respectively. Overall intensive care unit mortality was 23.7 per cent (23/97), 13.4 per cent (13/97) of which died during hospitalisation and 10.3 per cent (10/97) within 28 days after discharge. uGGT is an acceptable marker for distinguishing between AKI 1 and no AKI.


2020 ◽  
Vol 8 (1) ◽  
pp. 32
Author(s):  
Waseem A. Shoda

Background: Evaluation of diagnostic ability of preoperative estimation of serum thyroglobulin (TG) to detect malignant thyroid nodules (TN) in comparison to the American College of Radiology, Thyroid imaging reporting and data system (ACR-TIRADS), fine needle aspiration cytology (FNAC) and intraoperative frozen section (IO-FS).Methods: 34 patients with ACR-TIRADS 2-4 TN were evaluated preoperatively for identification of malignancy and all underwent total thyroidectomy with bilateral neck block dissection if indicated. Results of preoperative investigations were statistically analyzed using the Receiver operating characteristics (ROC) curve analysis as predictors for malignancy in comparison to postoperative paraffin sections.Results: Preoperative serum TG levels had 100% sensitivity and negative predictive value, while ACR-TIRADS scoring had 100% specificity and positive predictive value with accuracy rates of 95.35% and 97.67% for TG and TIRADS, respectively. ROC curve analysis defined preoperative ACR-TIRADS class and serum TG as highly diagnostic than FNAC for defining malignancy with non-significant difference between areas under curve for TIRADS and TG. For cases had intermediate risk of malignancy on TIRADS, IO-FS had missed 3, FNAC missed 4, while serum TG levels were very high in the 13 cases and were defined by ROC curve as the only significant predictor for malignancy.Conclusions: Preoperative estimation of serum TG showed higher diagnostic validity than FNAC, high predictability of cancer and ability to verify the intermediate findings on TIRADS. Combined preoperative TIRADS and TG estimation could accurately discriminate malignant TN with high accuracy and spare the need for preoperative FNAC or IO-FS. 


2021 ◽  
Author(s):  
Wenqing Shi ◽  
Shinan Wu ◽  
Tie Sun ◽  
Huiye Shu ◽  
Qichen Yang ◽  
...  

Abstract Background: Gastric cancer (GC) is one of the most common malignancies in the population. Although the incidence of GC has reduced, patient prognosis remains poor. Ocular metastases (OM) from GC are rare, and the occurrence of OM is often indicative of severe disease. The purpose of this study was to explore the risk factors for OM of GC.Methods: A total of 1165 older adult patients with GC were enrolled in this study from June 2003 to May 2019 and divided into OM and non-ocular metastasis (NOM) groups. Chi-square and independent samples t tests were used to determine whether differences in demographic characteristics and serological indicators (SI) between the two groups were significant. In addition, binary logistic regression was used to analyze the value of various SI as risk factors for OM in patients with GC. The statistical threshold was set as P < 0.05. Finally, receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of various SI in differentiating the occurrence of OM in patients with GC. Results: The incidence of OM in older adults with GC was 1.1%. Adenocarcinoma was the most common type of GC in both groups, and there was no significant difference in demographic characteristics, including sex and age between the groups. Low-density lipoprotein (LDL), carbohydrate antigen-724 (CA724), and carcinoembryonic antigen levels were significantly higher in the OM group than the NOM group, while those of apolipoprotein A1 (ApoA1) were significantly lower in the OM than the NOM group. Binary logistic analysis showed that LDL, ApoA1, and CA724 were independent risk factors for OM in patients with GC (P < 0.001,P = 0.033, and P = 0.008, respectively). ROC curve analysis generated area under the curve (AUC) values of 0.881, 0.576, and 0.906 for LDL, ApoA1, and CA724, respectively. In addition, combined analysis of LDL, ApoA1, and CA724 generated the highest AUC value of 0.924 (P < 0.001).Conclusion: Among SI, LDL, ApoA1, and CA724 have predictive value for the occurrence of OM in GC, with the three factors combined having the highest value.


2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi18-vi18
Author(s):  
Yoshiko Okita ◽  
Koji Takano ◽  
Soichiro Tateishi ◽  
Motohisa Hayashi ◽  
Mio Sakai ◽  
...  

Abstract Background: Glioblastoma is a highly infiltrative tumor. In the non-enhancing T2-weighted hyperintense area, differentiating between non-enhancing tumors (NETs) and vasogenic edema is challenging. Neurite orientation dispersion and density imaging (NODDI) is a new diffusion MRI technique that reveals the inhomogeneity of the brain microstructure. The aim of this study is to differentiate between NETs and edema in glioblastomas using NODDI. Methods: Data were collected from 20 patients with glioblastoma as well as three patients with metastasis and two with meningioma (control), who underwent MRI as part of pre-surgical examination. The MRI data included T2- and T1-weighted contrast-enhanced images and NODDI images. Three neurosurgeons manually placed the volume of interest (VOI) on the NETs and edema based on the previous reports. ICVF, ODI, ISOVF, FA, and ADC were calculated for each VOI. Results: Fifteen and 13 VOIs were placed on NETs and edema, respectively. Each parameter was measured and the unpaired t-test revealed a significant difference between NETs and edema (p &lt;0.0001). The ROC curve analysis revealed a large difference in the ADC, FA, and ISOVF between NETs and edema compared to ICVF and ODI. Principal component analysis of the five parameters showed that ADC, ISOVF, and FA contributed to the differentiation between NETs and edema. Multiple logistic regression analysis was performed with the three aforementioned parameters. A predictive formula could be created to discriminate between NETs and edema, following the use of which, the ROC curve revealed an AUC value of 0.8891. Furthermore, this formula was applied to the edematous regions of the images of the negative control group, and the prediction degree of the tumor was well below 0.5, thus enabling differentiation as edema.Conclusions: NODDI may prove to be a useful tool to discriminate between NETs and edema in the non-contrast T2 hyperintensity region of glioblastoma.


2020 ◽  
Author(s):  
Liangna Deng ◽  
Guojing Zhang ◽  
Xiaoqiang Lin ◽  
Mengyuan Jing ◽  
Tao Han ◽  
...  

Abstract Background: To investigate the spectral computed tomography (CT) findings of peripheral adenocarcinoma (P-AC) and peripheral squamous cell carcinoma (P-SCC) in lung. Methods: In this retrospective study, A total of 273 patients (150 patients with P-AC and 123 patients with P-SCC) confirmed by surgery and pathology who underwent chest contrast enhanced CT scan with GSI mode, including arterial phase (AP) and venous phase (VP). During two phases, The CT40keV, CT70keV, CT100keV values, iodine concentration (IC), water concentration (WC), effective atomic number (Zeff) were measured and the slope of the spectral curve (K) was calculated. Differences between two groups were compared using two-sample t-test, Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC) was also calculated to calculate diagnostic efficacies.Results: There was significant difference in gender between the two groups (P < 0.05), No significant difference between other clinical features and symptoms (P > 0.05). For AP and VP, the CT40keV, CT70keV, K70keV, IC and Zeff of P-AC were significantly higher than those of P-SCC (P<0.05), but there was no significant difference in WC and CT100keV between the two groups. ROC curve analysis showed that the combination of all quantitative parameters in AP and VP had the best diagnostic performance, with the area under the curve, sensitivity and specificity of 92%, 88%, and 84%, respectively.Conclusions: Spectral CT can provide reference for the differentiation of P-AC and P-SCC.


2022 ◽  
Vol 21 ◽  
pp. 153303382110658
Author(s):  
Wen-Qing Shi ◽  
Shi-Nan Wu ◽  
Tie Sun ◽  
Hui-Ye Shu ◽  
Qi-Chen Yang ◽  
...  

Objective: The purpose of this study was to explore the risk factors for Ocular metastasis (OM) of Gastric cancer (GC). Methods: This is a retrospective cohort study. A total of 1165 patients with GC were enrolled in this study and divided into OM and non-ocular metastasis (NOM) groups. Chi-square and independent samples t tests were used to determine whether differences in demographic characteristics and serological indicators (SI) between the two groups were significant. In addition, binary logistic regression was used to analyze the value of various SI as risk factors for OM in patients with GC. The statistical threshold was set as P < .05. Finally, receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of various SI in differentiating the occurrence of OM in patients with GC. Results: The incidence of OM in older adults with GC was 1.1%. Adenocarcinoma was the most common type of GC in both groups, and there was no significant difference in demographic characteristics between the groups. Low-density lipoprotein (LDL), carbohydrate antigen-724 (CA724), and carcinoembryonic antigen levels were significantly higher in the OM group than the NOM group, while those of apolipoprotein A1 (ApoA1) were significantly lower in the OM than the NOM group. Binary logistic analysis showed that LDL, ApoA1, and CA724 were independent risk factors for OM in patients with GC ( P < .001, P = .033, and P = .008, respectively). ROC curve analysis generated area under the curve (AUC) values of 0.881, 0.576, and 0.906 for LDL, ApoA1, and CA724, respectively. In addition, combined analysis of LDL, ApoA1, and CA724 generated the highest AUC value of 0.924 ( P < .001). Conclusion: Among SI, LDL, ApoA1, and CA724 have predictive value for the occurrence of OM in GC, with the three factors combined having the highest value.


2021 ◽  
Author(s):  
Benshuo Cai ◽  
Xinni Na

Abstract Background: The role of repeat cerclage (RC) as a remedy for patients with prolapsed membranes after prior cerclage remains controversial. We aimed to investigate whether gestational age (GA) could be used as a valuable factor for predicting pregnancy outcome following RC in women with prolapsed membranes after prior cerclage. Methods: We retrospectively investigated the clinical data of 29 patients who underwent RC resulting from prolapsed membrane after prior cerclage. Receiving operating characteristic (ROC) curve analysis and univariate analysis were performed to determine predictive factors. Patients were divided into two groups according to GA at RC, GA<24.2 weeks and GA≥24.2 weeks. Pregnancy outcomes were compared between groups.Results: The mean GA at prior cerclage was 16.5 weeks; mean GA at RC was 23.6 weeks. The mean GA at delivery was 27.8 weeks with a 69.0% neonatal survival rate. ROC curve and univariate analysis demonstrated that GA at RC was significantly predictive for neonatal survival (area under the curve: 0.928; p=0.000). Using a GA cut-off of ≥24.2 weeks at RC, the sensitivity and specificity of predicting neonatal survival were 93.75% and 61.54%, respectively. There was a significant difference in neonatal survival rate between the GA <24.2 weeks group and GA ≥24.2 weeks group (38.5% vs. 93.8%, p=0.003). Kaplan–Meier survival curves showed a lower incidence of neonatal death in the GA ≥24.2 weeks group (6.3%) compared with GA <24.2 weeks group (61.5%, p=0.023).Conclusions: GA could be a valuable factor for predicting pregnancy outcome post-RC in women with prolapsed membrane after prior cerclage.


2020 ◽  
Vol EJMM29 (4) ◽  
pp. 9-15
Author(s):  
Rania A. El-Kady ◽  
Mohammed M. El-Naggar ◽  
ehab A. Abd El-Shakour ◽  
Monir H. Bahgat

Background: Hepatocellular carcinoma (HCC) is amongst the most common malignant tumors that carries a poor prognosis. Clinically, alpha-fetoprotein (AFP) is the most extensively used serum biomarker for diagnosing HCC. Objectives: The current study was conducted to explore the diagnostic value of serum levels of alpha-fetoprotein-L3 (AFP-L3) and Golgi protein 73 (GP73) regarding HCC, and to determine the diagnostic accuracy of these biomarkers when used individually as well as in combination with AFP. Methodology: Blood samples were collected from 50 patients with HCV-related cirrhosis (25 subjects with HCC and 25 without HCC) recruited from the outpatient clinics of the Specialized Internal Medicine Hospital, Mansoura University, Egypt. Serum concentrations of AFP-L3 and GP73 were evaluated using enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of AFP-L3 and GP73 was determined by receiver operating characteristic (ROC) curve analysis. Results: Overall, the median serum level of AFP-L3 was higher in the HCC group compared to the cirrhotic group (p=0.05). Moreover, a statistically-significant difference was observed between the median serum value of GP73 in HCC patients compared to those with cirrhosis (p < 0.001). The ROC curve analysis showed that the area under the ROC curve (AUROC) values for AFP, AFP-L3 and GP73 were 0.88, 0.67 and 0.83, respectively. Of the 3 biomarkers, GP73 demonstrated the highest sensitivity (88%). The AUROC for AFP and AFP-L3 combination was 0.85, whereas that for AFP and GP73 was 0.90. Conclusion: Our findings indicate that GP73 is more sensitive than AFP and AFP-L3 in diagnosing HCC. Furthermore, the combined determination of GP73 and AFP could improve the diagnostic ability of HCC.


2019 ◽  
Author(s):  
Yonghua Xiang ◽  
Xuehua Zhang ◽  
Jun Qiu ◽  
Qing Gan ◽  
Ke Jin

Abstract Purpose The purpose of this study was to compare the differences between obstructed and unobstructed TAPVC using echocardiography, then to predict PVO by assessing clinical and echocardiographic parameters. Methods We conducted a retrospective study included 70 patients with TAPVC between 2014 and 2018. The morphological and hemodynamic echocardiographic parameters were observed and measured. The clinical and echocardiographic parameters that existed difference between obstructed and unobstructed TAPVC were selected to predict PVO by running ROC curve analysis. Results Between obstructed and unobstructed TAPVC, there were significant differences in ASD size, PA Vmax, MV VE, LVFS, LVEF, SV and the incidence of PDA, but there was no significant difference in birth weight. The first admission age of obstructed TAPVC was earlier than unobstructed type. The ROC curve analysis for the first admission age in predicting PVO showed the sensitivity and specificity were 76.7%, 80% respectively. The ROC curve analysis for multiple echocardiographic parameters showed the sensitivity and specificity were 82.6%, 100% respectively. Conclusions The presence of PVO led to anatomical and functional abnormity of patients with TAPVC, and then led to hospitalize earlier. The first admission age was a simple and feasible parameter in predicting PVO. The integrated use of multiple echocardiographic parameters had an excellent value in predicting PVO.


2020 ◽  
pp. 107110072096513
Author(s):  
Stephanie P. Hao ◽  
Elysia A. Masters ◽  
Mark J. Ninomiya ◽  
Christopher A. Beck ◽  
Edward M. Schwarz ◽  
...  

Background: Conventional bacterial cultures frequently fail to identify the dominant pathogen in polymicrobial foot infections, in which Staphylococcus aureus is the most common infecting pathogen. Previous work has shown that species-specific immunoassays may be able to identify the main pathogen in musculoskeletal infections. We sought to investigate the clinical applicability of a S. aureus immunoassay to accurately identify the infecting pathogen and monitor its infectivity longitudinally in foot infection. We hypothesized that this species-specific immunoassay could aid in the diagnosis of S. aureus and track the therapeutic response in foot infections. Methods: From July 2015 to July 2019, 83 infected foot ulcer patients undergoing surgical intervention (debridement or amputation) were recruited and blood was drawn at 0, 4, 8, and 12 weeks. Whole blood was analyzed for S. aureus–specific serum antibodies (mix of historic and new antibodies) and plasmablasts were isolated and cultured to quantify titers of newly synthesized antibodies (NSAs). Anti– S. aureus antibody titers were compared with culture results to assess their concordance in identifying S. aureus as the pathogen. The NSA titer changes at follow-ups were compared with wound healing status to evaluate concordance between evolving host immune response and clinically resolving or relapsing infection. Results: Analysis of serum for anti– S. aureus antibodies showed significantly increased titers of 3 different anti– S. aureus antibodies, IsdH ( P = .037), ClfB ( P = .025), and SCIN ( P = .005), in S. aureus culture-positive patients compared with culture-negative patients. Comparative analysis of combining antigens for S. aureus infection diagnosis increased the concordance further. During follow-up, changes of NSA titers against a single or combination of S. aureus antigens significantly correlated with clinically resolving or recurring infection represented by wound healing status. Conclusion: In the management of foot infection, the use of S. aureus–specific immunoassay may aid in diagnosis of the dominant pathogen and monitoring of the host immune response against a specific pathogen in response to treatment. Importantly, this immunoassay could detect recurrent foot infection, which may guide a surgeon’s decision to intervene. Level of Evidence: Level II, prospective comparative study.


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