scholarly journals TO006NON-INVASIVE DIAGNOSIS OF BK VIRUS-ASSOCIATED NEPHROPATHY USING URINARY PROTEOMICS IN KIDNEY ALLOGRAFT PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Martin Pejchinovski ◽  
David Marx ◽  
Jochen Metzger ◽  
Jérôme Olagne ◽  
Sophie Caillard ◽  
...  
Keyword(s):  
T Cell ◽  
Bk Virus ◽  
Support Vector ◽  
P Value ◽  
True Negative ◽  
Kidney Allograft ◽  
Patient Groups ◽  
Peptide Profiles ◽  
Urinary Peptide ◽  
Peptide Marker

Abstract Background and Aims BK virus-associated nephropathy (BKvN) is an important complication occurring after kidney transplantation. Its treatment mainly relies on lowering immune suppression. BKvN’s histological aspect can mimic T cell-mediated rejection (TCMR) and other inflammatory conditions featuring tubulitis and interstitial infiltrate. At present, the screening strategy consists of measuring urinary and blood viral loads of BKv. Upon rising BK viremia, BKvN diagnosis is established by a graft biopsy. Biopsies are invasive and are not suitable for repeated screening. Therefore, the aim of this case-control study was to establish a urinary proteome-based test for BKvN diagnosis. Method Urine was obtained from 700 allograft recipients prior to either protocol or „for cause“ biopsies during the first year of post-transplantation surveillance. Aside from normal biopsy findings (N=294), the histological diagnoses included BKvN (N=50), IFTA II-III (N=145), glomerulonephritis (N=17) and T cell-mediated, antibody-mediated, mixed or borderline rejection episodes (N=194). From all patients, relevant clinical and demographic data including Banff classification scores, HLA mismatches and the presence of donor-specific antibodies was collected at the date of sample collection and in further clinical follow-up. BKvN cases were defined as having SV40-positive immunostaining on allograft biopsy. BKvN patients were considered as cases and all other recipients were considered as controls. Patient’s urinary peptide profiles were generated using capillary electrophoresis coupled to mass spectrometry consisting of 9430 different peptides in the mass range of 0.8 to 20 kDa. Results The CE-MS peptide profiles of randomly selected 30 BKvN cases and 307 kidney allograft controls (one sample per patient) were statistically analyzed to identify the most discriminative peptide markers for BKvN. In total, there were 117 peptides detected to have significantly different urinary excretion rates between both patient groups after false discovery rate adjustment for multiple testing. Thirty-two of these peptides were selected by cross-validated variable selection to establish a Support Vector Machine-based multi-marker model. Applying the 32-peptide marker model to an independent validation cohort consisting of 20 BKvN cases and 343 controls resulted in an area under the receiver operating characteristic curve of 0.86 and a 95% confidence interval from 0.82 to 0.89 with the p-value below 0.0001 and sensitivities and specificities for BKvN diagnosis of 85 and 76 %, respectively. Most notably, distribution of the classification values (figure 1) in the different patient groups of the validation set indicated specificities of the peptide marker model for TCMR/borderline of 85% (17 of 20 true negative classifications) and for viruria/viremia of 73% (8 of 11 true negative classifications) Conclusion In conclusion, the established urinary peptide marker model might serve as a non-invasive diagnostic test for BKvN and its differentiation from TCMR and states of isolated viruria or viremia.

Factors that Influence the Durability of Transplanted Kidneys in South Africa

2019 ◽  
Vol 21 (2) ◽  
Author(s):  
Hillary Ndemera ◽  
Busisiwe R. Bhengu
Keyword(s):  
South Africa ◽  
Kidney Transplant ◽  
Lifestyle Modification ◽  
P Value ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kidney Allograft ◽  
Factors Influencing ◽  
Allograft Loss ◽  
Transplanted Kidneys

Kidney transplantation is the cornerstone for renal treatment in patients with end-stage renal failure. Despite improvements in short-term outcomes of renal transplantation, kidney allograft loss remains a huge challenge. The aim of the study was to assess factors influencing the durability of transplanted kidneys among transplant recipients in South Africa. A descriptive cross-sectional study design was used. A random sampling was used to select 171 participants. Data were collected through structured face-to-face interviews developed from in-depth consideration of relevant literature. Data were coded and entered into the SPSS software, version 24. The entered data were analysed using descriptive and inferential statistics. The results revealed that the average durability of transplanted kidneys was 9.07 years among selected kidney transplant recipients in South Africa. Factors associated with the durability of transplanted kidneys included age, the sewerage system and strict immunosuppressive adherence, all with a P-value = .000, followed by the mode of transport (P-value = .001) and support system (P-value = .004). Other variables including demographics, the healthcare system, medication and lifestyle modification engagement were not associated with the durability of transplanted kidneys. Understanding the factors influencing the durability of transplanted kidneys among kidney transplant recipients in South Africa is crucial. The study revealed associated factors and gaps which may be contributory factors to kidney allograft loss. This study provides an opportunity to introduce specific interventions to nephrology professionals to promote prolonged graft durability. It is recommended that a specific intervention model be developed, which targets South African kidney recipients taking into account the significant variables in this study and the socio-economic status of the country.

Evaluation of Positive T- and B-Cell Gene Rearrangement Studies Among Patients Without a Definitive Diagnosis by Other Assays

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S35-S36
Author(s):  
Hadrian Mendoza ◽  
Christopher Tormey ◽  
Alexa Siddon
Keyword(s):  
T Cell ◽  
False Positive ◽  
Gene Rearrangement ◽  
Hematologic Malignancy ◽  
False Negative ◽  
False Positives ◽  
False Negatives ◽  
True Negative ◽  
Flow Cytometric ◽  
Pathology Reports

Abstract In the evaluation of bone marrow (BM) and peripheral blood (PB) for hematologic malignancy, positive immunoglobulin heavy chain (IG) or T-cell receptor (TCR) gene rearrangement results may be detected despite unrevealing results from morphologic, flow cytometric, immunohistochemical (IHC), and/or cytogenetic studies. The significance of positive rearrangement studies in the context of otherwise normal ancillary findings is unknown, and as such, we hypothesized that gene rearrangement studies may be predictive of an emerging B- or T-cell clone in the absence of other abnormal laboratory tests. Data from all patients who underwent IG or TCR gene rearrangement testing at the authors’ affiliated VA hospital between January 1, 2013, and July 6, 2018, were extracted from the electronic medical record. Date of testing; specimen source; and morphologic, flow cytometric, IHC, and cytogenetic characterization of the tissue source were recorded from pathology reports. Gene rearrangement results were categorized as true positive, false positive, false negative, or true negative. Lastly, patient records were reviewed for subsequent diagnosis of hematologic malignancy in patients with positive gene rearrangement results with negative ancillary testing. A total of 136 patients, who had 203 gene rearrangement studies (50 PB and 153 BM), were analyzed. In TCR studies, there were 2 false positives and 1 false negative in 47 PB assays, as well as 7 false positives and 1 false negative in 54 BM assays. Regarding IG studies, 3 false positives and 12 false negatives in 99 BM studies were identified. Sensitivity and specificity, respectively, were calculated for PB TCR studies (94% and 93%), BM IG studies (71% and 95%), and BM TCR studies (92% and 83%). Analysis of PB IG gene rearrangement studies was not performed due to the small number of tests (3; all true negative). None of the 12 patients with false-positive IG/TCR gene rearrangement studies later developed a lymphoproliferative disorder, although 2 patients were later diagnosed with acute myeloid leukemia. Of the 14 false negatives, 10 (71%) were related to a diagnosis of plasma cell neoplasms. Results from the present study suggest that positive IG/TCR gene rearrangement studies are not predictive of lymphoproliferative disorders in the context of otherwise negative BM or PB findings. As such, when faced with equivocal pathology reports, clinicians can be practically advised that isolated positive IG/TCR gene rearrangement results may not indicate the need for closer surveillance.

scholarly journals Two-Step Urban Water Index (TSUWI): A New Technique for High-Resolution Mapping of Urban Surface Water

2018 ◽  
Vol 10 (11) ◽  
pp. 1704 ◽  
Author(s):  
Wei Wu ◽  
Qiangzi Li ◽  
Yuan Zhang ◽  
Xin Du ◽  
Hongyan Wang
Keyword(s):  
Surface Water ◽  
High Resolution ◽  
Urban Surface ◽  
Mapping Technique ◽  
Support Vector ◽  
Svm Classifier ◽  
P Value ◽  
Urban Water ◽  
Water Index ◽  
Water Mapping

Urban surface water mapping is essential for studying its role in urban ecosystems and local microclimates. However, fast and accurate extraction of urban water remains a great challenge due to the limitations of conventional water indexes and the presence of shadows. Therefore, we proposed a new urban water mapping technique named the Two-Step Urban Water Index (TSUWI), which combines an Urban Water Index (UWI) and an Urban Shadow Index (USI). These two subindexes were established based on spectral analysis and linear Support Vector Machine (SVM) training of pure pixels from eight training sites across China. The performance of the TSUWI was compared with that of the Normalized Difference Water Index (NDWI), High Resolution Water Index (HRWI) and SVM classifier at twelve test sites. The results showed that this method consistently achieved good performance with a mean Kappa Coefficient (KC) of 0.97 and a mean total error (TE) of 2.28%. Overall, classification accuracy of TSUWI was significantly higher than that of the NDWI, HRWI, and SVM (p-value < 0.01). At most test sites, TSUWI improved accuracy by decreasing the TEs by more than 45% compared to NDWI and HRWI, and by more than 15% compared to SVM. In addition, both UWI and USI were shown to have more stable optimal thresholds that are close to 0 and maintain better performance near their optimum thresholds. Therefore, TSUWI can be used as a simple yet robust method for urban water mapping with high accuracy.

scholarly journals A conditional predictive p-value to compare a multinomial with an overdispersed multinomial in the analysis of T-cell populations

Biostatistics ◽  
2013 ◽  
Vol 15 (1) ◽  
pp. 129-139 ◽  
Author(s):  
Q. Pei ◽  
C. L. Zuleger ◽  
M. D. Macklin ◽  
M. R. Albertini ◽  
M. A. Newton
Keyword(s):  
T Cell ◽  
Cell Populations ◽  
P Value

scholarly journals Detection of Fracture Bones in X-ray Images Categorization

2020 ◽  
pp. 1-11
Author(s):  
Adigun Oyeranmi ◽  
Babatunde Ronke ◽  
Rufai Mohammed ◽  
Aigbokhan Edwin
Keyword(s):  
Feature Extraction ◽  
Performance Metrics ◽  
Confusion Matrix ◽  
False Negative ◽  
Support Vector ◽  
Kappa Statistics ◽  
Fracture Detection ◽  
True Negative ◽  
Research Attention ◽  
X Ray

Fractured bone detection and categorization is currently receiving research attention in computer aided diagnosis system because of the ease it has brought to doctors in classification and interpretation of X-ray images.  The choice of an efficient algorithm or combination of algorithms is paramount to accurately detect and categorize fractures in X-ray images, which is the first stage of diagnosis in treatment and correction of damaged bones for patients. This is what this research seeks to address. The research design involves data collection, preprocessing, segmentation, feature extraction, classification and evaluation of the proposed method. The sample dataset were x-ray images collected from the Department of Radiology, National Orthopedic Hospital, Igbobi-Lagos, Nigeria as well as Open Access Medical Image Repositories. The image preprocessing involves the conversion of images in RGB format to grayscale, sharpening and smoothing using Unsharp Masking Tool.  The segmentation of the preprocessed image was carried out by adopting the Entropy method in the first stage and Canny edge method in the second stage while feature extraction was performed using Hough Transformation. Detection and classification of fracture image employed a combination of two algorithms;  K-Nearest Neighbor (KNN) and Support Vector Machine (SVM) for detecting fracture locations based on four classification types: (normal, comminute, oblique and transverse).Two performance assessment methods were employed to evaluate the developed system. The first evaluation was based on confusion matrix which evaluates fracture and non-fracture on the basis of TP (True Positive), TN (True negative), FP (False Positive) and FN (False Negative). The second appraisal was based on Kappa Statistics which evaluates the type of fracture by determining the accuracy of the categorized fracture bone type. The result of first assessment for fracture detection shows that 26 out of 40 preprocessed images were fractured, resulting to the following three values of performance metrics: accuracy value of 90%, sensitivity of 87% and specificity of 100%. The Kappa coefficient error assessment produced accuracy of 83% during classification. The proposed method can find suitable use in categorization of fracture types on different bone images based on the results obtained from the experiment.

scholarly journals Pretransplant BK virus-specific T-cell-mediated immunity and serotype specific antibodies may have utility in identifying patients at risk for BK virus associated haemorrhagic cystitis after allogeneic HSCT

2021 ◽  
Author(s):  
Marketa Stastna-Markova ◽  
Eva Hamsikova ◽  
Petr Hainz ◽  
Petr Hubacek ◽  
Marie Kroutilova ◽  
...  
Keyword(s):  
At Risk ◽  
T Cell ◽  
Cell Response ◽  
Bk Virus ◽  
T Cell Response ◽  
Cell Mediated Immunity ◽  
Haemorrhagic Cystitis ◽  
Hematopoietic Stem ◽  
Specific Antibodies ◽  
Clinical Risk

BK polyomavirus (BKV) persists lifelong in the urinary tract with asymptomatic urinary shedding in healthy individuals. In immunocompromised persons after transplantation of hematopoietic stem cells (HSCT) the BKV high-rate replication is associated with haemorrhagic cystitis (HC) with a reported incidence of 17 %. Numerous studies of reconstitution of the immune system after HSCT have established the principal role of T cell effectors in the control of viral replication and reactivation. The value of pretransplant BKV-specific antibodies in transplanted patients for the protection from viral disease was long considered insignificant. We hypothesized that the status of BKV immunity prior to HSCT could provide evidence for the BKV tendency to reactivate and that examining the level of subtype-specific antibodies and T-cell response in individual patients could help to predict the risk of BKV reactivation and HC. Evaluation of the risk of HC in relation to pretransplant anti-BKV1,2,4 IgG levels together with clinical factors known before transplantation revealed that patients with medium anti-BKV IgG and significant clinical risk (SR) have a very significantly increased HC risk in comparison with the reference group of low anti-BKV IgG level and low clinical risk (LR) (P=0.0009). Analysis of pretransplant T cell immunity to BKV antigens VP1 and LTag has shown that magnitude of IFN-gamma T cell response inversely corelated with posttransplant DNAuria. We hypothesize that the control of BKV latency by BKV specific T cells before HSCT would be one of the factors that influence BKV reactivation after HSCT. Our study has shown that prediction using a combination of clinical and immunological pretransplant risk factors can help early identification of patients who are at risk of developing BKV disease after HSCT.

T-cell clonality in peripheral blood as a predictor of progression to systemic treatment in patients with stage IB mycosis fungoides (MF).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19538-e19538
Author(s):  
Suravi Raychaudhuri ◽  
Charli-Joseph Yann ◽  
Michelle Mintz ◽  
Laura Pincus ◽  
Chiung-Yu Huang ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Systemic Treatment ◽  
Rank Test ◽  
P Value ◽  
Advanced Stage ◽  
Stage Ib ◽  
Log Rank Test ◽  
Secondary Outcomes

e19538 Background: A major unmet clinical need in the care of early-stage MF patients is the identification of those with a high risk of failing skin directed therapy or progressing to advanced disease. Herein, we inquired if the identification of a clonal T-cell receptor (TCR) gene rearrangement by PCR in peripheral blood could predict the clinical outcome, particularly the need for systemic treatment, in patients with stage IB MF. Methods: This is a retrospective cohort study of patients with stage IB MF who underwent peripheral blood TCR clonality analysis by PCR. The primary outcome of the study was time from diagnosis to initiation of systemic treatment. Secondary outcomes were: (1) time to progression to advanced-stage disease (stages IIB-IV) and (2) overall survival. Patients were censored at time of last clinical follow up. Log rank test was used to compare the survival distributions of the two groups; p value < 0.05 was considered significant. Results: From May 2014 to October 2019, 56 consecutive stage IB pts with > 6 months follow up were included in this analysis. Peripheral blood TCR clonality status was available in 42 patients: 18 pts had a positive TCR clone and 24 did not. Median follow up time was 36 months (range 8.5 – 198 months). At 3 years, 39% of patients with peripheral clone had progressed to systemic treatment versus 8% of those without a peripheral clone (log rank test, p-value = 0.003). For the secondary outcomes, at 3 years 17% of patients with peripheral clone had progressed to advanced stage versus 4% of those without (log rank test, p-value = 0.10); 5% of patients with peripheral clone had died versus 0% of those without (log rank test, p-value = 0.03). Conclusions: Detection of a predominant TCR clone by PCR in the peripheral blood is an important prognostic marker in the initial workup of MF, as its presence is highly correlated with subsequent progression to systemic treatment and death. If this finding is validated, it can be used to risk stratify and individualize therapy for MF patients.[Table: see text]

scholarly journals Volatile organic compound breath signatures of children with cystic fibrosis by real-time SESI-HRMS

2020 ◽  
Vol 6 (1) ◽  
pp. 00171-2019 ◽  
Author(s):  
Ronja Weber ◽  
Naemi Haas ◽  
Astghik Baghdasaryan ◽  
Tobias Bruderer ◽  
Demet Inci ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
High Resolution ◽  
Organic Compound ◽  
Real Time ◽  
Volatile Organic Compound ◽  
Lung Damage ◽  
Support Vector ◽  
P Value ◽  
Large Set ◽  
Volatile Organic

Early pulmonary infection and inflammation result in irreversible lung damage and are major contributors to cystic fibrosis (CF)-related morbidity. An easy to apply and noninvasive assessment for the timely detection of disease-associated complications would be of high value. We aimed to detect volatile organic compound (VOC) breath signatures of children with CF by real-time secondary electrospray ionisation high-resolution mass spectrometry (SESI-HRMS).A total of 101 children, aged 4–18 years (CF=52; healthy controls=49) and comparable for sex, body mass index and lung function were included in this prospective cross-sectional study. Exhaled air was analysed by a SESI-source linked to a high-resolution time-of-flight mass spectrometer. Mass spectra ranging from m/z 50 to 500 were recorded.Out of 3468 m/z features, 171 were significantly different in children with CF (false discovery rate adjusted p-value of 0.05). The predictive ability (CF versus healthy) was assessed by using a support-vector machine classifier and showed an average accuracy (repeated cross-validation) of 72.1% (sensitivity of 77.2% and specificity of 67.7%).This is the first study to assess entire breath profiles of children with SESI-HRMS and to extract sets of VOCs that are associated with CF. We have detected a large set of exhaled molecules that are potentially related to CF, indicating that the molecular breath of children with CF is diverse and informative.

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