Clinical and Host Biological Factors Predict Colectomy Risk in Children Newly Diagnosed With Ulcerative Colitis

Author(s):  
Jeffrey S Hyams ◽  
Michael Brimacombe ◽  
Yael Haberman ◽  
Thomas Walters ◽  
Greg Gibson ◽  
...  

Abstract Background Develop a clinical and biological predictive model for colectomy risk in children newly diagnosed with ulcerative colitis (UC). Methods This was a multicenter inception cohort study of children (ages 4-17 years) newly diagnosed with UC treated with standardized initial regimens of mesalamine or corticosteroids (CS) depending upon initial disease severity. Therapy escalation to immunomodulators or infliximab was based on predetermined criteria. Patients were phenotyped by clinical activity per the Pediatric Ulcerative Colitis Activity Index (PUCAI), disease extent, endoscopic/histologic severity, and laboratory markers. In addition, RNA sequencing defined pretreatment rectal gene expression and high density DNA genotyping by the Affymetrix UK Biobank Axiom Array. Coprimary outcomes were colectomy over 3 years and time to colectomy. Generalized linear models, Cox proportional hazards multivariate regression modeling, and Kaplan-Meier plots were used. Results Four hundred twenty-eight patients (mean age 13 years) started initial theapy with mesalamine (n = 136), oral CS (n = 144), or intravenous CS (n = 148). Twenty-five (6%) underwent colectomy at ≤1 year, 33 (9%) at ≤2 years, and 35 (13%) at ≤3 years. Further, 32/35 patients who had colectomy failed infliximab. An initial PUCAI ≥ 65 was highly associated with colectomy (P = 0.0001). A logistic regression model predicting colectomy using the PUCAI, hemoglobin, and erythrocyte sedimentation rate had a receiver operating characteristic area under the curve of 0.78 (95% confidence interval [0.73, 0.84]). Addition of a pretreatment rectal gene expression panel reflecting activation of the innate immune system and response to external stimuli and bacteria to the clinical model improved the receiver operating characteristic area under the curve to 0.87 (95% confidence interval [0.82, 0.91]). Conclusions A small group of children newly diagnosed with severe UC still require colectomy despite current therapies. Our gene signature observations suggest additional targets for management of those patients not responding to current medical therapies.

2020 ◽  
Author(s):  
Brian J. Park ◽  
Vlasios S. Sotirchos ◽  
Jason Adleberg ◽  
S. William Stavropoulos ◽  
Tessa S. Cook ◽  
...  

AbstractPurposeThis study assesses the feasibility of deep learning detection and classification of 3 retrievable inferior vena cava filters with similar radiographic appearances and emphasizes the importance of visualization methods to confirm proper detection and classification.Materials and MethodsThe fast.ai library with ResNet-34 architecture was used to train a deep learning classification model. A total of 442 fluoroscopic images (N=144 patients) from inferior vena cava filter placement or removal were collected. Following image preprocessing, the training set included 382 images (110 Celect, 149 Denali, 123 Günther Tulip), of which 80% were used for training and 20% for validation. Data augmentation was performed for regularization. A random test set of 60 images (20 images of each filter type), not included in the training or validation set, was used for evaluation. Total accuracy and receiver operating characteristic area under the curve were used to evaluate performance. Feature heatmaps were visualized using guided backpropagation and gradient-weighted class activation mapping.ResultsThe overall accuracy was 80.2% with mean receiver operating characteristic area under the curve of 0.96 for the validation set (N=76), and 85.0% with mean receiver operating characteristic area under the curve of 0.94 for the test set (N=60). Two visualization methods were used to assess correct filter detection and classification.ConclusionsA deep learning model can be used to automatically detect and accurately classify inferior vena cava filters on radiographic images. Visualization techniques should be utilized to ensure deep learning models function as intended.


2019 ◽  
Vol 31 (1) ◽  
pp. 199
Author(s):  
E. Mellisho ◽  
M. Briones ◽  
F. O. Castro ◽  
L. Rodriguez-Alvarez

Extracellular vesicles (EV) secreted by blastocysts might be relevant to predict competence of embryos produced in vitro. The aim of this study was to develop a model to select competent embryos that combines blastocyst morphokinetics data and morphological parameters of EV secreted during blastulation (Days 5-7.5). Embryos were cultured in groups up to Day 5; morulae were selected and individually cultured in SOFaa depleted of EV until Day 7.5 after IVF. Embryo competence was determined by in vitro post-hatching development up to Day 11. A retrospective classification of blastocyst and culture media was performed based on blastulation time [early (EB) or late (LB)] and competence at Day 11 [competent (C) or non-competent (NC)]. The EV were isolated from culture media of individual embryos, their properties determined by nanoparticle tracking analysis. The model was based on a binary logistic regression to describe the dichotomous-dependent variable of the blastocyst (C=1 and NC=0). A set of independent variables of blastocyst morphokinetics (blastulation time, blastocyst stage, blastocyst quality and blastocyst diameter at Day 7.5) and EV morphological parameters [mean size (ME), mode size (MO) and particle concentration (CO)] were analysed with multiple regression. The analysis generated the coefficients and their standard errors and significance level of an equation to calculate a probability, where values between 0.5 and 1 predict competent embryos. To verify the predictive power of the algorithm, the following indicators were used: the receiver operating characteristic with the determination of area under the curve, percentage correct predictions, and Omnibus tests. Statistical significance was determined at the P<0.05 level. A rough guide for classifying the accuracy of a predictive model is as follows: 0.9 to 1=excellent, 0.8 to 0.9=good, 0.7 to 0.8=fair, 0.6 to 0.7=poor, 0.5 to 0.6=fail. A total of 254 embryos were used in this study; from them, 73 were classified in C-EB, 68 in NC-EB, 61 in C-LB and 52 in NC-LB. Initially, all independent variables were analysed in model 1; the most significant predictors associated with embryo competence were blastocyst stage, blastocyst quality, blastocyst diameter, ME and CO (P<0.05). In model 2 no significant variables were excluded (blastulation time and MO). The statistical test of predictive power indicates that models 1 and 2 achieved a receiver operating characteristic-area under the curve of 0.853 (95% confidence interval, 0.806-0.9; P<0.001) and correct predictions of 77.2 and 77.6%, respectively. When EV characteristics were excluded and the model considers only variables from the embryo, the receiver operating characteristic-area under the curve value was 0.714 (95% confidence interval, 0.651-0.777; P<0.001) and correct predictions was reduced to 65.4. Model 2 was consider the most appropriate from the practical point of view because it avoids disturbing embryo culture during blastulation. The results indicate that incorporating EV properties increases accuracy of embryo selection, supporting the possibility to improve conventional methods by combining blastocyst morphology and characteristics of EV obtained by nanoparticle tracking analysis. This work was supported by Fondecyt 1170310.


2021 ◽  
Vol 8 (1) ◽  
pp. 1-88
Author(s):  
Ashish Awasthi ◽  
Jamie Barbour ◽  
Andrew Beggs ◽  
Pradeep Bhandari ◽  
Daniel Blakeway ◽  
...  

Background Chronic ulcerative colitis is a large bowel inflammatory condition associated with increased colorectal cancer risk over time, resulting in 1000 colectomies per year in the UK. Despite intensive colonoscopic surveillance, 50% of cases progress to invasive cancer before detection. Detecting early (precancer) molecular changes by analysing biopsies from routine colonoscopy should increase neoplasia detection. Objectives To establish a deoxyribonucleic acid (DNA) marker panel associated with early neoplastic changes in ulcerative colitis patients. To develop the DNA methylation test for high-throughput analysis within the NHS. To prospectively evaluate the test within the existing colonoscopy surveillance programme. Design Module 1 analysed 569 stored biopsies from neoplastic and non-neoplastic sites/patients using pyrosequencing for 11 genes that were previously reported to have altered promoter methylation associated with colitis-associated neoplasia. Classifiers were constructed to predict neoplasia based on gene combinations. Module 2 translated analysis to a NHS laboratory, assessing next-generation sequencing to increase speed and reduce cost. Module 3 applied the molecular classifiers within a prospective diagnostic accuracy study, in the existing ulcerative colitis surveillance programme. Comparisons were made between baseline and reference colonoscopies undertaken in a stratified patient sample 6–12 months later. Setting Thirty-one UK hospitals. Participants Patients with chronic ulcerative colitis, either for at least 10 years and extensive disease, or with primary sclerosing cholangitis. Interventions An optimised DNA methylation classifier tested on routine mucosal biopsies taken during colonoscopy. Main outcome Identifying ulcerative colitis patients with neoplasia. Results Module 1 selected five genes with specificity for neoplasia. The optimism-adjusted area under the receiver operating characteristic curve for neoplasia was 0.83 (95% confidence interval 0.79 to 0.88). Precancerous neoplasia showed a higher area under the receiver operating characteristic curve of 0.88 (95% confidence interval 0.84 to 0.92). Background mucosa had poorer discrimination (optimism-adjusted area under the receiver operating characteristic curve was 0.68, 95% confidence interval 0.62 to 0.73). Module 2 was unable to develop a robust next-generation sequencing assay because of the low amplification rates across all genes. In module 3, 818 patients underwent a baseline colonoscopy. The methylation assay (testing non-neoplastic mucosa) was compared with pathology assessments for neoplasia and showed a diagnostic odds ratio of 2.37 (95% confidence interval 1.46 to 3.82; p = 0.0002). The probability of dysplasia increased from 11.1% before testing to 17.7% after testing (95% confidence interval 13.0% to 23.2%), with a positive methylation result suggesting added value in neoplasia detection. To determine added value above colonoscopy alone, a second (reference) colonoscopy was performed in 193 patients without neoplasia. Although the test showed an increased number of patients with neoplasia associated with primary methylation changes, this failed to reach statistical significance (diagnostic odds ratio 3.93; 95% confidence interval 0.82 to 24.75; p = 0.09). Limitations Since the inception of ENDCaP-C, technology has advanced to allow whole-genome or methylome testing to be performed. Conclusions Methylation testing for chronic ulcerative colitis patients cannot be recommended based on this study. However, following up this cohort will reveal further neoplastic changes, indicating whether or not this test may be identifying a population at risk of future neoplasia and informing future surveillance programmes. Trial registration Current Controlled Trials ISRCTN81826545. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership, and will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 1. See the NIHR Journals Library website for further project information.


Rheumatology ◽  
2020 ◽  
Author(s):  
Kelvin Y C Yu ◽  
Susan Yung ◽  
Mel K M Chau ◽  
Colin S O Tang ◽  
Desmond Y H Yap ◽  
...  

Abstract Objectives We investigated circulating syndecan-1, HA and thrombomodulin levels in patients with biopsy-proven Class III/IV ± V LN and their clinico-pathological associations. Patients with non-renal SLE or non-lupus chronic kidney disease, and healthy subjects served as controls. Methods Serum syndecan-1, HA and thrombomodulin levels were determined by ELISAs. Results Syndecan-1, HA and thrombomodulin levels were significantly higher during active LN compared with remission (P < 0.01, for all), and correlated with the level of proteinuria, estimated glomerular filtration rate, anti-dsDNA antibodies, complement 3 and serum creatinine. Longitudinal studies showed that syndecan-1 and thrombomodulin levels increased prior to clinical renal flare by 3.6 months, while HA level increased at the time of nephritic flare, and the levels decreased in parallel with treatment response. Receiver operating characteristic curve analysis showed that syndecan-1 and thrombomodulin levels distinguished patients with active LN from healthy subjects, LN patients in remission, patients with active non-renal lupus and patients with non-lupus chronic kidney disease (receiver operating characteristic area under curve of 0.98, 0.91, 0.82 and 0.95, respectively, for syndecan-1; and area under curve of 1.00, 0.84, 0.97 and 0.79, respectively, for thrombomodulin). HA level distinguished active LN from healthy subjects, LN patients in remission and non-lupus chronic kidney disease (receiver operating characteristic area under curve of 0.82, 0.71 and 0.90, respectively) but did not distinguish between renal vs non-renal lupus. Syndecan-1 and thrombomodulin levels correlated with the severity of interstitial inflammation, while HA level correlated with chronicity grading in kidney biopsies of active LN. Conclusion Our findings suggest potential utility of serum syndecan-1, thrombomodulin and HA levels in clinical management, and their potential contribution to LN pathogenesis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bianca M. Leca ◽  
Maria Mytilinaiou ◽  
Marina Tsoli ◽  
Andreea Epure ◽  
Simon J. B. Aylwin ◽  
...  

AbstractProlactinomas represent the most common type of secretory pituitary neoplasms, with a therapeutic management that varies considerably based on tumour size and degree of hyperprolactinemia. The aim of the current study was to evaluate the relationship between serum prolactin (PRL) concentrations and prolactinoma size, and to determine a cut-off PRL value that could differentiate micro- from macro-prolactinomas. A retrospective cohort study of 114 patients diagnosed with prolactinomas between 2007 and 2017 was conducted. All patients underwent gadolinium enhanced pituitary MRI and receiver operating characteristic (ROC) analyses were performed. 51.8% of patients in this study were men, with a mean age at the time of diagnosis of 42.32 ± 15.04 years. 48.2% of the total cohort were found to have microadenomas. Baseline serum PRL concentrations were strongly correlated to tumour dimension (r = 0.750, p = 0.001). When performing the ROC curve analysis, the area under the curve was 0.976, indicating an excellent accuracy of the diagnostic method. For a value of 204 μg/L (4338 mU/L), sensitivity and specificity were calculated at 0.932 and 0.891, respectively. When a cut off value of 204 μg/L (4338 mU/L) was used, specificity was 93.2%, and sensitivity 89.1%, acceptable to reliably differentiate between micro- and macro- adenomas.


Pneumologie ◽  
2021 ◽  
Author(s):  
P. Luu ◽  
S. Tulka ◽  
S. Knippschild ◽  
W. Windisch ◽  
M. Spielmanns

Zusammenfassung Einleitung Akute COPD-Exazerbationen (AECOPD) im Rahmen einer pneumologischen Rehabilitation (PR) sind häufige und gefährliche Komplikationen. Neben Einschränkungen der Lebensqualität führen sie zu einem Unterbrechung der PR und gefährden den PR-Erfolg. Eine Abhängigkeit zwischen dem Krankheitsstatus und einem erhöhten Risiko für eine AECOPD ist beschrieben. Dabei stellt sich die Frage, ob der Charlson Comorbidity Index (CCI) oder die Cumulative Illness Rating Scale (CIRS) dafür geeignet sind, besonders exazerbationsgefährdete COPD-Patienten in der PR im Vorfeld zu detektieren. Patienten und Methoden In einer retrospektiven Untersuchung wurden die Daten von COPD-Patienten, welche im Jahr 2018 eine PR erhielten, analysiert. Primärer Endpunkt der Untersuchung war die Punktzahl im CCI. Alle Daten wurden dem Klinikinformationssystem Phönix entnommen und COPD-Exazerbationen erfasst. Die laut Fallzahlplanung benötigten 44 Patienten wurden zufällig (mittels Zufallsliste für jede Gruppe) aus diesem Datenpool rekrutiert: 22 Patienten mit und 22 ohne Exazerbation während der PR. CCI und CIRS wurden für die eingeschlossenen Fälle für beide Gruppen bestimmt. Die Auswertung des primären Endpunktes (CCI) erfolgte durch den Gruppenvergleich der arithmetischen Mittel und der Signifikanzprüfung (Welch-Tests). Weitere statistische Lage- und Streuungsmaße wurden ergänzt (Median, Quartile, Standardabweichung).Zusätzlich wurde mittels Receiver Operating Characteristic (ROC)-Analyse sowohl für den CCI als auch für den CIRS ein optimaler Cutpoint zur Diskriminierung in AECOPD- und Nicht-AECOPD-Patienten gesucht. Ergebnisse 244 COPD-Patienten erhielten eine stationäre PR von durchschnittlich 21 Tagen, wovon 59 (24 %) während der PR eine behandlungspflichtige AECOPD erlitten. Die ausgewählten 22 Patienten mit einer AECOPD hatten einen mittleren CCI von 6,77 (SD: 1,97) und die 22 Patienten ohne AECOPD von 4,32 (SD: 1,17). Die Differenz von –2,45 war zu einem Signifikanzniveau von 5 % statistisch signifikant (p < 0,001; 95 %-KI: [–3,45 ; –1,46]). Die ROC-Analyse zeigte einen optimalen Cutpoint für den CCI bei 6 mit einer Sensitivität zur Feststellung einer AECOPD von 81,8 % und einer Spezifität von 86.,4 % mit einem Wert der AUC (area under the curve) von 0,87. Der optimale Cutpoint für den CIRS war 19 mit einer Sensitivität von 50 %, einer Spezifität von 77,2 % und einer AUC von 0,65. Schlussfolgerung COPD-Patienten mit einer akuten Exazerbation während der pneumologischen Rehabilitation haben einen höheren CCI. Mithilfe des CCI lässt sich mit einer hohen Sensitivität und Spezifität das Risiko einer AECOPD von COPD-Patienten im Rahmen eines stationären PR-Programms einschätzen.


2012 ◽  
Vol 47 (3) ◽  
pp. 264-272 ◽  
Author(s):  
Gary B. Wilkerson ◽  
Jessica L. Giles ◽  
Dustin K. Seibel

Context: Poor core stability is believed to increase vulnerability to uncontrolled joint displacements throughout the kinetic chain between the foot and the lumbar spine. Objective: To assess the value of preparticipation measurements as predictors of core or lower extremity strains or sprains in collegiate football players. Design: Cohort study. Setting: National Collegiate Athletic Association Division I Football Championship Subdivision football program. Patients or Other Participants: All team members who were present for a mandatory physical examination on the day before preseason practice sessions began (n  =  83). Main Outcome Measure(s): Preparticipation administration of surveys to assess low back, knee, and ankle function; documentation of knee and ankle injury history; determination of body mass index; 4 different assessments of core muscle endurance; and measurement of step-test recovery heart rate. All injuries were documented throughout the preseason practice period and 11-game season. Receiver operating characteristic analysis and logistic regression analysis were used to identify dichotomized predictive factors that best discriminated injured from uninjured status. The 75th and 50th percentiles were evaluated as alternative cutpoints for dichotomization of injury predictors. Results: Players with ≥2 of 3 potentially modifiable risk factors related to core function had 2 times greater risk for injury than those with &lt;2 factors (95% confidence interval  =  1.27, 4.22), and adding a high level of exposure to game conditions increased the injury risk to 3 times greater (95% confidence interval  =  1.95, 4.98). Prediction models that used the 75th and 50th percentile cutpoints yielded results that were very similar to those for the model that used receiver operating characteristic-derived cutpoints. Conclusions: Low back dysfunction and suboptimal endurance of the core musculature appear to be important modifiable football injury risk factors that can be identified on preparticipation screening. These predictors need to be assessed in a prospective manner with a larger sample of collegiate football players.


2021 ◽  
pp. 096228022110605
Author(s):  
Luigi Lavazza ◽  
Sandro Morasca

Receiver Operating Characteristic curves have been widely used to represent the performance of diagnostic tests. The corresponding area under the curve, widely used to evaluate their performance quantitatively, has been criticized in several respects. Several proposals have been introduced to improve area under the curve by taking into account only specific regions of the Receiver Operating Characteristic space, that is, the plane to which Receiver Operating Characteristic curves belong. For instance, a region of interest can be delimited by setting specific thresholds for the true positive rate or the false positive rate. Different ways of setting the borders of the region of interest may result in completely different, even opposing, evaluations. In this paper, we present a method to define a region of interest in a rigorous and objective way, and compute a partial area under the curve that can be used to evaluate the performance of diagnostic tests. The method was originally conceived in the Software Engineering domain to evaluate the performance of methods that estimate the defectiveness of software modules. We compare this method with previous proposals. Our method allows the definition of regions of interest by setting acceptability thresholds on any kind of performance metric, and not just false positive rate and true positive rate: for instance, the region of interest can be determined by imposing that [Formula: see text] (also known as the Matthews Correlation Coefficient) is above a given threshold. We also show how to delimit the region of interest corresponding to acceptable costs, whenever the individual cost of false positives and false negatives is known. Finally, we demonstrate the effectiveness of the method by applying it to the Wisconsin Breast Cancer Data. We provide Python and R packages supporting the presented method.


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