Artificial Intelligence in Gastrointestinal Endoscopy.

Artificial intelligence (AI) is rapidly integrating into modern technology and clinical practice. Although in its nascency, AI has become a hot topic of investigation for applications in clinical practice. Multiple fields of medicine have embraced the possibility of a future with AI assisting in diagnosis and pathology applications. In the field of gastroenterology, AI has been studied as a tool to assist in risk stratification, diagnosis, and pathologic identification. Specifically, AI has become of great interest in endoscopy as a technology with substantial potential to revolutionize the practice of a modern gastroenterologist. From cancer screening to automated report generation, AI has touched upon all aspects of modern endoscopy. Here, we review landmark AI developments in endoscopy. Starting with broad definitions to develop understanding, we will summarize the current state of AI research and its potential applications. With innovation developing rapidly, this article touches upon the remarkable advances in AI-assisted endoscopy since its initial evaluation at the turn of the millennium, and the potential impact these AI models may have on the modern clinical practice. As with any discussion of new technology, its limitations must also be understood to apply clinical AI tools successfully

Genomic Classifier Augments the Role of Pathological Features in Identifying Optimal Candidates for Adjuvant Radiation Therapy in Patients With Prostate Cancer: Development and Internal Validation of a Multivariable Prognostic Model.

Purpose Despite documented oncologic benefit, use of postoperative adjuvant radiotherapy (aRT) in patients with prostate cancer is still limited in the United States. We aimed to develop and internally validate a risk-stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Patient and Methods Our cohort included 512 patients with prostate cancer treated with radical prostatectomy at one of four US academic centers between 1990 and 2010. All patients had ≥ pT3a disease, positive surgical margins, and/or pathologic lymph node invasion. Multivariable Cox regression analysis tested the relationship between available predictors (including Decipher score) and clinical recurrence (CR), which were then used to develop a novel risk-stratification tool. Our study adhered to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for development of prognostic models. Results Overall, 21.9% of patients received aRT. Median follow-up in censored patients was 8.3 years. The 10-year CR rate was 4.9% vs. 17.4% in patients treated with aRT versus initial observation ( P \u3c .001). Pathologic T3b/T4 stage, Gleason score 8-10, lymph node invasion, and Decipher score \u3e 0.6 were independent predictors of CR (all P \u3c .01). The cumulative number of risk factors was 0, 1, 2, and 3 to 4 in 46.5%, 28.9%, 17.2%, and 7.4% of patients, respectively. aRT was associated with decreased CR rate in patients with two or more risk factors (10-year CR rate 10.1% in aRT v 42.1% in initial observation; P = .012), but not in those with fewer than two risk factors ( P = .18). Conclusion Using the new model to indicate aRT might reduce overtreatment, decrease unnecessary adverse effects, and reduce risk of CR in the subset of patients (approximately 25% of all patients with aggressive pathologic disease in our cohort) who benefit from this therapy

Subsidizing Religious Participation through Groups: A Model of the “Megachurch” Strategy for Growth

Either despite or because of their non-traditional approach, megachurches have grown significantly in the United States since 1980. This paper models religious participation as an imperfect public good which, absent intervention, yields suboptimal participation by members from the church’s perspective. Megachurches address this problem in part by employing secular-based group activities to subsidize religious participation that then translates into an increase in the attendees’ religious investment. This strategy not only allows megachurches to attract and retain new members when many traditional churches are losing members but also results in higher levels of an individual’s religious capital. As a result, the megachurch may raise expectations of members’ levels of commitment and faith practices. Data from the FACT2000 survey provide evidence that megachurches employ groups more extensively than other churches, and this approach is consistent with a strategy to use groups to help subsidize individuals’ religious investment. Religious capital rises among members of megachurches relative to members of non-megachurches as a result of this strategy

A noninvasive multi-analyte diagnostic assay: Combining protein and DNA markers to stratify bladder cancer patients

Purpose: The authors recently reported the development of a noninvasive diagnostic assay using urinary matrix metalloproteinases (MMPs) as monitors of disease-free status and bladder cancer in high-risk populations. Using an approach called clinical intervention determining diagnostic (CIDD), they identified with high confidence those patients who could be excluded from additional intervention. To maximize performance, MMPs were combined with DNAbased markers and CIDD was applied to a population of patients undergoing monitoring for recurrence. Patients and methods: Urine samples were obtained from 323 patients, 48 of whom had a recurrence and 275 of whom did not have cancer upon cytoscopic evaluation. Twist1 and Nid2 methylation status was determined using methylation-specific polymerase chain reaction, FGFR3 mutational status by quantitative PCR, and MMP levels by enzyme-linked immunosorbent assay. Results: Using a combination of these DNA and protein markers, the authors identified with high confidence (97% negative predicted value) those patients who do not have cancer. Cutoffs were adjusted such that at 92% sensitivity, 51% of disease-free patients might be triaged from receiving further tests. Conclusion: The multi-analyte diagnostic readout assay described here is the first to combine protein and DNA biomarkers into one assay for optimal clinical performance. Using this approach, the detection of FGFR3 mutations and Twist1 and Nid2 methylation in the urine of patients undergoing bladder cancer recurrence screening increase the sensitivity and negative predictive value at an established MMP protein cutoff. This noninvasive urinary diagnostic assay could lead to the more efficient triage of patients undergoing recurrence monitoring

The Ford Nuclear Reactor Control System

Submitted for presentation at the Fall Meeting of the American Nuclear Society held in New York on October 28, 1957.http://deepblue.lib.umich.edu/bitstream/2027.42/86114/1/MMPP FNR Control 28 Oct 1957 ANS.PDF-

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient\u27s progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. ©2017 AACR

Establishing key research questions for the implementation of artificial intelligence in colonoscopy - a modified Delphi method

Background and Aims Artificial intelligence (AI) research in colonoscopy is progressing rapidly but widespread clinical implementation is not yet a reality. We aimed to identify the top implementation research priorities. Methods An established modified Delphi approach for research priority setting was used. Fifteen international experts, including endoscopists and translational computer scientists/engineers from 9 countries participated in an online survey over 9 months. Questions related to AI implementation in colonoscopy were generated as a long-list in the first round, and then scored in two subsequent rounds to identify the top 10 research questions. Results The top 10 ranked questions were categorised into 5 themes. Theme 1: Clinical trial design/end points (4 questions), related to optimum trial designs for polyp detection and characterisation, determining the optimal end-points for evaluation of AI and demonstrating impact on interval cancer rates. Theme 2: Technological Developments (3 questions), including improving detection of more challenging and advanced lesions, reduction of false positive rates and minimising latency. Theme 3: Clinical adoption/Integration (1 question) concerning effective combination of detection and characterisation into one workflow. Theme 4: Data access/annotation (1 question) concerning more efficient or automated data annotation methods to reduce the burden on human experts. Theme 5: Regulatory Approval (1 question) related to making regulatory approval processes more efficient. Conclusions This is the first reported international research priority setting exercise for AI in colonoscopy. The study findings should be used as a framework to guide future research with key stakeholders to accelerate the clinical implementation of AI in endoscopy

Novi pristup spektrofotometrijskom određivanju metronidazola i tinidazola koristeći p-dimetilaminobenzaldehid

A new approach to the spectrophotometric determination of metronidazole (MZ) and tinidazole (TZ) has been developed. The procedure involves coupling of diazotized nitroimidazoles with p-dimethylaminobenzaldehyde (DMAB) to form a greenish-yellow solution. Optimal temperature and time for diazotization were 0 oC (iced) and 3 minutes and 30 oC and 2 minutes for coupling was, respectively, for both MZ and TZ. Coloured adducts of MZ and TZ showed peaks at 406 nm and 404 nm, respectively, which were selected as analytical wavelengths. The reaction with p-DMAB occurred in a 1:1 mole ratio. Beer’s law was obeyed within the 4.8–76.8 µg mL1 concentration range with low limits of detection. The azo adducts were stable for over a week. Molar absorptivities were 1.10 x 103 (MZ) and 1.30 x 103 L mol1 cm1 (TZ). Overall recoveries of MZ and TZ from quality control samples were 103.2 ± 1.3 and 101.9 ± 1.3 % over three days. There was no interference from commonly utilized tablet excipients. No significant difference was obtained between the results of the new method and the BP titrimetric procedures. The azo approach using the p-dimethylaminobenzaldehyde procedure described in this paper is simple, fast, accurate and precise. It is the first application of DMAB as a coupling component in the diazo coupling reaction.U radu je opisan novi način spektrofotometrijskog određivanja metronidazola (MZ) i tinidazola (TZ). Postupak uključuje reakciju diazotiranog nitroimidazola s p-dimetilaminobenzaldehidom (DMAB), pri čemu nastaje zelenkasto-žuta otopina. Optimalna temperatura i vrijeme za diazotaciju su 0 oC (ledena kupelj) i 3 minute, a za reakciju kondenzacije 30 oC i 2 minute. Obojeni adukti imaju maksimum apsorpcije pri 406, odnosno 404 nm pa su te valne duljine izabrane za analitički postupak. Reakcija s p-DMAB zbiva se u množinskom omjeru 1:1. Reakcija slijedi Beerov zakon u koncentracijskom rasponu 4,8–76,8 µg mL1 s niskim granicama detekcije. Azo adukti su stabilni preko tjedan dana. Molarna apsorptivnost bila je 1,10 × 103 (MZ), odnosno 1,30 × 103 L mol1 cm1 (TZ). Ukupni povrat MZ i TZ iz kontrolnih uzoraka bio je 103,2 ± 1,3, odnosno 101,9 ± 1,3 % tijekom tri dana. Nije zamijećena nikakva interferencija uobičajenih pomoćnih tvari koje se koriste za tabletiranje. Ne postoji značajna razlika između rezultata dobivenih novom metodom i rezultata dobivenih BP titrimetrijskim postupkom. Metoda određivanja opisana u ovom radu je jednostavna, brza, pogodna, točna i precizna i po prvi puta uključuje DMAB u reakciji diazo kopulacije

Association of patients' sex with treatment outcomes after intravesical bacillus Calmette-Guérin immunotherapy for T1G3/HG bladder cancer.

Purpose: To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Guérin (BCG) for T1G3/HG urinary bladder cancer (UBC). Materials and methods: We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression. Results: A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78-1.60, p = 0.55). Conclusion: Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response

RISK FACTORS FOR RESIDUAL DISEASE AT RE-TUR IN T1G3 BLADDER CANCER

INTRODUCTION AND OBJECTIVES: Goals of transurethral resection of a bladder tumour (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumours is not uncommon and is the reason why the European Guidelines recommended a reTUR for all T1 tumours. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumour factors that may influence the presence of residual disease at re-TUR. METHODS: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 75.4% had multifocal tumours, 42.7% of tumours were more than 3 cm in diameter and 25.8% had concomitant CIS. We analyse this subgroup of patients who underwent re-TUR: there was no residual disease in 267 patients (28.6%) and residual disease in 667 patients (71.4%): Ta in 378 (40.5%) and T1 in 289 (30.9%) patients. Age, gender, tumour status (primary/recurrent), previous intravesical therapy, tumour size, tumour multi-focality, presence of concomitant CIS, and muscle in the specimen were analysed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions. RESULTS: The following were not risk factors for residual disease: age, gender, tumour status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumours, tumours > 3 cm, and presence of concomitant CISDue to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, p ¼ 0.15, while the presence of CIS only remained significant in the model with tumor size, p < 0.001. CONCLUSIONS: The most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumours and tumours more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease