Bladder CancerPub Date : 2024-10-23eCollection Date: 2024-01-01DOI: 10.3233/BLC-240017
Joep J de Jong, Florus C de Jong, Angelique C J van der Made, Niels J van Casteren, Hossain Roshani, Eric H G M Oomens, Rob C M Pelger, Ewout W Steyerberg, Joost L Boormans, Chris H Bangma, Tahlita C M Zuiverloon, Ellen C Zwarthoff
{"title":"A Molecular Urine Assay to Detect Recurrences During Surveillance of High-Risk Non-Muscle Invasive Bladder Cancer.","authors":"Joep J de Jong, Florus C de Jong, Angelique C J van der Made, Niels J van Casteren, Hossain Roshani, Eric H G M Oomens, Rob C M Pelger, Ewout W Steyerberg, Joost L Boormans, Chris H Bangma, Tahlita C M Zuiverloon, Ellen C Zwarthoff","doi":"10.3233/BLC-240017","DOIUrl":"10.3233/BLC-240017","url":null,"abstract":"<p><strong>Background: </strong>High-risk non-muscle invasive bladder cancer (HR-NMIBC) patients require long-term surveillance with cystoscopies, cytology and upper tract imaging. Previously, we developed a genomic urine assay for surveillance of HR-NMIBC patients with high sensitivity and anticipatory value.</p><p><strong>Objective: </strong>We aimed to validate the performance of the assay in an unselected prospectively collected cohort of HR-NMIBC patients under surveillance.</p><p><strong>Methods: </strong>We included patients from five centers and collected urine sample pairs (evening and morning urines) prior to cystoscopy. Mutation status (<i>FGFR3/TERT)</i> and methylation status (<i>OTX1)</i> was analyzed on DNA from voided urine specimens. A test was considered positive if≥1 alteration was detected in at least one urine sample. The primary endpoint was tumor recurrence. Sensitivity and specificity were determined. A generalized mixed effects model was used to adjust for within-patient correlation. Cox proportional hazard analyses with time-dependent covariates assessed the anticipatory effect of the urine assay.</p><p><strong>Results: </strong>In total, 204 patients and 736 sample pairs were collected. Sixty-three recurrences were diagnosed for which we had concomitant assay results. On cross-sectional analyses, the assay detected 75% (95% CI 62.1% -84.7%) of recurrences, with a specificity of 70% (95% CI 66.4% -73.5%). Furthermore, mixed effects model analyses revealed <i>OTX1</i> (<i>p</i> = 0.005) and <i>TERT</i> (<i>p</i> = 0.004) as significant predictors for disease recurrence. Median follow-up was 25.3 months (IQR 18.6-30.7). Twenty-nine tumors were diagnosed without concomitant urine samples, which included recurrences detected after urine collection ended. Longitudinal analyses showed that a positive urine assay predicted a recurrence over time (HR 3.5, <i>p</i> < 0.001). Furthermore, a recurrence during the study period was also a predictor for developing future recurrences (HR 2.1, p < 0.001).</p><p><strong>Conclusions: </strong>This study validates the performance of a previously developed urine assay in an unselected cohort of HR-NMIBC patients under surveillance. With a robust sensitivity/specificity and a strong anticipatory effect, this assay proves a useful adjunct ready for evaluation in a future randomized controlled trial.</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"10 3","pages":"233-242"},"PeriodicalIF":1.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bladder CancerPub Date : 2024-10-23eCollection Date: 2024-01-01DOI: 10.3233/BLC-230105
Tyler F Stewart, Healther Chalfin, Nicholas Simon, Alan Tan, Andrea Apolo, Rana R McKay
{"title":"Perioperative Use of ctDNA to Guide Treatment for Urothelial Carcinoma: The Future is Now.","authors":"Tyler F Stewart, Healther Chalfin, Nicholas Simon, Alan Tan, Andrea Apolo, Rana R McKay","doi":"10.3233/BLC-230105","DOIUrl":"10.3233/BLC-230105","url":null,"abstract":"<p><p> Muscle-invasive bladder cancer represents a potentially curable disease, yet often disease recurs and is ultimately fatal. Outcomes for patients with localized urothelial carcinoma are heterogeneous with some patients cured with surgery alone, deriving no benefit from perioperative systemic therapy, while others are left with residual disease and may benefit from additional therapy. Neoadjuvant chemotherapy increases cure rates but comes with significant toxicity. Recently, adjuvant nivolumab has demonstrated significant improvement in disease free survival (DFS), and overall survival analysis is pending. With more therapies approved for urothelial cancer within the last 5 years than ever before, there is incredible potential to improve clinical outcomes and potentially cure more patients with integrated multimodal therapy. Biomarkers are needed to dichotomize those most likely to benefit from perioperative systemic therapy for residual disease, and de-escalate therapy for those likely to be cured with surgery alone. Ultrasensitive assays for circulating tumor DNA (ctDNA) have emerged as a method to identify patients at high risk of recurrence after definitive therapy and may benefit from escalated therapy, while also identifying those least likely to benefit from systemic therapy. Studies have demonstrated that the presence of ctDNA after surgery is prognostic of disease recurrence across multiple cancer types, including bladder cancer, but questions remain as to the utility of these tests, and whether they can be predictive of benefit of adjuvant therapy. Although these liquid biopsies hold significant promise to transform perioperative treatment, prospective studies are needed to validate their utility as prognostic and predictive biomarkers. To bridge this knowledge gap, contemporary clinical trials are incorporating ctDNA as an integral biomarker to guide therapy for MIBC.</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"10 3","pages":"183-198"},"PeriodicalIF":1.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bladder CancerPub Date : 2024-10-23eCollection Date: 2024-01-01DOI: 10.3233/BLC-249007
Mark S Soloway, Neil A Abrahams, Nat Pinnar
{"title":"Challenging Cases in Urothelial Cancer: Case 33.","authors":"Mark S Soloway, Neil A Abrahams, Nat Pinnar","doi":"10.3233/BLC-249007","DOIUrl":"https://doi.org/10.3233/BLC-249007","url":null,"abstract":"","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"10 3","pages":"243-245"},"PeriodicalIF":1.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bladder CancerPub Date : 2024-10-23eCollection Date: 2024-01-01DOI: 10.3233/BLC-240036
Parminder Singh, Leslie Ballas, Guru P Sonpavde, Ronald C Chen, Rick Bangs, Brian C Bauman, Himanshu Nagar, Scott E Delacroix, Seth P Lerner, Jason A Efstathiou
{"title":"Eligibility and Endpoints for Clinical Trials in Trimodality Therapy for Bladder Cancer.","authors":"Parminder Singh, Leslie Ballas, Guru P Sonpavde, Ronald C Chen, Rick Bangs, Brian C Bauman, Himanshu Nagar, Scott E Delacroix, Seth P Lerner, Jason A Efstathiou","doi":"10.3233/BLC-240036","DOIUrl":"10.3233/BLC-240036","url":null,"abstract":"<p><strong>Background: </strong>Trimodality therapy (TMT) is a viable option for muscle-invasive localized bladder cancer, providing an alternative to radical cystectomy in properly selected patients. The approval of novel therapeutics in different stages of bladder cancer treatment has sparked interest in exploring concurrent systemic therapies with radiation in clinical trials to enhance long-term outcomes. Achieving uniformity in trial eligibility criteria and endpoint definitions is imperative in describing clinical significance, comparing trials, and changing standard of care guidelines.</p><p><strong>Objective: </strong>To delineate eligibility criteria and appropriate endpoints for TMT clinical trials in an attempt to achieve uniformity in trial eligibility criteria and endpoint definitions which will then help move the field of bladder preservation forward and improve the current standard of care.</p><p><strong>Methods: </strong>An expert panel, comprising individuals with extensive experience in bladder cancer clinical trials, clinical practice focused on bladder cancer treatment, and patient advocacy, was assembled. The panel systematically reviewed phase II/III clinical trials previously published and assessing the role of radiation in definitive therapy with the specific goal of preserving native bladder function during bladder cancer treatment. Recommendations were summarized based on review of these trials and past experiences of the investigators. To ensure a holistic perspective, the summary was further subjected to rigorous reevaluation by a patient advocate, who added valuable insights from a patient's standpoint. The resulting consensus statements were summarized in this publication to contribute to the evolving landscape of bladder cancer research and treatment.</p><p><strong>Results: </strong>The eligibility criteria for TMT should be pragmatic to encompass patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, bladder cancer stage T2-T4a N0±N1M0, unilateral tumor-associated hydronephrosis, attempted maximal transurethral resection of bladder tumor (TURBT), both pure urothelial carcinoma and/or mixed histologic subtypes (excluding rare and aggressive small cell variants) and patients who are non- cystectomy candidates. Bladder intact event-free survival (BIEFS) is proposed as a suitable endpoint for registration trials designed to compare two different treatment interventions, defined as the time from randomization to muscle-invasive or locoregional recurrence, systemic recurrence, radical cystectomy from any cause, or death from any cause. Overall survival is deemed an appropriate secondary endpoint or a co-primary end point as recent improvements in systemic therapy can produce significant improvement in long-term outcomes. Primary and secondary endpoints should be supported with patient-reported quality of life assessments, when available.</p><p><strong>Conclusions: </strong>The standardizati","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"10 3","pages":"199-213"},"PeriodicalIF":1.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bladder CancerPub Date : 2024-10-23eCollection Date: 2024-01-01DOI: 10.3233/BLC-240048
Ivy Beeren, Carlos Koops, Antoine G van der Heijden, Katja K H Aben, Lambertus A L M Kiemeney, J Alfred Witjes, Alina Vrieling
{"title":"Lifestyle Advice to Patients with Bladder Cancer: A National Survey of Dutch Urologists.","authors":"Ivy Beeren, Carlos Koops, Antoine G van der Heijden, Katja K H Aben, Lambertus A L M Kiemeney, J Alfred Witjes, Alina Vrieling","doi":"10.3233/BLC-240048","DOIUrl":"10.3233/BLC-240048","url":null,"abstract":"<p><strong>Background: </strong>Not much is known about the extent to which urologists discuss lifestyle with patients with bladder cancer (BC), despite patients considering urologists as an important source of information and motivation.</p><p><strong>Objective: </strong>To determine how often lifestyle is asked about, advised on, and referred for by Dutch urologists to patients with BC, as well as to evaluate urologists' perceptions and barriers.</p><p><strong>Methods: </strong>An anonymous online survey was sent to Dutch urologists. The survey included questions on demographics, awareness of guidelines, clinical practice (asking about, advising on, and referring for lifestyle), perceptions, and barriers with regard to smoking, body weight, physical activity, diet, alcohol consumption, and fluid intake.</p><p><strong>Results: </strong>Most of the 49 respondents were male, affiliated with a non-academic hospital, and had over 10 years of experience. Smoking appeared to be the only lifestyle factor that patients are advised on, with 90% of urologists advising > 75% of their patients. Advice on other lifestyle factors was far less common, with 63-92% of urologists giving < 50% of their patients advice. Referral rates were low for all lifestyle factors. Lifestyle advice was generally perceived as (very) important. Almost all respondents reported one or more barriers in giving lifestyle advice. A lack of time and a perceived lack of patient interest and motivation were reported most.</p><p><strong>Conclusions: </strong>Apart from advice on smoking cessation, lifestyle advice is not frequently provided by urologists to patients with BC. Although urologists perceive lifestyle as important, they report several barriers to providing lifestyle advice and referring patients.</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"10 3","pages":"215-220"},"PeriodicalIF":1.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bladder CancerPub Date : 2024-09-14DOI: 10.3233/blc-240032
Sandeep Gurram, Nityam Rathi
{"title":"Device-Assisted Therapy in Non-Muscle-Invasive Bladder Cancer","authors":"Sandeep Gurram, Nityam Rathi","doi":"10.3233/blc-240032","DOIUrl":"https://doi.org/10.3233/blc-240032","url":null,"abstract":"<h4><span>Abstract</span></h4><p>Intravesical therapy is a critical component in the management of non-muscle-invasive bladder cancer (NMIBC), as it reduces rates of disease recurrence and progression. However, the presence of physiologic barriers in the urothelium reduces the penetration and distribution of intravesical chemotherapy, thereby limiting the therapeutic potential. Much progress to overcome this challenge has been made in the realm of intravesical device-assisted therapy. Novel device-assisted treatments include hyperthermia, the radiofrequency-induced thermochemotherapy effect, electromotive drug administration, and implantable drug delivery systems. Notably, chemotherapy enhanced by these device-assisted systems has shown improved oncologic efficacy relative to standard intravesical chemotherapy and comparable outcomes relative to Bacillus Calmette-Guérin (BCG) therapy in patients with intermediate- or high-risk NMIBC. Recent studies also support the utility of device-assisted therapy as a salvage treatment option in patients with BCG-unresponsive disease. Ongoing randomized controlled trials and prospective investigations will further help clarify indications and long-term safety outcomes of these treatment modalities in NMIBC. Herein, we present a comprehensive review of device-assisted therapies and discuss their clinical utilities for the management of NMIBC in the modern era.</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"35 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142262017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bladder CancerPub Date : 2024-07-16DOI: 10.3233/blc-240012
Mariya Vladimirovna Berkut, Alexey Michaylovich Belyaev, Tatyana Yurievna Galunova, Nikolay Ivanovich Tyapkin, Sergey Aleksandrovich Reva, Alexander Konstantinovich Nosov
{"title":"Effectiveness of Prolonged Antibiotic Prophylaxis in Radical Cystectomy: Preliminary Analysis of the MACS Randomized Clinical Trial","authors":"Mariya Vladimirovna Berkut, Alexey Michaylovich Belyaev, Tatyana Yurievna Galunova, Nikolay Ivanovich Tyapkin, Sergey Aleksandrovich Reva, Alexander Konstantinovich Nosov","doi":"10.3233/blc-240012","DOIUrl":"https://doi.org/10.3233/blc-240012","url":null,"abstract":"<h4><span>Abstract</span></h4><h3><span></span>BACKGROUND:</h3><p>Standard 24-hour antibiotic prophylaxis is widely employed to minimize the risk of infection complications within 30 days following radical cystectomy. However, a considerable variety of protocols and drug combinations don’t prevent a high complication rate, ranging from 37 to 67%. This paper presents the interim analysis of the MACS clinical trial, comparing antibiotic prophylaxis regimens by duration.</p><h3><span></span>OBJECTIVE:</h3><p>To evaluate the rate of infection complications within 30 days following radical cystectomy by comparing standard 24-hour antibiotic prophylaxis (Group A) with a prolonged 120-hour regimen (Group B).</p><h3><span></span>METHODS:</h3><p>Patients were randomized in a 1 : 1 ratio. The primary endpoint was the evaluation of the frequency of infection complications. The secondary endpoints were the rate of re-administrating antibiotics and the dynamics of the inflammation biomarker.</p><h3><span></span>RESULTS:</h3><p>A total of 78 patients (85.0% of the sample size) were enrolled (Group A: 40 and Group B: 38). The baseline and perioperative features were balanced between groups. The overall complication rate was higher in Group A (65.0% vs. 41.1%, <i>p</i> = 0.043). The infection complication rate was 2.7 times higher in the standard antibiotic prophylaxis group: 37.5% compared to 18.4% cases in Group B (<i>p</i> = 0.041), and upper urinary tract infection was more frequent in Group A (22.5% vs. 2.6%). The prolonged antibiotic prophylaxis reduced the overall frequency of infection complications compared with standard 24-hour prophylaxis (RR = 0.12; 95% CI 0.02–0.88; <i>p</i> = 0.037).</p><h3><span></span>CONCLUSIONS:</h3><p>In this interim analysis, the administration of prolonged antibiotic prophylaxis over 120 hours appears to be safe and feasible, demonstrating a reduction in the total number of complications, particularly infection complications.</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"44 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141742410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bladder CancerPub Date : 2024-06-18eCollection Date: 2024-01-01DOI: 10.3233/BLC-249005
Edward M Messing
{"title":"Urologists and Advanced Practice Providers Evaluating Hematuria.","authors":"Edward M Messing","doi":"10.3233/BLC-249005","DOIUrl":"10.3233/BLC-249005","url":null,"abstract":"","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"10 2","pages":"161-162"},"PeriodicalIF":1.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11308636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bladder CancerPub Date : 2024-05-31DOI: 10.3233/blc-240002
Avani Desai, Lucas Bouknight, Thomas Reed, Dana Mueller, Chelsea Osterman, Michael Repka, Tracy Rose, Angela B. Smith
{"title":"Factors Influencing Patient Decision-Making in the Treatment of Muscle-Invasive Bladder Cancer","authors":"Avani Desai, Lucas Bouknight, Thomas Reed, Dana Mueller, Chelsea Osterman, Michael Repka, Tracy Rose, Angela B. Smith","doi":"10.3233/blc-240002","DOIUrl":"https://doi.org/10.3233/blc-240002","url":null,"abstract":"<h4><span>Abstract</span></h4><h3><span></span>BACKGROUND:</h3><p>In 2023, an estimated 82,290 individuals were diagnosed with bladder cancer in the United States. For muscle-invasive bladder cancer (MIBC), the American Urological Association recommends offering radical cystectomy with cisplatin-based neoadjuvant chemotherapy. However, patients are increasingly requesting alternative treatments.</p><h3><span></span>OBJECTIVE:</h3><p>To describe factors influencing selection of radical cystectomy with cisplatin-based neoadjuvant chemotherapy (NAC + RC), radical cystectomy monotherapy (RC), or tri-modality therapy (TMT) among patients with MIBC.</p><h3><span></span>METHODS:</h3><p>Individual, semi-structured phone interviews were conducted with 18 adults who underwent MIBC treatment at the University of North Carolina, recruiting six patients each from three treatment groups: 1) NAC + RC, 2) RC, and 3) TMT. Interview transcriptions were qualitatively analyzed using QSR NVivo, with major themes and sub-themes extracted. Patients also completed the Shared Decision-Making Questionnaire (SDM-Q-9; range 0–100).</p><h3><span></span>RESULTS:</h3><p>Concern for survival and risks, quality of life, and varied patient preferences for involvement influenced the decision-making process. Concern surrounding sexual function, bladder preservation, and urostomy bags drove patients towards TMT. High levels of shared decision-making were observed overall, with a median SDM-Q-9 score of 95 (IQR 89–100). Patients undergoing TMT reported the highest median SDM-Q-9 score (97, IQR 94–100), while those receiving radical cystectomy alone had the lowest (66, IQR 37–96).</p><h3><span></span>CONCLUSIONS:</h3><p>Patients with MIBC described a multifaceted treatment decision-making process, highlighting key influences, concerns, and unmet needs. Understanding this process can help address misconceptions and align treatment choices with patient goals. Physicians can use these insights to engage in shared decision-making, ultimately improving patient experiences and outcomes.</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"111 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141255156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}