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Clinical Validation of a Circulating Tumor DNA-Based Blood Test to Screen for Colorectal Cancer
Shaukat, Aasma; Burke, Carol A; Chan, Andrew T; Grady, William M; Gupta, Samir; Katona, Bryson W; Ladabaum, Uri; Liang, Peter S; Liu, Julia J; Putcha, Girish; Robertson, Douglas J; Schoen, Robert E; Meng, Zhen; Piscitello, Andrew; Sun, Chung-Kai; Xu, Chuanbo; Lin, C Jimmy; Lee, Lilian C; Baldo, Lance; Levin, Theodore R; ,
IMPORTANCE/UNASSIGNED:Colorectal cancer screening is widely recommended but underused. Blood-based screening offers the potential for higher adherence compared with endoscopy or stool-based testing but must first be clinically validated in a screening population. OBJECTIVE/UNASSIGNED:To evaluate the clinical performance of an investigational blood-based circulating tumor DNA test for colorectal cancer detection in an average-risk population using colonoscopy with histopathology as the reference method. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Prospective, multicenter, cross-sectional observational study enrolling participants between May 2020 and April 2022 who were asymptomatic adults aged 45 to 85 years, at average risk of colorectal cancer, and willing to undergo a standard-of-care screening colonoscopy. Participants, staff, and pathologists were blinded to blood test results, and laboratory testing was performed blinded to colonoscopy findings. The study was conducted at 201 centers across 49 US states and the United Arab Emirates. Site-based and mobile phlebotomy were used for blood collection. EXPOSURES/UNASSIGNED:Participants were required to complete a screening colonoscopy after blood collection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary end points were sensitivity for colorectal cancer, specificity for advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions), negative predictive value for advanced colorectal neoplasia, and positive predictive value for advanced colorectal neoplasia. The secondary end point was sensitivity for advanced precancerous lesions. RESULTS/UNASSIGNED:The median age of participants in the evaluable cohort (n = 27 010) was 57.0 years, and 55.8% were women. Sensitivity for colorectal cancer was 79.2% (57/72; 95% CI, 68.4%-86.9%) and specificity for advanced colorectal neoplasia was 91.5% (22 306/24 371; 95% CI, 91.2%-91.9%). The negative predictive value for advanced colorectal neoplasia was 90.8% (22 306/24 567; 95% CI, 90.7%-90.9%) and the positive predictive value for advanced colorectal neoplasia was 15.5% (378/2443; 95% CI, 14.2%-16.8%). All primary end points met prespecified acceptance criteria. The sensitivity for advanced precancerous lesions was 12.5% (321/2567; 95% CI, 11.3%-13.8%), which did not meet the prespecified acceptance criterion. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In an average-risk colorectal cancer screening population, a blood-based test demonstrated acceptable accuracy for colorectal cancer detection, but detection of advanced precancerous lesions remains a challenge, and ongoing efforts are needed to improve test sensitivity. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04369053.
PMID: 40455622
ISSN: 1538-3598
CID: 5862132
Sarcopenia Is a Risk Factor for Postoperative Complications Among Older Adults With Inflammatory Bowel Disease
Minawala, Ria; Kim, Michelle; Delau, Olivia; Ghiasian, Ghoncheh; McKenney, Anna Sophia; Da Luz Moreira, Andre; Chodosh, Joshua; McAdams-DeMarco, Mara; Segev, Dorry L; Adhikari, Samrachana; Dodson, John; Shaukat, Aasma; Dane, Bari; Faye, Adam S
BACKGROUND:Sarcopenia has been associated with adverse postoperative outcomes in older age cohorts, but has not been assessed in older adults with inflammatory bowel disease (IBD). Further, current assessments of sarcopenia among all aged individuals with IBD have used various measures of muscle mass as well as cutoffs to define its presence, leading to heterogeneous findings. METHODS:In this single-institution, multihospital retrospective study, we identified all patients aged 60 years and older with IBD who underwent disease-related intestinal resection between 2012 and 2022. Skeletal Muscle Index (SMI) and Total Psoas Index (TPI) were measured at the superior L3 endplate on preoperative computed tomography scans and compared through receiver operating characteristic curve. We then performed multivariable logistic regression to assess risk factors associated with an adverse 30-day postoperative outcome. Our primary outcome included a 30-day composite of postoperative mortality and complications, including infection, bleeding, cardiac event, cerebrovascular accident, acute kidney injury, venous thromboembolism, reoperation, all-cause rehospitalization, and need for intensive care unit-level care. RESULTS:A total of 120 individuals were included. Overall, 52% were female, 40% had ulcerative colitis, 60% had Crohn's disease, and median age at time of surgery was 70 years (interquartile range: 65-75). Forty percent of older adults had an adverse 30-day postoperative outcome, including infection (23%), readmission (17%), acute kidney injury (13%), bleeding (13%), intensive care unit admission (10%), cardiac event (8%), venous thromboembolism (7%), reoperation (6%), mortality (5%), and cerebrovascular accident (2%). When evaluating the predictive performance of SMI vs TPI for an adverse 30-day postoperative event, SMI had a significantly higher area under the curve of 0.66 (95% CI, 0.56-0.76) as compared to 0.58 (95% CI, 0.48-0.69) for TPI (P = .02). On multivariable logistic regression, prior IBD-related surgery (adjusted odds ratio [adjOR] 6.46, 95% CI, 1.85-22.51) and preoperative sepsis (adjOR 5.74, 95% CI, 1.36-24.17) significantly increased the odds of adverse postoperative outcomes, whereas increasing SMI was associated with a decreased risk of an adverse postoperative outcome (adjOR 0.88, 95% CI, 0.82-0.94). CONCLUSIONS:Sarcopenia, as measured by SMI, is associated with an increased risk of postoperative complications among older adults with IBD. Measurement of SMI from preoperative imaging can help risk stratify older adults with IBD undergoing intestinal resection.
PMID: 39177976
ISSN: 1536-4844
CID: 5681162
Current Perspectives on Colorectal Cancer Screening and Surveillance in the Geriatric Population
Udaikumar, Jahnavi; Nimmagadda, Rithish; Ingawale, Sushrut; Lella, Vindhya Vasini; Vijayakumar, Keerthika; Faye, Adam S; Shaukat, Aasma
PURPOSE OF REVIEW/OBJECTIVE:Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with 44% of deaths occurring in individuals aged 75 years and older. With 78 million adults over 65 years projected by 2035, optimizing CRC screening and surveillance is crucial. This review examines guidelines, risks, and personalized approaches. RECENT FINDINGS/RESULTS:CRC screening reduces incidence by 17-33% and mortality by 11-53%. Colonoscopy lowers mortality by 61% but has a 6.8% complication rate in those aged 75 years and older. The risk of gastrointestinal bleeding is 8.7 per 1,000 for polypectomy, and perforation occurs in 0.6 per 1,000. Frailty indices assess suitability, but surveillance guidelines lack clear discontinuation criteria. Screening should balance risk, complications, and health status. It may be cost-effective up to age 86 years in healthy individuals, but more research is needed to refine surveillance strategies and reduce overtreatment in older adults.
PMID: 40455318
ISSN: 1534-312x
CID: 5862092
Severe Polypharmacy Increases Risk of Hospitalization Among Older Adults with IBD
Drittel, Darren; Schreiber-Stainthorp, William; Delau, Olivia; Gurunathan, Sakteesh V; Chodosh, Joshua; Segev, Dorry L; McAdams-DeMarco, Mara; Katz, Seymour; Dodson, John; Shaukat, Aasma; Faye, Adam S
BACKGROUND:As the inflammatory bowel disease (IBD) patient population is aging, the prevalence of polypharmacy is rising. However, data exploring the prevalence, risk factors, and clinical outcomes associated with polypharmacy among older adults with IBD are limited. AIMS/OBJECTIVE:To determine (i) prevalence of polypharmacy (≥5 medications) and potentially inappropriate medication (PIM) utilization in older adults with IBD, (ii) changes in medications over time (iii) predictors of polypharmacy, and (iv) the impact of polypharmacy/PIMs on one-year hospitalization rates. METHODS:We conducted a retrospective single-center study of older adults with IBD from September 1st 2011 to December 31st 2022. Wilcoxon-signed rank and McNemar's tests were used to assess changes in polypharmacy between visits, with ordinal logistic regression and Cox proportional hazards models used to determine risk factors for polypharmacy and time to hospitalization, respectively. RESULTS:Among 512 older adults with IBD, 74.0% experienced polypharmacy at initial visit, with 42.6% receiving at least one PIM. Additionally, severe polypharmacy (≥10 medications) was present among 28.6% individuals at index visit and increased to 38.6% by last visit (p<0.01). Multivariable analysis revealed that age ≥70 years, BMI ≥30.0 kg/m2, prior IBD-related surgery, and the presence of comorbidities were associated with polypharmacy. Moreover, severe polypharmacy (adjHR 1.95, 95%CI 1.29-2.92), as well as PIM use (adjHR 2.16, 95%CI 1.37-3.43) among those with polypharmacy, were significantly associated with all-cause hospitalization within a year of index visit. DISCUSSION/CONCLUSIONS:Severe polypharmacy was initially present in more than 25% of older adults with IBD and increased to 34% within 4 years of index visit. Severe polypharmacy, as well as PIM utilization among those with polypharmacy, were also associated with an increased risk of hospitalization at one-year, highlighting the need for deprescribing efforts in this population.
PMID: 39162710
ISSN: 1572-0241
CID: 5680582
Fact or Myth? Black Patients Do Not Want to Participate in Clinical Trials
Mills, Krystal; Figueroa, Francisco; Knight, RaKetra; Ekpo, Emem; Lee, Lilian C; Baldo, Lance; Xu, Chuanbo; Wang, Siqi; Adelman, Robert M; Pemu, Priscilla; Levin, Theodore; Shaukat, Aasma; Liu, Julia J
OBJECTIVES/OBJECTIVE:To assess strategies for optimizing participation of underserved minorities in a blood-based early CRC detection test study (PREEMPT CRC; NCT04369053) at a hospital serving primarily Black patients. METHODS:Culturally sensitive, racially congruent research staff approached patients undergoing average-risk screening colonoscopy. Consent/study procedures were synchronized with clinical appointments. Enrolled and not-enrolled patient characteristics were compared. Recruitment was compared with other study sites. RESULTS:247/509 eligible participants enrolled; most identified as Black (88.7%). No baseline characteristics were associated with participation. Recruitment was high compared to other sites (11th centile). CONCLUSIONS:Recruitment barriers for Black individuals can be overcome when easy, culturally sensitive access is facilitated.
PMID: 39878425
ISSN: 2155-384x
CID: 5780892
Optimizing Bowel Preparation Quality for Colonoscopy: Consensus Recommendations by the US Multi-Society Task Force on Colorectal Cancer
Jacobson, Brian C; Anderson, Joseph C; Burke, Carol A; Dominitz, Jason A; Gross, Seth A; May, Folasade P; Patel, Swati G; Shaukat, Aasma; Robertson, Douglas J
This document is an update to the 2014 recommendations for optimizing the adequacy of bowel cleansing for colonoscopy from the US Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. The US Multi-Society Task Force developed consensus statements and key clinical concepts addressing important aspects of bowel preparation for colonoscopy. The majority of consensus statements focus on individuals at average risk for inadequate bowel preparation. However, statements addressing individuals at risk for inadequate bowel preparation quality are also provided. The quality of a bowel preparation is defined as adequate when standard screening or surveillance intervals can be assigned based on the findings of the colonoscopy. We recommend the use of a split-dose bowel preparation regimen and suggest that a 2 L regimen may be sufficient. A same-day regimen is recommended as an acceptable alternative for individuals undergoing afternoon colonoscopy, but we suggest that a same-day regimen is an inferior alternative for individuals undergoing morning colonoscopy. We recommend limiting dietary restrictions to the day before a colonoscopy, relying on either clear liquids or low-fiber/low-residue diets for the early and midday meals. We suggest the adjunctive use of oral simethicone for bowel preparation before colonoscopy. Routine tracking of the rate of adequate bowel preparations at the level of individual endoscopists and at the level of the endoscopy unit is also recommended, with a target of >90% for both rates.
PMID: 40035345
ISSN: 1572-0241
CID: 5818562
Optimizing bowel preparation quality for colonoscopy: consensus recommendations by the US Multi-Society Task Force on Colorectal Cancer
Jacobson, Brian C; Anderson, Joseph C; Burke, Carol A; Dominitz, Jason A; Gross, Seth A; May, Folasade P; Patel, Swati G; Shaukat, Aasma; Robertson, Douglas J
This document is an update to the 2014 recommendations for optimizing the adequacy of bowel cleansing for colonoscopy from the US Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. The US Multi-Society Task Force developed consensus statements and key clinical concepts addressing important aspects of bowel preparation for colonoscopy. The majority of consensus statements focus on individuals at average risk for inadequate bowel preparation. However, statements addressing individuals at risk for inadequate bowel preparation quality are also provided. The quality of a bowel preparation is defined as adequate when standard screening or surveillance intervals can be assigned based on the findings of the colonoscopy. We recommend the use of a split-dose bowel preparation regimen and suggest that a 2 L regimen may be sufficient. A same-day regimen is recommended as an acceptable alternative for individuals undergoing afternoon colonoscopy, but we suggest that a same-day regimen is an inferior alternative for individuals undergoing morning colonoscopy. We recommend limiting dietary restrictions to the day before a colonoscopy, relying on either clear liquids or low-fiber/low-residue diets for the early and midday meals. We suggest the adjunctive use of oral simethicone for bowel preparation before colonoscopy. Routine tracking of the rate of adequate bowel preparations at the level of individual endoscopists and at the level of the endoscopy unit is also recommended, with a target of >90% for both rates.
PMID: 40047767
ISSN: 1097-6779
CID: 5818572
Impact of Artificial Intelligence on Clinical Research
El Zoghbi, Maysaa; Malhotra, Ashish; Bilal, Mohammad; Shaukat, Aasma
Artificial intelligence (AI) has potential to significantly impact clinical research when it comes to research preparation and data interpretation. Development of AI tools that can help in performing literature searches, synthesizing and streamlining data collection and analysis, and formatting of study could make the clinical research process more efficient. Several of these tools have been developed and trialed and many more are being rapidly developed. This article highlights the AI applications in clinical research in gastroenterology including its impact on drug discovery and explores areas where further guidance is needed to supplement the current understanding and enhance its use.
PMID: 40021240
ISSN: 1558-1950
CID: 5801482
Optimizing Bowel Preparation Quality for Colonoscopy: Consensus Recommendations by the US Multi-Society Task Force on Colorectal Cancer
Jacobson, Brian C; Anderson, Joseph C; Burke, Carol A; Dominitz, Jason A; Gross, Seth A; May, Folasade P; Patel, Swati G; Shaukat, Aasma; Robertson, Douglas J
This document is an update to the 2014 recommendations for optimizing the adequacy of bowel cleansing for colonoscopy from the US Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy. The US Multi-Society Task Force developed consensus statements and key clinical concepts addressing important aspects of bowel preparation for colonoscopy. The majority of consensus statements focus on individuals at average risk for inadequate bowel preparation. However, statements addressing individuals at risk for inadequate bowel preparation quality are also provided. The quality of a bowel preparation is defined as adequate when standard screening or surveillance intervals can be assigned based on the findings of the colonoscopy. We recommend the use of a split-dose bowel preparation regimen and suggest that a 2 L regimen may be sufficient. A same-day regimen is recommended as an acceptable alternative for individuals undergoing afternoon colonoscopy, but we suggest that a same-day regimen is an inferior alternative for individuals undergoing morning colonoscopy. We recommend limiting dietary restrictions to the day before a colonoscopy, relying on either clear liquids or low-fiber/low-residue diets for the early and midday meals. We suggest the adjunctive use of oral simethicone for bowel preparation before colonoscopy. Routine tracking of the rate of adequate bowel preparations at the level of individual endoscopists and at the level of the endoscopy unit is also recommended, with a target of >90% for both rates.
PMID: 40047732
ISSN: 1528-0012
CID: 5814492
Optimal Approach to Colorectal Cancer Screening
Wang, Christina; Shaukat, Aasma
Rates of colorectal cancer (CRC) screening in the United States continue to fall short of guideline-recommended benchmarks. Challenges to increasing CRC screening include racial disparities, barriers at multiple levels of the health care system, and inadequate completion of 2-step screening. With new options for CRC screening and employment of programmatic strategies for screening by physicians, patients will have more opportunities to initiate and complete testing, which can ultimately improve CRC detection and prevention. This article highlights the current state of and optimal approach to CRC screening.
PMCID:11920019
PMID: 40115656
ISSN: 1554-7914
CID: 5813702