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Efficacy and safety of fruquintinib in refractory metastatic colorectal cancer: a systematic review and meta-analysis

Udaikumar, Jahnavi; Ingawale, Sushrut; Nimmagadda, Rithish; Kuppili, Satwik; Lella, Vindhya Vasini; Suvvari, Tarun Kumar; Cheloff, Abraham; Bellamkonda, Amulya; Giri, Suprabhat; Oberstein, Paul; Shaukat, Aasma
BACKGROUND/UNASSIGNED:Metastatic colorectal cancer (mCRC) remains a leading cause of cancer-related mortality, emphasizing the need for effective later-line therapies. Fruquintinib, a selective vascular endothelial growth factor receptor (VEGFR)1-3 inhibitor, has emerged as a promising option for refractory mCRC. This systematic review and meta-analysis evaluates its efficacy and safety, both as monotherapy and in combination with programmed death-1 (PD-1) inhibitors. METHODS/UNASSIGNED:Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was conducted across PubMed, Embase, Online Vendor of International Databases (OVID), Cochrane Library, and ClinicalTrials.gov (2010-2025). Included studies were randomized controlled trials (RCTs) or real-world data on fruquintinib in mCRC after at least two prior therapies. Real-world evidence was included to complement RCT findings, as it captures broader populations, treatment patterns, and outcomes not fully reflected in controlled trial settings. Primary outcomes were progression-free survival (PFS) and overall survival (OS); secondary outcomes included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). Pooled hazard ratios (HRs) and event rates were calculated using a random-effects model. RESULTS/UNASSIGNED:. 4.0%, P=0.04). In cross-study comparisons, monotherapy appeared to yield numerically longer PFS, although this was not based on head-to-head trials. AEs occurred in 86.7%, with grade ≥3 in 30.9%, most often hypertension (8.1%) and hand-foot skin reaction (5.8%). High heterogeneity was observed for several outcomes including AEs and DCR. CONCLUSIONS/UNASSIGNED:Fruquintinib significantly improves PFS and disease control in refractory mCRC with manageable toxicity. Limitations include heterogeneity across studies, with most conducted in predominantly Chinese cohorts. Further studies should explore optimal combination strategies and biomarker-based selection.
PMCID:12780613
PMID: 41522768
ISSN: 2078-6891
CID: 5985902

Primary Sclerosing Cholangitis in the Absence of Inflammatory Bowel Disease Increases the Risk of Colorectal Cancer: A Multi-Centre Propensity Score Matched Analysis

Alsakarneh, Saqr; Aburumman, Razan; Bilal, Mohammad; Faye, Adam S; Hashash, Jana G; Shaukat, Aasma
INTRODUCTION/BACKGROUND:Patients with primary sclerosing cholangitis (PSC) and concomitant inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC). However, the risk of CRC in patients with PSC without IBD remains uncertain. We aimed to evaluate the risk of CRC in patients with PSC without a history of IBD using a large national database. METHODS:We conducted a retrospective cohort study using the TriNetX database to identify patients ≥ 18 years with PSC. Patients were then divided into two groups, PSC with IBD (PSC-IBD cohort) and PSC without IBD (PSC non-IBD cohort), and were matched with patients without a history of PSC or IBD (non-PSC/non-IBD group) by using 1:1 propensity score matching. The primary outcome was the risk of first diagnosis of CRC. With censoring applied, Kaplan-Meier analysis with hazard ratios (HRs) and 95% CIs was used to compare time-to-event rates at daily time intervals. RESULTS:PSC patients without IBD were at increased risk of CRC compared to the non-PSC/IBD cohort (aHR = 2.91; 95% CI: 1.6-6.0). Patients with PSC and IBD exhibited a higher risk of CRC (aHR = 6.5; 95% CI: 3.78-11.2), especially among the UC cohort (aHR = 6.3; 95% CI: 3.2-12.4). Patients with PSC were at increased risk of various gastrointestinal malignancies (aHR = 10.5; 95% CI: 7.3-15; p < 0.0001), including hepatobiliary cancers, pancreatic cancer, and hepatocellular carcinoma. DISCUSSION/CONCLUSIONS:Our findings provide real-world evidence that PSC is an independent risk factor for colorectal cancer, even in the absence of concomitant IBD. These results support the need for further research to determine whether patients with isolated PSC may benefit from tailored CRC surveillance strategies.
PMID: 40704424
ISSN: 1365-2036
CID: 5985592

A randomized clinical trial of multi-level intervention to improve colorectal cancer screening rates at multiple federally qualified health care centers in New York City

Shaukat, Aasma; Hu, Jiyuan; Zhao, Yanan; Faulx, Gregory; Augustin, Ashley; Murphy, Sean; Stevens, Elizabeth; Ravenell, Joseph; Makarov, Danil; Napolitano, Daniel
INTRODUCTION/BACKGROUND:Colorectal cancer (CRC) screening rates among patients receiving care at multiple federally qualified health care centers (FQHCs) in New York city are low. Proactive outreach through mailed fecal immunochemical tests (FIT), reminders and navigation are evidence based interventions to improve CRC screening rates but remain untested in this study population. OBJECTIVE:To evaluate the effectiveness, implementation, and cost-effectiveness of a multilevel proactive outreach strategy to improve CRC screening rates among underserved adults in Brooklyn, New York. METHODS:This is a randomized controlled trial across five FQHCs serving predominantly Black and low-income populations. Adults aged 45-75 who are overdue for CRC screening are randomized to usual care or a multi-level proactive intervention. The intervention includes mailed education and FIT kits, patient navigation, and support for colonoscopy scheduling and follow-up. The primary outcome is CRC screening completion (FIT or colonoscopy) within six months. Secondary outcomes include colonoscopy follow-up after a positive FIT, implementation barriers and facilitators, and cost-effectiveness. RESULTS:A total of 1379 participants have been enrolled through May 2025. DISCUSSION/CONCLUSIONS:This trial addresses a critical gap in CRC prevention by testing a scalable, multilevel outreach model tailored to underserved populations. Findings will inform future strategies to enhance screening rates while reducing screening disparities through sustainable FQHC-based programs.
PMID: 41326264
ISSN: 1559-2030
CID: 5974742

COVID-19 Infection Before or After Colorectal Cancer Diagnosis Is an Independent Predictor of Mortality and Treatment Delays Compared to Patients Who Never Tested Positive

Qureshi, Imran; Rella, Steven; Shaukat, Aasma
BACKGROUND:Given COVID-19's emergence as a new entity and colorectal cancer's (CRC) rising incidence in certain populations, we conducted this retrospective cohort study to determine the link between COVID-19 and the mortality of those with CRC and how socioeconomic factors influence it. METHODS:Using the National Cancer Database (NCDB), we used logistic regression to get the odds ratio (OR) for delayed treatment and Cox proportional hazards modeling for each stage to get the adjusted hazard ratios (HR) of mortality. RESULTS:COVID-19 positivity was associated with higher mortality and delayed treatment. The association of race, ethnicity, insurance, urbanization, comorbidity burden, education levels, and income varied by when the patient tested positive relative to colorectal cancer diagnosis. CONCLUSIONS:This implies that vaccinations may be a part of management and that CRC patients who develop COVID-19 infection may warrant closer follow-up during treatment.
PMCID:12645226
PMID: 41288018
ISSN: 2045-7634
CID: 5968162

Benchmarking proprietary and open-source language and vision-language models for gastroenterology clinical reasoning

Safavi-Naini, Seyed Amir Ahmad; Ali, Shuhaib; Shahab, Omer; Shahhoseini, Zahra; Savage, Thomas; Rafiee, Sara; Samaan, Jamil S; Al Shabeeb, Reem; Ladak, Farah; Yang, Jamie O; Echavarria, Juan; Babar, Sumbal; Shaukat, Aasma; Margolis, Samuel; Tatonetti, Nicholas P; Nadkarni, Girish; El Kurdi, Bara; Soroush, Ali
This study evaluated the effectiveness of large language models (LLMs) and vision-language models (VLMs) in gastroenterology. We used board-style multiple-choice questions to assess the performance of both proprietary and open-source LLMs and VLMs-including GPT, Claude, Gemini, Mistral, Llama, Mixtral, Phi, and Qwen, across different interfaces, computing environments, and levels of compression (quantization). Among the proprietary models, o1-preview (82.0%) and Claude3.5-Sonnet (74.0%) had the highest accuracy, outperforming the top open-source models: Llama3.3-70b (65.7%) and Qwen-2.5-72b (61.0%). Among the small quantized open-source models, the 8-bit Llama 3.2-11b (51.7%) and 6-bit Phi3-14b (48.7%) performed the best, with scores comparable to their full-precision counterparts. Notably, VLM accuracy on image-containing questions improved (~10%) when given human-generated captions, remained unchanged with original images, and declined with LLM-generated captions. Further research is warranted to evaluate model capabilities in real-world clinical decision-making scenarios.
PMID: 41310206
ISSN: 2398-6352
CID: 5968702

Advancing Health Equity Through Telehealth: A Systematic Review and Meta-analysis of Remote vs. In-person Weight-loss Interventions among Black Women with Obesity [Review]

Farooque, Umar; Murtaza, Meer; Umer, Muhammad; Johar, Ayesha; Aparna, Fnu; Khan, Aqsa Riaz; Kumar, Anish; Ahmed, Nazeer; Qadri, Syeda Hafsa; Idrees, Hiba; Ullah, Aman; Aliyeva, Turkan; Shaukat, Aasma
ISI:001596212800001
ISSN: 2162-4968
CID: 5966212

A Retrospective Cohort Propensity-Matched Analysis of Colorectal Cancer Risk in Isolated Small Intestinal Crohn's Disease

Alsakarneh, Saqr; Al Ta'ani, Omar; Quezada, Sandra; Raufman, Jean-Pierre; Shaukat, Aasma; Ghoz, Hassan
PMCID:12547917
PMID: 41142519
ISSN: 2772-5723
CID: 5960932

Clostridioides difficile Infection Is Associated With Increased Colectomy Risk in Acute Severe Ulcerative Colitis Treated With Infliximab

Kahan, Tamara F; Delau, Olivia; Hong, Simon; Holmer, Ariela; Dodson, John; Shaukat, Aasma; Chodosh, Joshua; Hudesman, David; Axelrad, Jordan E; Faye, Adam S
BACKGROUND:Infliximab (IFX) is commonly used in the management of acute severe ulcerative colitis (ASUC), yet up to 30% of individuals still require colectomy within 1 year. Clinical data characterizing these patients, however, are limited. AIMS/OBJECTIVE:We aimed to determine risk factors for colectomy among patients with ASUC who received in-hospital IFX treatment. METHODS:We performed a retrospective analysis of patients with ASUC who were treated with at least one dose of IFX while admitted between 2014 and 2022. Cox proportional hazards (PH) models were used to assess demographic, clinical, and laboratory risk factors for colectomy within 30 days and 1 year of IFX initiation. RESULTS:Overall, 36/170 (21.2%) patients underwent colectomy within 1 year of IFX initiation, with 22 (12.9%) individuals requiring colectomy within 30 days. On univariable analysis, concomitant Clostridioides difficile infection during admission, a ≤50% decrease in C-reactive protein (CRP) and experiencing 3 or more bowel movements per day within 48 hours after an initial IFX dose were significantly associated with 1-year colectomy. On multivariable Cox PH analysis, C. difficile infection during admission (aHR=2.92, 95% CI: 1.12-7.58) and a higher CRP/albumin ratio on admission (aHR=1.13, 95% CI: 1.01-1.27) were associated with increased colectomy risk within 1 year of IFX initiation. CONCLUSIONS:C. difficile infection and a higher CRP/albumin ratio on admission are associated with decreased time to colectomy within 1 year of IFX among patients presenting with ASUC. These factors may aid in early risk stratification to minimize delays in JAK-inhibitor initiation or surgical referral.
PMID: 41201306
ISSN: 1539-2031
CID: 5960342

Efficacy, Safety, and Metabolic Outcomes of Primary Obesity Surgery Endoluminal 2 (POSE-2) for Obesity: A Systematic Review and Meta-Analysis

Farooque, Umar; Qadri, Syeda Hafsa; da Silva, Ana Beatriz Nardelli; Malaj, Andela; Aparna, Fnu; Murtaza, Meer; Ahsan, Waseh; Warsi, Arshia; Badurdeen, Dilhana; Shaukat, Aasma
Primary Obesity Surgery Endoluminal 2 (POSE-2) is a minimally invasive endoscopic bariatric procedure. We conducted a systematic review and meta-analysis of one randomized controlled trial (RCT) and three observational studies (N = 210) to evaluate its efficacy, safety, and metabolic outcomes (HbA1c, glucose, cholesterol, triglycerides, LDL, and liver enzymes). Pooled percent total body weight loss (%TBWL) was 13.23% (I2 = 87%) at 3 months, 16.22% (I2 = 76%) at 6 months, and 16.17% (I2 = 0%) at 12 months, showing high heterogeneity early but consistency by 12 months. Percent excess weight loss (%EWL) at 12 months was 56.95% (I2 = 0%). HbA1c improved at 6 months (SMD = -0.67, p = 0.036, I2 = 0%), exceeding the minimal clinically important difference (-0.5%), and cholesterol decreased significantly (SMD = -0.25, p = 0.013, I2 = 0%). Fasting glucose and liver enzymes showed nonsignificant favorable trends with high heterogeneity for ALT/AST (I2 > 90%). Adverse events were infrequent (2.5-5%), mostly mild, with rare perforations or bleeding. POSE-2 demonstrates promising weight loss and selected metabolic improvements in HbA1c and cholesterol with a favorable short-term safety profile, though evidence is limited to four studies with small sample size, short follow-up, and variable heterogeneity, highlighting the need for larger, longer RCTs.
PMID: 41023533
ISSN: 1708-0428
CID: 5959162

Advancing Health Equity Through Telehealth: A Systematic Review and Meta-analysis of Remote vs. In-person Weight-loss Interventions among Black Women with Obesity

Farooque, Umar; Murtaza, Meer; Umer, Muhammad; Johar, Ayesha; Aparna, Fnu; Khan, Aqsa Riaz; Kumar, Anish; Ahmed, Nazeer; Qadri, Syeda Hafsa; Idrees, Hiba; Ullah, Aman; Aliyeva, Turkan; Shaukat, Aasma
INTRODUCTION/BACKGROUND:Obesity is a major public health issue in the U.S., with Black women disproportionately affected. Structural barriers like poverty, limited healthcare access, and lower education hinder weight management. Telehealth may improve health equity, but its effectiveness versus in-person care for Black women with obesity is unclear. This review compares both approaches to guide equitable care. METHODS:We conducted a PRISMA-compliant systematic review and meta-analysis, searching PubMed, Embase, and Cochrane through April 2025. Eligible were randomized controlled trials (RCTs) compared remote ± in-person vs. in-person weight-loss interventions among Black women with obesity. Random-effects models pooled changes in weight, BMI, blood pressure, and lipids. Risk of bias was assessed with RoB-2, and GRADE evaluated evidence certainty. RESULTS:Four RCTs (N = 576) were included. The analysis found no statistically significant differences in primary outcomes of weight change (SMD - 0.22, 95% CI: - 0.68; 0.24), percentage weight loss (SMD - 0.80, 95% CI: - 3.86; 2.26), and BMI (SMD - 0.26, 95% CI: - 1.61; 1.11). Secondary outcomes, such as blood pressure and lipid profiles (HDL, LDL, total cholesterol, triglycerides), also showed no statistically significant difference across intervention formats. Risk of bias was generally low, but evidence certainty ranged from moderate to very low. CONCLUSION/CONCLUSIONS:Remote weight-loss interventions via telehealth showed no significant short-term differences compared with in-person programs among Black women with obesity. Telehealth may offer a comparable alternative, but small sample size and limited follow-up preclude firm conclusions. Larger, longer-term, and culturally tailored trials are needed to confirm long-term impact and address digital equity.
PMID: 41114750
ISSN: 2162-4968
CID: 5956642