High-Impact Clinical Trials and Studies

Comparative Effectiveness of Semaglutide and Tirzepatide vs Bariatric Surgery Avery Brown, MD, Suhani S Patel, MPH, Babak Orandi, MD, FACS, Dorry Segev, MD, PhD, Akuezunkpa Ude Welcome, MD, Manish S Parikh, MD, FACS, Karan R Chhabra, MD NYU Langone Health, New York, NY; Bellevue Hospital, New York, NY Introduction: GLP-1 receptor agonist (GLP1-RA) use is increasing exponentially. Few studies directly compare the effectiveness of the newer GLP1-RAs (semaglutide and tirzepatide) to bariatric surgery, the gold-standard treatment for obesity and diabetes. Methods: We identified 51,085 patients aged ≥18 years prescribed injectable semaglutide or tirzepatide, compared with 24,344 patients who underwent minimally invasive sleeve gastrectomy or Roux-en-Y gastric bypass at 2 large urban health systems from 2018 to 2024. Percent total weight loss (%TWL) was followed for 3 years post-treatment. To account for GLP1-RA discontinuation, we performed intention-to-treat (any patients prescribed GLP-RAs) and per-protocol (patients with 1-year continuous GLP1-RA treatment) analyses using average treatment effect weighting based on age, BMI, and baseline comorbidity. Results: A total of 51,085 patients were included for analysis (38,545 GLP1, 12,540 surgery patients). GLP1-RA patients had a significantly higher rate of diabetes, hyperlipidemia, and COPD compared with surgery patients. In the weighted intention-to-treat analysis, bariatric surgery was associated with more weight loss at all time points: 3 year %TWL: -23.3 [-23.5, -23.1] for surgery vs -4.0 [-4.1, -3.8] for GLP1-RAs. In the weighted per-protocol analysis of patients with 1-year continuous GLP1-RA use, surgery patients still had significantly more weight loss at all time points: 3 year %TWL: -22.2 [-22.5, -21.9] for surgery vs -5.9 [-6.3, -5.5] for GLP1-RAs, Figure 1. Conclusion: Bariatric surgery is associated with superior sustained, long-term weight loss compared with GLP-1RAs among patients eligible for both options.Figure 1Efficacy of a Novel Local Prolonged-Release Incisional Doxycycline on Surgical Site Infection Prophylaxis in Abdominal Colorectal Surgery: The Shield II Phase 3 Randomized Clinical Trial Shmuel Sharoni, MD, Steven Colquhoun, MD, FACS, Oded Zmora, MD, FACS PolyPid LTD, Petah Tikva, Israel; Augusta University, Augusta, GA; Shamir MC, Matan, Israel Introduction: Despite advanced infection control practices, surgical site infection (SSI) remains a challenge. D-PLEX100, a novel local prolonged-release incisional doxycycline, was evaluated as an adjunct to standard systemic antibiotic prophylaxis to determine its efficacy in reducing SSI. Methods: SHIELDII was a prospective, randomized, controlled, double-blind, multinational Phase-3 study. Patients undergoing abdominal colorectal surgery with planned abdominal incision length >20 cm were randomized to D-PLEX100 plus standard-of-care (SoC) systemic antibiotics (n = 405) or SoC alone (n = 393). The primary outcome was a combination of adjudicated incisional SSI, reintervention at the target incision site, and mortality. Key secondary endpoints included the incidence of adjudicated SSI and ASEPSIS scores >20. Results: In the intention-to-treat population, there was a significant 38% risk reduction of the primary efficacy outcome in the D-PLEX100 arm (10.9%, 44/405) compared with the SOC arm (18.1%, 71/393) (ARR 7.2%, 95% CI -12.1 to -2.3; p = 0.0039). The incidence of adjudicated incisional SSI indicated a 58% risk reduction in D-PLEX100 arm (3.8% in D-PLEX100 vs 9.5% in SoC; absolute risk reduction (ARR) 5.8%, 95% CI -9.3 to -2.3; p = 0.0013). Additionally, fewer patients in D-PLEX100 arm had ASEPSIS scores >20 (2.0% in D-PLEX100 vs 5.6% in SoC; p = 0.0103). D-PLEX100 safety profile did not show significant difference between the groups. Conclusion: D-PLEX100 in addition to SoC prophylaxis significantly reduced the incidence of incisional SSI and primary outcome events. These results represent a clinically meaningful improvement in outcomes for patients undergoing major abdominal colorectal surgery and support the incorporation of D-PLEX100 into standard prophylactic surgical protocols to reduce SSI-related complication. FLOT vs SOX Neoadjuvant Chemotherapy: First Prospective Survival Comparison in Locally Advanced Gastric Cancer Birendra K Sah, MBBS, PhD, FACS Ruijin Hospital Shanghai Jiaotong University School of Medicine, Shanghai, China Introduction: Both fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) and S-1 and oxaliplatin (SOX) neoadjuvant regimens are widely used for locally advanced gastric cancer; however, direct head-to-head survival data are lacking. This study provides the first prospective comparison of long-term survival outcomes between these regimens. Methods: We conducted an open-label, randomized, phase-2 trial (NCT03636893) in China. Patients with locally advanced gastric cancer (cT3-4b, cN1-3, cM0) were randomized to receive neoadjuvant FLOT (4 cycles) or SOX (3 cycles) before D2 gastrectomy. Primary endpoints were overall survival (OS) and disease-free survival (DFS) analyzed by intention-to-treat with median follow-up of 65.7 months through May 2025. Results: A total of 74 patients were randomized (40 FLOT, 34 SOX) with complete long-term follow-up achieved for all patients. Both regimens demonstrated exceptional survival: median OS was 61.5 months for FLOT vs 67.8 months for SOX (hazard ratio [HR] 1.101, p = 0.759). disease-free survival (DFS) showed equivalent outcomes (23.0 vs 25.5 months, HR 1.060, p = 0.842). Clinicopathological factors proved more prognostic than regimen choice: complete/subtotal tumor regression achieved 80.5-month median survival vs 47.6 months for partial response (p = 0.017). Gastrectomy type emerged as the strongest independent survival predictor (HR 3.619 for total vs partial gastrectomy, p = 0.010). Conclusion: This definitive analysis establishes equivalent excellent survival between FLOT and SOX regimens, both achieving median OS exceeding 5 years. Treatment selection should be individualized based on patient factors rather than survival expectations, with focus on optimizing pathological response and surgical approach. Landmark Results from a Prospective Feasibility Trial Evaluating Circulating Tumor DNA as a Biomarker in Patients with Localized Pancreatic Cancer Krishay Sridalla, BA, Dominic J Vitello, MD, MS, Madison Cox, BA, Larissa Masnyk, BA, Amy Wells, MS, Vishvetha Rengaraju, BS, Alex Horowitz, BA, Jasmine Machhi, BS, Qiang Zhang, MD, PhD, Akhil Chawla, MD, FACS Northwestern University Feinberg School of Medicine, Chicago, IL; The Ohio State University College of Medicine, Columbus, OH; Midwestern University Chicago College of Osteopathic Medicine, Downers Grove, IL Introduction: Circulating tumor DNA (ctDNA) is an emerging blood-based biomarker in pancreatic ductal adenocarcinoma (PDAC). We present results from a prospective feasibility trial evaluating ctDNA as a biomarker in localized PDAC. Methods: Patients with localized PDAC were enrolled at an academic institution between October 2020 and November 2024 (NCT04616131). Patients underwent targeted next-generation sequencing (NGS) evaluating over 105 genes at diagnosis, after neoadjuvant chemotherapy (NAC), and after local therapy. The prognostic significance of KRAS-mutant ctDNA detection was evaluated through Kaplan-Meier analysis and multivariable Cox regression. Results: This analysis included 253 blood samples from 119 patients with a median follow-up time of 17.8 months. KRAS-mutant ctDNA was detected in 17.7% at diagnosis, decreased to 5.3% after NAC (17.7% vs 5.3%; p = 0.018), and was detected in 8.2% after surgical resection. KRAS-mutant ctDNA detection at diagnosis was associated with inferior overall survival (OS; 11.2 vs 27.2 months; p < 0.001; Figure 1) and remained an independent predictor of shorter survival (adjusted hazard ratio [aHR] 6.1; 95% CI 2.5-14.8), while CA 19-9 was not. A quantitative increase in mutational burden during treatment, measured by maximum allele frequency, independently predicted shorter OS (aHR 1.19; 95% CI: 1.02-1.39), whereas changes in CA 19-9 did not. Conclusion: In the largest prospective cohort to date, ctDNA was prognostic in localized PDAC patients undergoing NAC and surgery. KRAS-mutant ctDNA at diagnosis and changes in mutational burden independently predicted shorter OS. This is the first study to establish the prognostic significance of ctDNA mutational burden and its dynamic change during NAC using NGS in localized PDAC.Figure 1Remote Monitoring for Lower Extremity Wound Management: A Randomized Controlled Trial Yuan-Haw Andrew Wu, MD, Laura M Drudi, MD, FACS, Midori White, MD, Chen Dun, PhD, MHS, Sherry G Leung, BA, Courtenay M Holscher, MD, PhD, Ronald Sherman, DPM, MBA, Christopher J Abularrage, MD FACS, Elizabeth Selvin, PhD, MPH, Caitlin W Hicks, MD, MS, FACS Division of Vascular Surgery and Endovascular Therapy, Johns Hopkins University, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Surgery, Albany Medical College, Albany, NY; Department of Vascular Surgery, Centre Hospitalier de l’Universitdé Montréal, Montreal, QC, Canada Introduction: Comprehensive in-person wound care is costly and burdensome for patients. We evaluated the efficacy of the Minuteful for Wound (Healthy.io) artificial intelligence (AI)-powered smartphone application for remotely monitoring complex lower extremity wounds. Methods: We performed a multicenter randomized controlled trial comparing remote monitoring vs standard in-person care for lower extremity wounds. Participants in both study arms underwent wound scanning using the smartphone application at the beginning and end of the study to capture wound status. Participants in the remote monitoring arm were instructed to perform weekly remote wound scans for 12 weeks, whereas participants in the control arm had standard biweekly in-person clinic visits. Wound healing at 12 weeks was compared for the remote monitoring vs standard care groups. Results: A total of 113 participants were randomized (mean age 65.1 ± 11.6 years, 35% female, 78.4% with diabetes), including 55 in the remote monitoring arm and 58 in the standard care arm. The mean baseline wound area was 8.5 cm² (interquartile range 0.96-10.4 cm²). Participants in the remote monitoring arm submitted a mean of 7.5 ± 4.9 scans over 12 weeks. There was a similar mean percentage reduction in wound area after 12 weeks in both study groups (remote:-54.9% vs standard:-52.3%, p = 0.47; Figure 1). The majority of participants in the remote monitoring arm reported the smartphone application was easy to use (94%), and 79% reported improved access to healthcare compared with standard care. Conclusion: Remote monitoring is a feasible, effective approach to complex lower extremity wound management that offers comparable outcomes and improved access to care without the burden of standard biweekly in-person visits.Figure 1Ten-Year Follow-Up of Antibiotics for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial Paulina Salminen, MD, PhD, FACS (Hon), Roosa Salminen, MD, Saija Hurme, MSc, Pia Nordström, MD, PhD, Hannu Paajanen, MD, PhD, Jukka-Pekka Mecklin, MD, PhD, Juha Grönroos, MD, PhD, Tero Rautio, MD, PhD University of Turku and Turku University Hospital, Turku, Finland; University of Oulu, Oulu, Finland; University of Turku, Turku, Finland; Tampere University Hospital, Tampere, Finland; Mikkeli Central Hospital, Mikkeli, Finland; Hospital Nova, Jyväskylä, Finland; Oulu University Hospital, Oulu, Finland Introduction: Antibiotic therapy is effective and safe alternative to appendectomy for uncomplicated acute appendicitis with no long-term results exceeding 5 years. Methods: We performed a 10-year follow-up of the APPendicitis ACuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotics at 6 Finnish hospitals from 11/2009 to 6/2012 (ClinicalTrials.govNCT01022567), where 530 patients (18-60 years) with CT-diagnosed uncomplicated acute appendicitis were randomized to appendectomy (n = 273) or antibiotics (n = 257). A 10-year analysis was performed, focused on appendicitis recurrence rate and possible appendiceal tumors in antibiotic patients with an intact appendix using MRI. Secondary outcomes included complication, quality of life (QOL), and patient satisfaction. Results: At 10-year follow-up, 253/257 (98.4%) patients after antibiotics were assessed for appendicitis recurrence with a cumulative appendectomy rate of 44.3% (95% CI 38.2%-50.4%; 112/253) and true appendicitis recurrence rate (appendicitis at histopathology) of 37.8% (95% CI 31.6%-44.1%; 87/230). A total of 102 out of 143 patients (71.3%) with an intact appendix underwent MRI. Two patients (2/212, 0.9%) had a suspected appendiceal tumor and underwent appendectomy with low-grade appendiceal mucinous neoplasm at histology with overall tumor prevalence of 1.2% (6/484, 4/272 tumors in the appendectomy group) in uncomplicated acute appendicitis. Overall 10-year cumulative complication rate after appendectomy was 27.4% (95% CI 21.6-33.3; 62/226) and 8.5% (95% CI 4.8-12.1; 19/224) after antibiotics (p < 0.001). There was no difference in QOL (387/530) between antibiotics and appendectomy (p = 0.18). Conclusion: Among patients initially treated with antibiotics for uncomplicated acute appendicitis, 10-year true appendicitis recurrence rate was 37.8% and appendectomy rate 44.3%. Risk of appendiceal tumors was very low, supporting the use of antibiotics as an alternative to appendectomy for uncomplicated acute appendicitis.

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