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Crohn's disease (CD) is an idiopathic inflammatory disorder of unknown etiology with genetic, immunologic, and environmental influences. The incidence of CD has steadily increased over the past several decades. The diagnosis and treatment of patients with CD has evolved since the last practice guideline was published. These guidelines represent the official practice recommendations of the American College of Gastroenterology and were developed under the auspices of the Practice Parameters Committee for the management of adult patients with CD. These guidelines are established for clinical practice with the intent of suggesting preferable approaches to medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. When exercising clinical judgment, health care providers should incorporate this guideline along with patient's needs, desires, and their values to care for patients fully and appropriately with CD. Shared decision-making with the patient is advocated. This guideline is intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are inflexible and rarely violated. To evaluate the level of evidence and strength of recommendations, we used the Grading of Recommendations Assessment, Development, and Evaluation system. The Committee reviews guidelines in depth, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments later.

Establishing vascular access early in out-of-hospital cardiac arrest (OHCA) is a crucial factor for improving prognosis. Clinical guidelines recommend both intravascular (IV) and intraosseous (IO) access, but the superiority of one technique over the other has yet to be determined. Our review aimed to compare the efficacy and safety of IV versus IO access in OHCA. A comprehensive search was conducted on PubMed/MEDLINE, Embase, and Cochrane Library from inception till January 2025 for randomized controlled trials or their subgroup analyses comparing IV versus IO access in adult OHCA patients. The data for clinical outcomes were extracted, and forest plots were generated using the random-effects model in the Review Manager 5.4. We included 6 studies reporting data for 19,811 patients. The pooled analysis demonstrated that IO access had significantly higher odds of successful vascular access on first attempt [odds ratio (OR), 1.25; 95% confidence interval (CI), 0.19–0.34], but this did not translate to improved survival to hospital discharge (OR, 1.23; 95% CI, 0.90–1.67), survival to hospital discharge with a favorable neurological outcome (OR, 1.28; 95% CI, 0.93–1.76), and return of spontaneous circulation (OR, 1.13; 95% CI, 0.67–1.93). Intravenous and intraosseous vascular access have similar effects on clinical outcomes in patients with OHCA. The preferred method for vascular access should depend on the responder’s feasibility and expertise.

PURPOSE Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC). METHODS In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc. RESULTS OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; P = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE. CONCLUSION This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.

Background: Evaluation of the performance of Cobas ® Pulse (Roche Diagnostics GmbH, Mannheim, Germany), a new blood glucose (BG) monitoring system (BGMS; referred to here as BGMSA) intended for point-of-care testing using samples from patients in diverse clinical settings by intended point-of-care test operators. Methods: Arterial, capillary, venous, or heel stick whole blood (WB) samples from patients in non-critical and critical care settings were collected and analyzed using BGMSA and the Nova StatStrip ® BGMS (Nova Biomedical, Waltham, MA; referred to here as BGMSB), and a hexokinase comparator (Cobas 6000 Analyzer Series; Roche Diagnostics GmbH). The blood glucose measurement accuracy was assessed by the Food and Drug Administration guidance criteria. Results: Two studies are presented. In the first, 2678 samples (622 arterial, 706 capillary, 1203 venous, 147 heel stick) were collected from 1577 patients in 14 US and three European sites. All accuracy criteria were met for arterial and venous samples considering all data combined. BGMSA showed better accuracy than BGMSB for arterial, venous, and heel stick, and similar results to BGMSB for capillary WB vs venous comparator. No endogenous interference from pO 2 , hematocrit, and sodium was identified. BGMSA was also accurate when analyzing contrived samples used to show accuracy over a wide range of glucose concentrations, alone and when combined with extreme hematocrit. In the second study, 117 capillary fingerstick samples collected at one US site were measured on both BGMSA and the comparator, and all accuracy criteria were met. No clinically significant medical risks were observed via Diabetes Technology Society Error Grids. Conclusions: BGMSA was effective for determining blood glucose in venous, arterial, neonatal arterial, neonatal heel stick, and capillary WB samples.

Background: Total ankle arthroplasty (TAA) using patient-specific instrumentation (PSI) has increased in popularity with evidence for decreased operative duration, fluoroscopy usage, and increased implant placement accuracy. To date, no comparisons have verified the accuracy of PSI in vivo using preoperative and postoperative weightbearing computed tomography (WBCT). Our study aims to supplement the literature by quantifying the accuracy and precision of PSI-guided implant positioning using WBCT. The primary study outcome is to identify positioning deviations in degrees or millimeters in any plane for talus and tibial PSI-guided resections and subsequent implant placement. Secondary outcomes were correlation and regression analyses performed to identify variables that correlate to resection or implant placement deviation, as well as comparison to existing radiography-based PSI techniques. Methods: This was a single-surgeon, single-implant consecutive patient retrospective study where preoperative and postoperative WBCTs were obtained. TAA was performed by the senior author with the same low-profile implant for all cases. Talus and tibial resection analysis was performed in computer-automated fashion on postoperative segmented WBCTs and is described as 3 possible deviations from plan (cut height in millimeters, sagittal slope, varus/valgus deviation). Overall deformity in this group was not severe. Implant placement factors independent of PSI guides are described as center-of-mass translations (mm) and axial rotation (degrees). Desired accuracy for the PSI system was within ±2 mm or ±2 degrees of the preoperative plan. Statistical analysis of data collected included Student t test and linear regression analyses. Results: Thirty patients were included. Four talus implants were excluded per intraoperative surgeon discretion (deviation from PSI plan, use of conventional instruments). All postoperative tibial measurements were within the desired limits, except for mediolateral center of mass positioning ( P = .003) and slope ( P = .013). Two of six talar parameters also diverged from preoperative measurements: axial rotation ( P = .015) and anteroposterior positioning ( P = .002). In addition, no correlations exceeding r = 0.5 were noted between preoperative deformity measurements and postoperative positioning. Conclusion: For the 26 ankles that did not require an intraoperative deviation from PSI plan and/or use of conventional instruments, total ankle replacement performed with PSI using WBCT results in component placement with relatively little deviation from the preoperative plan. In addition, the lack of correlation between preoperative deformity and implant placement suggests that the magnitude of preoperative deformity in this group was not associated with the accuracy of PSI-guided component positioning. Level of Evidence: Level III, retrospective cohort study.

e13162 Background: BRCA1/2 mutations impair homologous recombination repair, forcing cancer cells to rely on alternative DNA repair pathways, such as those mediated by poly(ADP-ribose) polymerase (PARP). PARP inhibitors (PARPis), like iniparib, olaparib, talazoparib, niraparib, and veliparib, exploit this dependency, inducing lethality in cells of BRCA-mutated, HER2-negative breast cancers (BRCAm, HER2-BC). Only 2 PARPis, talazoparib and olaparib, are FDA-approved for BRCAm, HER2-BC. However, the treatment with the highest efficacy remains unclear. We conducted a network meta-analysis (NMA) of randomised controlled trials (RCTs) to compare the efficacy of PARPis in treating BRCAm, HER2-BC. Methods: We systematically searched PubMed, Cochrane CENTRAL, SCOPUS, and ClinicalTrials.gov (up to December 2024) for randomized controlled trials (RCTs) following PRISMA-NMA guidelines. Primary outcome was overall survival(OS), with hazard ratios (HRs) and 95% confidence intervals (CIs). Secondary outcome was progression-free survival (PFS). Survival times were converted to HRs under the assumption of exponential distribution. Standard of care (SOC) was defined as taxane/anthracycline-based regimens with additional platinum-based chemotherapy. Physician's choice chemotherapy (PCT) included capecitabine, eribulin, gemcitabine, or vinorelbine. A frequentist approach with random-effects modeling was used to pool estimates, and P-scores ranked treatment efficacy. Heterogeneity and inconsistency were assessed using τ², I², and Q-statistics. Analyses were conducted in R version 4.4.1. Results: 8 studies including 4432 participants incorporating 8 pairwise comparisons and 7 treatments were analyzed for OS. Compared to SOC (reference), HRs of OS were significantly reduced with talazoparib+SOC (HR = 0.49, 95% CI: 0.32–0.74; P = 0.64), olaparib+SOC (HR = 0.46, 95% CI: 0.36–0.59; P = 0.69), niraparib+SOC (HR = 0.44, 95% CI: 0.26–0.76; P = 0.76), and veliparib+SOC (HR = 0.38, 95% CI: 0.29–0.48; P = 0.91). No heterogeneity or inconsistency was detected (τ² = 0; I² = 0; Q = 1.27, p = 0.53). For PFS, iniparib/gemcitabine, talazoparib, olaparib, and niraparib showed significant reduction in HR with increasing order of P-scores, in combination with SOC. Conclusions: Veliparib combined with SOC showed the highest OS improvement, while niraparib ranked highest for PFS, followed by talazoparib and olaparib. Further trials are needed to confirm these findings and refine treatment strategies for BRCAm, HER2-BC.

e24020 Background: Transcatheter aortic valve replacement (TAVR) is a widely adopted treatment for severe aortic stenosis, but outcomes in cancer survivors with prior chest radiation therapy (C-XRT) remain uncertain. This study compares the clinical outcomes of TAVR between patients with a history of C-XRT and those without prior radiation exposure (control group). Methods: Patients with prior chest radiation therapy (C-XRT) were compared to a control group without radiation exposure to evaluate key clinical endpoints. For each endpoint, odds ratios (OR) and 95% confidence intervals (CI) were determined, and heterogeneity was analyzed using the I² statistic. A p-value of <0.05 was considered statistically significant. Results: Nine studies were included in the meta-analysis, encompassing 3083 C-XRT and 8891 control patients. Patients with prior C-XRT showed significantly higher long-term mortality (OR 1.84, 95% CI [1.08, 3.13], p=0.02) compared to controls. Other outcomes, including access-related vascular complications, Acute Kidney Injury, Congestive heart failure, major bleeding, need for pacemaker, short-term mortality, and stroke, did not demonstrate significant differences between the groups. Conclusions: Cancer survivors with prior chest radiation therapy undergoing TAVR may experience higher long-term mortality compared to patients without radiation exposure. However, no significant differences were observed in other major outcomes. These findings suggest that while TAVR is a viable treatment for C-XRT patients, long-term risks require further investigation to optimize patient selection and management strategies. Outcomes. Outcome OR 95% Confidence Interval P value Access related vascular complications 1.12 [0.85, 1.48] 0.43 Acute kidney injury 0.54 [0.20, 1.50] 0.24 Congestive heart failure 1.38 [0.88, 2.17] 0.16 Long term mortality 1.84 [1.08, 3.13] 0.02 Major bleeding 0.96 [0.78, 1.17] 0.67 Need for pacemaker 1.05 [0.88, 1.26] 0.57 Short term mortality 1.66 [0.97, 2.84] 0.06 Stroke 1.25 [0.74, 2.11] 0.39

8501 Background: TROPION-Lung02 (NCT04526691) evaluated the TROP2-directed antibody-drug conjugate (ADC) Dato-DXd plus pembro combination with or without Pt-CT in aNSCLC. Here we report primary analyses of pts receiving combination therapy in the 1L setting. Methods: Pts across 6 cohorts were dosed with Dato-DXd (4 or 6 mg/kg) plus pembro 200 mg alone (doublet) or with pembro plus Pt-CT (triplet; cisplatin 75 mg/m 2 or carboplatin AUC 5) Q3W. PD-L1 expression (tumor proportion score) was assessed locally by immunohistochemistry (22C3 assay). Primary objectives were safety and tolerability; efficacy was a secondary objective. Results: As of Apr 29, 2024, 96 pts received either the doublet (n=42) or triplet (n=54) combination as 1L therapy; 29% and 15% of pts were ongoing, respectively. Median ages were 65 (doublet) and 64 years (triplet). Median treatment durations were 9.7 and 5.8 months, respectively. Stomatitis (doublet, 57%; triplet, 33%) and nausea (doublet, 42%; triplet, 48%), primarily Gr 1–2, were the most common adverse events (AEs) across both regimens. Treatment related serious AEs occurred in 5 (12%) and 12 (22%) pts in each cohort and no deaths related to study drug were seen. Efficacy outcomes, including by histology, are summarized in the Table. Biomarker analyses, including efficacy by PD-L1 status, will be presented. Conclusions: In this largest data set to date evaluating an ADC combined with an anti-PD-1/L1 agent in the 1L setting, the combination of Dato-DXd plus pembro treatment both with and without Pt-CT elicited durable antitumor activity in pts with aNSCLC. Tolerability of the combinations was as expected, based on known profiles of the individual agents. Clinical trial information: NCT04526691 . All 1L (n=96) 1L, Nonsquamous (n=75) 1L, Squamous (n=21) Response, n (%) Doublet (n=42) Triplet (n=54) Doublet (n=33) Triplet (n=42) Doublet (n=9) Triplet (n=12) Confirmed objective response rate 23 (55) 30 (56) 17 (52) 24 (57) 6 (67) 6 (50) Complete response 1 (2) 2 (4) 1 (3) 2 (5) 0 0 Partial response 22 (52) 28 (52) 16 (49) 22 (52) 6 (67) 6 (50) Stable disease 14 (33) 18 (33) 12 (36) 14 (33) 2 (22) 4 (33) Progressive disease 3 (7) 2 (4) 3 (9) 1 (2) 0 1 (8) Disease control rate a 37 (88) 48 (89) 29 (88) 38 (91) 8 (89) 10 (83) Median duration of response, mo (95% CI) 20.1 (9.7–NE) 13.7 (5.7–NE) 24.9 (9.7–NE) 18.0 (8.0–NE) 12.0 (5.5–NE) 5.5 (4.1–NE) Median PFS, mo (95% CI) 11.2 b (8.2–21.3) 6.8 c (5.5–11.1) 11.2 (6.1–21.3) 10.8 (5.5–17.3) 10.2 (0.4–NE) 6.7 (1.0–8.2) a Proportion of pts with confirmed CR + PR + SD at 12 wks. b.c Median (95% CI) PFS follow-up, mo: b 17.3 (11.3−26.8); c 23.5 (17.3−27.9). mo, months; NE, not evaluable.

e24024 Background: Patients with active cancer undergoing trans catheter aortic valvular replacement (TAVR) face a higher risk of adverse outcomes due to the interplay between cancer and cardiovascular disease. Although TAVR is increasingly used in high-risk populations, data on outcomes for these patients remain limited. This systematic review and meta-analysis aim to evaluate the clinical outcomes associated with TAVR in patients with active cancer compared to non-cancer controls, providing insights to inform clinical decision-making in this unique group. Methods: A systematic search of major databases (PubMed, Embase, OVID, Web of Science, Scopus) was conducted to identify studies comparing clinical outcomes of TAVR between patients with active cancer and those without cancer. Key outcomes included measures of mortality, procedural complications, and post-procedure adverse events. The Mantel-Haenszel method was used for pooled analysis, applying random-effects or fixed-effects modeling based on heterogeneity assessed by Higgins I². Statistical significance was set at a p-value < 0.05. Results: Twelve studies involving 5,73,192 patients (67,684 active cancer, 505508 control) were included. Patients with active cancer undergoing TAVR have significantly higher risks of short-term mortality (OR 1.31, 95% CI [1.15, 1.49], p < 0.0001), long-term mortality (OR 2.24, 95% CI [1.85, 2.70], p < 0.0001), and major bleeding complications (OR 1.80, 95% CI [1.68, 1.92], p < 0.0001). There were no statistically significant differences in cardiovascular mortality (OR 1.33, 95% CI [0.94, 1.89], p = 0.11), myocardial infarction (OR 1.60, 95% CI [0.82, 3.11], p = 0.17), stroke (OR 0.61, 95% CI [0.28, 1.35], p = 0.22), AKI (OR 0.92, 95% CI [0.49, 1.73], p = 0.80), or the need for permanent pacemaker implantation (OR 1.12, 95% CI [0.85, 1.48], p = 0.42). Conclusions: Patients with active cancer undergoing TAVR face significantly higher risks of mortality and major bleeding compared to non-cancer controls. However, the risks of cardiovascular mortality, MI, stroke, AKI, and the need for permanent pacemaker implantation are comparable to those of non-cancer controls. Careful risk assessment and management are crucial for optimizing outcomes in this vulnerable population, and further studies are needed to refine treatment strategies. Odds ratios of all outcomes. Outcomes OR Confidence Interval (95% CI) p-value Short term mortality 1.31 [1.15, 1.49] < 0.0001 Long term mortality 2.24 [1.85, 2.70] < 0.00001 Major bleeding 1.8 [1.68, 1.92] < 0.00001 Cardiovascular mortality 1.33 [0.94, 1.89] 0.11 Myocardial Infarction 1.6 [0.82, 3.11] 0.17 Stroke 0.61 [0.28, 1.35] 0.22 Acute Kidney Injury 0.92 [0.49, 1.73] 0.8 Need for permanent pacemaker implantation 1.12 [0.85, 1.48] 0.42