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Abstract Background A subset of risankizumab (RZB)-treated patients experience suboptimal or secondary loss of response to standard dosing. We explored factors associated with future RZB dose-optimization, and outcomes of optimization in a multicenter consortium of adults with Crohn’s Disease (CD). Methods Baseline characteristics at time of RZB initiation and subsequent clinical, endoscopic, and biochemical outcomes were collected in a multi-center cohort. Outcomes for dose-optimized RZB were reported as clinical response and remission (based on HBI or PGA when HBI unavailable), endoscopic remission (based on SEMA-CD or absence of ulcers when SEMA-CD not available), and biochemical response. Characteristics were compared between standard and dose-optimized groups using chi-square and two-sample t-tests. Additional models adjusting for age and sex assessed predictors of dose optimization. Results We identified 309 patients treated with standard dose and 58 for whom dose-optimized RZB was recommended. Of the 58, 29 were excluded from outcomes analysis due to lack of follow-up (n = 19) or insurance denial of dose optimization (n = 10). Demographic information is outlined in Table 1. Baseline characteristics associated with future dose optimization included number of prior advanced therapies (ATs) (OR, 1.29, p < 0.001), prior anti-TNF (OR,4.06; p = 0.022), and prior ustekinumab (UST) use (OR,1.82; p = 0.053) (Table 2). The 29 patients included in the outcome analysis received dose-optimized RZB for primary non-response (n = 2), partial response (n = 23), or secondary loss of response (n = 4) after a median of 321 days (IQR, 234-440) from index RZB start. Median follow-up after dose optimization was 217 days (IQR, 147-331). All patients were AT-exposed (Table 1). Baseline clinical symptoms were present in 27 patients (93.1%), with median HBI of 6.5 (IQR, 6.0-8.0). Active endoscopic disease was observed in 11/12 patients (91.7%) who had baseline endoscopy. Dosing was every 4 weeks in 19 (65.5%), every 6 weeks in 9 (31.0%), and combined IV re-induction plus every 4-weeks in 1 (3.4%) patient. Clinical response and remission was seen in 16 (55.2%) and 12 (41.4%) patients, respectively. A ≥ 50% CRP reduction was seen in 5/12 (41.7%) patients with baseline elevated CRP. Among 7 patients with baseline active endoscopic disease with available follow-up, 3 (42.9%) achieved endoscopic remission. No adverse events were reported. Conclusion In this multi-center retrospective cohort, prior AT-exposure (especially anti-TNF) was associated with need for RZB dose-optimization. Dose optimization successfully captured clinical response in a significant proportion of patients who experienced partial response or loss of response to RZB. Conflict of interest: Johnson, Amanda: Research grant: Abbvie, Spyre Therapeutics Ramesh, Prajith Raj: None Said, Hyder: No conflict of interest Huang, Katherine: No conflict of interest Devi, Jalpa: none Pekow, Joel R.: CVS Health - Consulting Abbvie, Eli Lilly, Pfizer, Johnson and Johnson - Stocks Alhobayb, Tamara: No conflict of interest Bassmeyer, Blake: No conflict of interest Mohamed, Mouhand: No conflict of interest Shivashankar, Raina: Abbvie and BMS - speaker bureau Janssen and Celltrion - grant for IBD fellowship funding Pfizer - consultant Rathi, Jaya: No conflict of interest Luu, Bryan: No conflict of interest Khan, Abdul: No conflict of interest Loftus, Jr, Edward: Grant: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Gilead, Janssen, Pfizer, Receptos, Robarts Clinical Trials, Takeda, Theravance, UCB. Personal Fees: AbbVie, Allergan, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, Iterative Scopes, Janssen, Ono Pharma, Pfizer, Sun Pharma, Takeda, UCB. Bishu, Shrinivas: None Patel, Anish: speaker: abbvie, J & J, Lilly, BMS, Pfizer, Phathom, Takeda consultant: abbvie Shukla, Richa: Speakers bureau - Abbvie and Lilly Yarur, Andres: Personal Fees: Consultant for Takeda, Pfizer, Roche, Merck, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Johnson and Johnson. Ungaro, Ryan: Personal Fees: AbbVie, Bristol Myers Squibb, Genentech, Lilly, Pfizer, Janssen, Takeda Deepak, Parakkal: Parakkal Deepak has received research support under a sponsored research agreement unrelated to the data in the abstract from AbbVie, Johnson and Johnson, Sanofi, Merck, Teva, Direct Biologics, Tr1x, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals, Roche Genentech, Eli Lilly, AstraZeneca, Spyre and Agomab, has received consulting fees from Johnson and Johnson, Abbvie, Merck, Sobi, Celltrion, Fresenius Kabi, Asahi Kasei Pharma, Sandoz and CorEvitas, LLC and has served on the board of the Srategic Alliance for Intercultural Advocacy in GI.

Background: Inclisiran, a small interfering RNA (siRNA), inhibits hepatic PCSK9 synthesis, leading to significant LDL-C reduction. Previous meta-analyses have addressed short-term efficacy; however, recent long-term data warranted an updated systematic review and meta-analysis to evaluate inclisiran’s lipid-lowering efficacy and safety in hyperlipidemic patients. Methods: A systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov was conducted from inception to April 2025 to identify randomized controlled trials (RCTs) comparing inclisiran with placebo or standard care in adults with hypercholesterolemia. Primary efficacy outcomes included percentage change in LDL-C, PCSK9, total cholesterol, apolipoprotein B (apo-B), and non-HDL-C. Safety outcomes included adverse events, cardiovascular events, and all-cause mortality. Data were analyzed using a random-effects model following PRISMA guidelines. Risk ratios (RR) and weighted mean differences (WMD) were calculated with 95% confidence intervals. The protocol was registered on PROSPERO (CRD420251059229). Results: Eleven RCTs with 5,601 patients were included; 3,135 received inclisiran and 2,466 received placebo. Inclisiran significantly reduced: LDL-C (WMD –48.99%, 95% CI: –54.29 to –43.69) PCSK9 (WMD –78.52%, 95% CI: –81.52 to –75.51) Total cholesterol (WMD –31.21%, 95% CI: –33.47 to –28.56) Apo-B (WMD –40.09%, 95% CI: –43.43 to –36.75) Non-HDL-C (WMD –35.22%, 95% CI: –41.25 to –29.20) Inclisiran showed no significant impact on all-cause mortality (RR 0.94; p=0.83), cardiovascular mortality (RR 1.19; p=0.60), myocardial infarction (RR 0.85; p=0.60), stroke (RR 0.89; p=0.86), or major adverse cardiovascular events (RR 0.80; p=0.07). Total adverse events were slightly higher with inclisiran (RR 1.06; p=0.02), but serious adverse events were not significantly different (RR 0.90; p=0.36). Injection site reactions were more common with inclisiran (RR 6.45; p<0.001). Conclusion: Inclisiran significantly reduces LDL-C, PCSK9, total cholesterol, apo-B, and non-HDL-C, confirming strong lipid-lowering efficacy. It is generally well tolerated, with a slightly higher incidence of mild injection site reactions but no increase in serious adverse events. Longer-term studies are needed to assess its effect on cardiovascular outcomes.

Abstract Background We aimed to evaluate the effectiveness and safety of risankizumab (RZB) for Crohn’s disease (CD) in routine clinical practice. Methods We performed a retrospective review of a multicenter consortium of CD patients treated with RZB. Co-primary outcomes were week 12 clinical remission (Harvey Bradshaw Index [HBI] score of ≤4 or physician global assessment in those without HBI or with ileostomy) and 6-month endoscopic remission (Simplified Endoscopic Mucosal Assessment for Crohn’s Disease of 0-1 or absence of ulcers). Secondary outcomes included steroid-free clinical remission, clinical response, radiographic response, cumulative clinical and endoscopic remission rates at 6 and 12 months, and adverse events. Results A total of 309 patients were included (median disease duration 14 years [IQR, 6-24]; median follow-up 7.1 months [IQR, 4.1-10.3]). Most patients (85.8%) were advanced therapy (AT)-exposed, and 169 (54.7%) had prior ustekinumab (UST) exposure. Week 12 clinical remission rates were 49.7% (98/197) overall, and 44.2% (50/113) vs 57.1% (48/84) in UST-exposed vs naïve patients (P = .073). Among those with active disease on baseline endoscopy (n = 122) who had an available follow-up at 6 months, 52.4% (22/42) achieved endoscopic remission. Cumulative rates of clinical and endoscopic remission at 12 months were 65.0% and 49.5%, respectively. Cumulative 12-month endoscopic remission was 33.9% (19/56) in UST-exposed and 68.1% (32/47) in UST-naïve patients (P &lt; .001). Risankizumab was well-tolerated with no new safety signals identified. Conclusions In this large multicenter cohort of patients with CD, RZB was well-tolerated and effective in achieving favorable clinical and endoscopic outcomes in both AT-exposed and naïve populations, including those with exposure to UST.

ABSTRACT There are limited and conflicting data on sex and urban‐rural disparities in outcomes of patients with pulmonary embolism (PE) in the reproductive age group. Our object was to assess sex disparities in the reproductive age group cohort. All adult non‐elective admissions in the reproductive age group (18−49 years) with a primary diagnosis of PE and with no missing sex/age data were identified using the National Inpatient Sample. Females and males were stratified into rural and urban location based on hospital information. Outcomes of interest included in‐hospital mortality, complication rates, variations in management, total hospitalization costs, and length of stay. During 01/01/2016 to 12/31/2020, 180,898 PE admissions aged 18−49 years were identified (rural—12,319 [6.8%]). Females comprised 54.8% and 55.1% of the rural and urban cohorts, respectively. Overall, compared to males, females in urban and rural regions had largely comparable rates of definitive PE interventions, except lower rates of catheter directed therapy (4.7 vs. 3.6%, p < 0.001) in females admitted to urban hospitals. Despite younger age, higher comorbidity, and lower utilization of PE interventions, females in both regions had similar unadjusted in‐hospital mortality (rural 1.1% vs. 1.0%; p = 0.93 and urban 1.8% vs. 1.7%; p = 0.78) and hospitalization costs compared to males. In conclusion, females of reproductive age group had comparable in‐hospital outcomes to males in both urban and rural areas. Females in urban areas had lower utilization of advanced PE interventions, potentially indicating selective management strategies in different settings.

Purpose: To present 5 cases of alemtuzumab-induced thyroid eye disease (AI-TED) and review the literature to highlight the natural history, severity, and outcomes as compared with conventional thyroid eye disease (TED). Methods: A multi-institutional retrospective case series of patients with AI-TED was compiled. Chart review evaluated for clinical characteristics, imaging findings, and treatment for AI-TED. Additionally, a comprehensive review of the literature identified all previously published cases of AI-TED. Results: Five new patients with AI-TED were included in this series. The average clinical activity score on presentation was 2.8 (range 1–4) and reached an average peak of 5.0 during the active phase of the disease (4–7). Patients were treated medically with selenium (40%) or monoclonal antibodies including teprotumumab or tocilizumab (40%). Surgical treatment with orbital decompression for compressive optic neuropathy was performed on 2 (40%) patients. Combined with 11 previously reported cases, these 16 patients with AI-TED had an average clinical activity score on presentation of 3.3. The average length of the AI-TED phase was 14.0 months, and all patients were treated with medical and/or surgical interventions for their disease. Conclusions: Clinical and imaging findings in AI-TED mirror that of conventional TED, however, AI-TED may present with greater severity. AI-TED may develop many months after Graves’ disease; therefore, providers should be aware of this association and monitor patients for the development of severe TED.

OBJECTIVES: Administrative and clinical efforts to improve hospital mortality and intensive care utilization commonly focus on patient rescue, where deteriorating patients are systematically identified and intervened upon. Patient rescue is known to depend on hospital context inclusive of technologic environment, structural features, and hospital organizational behavioral features. With widespread adoption of electronic medical records, early warning score (EWS) systems, which assign points to clinical data elements, are increasingly promoted as a tool for timely patient rescue by referencing their prediction of patient deterioration. We describe the extent to which EWS intervention studies describe the hospital environment of the intervention—details that would be critical for hospital leaders attempting to determine the real-world utility of EWSs in their own hospitals. DATA SOURCES: We searched CINAHL, PubMed, and Scopus databases for English language EWS implementation research published between 2009 and 2021 in adult medical-surgical inpatients. STUDY SELECTION: Studies including pediatric, obstetric, psychiatric, prehospital, outpatient, step-down, or ICU patients were excluded. DATA EXTRACTION: Two investigators independently reviewed titles/abstracts for eligibility based on prespecified exclusion criteria. DATA SYNTHESIS: We identified 1,434 studies for title/abstract screening. In all, 352 studies underwent full-text review and 21 studies were summarized. The 21 studies (18 before-and-after, three randomized trials) detailed 1,107,883 patients across 54 hospitals. Twelve reported the staff composition of an EWS response team. Ten reported the proportion of surgical patients. One reported nursing ratios; none reported intensive care staffing with in-house critical-care physicians. None measured changes in bed utilization or availability. While 16 qualitatively described resources for education/technologic implementation, none estimated costs. None described workforce composition such as team stability or culture of safety in the hospitals. CONCLUSIONS: Despite hundreds of EWS-related publications, most do not report details of hospital context that would inform decisions about real-world EWS adoption. To make informed decisions about whether EWS implementation improves hospital quality, decision-makers may require alternatives such as peer networks and implementation pilots nested within local health systems.

In the last few decades, carcinogenesis has been extensively explored and substantial research has identified immunogenic involvement in various types of cancers. As a result, immune checkpoint blockers and other immune-based therapies were developed as novel immunotherapeutic strategies. However, despite being a promising therapeutic option, immunotherapy has significant constraints such as a high cost of treatment, unpredictable toxicity, and clinical outcomes. miRNAs are non-coding, small RNAs actively involved in modulating the immune system’s multiple signalling pathways by binding to the 3′-UTR of target genes. miRNAs possess a unique advantage in modulating multiple targets of either the same or different signalling pathways. Therefore, miRNA follows a ‘one drug multiple target’ hypothesis. Attempts are made to explore the therapeutic promise of miRNAs in cancer so that it can be transported from bench to bedside for successful immunotherapeutic results. Therefore, in the current manuscript, we discussed, in detail, the mechanism and role of miRNAs in different types of cancers relating to the immune system, its diagnostic and therapeutic aspect, the effect on immune escape, immune-checkpoint molecules, and the tumour microenvironment. We have also discussed the existing limitations, clinical success and the prospective use of miRNAs in cancer.

4013 Background: Intensive postoperative surveillance is associated with improved survival and recommended for patients with late stage (stage IIB & III) colon cancer. We hypothesized that stage I & IIA colon cancer patients would experience similar benefits. Methods: Secondary analysis of data from the Clinical Outcomes of Surgical Therapy trial was performed by analyzing results according to TNM stage; early (stage I & IIA; 537 patients) and late (stage IIB & III; 254 patients) stage disease. Five-year recurrence rates were higher in patients with late (35.7%) versus early stage disease (9.5%). Early and late stage salvage rates, recurrence patterns and methods of first detection were compared by χ2 test. Results: Salvage rates for early and late stage disease patients with recurrence were the same (35.9% versus 37%, p=0.9 respectively). Median survival following second surgery after recurrence was 35.8 months late stage and 51.2 months for early stage patients respectively. Sites of first recurrence did not significantly differ between late and early stage disease: liver (37.4% vs. 27.2%); lung (29.7% vs.23.6%); intraabdominal (24.2% vs.10.9%); and locoregional (12.1% vs.10.9%). Methods of first detection of recurrence were also not significantly different: CEA (37.4% vs. 29.1%); CT scan (26.4% vs. 23.6%); chest X-ray (12.1% vs. 7.3%); and colonoscopy (8.8% vs. 12.7%), for late versus early stage disease, respectively. Conclusions: Patients with early stage colon cancer have similar sites of recurrence, and receive similar benefit from post-recurrence therapy as later stage patients; implementation of existing surveillance guidelines for early stage patients is appropriate. No significant financial relationships to disclose.