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Background Vedolizumab is an anti-α4β7 integrin antibody used to treat moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD). This post hoc analysis of patient-reported outcomes (PROs) from the VISIBLE 1 (NCT02611830) and 2 (NCT02611817) phase 3 studies evaluated onset of treatment effect on patient-reported symptoms during 6-week vedolizumab induction. Methods Patient-reported stool frequency (SF) and rectal bleeding (RB) (UC Mayo score), and SF and abdominal pain (AP) in CD were collected via electronic diary from VISIBLE patients receiving one or more open-label intravenous (IV) vedolizumab induction doses (weeks 0 and 2). PRO data were analyzed using descriptive statistics. Results Data from 994 patients (UC 383, CD 611) showed mean ratings for all PROs declined consistently week-on-week from baseline through week 6, with early onset of improvement. By week 2, 22% of patients with UC reported RB improvement (≥1-point reduction in RB subscore, 7-day mean), rising to 45% by week 6. By week 6, 18% of patients with UC achieved SF improvement (SF subscore 0; 21% antitumor necrosis factor alpha [anti-TNFα] naive, 13% anti-TNFα experienced). SF improvement in patients with CD (reduction of ≥3 stools, 7-day mean) was achieved by 32% at week 6 (34% anti-TNFα naive, 30% anti-TNFα experienced). Fewer patients with CD reported severe/moderate AP at week 6 (5.1%/28.5%) than baseline (14.6%/61.5%). SF decline appeared greater and faster for anti-TNFα-naive vs. anti-TNFα-experienced patients (UC and CD). Conclusion Results indicate early onset of patient-reported UC and CD symptom improvement during vedolizumab IV induction in VISIBLE 1 and 2.

Background and objectives: Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic deposition of fat in the liver, in the absence of other secondary causes of fat buildup. The relationship between NAFLD, including alanine aminotransferase (ALT), and glycated haemoglobin (HbA1c), is important for predicting the severity of disease and prognosis. This study aims to investigate the association of HbA1c in type 2 diabetes mellitus (T2DM) patients with NAFLD via measuring the ALT levels. Materials and methods: This retrospective cross-sectional study enroled 130 patients with T2DM and NAFLD. The association between levels of HbA1c and ALT in patients of NAFLD with controlled and uncontrolled T2DM, respectively, was investigated. Stratification was done based on gender and diabetic control, using HbA1c levels as a marker of glycemic control. Serum ALT levels were also compared in both groups. Results: The mean age of the participants was 50.2±5.7 years. The total participants were 130, of which 77 (59.3%) were females and 53 (40.7%) were males. The numbers of patients having uncontrolled T2DM (HbA1c>7%), and controlled T2DM (HbA1c <7%) were 78 (60%) and 52 (40%), respectively. Moreover, 46 (35.3%) females and 32 (24.7%) males had uncontrolled T2DM, and 31 (23.8%) females and 21 (16.2%) males had controlled T2DM. The mean ALT level for uncontrolled and controlled T2DM in female patients was found to be 24.6±3.4 and 13.5±2.4, respectively, (P <0.05). For male patients, it was found to be 54.0±4.9 and 29.1±5.4, respectively (P=0.008). Conclusion: There is a positive association between elevated HbA1c and ALT levels in T2DM patients with NAFLD.

AbstractBackgroundPatients with sinonasal malignancy (SNM) present with significant sinonasal quality of life (QOL) impairment. Global sinonasal QOL as measured by the 22‐item Sinonasal Outcomes Test (SNOT‐22) has been shown to improve with treatment. This study aims to characterize SNOT‐22 subdomain outcomes in SNM.MethodsPatients diagnosed with SNM were prospectively enrolled in a multi‐center patient registry. SNOT‐22 scores were collected at the time of diagnosis and through the post‐treatment period for up to 5 years. Multivariable regression analysis was used to identify drivers of variation in SNOT‐22 subdomains.ResultsNote that 234 patients were reviewed, with a mean follow‐up of 22 months (3 months–64 months). Rhinologic, psychological, and sleep subdomains significantly improved versus baseline (all p < 0.05). Subanalysis of 40 patients with follow‐up at all timepoints showed statistically significant improvement in rhinologic, extra‐nasal, psychological, and sleep subdomains, with minimal clinically important difference met between 2 and 5 years in sleep and psychological subdomains. Adjuvant chemoradiation was associated with worse outcomes in rhinologic (adjusted odds ratio (5.22 [1.69–8.66])), extra‐nasal (2.21 [0.22–4.17]) and ear/facial (5.53 [2.10–8.91]) subdomains. Pterygopalatine fossa involvement was associated with worse outcomes in rhinologic (3.22 [0.54–5.93]) and ear/facial (2.97 [0.32–5.65]) subdomains. Positive margins (5.74 [2.17–9.29]) and surgical approach—combined versus endoscopic (3.41 [0.78–6.05])—were associated with worse psychological outcomes. Adjuvant radiation (2.28 [0.18–4.40]) was associated with worse sleep outcomes.ConclusionsSinonasal QOL improvements associated with treatment of SNM are driven by rhinologic, extra‐nasal, psychological, and sleep subdomains.

Abstract Single case studies of extraordinary disease resilience may provide therapeutic insight into conditions for which no definitive treatments exist. An otherwise healthy 35-year-old man (patient-R) with the canonical pathogenic ACVR1R206H variant and the classic congenital great toe malformation of fibrodysplasia ossificans progressiva (FOP) had extreme paucity of post-natal heterotopic ossification (HO) and nearly normal mobility. We hypothesized that patient-R lacked a sufficient post-natal inflammatory trigger for HO. A plasma biomarker survey revealed a reduction in total matrix metalloproteinase-9 (MMP-9) compared to healthy controls and individuals with quiescent FOP. Whole exome sequencing identified compound heterozygous variants in MMP-9 (c.59C &gt; T, p.A20V and c.493G &gt; A, p.D165N). Structural analysis of the D165N variant predicted both decreased MMP-9 secretion and activity that were confirmed by enzyme-linked immunosorbent assay and gelatin zymography. Further, human proinflammatory M1-like macrophages expressing either MMP-9 variant produced significantly less Activin A, an obligate ligand for HO in FOP, compared to wildtype controls. Importantly, MMP-9 inhibition by genetic, biologic, or pharmacologic means in multiple FOP mouse models abrogated trauma-induced HO, sequestered Activin A in the extracellular matrix (ECM), and induced regeneration of injured skeletal muscle. Our data suggest that MMP-9 is a druggable node linking inflammation to HO, orchestrates an existential role in the pathogenesis of FOP, and illustrates that a single patient’s clinical phenotype can reveal critical molecular mechanisms of disease that unveil novel treatment strategies.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at increased risk of developing respiratory infections. Respiratory syncytial virus (RSV) is a common respiratory virus with adverse outcomes in older adults. This study aimed to determine whether patients with IBD are at increased risk of a serious infection due to RSV. METHODS: We conducted a retrospective study using the multi-institutional research network TriNetX to assess the risk of hospitalization in a cohort of patients with IBD compared with that in a non-IBD control cohort with RSV infection from January 1, 2007, to February 27, 2023. One-to-one (1:1) propensity score matching was performed for demographic variables and RSV risk factors between the 2 cohorts. Risk was expressed as adjusted odds ratio (aOR) with 95% confidence interval (CI). RESULTS: There were 794 patients in the IBD-RSV cohort and 93,074 patients in the non–IBD-RSV cohort. The mean age of the IBD-RSV cohort was 55.6 ± 20 years, 59% were female, 80% were White, and 56.9% had Crohn's disease. The IBD-RSV cohort was at an increased risk of hospitalization (aOR 1.30, 95% CI 1.06–1.59). There was no difference in the risk (aOR 0.83, 95% CI 0.58–1.19) of a composite outcome of hospitalization-related complications between the 2 cohorts. Recent systemic corticosteroid use (<3 months) was associated with an increased risk of hospitalization (aOR 1.86, 95% CI 1.30–2.59) in the IBD-RSV cohort. DISCUSSION: We found that adult patients with IBD and RSV infection are at an increased risk of hospitalization and may benefit from the new RSV vaccine recommended for adults aged 60 years and older.

Abstract Background and Aims Previously published long-term safety data reported a favourable ustekinumab safety profile for the treatment of inflammatory bowel disease [IBD]. We present the final cumulative safety data from pooled ustekinumab IBD phase 2/3 clinical studies through 5 years in Crohn’s disease [CD] and 4 years in ulcerative colitis [UC]. Methods In phase 3 studies, patients received a single intravenous placebo or ustekinumab [130 mg or ~6 mg/kg] induction dose followed by subcutaneous maintenance doses of placebo or ustekinumab [90 mg q8w or q12w]. Analyses included all patients who received one dose of study treatment and included patients who were biologic-naïve and patients with a history of biologic failure. Safety outcomes are summarized and presented using number of events per 100 patient-years of follow-up and corresponding 95% confidence intervals. Results In this final pooled safety analysis, 2575 patients were treated with ustekinumab with 4826 patient-years of follow-up. Rates of key safety events, including major adverse cardiac events and malignancies, were similar between placebo and ustekinumab or not higher for ustekinumab. Opportunistic infections, including tuberculosis, and malignancies were reported infrequently. Rates of key safety events in the IBD group were no higher in the ustekinumab group than in the placebo group for both patients who were biologic-naïve or who had a history of biologic failure. No lymphomas or cases of posterior reversible encephalopathy syndrome [formerly known as reversible posterior leukoencephalopathy syndrome] were reported. Conclusion The final cumulative ustekinumab safety data through 5 years in CD and 4 years in UC demonstrated favourable safety compared to placebo and continue to support the well-established safety profile across all approved indications. Clinical trials.gov numbers NCT00265122, NCT00771667, NCT01369329, NCT01369342, NCT01369355, NCT02407236

Abstract Photogrammetry scans has directed attention to the development of advanced camera systems to improve the creation of three-dimensional (3D) models, especially for educational and medical-related purposes. This could be a potential cost-effective method for neuroanatomy education, especially when access to laboratory-based learning is limited. The aim of this study was to describe a new photogrammetry system based on a 5 Digital Single-Lens Reflex (DSLR) cameras setup to optimize accuracy of neuroanatomical 3D models. One formalin-fixed brain and specimen and one dry skull were used for dissections and scanning using the photogrammetry technique. After each dissection, the specimens were placed inside a new MedCreator® scanner (MedReality, Thyng, Chicago, IL) to be scanned with the final 3D model being displayed on SketchFab® (Epic, Cary, NC) and MedReality® platforms. The scanner consisted of 5 cameras arranged vertically facing the specimen, which was positioned on a platform in the center of the scanner. The new multi-camera system contains automated software packages, which allowed for quick rendering and creation of a high-quality 3D models. Following uploading the 3D models to the SketchFab® and MedReality® platforms for display, the models can be freely manipulated in various angles and magnifications in any devices free of charge for users. Therefore, photogrammetry scans with this new multi-camera system have the potential to enhance the accuracy and resolution of the 3D models, along with shortening creation time of the models. This system can serve as an important tool to optimize neuroanatomy education and ultimately, improve patient outcomes.

TPS714 Background: 1st-line induction platinum-based chemotherapy followed by switch maintenance Av is the current preferred standard of care in patients (pts) with aUC who do not progress after platinum-based chemotherapy. There is an significant need to further improve outcomes by combining Av with an effective, non-cross resistant therapy with non-overlapping toxicity. CABO is an oral inhibitor of MET, VEGFR and TAM family receptors involved in tumor growth, angiogenesis and immune cell regulation and has shown efficacy in UC in combination with PD-1/PD-1L1 inhibitor. We hypothesized that CABO-Av combination would improve survival vs Av alone and have an acceptable safety profile as switch maintenance therapy in mUC. Methods: MAIN-CAV is a phase III randomized, multicenter, international trial for pts with locally advanced/metastatic UC (including cN3M0 only)) who do not progress after 4-6 cycles of any platinum-based chemotherapy (gem-cis, gem-carbo, MVAC or ddMVAC). 654 adults are randomized 1:1 within 3-10 weeks (wk) after last dose of chemotherapy to receive Av 800 mg IV every 2 wk or Av and CABO 40 mg daily for up to 2 yrs. Key eligibility criteria include ECOG PS 0-1, no prior use of anti-PD(L)1, no CNS metastases, no major surgery within 4 wks, no uncontrolled hypertension or cardiovascular disorders. Pts are stratified based on 1) best response to 1L chemotherapy: complete vs partial response vs stable disease and 2) presence vs absence of visceral metastases. The primary endpoint is overall survival (OS) with assumptions of 1-sided alpha 0.025, power 80%, median OS 21 months (mo) with Av and hazard ratio 0.75, thus hypothesizing median OS 28 mo on CABO-Av. Key secondary endpoints include progression-free survival, safety, tolerability, and efficacy of CABO-Av vs Av alone based on RECIST 1.1 and iRECIST criteria (and PD-L1 status).Quality of life (QOL) are assessed using EQ-5D-5L, PROMIS-Fatigue 4a, EORTC QLQ-C30, EORTC QLQ-BLM30 between pts on CABO-Av vs Av alone. Biomarkers of response and resistance to Av will be assessed using baseline archival tissues, baseline and serial blood, ctDNA, stool and urine. Imaging studies will test the correlation of established and new radiomic signatures with survival, adverse events and QOL and incorporate both radiologic and biologic features to assess their potential association with outcomes. This trial would be the first to systematically address whether adding the multitargeted TKI, CABO, to Av improves survival vs Av alone as 1L maintenance therapy. https://acknowledgments.alliancefound.org . Support: U10CA180821, U10CA180882; U24CA196171, U10CA180863 (CCTG); Clinical trial information: NCT05092958 .