Real-world Cohort Of Patients Research Articles

Treatment of Acute Myocardial Infarction and Cardiogenic Shock: Outcomes of the RECOVER III Postapproval Study by Society of Cardiovascular Angiography and Interventions Shock Stage.

The Society for Cardiovascular Angiography and Interventions proposed a staging system (A-E) to predict prognosis in cardiogenic shock. Herein, we report clinical outcomes of the RECOVER III study for the first time, according to Society for Cardiovascular Angiography and Interventions shock classification. The RECOVER III study is an observational, prospective, multicenter, single-arm, postapproval study of patients with acute myocardial infarction with cardiogenic shock undergoing percutaneous coronary intervention with Impella support. Patients enrolled in the RECOVER III study were assigned a baseline Society for Cardiovascular Angiography and Interventions shock stage. Staging was then repeated within 24 hours after initiation of Impella. Kaplan-Meier survival curve analyses were conducted to assess survival across Society for Cardiovascular Angiography and Interventions shock stages at both time points. At baseline assessment, 16.5%, 11.4%, and 72.2% were classified as stage C, D, and E, respectively. At ≤24-hour assessment, 26.4%, 33.2%, and 40.0% were classified as stage C, D, and E, respectively. Thirty-day survival among patients with stage C, D, and E shock at baseline was 59.7%, 56.5%, and 42.9%, respectively (P=0.003). Survival among patients with stage C, D, and E shock at ≤24 hours was 65.7%, 52.1%, and 29.5%, respectively (P<0.001). After multivariable analysis of impact of shock stage classifications at baseline and ≤24 hours, only stage E classification at ≤24 hours was a significant predictor of mortality (odds ratio, 4.8; P<0.001). In a real-world cohort of patients with acute myocardial infarction with cardiogenic shock undergoing percutaneous coronary intervention with Impella support, only stage E classification at ≤24 hours was significantly predictive of mortality, suggesting that response to therapy may be more important than clinical severity of shock at presentation.

REAL WORLD EFFECTIVENESS OF JAK INHIBITOR UPADACITINIB IN ULCERATIVE COLITIS VERSUS CROHN’S DISEASE IN AN IBD TERTIARY CARE CENTER

Abstract BACKGROUND Upadacitinib is a selective Janus kinase inhibitor approved for the management of Crohn’s Disease (CD) and Ulcerative Colitis (UC). AIMS To compare response to upadacitinib between patients with UC and CD in a real world tertiary care center. METHODS Retrospective cohort study of adult patients with CD vs UC seen at UCSF Colitis and Crohn’s Disease Center from 2019-2023. The primary outcome was endoscopic remission as noted in post-induction staging scope. Endoscopic remission was assessed using SES-CD and Mayo scores for CD and UC, respectively. Outcomes were assessed at 3 or 6 months after starting upadacitinib for UC and CD, respectively. Failure was considered failure to meet remission criteria, change in medications shortly after induction, or surgery. RESULTS A total of 60 patients were reviewed, 26 with Crohn’s Disease and 34 with Ulcerative Colitis, who had taken Upadacitinib and had post-induction follow up data in EHR review. 10 patients with CD achieved remission (38.5%) compared to 17 patients with UC (50%). This difference was found to be nonsignificant (P=0.38). CONCLUSION In this real-world cohort of IBD patients seen at a tertiary care center, there was no significant difference in response between patients with CD or UC.

P893 Transition from intravenous to subcutaneous infliximab: effectiveness in a cohort of patients with inflammatory bowel disease

Abstract Background Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), is a group of chronic inflammatory disorders. Biologics are indicated for patients failing conventional maintenance therapy with moderate to severe activity. Different routes of administration, intravenous (IV), subcutaneous (SC) or oral have been approved. For chronic diseases such as IBD, some patients may prefer self-administered SC dosing to IV dosing as a less time-intensive and more convenient treatment option. This study aims to evaluate evaluate the success of infliximab subcutaneous administration after switching from intravenous administration in IBD patients. Methods The transition from IV to SC administration was proposed to 60 IBD patients in clinical remission. Data on medical history and laboratory tests were collected from electronic health records. Moreover, patients filled a paper questionnaire 8 weeks after the switch focused on the level of satisfaction and onset of adverse event (AE). Results Overall 60 patients were enrolled for switching from IV to SC therapy. Most of patients (&amp;gt;80%) did not experience any difficulties in handling the device and respected the correct time-table of administration. The switch was a complete success in 50 out of 60 patients (83.3%). Ten patients stopped subcutaneous formulation: five of these switched back to intravenous formulation for adverse event or patient’s preference, four swap or swop to other therapy and one withdraw from biologic. No predictor of loss of response was found at multivariate analysis. Faecal calprotectin and C-reactive protein values significantly improve after the switch at 3, 6 and 12 months (p= 0.03, p= 0.004, p = 0.01 and p= 0.06, p= 0.001, p= 0.007 respectively). About 16.7 % of patients had at least one side effect after switching. Local pain and swelling at site of injection were the most common AEs. The vast majority of AE were mild and lasted only a few days. No serious AEs were reported and no patient was hospitalized. Conclusion Effectiveness of switching from intravenous to subcutaneous infliximab administration in IBD patients is confirmed in our real world cohort of patients.

P326 Impact of disease flares on resource use, health-related quality of life and productivity in untreated Crohn’s Disease patients in US: an analysis of national health and wellness survey data

Abstract Background Patients with Crohn’s Disease (CD) alternate periods of exacerbation, flares, and periods of remission. The periods of flares can be debilitating to patients causing significant discomfort impacting the patient’s health-related quality of life (HRQoL). Despite symptoms, many patients do not receive treatments for their condition thus our objective was to describe the burden related to healthcare resource utilization (HRU), HRQoL and work productivity among a real-world cohort of patients who are not receiving any prescribed medications for CD. Methods The 2019 National Health and Wellness US Survey (NHWS) data was analyzed. NHWS is a self-administered Institutional review board (IRB) approved, internet-based annual survey that assesses numerous health conditions, demographic characteristics, medical history, healthcare utilization, attitudes, and outcomes. Respondents currently not taking prescription treatment for CD were categorized by flare frequency as infrequent (0-2 flares/year), intermediate (3-6/year), and frequent (&amp;gt;1/month to &amp;lt;7/week). HRU included HCP visits, gastroenterologist visits, emergency room (ER) visits and hospitalizations. HRQoL was assessed using the 5-dimension EuroQoL questionnaire (EQ5D), and work activity impairment using the Work Productivity and Activity Impairment questionnaire. Results A total of 74,994 respondents participated in the survey, of whom 577 reported being diagnosed with CD and 231 (40.0%) of whom were not taking prescription treatment for CD. Fifty-six percent of the untreated sample reported having mild disease. Among the untreated patients, 37% reported infrequent, 21% intermediate and 42% frequent flares. The mean age of patients with frequent flares was lower than those with infrequent or intermediate flares (infrequent: 51 years; intermediate: 45 years; frequent: 41 years). The mean EQ5D summary score decreased as the frequency of flares increased (infrequent: 0.77, intermediate: 0.66 and frequent: 0.63). Patients with frequent flares had higher gastroenterologists, ER and hospitalization rates compared to patient with infrequent of intermediate flares (Table 1). Overall work impairment was reported by 40%, 52% and 63% of patients with infrequent, intermediate, and frequent flares respectively (Figure 1). Conclusion This real-world analysis shows up to two-thirds of untreated CD patients present intermediate or frequent flares. In addition, those with frequent flares experienced poorer HRQoL, lower work productivity, and had higher healthcare resource use. This study reveals a high level of disease burden in patients who are not receiving treatment, the majority of whom reported to have ‘mild’ disease.

P1072 Upadacitinib appears effective in inducing clinical, biochemical, endoscopic and histologic improvements in previously treatment refractory Ulcerative Colitis

Abstract Background Upadacitinib is a novel, oral agent which acts by inhibition of JAK signaling. It has proven efficacy in large-scale, randomised trials for the treatment of UC. We report our real-world experience of upadacitinib as induction therapy in a single centre study of UC patients, including patients who were refractory or intolerant of other advanced therapies. Methods We performed a retrospective analysis of outcomes in patients who were commenced on upadacitinib for UC at a tertiary IBD centre between October 2022 to October 2023. The parameters used to assess disease activity were the Simple Clinical Colitis Activity Index (SCCAI), faecal calprotectin (FCP), Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Nancy Histological Index (NHI). Clinical response was defined as a reduction of SCCAI of ≥3 points, clinical remission as SCCAI of ≤2, biochemical remission as FC&amp;lt;150ug/g. Endoscopic remission was defined as UCEIS 0-1 and histological remission as NHI 0-1. Medical records were reviewed for patient-reported adverse events. Wilcoxon matched-pairs signed rank test was used to compare pre- and post-treatment continuous variables. Results 42 patients were started on 45mg once daily upadacitinib over this period. 20 were female, the mean age was 39. 31 had left sided disease, 8 had pancolitis. 39 (93%) patients had prior experience of advanced therapy and 22 (52%) had ≥2 prior therapies. At baseline, mean SCCAI was 7 (1-15), and mean FCP 1328 (42-6810) μg/g. Baseline endoscopy demonstrated a mean UCEIS of 5 (3-7) and baseline histology a mean NHI of 3 (1-4). At the 6-week follow up, paired data on clinical and biochemical responses were available in 23 and 27 patients respectively, showing an improvement to a mean SCCAI of 3 (p=0.0004) and mean FCP of 491 μg/g (p=0.002). 16 (70%) achieved clinical response, 14 (61%) were in clinical remission. 15 (56%) had a reduction in FCP to &amp;lt;150 μg/g. Endoscopic reevaluation took place after a minimum of 12 weeks on treatment. Paired endoscopic outcomes in 20 patients demonstrated an improvement of UCEIS to a mean of 1 (p&amp;lt;0.0001), with 16 (80%) patients in endoscopic remission. Week 12 histology showed improvement to a mean NHI of 2 (p&amp;lt;0.0001, n=19), with 9 (47%) patients achieving histological remission. 6 (14%) patients were non-responders. 3 required a colectomy, 2 necessitated a switch in medical therapy, 1 remained on extended induction. 3 patients (7%) reported facial acne as an adverse event, no others were reported. Conclusion Upadacitinib appears effective at inducing significant clinical, biochemical, endoscopic and histological improvements within 12 weeks, amongst a real-world cohort of patients with moderate-to-severe UC that has proved refractory to other advanced therapies.

P905 Symptomatic remission and IUS improvements in a multi-national real-world cohort of UC patients treated with Upadacitinib - First results from the IBD-DACH study EUROPE

Abstract Background Upadacitinib (UPA) is an oral, reversible and selective Januskinase-inhibitor (JAKi) that was approved for the treatment of several immune-mediated inflammatory diseases, including moderate to severe ulcerative colitis (UC) (1). While the efficacy of UPA has been demonstrated in clinical trials in UC, real-word (RW) evidence on the effectiveness and safety of UPA in UC remains scarce (2). Here, we shed light on the clinical and sonographic results after 2 and 8 weeks of UPA induction in a large, multinational RW cohort of UC patients. Methods EUROPE is an ongoing, prospective, non-interventional, multi-country study in patients with active UC who initiate therapy with UPA. The study assesses the early clinical effectiveness and the predictive value of early disease improvements including sonographic parameters for the long-term outcome after 52 and 104 weeks. For this interim analysis, we report clinical and sonographic results at baseline (BL), week 2 (2W) and week 8 (8W) of 124 UC patients with a visit after 8W until August 2023. For 75 patients, sonographic BL data for the most affected bowel segment was available. Results Of the 124 UC patients, most were male (60.5%, n = 75) with a median age and disease duration of 37.5 years (27.5 – 50.9) and 6.58 years (2.40–12.13). Almost half of all patients had a pancolitis (48.4%, n = 60) The vast majority of patients was bio-experienced (85.5%, n = 106), a third had been exposed to ≥ 3 biologicals (28.2%, n = 35). At BL, patients had a median bowel wall thickness (BWT) of 5.0 mm (3.8-7.0) in the sigmoid colon. It was the most affected segment in 44.4% of patients (n = 55). Disease activity per paMayo score was 3.0 (2.0-5.0) points, with 72.6% (n = 90) and 38.8% (n = 48) of patients reporting ≥ 3 more stools than usual/day and blood in most stools or bleeding without stool, respectively. At 2W after UPA induction, stool frequency and rectal bleeding substantially improved as reflected by the rate of patients in symptomatic remission significantly increasing from 16.9% (n = 21) at BL to 43.5% (n = 54) at 2W and to 64.5% (n = 80) at W8 (both p &amp;lt; 0.001 vs. BL, fig.1). BWT was reduced significantly as early as 2W (n = 48; p &amp;lt; 0.001) and was ≤ 3mm in more than half of all patients. Considering the overall population, 156 patients were included in the safety analysis. Of these, 23.7% (n = 37) experienced an adverse event of which most were non-serious. Conclusion In this first interim analysis of the EUROPE study, UPA treatment in UC was associated with early clinical and sonographic improvement, with most patients achieving symptomatic remission and/or normalization of BWT by week 8 of treatment. 1-SmPC Upadacitinib 2-Danese, Vermeire et al. Lancet. 2022 Jun 4;399(10341):2113-2128

P718 Observational real-world evidence on the efficacy and safety of Janus Kinase inhibitors (JAKi) in the treatment of moderate to severe Active Ulcerative Colitis (UC)

Abstract Background Janus kinase inhibitors (JAKi) are the first orally administered treatment for Ulcerative Colitis (UC). The JAK family comprises of four intracellular tyrosine kinases inhibitors (JAK1, JAK2, JAK3 and Tyrosine Kinase 2). Inhibition of the JAK kinases lead to dampening of the inflammatory cytokines which drive Inflammatory Bowel Disease (IBD). Tofacitinib was the first generation pan-JAKi. This was followed by second generation JAKi: Filgotinib and Upadacinib which preferentially inhibit JAK1. We report on the real-world evidence on the efficacy and safety of JAKi in the treatment of UC in a tertiary IBD treatment centre. Methods Patients attending the IBD clinic at weeks 8-12 of initiation of therapy were included. Baseline demographics, disease activity and previous therapies were recorded. Clinical response was measured using the SCCAI and biochemical response was measured using calprotectin and CRP. We defined clinical response as ≥3 points reduction from baseline SCCAI, and clinical remission as SCCAI Score of &amp;lt;2.5, and / or biochemical remission as a CRP of less than 5 mg/L and a calprotectin level of &amp;lt; 250 mg/g. We also assessed treatment persistence, and the reasons for treatment cessation. Results The UC populations are shown in Table 1. 52 patients were included and an additional 24 patients who discontinued therapy early on were assessed to review secondary outcomes. Table 1 summarises the comparative outcomes of the JAKi. 81% and 63% of patients achieved clinical and biochemical remission respectively. Overall, 31% discontinued treatment due to lack of efficacy or adverse events. 60% of patients reported adverse events (AEs), 25 % of patients discontinued treatment due to AEs and 84% of patients continued treatment despite reporting AEs. The most common AEs were hypercholesteremia and cold and flu like symptoms and the most common AEs related with treatment discontinuation were recurrent infection or persistent deranged liver functions contributed to patients’ history of primary sclerosing cholangitis. No Serious Adverse Events were reported. 60% of patients on tofacitinib developed side effects and persisted with therapy, which included hypercholesteremia (67%), shingles (11%), flu like symptom (11%) and hair loss (11%). 53% had side effects with Filgotinib; hypercholesteremia (25%), cold like symptoms (25%), chest infection (13%), shingles (13%), acne (13%). 68% developed side effects with Upadacitinib; reports of acne (20%), cold and flu (33%), shingles and mood swings (7%) and high cholesterol (67%). Conclusion In this real-world cohort of UC patients, JAKi was effective in inducing remission and had an acceptable safety profile. The observed safety profile was as expected compared to clinical data results.

P698 Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentre Real-World Observational Study

Abstract Background Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicentre cohort of Brazilian patients with UC. Methods We conducted a multicentre retrospective observational cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of zero) within one year from baseline. Secondary endpoints included clinical response between weeks 12-16, endoscopic response within one year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety. Results A total of 50 patients were included (female, n=36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n=38, 76.0%), and 43 (86.0%) were steroid-dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n=31; vedolizumab [VDZ], n=27). The co-primary endpoints of clinical remission and endoscopic remission at 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 67.4%, and 50.0%, respectively. The UST treatment persistence rates at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and three patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-six adverse events (AEs) were reported, 15 of which were considered as serious AEs. Conclusion This is the first real-world experience study to report the effectiveness and safety of UST specifically in a Latin American population. In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.

P1232 Alterations in microbial composition in patients with newly diagnosed Crohn's disease over a course of one year: data from a prospective longitudinal real-world study

Abstract Background Gut microbial composition in Crohn's disease (CD) is variable, changing with specific interventions. We aimed to explore the dynamics in microbial alterations in a cohort of patients with newly diagnosed Crohn's disease (ndCD) over one year. Methods This was a prospective longitudinal real-world study of patients with ndCD1 naïve to therapy who were treated at the physician's discretion. Clinical outcomes at one year were corticosteroid-free clinical remission (CSFR) and biochemical remission ([BR], CRP&amp;lt;1mg/dL and FC&amp;lt;150ug/g). We sequenced paired stool samples from diagnosis and after one year using 16S rRNA gene (V4) and analyzed changes in diversity and dysbiosis indices. A linear mixed-effect model was constructed to identify factors associated with microbial alterations and to identify specific genera that drove the alterations while controlling for confounders. Results Seventy-five patients completed one-year follow-up (49.3% female, median age 27 years [IQR 22-38.5], therapeutic interventions: 45 patients on biological therapies [43 anti-TNF], 26 antibiotics, 10 corticosteroids, 5 underwent surgery, and 59 various nutritional interventions). Rates of CSFR, BR, and conjoined CSFR-BR at one-year post-diagnosis were 64%, 56%, and 45.3%, respectively. We observed an overall significant increase in microbial Shannon diversity (H index), p&amp;lt;0.001, and decreased microbial dysbiosis index (MDI), p=0.007, from baseline to one year. On subgroup analysis, these alterations were significant among patients who achieved the clinical outcomes (all p&amp;lt;0.05) and even more prominent among patients who were on biological therapies (both indices p&amp;lt;0.001). Notably, in the biological therapy subgroup, the microbial composition at diagnosis was less diverse and more dysbiotic than in the non-biological subgroup. In the latter, microbial composition at diagnosis was less disrupted and remained relatively stable over time. Linear mixed model analysis corroborated a positive association between biological therapy and the positive dynamics in microbial indices (H-index, p=0.020 and MDI, p=0.040). Fifteen specific genera drove the microbial alterations over time (Table 1), while alterations in the relative abundance of some genera correlated with changes in clinical biomarkers and clinical indices (Figure 1). Conclusion The microbial composition of this real-world cohort of patients with ndCD improved over the course of one year, which was significant for patients who achieved clinical outcomes and was more prominent for patients requiring biological therapy. In this subgroup, the microbial signature was less diverse and more dysbiotic when diagnosed; this likely led the significant improvement over time. 1 Yanai H,et al. Crohns Colitis 360 2023;5:otad064

External validation of the ARCAD nomogram in a real-world cohort of patients with stage IV colorectal cancer (CRC).

38 Background: The ARCAD CRC nomogram is designed to predict 1-yr survival in stage 4 CRC to assist with prognostication (Sjoquist, JNCI, 2018). However, this nomogram was developed using patients (pts) enrolled in clinical trials. We sought to externally validate these data in a real-world cohort. Methods: We used the Flatiron database from nationwide records collected from 2013-2020 to create a retrospective Flatiron real-world cohort (FRWC) of pts with histologically confirmed stage 4 CRC. Pts with baseline blood tests prior to treatment (Tx) who had received at least 1 line of Tx were included. Missing data (&lt;8.5%) were imputed using R package MissForest. A multivariable Cox proportional hazards model for overall survival (OS) was applied to fit the reduced model derived from the published ARCAD nomogram as variables from the full model such as number and sites of metastasis were unavailable in Flatiron. The C-index was used to validate the fitted models. The area under a time-dependent ROC (AUROC) analysis was applied to indicate the model prediction performance. Results: A total of 9710 pts, 5740 of whom were deceased were analyzed. The FRWC was older (64 vs 61) and had a poorer ECOG-PS (2+ 14.7% vs 4.2%) compared to the ARCAD. A reduced ARCAD nomogram was derived from the full model (Table). The reduced nomogram calibration was as good as the full model (C-index 0.67 vs 0.68). The 1-yr OS prediction in FRWC using the reduced ARCAD nomogram was good with an AUROC of 0.74. The predictive and observed 1-yr OS using the reduced ARCAD nomogram in the FRWC was 0.640 (95% CI 0.637, 0.644) and 0.727 (95% CI 0.718,0.736). Conclusions: The ARCAD nomogram was validated in the very large FRWC. The observed underestimation of survival by the ARCAD nomogram in the FRWC is likely due to recent advances in Tx options for CRC including targeted- or immunotherapy as the FRWC is more recent compared to pts enrolled in the ARCAD cohort (1997-2012). Our findings indicate that the ARCAD nomogram is a promising decision-making tool for clinicians to predict 1-yr OS in real-world populations. [Table: see text]

Racial/ethnic disparities in the effectiveness of atezolizumab plus bevacizumab (A+B) vs. tyrosine kinase inhibitors (TKIs) among veterans with unresectable hepatocellular carcinoma (uHCC).

448 Background: The etiology of liver disease and HCC often differs by race and ethnicity, which may lead to potential differential effectiveness of immunotherapy (IO) by race/ethnicity. However, clinical trials for HCC have historically had limited racial diversity. Emerging data has characterized the real-world effectiveness of A+B, the standard of care for first-line (1L) uHCC. This study assessed whether there is racial/ethnic difference in the effectiveness of A+B compared to TKIs, including sorafenib (S) or lenvatinib (L). Methods: A population-based retrospective analysis was conducted using data from the Veterans Health Administration (VHA) Data Warehouse. Non-Hispanic White, African American (AA), and Hispanic patients diagnosed with uHCC between 2017 and 2022 who initiated 1L A+B (on or after 2020), S, or L were selected. Kaplan-Meier analyses and multivariable Cox regression analysis with race/ethnicity as a treatment modifier (adjusting for age, region, extrahepatic metastases, etiology, presence of cirrhosis, comorbidity index, prior local therapies, Child-Pugh [CP] class, and Albumin-Bilirubin [ABLI] grades) were conducted to investigate the racial/ethnic differences in the effectiveness of A+B vs S or L. Results: Of 1,738 patients, 1,140 were White (20% A+B, 56% S, 24% L), 437 were AA (25% A+B, 50% S, 25% L), and 161 were Hispanic (22% A+B, 57% S, 21% L). Compared to Whites, a significantly higher proportion of AAs had underlying hepatitis C (87% vs 56%, p&lt;0.05). There was a trend towards a lower proportion of CP B and C and less ascites in AAs compared to Whites. Table shows median OS (mOS) by race and regimen, along with hazard ratios (HRs) from the multivariate analysis. The survival benefit associated with A+B compared with S or L was numerically greater in AA patients versus White patients, although the difference did not achieve statistical significance. Conclusions: In this real-world cohort of 1L uHCC patients, A+B demonstrated a significant survival advantage over TKIs across racial/ethnic groups. Understanding the factors contributing to the effectiveness of A+B across racial/ethnic groups could provide valuable insights for guiding future trials and initiatives aimed at addressing racial disparities in HCC. [Table: see text]

Real-world adoption of 3 months of adjuvant oxaliplatin chemotherapy in patients with stage III colorectal cancer (CRC).

83 Background: Based on the IDEA analysis, 3 months (mos) of adjuvant chemotherapy (ACT) with CAPOX has emerged as an option for both low-risk and high-risk stage III CRC. This has resource utilization, cost and toxicity benefits (particularly less neurotoxicity) without compromising efficacy. This study examines the patterns of uptake of CAPOX vs FOLFOX and duration of ACT in a contemporary post-COVID real-world cohort of patients (pts) in the province of British Columbia (BC), Canada. Methods: The provincial pharmacy database was used to identify pts with resected stage III CRC who received adjuvant CAPOX or FOLFOX between January 2021 and December 2022. Pts with rectal cancer requiring neoadjuvant chemotherapy or radiotherapy were excluded. Demographic, tumor, and treatment information was collected. “High-risk features” were defined as pT4 or pN2 tumors. “Urban” setting was defined based on the population size of the regional health authority. Descriptive statistical analyses were performed to examine baseline characteristics and Fisher’s exact test was used to examine univariate associations. Results: 452 pts were included, of which 234 (52%) and 218 (48%) were planned to receive 3 and 6 mos of ACT respectively (see table). Within the 3 mos group, 226 (97%) received CAPOX. Within the 6 mos group, there was a 51%/49% split between CAPOX/FOLFOX. By univariate analysis, factors associated with 3 mos of CAPOX vs 6 mos of ACT were age &gt;70y (P=0.039), low/intermediate grade (P=0.005) and low-risk stage III disease (P&lt;0.0001). 29% of pts planned for 6 mos of oxaliplatin ACT had low-risk disease, with 52% of these receiving CAPOX. Conclusions: 3 mos of adjuvant CAPOX is an accepted option for nearly all pts with stage III disease with consequent less neurotoxicity and fewer treatment visits. Yet, in this contemporary cohort, use of 3 mos of adjuvant CAPOX remains low and is associated with older age and low-risk disease. 6 mos of oxaliplatin is still being offered to pts with low-risk disease. Exploration of patient preferences, real-world treatment and time toxicities, and resource costs may improve more widespread adoption of 3 mos of adjuvant CAPOX in stage III CRC. [Table: see text]

Repeat thrombectomy after large vessel re-occlusion: a propensity score matched analysis of technical and clinical outcomes

BackgroundEndovascular thrombectomy (EVT) remains the standard of care for acute large vessel occlusion (LVO) stroke. However, the safety and efficacy of repeat thrombectomy (rEVT) in recurrent LVO remains unclear. This...

Real-world Effectiveness and Safety of Risankizumab in Patients with Moderate to Severe Multirefractory Crohn's Disease: A Belgian Multicentric Cohort Study.

As real-world data on risankizumab in patients with moderate to severe Crohn's disease (CD) are scarce, we evaluated its effectiveness and safety in multirefractory Belgian patients. Data from consecutive adult CD patients who started risankizumab before April 2023 were retrospectively collected at 6 Belgian centers. Clinical remission and response were defined using the 2-component patient-reported outcome. Endoscopic response was defined as a decrease in baseline Simple Endoscopic Score with ≥50%. Both effectiveness end points were evaluated at week 24 and/or 52, while surgery-free survival and safety were assessed throughout follow-up. A total of 69 patients (56.5% female, median age 37.2 years, 85.5% exposed to ≥4 different advanced therapies and 98.6% to ustekinumab, 14 with an ostomy) were included. At week 24, 61.8% (34 of 55) and 18.2% (10 of 55) of patients without an ostomy achieved steroid-free clinical response and remission, respectively. At week 52, these numbers were 58.2% (32 of 55) and 27.3% (15 of 55), respectively. Endoscopic data were available in 32 patients, of whom 50.0% (16 of 32) reached endoscopic response within the first 52 weeks. Results in patients with an ostomy were similar (steroid-free clinical response and remission, 42.9% and 14.3%, respectively). During a median follow-up of 68.3 weeks, 18.8% (13 of 69) of patients discontinued risankizumab, and 20.3% (14 of 69) of patients underwent CD-related intestinal resections. The estimated surgery-free survival at week 52 was 75.2%. No new safety issues were observed. In this real-world cohort of multirefractory CD patients, risankizumab was effective in inducing both clinical remission and endoscopic response. Risankizumab was well tolerated with no safety issues.

The frequency of gene variant reclassification and its impact on clinical management in the inherited arrhythmia clinic

BackgroundGenetic testing in the inherited arrhythmia clinic informs risk stratification, clinical management, and family screening. Periodic review of variant classification is recommended as supporting evidence accrues over time. However, there is limited reporting of real-world data on the frequency and impact of variant reclassification. ObjectiveThe purpose of this study was to determine the burden of variant reclassification in our inherited arrhythmia clinic and the impact on clinical management. MethodsGenetic testing reports for patients referred to our clinic from 2004–2020 were reviewed. Reported variants were reinvestigated using ClinVar, VarSome, and a literature review. Classification was updated using the American College of Medical Genetics and Genomics (ACMG) criteria and tested for association with arrhythmic events and modification of medical management. ResultsWe identified 517 patients (median age 37 years) who underwent gene panel testing. A variant of uncertain significance (VUS) was reported for 94 patients (18.2%) and more commonly identified when using large gene panels (P <.001). A total of 28 of 87 unique VUSs (32.2%) were reclassified to pathogenic/likely pathogenic (n = 11) or benign/likely benign (n = 17). Of 138 originally reported pathogenic variants, 7 (5.1%) lacked support using ACMG criteria. Variant reclassification was not associated with arrhythmic events; however, it did impact genotype-specific counseling and future therapeutic options. ConclusionIn our large real-world patient cohort, we identify a clinically important proportion of both pathogenic variants and VUSs with evidence for reclassification. These findings highlight the need for informed pretest counseling, a regular structured review of variants reported in genetic testing, and the potential benefits to patients for supporting genotype-guided therapy.

Salt sensitivity risk derived from nocturnal dipping and 24-h heart rate predicts long-term blood pressure reduction following renal denervation.

Renal denervation (RDN) has been consistently shown in recent sham-controlled clinical trials to reduce blood pressure (BP). Salt sensitivity is a critical factor in hypertension pathogenesis, but cumbersome to assess by gold-standard methodology. Twenty-four-hour average heart rate (HR) and mean arterial pressure (MAP) dipping, taken by ambulatory blood pressure monitoring (ABPM), stratifies patients into high, moderate, and low salt sensitivity index (SSI) risk categories. We aimed to assess whether ABPM-derived SSI risk could predict the systolic blood pressure reduction at long-term follow-up in a real-world RDN patient cohort. Sixty participants had repeat ABPM as part of a renal denervation long-term follow-up. Average time since RDN was 8.9 ± 1.2 years. Based on baseline ABPM, participants were stratified into low (HR < 70 bpm and MAP dipping > 10%), moderate (HR ≥70 bpm or MAP dipping ≤ 10%), and high (HR ≥ 70 bpm and MAP dipping ≤ 10%) SSI risk groups, respectively. One-way ANOVA indicated a significant treatment effect ( P = 0.03) between low ( n = 15), moderate ( n = 35), and high ( n = 10) SSI risk with systolic BP reduction of 9.6 ± 3.7 mmHg, 8.4 ± 3.5 mmHg, and 28.2 ± 9.6 mmHg, respectively. Baseline BP was not significantly different between SSI Risk groups ( P = 0.18). High SSI risk independently correlated with systolic BP reduction ( P = 0.02). Our investigation indicates that SSI risk may be a simple and accessible measure for predicting the BP response to RDN. However, the influence of pharmacological therapy on these participants is an important extraneous variable requiring testing in prospective or drug naive RDN cohorts.

Characteristics and outcomes of patients with tricuspid regurgitation and advanced heart failure.

To evaluate the role of tricuspid regurgitation in advanced heart failure. The multicenter observational HELP-HF registry enrolled consecutive patients with heart failure and at least one 'I NEED HELP' criterion evaluated at four Italian centers between January 2020 and November 2021. Patients with no data on tricuspid regurgitation and/or receiving tricuspid valve intervention during follow-up were excluded. The population was stratified by no/mild tricuspid regurgitation vs. moderate tricuspid regurgitation vs. severe tricuspid regurgitation. Variables independently associated with tricuspid regurgitation, as well as the association between tricuspid regurgitation and clinical outcomes were investigated. The primary outcome was all-cause mortality. Among the 1085 patients included in this study, 508 (46.8%) had no/mild tricuspid regurgitation, 373 (34.4%) had moderate tricuspid regurgitation and 204 (18.8%) had severe tricuspid regurgitation. History of atrial fibrillation, any prior valve surgery, high dose of furosemide, preserved left ventricular ejection fraction, moderate/severe mitral regurgitation and pulmonary hypertension were found to be independently associated with an increased likelihood of severe tricuspid regurgitation. Estimated rates of 1-year all-cause death were of 21.4, 24.5 and 37.1% in no/mild tricuspid regurgitation, moderate tricuspid regurgitation and severe tricuspid regurgitation, respectively (log-rank P < 0.001). As compared with nonsevere tricuspid regurgitation, severe tricuspid regurgitation was independently associated with a higher risk of all-cause mortality (adjusted hazard ratio 1.38, 95% confidence interval 1.01-1.88, P = 0.042), whereas moderate tricuspid regurgitation did not. In a contemporary, real-world cohort of patients with advanced heart failure, several clinical and echocardiographic characteristics are associated with an increased likelihood of severe tricuspid regurgitation. Patients with severe tricuspid regurgitation have an increased risk of mortality.

Alterations in the innate and adaptive immune system in a real-world cohort of multiple sclerosis patients treated with ocrelizumab

B cell depletion by the anti-CD20 antibody ocrelizumab is effective in relapsing-remitting (RR) and primary progressive (PP) multiple sclerosis (MS). We investigated immunological changes in peripheral blood of a real-world MS cohort after 6 and 12 months of ocrelizumab.All RRMS and most PPMS patients (15/20) showed treatment response. Ocrelizumab not only reduced CD20+ B cells, but also numbers of CD20+ T cells. Absolute numbers of monocytes, dendritic cells and CD8+ T cells were increased, while CD56hi natural killer cells were reduced after ocrelizumab. The residual B cell population shifted towards transitional and activated, IgA+ switched memory B cells, double negative B cells, and antibody-secreting cells. Delaying the treatment interval by 2–3 months increased mean B cell frequencies and enhanced naive B cell repopulation. Ocrelizumab reduced plasma levels of interleukin(IL)-12p70 and interferon(IFN)-α2.These findings will contribute to understanding ineffective treatment responses, dealing with life-threatening infections and further unravelling MS pathogenesis.

Clinical signs and symptoms of Wilson disease in a real-world cohort of patients in the United States: a medical chart review study

IntroductionThere are limited data from the United States regarding the real-world signs and symptoms of Wilson disease (WD). This retrospective, observational medical chart review was conducted to identify real-world characteristics of patients with WD in the United States, as well as WD signs and symptoms at diagnosis and over time.MethodsDe-identified clinical data were abstracted from medical charts of US patients diagnosed with WD between January 1, 2012, and June 30, 2017. Hepatic, neurologic, and psychiatric biochemical findings, signs, and symptoms were characterized at diagnosis and follow-up/during treatment.ResultsIn total, 225 WD patients were included in the study. The mean (SD) age at diagnosis was 24.7 (9.8) years, and 65.3% were male. Median (Q1–Q3) follow-up after diagnosis was 39.5 (33.8–60.4) months. The most common disease presentation at WD diagnosis was combined neurologic/psychiatric and hepatic (52.9%), followed by neurologic/psychiatric (20.0%), hepatic (16.9%), and asymptomatic (10.2%). Common clinical characteristics at diagnosis were Kayser-Fleischer rings (77.2%), low ceruloplasmin levels (95.2%), high hepatic copper (97.8%), elevated 24-hour urinary copper excretion (90.2%), and abnormal liver function tests (38.7%–85.1%). At diagnosis, the most common biochemical findings or hepatic sign/symptoms were abnormal liver enzymes (50.7%), abdominal pain (16.6%), and fatigue (15.7%). The most common neurologic signs/symptoms were headache (18.3%), dysarthria (17.4%), and ataxia (17.0%). Common psychiatric signs/symptoms included anxiety/depression/other mood changes (36.2%), emotional lability (12.8%), and increased irritability/anger outbursts (9.2%). Prevalence of biochemical abnormalities or signs/symptoms among patients at diagnosis and after ~1-year follow-up were neurologic (60.1% and 44.0%), hepatic (69.6% and 37.8%), and psychiatric (53.7% and 37.6%), respectively. Common new onset symptoms at ~1-year post-WD diagnosis were abnormal liver enzymes (5.6%), headache (6.2%), and anxiety/depression/other mood changes (7.2%).ConclusionsThese real-world, descriptive data highlight the clinical complexity and heterogeneity of WD and the need for better education about diagnostic testing and multidisciplinary support. Although rare, the neurologic, psychiatric, and hepatic signs/symptoms of WD have a substantial clinical impact.

American Gastroenterological Association-Proposed Fecal Calprotectin Cutoff of 50 ug/g is Associated With Endoscopic Recurrence in a Real-World Cohort of Patients With Crohn’s Disease Post-ileocolic Resection

Abstract Background Fecal calprotectin (FC) is a reliable predictor of active bowel inflammation in postoperative Crohn’s disease (CD), but cutoffs vary between studies. Recent guidelines recommend a cutoff of &amp;lt;50 ug/g to avoid routine endoscopy in patients at low pretest probability for CD recurrence. We evaluated the performance of this threshold in a real-world CD cohort after ileocolic resection (ICR). Methods In this retrospective study, patients with CD post-ICR between 2009 to 2020 with FC &amp;gt; 60 days but &amp;lt; 1 year of surgery were included from a multicenter database. Established risk factors and/or biologic prophylaxis (biologic within 90 days of surgery) defined pretest probability. Those without postoperative colonoscopy were excluded. Rates of endoscopic recurrence, defined as Rutgeerts score ≥ i2b at any time after surgery, were compared between FC &amp;lt; 50 versus ≥ 50 ug/g. Student’s t-test and Fisher’s exact test were utilized for statistical analysis. All postoperative FCs were matched to closest colonoscopy within 1 year to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results Thirty-seven patients categorized as either low-risk or high-risk and received biologic prophylaxis and had postoperative colonoscopy were included. Median time to first FC was 217 days (IQR 131–288). 15 (41%) patients had initial FC &amp;lt; 50 ug/g versus 22 (59%) ≥50 ug/g. Median time to first colonoscopy was 234 days (IQR 189–369). Compared to initial FC ≥ 50 ug/g, FC &amp;lt; 50ug/g experienced less endoscopic recurrence (0% vs. 36%, P = .005). Median time to first endoscopic recurrence in FC ≥ 50 ug/g was 145 days. There were 39 matched pairs of FC and colonoscopy. At an FC cutoff of 50 ug/g, calculated sensitivity was 90% and NPV was 93%, whereas specificity and PPV were 48% and 38%, respectively. Conclusions In this real-world cohort, FC &amp;lt; 50 ug/g is a useful cutoff to exclude endoscopic recurrence in a post-ICR CD population that is at low pretest probability of recurrence.