Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) are effective in managing chronic kidney disease (CKD) and type 2 diabetes (T2D). However, there are concerns about an increased risk of diabetic ketoacidosis (DKA) associated with the use of SGLT2i, particularly in patients with CKD. The is a population-based, new-user, active comparator cohort study comparing SGLT2i vs. GLP1RA initiators using three U.S. healthcare databases: Optum's de-identified Clinformatics® Data Mart (2014-2024), Merative MarketScan (2014-2022), and Medicare Fee-for-Service (2014-2020). The exposure is initiation of either SGLT2i or GLP1RA, defined as a new prescription without prior use in 365 days. The primary outcome was hospitalization with DKA identified via inpatient ICD-9/10 codes. Incidence rates (IRs), rate differences (RDs), and hazard ratios (HRs) were calculated. After 1:1 propensity score matching, the study population included 143,858 patients, 71,929 in the SGLT2i arm and 71,929 in the GLP1RA arm. The mean age (standard deviation) was 71.28 (8.16) years, and 48.8% were female. Patients initiating SGLT2i had higher risk of hospitalization with DKA compared to GLP1RA initiators (IR 4.37 vs. 3.13 events per 1,000 person-years; RD 1.23 [95% CI 0.54, 1.92]; HR 1.40 [95% CI 1.16, 1.68]). The number needed to harm was 813 per 1,000 person-years for SGLT2i compared to GLP1RA initiation. Results remained consistent in subgroup analyses stratified by age (<70 vs. ≥70 years), sex, body mass index (<30 vs. ≥30 kg/m2), frailty status, baseline cardiovascular disease, diabetic retinopathy, hyperglycemia, metformin use, and insulin use. The incidence rate of DKA among SGLT2i and GLP1RA initiators remained low overall. However, SGLT2i use was associated with a 40% increased risk of hospitalization with DKA compared to GLP1RA use among patients with CKD stages 3-4 and T2D. Clinicians should remain vigilant when monitoring patients with CKD and T2D treated with SGLT2i.

Background and study aimsDuring the COVID-19 pandemic the National Health Service introduced colon capsule endoscopy (CCE) as an alternative to colonoscopy in patients awaiting 3-year post-polypectomy surveillance. We determined the safety, diagnostic accuracy, and utility of CCE in this clinical setting.Patients and methodsConsenting patients awaiting 3-year post-polypectomy surveillance underwent CCE or colonoscopy. For those having CCE, risk-based guidance was developed directing to: 1) immediate colorectal endoscopic intervention; 2) deferred intervention; or 3) discharge. The safety, comparative and paired diagnostic accuracy, and colonoscopy capacity spared by CCE were determined.ResultsThere were 464 CCE and 78 colonoscopy patients recruited. CCE patients were younger (mean 62 years versus 68 years). CCE was safely tolerated in 99% of patients. More ≥ 10 mm and 6- to 9-mm polyps were detected in the CCE cohort than the colonoscopy comparator cohort. This was on an intention to investigate basis and in those who had complete and adequately prepared examinations. Two hundred and five CCE patients had an urgent colonoscopy or flexible sigmoidoscopy and their paired findings were matched. Per patient sensitivities for ≥ 10 mm and 6- to 9-mm polyps were 92% and 90%, respectively. Two-thirds of patients entered a modified management pathway after CCE with 25% being discharged and 27% having a procedure deferral for up to 3 years. CCE completion and bowel preparation adequacy rates were 78% and 73% respectively. No colorectal cancer was detected.ConclusionsCCE is a safe diagnostic of colorectal polyps. In surveillance, its "filter function" complements existing colorectal diagnostic services by providing capacity and choice.

ObjectiveTo evaluate procedure-related preterm birth (PTB) following third-trimester selective termination (ST) in DC twins and to compare delivery timing with expectantly managed discordant DC twins and non-anomalous DC twins.MethodsA retrospective cohort study was conducted of all DC twin pregnancies undergoing third-trimester ST (> 28 weeks) at a tertiary care center (2003–2023). Pregnancies were classified as having procedure-related complications (delivery ≤ 4 weeks) or uneventful (delivery > 4 weeks). Comparator cohorts included expectantly managed discordant DC twins and non-anomalous DC twins. Outcomes included timing of delivery, cumulative incidence of PTB, and risk factor analysis.Results90 women with DC twin pregnancies elected for ST and 85 procedures were completed. Outcome was available for 81 cases; 48 (59.3%) delivered ≤ 4 weeks after ST and 33 (40.7%) delivered later. Clinical chorioamnionitis was more common within the group delivered ≤ 4 weeks (35.4% vs. 0%; p = 0.001). Cumulative PTB incidence showed accelerated delivery between 32 and 34 weeks after ST. Independent risk factors for delivery ≤ 4 weeks included polyhydramnios (OR 5.68) and reduction of the presenting fetus (OR 6.51). Comparator cohorts exhibited substantially lower PTB incidence.ConclusionThird-trimester ST in DC twins is associated with high PTB risk, but excellent co-twin survival. The first 4 weeks after ST represent a critical vulnerability period, and risk is strongly influenced by identifiable preprocedural factors. These findings support individualized counseling, later scheduling in high-risk pregnancies, should be considered.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00404-026-08305-6.

The cardiovascular-kidney-metabolic (CKM) syndrome, estimated to affect up to 90% of U.S. adults, is increasingly recognized as a disease spectrum that requires an interdisciplinary approach. The purpose of this descriptive study was to characterize the patients and the clinical outcomes of a specialized cardio-nephrology inpatient service. These data were compared to data from comparable patients prior to the service's launch. This was a retrospective observational study of a specialized Kidney-Heart service that was launched at the University of Washington in 2020 to serve as the nephrology service for patients hospitalized with primary cardiac disease. Chart review was pursued to obtain patient demographics, reason for consult and hospital outcomes in the first 2.5 years of the service. We also obtained data from a historical cohort of patients with a cardiology diagnosis seen by the general nephrology consult service as a comparator. Descriptive analyses were performed to characterize demographics, consult categories, and primary reasons for hospitalization in patients seen on the Kidney-Heart Service versus the historical cohort. The mean age for the patients seen on the Kidney-Heart Service was 63 (SD 15) vs. 60 (SD 15) years in the comparator cohort (p<0.001). For the Kidney-Heart Service, AKI was the most common reason for consult (57.7%), followed by CKD G5D (30.9%), diuretic management (8.9%) and electrolyte abnormalities (7.8%). Patients seen by the Kidney-Heart Service were most commonly hospitalized for decompensated heart failure and cardiogenic shock (46.9%). Use of mechanical circulatory support was common (22%), and 48.2% of those patients required dialysis. AKI dialysis (36.7 vs 42%, p=0.05) and mortality rates (16.5% vs. 25%, p<0.01) were lower in the Kidney-Heart service cohort vs. the comparator cohort, although mean lengths of stay were longer (14 vs 11 days, p<0.001.) Follow- up in nephrology clinic within the University of Washington system was low for AKI patients at 1.7%. Our single-center experience demonstrates a model by which a specialized cardio-nephrology service can be implemented and provide care for complex patients. Further implementation clinical trials are needed to determine whether integrated care models can improve CKM outcomes.

Background: Patients with type 2 diabetes mellitus (T2DM) and inflammatory bowel disease (IBD) face elevated risk of hepatobiliary complications. The biliary safety of GLP-1 and dual GLP-1/GIP receptor agonists in this population is uncertain. Methods: We conducted a retrospective cohort study using the TrinetX LIVE global health research network. Adults (≥18 years) with coexisting T2DM and IBD were assigned to exposure (semaglutide or tirzepatide) or comparator (no GLP-1/GIP therapy) cohorts. The index was first prescription (or matched date). Primary outcomes—cholelithiasis, cholecystitis, choledocholithiasis, and cholangitis—were identified by ICD-10 codes. Propensity score matching (1:1 greedy nearest neighbor; caliper 0.1 SD) balanced demographics, comorbidities, GI surgeries, and antidiabetic medications. Results: After propensity score matching, 32,052 patients were included (16,026 per cohort), achieving excellent covariate balance with standardized mean differences < 0.1 for nearly all variables. GLP-1/GIP agonist use was associated with significantly lower risks of multiple biliary complications. Cholelithiasis occurred in 3.5% of GLP-1/GIP users compared with 6.3% of nonusers (risk ratio [RR] 1.81, 95% CI 1.64–2.00; hazard ratio [HR] 1.27, 95% CI 1.14–1.41; p < 0.001). Cholecystitis similarly occurred less frequently among users (0.8% vs. 2.2%; RR 2.74, 95% CI 2.24–3.34; HR 1.85, 95% CI 1.50–2.27; p < 0.001). Choledocholithiasis was also reduced in the GLP-1/GIP cohort (0.6% vs. 1.5%; RR 2.72, 95% CI 2.14–3.46; HR 1.90, 95% CI 1.48–2.44; p < 0.001). Cholangitis events were rare in both groups (0.1% vs. 0.2%) with no significant difference on survival analysis (HR 1.07, 95% CI 0.58–1.97; p = 0.08). Conclusions: In adults with T2DM and IBD, GLP-1 and dual GLP-1/GIP receptor agonists are associated with substantially reduced risks of gallstone-related complications. These real-world data support the gastrointestinal safety of GLP-1–based therapy in a high-risk population and suggest possible biliary protective effects warranting prospective, agent-specific studies.

Objective The potential risk of diagnostic conversion from unipolar depression to bipolar disorder with antidepressant use, particularly serotonin-norepinephrine reuptake inhibitors (SNRIs) versus selective serotonin reuptake inhibitors (SSRIs), remains debated. This study aims to investigate the relationship between SSRI and SNRI use and the risk of diagnostic conversion. Methods We conducted a retrospective cohort study using the Korean version of the Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM). The target cohort comprised patients prescribed SNRIs, while the comparator cohort included those prescribed SSRIs. The primary outcome was a new diagnosis of bipolar disorder occurring at least six months after antidepressant initiation. Results After propensity score adjustment, no significant difference in the risk of diagnostic conversion was observed between SSRI and SNRI users. In the distributed network analysis, SNRI use was not significantly associated with an increased risk of diagnostic conversion compared to SSRI use after both 1:1 propensity score matching (hazard ratio [HR] = 1.28, 95% confidence interval [95% CI]: 0.90–1.82; I 2 = 24.1%) and 1:2 propensity score matching (HR = 1.16, 95% CI: 0.88–1.53, I 2 = 0%). Conclusions This study observed no significant difference in the risk of diagnostic conversion to bipolar disorder between SSRI and SNRI users.

Background:Patients with type 2 diabetes (T2DM) are at risk of developing urinary tract infections (UTIs). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a common medication associated with UTIs in these patients. However, emerging data show that other medications may be more frequently prescribed prior to UTI diagnosis.Objectives:Explore the correlation of newly prescribed medications in patients with the diagnosis of T2DM prior to an incidence of UTI and compare it to those without a UTI.Design:This observational case-control study aimed to explore the correlation between the incidence of UTIs in patients with T2DM and new prescription medication fills.Methods:Data were retrieved from national prescription and medical claims database IQVIA PharMetric® Plus for Academics between 2018 to 2021. The exposed cohort included patients with T2DM and an encounter for UTI. The comparator cohort was developed using propensity score matching and consisted of patients with T2DM and a health care encounter, but without a diagnosis of UTI.Results:A total of 31,746 patients met study criteria, with 15,873 in both the exposed and matched comparator cohorts. The medications with the largest percentage point difference were opioids at 3.70 (p-value <0.001), statins at 3.42 (p-value <0.001), amoxicillin at 2.48 (p-value <0.001), metformin at 2.45 (p-value <0.001), and PPIs at 2.19 (p-value <0.001). SGLT2i were the 19th most prescribed medication class.Conclusion:Opioids, statins, amoxicillin, metformin, and PPIs were the top 5 medications prescribed prior to the UTI event based on percentage point difference. SGLT2i were not in the top 10 medications initiated prior to UTI. This adds to existing literature that other new start medications may be correlated with a higher risk of developing a UTI such as opioids and PPIs than SGLT2 inhibitors in patients with T2DM.

SA42 Feasibility Assessment of a Real-World Comparator Cohort Using Multiple Qualifying Index Lines of Therapy (LOTs) in Third-Line or Later (3L+) Diffuse Large B-cell Lymphoma (DLBCL)

Hospital mortality, withdrawal of life-sustaining therapy decisions and early secondary brain insults for critically ill traumatic brain injury patients in England, Wales and Northern Ireland (2009–2024): an observational cohort study

Introduction: Abrocitinib is an oral Janus kinase inhibitor (JAKi) approved in the US for adults with moderate-to-severe atopic dermatitis (AD). A post-approval prospective observational study assessing long-term safety of abrocitinib in AD patients from the US and Canada using the CorEvitas AD Registry from 2022 to 2034 is ongoing. This analysis estimated the incidence rates (IRs) of prespecified delayed (eg, malignancies) and acute-onset (eg, serious infections) safety events separately in AD patients exposed to abrocitinib and in a comparator cohort exposed to biologic and non-biologic (non-JAKi) chronic systemic AD treatments. Procedure/Study: AD patients ≥18 years enrolled in the Registry during 14 Jan 2022 - 3 Jul 2024 who received abrocitinib or a comparator drug within 12 months prior to, at or after Registry enrollment were included in the study. Crude IRs for each safety event [number of first events per 100 patient-years (PY)] and 95% confidence intervals (CI) based on Poisson counts were calculated. Results: Delayed-onset outcomes: Mean (±SD) age of patients was 47.0 (±18.6) and 51.5 (±18.6) years in the abrocitinib (n=100) and comparator cohort (n=1096), respectively. The abrocitinib cohort was comprised of 51.0% female and 65.0% White compared to 57.1% female and 72.5% White in the comparator cohort. The total follow-up exposure time in the abrocitinib and comparator cohorts was 87.3 and 1168.0 PY, respectively. There were 0 and 17 total malignancies in the abrocitinib and comparator cohorts, with an IR per 100 PY of 0.0 (95% CI: 0.0-4.2) and 1.5 (95% CI: 0.9-2.4), respectively. Acute-onset outcomes: Mean (±SD) age of patients was 46.6 (±18.3) and 51.4 (±18.4) years in the abrocitinib (n=88 exposures) and comparator cohort (n=996 exposures), respectively. Of the total abrocitinib exposures, 53.4% were female and 61.4% White compared to 58% female and 72.9% White in the comparator exposures. The total follow-up exposure time in the abrocitinib and comparator cohorts was 58.7 and 833.8 PY, respectively. The number of events and IRs per 100 PY (95% CI) in the abrocitinib cohort were as follows: major adverse cardiac events (MACE), retinal detachment (RD), thrombosis and hepatotoxicity [n=0]; opportunistic infection (OI) [n=1, 1.7 (0.0-9.6)]; serious infections (SI) [n=2, 3.4 (0.4-12.4)]. The number of events and IRs per 100 PY (95% CI) in the comparator cohort were as follows: RD and hepatotoxicity [n=0]; MACE and thrombosis [n=2, 0.2 (0.0-0.9)], OI [n=6, 0.7 (0.3-1.6)]; SI [n=11, 1.3 (0.7-2.4)]. Conclusion: During 2 years, no new safety signals and a low incidence of prespecified safety events was observed in the abrocitinib cohort, aligning with the known safety profile of abrocitinib. Funding/Disclosures: This study was funded by Pfizer.

Sexual side effects of serotonergic drugs are well documented. However, observational evidence comparing specific antidepressants remains sparse. The aim of this study was to compare the risk of developing healthcare-recorded sexual dysfunction among male patients after initiating treatment with citalopram, sertraline, venlafaxine, or mirtazapine. We conducted a new-user, active comparator cohort study of adult males in Denmark who started treatment with any of the study drugs between 2001 and 2015, allowing multiple cohort entries per person. Data from Danish national healthcare registers included 170,580 new treatment episodes of citalopram, 67,721 of mirtazapine, 51,984 of sertraline, and 19,820 of venlafaxine. A separate analysis examined patients with prior depression-related hospital visits. Results were reported as incidence rates as well as unmatched and propensity score-matched hazard ratios. In our primary analysis with 1-year follow-up and washout periods, incidence rates ranged from 18.80 (95% CI 17.60-20.00) to 28.5 (95% CI 26.00-31.30) per 1000 person-years. Venlafaxine was associated with the highest risk of healthcare-recorded sexual dysfunction compared with citalopram (hazard ratio [HR] 1.27; 95% CI 1.02-1.46), which was particularly pronounced among those with previous hospital contact for depression (HR 1.93; 95% CI 1.14-1.27). No significant difference was observed for sertraline (HR 0.99; 95% CI 0.90-1.09), while mirtazapine demonstrated modest evidence of a lower risk relative to citalopram (HR 0.87; 95% CI 0.81-0.93). Findings remained consistent across all analyses. The risk of developing sexual dysfunction varies across antidepressant treatment. Healthcare providers should discuss the potential for sexual side effects, particularly when multiple treatment options are available.

Objective: While prior studies have examined the clinical risk of arrhythmias associated with lamotrigine (LTG), potentially due to a delay in cardiac conduction, it remains unknown whether this risk of cardiac events translates into an economic outcome. To address this knowledge gap, we conducted a comparative healthcare cost study between patients prescribed LTG and those receiving other commonly used comparator agents. Methods: We conducted a retrospective cohort study using Merative MarketScan ® Commercial Claims Database (January 2017 through June 2021). The index date was defined as the date of the first prescription of LTG or comparator drugs (lithium, quetiapine, valproate, or risperidone) for a diagnosis of bipolar I disorder. We included adults who were continuously enrolled in the database for both the 6-month pre- and post-index periods. The outcome was all-cause healthcare costs. To assess the impact of LTG on the outcome, we used difference-in-difference (DiD) approach: comparing cost changes from the 6-month pre-index to post-index periods between propensity-score matched LTG and comparator cohorts. The DiD estimate was derived from a generalized linear model (GLM). To assess robustness, we analyzed 6-month post-index costs using a new propensity score–matched cohort adjusted for baseline characteristics. Results: The matched cohort included 21,128 pairs of patients with well-balanced baseline characteristics, except for geographic region. The median age in both groups was 32 years, and 65% were female. In the LTG group, 6-month healthcare costs decreased by $1,479 (SD $20,073) after the index date, which was less than the $1,740 reduction ($20,082) observed in the control group. However, the DiD estimate from GLM showed that the treatment effect was not statistically significant (β = 261.2, p = 0.181), indicating no significant difference in pre-post healthcare costs between the LTG and matched controls. The result of the secondary analysis was similar to that of the primary analysis, aligning in direction with the main estimates. Conclusions: The impact of LTG and the control group on healthcare costs was similar. This all-cause cost comparison will be followed by an analysis of cardiovascular healthcare resource utilization and costs to provide further insight into the composite impact of the LTG use on cardiac outcome from the healthcare payer’s perspective.

Surzetoclax (ABBV-453) in combination with daratumumab and dexamethasone in biomarker-selected patients with Relapsed/Refractory multiple myeloma: A Phase 1/2, multicenter, open-label platform study

Immune exhaustion limits CD19 CAR-T efficacy in Richter's transformation

Diagnostic evaluation methods and prognostic impact of FLT3-ITD microclones in Acute Myeloid Leukemia (AML): A retrospective multicenter study on behalf of the EHA AML-specialized working group (SWG)

Allogeneic hematopoietic stem cell transplantation in high-altitude hypoxia preserves graft-versus-leukemia without acute gvhd

C-CBL mutations affecting residue 371 confer dismal prognosis in MDS and CMML

Epcoritamab monotherapy provides superior efficacy vs non–anthracycline-containing regimens in newly diagnosed elderly DLBCL patients deemed unsuitable for anthracycline-containing regimens: A match-adjusted comparative efficacy analysis

ABSTRACTAimHyperuricaemia, a common comorbidity among people with chronic kidney disease, is widely treated with uric acid‐lowering agents such as allopurinol and febuxostat. Cardiovascular outcomes of people with chronic kidney disease receiving allopurinol or febuxostat have been controversial. The present study evaluated the risk of cardiovascular events associated with allopurinol or febuxostat treatment in people with chronic kidney disease.MethodsWe conducted a new‐user active comparator cohort study using a nationwide insurance claims database in Japan. Individuals with an estimated glomerular filtration rate < 60 mL/min/1.73 m2 who were newly prescribed allopurinol or febuxostat were included. The primary outcome was a composite of cardiovascular events, including fatal and non‐fatal acute myocardial infarction, fatal and non‐fatal stroke, and all‐cause death. Hazard ratios were estimated using a multivariate Cox regression model. A sensitivity analysis was performed using an inverse probability of treatment weighting (IPTW) Cox regression model.ResultsA total of 1673 and 7805 individuals were included in the allopurinol and febuxostat treatment groups, respectively. The febuxostat group had a similar incidence of the composite outcome as the allopurinol group (hazard ratio 0.93, 95% confidence interval: 0.79–1.08, p = 0.33). The hazard ratio for febuxostat compared with allopurinol treatment did not vary across different estimated glomerular filtration rate levels. The sensitivity analysis using IPTW showed similar results.ConclusionIn conclusion, no statistically significant difference in the risk of cardiovascular events was observed in people with chronic kidney disease who were newly prescribed febuxostat compared with those newly treated with allopurinol.

Abstract Disclosure: J. Gore: None. K.G. Romo: None. A.A. Noor: None. A. Zia: None. S. Sharma: None. G.I. Uwaifo: None. Introduction: Exocrine Pancreatic insufficiency (EPI) is an underdiagnosed disease of multivariate etiology resulting in extensive damage to the exocrine pancreas function which requires enzyme replacement therapy. While many patients with EPI also have diabetes (DM), the risk for future diabetes onset among those without is not well defined. Methods: A retrospective records review of the Electronic Health records from a large regional health care system from Jan 2017 to Jan 2020 was obtained to identify patients with EPI with and without DM at the start of the observation period. Evaluation of the incident rate of new DM diagnoses during the period of observation was obtained. A comparator cohort of patients with obesity with and without DM from the same health system was also evaluated for new DM diagnoses over the same time period. Results: Of a total patient population of 1.327 million, 1,798 patients with EPI were identified with 431 having DM at the start of observation (∼ 24% prevalence). By the end of the observation period there were 813 patients with DM (∼ 45.2% final prevalence) and a consequent incident rate of 21.2 % in 3 years. Of the EPI patients, 45.2% had DM, 33.8% had pancreatitis and 12.8% had cystic fibrosis. Pancreatic cancer (27.7%) and pancreatic surgery (2.9%) were the other most common etiologic associations. 849, 380 patients were obese at the start of the observation period with DM prevalence of 15.8%. The mean BMI for the Obese cohort was 33.58 kg/ m2. Despite having a mean BMI of 26.56kg/m2, EPI patients without DM had a greater diabetes incidence rate than obese patients without DM but no EPI from the same practice population over the same observation period (21.2% vs 11.4%). Conclusion: While EPI is associated with a high prevalence of DM, it is also important to be aware that it is associated with a similarly high-risk potential for incident DM development exceeding that associated with obesity. Consequently, non-diabetic EPI patients need ongoing clinical surveillance of glycemic profile prospectively to enable early detection of DM onset with its attendant cardiometabolic complications. Presentation: Monday, July 14, 2025