Citations

ABSTRACT Rituximab, gemcitabine, and oxaliplatin (R‐GemOx) is a commonly used chemoimmunotherapy regimen for relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL), but there are limited real‐world data. In a multicenter retrospective study from a cohort of eight US academic centers (LEO CReWE), we evaluated 183 patients with R/R DLBCL and high‐grade B cell lymphoma treated with R‐GemOx, including subgroups treated without intent for consolidation with autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR) T cell therapy ( n = 100), those utilizing R‐GemOx as a bridge to ASCT or CAR T ( n = 83), and those aged 70 and older ( n = 71). Overall response rates (ORRs) for all patients treated with R‐GemOx were 45% with a complete response (CR) rate of 29%. The median event‐free survival (EFS) was 2.3 months, and the median overall survival (OS) was 13.5 months. Patients receiving R‐GemOx without intent for ASCT or CAR T had ORR and CR rates of 33% and 18%, respectively, with median EFS and OS of 2.0 and 9.5 months, respectively. Patients receiving R‐GemOx as a bridge to ASCT or CAR T had ORR and CR rates of 57% and 36%, respectively, with median EFS and OS of 3.5 and 17.4 months, respectively. Patients receiving R‐GemOx aged 70 and older had ORR and CR rates of 53% and 33%, respectively, with median EFS and OS of 2.2 and 13.9 months, respectively. These data provide a benchmark for R‐GemOx in the rapidly evolving landscape of R/R DLBCL therapies.

Abstract We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer’s disease (ADAD). A total of 550 variants in the APP, PSEN1 and PSEN2 genes were identified, of which 279 were classified as pathogenic or likely pathogenic based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria, utilizing data from the Dominantly Inherited Alzheimer Network (DIAN), literature and public databases. Symptomatic age at onset (AAO) data were estimated for 227 of these variants, allowing detailed characterization of their frequency, pathogenicity and AAO. Importantly, 226 variants met eligibility criteria for inclusion in disease-modifying clinical trials. Furthermore, we demonstrated the predictive value of mean variant AAO and parental AAO in predicting symptomatic AAO, validated against converters who became symptomatic during follow-up in the DIAN Observational Study. This dataset provides critical insights into the global landscape of ADAD and reveals the genetic and AAO heterogeneity of ADAD variants while refining variant trial eligibility criteria.

Importance: Many patients who would benefit from minimally invasive surgery (MIS) have open surgery; robotic-assisted surgery (RAS) addresses some of the limitations of laparoscopic surgery and could increase rates of MIS across different patient populations. Objective: To determine whether the introduction of RAS increases MIS rates and whether increases are seen across different patient populations undergoing common general surgery procedures. Design: A retrospective cohort study was performed to compare rates of MIS in the year before and after the index date for hospitals that did and did not introduce RAS. Generalized estimating equation regression models were used to compare rates in MIS over time. Setting: PINC AI Healthcare Database, an all-payor discharge database of hospitals in the United States. Participants: Hospitals that performed cholecystectomy, inguinal hernia repair, ventral hernia repair, and colorectal resection from 2016 to 2022. Exposure: RAS hospitals performing at least 1 common general surgery procedure using RAS. Main Outcome and Measure: The primary analysis examined rates of MIS, defined as the rate of common general surgeries that were minimally invasive (laparoscopic or RAS) in a hospital. The secondary analysis examined MIS rates for common general surgeries, across age, sex, race, ethnicity, and payor. Results: Of 408 hospitals included in the study, 153 (38%) introduced RAS for common general surgeries. The relative MIS rate for hospitals that introduced RAS compared with hospitals that did not went from 1.08 (95% confidence interval [CI], 1.02–1.14; P < 0.01) before the index date to 1.15 (95% CI, 1.09–1.22; P < 0.01) after the index date (P interaction < 0.01), indicating a larger increase in MIS rates among hospitals introducing RAS. MIS rates increased significantly more in hospitals that introduced RAS across patient age, sex, ethnicity, race, and payor compared with hospitals that did not introduce RAS. Conclusions and Relevance: Hospitals that introduced RAS for common general surgery procedures were associated with an increase in MIS rates across different patient populations compared with hospitals that did not introduce RAS.

Abstract Chimeric antigen receptor (CAR) T-cell products axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel) are approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Emerging evidence indicates that delayed CAR T-cell infusion, including prolonged time from leukapheresis to infusion, known as vein-to-vein time (V2Vt), may adversely impact clinical outcomes. We conducted a systematic literature review (SLR) and meta-analysis to identify differences in V2Vt in patients with R/R LBCL treated with axi-cel, tisa-cel, or liso-cel. The impact of V2Vt (&lt;28 days vs ≥28 to &lt;40 days vs ≥40 days) on effectiveness and safety outcomes was evaluated in patients treated with axi-cel enrolled in a post-authorization safety study using the Center for International Blood and Marrow Transplant Research data. SLR and meta-analysis showed that patients treated with axi-cel had the shortest median V2Vt (30.6 days) compared with tisa-cel (48.4 days) or liso-cel (35.9 days). Real-world analysis of patients treated with axi-cel demonstrated that V2Vt ≥40 days was associated with significantly lower complete response rate than V2Vt &lt;28 days (odds ratio [OR], 0.61) or ≥28 to &lt;40 days (OR, 0.66) and significantly worse overall survival than V2Vt &lt;28 days (hazard ratio [HR], 1.33) or ≥28 to &lt;40 days (HR, 1.36). Higher prolonged thrombocytopenia rates were observed in patients with axi-cel V2Vt ≥28 to &lt;40 days or ≥40 days compared with &lt;28 days (OR, 1.44 or 1.95, respectively). Together, these results show the impact of V2Vt on patient outcomes with axi-cel therapy and that earlier infusion with CD19-CAR therapies may be beneficial.

Background The contact aspiration (CA) technique is often used to perform endovascular thrombectomy (EVT) for acute ischemic stroke (AIS); however, rescue strategies are necessary if CA fails to achieve recanalization. This study investigates the outcomes of incorporating stent retriever (SR) thrombectomy in the rescue strategy following failed CA. Methods EVT patients with failed CA attempts were identified from a large multicenter registry and stratified by rescue technique: CA alone or incorporating SR in the rescue strategy. Outcomes included successful recanalization, 90-day functional outcomes (defined by the modified Rankin Scale (mRS) score), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. Results Among 1885 patients with failed CA attempts, conversion to SR was associated with higher recanalization rates (85.2% vs 80.6%; p=0.03), higher rates of second-pass recanalization (31.2% vs 23.4%; p<0.001), and better 90-day outcomes (mRS 0–2: 35.2% vs 29.9%; p=0.04) when compared with repeated CA attempts. Trevo SRs showed higher odds of successful recanalization (adjusted odds ratio (aOR)=1.9; p=0.02), second-pass recanalization (aOR=1.7; p=0.01), and reduced odds of sICH (aOR=0.3; p=0.02). EmboTrap SRs were associated with higher odds of 90-day mortality (aOR=2.6; p=0.004) and sICH (aOR=2.9; p=0.04) and lower odds of recanalization (aOR=0.5; p=0.03). Conclusions Incorporating SR in the rescue strategy after a failed CA improves recanalization rates and functional outcomes. Trevo SRs demonstrated superior efficacy and safety when incorporated into the rescue strategy.

Background: Multiple randomized clinical trials failed to show benefit of anticoagulation over antiplatelets in the secondary prevention for embolic stroke of undetermined source (ESUS). However, the benefit of combination antithrombotic regimens remains unexplored in the same patient population. Methods: This is a subgroup analysis of a multicenter retrospective observational cohort of consecutive adult patients with ESUS (n=27 sites, 2015-2024). Comparisons were made between patients treated with single (SAPT) or dual antiplatelet therapy (DAPT), exclusive anticoagulation (AC) (direct oral anticoagulant, vitamin K antagonist, low molecular weight heparin) and combination anticoagulation and antiplatelet therapy initiated within the first 7 days of index stroke. The primary composite outcome of recurrent ischemic stroke, major bleeding, or death was assessed using unadjusted and adjusted Cox proportional hazards regression. Secondary outcomes were individual outcomes of recurrent ischemic stroke, major bleeding, or death. Results: Of the 2201 included patients, 1456 (66.1%) were on SAPT, 527 (23.9%) were on DAPT, 195 (8.8%) were on exclusive AC and 23 (1.0%) were on AC+AP (all of which were on DAPT). Patients treated with AC+AP were older (median 66 years [IQR 51-78]), more likely to have history of hypertension, stroke, hyperlipidemia, PFO and left atrial enlargement. Compared to SAPT, all treatment strategies were associated with similar risk of the primary outcomes in the unadjusted and adjusted cox regression. Similarly, there was no difference in individual outcomes including recurrent stroke, major bleeding and death in the adjusted cox regression. However, there was an increased risk of major bleeding with AC+AP in the unadjusted cox regression (HR 4.0, [95% CI 1.2-12.8], p=0.02) but not in the adjusted model when compared to SAPT. Also, DAPT was associated with lower risk of death than SAPT in the unadjusted model (HR 0.61 [95% CI 0.4-0.8],p=0.005) but not the adjusted model. Additionally, when adjusted by the HASBLED score, there was no difference in major bleeding when AC+AP was compared to SAPT. Conclusion: Over 90% of ESUS patients in this cohort were prescribed SAPT or DAPT. Antithrombotic therapy with DAPT, exclusive AC, or AC+AP was not associated with any lower risk of recurrent ischemic stroke, major bleeding and death compared with SAPT in an unselected cohort of ESUS patients.

Background: CT perfusion (CTP) imaging is an important tool for identifying candidates for mechanical thrombectomy (MT). This modality is increasingly available in regional facilities, but whether pre-transfer perfusion imaging studies may be relied upon for treatment decisions is unclear. We analyzed a cohort of stroke transfers to quantify changes in CTP imaging profiles over time. Methods: A cohort of confirmed ischemic stroke patients who received CTP before and after transfer to a large mid-western comprehensive stroke center (CSC) were identified. We compared perfusion mismatch (MM), core infarct volume (CIV), and favorability of imaging for mechanical thrombectomy (MT) candidacy (defined as the presence of LVO and MM/CIV ratio of >1.8) between studies. Regression models were used to examine predictors of CIV growth including hypoperfusion intensity ratio (HIR) and time between studies. Results: Over a 24-month period, 61 patients met inclusion criteria. Median age was 71 (IQR 60-80), 52% were female, median NIHSS was 14 (IQR 4-19), and most patients had occlusion of the internal carotid and/or middle cerebral arteries (77%). The median time from last known well (LKW) to initial CT was 148 minutes (IQR 71-620) and median time between imaging studies was 149 minutes (IQR 126-194). Median CIV growth was 0 mL (IQR 0-6) and 8% (5/61) had growth ≥25 mL. In linear regression, higher HIR predicted CIV growth (β=24.3, p=0.04), but time from LKW to presentation and time between imaging studies did not. Imaging studies taken at the regional and CSC sites demonstrated excellent agreement in classifying patients as candidates for MT (kappa 0.778 [95% CI: 0.611-0.944]). A favorable regional CTP profile was 93% sensitive for MT delivery at the CSC with a positive predictive value of 63%. Conclusion: In our cohort, CIV growth between facilities was minimal despite relatively long interfacility transport times and was predicted by the regional HIR. A favorable regional imaging profile demonstrated high agreement with the imaging result at the CSC and was strongly associated with MT treatment.