Citations

Background Despite significant cardiac involvement in sarcoidosis, real‐world data on death due to cardiovascular disease among patients with sarcoidosis is not well established. Methods and Results We queried the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database for data on patients with sarcoidosis aged ≥25 years from 1999 to 2020. Diseases of the circulatory system except ischemic heart disease were listed as the underlying cause of death, and sarcoidosis was stated as a contributing cause of death. We calculated age‐adjusted mortality rate (AAMR) per 1 million individuals and determined the trends over time by estimating the annual percentage change using the Joinpoint Regression Program. Subgroup analyses were performed on the basis of demographic and geographic factors. In the 22‐year study period, 3301 cardiovascular deaths with comorbid sarcoidosis were identified. The AAMR from cardiovascular deaths with comorbid sarcoidosis increased from 0.53 (95% CI, 0.43–0.65) per 1 million individuals in 1999 to 0.87 (95% CI, 0.75–0.98) per 1 million individuals in 2020. Overall, women recorded a higher AAMR compared with men (0.77 [95% CI, 0.74–0.81] versus 0.58 [95% CI, 0.55–0.62]). People with Black ancestry had higher AAMR than people with White ancestry (3.23 [95% CI, 3.07–3.39] versus 0.39 [95% CI, 0.37–0.41]). A higher percentage of death was seen in the age groups of 55 to 64 years in men (23.11%) and women (21.81%), respectively. In terms of US census regions, the South region has the highest AAMR from cardiovascular deaths with comorbid sarcoidosis compared with other regions (0.78 [95% CI, 0.74–0.82]). Conclusions The increase of AAMR from cardiovascular deaths with comorbid sarcoidosis and higher cardiovascular mortality rates among adults aged 55 to 64 years highlight the importance of early screening for cardiovascular diseases among patients with sarcoidosis.

Abstract Several reports of concurrent MYC, BCL2, BCL6, and CCND1 rearrangements in high-grade B-cell lymphoma (HGBL) have been recently described. Herein, we aimed to delineate the scope of this entity through a review of HGBL with a “quadruple-hit” genetic profile identified at our institution. We performed a retrospective review (2015-2023) at our institution of B-cell lymphoma (BCL) cases that were evaluated with concurrent MYC, BCL2, and BCL6 break-apart and IGH::MYC and IGH::CCND1 dual-color dual-fusion fluorescence in situ hybridization studies. Of 203 cases meeting inclusion criteria, 2 (1%) with a quadruple-hit genetic profile were identified. Case 1 represented a 59-year-old female with widespread lymphadenopathy and a diagnosis of HGBL who exhibited primary refractoriness to dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) chemotherapy. Case 2 represented a 58-year-old male with mediastinal and abdominal lymphadenopathy and a diagnosis of large BCL who died from disease after 1 cycle of DA-EPOCH-R chemotherapy. Similarly, a literature review of 7 previously reported cases of HGBL with a quadruple-hit profile also demonstrated aggressive disease behavior. Our study adds 2 new cases to the rarely encountered quadruple-hit HGBL, and a brief meta-analysis of the 9 available cases indicates aggressive disease behavior conferred by this constellation of genetic events.

Abstract Traditional cancer research methodologies predominantly focus on 2D tumor modeling, including spatial profiling and AI-driven analysis at the 2D level. To advance beyond these limitations, we implemented Holotomography (HT), a 3D, label-free optical imaging method. This technique, leveraging refractive index contrasts, allows for enhanced visualization of tumor tissues, organoids, and cells in three dimensions. Using serial H&E sections and unstained slides, we created detailed 3D tumor models in gastric cancer, providing insights into tumor, immune, and stromal composition, as well as cell-cell interactions and extracellular matrix characteristics. AI algorithms further enhanced our 3D tumor modeling, offering novel perspectives on the initiation and progression of tumor, immune, and stromal components at the subcellular level. Analyzing gastric tumors treated with immune checkpoint inhibitors before, during, and after treatment revealed dynamic changes in spatial composition over time, offering unique insights into the evolution of the 3D tumor ecosystem. Additionally, by integrating spatial transcriptomic and in situ molecular imaging data, we developed a novel Multimodal 3D Tumor Model. This model not only uncovers subcellular-level molecular characteristics but also elucidates cellular interactions during treatment, suggesting potential biomarkers and therapeutic approaches. Lastly, by constructing 3D cellular interaction networks incorporating true 3D interactions, we provided an in-depth view of cellular communication within the tumor microenvironment. This pioneering approach, representing the first Multimodal 3D Tumor Model at the subcellular level, offers novel insights into gastric cancer's spatial evolution, potentially revolutionizing our understanding and treatment of gastric cancer. Citation Format: Yoon Ho Choi, Minji Kim, Katya Redekop, Inyeop Jang, Jean R. Clemenceau, Isabel Barnfather, Sumanth Reddy Nakkireddy, Changjin Hong, Sunho Park, Ji-Youn Sung, Jeong Hwan Park, Shitara Kohei, Aoki Yu, Sung Hak Lee, Sam Wang, Jaeho Cheong, Tae Hyun Hwang. AI-driven multimodal 3D tumor modeling with spatial molecular insights for predicting ICI response in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7400.

Abstract Background Long‐term outcomes of sterile lead management strategies of lead abandonment (LA) or transvenous lead extraction (TLE) remain unclear. Methods We performed a retrospective study of a population residing in southeastern Minnesota with follow‐up at the Mayo Clinic and its health systems. Patients who underwent LA or TLE of sterile leads from January 1, 2000, to January 1, 2011, and had follow‐up for at least 10 years or until their death were included. Results A total of 172 patients were included in the study with 153 patients who underwent LA and 19 who underwent TLE for sterile leads. Indications for subsequent lead extraction arose in 9.1% ( n = 14) of patients with initial LA and 5.3% ( n = 1) in patients with initial TLE, after an average of 7 years. Moreover, 28.6% of patients in the LA cohort who required subsequent extraction did not proceed with the extraction, and among those who proceeded, 60% had clinical success and 40% had a clinical failure. Subsequent device upgrades or revisions were performed in 18.3% of patients in the LA group and 31.6% in the TLE group, with no significant differences in procedural challenges (5.2% vs. 5.3%). There was no difference in 10‐year survival probability among the LA group and the TLE group ( p = .64). Conclusion An initial lead abandonment strategy was associated with more complicated subsequent extraction procedures compared to patients with an initial transvenous lead extraction strategy. However, there was no difference in 10‐year survival probability between both lead management approaches.

BACKGROUND AND OBJECTIVES: First pass effect (FPE) is a metric increasingly used to determine the success of mechanical thrombectomy (MT) procedures. However, few studies have investigated whether the duration of the procedure can modify the clinical benefit of FPE. We sought to determine whether FPE after MT for anterior circulation large vessel occlusion acute ischemic stroke is modified by procedural time (PT). METHODS: A multicenter, international data set was retrospectively analyzed for anterior circulation large vessel occlusion acute ischemic stroke treated by MT who achieved excellent reperfusion (thrombolysis in cerebral infarction 2c/3). The primary outcome was good functional outcome defined by 90-day modified Rankin scale scores of 0–2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. We fit-adjusted logistic regression models and used marginal effects to assess the interaction between PT (≤30 vs >30 minutes) and FPS, adjusting for potential confounders including time from stroke presentation. RESULTS: A total of 1310 patients had excellent reperfusion. These patients were divided into 2 cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and >30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant ( P = .018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs 46.7%, P = .001). However, there was no significant difference in the adjusted predicted probability of good outcome in individuals with PT >30 minutes. This relationship appeared identical in models with PT treated as a continuous variable. CONCLUSION: FPE is modified by PT, with the added clinical benefit lost in longer procedures greater than 30 minutes. A comprehensive metric for MT procedures, namely, FPE 30 , may better represent the ideal of fast, complete reperfusion with a single pass of a thrombectomy device.

Background and Aims: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). Approach and Results: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP, rs9842969, (0.51, [0.40–0.65]); 5p15.33, TERT, rs2242652, (0.70, (0.62–0.79]); 19q13.11, TM6SF2, rs58542926, (1.49, [1.29–1.72]); 19p13.11 MAU2, rs58489806, (1.53, (1.33–1.75]); and 22q13.31, PNPLA3, rs738409, (1.66, [1.51–1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74–0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. Conclusions: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

Abstract Emerging studies have identified the critical roles of tissue-resident memory CD8+ T (TRM) and B (BRM) cells in the protection against mucosal viral infections, but the underlying mechanisms regulating robust development of TRM and BRM cells remain incompletely understood. We have recently shown that tissue-resident helper CD4+ T (TRH) cells, developed following influenza virus infection, function to sustain the optimal maintenance of TRM and BRM cells at the mucosal surface. In this study, we have explored the cellular and molecular cues modulating lung TRH persistence after influenza infection in C57BL/6 mice. We found that TRH cells were colocalized in tertiary lymphoid structures (TLSs) with local B cells. Abolishing TLSs or the depletion of B cells impaired lung TRH cell numbers. Of note, we found that persistent TCR signaling is needed for the maintenance of TRH cells after the clearance of infectious influenza virus. Furthermore, selective ablation of B cell–derived MHC class II resulted in partial reduction of lung TRH cell number after influenza infection. Our findings suggest that the interaction between lung-resident TRH cells and B cells, along with persistent Ag stimulation, is required to maintain TRH cells after respiratory viral infection.

AbstractINTRODUCTIONPatients with dementia with Lewy bodies (DLB) may have Alzheimers disease (AD) pathology that can be detected by plasma biomarkers. Our objective was to evaluate plasma biomarkers of AD and their association with positron emission tomography (PET) biomarkers of amyloid and tau deposition in the continuum of DLB, starting from prodromal stages of the disease.METHODSThe cohort included patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD), mild cognitive impairment with Lewy bodies (MCI‐LB), or DLB, with a concurrent blood draw and PET scans.RESULTSAbnormal levels of plasma glial fibrillary acidic protein (GFAP) were found at the prodromal stage of MCI‐LB in association with increased amyloid PET. Abnormal levels of plasma phosphorylated tau (p‐tau)‐181 and neurofilament light (NfL) were found at the DLB stage. Plasma p‐tau‐181 showed the highest accuracy in detecting abnormal amyloid and tau PET in patients with DLB.DISCUSSIONThe range of AD co‐pathology can be detected with plasma biomarkers in the DLB continuum, particularly with plasma p‐tau‐181 and GFAP.

AbstractBackgroundThe real‐world data on the safety profile of transvenous lead extraction (TLE) for infected cardiac implantable electronic devices (CIED) among elderly patients is not well‐established. This study aimed to evaluate the hospital outcomes between patients of different age groups who underwent TLE for infected CIED.MethodUsing the Nationwide Readmissions Database, our study included patients aged ≥18 years who underwent TLE for infected CIED between 2017 and 2020. We divided the patients into four groups: Group A. Young (<50 years), Group B. Young intermediate (50–69 years old), Group C. Older intermediate (70–79 years old), and Group D. Octogenarian (≥80 years old). We then analyzed the in‐hospital outcome and 30‐day readmission between these age groups.ResultsA total of 10,928 patients who were admitted for TLE of infected CIED were included in this study: 982 (9.0%) patients in group A, 4,234 (38.7%) patients in group B, 3,204 (29.3%) patients in group C and 2,508 (23.0%) of patients in group D. Our study demonstrated that the risk of early mortality increased with older age (Group B vs. Group A: OR: 1.92, 95% CI: 1.19‐3.09, p < .01; Group C vs. Group A: OR: 2.47, 95% CI: 1.51‐4.04, p < .01; Group D vs. Group A: OR: 2.82, 95% CI: 1.69‐4.72, p < .01). The risk of non‐home discharge also increased in elderly groups (Group B vs. Group A: OR: 1.89; 95% CI: 1.52‐2.36; p < .01; Group C vs. Group A: OR: 2.82; 95% CI 2.24‐3.56; p < .01; Group D vs. Group A: OR: 4.16; 95% CI: 3.28‐5.28; p < .01). There was no significant difference in hospitalization length and 30‐day readmission between different age groups. Apart from a higher rate of open heart surgery in group A, the procedural complications were comparable between these age groups.ConclusionElderly patients had worse in‐hospital outcomes in early mortality and non‐home discharge following the TLE for infected CIED. There was no significant difference between elderly and non‐elderly groups in prolonged hospital stay and 30‐day readmission. Elderly patients did not have a higher risk of procedural complications.

AbstractBackgroundThe real‐world data on the safety profile of ventricular tachycardia (VT) ablation among elderly patients is not well‐established. This study aimed to evaluate the procedural outcomes among those aged 18–64 years versus those aged ≥65 years who underwent catheter ablation of VT.MethodUsing the Nationwide Readmissions Database, our study included patients aged ≥18 years who underwent VT catheter ablation between 2017 and 2020. We divided the patients into non‐elderly (18–64 years old) and elderly age groups (≥65 years old). We then analyzed the in‐hospital procedural outcome and 30‐day readmission between these two groups.ResultsOur study included 2075 (49.1%) non‐elderly patients and 2153 (50.9%) elderly patients who underwent VT ablation. Post‐procedurally, elderly patients had significantly higher rates of prolonged index hospitalization (≥7 days; 35.5% vs. 29.3%, p < .01), non‐home discharge (13.4% vs. 6.0%, p < .01), 30‐day readmission (17.0% vs. 11.4%, p < .01), and early mortality (5.5% vs. 2.4%, p < .01). There was no significant difference in the procedural complications between two groups, namely vascular complications, hemopericardium/cardiac tamponade, cerebrovascular accident (CVA), major bleeding requiring blood transfusion, and systemic embolization. Through multivariable analysis, the elderly group was associated with higher odds of early mortality (OR: 7.50; CI 1.86–30.31, p = .01), non‐home discharge (OR: 2.41; CI: 1.93–3.00, p < .01) and 30‐day readmission (OR: 1.58; CI 1.32–1.89, p < .01).ConclusionElderly patients have worse in‐hospital outcome, early mortality, non‐home discharge, and 30‐day readmission following catheter ablation for VT. There was no significant difference between elderly and non‐elderly groups in the procedural complications.