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Role of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide/Glucagon-Like Peptide-1 Receptor Agonists in Management of Cardiovascular-Kidney-Metabolic (CKM) Conditions.
No full textUse of glucagon-like peptide-1 (GLP-1) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, initially developed as glucose-lowering therapies for the management of type 2 diabetes, continues to expand in parallel with our understanding of their beneficial effects on cardiovascular-kidney-metabolic conditions. Large clinical outcome trials have established GLP-1 receptor agonists as guideline-directed therapies to improve glycemia, achieve, and maintain weight management goals, and mitigate cardiovascular and kidney risk, with early evidence suggesting similar benefits with the dual GIP/GLP-1 receptor agonist tirzepatide
DRUG AND SINGLE-CELL GENE EXPRESSION INTEGRATION IDENTIFIES SENSITIVE AND RESISTANT GLIOBLASTOMA CELL POPULATIONS.
No full textGlioblastoma (GBM) remains the most common and lethal adult malignant primary brain cancer with few treatment options. A significant issue hindering GBM therapeutic development is intratumor heterogeneity. GBM tumors contain neoplastic cells within a spectrum of different transcriptional states. Identifying effective therapeutics requires a platform that predicts the differential sensitivity and resistance of these states to various treatments. Here, we developed a novel framework, ISOSCELES (Inferred cell Sensitivity Operating on the integration of Single-Cell Expression and L1000 Expression Signatures), to quantify the cellular drug sensitivity and resistance landscape. Using single-cell RNA sequencing of newly diagnosed and recurrent GBM tumors, we identified compounds from the LINCS L1000 database with transcriptional response signatures selectively discordant with distinct GBM cell states. We validated the significance of these finding
The need for future coronary access in older medicare beneficiaries following transcatheter aortic-valve replacement.
No full textBACKGROUND: While approximately 17% of patients less than 80 years old require coronary access in the 7 years following their TAVR, the need for coronary access among older TAVR patients is unknown.
METHODS: We examined the percentage of Medicare beneficiaries aged 80-90 years that require coronary access [percutaneous coronary intervention (PCI) or angiogram] in the 8 years following their TAVR using data from the Medicare 5% Standard Analytic File (2011-2021). The need for coronary access in older patients was estimated for all TAVRs, TAVR patients with and without a history of PCI, and TAVR patients with and without coronary artery disease (CAD) using time-to-event models adjusted for age, sex, race, region, ECI score, concomitant CABG, CAD, PCI, and current or recent smoker status. Multivariate log-gamma regressions were used to estimate the total cost of hospitalizations requiring coronary access post-TAVR.
RESULTS: A total of 6845 patients met inclusion criteria. The incidence rates for undergoing PCI or angiogram at 1, 3, 5, and 8 years were 1.9%, 4.0%, 5.5%, and 6.3%, respectively. TAVR patients with PCI demonstrated higher rates of coronary intervention compared to those without PCI (10.2% vs. 6.2% at 8 years, respectively). Similarly, TAVR patients with a prior CAD diagnosis exhibited increased rates of coronary intervention compared to those without a prior CAD diagnosis (7.4% vs. 2.1% at 8 years, respectively). The mean adjusted cost of hospitalizations requiring coronary access was 27,865-$32,665].
CONCLUSIONS: Approximately 6.8% of older TAVR patients require coronary access in the 8 years following their index procedure. The presence of a prior PCI or CAD diagnosis is associated with an increased requirement for subsequent coronary access
Addressing housing as a health-related social need: insights from a Medicaid Housing Pilot in Oregon
No full textRecurrence and Survival Following Robotic Resection of Thymomas Greater Than Five Centimeters.
No full textBACKGROUND AND METHODS: Minimally invasive large thymoma resection remains controversial given the paucity of long-term oncological outcomes. We described the recurrence and survival of patients with thymomas ≥ 5 cm resected robotically.
METHODS: Consecutive thymoma resections between January 2006 and December 2022 were reviewed. Thymic carcinoma/neuroendocrine tumors, induction therapy treatment, and Stage IV disease were excluded. For thymomas ≥ 5 cm, open versus robotic resections were compared. With robotic resections, thymomas ≥/\u3c 5 cm were compared. The outcomes were freedom from recurrence (FFR) and overall survival (OS).
RESULTS: There were 40 thymomas ≥ 5 cm (15 open and 25 robotic) and 52 robotic thymoma \u3c 5 cm resections. Median follow-up was 5 years with 4 (4%) patients having recurrences and 5 (5%) demised. In thymomas ≥ 5 cm, patients were similar, except for higher comorbidities in the open cohort. Five-year FFR (p = 0.42) and OS (p = 0.34) were comparable. Patients with robotic resection of thymomas ≥/\u3c 5 cm were similar, except those \u3c 5 cm were more frequently Masaoka-Koga Stage II. Five-year FFR (p = 0.62) and OS (p = 0.62) were similar.
CONCLUSIONS: Resectable large thymomas, ≥ 5 cm, can be approached robotically with similar recurrence and survival when compared to open or smaller robotic resections. In otherwise appropriate thymomas, considerations such as location and proximity to surrounding structures, over size alone, should guide the approach
Predictors of atrial fibrillation freedom postablation with the pentaspline pulsed field ablation catheter: Subanalysis of the ADVENT Study.
No full textBACKGROUND: Pulsed field ablation (PFA) has proven to be at least noninferior to thermal ablation for paroxysmal atrial fibrillation (AF). Predictors of AF freedom for PFA have not yet been described.
OBJECTIVE: The purpose of this study was to identify clinical and procedural predictors of treatment success in paroxysmal AF patients treated with the pentaspline PFA catheter.
METHODS: ADVENT (Randomized Controlled Trial for Pulsed Field Ablation versus Standard of Care Ablation for Paroxysmal Atrial Fibrillation) was a prospective randomized trial comparing PFA to thermal ablation with centers designated to randomize patients to either radiofrequency or cryoballoon ablation. Hazard ratios were estimated to evaluate clinical and procedural characteristics associated with ablation success. Subgroup analyses were performed by ablation modality and operator/center experience.
RESULTS: Of the 607 randomized patients (age 62.4 years, 34.6% female), treatment failure was documented in 26.7% of PFA and 28.7% of thermal ablation patients. The most common failure was arrhythmia recurrence (73.8% vs 76.5%) with no difference in subtype (non-AF arrhythmia: 12.1% PFA vs 14.6% thermal). Patients who previously failed Class I/III antiarrhythmic drugs (AADs) were more likely to benefit from PFA (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.44-0.96). Shorter left atrial dwell time was associated with higher success (HR 0.48, 95% CI 0.30-0.76), and a trend toward better outcomes was noted for patients enrolled during the second half of the trial (75.5% vs 69.9%, P = .17). PFA patients had similar success across radiofrequency and cryoballoon centers.
CONCLUSION: PFA with the pentaspline catheter is not associated with a higher incidence of postablation atypical flutters/tachycardias. Patients with previous Class I/III AAD failure are more likely to benefit from PFA and greater operator experience, irrespective of previous thermal modality, may be associated with better outcomes
Improved survival at the population level for patients with advanced Merkel cell carcinoma following availability of immunotherapy.
No full textBACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer with poor survival rates. Immune checkpoint inhibitors (ICIs) were Food and Drug Administration-approved for advanced MCC in 2017, but their real-world survival impact remains unclear.
OBJECTIVE: Evaluate whether ICI introduction in the United States corresponded with improved survival.
METHODS: This cohort study analyzed Surveillance, Epidemiology, and End Results data for MCC patients diagnosed from 2010 to 2021, grouped by 3-year periods, to calculate 2-year overall and relative survival.
RESULTS: For 453 patients with metastatic MCC, 2-year relative survival improved from 23% (2010-2012) to 37% (2013-2015), 42% (2016-2018), and 54% (2019-2021) (P \u3c .001). Median overall survival also increased from 9 to 16 months among these patients. In 4786 MCC patients overall, 2-year relative survival rose from 73% (2010-2012) to 81% (2019-2021) (P = .004), while overall survival improved from 67% to 72% (P = .012).
LIMITATIONS: Surveillance, Epidemiology, and End Results lacks case-level data to link ICI treatment directly to survival, although ICIs represent the major recent treatment advance for MCC.
CONCLUSIONS: The introduction of ICIs aligns with a \u3e2-fold increase in survival for advanced MCC patients at the population level, translating to ∼220 fewer deaths per year in the United States
Commercial hybrid graft versus traditional arch replacement with frozen elephant trunk: A multi-institutional comparison.
No full textObjective: Traditional total arch replacement with frozen elephant trunk requires 2 separate grafts in the descending thoracic aorta and arch, and frequently requires a graft-to-graft anastomosis, which is prone to bleeding. The Thoraflex (Terumo Aortic) device treats the arch and descending thoracic aorta in a single device but has not been compared directly to traditional total arch replacement with frozen elephant trunk and has not been studied in a real-world context in the United States.
Methods: A consecutive sample of total arch replacement with frozen elephant trunk patients across 5 different institutions between January 2018 and January 2024, identified 438 patients of which 83 out of 438 (18.9%) had a Thoraflex device. Propensity score matching in a 1:2 ratio identified 166 well-matched controls. Groups were compared across perioperative outcomes.
Results: One hundred forty out of 438 (32%) patients presented with acute type A dissection, 112 out of 438 (26%) had an aneurysm, and 87 out of 438 (20%) had chronic dissection with a previous proximal repair. One hundred thirty-two out of 438 (30%) underwent surgery on an emergency or emergency/salvage basis. Median (interquartile range [IQR]) crossclamp times in the Thoraflex and traditional matched groups were 71 (IQR, 48-105) and 82 (IQR, 62-123), respectively, (P = .012). Total circulatory arrest times were 19 minutes (IQR, 13-32 minutes) and 23 minutes (IQR, 17-37 minutes), respectively (P = .009). Total procedure times were 6.1 hours (IQR, 5.2-7.3 hours) and 6.8 hours (IQR, 5.7-8.2 hours), respectively (P = .012). The operative mortality, stroke, and paralysis rates were 11 out of 83 (13%), 16 out of 83 (19%), and 4 out of 83 (5%), respectively, in the Thoraflex group and were not significantly different than matched controls.
Conclusions: The Thoraflex hybrid device facilitates shorter crossclamp and circulatory arrest times for arch replacement, with similar observed mortality and stroke rates compared with matched controls
Deep Learning Methods in the Imaging of Hepatic and Pancreaticobiliary Diseases.
No full textReports indicate a growing role for artificial intelligence (AI) in the evaluation of pancreaticobiliary and hepatic conditions. A key focus is differentiating between benign and malignant lesions, which is crucial for treatment decisions. AI improves diagnostic accuracy through high sensitivity and specificity, while CNN algorithms enhance image analysis and reduce variability. These advancements aim to match the accuracy of pathologists in cancer detection. In addition, AI aids in identifying diagnostic markers, as early detection is essential. This article reviews the applications of machine learning and deep learning in the diagnosis of hepatic and pancreaticobiliary diseases. Although the use of AI in these specialized areas of gastroenterology is primarily confined to experimental trials, current models demonstrate significant potential for enhancing the detection, evaluation, and treatment planning of hepatic and pancreaticobiliary conditions
Phase 2 trial of perioperative chemo-immunotherapy for gastro-esophageal adenocarcinoma: The role of M2 macrophage landscape in predicting response.
No full textWe present the clinical results of a phase 2 trial combining neoadjuvant docetaxel, cisplatin, 5 Flourouracil, and the PD-L1 inhibitor avelumab in locally advanced gastro-esophageal adenocarcinoma (GEA). Fifty-one patients receive neoadjuvant therapy with 50 proceeding to surgery. Grade 3-4 adverse events occur in 40%; complete/major pathological response is found in 7/50 (14%) and 9/50 (18%), with 2-year disease-free survival of 67.5%. There is no correlation between tumor regression and PD-L1 or mismatch repair (MMR) status. Multiplex immunohistochemistry and longitudinal single-cell transcriptomic profiling reveal alterations in certain innate immune cell populations, particularly noting an M2-tumor-associated macrophage (M2-TAM) proliferation in non-responding tumors. These findings describe the effective nature of this treatment regimen for GEA and reveal associated features of the inflammatory milieux associated with response to chemo-immunotherapy. The specific character of the inflammatory environment in non-responders may, in the future, help personalize treatment. This study was registered at ClinicalTrials.gov (NCT03288350)