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EVEREST-2: A seamless phase 1/2 study of A2B694, a logic-gated Tmod chimeric antigen receptor T-cell (CAR T) therapy, in patients with pancreatic cancer (PANC) or other mesothelin (MSLN)-expressing solid tumors and human leukocyte antigen (HLA)–A*02 loss o
Spencer, Kristen , Grierson, Patrick , Mitchell, Jasmine , Lin, Yi , Vu, Peter , Morelli, Maria Pia , Kundranda, Madappa N. , Dorigo, Oliver , Maloney, David G. , Ward, Jeffrey D. , Welch, John S. , Molina, Julian R. , Go, William Y., Hecht, J. Randolph, Punekar, Salman R. , Castria, Tiago Biachi De , Zhen, David B. , Ward, Jeffrey, Eng, Cathy , Maus, Marcela V , Simeone, Diane M.

Mayo Clinic

Journal of Clinical Oncology | January 27, 2025 | Volume: 43 | Issue: 4_suppl | Pages: No page available

10.1200/jco.2025.43.4_suppl.tps788 Get It

TPS788 Background: MSLN is a desirable candidate for targeted therapy given its limited expression in normal tissues and its overexpression in several malignancies, including PANC, mesothelioma, non-small cell lung, and ovarian cancers (TCGA 2022). MSLN-targeted CAR T and T-cell receptor therapies have shown promising clinical activity; however, on-target, off-tumor toxicity, including fatal events, have occurred (1-3). Autologous logic-gated Tmod CAR T therapies address the challenges of on-target, off-tumor toxicity by combining 2 CARs: activating and blocking receptors. The activator recognizes a tumor-associated antigen present on the surface of both tumor and normal cells; the blocker prevents CAR T activity when it binds HLA-A*02, which is present in normal cells and often lost in tumor cells. Thus, in patients with tumor-associated HLA-A*02 LOH, the blocker prevents on-target, off-tumor toxicity on normal cells due to retained HLA-A*02 expression (4). HLA-A*02 LOH is observed in various solid tumors, including ~20% of PANC (5). Two autologous CAR T therapies are currently under investigation: A2B530, targeting carcinoembryonic antigen, in the EVEREST-1 trial, and A2B694, targeting MSLN, in the EVEREST-2 trial, described herein. A2B694 may provide a therapeutic window to treat patients with PANC and other MSLN-expressing solid tumors exhibiting HLA-A*02 LOH due to its unique discriminatory mechanism. Methods: EVEREST-2 (NCT06051695) is a first-in-human, phase 1/2, open-label, nonrandomized study to evaluate the safety and efficacy of A2B694 for recurrent unresectable, locally advanced, or metastatic cancers with MSLN expression, including PANC. Eligible patients must have exhausted options of potentially curative therapy and have recurrent disease. Enrollment to EVEREST-2 occurs through the prescreening study BASECAMP-1 (NCT04981119), in which patients with tumor-associated HLA-A*02 LOH are identified via next-generation sequencing (Tempus AI, Inc) and leukapheresis product is collected. A2B694 is manufactured from cryopreserved T cells when clinically appropriate for patients. The primary objective of phase 1 is to evaluate the safety and tolerability of A2B694 and identify the recommended phase 2 dose (RP2D). The dose-expansion phase will confirm RP2D and collect biomarker data to further characterize A2B694. Phase 2 will assess the primary endpoint overall response rate per RECIST v1.1 and secondary endpoints progression-free survival and overall survival. The first patient was dosed on April 24, 2024 and dose escalation is ongoing. 1. Beatty, et al. Gastroenterology . 2018. 2. Haas, et al. Mol Ther . 2023. 3. Hong, et al. ESMO 2021. Abstr 9590. 4. Hamburger, et al. Mol Immunol . 2020. 5. Hecht, et al. J Clin Oncol . 2022. Clinical trial information: NCT06051695 .
A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia
Sepúlveda, Hugo , Arteaga-Vazquez, Leo J., Blouin, Chad, Binder, Moritz , Chou, Wen‐Chien , Patnaik, Mrinal M. , Rao, Anjana , Binder, Moritz , Chou, Wen-Chien , Dong, Zhen , Fernandez, Jenna , Tien, Hwei‐Fang , Faulkner, Geoffrey J. , Myers, Samuel A.

Mayo Clinic

Proceedings of the National Academy of Sciences | January 3, 2025 | Volume: 122 | Issue: 1 | Pages: No page available

10.1073/pnas.2413302121 | PMID 39752521 Get It

ASXL transcriptional regulator 1 (ASXL1) is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside DNA methyltransferase 3 alpha (DNMT3A) and Tet methylcytosine dioxygenase 2 ( TET2) . CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML) and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways, respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing derepression of silenced elements in heterochromatin. In contrast, the mechanisms that connect mutant ASXL1 and CH are not yet fully understood. CH/CMML-associated ASXL1 mutations encode C-terminally truncated proteins that enhance the deubiquitinase activity of the ASXL-BAP1 “PR-DUB” deubiquitinase complex, which removes monoubiquitin from H2AK119Ub. Here, we show that ASXL1 mutant proteins interact with the euchromatic histone lysine methyltransferases 1 and 2 (EHMT1–EHMT2) complex, which generates H3K9me1 and me2, the latter a repressive modification in constitutive heterochromatin. Compared to cells from age-matched wild-type mice, we found that expanded myeloid cells from old (≥18-mo-old) Asxl1tm/+ mice, a heterozygous knock-in mouse model of CH, display genome-wide decreases of H3K9me2, H3K9me3, and H2AK119Ub as well as an associated increase in expression of transposable elements (TEs) and satellite repeats. Increased TE expression was also observed in monocytes from ASXL1 -mutant CMML patients compared to monocytes from healthy controls. Our data suggest that mutant ASXL1 proteins compromise the integrity of both constitutive and facultative heterochromatin in an age-dependent manner by reducing the levels of H3K9me2/3 and H2AK119Ub. This increase in TE expression correlated with increased expression of nearby genes, including many interferon-inducible (inflammation-associated) genes (ISGs).
Intravascular Imaging‐Guided Versus Angiography‐Guided Percutaneous Coronary Intervention in Patients With ST‐Segment Elevation Myocardial Infarction in the United States
Krittanawong, Chayakrit , Ang, Song Peng , Maitra, Neil Sagar , Wang, Zhen , Jneid, Hani , Sharma, Samin K. , Jneid, Hani , Ang, Song P , Krittanawong, Chayakrit , Alam, Mahboob

Mayo Clinic

Catheterization and Cardiovascular Interventions | December 31, 2024 | Volume: 105 | Issue: 4 | Pages: 745-751

10.1002/ccd.31389 | PMID 39737533 Get It

ABSTRACTBackgroundThe role of Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) is still unclear in patients with STEMI undergoing PCI in the current second‐generation DES era.AimsThis study aimed to evaluate the trends and outcomes of IVUS‐guided PCI in patients with STEMI.MethodsWe used the National Inpatient Sample (NIS) database from 2016 to 2021. The primary endpoint of this study is all‐cause in‐hospital mortality. Secondary endpoints include trends of PCI hospitalizations, trends of mortality, length of stay, and cost of hospitalization.ResultsThere were data for 819,645 hospitalizations for STEMI, of which 91.2% (n = 74,7860) utilized angiography‐guided PCI, 8.4% (n = 68,985) utilized IVUS‐guided PCI and 0.3% (n = 2800) utilized OCT‐guided PCI. In‐hospital mortality for IVUS‐guided PCI was 4.6% (n = 3190) versus 6.0% (n = 44,935) for angiography‐guided PCI with an adjusted OR 0.75 (0.68–0.81, p < 0.001). In‐hospital mortality for OCT‐guided PCI was 3.4% (n = 95) versus 6.0% (n = 44,935) for angiography‐guided PCI with an adjusted OR 0.67 (0.43–1.06, p = 0.09).ConclusionsIVUS/OCT‐guidance was increasingly utilized over the years and was associated with a significantly reduced adjusted odds of in‐hospital mortality. Large‐scale, long‐term randomized data are needed to better ascertain where IVUS/OCT may be best utilized for optimization of PCI for STEMI.
Impact of smoking on the detection of brain aneurysms in general population screening: a systematic review and meta-analysis
Ghoche, Maged T. , Maroufi, Seyed Farzad , Maalouf, Jorge Fouad , Pachón-Londoño, María José , Nguyen, Brandon , Halpin, Brooke S. , Turcotte, Evelyn L. , Patra, Devi P. , Krishna, Chandan , Turkmani, Ali , Ogilvy, Christopher S., Ogilvy, Christopher S. , Patra, Devi, Ogilvy, Christopher S , Maalouf, Joy M. El, Wang, Zhen , Bendok, Bernard R.

Mayo Clinic

Journal of Neurosurgery | December 27, 2024 | Volume: 142 | Issue: 5 | Pages: 1397-1405

10.3171/2024.7.jns241015 | PMID 39729618 Get It

OBJECTIVE While the relationship between smoking and subarachnoid hemorrhage is well established, data regarding the probability of detecting unruptured intracranial aneurysms (UIAs) in smokers remain sparse. The aim of this systematic review and meta-analysis is to provide a comprehensive understanding of the relationship between smoking and the likelihood of identifying UIAs in healthy asymptomatic patients who underwent brain imaging for indications unrelated to UIAs. METHODS A systematic review was conducted following the PRISMA guidelines. The PubMed and Scopus databases were searched for studies published before March 2024 that reported on the presence of UIAs in healthy asymptomatic patients who had undergone brain imaging for indications unrelated to UIAs. Three independent reviewers assessed the eligibility of all retrieved studies. Risk of bias for the included observational studies was assessed using the methodological index for non-randomized studies. Data on UIA prevalence, smoking status, and patient and aneurysm characteristics were extracted. The association between smoking and the presence of UIA was studied. A prevalence proportional meta-analysis was conducted across the included studies. A meta-analysis was performed with a random-effects model by using summary statistics from the included studies. RESULTS Six studies involving 47,788 patients who had undergone brain imaging were identified for quantitative analysis. The pooled UIA prevalence in the sample was 3.07% (95% CI 2.27%–4.16%). Patients who smoked had higher rates of aneurysm detection than the patients who did not smoke (pooled prevalence of 2.96%, 95% CI 2.68%–3.27% vs 2.23%, 95% CI 2.08%–2.39%). Although the relation between the two was not statistically significant (p = 0.06), smoking was associated with higher odds for UIA detection, yielding an OR of 1.34 (95% CI 1.07–1.67) with an I 2 value of 53%. CONCLUSIONS This study suggests a potentially higher risk of UIAs in patients who smoked than in those who never smoked. However, the results of this meta-analysis revealed that smoking was not statistically associated with higher UIA detection. This result could be explained by the limited number of studies published on this topic. If these findings reach statistical significance in future larger studies, it could justify revising guidelines to include cigarette smokers in intracranial aneurysm screening.
Accuracy of a Bleeding Assessment Tool in Predicting the Diagnosis of an Inherited Bleeding Disorder: Systematic Review and Meta-Analysis
Al‐Huniti, Ahmad , Rand, Margaret L. , Kearney, Susan , Pruthi, Rajiv K. , Abdallah, Heba, Sharathkumar, Anjali , Sridharan, Meera , Wang, Zhen

Mayo Clinic

Blood | December 5, 2024 | Volume: 144 | Issue: Supplement 1 | Pages: 1217-1217

10.1182/blood-2024-202703 Get It

Introduction Assessing bleeding symptoms is essential for diagnosing bleeding disorders. Bleeding assessment tools (BATs) were developed to standardize the collection of bleeding symptoms and their severity, thereby enhancing the diagnostic accuracy. However, their diagnostic precision across various inherited bleeding disorders remains unclear. Therefore, we conducted a systematic literature and meta-analysis to evaluate the diagnostic accuracy of BATs in pediatric and adult populations. This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of BATs in pediatric and adult populations. Objective: To evaluate the diagnostic effectiveness of BATs in identifying laboratory-confirmed inherited bleeding disorders. Methods Literature Search Strategy: A comprehensive systematic literature search was conducted across Scopus, Embase, Web of Science, MEDLINE, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, and the World Health Organization databases from inception until January 27, 2024 Study Selection: Two independent reviewers screened titles and abstracts using Covidence (Covidence systematic review software, Veritas Health Innovation). Data extraction was performed independently by two authors reviewing and collecting data in duplicate from all selected articles. Eligibility Criteria: Included studies reported on the diagnostic accuracy of any BAT in diagnosing inherited bleeding disorders. Exclusion criteria included abstracts, review articles, case reports/series, studies focusing solely on distinguishing specific bleeding disorders, and those lacking sufficient data to assess test accuracy. Quality Assessment: Risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Two authors assessed each article independently and each study was categorized as having a low, moderate, or high risk of bias. Results Of 7,009 studies identified, 31 met the inclusion criteria, comprising 6,962 patients (2,152 with bleeding disorders, 4,810 controls). Most studies (74%) were prospective. Studies assessed various bleeding disorders: 39% all types, 32% von Willebrand Disease (VWD), 10% Inherited Platelet Function Disorder (IPFD), 10% both VWD and IPFD, and 10% other rare disorders. The ISTH-BAT was the most frequently used tool (47%), followed by MCMDM-1 VWD (21%) and PBQ (18%). The pooled prevalence of confirmed bleeding disorder in all prospective studies was 32% (range, 3%-71%). The pooled sensitivity for BAT in all included studies (31 studies) was 82% (95% CI, 76.5%-86.7%) and the specificity was 66% (95% CI, 54%-76%). Subgroup analysis revealed that the ISTH-BAT (studies: BD 6, VWD 5, IPFD 3, GT/BSS 2), had a sensitivity of 77% (95% CI, 69%-84%) and a specificity of 70% (95% CI, 58%-80%), the MCMDM-1 VWD (studies: VWD 4, BD 2, GT/BSS 1) had sensitivity of 78% (95% CI, 61%-89%) and a specificity of 79% (95% CI, 54%-92%) , and the Pediatric Bleeding Questionnaire (studies: BD 3, VWD 2, VWD/IPFD 1) had a sensitivity of 93% (95% CI, 85%-97%) and a specificity of 73% (95% CI, 41%-92%) . The sensitivity and specificity of BATs for studies investigating all types of bleeding disorders (12 studies) soley VWD (10 studies), and soley IPFD (3 studies) were 80% (95% CI, 67%-88%) and 50% (95% CI, 34%-67%) , 79% (95% CI, 71%-86%) and 83% (95% CI, 59%-95%), and 85% (95% CI, 79%-89%) and 74% (95% CI, 56%-86%), respectively. Significant heterogeneity was observed across studies in terms of populations, BATs used, and diagnostic methods. This heterogeneity limits the generalizability of the results and suggests that BAT performance may vary depending on the specific clinical context and patient population. Additionally, 26% of studies were classified as having a high risk of bias, potentially affecting the reliability of some findings. Conclusion Despite heterogeneity, this meta-analysis supports the use of BATs as valuable screening tools for inherited bleeding disorders, demonstrating generally high sensitivity across various patient populations. However, the variability in specificity across different disorders and tools underscores the need for careful selection and interpretation of BATs in clinical practice. Further standardization of BATs and diagnostic criteria could improve their utility in diverse clinical settings.
Development of a Risk Prediction Model for 6-Month Early Mortality in Patients with Systemic Light Chain Amyloidosis Treated with Daratumumab-Based Frontline Therapy
Bazarbachi, Abdul-Hamid, Zanwar, Saurabh , Bodanapu, Geethika , Chen, Gui-Zhen , Kumar, Shaji , Lentzsch, Suzanne , Patwari, Anannya , Wang, Shikun , Cowan, Andrew J., Mellgard, George , Bazarbachi, Abdul Hamid , Hegenbart, Ute , Bhutani, Divaya , Chen, Guizhen, D’Souza, Anita , Dispenzieri, Angela , Gertz, Morie A. , Milani, Paolo , Muchtar, Eli , Palladini, Giovanni , Sanchorawala, Vaishali , Schönland, Stefan , Chakraborty, Rajshekhar

Mayo Clinic

Blood | December 5, 2024 | Volume: 144 | Issue: Supplement 1 | Pages: 287-287

10.1182/blood-2024-202589 Get It

Background: Despite substantial improvements in early mortality (EM) for patients with systemic light chain amyloidosis (AL), rates remained high in the bortezomib-era, at approximately 25% (Muchtar et al. Blood. 2017). However, the therapeutic landscape in AL amyloidosis has changed with the ANDROMEDA trial, which led to the approval of daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone (Dara-VCd) in the frontline setting. The incidence and predictors of EM in the context of daratumumab-based frontline therapy have not been studied. Methods: We performed an international multicenter retrospective cohort study of all consecutive patients with newly diagnosed AL treated with frontline Dara-VCd or Dara-Vd, and followed until 12/31/2023. EM was defined as death from any cause within 6 months of treatment initiation. Our primary objective was to identify the rate and significant predictors of EM. Univariate logistic regression was used to identify significant predictors of EM, which were then included in a multivariate logistic regression model. The receiver operator characteristic (ROC) analysis was used to determine the best threshold values that discriminated EM rates for the following continuous variables: age, dFLC (involved-uninvolved), eGFR, NT-proBNP, albumin, and high-sensitivity Troponin-T (hs-TnT). Other variables tested in univariate analysis were the following: ECOG performance status, NYHA functional class, sex, race, light chain isotype, percent bone marrow plasma cells, status of the following cytogenetic abnormalities-t(11;14), +1q, hyperdiploidy, del(13q), high-risk translocations, and del(17p), and the number of organs involved (2 vs 1). To build the clinical prediction score, each variable was weighted according to the β coefficient (natural logarithm of odds ratio) obtained from the multivariable regression. The β coefficients were rounded to the nearest 0.5 and multiplied by 2 to obtain an even number. Results The study cohort included 335 AL patients treated with daratumumab-based frontline therapy (92.2% Dara-VCd, 7.8% Dara-Vd), with all surviving patients having at least 6 months of follow-up. The median age at diagnosis was 66.5 years (range, 59.4 - 71.3), and 6.7% (n = 22) were Non-Hispanic blacks. Median dFLC at diagnosis was 22.91 mg/dL (range, 0.2-1093.4), and median NT-proBNP was 2415 pg/mL (range, 13-70,000). Mayo 2004 stages IIIA/IIIB represented 44% of the total cohort, with 17% having ECOG ≥ 2 and 25.4% having NYHA Class III/IV symptoms. The cumulative incidence of EM was 10.7%, with the incidence in patients with Mayo 2004 stage I, II, IIIA, and IIIB being 0%, 8%, 12.5%, and 25% respectively. On univariate analysis with unadjusted odds ratio (OR), the following variables significantly predicted EM: Age ≥ 75 (OR=2.8, p=0.013) ECOG ≥ 2, (OR 4.9, p&lt;0.001), NYHA Class ≥ III (OR=4.95, p&lt;0.001), dFLC ≥9 mg/dL (OR, 10.18, p=0.023), eGFR &lt;33 mL/min/1.73 m2 (OR=2.7, p=0.026), NT-proBNP &gt;5276 pg/mL (OR=7.69, p &lt;0.001), hs-TnT &gt;70 ng/L (OR=5.88, p&lt;0.001), and absence of t(11; 14) (OR=2.33, p=0.041). These variables were entered into multivariate regression, except for ECOG and NYHA, which were combined to create a single variable (values ranging from 0-8), and hs-TnT was dropped due to substantial missing data as centers used different troponin assays. NT-proBNP was rounded to 5300 pg/ml for ease of clinical application. Based on the multivariate analysis, the following scores were assigned to each variable: Age ≥75 (2.0), ECOG+NYHA (1.0 x combined score), NT-proBNP &gt;5,300 pg/ml (2.0), and absence of t(11;14) (3.0). This led to a score ranging from 1-15, and two risk-groups: low-risk (score &lt;9; 87.5%) and high-risk (score ≥9; 12.5%). The respective cumulative incidence of EM was 6.1% versus 50% (p&lt;0.001). The c-index of the model was 0.725 (95% CI, 0.676-0.774). Conclusion: Using variables that are readily available in the clinic, we have developed a two-tiered risk-prediction model for EM in AL amyloidosis in the context of daratumumab-based frontline therapy. The model needs to be externally validated in an independent dataset.
Predictors of Early Safety Outcomes with Axicabtagene Ciloleucel (axi-cel) in Patients with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)
Strouse, Christopher , Vallurupalli, Anusha , Jacobson, Caron A. , Baird, John H. , Patel, Dilan A. , Dahiya, Saurabh , Hemmer, Michael, Du, Bing, Spooner, Clare, Mirjah, Debbie L., Hu, Zhen‐Huan , Pasquini, Marcelo C. , Strouse, Christopher S , Farooq, Umar , Shouval, Roni , Moskop, Amy , Locke, Frederick L. , Strati, Paolo , Du, Brad, Kim, Jaeyeon , Lin, Yi

Mayo Clinic

Blood | December 5, 2024 | Volume: 144 | Issue: Supplement 1 | Pages: 609-609

10.1182/blood-2024-207976 Get It

Background: Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are known safety concerns following chimeric antigen receptor (CAR) T-cell therapy. Axi-cel, a CAR T-cell therapy approved in the US for adults with R/R LBCL after ≥ 1 line of prior therapy (2L+), has been administered in the outpatient setting, where a common cause for post-infusion hospital admissions were CAR T-cell-related toxicities (Furqan et al., 2024). Due to reimbursement policies in the US, patients at higher risk for safety events requiring inpatient care within 3 days of infusion may not be ideal candidates for outpatient care. We sought to identify what pre-infusion characteristics may put patients more at risk for developing early CRS and ICANS after axi-cel. Methods : Patients receiving axi-cel for R/R LBCL 2L+ between 01/2021−10/2023 registered in the Center for International Blood and Marrow Transplant Research (CIBMTR) observational database were potentially eligible for analysis. Patients with prior non-transplant cellular therapy or missing data for analysis were excluded. Primary endpoints were onset of early CRS and early ICANS, defined as an any grade event within 3 calendar days of axi-cel infusion (date of infusion is defined as Day 0 and onset of CRS/ICANS before the end of Day 3 is an early event). Early Grade ≥ 2 and early Grade ≥ 3 CRS and ICANS (onset of CRS/ICANS before the end of Day 3 and maximum Grade ≥ 2 and ≥ 3 per ASTCT Criteria) were also evaluated. Patient demographics, ECOG PS, comorbidities, disease characteristics at diagnosis and prior to infusion, line of therapy (LoT), lab assessments prior to infusion, and infusion-related attributes were evaluated by univariate screening and multivariable regression for development of early CRS or early ICANS. Results: A total of888 patients from 105 centers were included in the analysis. Median age was 63 years (45% ≥ 65 years) and 66% were male. At LBCL diagnosis, 22% of patients had a histological transformation. Prior to infusion, 5% of patients had ECOG PS ≥ 2 and 70% had at least 1 clinically significant comorbidity. Half (50%) of patients received axi-cel with 1 prior LoT (2L) and 10% of patients underwent a prior autologous hematopoietic cell transplant. Median time from leukapheresis to infusion was 30 days (interquartile range [IQR] 27−34). Bridging therapy of any type was administered in 59%, and systemic bridging therapy in 48%, of patients and 14% of patients were intended to be treated in the outpatient setting. Thirty percent of patients had chemo-sensitive disease prior to infusion. Median follow-up post-infusion was 12.3 months (range 3−38). Median time to onset of CRS was 4 days (IQR 2−6) and 84% of patients experienced CRS at any time. Early any grade (Grade ≥ 3) CRS was observed in 47% (3%) of patients. In the multivariate analysis of early any grade CRS, only prior LoT (≥ 2 vs 1) was associated with lower risk (OR 0.71; 95% CI 0.55−0.94), but this association was not seen in the analyses of early Grade ≥ 2 nor early Grade ≥ 3 CRS. Notably, 47% and 52% of patients with ≥ 2 vs 1 prior LoT, respectively, only experienced early Grade 1 CRS (defined as fever only). In the analysis of early Grade ≥ 3 CRS, only ECOG PS 0−1 was associated with lower risk vs patients with ECOG PS ≥ 2 (OR 0.17; 95% CI 0.06−0.48). Median time to onset of ICANS was 7 days (IQR 5−9) and 47% of patients experienced ICANS at any time. Early any grade (Grade ≥ 3) ICANS occurred in 9% (5%) of patients. After multivariate adjustment, age &lt; 65 vs ≥ 65 (OR 0.38 [95% CI 0.23−0.62]) and 1 vs ≥ 2 prior LoT (OR 0.58 [95% CI 0.36−0.95]) were associated with lower risk of early any grade ICANS. Age &lt; 65 vs ≥ 65 was also associated with lower risk of early Grade ≥ 3 ICANS (OR 0.31 [95% CI 0.15−0.61]), as was ECOG PS 0−1 vs ECOG PS ≥ 2 (OR 0.30 [95% CI 0.11−0.83]). Comorbidities were evaluated and no significant associations with early CRS nor early ICANS were found. Conclusions: This analysis of readily available clinical variables in a real-world contemporary cohort of patients treated with axi-cel demonstrates that younger patients and patients with better ECOG PS have lower risk of early CRS and early ICANS. Axi-cel in 2L setting, vs 3L+, is associated with lower risk of early any grade ICANS and comparable early Grade ≥ 2 CRS, but a higher risk of early fever. These results further enable a more informed decision of patient selection for physicians, which is critical for the success of outpatient administration.
Accuracy of Fecal Polymerase Chain Reaction Testing in Clarithromycin-Resistant Helicobacter Pylori: A Systematic Review and Meta-Analysis
Qady, Ahmed Al , Salih, Mohamed, Ali, Marriam, Menakuru, Sasmith, Nayar, Kapil Dev, Wang, Zhen , Bi, Yan , Al Qady, Ahmed , Aldhaleei, Wafa, Harris, Dana, Aldhaleei, Wafa Ali , Nayar, Kapil Dev, Stancampiano, Fernando F. , Harris, Dana M.

Mayo Clinic

Clinical and Translational Gastroenterology | December 2, 2024 | Volume: 16 | Issue: 2 | Pages: e00792

10.14309/ctg.0000000000000792 | PMID 39620581 Get It

INTRODUCTION: The increasing prevalence of clarithromycin (CLA)-resistant Helicobacter pylori (H. pylori) strains poses a significant challenge in the management of H. pylori infections. This systematic review and meta-analysis investigates the diagnostic accuracy of polymerase chain reaction (PCR) in identifying CLA-resistant H. pylori strains in stool. METHODS: A comprehensive literature search was conducted using PubMed, Embase, and Cochrane databases from database inception to April 30, 2023. Eligible studies evaluated the effectiveness of PCR stool tests in detecting CLA-resistant H. pylori strains in adults (>18-year-old). Studies of pediatric populations, alternative methods to PCR or stool samples, and reference tests other than gastric biopsy were excluded. The bivariate random-effects model was used to pool diagnostic accuracy from the included studies. RESULTS: The analysis of 11 prospective diagnostic studies with a total of 866 patients showed a pooled sensitivity of 0.97 (95% CI: 0.9–0.99) and a pooled specificity of 0.98 (95% CI: 0.81–1.00). Subgroup analysis based on the used technique demonstrated consistent findings without notable variations. The diagnostic odds ratio was calculated at 1843.92 (95% CI: 134.28–25,321.3). The positive likelihood ratio was determined as 51.02 (95% CI: 4.61–564.5), while the negative likelihood ratio was found to be 0.03 (95% CI: 0.01–0.1). DISCUSSION: PCR testing for clarithromycin-resistant H. pylori was highly sensitive and specific across studies with proven reliability in clinical practice, particularly in outpatient settings. Their implementation offers cost-effectiveness and the potential for tailored treatment strategies, holding promise for improved patient outcomes.
Conservative Approach versus Percutaneous Coronary Intervention in Patients with Spontaneous Coronary Artery Dissection from a National Population-Based Cohort Study
Krittanawong, Chayakrit , Rodriguez, Beatriz Castillo , Qadeer, Yusuf Kamran , Wang, Zhen , Sharma, Samin K. , Jneid, Hani , Krittanawong, Chayakrit , Ang, Song Peng , Wang, Zhen, Alam, Mahboob

Mayo Clinic

Reviews in Cardiovascular Medicine | November 27, 2024 | Volume: 25 | Issue: 11 | Pages: No page available

10.31083/j.rcm2511404 | PMID 39618857 Get It

Background: Spontaneous coronary artery dissection (SCAD) is a rare and often underdiagnosed cause of acute coronary syndrome (ACS), predominantly affecting younger women without traditional cardiovascular risk factors. The management of SCAD remains a subject of debate, likely secondary to inconclusive evidence. This study aims to compare the clinical outcomes of SCAD patients treated with optimal medical therapy (OMT) versus those who underwent percutaneous coronary intervention (PCI) using a national population-based cohort. Methods: We conducted a retrospective analysis using the National Inpatient Sample (NIS) database from 2016 to 2020. The study included patients identified with SCAD using the ICD-10-CM (the International Classification of Diseases, Tenth Revision, Clinical Modification) code I25.42. We excluded individuals who did not receive PCI or coronary angiography, those who underwent coronary artery bypass grafting, and patients with incomplete records. The primary outcome was in-hospital mortality, while secondary outcomes included acute kidney injury, cardiac arrest, cardiogenic shock, use of temporary mechanical circulatory support, cost of hospitalization, and length of stay. National estimates were obtained using discharge weights, and statistical comparisons were performed using chi-square tests and linear regression. Multivariate logistic regression was employed to identify predictors of mortality and other outcomes. Results: A total of 31,105 SCAD patients were included in the study, with 10,480 receiving OMT and 20,625 undergoing PCI. Patients in the PCI group were older (mean age 64 vs. 54 years) and had higher comorbidities compared to those in the OMT group. The proportion of SCAD patients receiving PCI declined from 72% in 2016 to 60% in 2020. In multivariable analysis, PCI was associated with increased in-hospital mortality (odds ratio (OR) 1.89, 95% confidence interval (CI) 1.24–2.90, p = 0.0003), cardiogenic shock (OR 2.29, 95% CI 1.71–3.07, p < 0.0001), use of a left ventricular assist device (LVAD) (OR 3.97, 95% CI 2.42–6.53, p < 0.0001), and an intra-aortic balloon pump (IABP) (OR 2.24, 95% CI 1.63–3.09, p < 0.0001). Trends also suggested an association between PCI and cardiac arrest, extracorporeal membrane oxygenation (ECMO), and acute kidney injury (AKI). The PCI group had significantly higher hospitalization costs and longer lengths of stay compared to the OMT group (both p < 0.001). Conclusions: In this large, national cohort study, SCAD patients who underwent PCI had significantly higher risks of adverse in-hospital outcomes, including mortality, compared to those treated with OMT. These findings underscore the importance of careful patient selection and the potential advantages of conservative management in SCAD, particularly in patients without severe or unstable presentations. Further research is needed to develop evidence-based guidelines for the optimal management of SCAD.
National Trends, Mortality and Outcomes in Intravascular Imaging-Guided Versus Angiography-Guided Percutaneous Coronary Intervention in the United States
Krittanawong, Chayakrit , Qadeer, Yusuf Kamran , Wang, Zhen , Jneid, Hani, Sharma, Samin, Krittanawong, Chayakrit , Ang, Song Peng , Alam, Mahboob , Jneid, Hani , Sharma, Samin

Mayo Clinic

Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine | November 22, 2024 | Volume: 23 | Issue: 4 | Pages: 202-206

10.1097/hpc.0000000000000363 | PMID 38768049 Get It

Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have become increasingly utilized in patients undergoing percutaneous coronary intervention (PCI). Despite these purported advantages, prior reports regarding the use of IVUS and OCT have indicated that contemporary use of intravascular imaging remains low with significant regional variation. Here, we present the findings of an updated contemporary analysis regarding the use of IVUS/OCT-guided PCI versus angiography-guided PCI in the United States. We also evaluated in-hospital mortality and clinical outcomes between IVUS/OCT-guided PCI versus angiography-guided PCI-only over million patients in the United States. There has been a significant decrease in the number of PCIs performed, while there has been increasing in the trend of IVUS/OCT-guided PCI over this period. Most importantly, we found that IVUS/OCT-guided PCI was associated with better clinical outcomes in terms of in-hospital mortality, compared with angiography-guided PCI.