tbuckley/cabot-search huggingface dataset:
A comparative immunological assessment of multiple clinical-stage adjuvants for the R21 malaria vaccine in nonhuman primates
Authors: Prabhu S. Arunachalam, NaYoung Ha, S. Moses Dennison, Rachel L. Spreng, Kelly E. Seaton, Peng Xiao, Yupeng Feng, Veronika I. Zarnitsyna, Dmitri Kazmin, Mengyun Hu, Jordan M. Santagata, Xia Xie, Kenneth Rogers, Lisa M. Shirreff, Claire Chottin, Alexandra J. Spencer, Sheetij Dutta, Katherine Prieto, Jean-Philippe Julien, Mark Tomai, Christopher B. Fox, Francois Villinger, Adrian V. S. Hill, Georgia D. Tomaras, Bali Pulendran
Journal: Science Translational Medicine (2024)

Authorization of the Matrix-M (MM)–adjuvanted R21 vaccine by three countries and its subsequent endorsement by the World Health Organization for malaria prevention in children are a milestone in the fight against malaria. Yet, our understanding of the innate and adaptive immune responses elicited by this vaccine remains limited. Here, we compared three clinically relevant adjuvants [3M-052 + aluminum hydroxide (Alum) (3M), a TLR7/8 agonist formulated in Alum; GLA-LSQ, a TLR4 agonist formulated in liposomes with QS-21; and MM, the now-approved adjuvant for R21] for their capacity to induce durable immune responses to R21 in macaques. R21 adjuvanted with 3M on a 0, 8, and 23–week schedule elicited anti-circumsporozoite antibody responses comparable in magnitude to the R21/MM vaccine administered using a 0-4-8–week regimen and persisted up to 72 weeks with a half-life of 337 days. A booster dose at 72 weeks induced a recall response similar to the R21/MM vaccination. In contrast, R21/GLA-LSQ immunization induced a lower, short-lived response at the dose used. Consistent with the durable serum antibody responses, MM and 3M induced long-lived plasma cells in the bone marrow and other tissues, including the spleen. Furthermore, whereas 3M stimulated potent and persistent antiviral transcriptional and cytokine signatures after primary and booster immunizations, MM induced enhanced expression of interferon- and T H 2-related signatures more highly after the booster vaccination. Collectively, these findings provide a resource on the immune responses of three clinically relevant adjuvants with R21 and highlight the promise of 3M as another adjuvant for malarial vaccines.
CHIP: a clonal odyssey of the bone marrow niche
Authors: Wolfgang E. Schleicher, Bridget Hoag, Marco De Dominici, James DeGregori, Eric M. Pietras
Journal: Journal of Clinical Investigation (2024)

Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the selective expansion of hematopoietic stem and progenitor cells (HSPCs) carrying somatic mutations. While CHIP is typically asymptomatic, it has garnered substantial attention due to its association with the pathogenesis of multiple disease conditions, including cardiovascular disease (CVD) and hematological malignancies. In this Review, we will discuss seminal and recent studies that have advanced our understanding of mechanisms that drive selection for mutant HSPCs in the BM niche. Next, we will address recent studies evaluating potential relationships between the clonal dynamics of CHIP and hematopoietic development across the lifespan. Next, we will examine the roles of systemic factors that can influence hematopoietic stem cell (HSC) fitness, including inflammation, and exposures to cytotoxic agents in driving selection for CHIP clones. Furthermore, we will consider how - through their impact on the BM niche - lifestyle factors, including diet, exercise, and psychosocial stressors, might contribute to the process of somatic evolution in the BM that culminates in CHIP. Finally, we will review the role of old age as a major driver of selection in CHIP.
Astrocytes: a star emerges in the control of reproductive hormones
Authors: Ali Abbara, Waljit S. Dhillo
Journal: Journal of Clinical Investigation (2024)

Kisspeptin is an essential neuropeptide sitting at the apex of the hypothalamo-pituitary-gonadal (HPG) endocrine axis to regulate gonadotropin-releasing hormone (GnRH) neurons and downstream reproductive hormones. Kisspeptin neurons integrate feedback from sex steroids facilitating regulation of the menstrual cycle and mediate the effects of metabolic stressors on the reproductive axis. In this issue of the JCI, Torres and colleagues describe another pathway for kisspeptin signaling in astrocytes to influence GnRH neuronal output. Astrocytes had kisspeptin receptors that activated canonical intracellular signaling pathways to constrain the magnitude of kisspeptin-induced GnRH neuronal stimulation. Additionally, the appositions between kisspeptin and GnRH neurons were dynamic during the ovarian cycle, with astrocyte kisspeptin signaling proposed as a putative modulator of this neuroplasticity. Importantly, astrocyte kisspeptin signaling also mediated susceptibility to metabolic stressors and the development of obesity-induced hypogonadism, underscoring the physiological and pathological importance of this pathway and revealing the importance of nonneuronal signaling in reproductive health.
A pathologically expanded, clonal lineage of IL-21–producing CD4+ T cells drives inflammatory neuropathy
Authors: Maryamsadat Seyedsadr, Madison F. Bang, Ethan C. McCarthy, Shirley Zhang, Ho-Chung Chen, Mahnia Mohebbi, Willy Hugo, Jason K. Whitmire, Melissa G. Lechner, Maureen A. Su
Journal: Journal of Clinical Investigation (2024)

Inflammatory neuropathies, which include chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain Barré syndrome (GBS), result from autoimmune destruction of the PNS and are characterized by progressive weakness and sensory loss. CD4+ T cells play a key role in the autoimmune destruction of the PNS. Yet, key properties of pathogenic CD4+ T cells remain incompletely understood. Here, we used paired single-cell RNA-Seq (scRNA-Seq) and single-cell T cell receptor–sequencing (scTCR-Seq) of peripheral nerves from an inflammatory neuropathy mouse model to identify IL-21–expressing CD4+ T cells that were clonally expanded and multifunctional. These IL-21–expressing CD4+ T cells consisted of 2 transcriptionally distinct expanded cell populations, which expressed genes associated with T follicular helper (Tfh) and T peripheral helper (Tph) cell subsets. Remarkably, TCR clonotypes were shared between these 2 IL-21–expressing cell populations, suggesting a common lineage differentiation pathway. Finally, we demonstrated that IL-21 receptor–KO (IL-21R–KO) mice were protected from neuropathy development and had decreased immune infiltration into peripheral nerves. IL-21 signaling upregulated CXCR6, a chemokine receptor that promotes CD4+ T cell localization in peripheral nerves. Together, these findings point to IL-21 signaling, Tfh/Tph differentiation, and CXCR6-mediated cellular localization as potential therapeutic targets in inflammatory neuropathies.
Genetic insights into the mechanisms of proliferative glomerulonephritis
Authors: Gentzon Hall
Journal: Journal of Clinical Investigation (2024)

Glomerular visceral epithelial cells (i.e., podocytes) are an essential component of the tripartite glomerular filtration barrier. Healthy podocytes are terminally differentiated cells with limited replicative capacity; however, inappropriate cell cycle reentry can be induced in podocytes by various injurious stimuli. In this issue of the JCI, Yamaguchi et al. report on a somatic mosaic gain-of-function mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic α subunit (p110α, encoded by PIK3CA). The study reveals that activating mutations of p110α can drive podocyte proliferation in PIK3CA-related overgrowth syndrome (PROS). They also showed that selective, small-molecule inhibitors of p110 may be useful for the treatment of proliferative glomerulonephritis.
Convergent generation of atypical prions in knockin mouse models of genetic prion disease
Authors: Surabhi Mehra, Matthew E.C. Bourkas, Lech Kaczmarczyk, Erica Stuart, Hamza Arshad, Jennifer K. Griffin, Kathy L. Frost, Daniel J. Walsh, Surachai Supattapone, Stephanie A. Booth, Walker S. Jackson, Joel C. Watts
Journal: Journal of Clinical Investigation (2024)

Most cases of human prion disease arise due to spontaneous misfolding of WT or mutant prion protein, yet recapitulating this event in animal models has proven challenging. It remains unclear whether spontaneous prion generation can occur within the mouse lifespan in the absence of protein overexpression and how disease-causing mutations affect prion strain properties. To address these issues, we generated knockin mice that express the misfolding-prone bank vole prion protein (BVPrP). While mice expressing WT BVPrP (I109 variant) remained free from neurological disease, a subset of mice expressing BVPrP with mutations (D178N or E200K) causing genetic prion disease developed progressive neurological illness. Brains from spontaneously ill knockin mice contained prion disease-specific neuropathological changes as well as atypical protease-resistant BVPrP. Moreover, brain extracts from spontaneously ill D178N- or E200K-mutant BVPrP-knockin mice exhibited prion seeding activity and transmitted disease to mice expressing WT BVPrP. Surprisingly, the properties of the D178N- and E200K-mutant prions appeared identical before and after transmission, suggesting that both mutations guide the formation of a similar atypical prion strain. These findings imply that knockin mice expressing mutant BVPrP spontaneously develop a bona fide prion disease and that mutations causing prion diseases may share a uniform initial mechanism of action.
Unleashing PD-1: a duel of immunity in aortic aneurysm formation
Authors: Zhenguo Wang, Y. Eugene Chen, Lin Chang
Journal: Journal of Clinical Investigation (2024)

Aortic aneurysms, particularly abdominal aortic aneurysms (AAAs), exhibit sex differences, with higher prevalence and severity in males than females, both in humans and experimental mouse models. In fact, male sex has been considered as the most potent nonmodifiable risk factor for AAA. Currently, there are no medications approved for the treatment of aortic aneurysms, despite the high lethality of ruptured aneurysms, which account for nearly 2% of all deaths. Moreover, the underlying molecular mechanisms mediating the sexual dimorphism of aortic aneurysms remain largely unknown. In this issue of the JCI, Mu et al. revealed a mechanism by which androgens, male sex hormones, exacerbate aortic aneurysms by suppressing programmed cell death protein 1 (PD-1) expression in T cells in an aldosterone and high salt-induced aortic aneurysm mouse model.
Striking a balance: the Goldilocks effect of CD8α expression on NK cells
Authors: Paarth B. Dodhiawala, Frank Cichocki
Journal: Journal of Clinical Investigation (2024)

NK cells are cytotoxic innate immune cells involved in antitumor immunity, and they provide a treatment option for patients with acute myeloid leukemia (AML). In this issue of the JCI, Cubitt et al. investigated the role of CD8α, a coreceptor present on approximately 40% of human NK cells. IL-15 stimulation of CD8α- NK cells induced CD8α expression via the RUNX3 transcription factor, driving formation of a unique induced CD8α (iCD8α+) population. iCD8α+ NK cells displayed higher proliferation, metabolic activity, and antitumor cytotoxic function compared with preexisting CD8α+ and CD8α- subsets. Therefore, CD8α expression can be used to define a potential dynamic spectrum of NK cell expansion and function. Because these cells exhibit enhanced tumor control, they may be used to improve in NK cell therapies for patients with AML.
Meningeal lymphatic vessel dysfunction driven by CGRP signaling causes migraine-like pain in mice
Authors: Jean-Leon Thomas, Emmanuelle A.D. Schindler, Christopher Gottschalk
Journal: Journal of Clinical Investigation (2024)

Migraines are a type of headache that occur with other neurological symptoms, but the pathophysiology remains unclear. In this issue of the JCI, Nelson-Maney and authors used constitutive and inducible knockouts of the CGRP receptor components, elegantly demonstrating an essential function of CGRP in modulating meningeal lymphatic vessels (MLVs) in migraine. CGRP was shown to induce rearrangement of membrane-bound gap junction proteins in MLVs, resulting in a reduced CSF flux into cervical lymph nodes. The authors also provided evidence of a primary role for CGRP in modulating neuro-immune function. Finally, by showing that blocking CGRP signaling in MLVs attenuated pain behavior associated with acute migraine in rodents, the authors provided a target for pharmacological blockade of CGRP in relation to primary headache disorders.
AB0257 IMPACT OF ANTI-JO1 POSITIVITY IN PHENOTYPING ANTISYNTHETASE SYNDROME
Authors: O. Dhrif, Z. Meddeb, M. Khaloui, I. Zamali, C. Abdelkefi, A. El Ouni, S. Toujani, M. Ben Ahmed, K. Bouslama, T. Laarbi, S. B’chir Hamzaoui
Journal: Annals of the Rheumatic Diseases (2024)
POS0978 DIRECT AND INDIRECT EFFECTS OF UPADACITINIB OR ADALIMUMAB ON PAIN IN PSORIATIC ARTHRITIS: RESULTS FROM A RANDOMIZED PHASE 3 STUDY
Authors: P. C. Taylor, D. A. Walsh, T. Takeuchi, B. Fautrel, J. Pope, K. Kato, A. Setty, T. Gao, D. Caballero, R. Lippe, A. Kavanaugh
Journal: Annals of the Rheumatic Diseases (2024)
POS0639 BENEFIT–RISK ANALYSIS OF UPADACITINIB VERSUS ADALIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS AND HIGHER OR LOWER RISK OF CARDIOVASCULAR DISEASE
Authors: G. R. Burmester, E. Mysler, P. C. Taylor, L. E. Kristensen, S. Hall, B. Wick-Urban, A. Garrison, T. Gao, N. Khan, S. Strengholt, R. Fleischmann
Journal: Annals of the Rheumatic Diseases (2024)
AB0507 ORAL MICROBIOME DISTURBANCES IN RHEUMATOID ARTHRITIS PATIENTS: FROM EARLY- TO LATE-STAGE
Authors: R. Dos-Santos, A. Tomé, F. Otero, M. Varela García, J. R. Maneiro, A. Mera Varela, M. Sanchez-Wonenburger, P. Castro-Santamaria, A. Mata, J. L. Puga-Guzmán, I. Álvarez, E. Campos, E. Perez-Pampín
Journal: Annals of the Rheumatic Diseases (2024)
POS1055 THE RISK OF MEDICATION-RELATED OSTEONECROSIS OF THE JAW (MRONJ) IN A PATIENT WITH OSTEOPOROSIS TREATED WITH ANTI-RESORPTIVE THERAPY AND UNDERGOING DENTAL CARE IS NEGLIGIBLE WITH A CTX THRESHOLD ABOVE 250
Authors: C. Ghio, R. Gravier-Dumonceau, P. Lafforgue, R. Giorgi, T. Pham
Journal: Annals of the Rheumatic Diseases (2024)
OP0311 THE ROLE OF 18FDG-PET IMAGING IN VEXAS SYNDROME: A MULTICENTRIC CASE SERIES AND A REVIEW OF THE LITERATURE
Authors: R. Bixio, S. Bindoli, A. Morciano, R. Padoan, E. Bertoldo, F. Aldegheri, F. Mastropaolo, G. Orsolini, G. Adami, D. Gatti, O. Viapiana, M. Rossini, P. Sfriso, A. Fassio
Journal: Annals of the Rheumatic Diseases (2024)
POS0945 SUSTAINABILITY OF RESPONSE WITH UPADACITINIB IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE PSORIATIC ARTHRITIS: WEEK 152 DATA FROM THE SELECT-PSA 1 AND SELECT-PSA 2 TRIALS
Authors: P. Sewerin, F. J. Blanco, E. Lubrano, R. Garcia Salinas, A. Bălănescu, R. Lippe, M. Ali, A. Setty, L. Zhou, P. J. Mease
Journal: Annals of the Rheumatic Diseases (2024)
POS0951 AN EXPLAINABLE ARTIFICIAL INTELLIGENCE ALGORITHM FOR AUTOMATED GENERATION OF VAN DER HEIJDE SHARP SCORE IN PSORIATIC ARTHRITIS
Authors: R. Janiczek, D. Govind, K. Broos, N. Fountoulakis, L. Noonan, S. Yamamoto, N. Zemlianskaia, C. S. Meyer, E. Scherer, M. Deman, P. Damasceno, P. S. Murphy, T. Rooney, E. C. Hsia, A. Beutler, K. Standish, S. S. F. Yip
Journal: Annals of the Rheumatic Diseases (2024)
AB0299 COMPARING SARC-F VERSUS DEXA FOR SARCOPENIA ASSESSMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS AND INTERMEDIATE/HIGH FRACTURE RISK
Authors: A. G. Rodriguez-Flores, A. C. Bardan-Inchaustegui, A. Carrazco-Chapa, G. Rodriguez-Orozco, G. J. Cervantes-Charles, A. P. Sanchez-Fonseca, C. M. Skinner-Taylor, R. Negrete-Lopez, J. A. Cardenas-de la Garza, D. A. Galarza-Delgado
Journal: Annals of the Rheumatic Diseases (2024)
POS0642 THE IMPACT OF FIBROMYALGIA ON MENTAL HEALTH, QUALITY OF LIFE AND COPING STRATEGIES IN RHEUMATOID ARTHRITIS PATIENTS
Authors: T. Manandhar, M. Sweeney, L. Carpenter, S. De Souza, E. Caton, J. Galloway, A. Cope, E. Nikiphorou, B. Kirkham, R. Moss-Morris, S. Norton, L. Zhao
Journal: Annals of the Rheumatic Diseases (2024)
POS0643 ASSOCIATION OF EARLY REMISSION ON CLINICAL AND PATIENT-REPORTED OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS: POST-HOC ANALYSIS OF DATA FROM THE SELECT-COMPARE STUDY
Authors: L. Gossec, J. Patel, A. Kadakia, S. Fang, Y. Peng, S. Strengholt, P. C. Taylor, A. Östör
Journal: Annals of the Rheumatic Diseases (2024)
OP0077 LONGITUDINAL ASSESSMENT OF BIOMARKERS IN NOBILITY, A RANDOMIZED, PHASE II CLINICAL TRIAL OF OBINUTUZUMAB FOR TREATMENT OF PROLIFERATIVE LUPUS NEPHRITIS
Authors: E. M. Vital, S. W. Tas, A. Malvar, C. M. Looney, H. Raghu, V. G. Anania, H. A. Mao, T. Wang, S. Williams, T. Schindler, E. Martins, J. A. Ross Terres, W. F. Pendergraft, R. A. Furie
Journal: Annals of the Rheumatic Diseases (2024)
POS0637 COST-EFFECTIVENESS ANALYSIS OF UPADACITINIB VERSUS ALTERNATIVE TREATMENT STRATEGIES FOR RHEUMATOID ARTHRITIS WITH INADEQUATE RESPONSE TO TNFi IN THE UNITED KINGDOM
Authors: P. C. Taylor, A. Kadakia, Y. Song, S. Strengholt, M. Fillbrunn, A. Jiang, M. Buch
Journal: Annals of the Rheumatic Diseases (2024)
POS0977 EFFECTS OF SECUKINUMAB ON ENTHESOPHYTE AND EROSION PROGRESSION IN PSORIATIC ARTHRITIS –A 48-WEEK PLACEBO-CONTROLLED DOUBLE-BLINDED RCT UTILIZING HIGH-RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY (HR-PQCT)
Authors: I. T. Cheng, Y. Jin, H. So, B. T. L. Lai, K. Y. S. Ying, K. Kwok, J. M. Lee, J. F. Griffith, V. W. Hung, L. Qin, L. S. Tam
Journal: Annals of the Rheumatic Diseases (2024)
AB0297 MULTIVARIATE REGRESSION ANALYSIS OF RISK FACTORS FOR HIGH RADIOFREQUENCY ECHOGRAPHIC MULTISPECTROMETRY (REMS) - BASED FRAGILITY SCORE OF THE LUMBAR SPINE
Authors: E. Bischoff, F. Bischoff, S. Vladeva, M. Kovachev, P. Kinov
Journal: Annals of the Rheumatic Diseases (2024)
POS0640 ANTIMALARIALS AND THE RISK OF OCULAR ADVERSE EVENTS IN RHEUMATOID ARTHRITIS: LOOKING BEYOND THE RARE OccURRENCE OF DRUG INDUCED RETINOPATHY
Authors: M. Bredemeier, S. Estefano Ramos, C. Solórzano, C. V. Tavares, A. M. Baier, A. Duarte, M. Pinheiro, B. S. Kahlow, M. V. S. De Vechi, R. Ranza, J. R. Miranda, V. Valim, G. Castro, M. Bertolo, M. D. F. Sauma, V. Fernandes, A. C. Medeiros-Ribeiro, R. Botelho, C. Brenol, H. M. Da Silveira de Carvalho, S. Studart, G. Da Rocha Castelar Pinheiro, L. Rocha, H. De Leon de Lima, I. Pereira, M. Ohira Gazzeta, A. M. Kakehasi, P. Louzada, A. L. S. Hayata, C. Lupo, I. G. Silveira, S. Kowalski, D. Titton, A. Ranzolin, R. Machado Xavier, I. M. Laurindo, M. Antonio Araujo Da Rocha Loures
Journal: Annals of the Rheumatic Diseases (2024)
AB0508 THE EFFECT OF COMBINATIONS OF CONVENTIONAL SYNTHETIC DMARDs ON THE SAFETY AND TREATMENT RETENTION OF BIOLOGIC AGENTS OR JAK INHIBITORS IN RHEUMATOID ARTHRITIS
Authors: S. Ramos, M. Bredemeier, C. Solórzano, C. V. Tavares, A. M. Baier, A. Duarte, M. Pinheiro, B. Stadler Kahlow, M. V. S. De Vechi, R. Ranza, J. R. Miranda, V. Valim, G. Castro, M. Bertolo, M. D. F. Sauma, V. Fernandes, A. C. Medeiros-Ribeiro, R. Botelho, C. Brenol, H. M. Da Silveira de Carvalho, S. Studart, G. Da Rocha Castelar Pinheiro, L. Rocha, H. De Leon de Lima, I. Pereira, M. Ohira Gazzeta, A. M. Kakehasi, P. Louzada, A. L. S. Hayata, C. Lupo, I. G. Silveira, S. Kowalski, D. Titton, A. Ranzolin, R. Machado Xavier, I. M. Laurindo, M. Antonio Araujo Da Rocha Loures
Journal: Annals of the Rheumatic Diseases (2024)
AB0408 BETTER DRUG RETENTION ON ANTI-IL17A COMPARED TO ANTI-TNF THERAPY DESPITE ITS INFERIOR EFFECT ON COMPOSITE JOINT INDEXES AND QUALITY OF LIFE IN PATIENTS WITH PsA–ANALYSIS FROM THE CZECH BIOLOGICS REGISTRY ATTRA
Authors: J. Zavada, J. Baranová, K. Pavelka, J. Vencovský, P. Horak, L. Šenolt
Journal: Annals of the Rheumatic Diseases (2024)
Rheumatoid arthritis patients harbour aberrant enteric bacteriophages with autoimmunity-provoking potential: a paired sibling study
Authors: Fanlei Hu, Xin Li, Kai Liu, Yanpeng Li, Yang Xie, Chaonan Wei, Shuyan Liu, Jing Song, Ping Wang, Lianjie Shi, Chun Li, Jing Li, Liling Xu, Jimeng Xue, Xi Zheng, Mingxin Bai, Xiangyu Fang, Xu Jin, Lulu Cao, Pei Hao, Jing He, Jun Wang, Chiyu Zhang, Zhanguo Li
Journal: Annals of the Rheumatic Diseases (2024)

Viruses have been considered as important participants in the development of rheumatoid arthritis (RA). However, the profile of enteric virome and its role in RA remains elusive. This study aimed to investigate the atlas and involvement of virome in RA pathogenesis.
AB0277 PREVALENCE AND RISK FACTORS OF SARCOPENIA IN YOUNG ADULTS WITH JUVENILE IDIOPATHIC ARTHRITIS
Authors: M. Kulyk, A. Novytska, R. Potomka, O. Ivashkivsky, T. Karasevska, H. Mostbauer, R. Lories, K. De Vlam, M. Dzhus
Journal: Annals of the Rheumatic Diseases (2024)
Leadless Ultrasound-Based Cardiac Resynchronization System in Heart Failure
Authors: Jagmeet P. Singh, Christopher A. Rinaldi, Prashanthan Sanders, Spencer H. Kubo, Simon James, Imran K. Niazi, Timothy Betts, Christian Butter, Toshimasa Okabe, Ryan Cunnane, Emad Aziz, Mauro Biffi, Amir Zaidi, Jeffrey Alison, Pascal Defaye, Angelo Aurrichio, Michael R. Gold, JoAnn Lindenfeld, Tyson Rogers, Mary Norine Walsh
Journal: JAMA Cardiology (2024)

Importance Approximately 40% of patients with heart failure (HF) who are eligible for cardiac resynchronization therapy (CRT) either fail to respond or are untreatable due to anatomical constraints. Objective To assess the safety and efficacy of a novel, leadless, left ventricular (LV) endocardial pacing system for patients at high risk for a CRT upgrade or whose coronary sinus (CS) lead placement/pacing with a conventional CRT system failed. Design, Setting, and Participants The SOLVE-CRT study was a prospective multicenter trial enrolling January 2018 through July 2022, with follow-up at 6 months. Data were analyzed from January 17, 2018, through February 15, 2023. The trial combined data from an initial randomized, double-blind study (n = 108) and a subsequent single-arm part (n = 75). It took place at 36 centers across Australia, Europe, and the US. Participants were nonresponders, previously untreatable (PU), or high-risk upgrades (HRU). All participants contributed to the safety analysis. The primary efficacy analysis (n = 100) included 75 PU-HRU patients from the single-arm part and 25 PU-HRU patients from the randomized treatment arm. Interventions Patients were implanted with the WiSE CRT System (EBR Systems) consisting of a leadless LV endocardial pacing electrode stimulated with ultrasound energy delivered by a subcutaneously implanted transmitter and battery. Main Outcomes and Measures The primary safety end point was freedom from type I complications. The primary efficacy end point was a reduction in mean LV end systolic volume (LVESV). Results The study included 183 participants; mean age was 68.1 (SD, 10.3) years and 141 were male (77%). The trial was terminated at an interim analysis for meeting prespecified stopping criteria. In the safety population, patients were either New York Heart Association Class II (34.6%) or III (65.4%). The primary efficacy end point was met with a 16.4% (95% CI, −21.0% to −11.7%) reduction in mean LVESV ( P = .003). The primary safety end point was met with an 80.9% rate of freedom from type I complications ( P &amp;amp;lt; .001), which included 12 study device system events (6.6%), 5 vascular events (2.7%), 3 strokes (1.6%), and 7 cardiac perforations which mostly occurred early in the study (3.8%). Conclusions and Relevance The SOLVE-CRT study has demonstrated that leadless LV endocardial pacing with the WiSE CRT system is associated with a reduction in LVESV in patients with HF. This novel system may represent an alternative to conventional CRT implants in some HF patient populations. Trial Registration ClinicalTrials.gov Identifier: NCT0292203
AB0407 IS THERE ANY DIFFERENCE BETWEEN SWITCHING AND CYCLING PATIENTS AFTER TUMOR NECROSIS FACTOR INHIBITOR (TNFi) FAILURE IN PSORIATIC ARTHRITIS? - CHARACTERIZATION OF A PORTUGUESE COHORT WITH ONE YEAR OF TREATMENT WITH TNFi AS THE FIRST BIOLOGICAL DMARD
Authors: C. Gomes, M. Diz Lopes, I. Santos, T. Beirão, M. Bernardes, L. Costa
Journal: Annals of the Rheumatic Diseases (2024)