tbuckley/cabot-search huggingface dataset:
G-CSF as a suitable alternative to GM-CSF to boost dinutuximab-mediated neutrophil cytotoxicity in neuroblastoma treatment
Authors: Paula Martinez Sanz, Dieke J van Rees, Lieke M J van Zogchel, Bart Klein, Panagiota Bouti, Hugo Olsman, Karin Schornagel, Ivana Kok, Ali Sunak, Kira Leeuwenburg, Ilse Timmerman, Miranda P Dierselhuis, Waleed M Kholosy, Jan J Molenaar, Robin van Bruggen, Timo K van den Berg, Taco W Kuijpers, Hanke L Matlung, Godelieve A M Tytgat, Katka Franke
Journal: Journal for ImmunoTherapy of Cancer (2021)

Current immunotherapy for patients with high-risk neuroblastoma involves the therapeutic antibody dinutuximab that targets GD2, a ganglioside expressed on the majority of neuroblastoma tumors. Opsonized tumor cells are killed through antibody-dependent cellular cytotoxicity (ADCC), a process mediated by various immune cells, including neutrophils. The capacity of neutrophils to kill dinutuximab-opsonized tumor cells can be further enhanced by granulocyte-macrophage colony-stimulating factor (GM-CSF), which has been shown in the past to improve responses to anti-GD2 immunotherapy. However, access to GM-CSF (sargramostim) is limited outside of Northern America, creating a high clinical need for an alternative method to stimulate dinutuximab responsiveness in the treatment of neuroblastoma. In this in vitro study, we have investigated whether clinically well-established granulocyte colony-stimulating factor (G-CSF) can be a potentially suitable alternative for GM-CSF in the dinutuximab immunotherapy regimen of patients with neuroblastoma.We compared the capacity of neutrophils stimulated either in vitro or in vivo with GM-CSF or G-CSF to kill dinutuximab-opsonized GD2-positive neuroblastoma cell lines and primary patient tumor material. Blocking experiments with antibodies inhibiting either respective Fc gamma receptors (FcγR) or neutrophil integrin CD11b/CD18 demonstrated the involvement of these receptors in the process of ADCC. Flow cytometry and live cell microscopy were used to quantify and visualize neutrophil-neuroblastoma interactions.We found that G-CSF was as potent as GM-CSF in enhancing the killing capacity of neutrophils towards neuroblastoma cells. This was observed with in vitro stimulated neutrophils, and with in vivo stimulated neutrophils from both patients with neuroblastoma and healthy donors. Enhanced killing due to GM-CSF or G-CSF stimulation was consistent regardless of dinutuximab concentration, tumor-to-neutrophil ratio and concentration of the stimulating cytokine. Both GM-CSF and G-CSF stimulated neutrophils required FcγRIIa and CD11b/CD18 integrin to perform ADCC, and this was accompanied by trogocytosis of tumor material by neutrophils and tumor cell death in both stimulation conditions.Our preclinical data support the use of G-CSF as an alternative stimulating cytokine to GM-CSF in the treatment of high-risk neuroblastoma with dinutuximab, warranting further testing of G-CSF in a clinical setting.
The 2021 Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibitor–based Combination Therapies for Treatment-naive Metastatic Clear-cell Renal Cell Carcinoma Are Standard of Care
Authors: Jens Bedke, Laurence Albiges, Umberto Capitanio, Rachel H. Giles, Milan Hora, Thomas B. Lam, Börje Ljungberg, Lorenzo Marconi, Tobias Klatte, Alessandro Volpe, Yasmin Abu-Ghanem, Saeed Dabestani, Sergio Fernández Pello, Fabian Hofmann, Teele Kuusk, Rana Tahbaz, Thomas Powles, Axel Bex
Journal: European Urology (2021)
SARS-CoV-2 N gene dropout and N gene Ct value shift as indicator for the presence of B.1.1.7 lineage in a commercial multiplex PCR assay
Authors: Paul Wollschläger, Daniel Todt, Nadja Gerlitz, Stephanie Pfaender, Thomas Bollinger, Andreas Sing, Alexandra Dangel, Nickolaus Ackermann, Klaus Korn, Armin Ensser, Eike Steinmann, Michael Buhl, Joerg Steinmann
Journal: Clinical Microbiology and Infection (2021)
Loss-of-function mutations in the melanocortin 4 receptor in a UK birth cohort
Authors: Kaitlin H. Wade, Brian Y. H. Lam, Audrey Melvin, Warren Pan, Laura J. Corbin, David A. Hughes, Kara Rainbow, Jian-Hua Chen, Katie Duckett, Xiaoming Liu, Jacek Mokrosiński, Alexander Mörseburg, Sam Neaves, Alice Williamson, Chen Zhang, I. Sadaf Farooqi, Giles S. H. Yeo, Nicholas J. Timpson, Stephen O’Rahilly
Journal: Nature Medicine (2021)
Mg Biodegradation Mechanism Deduced from the Local Surface Environment under Simulated Physiological Conditions
Authors: Jorge Gonzalez, Sviatlana V. Lamaka, Di Mei, Nico Scharnagl, Frank Feyerabend, Mikhail L. Zheludkevich, Regine Willumeit‐Römer
Journal: Advanced Healthcare Materials (2021)

Abstract Although certified magnesium‐based implants are launched some years ago, the not well‐defined Mg degradation mechanism under physiological conditions makes it difficult to standardize its use as a degradable biomaterial for a wide range of implant applications. Among other variables influencing the Mg degradation mechanism, monitoring the pH in the corrosive solution and, especially, at the corroding interface is important due to its direct relation with the formation and stability of the degradation products layer. The interface pH (pH at the Mg/solution interface) developed on Mg‐2Ag and E11 alloys are studied in situ during immersion under dynamic conditions (1.5 mL min ‐1 ) in HBSS with and without the physiological amount of Ca 2+ cations (2.5 × 10 ‐3 m ). The results show that the precipitation/dissolution of amorphous phosphate‐containing phases, that can be associated with apatitic calcium‐phosphates Ca 10‐ x (PO 4 ) 6‐ x (HPO 4 or CO 3 ) x (OH or ½ CO 3 ) 2‐ x with 0 ≤ x ≤ 2 (Ap‐CaP), promoted in the presence of Ca 2+ generates an effective local pH buffering system at the surface. Thus, high alkalinization is prevented, and the interface pH is stabilized in the range of 7.6 to 8.5.
Wearable sensors enable personalized predictions of clinical laboratory measurements
Authors: Jessilyn Dunn, Lukasz Kidzinski, Ryan Runge, Daniel Witt, Jennifer L. Hicks, Sophia Miryam Schüssler-Fiorenza Rose, Xiao Li, Amir Bahmani, Scott L. Delp, Trevor Hastie, Michael P. Snyder
Journal: Nature Medicine (2021)
Tripartite Separation of Glomerular Cell Types and Proteomes from Reporter-Free Mice
Authors: Favian A. Hatje, Uta Wedekind, Wiebke Sachs, Desiree Loreth, Julia Reichelt, Fatih Demir, Christopher Kosub, Lukas Heintz, Nicola M. Tomas, Tobias B. Huber, Sinah Skuza, Marlies Sachs, Stephanie Zielinski, Markus M. Rinschen, Catherine Meyer-Schwesinger
Journal: Journal of the American Society of Nephrology (2021)

The glomerulus comprises podocytes, mesangial cells, and endothelial cells, which jointly determine glomerular filtration. Understanding this intricate functional unit beyond the transcriptome requires bulk isolation of these cell types for biochemical investigations. We developed a globally applicable tripartite isolation method for murine mesangial and endothelial cells and podocytes (timMEP).
POS0642 THE IMPACT OF AGE ON DISCONTINUATION OF BIOLOGIC DMARDs IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: V. Rivera Teran, S. Sicsik, D. Vega-Morales, F. Irazoque-Palazuelos, D. Miranda, J. C. Casasola, S. Carrilo, A. Peña, A. Castillo Ortiz, O. E. Muñoz-Monroy, S. Duran Barragan, A. Paz, E. Torres Valdéz, L. F. Valdés Corona, D. X. Xibille Friedmann, E. Zamora, A. Ramos, N. Santana, M. Vazquez, F. Guerrero, C. Zepeda, K. Alvarado, M. Rivera, D. Alpizar-Rodriguez
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rheumatoid arthritis (RA) is the most common autoimmune disease. Older patients treated with biologic DMARDs (bDMARDs) are at a significantly greater risk of adverse effects (AEs) [1]. However, the rate of drug discontinuation because of adverse effects caused by bDMARDs has not differed in elderly compared to younger patients in different registries. Objectives: Determine if drug discontinuation of bDMARDs differs by age in patients with rheumatoid arthritis in the Mexican Adverse Events Registry (BIOBADAMEX). Methods: BIOBADAMEX is a Mexican ongoing cohort of patients using bDMARDs since 2016. In this analysis we included all patients with diagnosis of RA with at least two assessments. Survival on bDMARDs was estimated using Kaplan-Meier analysis. Predictors of discontinuation, including age older than median age in the sample were investigated by Cox regression analyses. Results: Among 743 patients in the registry, 497 had RA diagnosis, from which, 214 had at least two assessments. At baseline, patients had a median (IQR) age of 53.4 (45-61) years old, median disease duration of 10.7 (6-17) months and median DAS28 of 4.7 (3-6). Conventional DMARDS were used by 185 (87%) patients and 94 (44%) patients used corticosteroids. Comorbidities were present in 194 (91%). The most common bDMARDs received at baseline were abatacept 59 (27%), tocilizumab 45(21%), adalimumab 31 (15%) and certolizumab 30 (14%). At the time of analysis, the median bDMARDs treatment duration was 21.0(13-34) months, 128 (59%) had discontinued treatment, 66 for inefficacy, 32 for adverse events and 30 for others. Fig 1 shows discontinuation rate curves in patients younger and older than median age. Cox proportional-hazards demonstrated no significant differences regarding age older than median age (HR 1.1, 95% CI 0.8-1.4, p=0.7), female sex (HR 1.2, 95% CI 0.7-1.9, p=0.44), use of corticosteroids (HR 1.2, 95% CI 0.9-1.6, p=0.20), comorbidities (HR 0.9, 95% 0.6-1.5, p=0.78), DAS28 (HR 0.9, 95% 0.9-1.1, p=0.93) or other factors. Figure 1. Discontinuation rate curves in patients younger and older than median age (&lt; 53.4 and &gt;=53.4 years old) Conclusion: This analysis did not show a role of age on discontinuation of bDMARDs in Mexican RA patients. Further longitudinal analyses will be performed including more patients to assess retention rate of bDMARDs and identify predictive variables of discontinuation in Mexican population. References: [1]Akter R, et al. Can Geriatr J. 2020 May 1;23(2):184-189. [2]Ikari Y, et al. Medicine (Baltimore). 2020 Dec 24;99(52):e23861. Disclosure of Interests: None declared
Generation of highly proliferative, rejuvenated cytotoxic T cell clones through pluripotency reprogramming for adoptive immunotherapy
Authors: Yohei Kawai, Ai Kawana-Tachikawa, Shuichi Kitayama, Tatsuki Ueda, Shoji Miki, Akira Watanabe, Shin Kaneko
Journal: Molecular Therapy (2021)

Adoptive immunotherapy has emerged as a powerful approach to cure cancer and chronic infections. Currently, the generation of a massive number of T cells that provide long-lasting immunity is challenged by exhaustion and differentiation-associated senescence, which inevitably arise during in vitro cloning and expansion. To circumvent these problems, several studies have proposed an induced pluripotent stem cell (iPSC)-mediated rejuvenation strategy to revitalize the exhausted/senescent T cell clones. Because iPSC-derived cytotoxic T lymphocytes (iPSC-CTLs) generated via commonly used monolayer systems have unfavorable, innate-like features such as aberrant natural killer (NK) activity and limited replication potential, we modified the redifferentiation culture to generate CD8αβ+CD5+CCR7+CD45RA+CD56−-adaptive iPSC-CTLs. The modified iPSC-CTLs exhibited early memory phenotype, including high replicative capacity and the ability to give rise to potent effector cells. In expansion culture with an optimized cytokine cocktail, iPSC-CTLs proliferated more than 1015-fold in a feeder-free condition. Our redifferentiation and expansion package of early memory iPSC-CTLs could supply memory and effector T cells for both autologous and allogeneic immunotherapies. Adoptive immunotherapy has emerged as a powerful approach to cure cancer and chronic infections. Currently, the generation of a massive number of T cells that provide long-lasting immunity is challenged by exhaustion and differentiation-associated senescence, which inevitably arise during in vitro cloning and expansion. To circumvent these problems, several studies have proposed an induced pluripotent stem cell (iPSC)-mediated rejuvenation strategy to revitalize the exhausted/senescent T cell clones. Because iPSC-derived cytotoxic T lymphocytes (iPSC-CTLs) generated via commonly used monolayer systems have unfavorable, innate-like features such as aberrant natural killer (NK) activity and limited replication potential, we modified the redifferentiation culture to generate CD8αβ+CD5+CCR7+CD45RA+CD56−-adaptive iPSC-CTLs. The modified iPSC-CTLs exhibited early memory phenotype, including high replicative capacity and the ability to give rise to potent effector cells. In expansion culture with an optimized cytokine cocktail, iPSC-CTLs proliferated more than 1015-fold in a feeder-free condition. Our redifferentiation and expansion package of early memory iPSC-CTLs could supply memory and effector T cells for both autologous and allogeneic immunotherapies.
AB0664 THE PSYCHOLOGICAL STATE OF THE PATIENTS WITH RHEUMATIC DISEASES AND HOSPITAL WORKERS DURING THE CORONAVIRUS DISEASE (COVID-19) OUTBREAK
Authors: T. Lisitsyna, D. Veltishchev, A. Borisova, E. Nasonov, A. Lila
Journal: Annals of the Rheumatic Diseases (2021)

Background: Patients with rheumatic diseases are more likely to suffer from anxiety-depressive disorders and, in the context of the current coronavirus pandemic, are most likely to be more susceptible to stress response, depression, and anxiety. Objectives: to evaluate the frequency of anxiety-depressive symptoms and stress levels in patients with various rheumatic diseases (RD) and hospital workers of the Moscow Institute of Rheumatology in Russia Methods: 148 RD inpatients, mostly with rheumatoid arthritis (44 (30%)), spondyloarthritis (31 (21%)), systemic lupus erythematosus (28 (19%)), systemic sclerosis (10 (7%)), primary Sjögren syndrome (7 (5%)), polymyositis (6 (4%)), and 32 hospital workers of the Nasonova Research Institute of Rheumatology were screened using the DASS-21 (The Depression, Anxiety, Stress scales-21, Lovibond S.H. &amp; Lovibond P.F. (1995)) in the period from July to November 2020. The majority of RD-patients and hospital workers were women (73 and 93% resp). The mean age (M±SD) of RD-patients and hospital workers was 43,2±16,2 and 40,7±14,6 years resp. Results: The frequency of depression (34,5% vs 34,4%), anxiety (41,9% vs 34,4%) and post-traumatic stress (27,7% vs 25,0%) in RD-patients were found to be comparable to that found among the hospital workers, and the level of anxiety was statistically significantly higher in patients (2,0 [1,0; 6,0] vs 1,0 [0; 4,5], p=0,038). There was no association of depression, anxiety and stress with RD activity. There was a weak positive correlation between the level of depression (R=0,30), anxiety (R=0,26) and stress (R=0,33) with a higher dose of glucocorticoids taken by patients, as well as a negative correlation between the severity of depression (R=-0,7) and stress (R=-0,17) with the age of patients and hospital workers. 19 (12,8%) of RD-patients and 7 (21,9%) of hospital workers had contracted COVID-19 in previous months. Survivors of the COVID-19, both among RD-patients and hospital workers, were more likely to experience symptoms of depression, anxiety and stress: accordingly, depression had 31,6% vs 27,9%, anxiety – 47,4% vs 41,9% and stress – 26,3% vs 28,7% RD-patients who had been ill or not, and among hospital workers: depression – 28,6% vs 36,0%, anxiety – 42,8% vs 28,0%, stress – 42,8% vs 20,0%. 66,4% of RD-patients and 71,9% of hospital workers reported that the pandemic had a psychological impact on them. Conclusion: The COVID-19 pandemic has had and continues to have a significant negative psychological impact on both RD-patients and hospital workers. About 25-47% of patients and hospital workers experienced significant level of depression, anxiety and stress, and their frequency was higher in those who had contracted COVID-19. Disclosure of Interests: None declared.
AB0768 NEUROLOGICAL MANIFESTATIONS IN GRANULOMATOSIS WITH POLYANGIITIS: ABOUT 11 CASES
Authors: O. Jomaa, O. Berriche, S. Arfa, A. Fraj, M. Belkhiri, R. Makhloufi, W. Romdhane, M. Hermassi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Granulomatosis with polyangiitis (GPA) is a rare systemic vasculitis, affecting mainly the superior airways, lungs and kidneys. Neurological impairment is frequent, described in 22 to 54% of cases, and rarely inaugurates the disease. Objectives: The objective of our work was to evaluate its prevalence and its different aspects. Methods: A retrospective study including 11 files of GPA patients followed over a period of 10 years in The Internal Medecine Department at Tahar Sfar Hospital Mahdia TUNISIA. Results: Neurological manifestations were reported in 5 patients: a pyramidal syndrome was noted in 3 patients with a normal cerebral MRI, a disabled headache was described in one patient with a normal cerebral MRI. Peripheral neuropathy in 2 cases, and the Electroneuromyogram objectified a mononeuropathy affecting the ulnar nerve, peroneal nerve, and musculocutaneous nerve in one patient and a distal sensitivomotor poly neuropathy in one patient. Cranial nerves damage was noted in two cases, one VII (1 case) and one V (1 case). Conclusion: Our study results, show the importance of timely diagnosis of these neurological manifestations, as their evolution will depend on the early GPA treatment. References: [1]doi: 10.1016/j.autrev.2017.07.007 Disclosure of Interests: None declared
POS0928 NETAKIMAB EFFICACY IN ANTI-TNF-NAIVE AND ANTI-TNF-EXPERIENCED PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: RESULTS OF SUBANALYSIS OF PHASE 3 ASTERA TRIAL
Authors: S. Erdes, V. Mazurov, T. Dubinina, I. Gaydukova, A. Kundzer, N. Soroka, A. Eremeeva
Journal: Annals of the Rheumatic Diseases (2021)

Background: According to previous studies, the effectiveness of interleukin-17 (IL-17) inhibitors was higher in anti-TNF-naïve patients with ankylosing spondylitis (AS) [1,2]. Netakimab (NTK) is a humanized anti-IL-17A antibody approved for the treatment of AS, psoriatic arthritis, moderate-to-severe plaque psoriasis in Russia and Belarus. Objectives: To compare the efficacy of NTK in anti-TNF-naïve patients with anti-TNF-experienced patients with active AS at week 16 of therapy. Methods: ASTERA ( NCT03447704 ) is an ongoing phase 3 placebo (PBO)-controlled clinical study, aimed at evaluating NTK efficacy in AS [3]. 228 adult patients with active AS (BASDAI ≥ 4) were randomly assigned (1:1) to receive 120 mg NTK or PBO subcutaneously at week 0,1,2 and then q2w. This analysis includes 112 patients in NTK group. Efficacy endpoints included ASAS20/40, ASAS5/6 and ASAS partial remission (PR) at week 16 of therapy. Results: 28 (25.0%) of 112 patients in NTK group had previous inadequate response/intolerance to anti-TNF (anti-TNF-IR): 24 (21.4%) – one anti-TNF, and 4 (3.6%) – two anti-TNF. 84 (75.0%) patients were TNF-naive. Achievement of ASAS criteria response at week 16 was similar in both groups (Table 1). Table 1. Efficacy of NTK at week 16 Parameter TNF-naïve (n = 84) anti-TNF-IR (n = 28) p-value* ASAS20, n (%) 52 (61.9%) 17 (60.7%) 0.91 ASAS40, n (%) 35 (41.7%) 11 (39.3%) 0.82 ASAS5/6, n (%) 39 (46.4%) 11 (39.3%) 0.51 ASAS(PR), n (%) 15 (17.9%) 4 (14.3%) 0.78 *- Fisher’s exact test Conclusion: NTK 120 mg provided sustained improvements in signs and symptoms of AS in anti-TNF-naive and anti-TNF-IR patients at 16 weeks of therapy. References: [1]Blair HA, Dhillon S. Secukinumab: A Review in Ankylosing Spondylitis. Drugs. 2016;76(10):1023-30. [2]Dougados M, et al. Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W). Ann Rheum Dis. 2020;79(2):176-185. [3]Mazurov VI, et al. Efficacy and safety of Netakimab, anti-IL-17A monoclonal antibody, in patients with ankylosing spondylitis. Results of phase III international, multicenter, randomized double-blind clinical trial BCD-085-5/ASTERA. Nauchno-Practicheskaya Revmatologia=Rheumatology Science and Practice. 2020;58 (4):376–386 (In Russ). Acknowledgements: This study was sponsored by JSC BIOCAD. Disclosure of Interests: Shandor Erdes: None declared, V Mazurov: None declared, Tatiana Dubinina: None declared, Inna Gaydukova Speakers bureau: Abbvie, Biocad, Eli Lilly, MSD, Novartis, Pfizer, Sandoz, Alena Kundzer: None declared, Nikolaj Soroka: None declared, Anna Eremeeva Employee of: Biocad
Impact of Policy and Funding Decisions on COVID-19 Surveillance Operations and Case Reports — South Sudan, April 2020–February 2021
Authors: Talya Shragai, Aimee Summers, Olu Olushayo, John Rumunu, Valerie Mize, Richard Laku, Sudhir Bunga
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Early models predicted substantial COVID-19-associated morbidity and mortality across Africa (1-3). However, as of March 2021, countries in Africa are among those with the lowest reported incidence of COVID-19 worldwide (4). Whether this reflects effective mitigation, outbreak response, or demographic characteristics, (5) or indicates limitations in disease surveillance capacity is unclear (6). As countries implemented changes in funding, national policies, and testing strategies in response to the COVID-19 pandemic, surveillance capacity might have been adversely affected. This study assessed whether changes in surveillance operations affected reporting in South Sudan; testing and case numbers reported during April 6, 2020-February 21, 2021, were analyzed relative to the timing of funding, policy, and strategy changes.* South Sudan, with a population of approximately 11 million, began COVID-19 surveillance in February 2020 and reported 6,931 cases through February 21, 2021. Surveillance data analyzed were from point of entry screening, testing of symptomatic persons who contacted an alert hotline, contact tracing, sentinel surveillance, and outbound travel screening. After travel restrictions were relaxed in early May 2020, international land and air travel resumed and mandatory requirements for negative pretravel test results were initiated. The percentage of all testing accounted for by travel screening increased >300%, from 21.1% to 91.0% during the analysis period, despite yielding the lowest percentage of positive tests among all sources. Although testing of symptomatic persons and contact tracing yielded the highest percentage of COVID-19 cases, the percentage of all testing from these sources decreased 88%, from 52.6% to 6.3% after support for these activities was reduced. Collectively, testing increased over the project period, but shifted toward sources least likely to yield positive results, possibly resulting in underreporting of cases. Policy, funding, and strategy decisions related to the COVID-19 pandemic response, such as those implemented in South Sudan, are important issues to consider when interpreting the epidemiology of COVID-19 outbreaks.
Durable remissions following combined targeted therapy in patients with CLL harboring <i>TP53</i> deletions and/or mutations
Authors: Paula Cramer, Eugen Tausch, Julia von Tresckow, Adam Giza, Sandra Robrecht, Christof Schneider, Moritz Fürstenau, Petra Langerbeins, Othman Al-Sawaf, Benedikt W. Pelzer, Anna Maria Fink, Kirsten Fischer, Clemens-Martin Wendtner, Barbara Eichhorst, Michael Kneba, Stephan Stilgenbauer, Michael Hallek
Journal: Blood (2021)
Abstract 15627: Leadless Pacemaker Therapy Results in Worsening Tricuspid Valve Function at 12 Months Post-Implant
Authors: Niek Beurskens, Fleur Tjong, Kosse Dasselaar, Rianne Bon, Reinoud Knops
Journal: Circulation (2018)

Introduction: Endocardial pacemaker leads are a well-known cause of clinically relevant tricuspid valve (TV) dysfunction. Lead-related TV dysfunction can potentially be mitigated by leadless pacema...