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Article ; Online: Emerging Therapies for Treatment-Resistant Hypertension: A Review of Lorundrostat and Related Selective Aldosterone Synthase Inhibitors.

Feldman, Jared M / Frishman, William H / Aronow, Wilbert S

2024

Abstract: The target-hypertension (Target-HTN) trial investigated the efficacy and safety of lorundrostat, an aldosterone synthase inhibitor, as an antihypertensive. Cohort 1 of the trial includes patients with suppressed plasma renin activity and elevated ... ...

Abstract	The target-hypertension (Target-HTN) trial investigated the efficacy and safety of lorundrostat, an aldosterone synthase inhibitor, as an antihypertensive. Cohort 1 of the trial includes patients with suppressed plasma renin activity and elevated aldosterone levels. Lorundrostat doses of 100 mg and 50 mg daily significantly decreased systolic blood pressure compared to the placebo group. Cohort 2 also demonstrated a reduction in systolic blood pressure with the 100 mg daily dose of lorundrostat. Lorundrostat is more selective for the inhibition of CYP11B2 versus CYP11B1, which makes it preferable to other aldosterone synthase inhibitors that inhibit cortisol synthesis, such as osilodrostat. Phase 3 trials are needed to validate the safety and efficacy of lorundrostat, and further research should be performed on other selective aldosterone synthase inhibitors such as baxdrostat, dexfadrostat, and BI 690517.
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	1294965-6
ISSN	1538-4683 ; 1061-5377
ISSN (online)	1538-4683
ISSN	1061-5377
DOI	10.1097/CRD.0000000000000665
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Article ; Online: A Personalized Cell-Based Therapy for Ischemic Heart Failure With Reduced Ejection Fraction: Safety and Feasibility Outcomes of the Roll-In Cohort of the CardiAMP Cell Therapy Trial and Review of Similar Trials.

Feldman, Jared M / Frishman, William H / Aronow, Wilbert S

Cardiology in review

2024

Abstract: CardiAMP Cell Therapy for Heart Failure trial is a prospective, multicenter, randomized, controlled, double-blinded trial that has been granted breakthrough designation by the United States Food and Drug Administration. This trial evaluates clinical ... ...

Abstract	CardiAMP Cell Therapy for Heart Failure trial is a prospective, multicenter, randomized, controlled, double-blinded trial that has been granted breakthrough designation by the United States Food and Drug Administration. This trial evaluates clinical outcomes of intramyocardial delivery of a high dose of autologous bone marrow mononuclear cells in chronic postmyocardial infarction heart failure patients. This trial represents the first attempt to personalize marrow-derived cell-based therapy for the treatment of ischemic heart failure with reduced ejection fraction. The roll-in cohort of 10 patients demonstrated improvements in 6-minute walk distance at 6 months (+47.8 m, P = 0.01), 12 months (+46.4 m, P = 0.06), and 24 months (+31 m), and improvements in New York Heart Association class at 3 months (P = 0.015) and 6 months (P = 0.037). Four patients were reduced to New York Heart Association class I at 24 months and Minnesota Living with Heart Failure Questionnaire score was improved in 6 of 10 patients at 24 months. The improved clinical outcomes demonstrated in CardiAMP are consistent with previous clinical trials including the Transendocardial Autologous Cells in Ischemic Heart Failure (TAC-HFT) trial, Prospective Randomized Trial of Direct Endomyocardial Implantation of Bone Marrow Cells for Treatment of Severe Coronary Artery Diseases (PROTECT-CAD), and REGENERATE-Ischemic Heart Disease trial.
Language	English
Publishing date	2024-02-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	1294965-6
ISSN	1538-4683 ; 1061-5377
ISSN (online)	1538-4683
ISSN	1061-5377
DOI	10.1097/CRD.0000000000000659
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Article ; Online: Review of the Etiology, Diagnosis, and Management of Left Ventricular Thrombus.

Feldman, Jared M / Frishman, William H / Aronow, Wilbert S

Cardiology in review

2023

Abstract: The incidence of left ventricular (LV) thrombus following acute myocardial infarction has declined significantly due to recent advancements in reperfusion and antithrombotic therapies. The development of LV thrombus depends on Virchow's triad: ... ...

Abstract	The incidence of left ventricular (LV) thrombus following acute myocardial infarction has declined significantly due to recent advancements in reperfusion and antithrombotic therapies. The development of LV thrombus depends on Virchow's triad: endothelial injury following myocardial infarction, blood stasis from LV dysfunction, and hypercoagulability. Diagnostic modalities for LV thrombus include transthoracic echocardiography and late gadolinium enhancement cardiac magnetic resonance imaging. Anticoagulation with direct oral anticoagulants or vitamin K antagonists for 3 months following initial diagnosis of LV thrombus remains the treatment of choice for LV thrombus. However, further evidence is needed to demonstrate the noninferiority of direct oral anticoagulants compared with vitamin K antagonists for the prevention of thromboembolic events.
Language	English
Publishing date	2023-06-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	1294965-6
ISSN	1538-4683 ; 1061-5377
ISSN (online)	1538-4683
ISSN	1061-5377
DOI	10.1097/CRD.0000000000000572
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Article ; Online: Review of the Etiology, Diagnosis, Classification, and Therapy of Right Heart Thrombi.

Feldman, Jared M / Frishman, William H / Aronow, Wilbert S

Cardiology in review

2023

Abstract: Right heart thrombi are a rare phenomenon associated with high mortality rates and embolization to the pulmonary bed. Diagnostic modalities include transthoracic echocardiography, contrast-enhanced echocardiography, and cardiac magnetic resonance imaging. ...

Abstract	Right heart thrombi are a rare phenomenon associated with high mortality rates and embolization to the pulmonary bed. Diagnostic modalities include transthoracic echocardiography, contrast-enhanced echocardiography, and cardiac magnetic resonance imaging. Several treatment options for right ventricular thrombus have been described in case reports and observational studies including anticoagulation, thrombolysis, catheter-based procedures, and surgical embolectomy. Various studies have demonstrated that thrombolysis and surgical embolectomy have better survival outcomes than anticoagulation alone. Present management strategies are supported by observational studies, and further research is needed to guide therapy.
Language	English
Publishing date	2023-11-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	1294965-6
ISSN	1538-4683 ; 1061-5377
ISSN (online)	1538-4683
ISSN	1061-5377
DOI	10.1097/CRD.0000000000000630
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Article ; Online: Review of the Etiology, Diagnosis, and Therapy of Left Atrial Thrombus.

Feldman, Jared M / Wang, Andy / Frishman, William H / Aronow, Wilbert S

Cardiology in review

2023

Abstract: Thrombi in the left atrial appendage (LAA) are an important cause of systemic thromboembolism in patients with atrial fibrillation. The gold standard for the diagnosis of LAA thrombi is a transesophageal echocardiogram, although cardiac multidetector ... ...

Abstract	Thrombi in the left atrial appendage (LAA) are an important cause of systemic thromboembolism in patients with atrial fibrillation. The gold standard for the diagnosis of LAA thrombi is a transesophageal echocardiogram, although cardiac multidetector computed tomography, intracardiac echocardiogram, and cardiac magnetic resonance imaging are alternative diagnostic imaging modalities. When an LAA thrombus is diagnosed, effective anticoagulation is recommended for at least 3 weeks or until thrombus resolution is confirmed on repeat transesophageal echocardiogram. Recent prospective research shows the efficacy of nonvitamin K oral anticoagulants in the treatment of LAA thrombus, which offers a promising alternative to vitamin K antagonists. As an alternative approach, left atrial aspiration thrombectomy has been described in case reports, though there is limited evidence comparing its efficacy to anticoagulation alone.
Language	English
Publishing date	2023-08-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1294965-6
ISSN	1538-4683 ; 1061-5377
ISSN (online)	1538-4683
ISSN	1061-5377
DOI	10.1097/CRD.0000000000000592
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Article ; Online: Mpox in the New York metropolitan area, Summer 2022.

Gnanaprakasam, Rachel / Keller, Marina / Glassman, Rebecca / El-Khoury, Marc Y / Chen, Donald S / Feola, Nicholas / Feldman, Jared / Chaturvedi, Vishnu

Journal of medical virology

2023 Volume 95, Issue 4, Page(s) e28699

Abstract: Early in the 2022 Mpox (MPX) global outbreak, caseloads in the New York Metropolitan area climbed rapidly before other US urban areas. This case series summarizes the authors' clinical experience detecting and treating MPX, during a quickly evolving ... ...

Abstract	Early in the 2022 Mpox (MPX) global outbreak, caseloads in the New York Metropolitan area climbed rapidly before other US urban areas. This case series summarizes the authors' clinical experience detecting and treating MPX, during a quickly evolving outbreak. Clinical outcomes were recorded with a focus on varied clinical presentation and outcomes such as complications and response to experimental tecovirimat therapy. A focal or multifocal rash was the most common presenting symptom in 91% of patients. Almost two-thirds (62%) of patients had anogenital involvement. Proctitis was one of the most painful presentations with 75% requiring antiviral treatment and three patients needing hospitalization for pain management. Most patients responded promptly to antiviral treatment with tecovirimat. Five out of 10 patients treated with tecovirimat reported symptom resolution within 48-72 h of therapy and another three saw resolution within first 96 h. Two patients had poor response to tecovirimat. This series includes the only reported case of an HIV positive, immunocompetent patient who experienced recurrent anal ulcers due to Mpox and required a second course of tecovirimat. Other unique presentations included urethritis, abscess formation and MPX infection postvaccination. Control of this current Mpox outbreak was possible due to timely diagnosis and the availability of both a licensed vaccine and an investigational drug.
MeSH term(s)	Humans ; Mpox (monkeypox) ; New York ; Antiviral Agents/therapeutic use ; Benzamides ; Isoindoles
Chemical Substances	Antiviral Agents ; Benzamides ; Isoindoles
Language	English
Publishing date	2023-03-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.28699
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Zs.A 1320: Show issues

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Article ; Online: Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds.

Wamhoff, Eike-Christian / Ronsard, Larance / Feldman, Jared / Knappe, Grant A / Hauser, Blake M / Romanov, Anna / Case, James Brett / Sanapala, Shilpa / Lam, Evan C / Denis, Kerri J St / Boucau, Julie / Barczak, Amy K / Balazs, Alejandro B / Diamond, Michael S / Schmidt, Aaron G / Lingwood, Daniel / Bathe, Mark

Nature communications

2024 Volume 15, Issue 1, Page(s) 795

Abstract: Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B ... ...

Abstract	Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B cell responses that may neutralize the platform. Here, we investigate thymus-independent DNA origami as an alternative material for multivalent antigen display using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, the primary target of neutralizing antibody responses. Sequential immunization of mice with DNA-based VLPs (DNA-VLPs) elicits protective neutralizing antibodies to SARS-CoV-2 in a manner that depends on the valency of the antigen displayed and on T cell help. Importantly, the immune sera do not contain boosted, class-switched antibodies against the DNA scaffold, in contrast to P-VLPs that elicit strong B cell memory against both the target antigen and the scaffold. Thus, DNA-VLPs enhance target antigen immunogenicity without generating scaffold-directed immunity and thereby offer an important alternative material for particulate vaccine design.
MeSH term(s)	Humans ; Animals ; Mice ; Antibody Formation ; Antibodies, Blocking ; Vaccines, Virus-Like Particle/genetics ; Antibodies, Neutralizing ; DNA ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus
Chemical Substances	spike protein, SARS-CoV-2 ; Antibodies, Blocking ; Vaccines, Virus-Like Particle ; Antibodies, Neutralizing ; DNA (9007-49-2) ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2024-01-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-44869-0
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Article ; Online: Humoral responses to the SARS-CoV-2 spike and receptor binding domain in context of pre-existing immunity confer broad sarbecovirus neutralization.

Hauser, Blake M / Sangesland, Maya / Lam, Evan C / Feldman, Jared / Balazs, Alejandro B / Lingwood, Daniel / Schmidt, Aaron G

Frontiers in immunology

2022 Volume 13, Page(s) 902260

Abstract: Since the emergence of SARS-CoV-2 (SARS-2), multiple vaccine candidates were developed and studied both preclinically and clinically. Nearly all are based on the SARS-2 spike glycoprotein or its receptor binding domain (RBD). Studies of these vaccine ... ...

Abstract	Since the emergence of SARS-CoV-2 (SARS-2), multiple vaccine candidates were developed and studied both preclinically and clinically. Nearly all are based on the SARS-2 spike glycoprotein or its receptor binding domain (RBD). Studies of these vaccine candidates have largely been in a SARS-2 naïve context. However, pre-existing immunity to SARS-2 acquired through infection or vaccination continues to increase. Evaluating future vaccine candidates in context of this pre-existing immunity is necessary to understand how immune responses are subsequently influenced. Here, we evaluated the serum and IgG
MeSH term(s)	Antibodies, Viral ; COVID-19/prevention & control ; Epitopes ; Humans ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus
Chemical Substances	Antibodies, Viral ; Epitopes ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-08-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.902260
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Article ; Online: Engaging an HIV vaccine target through the acquisition of low B cell affinity.

Ronsard, Larance / Yousif, Ashraf S / Nait Mohamed, Faez Amokrane / Feldman, Jared / Okonkwo, Vintus / McCarthy, Caitlin / Schnabel, Julia / Caradonna, Timothy / Barnes, Ralston M / Rohrer, Daniel / Lonberg, Nils / Schmidt, Aaron / Lingwood, Daniel

Nature communications

2023 Volume 14, Issue 1, Page(s) 5249

Abstract: Low affinity is common for germline B cell receptors (BCR) seeding development of broadly neutralizing antibodies (bnAbs) that engage hypervariable viruses, including HIV. Antibody affinity selection is also non-homogenizing, insuring the survival of low ...

Abstract	Low affinity is common for germline B cell receptors (BCR) seeding development of broadly neutralizing antibodies (bnAbs) that engage hypervariable viruses, including HIV. Antibody affinity selection is also non-homogenizing, insuring the survival of low affinity B cell clones. To explore whether this provides a natural window for expanding human B cell lineages against conserved vaccine targets, we deploy transgenic mice mimicking human antibody diversity and somatic hypermutation (SHM) and immunize with simple monomeric HIV glycoprotein envelope immunogens. We report an immunization regimen that focuses B cell memory upon the conserved CD4 binding site (CD4bs) through both conventional affinity maturation and reproducible expansion of low affinity BCR clones with public patterns in SHM. In the latter instance, SHM facilitates target acquisition by decreasing binding strength. This suggests that permissive B cell selection enables the discovery of antibody epitopes, in this case an HIV bnAb site.
MeSH term(s)	Humans ; Animals ; Mice ; AIDS Vaccines ; B-Lymphocytes ; Memory B Cells ; Receptors, Antigen, B-Cell/genetics ; Broadly Neutralizing Antibodies ; HIV Antigens ; Mice, Transgenic ; HIV Infections/prevention & control
Chemical Substances	AIDS Vaccines ; Receptors, Antigen, B-Cell ; Broadly Neutralizing Antibodies ; HIV Antigens
Language	English
Publishing date	2023-08-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-40918-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds.

Wamhoff, Eike-Christian / Ronsard, Larance / Feldman, Jared / Knappe, Grant A / Hauser, Blake M / Romanov, Anna / Lam, Evan / Denis, Kerri St / Boucau, Julie / Barczak, Amy K / Balazs, Alejandro B / Schmidt, Aaron / Lingwood, Daniel / Bathe, Mark

bioRxiv : the preprint server for biology

2023

Abstract: Multivalent antigen display is a well-established principle to enhance humoral immunity. Protein-based virus-like particles (VLPs) are commonly used to spatially organize antigens. However, protein-based VLPs are limited in their ability to control ... ...

Abstract	Multivalent antigen display is a well-established principle to enhance humoral immunity. Protein-based virus-like particles (VLPs) are commonly used to spatially organize antigens. However, protein-based VLPs are limited in their ability to control valency on fixed scaffold geometries and are thymus-dependent antigens that elicit neutralizing B cell memory themselves, which can distract immune responses. Here, we investigated DNA origami as an alternative material for multivalent antigen display in vivo, applied to the receptor binding domain (RBD) of SARS-CoV2 that is the primary antigenic target of neutralizing antibody responses. Icosahedral DNA-VLPs elicited neutralizing antibodies to SARS-CoV-2 in a valency-dependent manner following sequential immunization in mice, quantified by pseudo- and live-virus neutralization assays. Further, induction of B cell memory against the RBD required T cell help, but the immune sera did not contain boosted, class-switched antibodies against the DNA scaffold. This contrasted with protein-based VLP display of the RBD that elicited B cell memory against both the target antigen and the scaffold. Thus, DNA-based VLPs enhance target antigen immunogenicity without generating off-target, scaffold-directed immune memory, thereby offering a potentially important alternative material for particulate vaccine design.
Language	English
Publishing date	2023-06-19
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.08.16.504128
Database	MEDical Literature Analysis and Retrieval System OnLINE

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