Publications by authors named "T Jason Meredith"

222 Publications

Extracorporeal Membrane Oxygenation-Supported Transcatheter Mitral Valve-in-Valve Replacement and Paravalvular Plugging for Critical Prosthetic Mitral Stenosis.

JACC Case Rep 2022 Apr 20;4(8):491-496. Epub 2022 Apr 20.

St Vincent's Hospital, Sydney, Australia.

We present the case of a patient with rapidly progressive bioprosthetic mitral valve stenosis in the setting of end-stage renal failure. Critical valve stenosis led to cardiogenic shock requiring full hemodynamic support. Emergent extracorporeal membrane oxygenation-supported transcatheter mitral valve-in-valve implantation was successfully undertaken as a life-saving measure with an excellent final result. ().
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http://dx.doi.org/10.1016/j.jaccas.2022.02.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044295PMC
April 2022

Rapid Inhibitor Discovery by Exploiting Synthetic Lethality.

J Am Chem Soc 2022 03 16;144(8):3696-3705. Epub 2022 Feb 16.

Department of Microbiology, Harvard University, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Synthetic lethality occurs when inactivation of two genes is lethal but inactivation of either single gene is not. This phenomenon provides an opportunity for efficient compound discovery. Using differential growth screens, one can identify biologically active compounds that selectively inhibit proteins within the synthetic lethal network of any inactivated gene. Here, based purely on synthetic lethalities, we identified two compounds as the only possible inhibitors of lipoteichoic acid (LTA) biosynthesis from a screen of ∼230,000 compounds. Both compounds proved to inhibit the glycosyltransferase UgtP, which assembles the LTA glycolipid anchor. UgtP is required for β-lactam resistance in methicillin-resistant (MRSA), and the inhibitors restored sensitivity to oxacillin in a highly resistant strain. As no other compounds were pursued as possible LTA glycolipid assembly inhibitors, this work demonstrates the extraordinary efficiency of screens that exploit synthetic lethality to discover compounds that target specified pathways. The general approach should be applicable not only to other bacteria but also to eukaryotic cells.
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http://dx.doi.org/10.1021/jacs.1c12697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9012225PMC
March 2022

Managing Fractures and Sprains.

Prim Care 2022 Mar 5;49(1):145-161. Epub 2022 Jan 5.

Department of Family Medicine, Offutt AFB/UNMC Family Medicine Residency Program, University of Nebraska Medical Center College of Medicine, 983075 Nebraska Medical Center, Omaha, NE 68198-3075, USA.

Primary care physicians are often the first to evaluate patients with extremity injuries. Identification of fractures and sprains and their proper management is paramount. After appropriate imaging is obtained, immobilization and determination of definitive management, either nonoperative or operative, is critical. Appropriate immobilization is imperative to injury healing. Nonsurgical management of upper extremity fractures often uses slings, short-term splinting, gutter splints, and/or short or long arm casts. Initial fracture stabilization of the lower extremity is usually accomplished with a posterior splint. Definitive management usually uses controlled ankle movement walker boots, hard-sole shoes, or casting.
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http://dx.doi.org/10.1016/j.pop.2021.10.007DOI Listing
March 2022

Importance of electromagnetic interactions between ICD and VAD devices-Mechanistic assessment.

Artif Organs 2022 Jun 15;46(6):1132-1141. Epub 2022 Jan 15.

Heart Failure and Transplant Unit, St Vincent's Hospital, Sydney, New South Wales, Australia.

Background: Implanted cardioverter defibrillators (ICDs) and left ventricular assist devices (LVADs) are established interventions that prolong life in advanced heart failure, but their combination has not been demonstrated as beneficial. Electromagnetic interference (EMI) produced by a LVAD can preclude ICD interrogation with external programmers. We undertook a systematic evaluation of the LVAD-ICD interaction "in-vitro" to clarify the extent of this interaction.

Methods: Using explanted ICDs and VADs in a mock physiological rig, we assessed interrogation and reprogramming of ICD devices in the presence of a running LVAD. When connectivity between the ICD programmer and the ICD failed, we attempted three different techniques to re-establish connectivity: (1) Electromagnetic shielding of the ICD with a pseudo-faraday cage; (2) altering the LVAD speed; and (3) increasing the distance between the VAD and the ICD.

Results: We tested a total of 24 ICDs from different manufacturers in the presence of the Heartware (HW) and HeartMate 3 (HM3) LVADs. With HW, we only observed interaction with Biotronik ICD devices at very close range (0-6 cm). With HM3, only Medtronic ICD devices showed no interaction. Interactions could be mitigated by increasing the VAD-ICD distance.

Conclusions: LVADs, notably the HM3, produce EMI that interferes with the communication between an ICD and its respective programmer. This may need to be considered when choosing the type of VAD to implant in patients with a previously implanted left-sided ICD. The only safe way to regain connectivity is to increase the distance between the VAD and the ICD, with patients raising their arm above their head.
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http://dx.doi.org/10.1111/aor.14167DOI Listing
June 2022

Heart Failure Therapies for the Prevention of HER2-Monoclonal Antibody-Mediated Cardiotoxicity: A Systematic Review and Meta-Analysis of Randomized Trials.

Cancers (Basel) 2021 Nov 3;13(21). Epub 2021 Nov 3.

Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.

Monoclonal antibodies including trastuzumab, pertuzumab, and antibody-drug conjugates, form the backbone of HER2-positive breast cancer therapy. Unfortunately, an important adverse effect of these agents is cardiotoxicity, occurring in approximately 10% of patients. There is increasing published data regarding prevention strategies for cardiotoxicity, though seldom used in clinical practice. We performed a systematic review and meta-analysis of randomized-controlled trials to evaluate pharmacotherapy for the prevention of monoclonal HER2-directed antibody-induced cardiotoxicity in patients with breast cancer. Online databases were queried from their inception until October 2021. Effects were determined by calculating risk ratios (RRs) and 95% confidence intervals (CI) or mean differences (MD) using random-effects models. We identified five eligible trials. In the three trials ( = 952) reporting data on the primary outcome of cardiotoxicity, there was no clear effect for patients assigned active treatment compared to control (RR = 0.90, 95% CI 0.63 to 1.29, = 0.57). Effects were similar for ACE-I/ARB and beta-blockers ( homogeneity = 0.50). Active treatment reduced the risk of HER2 therapy interruptions (RR = 0.57, 95% CI 0.43 to 0.77, < 0.001) with similar findings for ACE-I/ARB and beta-blockers ( homogeneity = 0.97). Prophylactic treatment with ACE-I/ARB or beta-blocker therapy may be of value for cardio-protection in patients with breast cancer prescribed monoclonal antibodies. Further, adequately powered randomized trials are required to define the role of routine prophylactic treatment in this patient group.
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http://dx.doi.org/10.3390/cancers13215527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583665PMC
November 2021
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