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  1. Article ; Online: Facial Transplantation: A Dilemma of the Four Basic Medical Ethics Principles.

    Leonard, Colin G / Leonard, David A

    Plastic and reconstructive surgery

    2022  Volume 149, Issue 6, Page(s) 1257e–1258e

    MeSH term(s) Ethics, Medical ; Facial Transplantation ; Humans
    Language English
    Publishing date 2022-05-25
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 208012-6
    ISSN 1529-4242 ; 0032-1052 ; 0096-8501
    ISSN (online) 1529-4242
    ISSN 0032-1052 ; 0096-8501
    DOI 10.1097/PRS.0000000000009102
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  2. Article ; Online: The Nuances of Hand Transplantation After Sepsis.

    Zuo, Kevin J / Leonard, David A / Shores, Jaimie T / Talbot, Simon G

    Transplantation

    2024  Volume 108, Issue 2, Page(s) 319–322

    Abstract: Vascularized composite allotransplantation (VCA) of the upper extremity is an established restorative procedure for selected patients with acquired upper limb loss. The majority of upper limb VCAs performed worldwide have been for victims of various ... ...

    Abstract Vascularized composite allotransplantation (VCA) of the upper extremity is an established restorative procedure for selected patients with acquired upper limb loss. The majority of upper limb VCAs performed worldwide have been for victims of various forms of trauma. However, in the developed world, amputation following severe sepsis seems to be an increasingly common indication for referral to hand transplant programs. Unlike trauma patients with isolated limb injuries, patients with amputations as a complication of sepsis have survived through a state of global tissue hypoperfusion and multisystem organ failure with severe, enduring effects on the entire body's physiology. This article reviews the unique considerations for VCA candidacy in postsepsis patients with upper limb amputation. These insights may also be relevant to postsepsis patients undergoing other forms of transplantation or to VCA patients requiring additional future solid organ transplants.
    MeSH term(s) Humans ; Hand Transplantation ; Vascularized Composite Allotransplantation/adverse effects ; Vascularized Composite Allotransplantation/methods ; Transplantation, Homologous ; Organ Transplantation/adverse effects ; Sepsis/etiology
    Language English
    Publishing date 2024-01-19
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000004665
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  3. Article ; Online: Commentary on "An experimental rodent model of whole eye transplantation for assessment of viability and immunological outcomes".

    Leonard, David A

    Journal of plastic, reconstructive & aesthetic surgery : JPRAS

    2019  Volume 72, Issue 10, Page(s) 1651–1652

    MeSH term(s) Animals ; Feasibility Studies ; Ophthalmologic Surgical Procedures ; Rodentia
    Language English
    Publishing date 2019-05-25
    Publishing country Netherlands
    Document type Journal Article ; Comment
    ZDB-ID 2217750-4
    ISSN 1878-0539 ; 1748-6815 ; 0007-1226
    ISSN (online) 1878-0539
    ISSN 1748-6815 ; 0007-1226
    DOI 10.1016/j.bjps.2019.05.043
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  4. Article ; Online: Hand transplantation: can we balance the risks and benefits?

    Kay, Simon P J / Leonard, David A

    The Journal of hand surgery, European volume

    2023  Volume 48, Issue 3, Page(s) 208–213

    Abstract: Asking 'can we balance the risks and benefits?' implies that a quantification of both risk and benefit in hand transplantation (here the terms hand transplant and hand transplantation refer to allotransplantation of the human hand or hand and part or all ...

    Abstract Asking 'can we balance the risks and benefits?' implies that a quantification of both risk and benefit in hand transplantation (here the terms hand transplant and hand transplantation refer to allotransplantation of the human hand or hand and part or all of the upper limb or limbs) is possible. Despite all we have learned in recent years about hand transplantation, much remains unknown. Even if reliable methods for quantification of risk and benefit were available, fundamental issues relating to effective communication across the gulf of lived experience between the (presumably) handed surgeon and the handless patient remain. Inherent complexities mean some consider hand transplantation an unsolved problem, but we believe the medical and technical considerations fall within the ambit of a competent multidisciplinary team, and that psychosocial and ethical challenges are open to management through robust frameworks for assessment and decision making, underpinned by an extended period of assessment and dialogue, with candid acknowledgement where uncertainty remains. This respects the patient's autonomy while addressing the need for a prolonged period of informing consent.
    MeSH term(s) Humans ; Hand Transplantation/methods ; Upper Extremity ; Hand ; Risk Assessment
    Language English
    Publishing date 2023-01-13
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2272801-6
    ISSN 2043-6289 ; 1753-1934
    ISSN (online) 2043-6289
    ISSN 1753-1934
    DOI 10.1177/17531934221132665
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  5. Article ; Online: More than skin deep: Mucosal pathology in facial vascularized composite allografts. Commentary on "Pathologies of oral and sinonasal mucosa following facial vascularized composite allotransplantation".

    Leonard, David A / Colvin, Robert B

    Journal of plastic, reconstructive & aesthetic surgery : JPRAS

    2020  Volume 74, Issue 7, Page(s) 1572–1573

    MeSH term(s) Composite Tissue Allografts ; Facial Transplantation ; Humans ; Mucous Membrane ; Skin ; Vascularized Composite Allotransplantation
    Language English
    Publishing date 2020-12-17
    Publishing country Netherlands
    Document type Journal Article ; Comment
    ZDB-ID 2217750-4
    ISSN 1878-0539 ; 1748-6815 ; 0007-1226
    ISSN (online) 1878-0539
    ISSN 1748-6815 ; 0007-1226
    DOI 10.1016/j.bjps.2020.12.031
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  6. Article ; Online: Vascularized Plexus Allotransplantation: A New Hope in Brachial Plexus Palsy?

    Farkash, Evan A / Leonard, David A

    Transplantation

    2018  Volume 103, Issue 1, Page(s) 17–18

    MeSH term(s) Animals ; Brachial Plexus ; Brachial Plexus Neuropathies ; Paralysis ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew
    Language English
    Publishing date 2018-07-26
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000002388
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  7. Article ; Online: Conformational flexibility in carbapenem hydrolysis drives substrate specificity of the class D carbapenemase OXA-24/40.

    Mitchell, Joshua M / June, Cynthia M / Baggett, Vincent L / Lowe, Beth C / Ruble, James F / Bonomo, Robert A / Leonard, David A / Powers, Rachel A

    The Journal of biological chemistry

    2022  Volume 298, Issue 7, Page(s) 102127

    Abstract: The evolution of multidrug resistance in Acinetobacter spp. increases the risk of our best antibiotics losing their efficacy. From a clinical perspective, the carbapenem-hydrolyzing class D β-lactamase subfamily present in Acinetobacter spp. is ... ...

    Abstract The evolution of multidrug resistance in Acinetobacter spp. increases the risk of our best antibiotics losing their efficacy. From a clinical perspective, the carbapenem-hydrolyzing class D β-lactamase subfamily present in Acinetobacter spp. is particularly concerning because of its ability to confer resistance to carbapenems. The kinetic profiles of class D β-lactamases exhibit variability in carbapenem hydrolysis, suggesting functional differences. To better understand the structure-function relationship between the carbapenem-hydrolyzing class D β-lactamase OXA-24/40 found in Acinetobacter baumannii and carbapenem substrates, we analyzed steady-state kinetics with the carbapenem antibiotics meropenem and ertapenem and determined the structures of complexes of OXA-24/40 bound to imipenem, meropenem, doripenem, and ertapenem, as well as the expanded-spectrum cephalosporin cefotaxime, using X-ray crystallography. We show that OXA-24/40 exhibits a preference for ertapenem compared with meropenem, imipenem, and doripenem, with an increase in catalytic efficiency of up to fourfold. We suggest that superposition of the nine OXA-24/40 complexes will better inform future inhibitor design efforts by providing insight into the complicated and varying ways in which carbapenems are selected and bound by class D β-lactamases.
    MeSH term(s) Acinetobacter baumannii/enzymology ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/metabolism ; Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Carbapenems/chemistry ; Carbapenems/metabolism ; Hydrolysis ; Microbial Sensitivity Tests ; Protein Conformation ; Substrate Specificity ; beta-Lactamases/chemistry ; beta-Lactamases/metabolism
    Chemical Substances Anti-Bacterial Agents ; Bacterial Proteins ; Carbapenems ; beta-Lactamases (EC 3.5.2.6) ; beta-lactamase OXA-24 (EC 3.5.2.6) ; beta-lactamase OXA-40, Acinetobacter baumannii (EC 3.5.2.6)
    Language English
    Publishing date 2022-06-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2022.102127
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  8. Article ; Online: Invited editorial from the social media editor of JPRAS; Leadership in the time of COVID-19.

    Lindsay, Karen J / Leonard, David A / Higgins, Gillian C / Robertson, Eleanor / Perks, Graeme

    Journal of plastic, reconstructive & aesthetic surgery : JPRAS

    2020  Volume 73, Issue 8, Page(s) 1405–1408

    MeSH term(s) Betacoronavirus ; COVID-19 ; Coronavirus Infections/epidemiology ; Health Facility Administration ; Health Priorities ; Humans ; Leadership ; Organizational Innovation ; Pandemics ; Pneumonia, Viral/epidemiology ; Research ; SARS-CoV-2 ; Safety Management ; Surgery, Plastic/organization & administration ; United Kingdom
    Keywords covid19
    Language English
    Publishing date 2020-06-18
    Publishing country Netherlands
    Document type Editorial
    ZDB-ID 2217750-4
    ISSN 1878-0539 ; 1748-6815 ; 0007-1226
    ISSN (online) 1878-0539
    ISSN 1748-6815 ; 0007-1226
    DOI 10.1016/j.bjps.2020.07.001
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  9. Article ; Online: Common clinical substitutions enhance the carbapenemase activity of OXA-51-like class D β-lactamases from Acinetobacter spp.

    Mitchell, Joshua M / Leonard, David A

    Antimicrobial agents and chemotherapy

    2014  Volume 58, Issue 11, Page(s) 7015–7016

    MeSH term(s) Acinetobacter/drug effects ; Acinetobacter/enzymology ; Acinetobacter/genetics ; Acinetobacter Infections/drug therapy ; Acinetobacter Infections/microbiology ; Ampicillin/pharmacology ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Carbapenems/metabolism ; Carbapenems/pharmacology ; Catalytic Domain ; Cross Infection/drug therapy ; Cross Infection/microbiology ; Humans ; Protein Folding ; beta-Lactamases/genetics ; beta-Lactamases/metabolism
    Chemical Substances Anti-Bacterial Agents ; Bacterial Proteins ; Carbapenems ; Ampicillin (7C782967RD) ; beta-Lactamases (EC 3.5.2.6) ; beta-lactamase OXA-51, Acinetobacter baumannii (EC 3.5.2.6) ; carbapenemase (EC 3.5.2.6)
    Language English
    Publishing date 2014-08-25
    Publishing country United States
    Document type Letter
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.03651-14
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  10. Article ; Online: Expanded Substrate Activity of OXA-24/40 in Carbapenem-Resistant Acinetobacter baumannii Involves Enhanced Binding Loop Flexibility.

    Staude, Michael W / Leonard, David A / Peng, Jeffrey W

    Biochemistry

    2016  Volume 55, Issue 47, Page(s) 6535–6544

    Abstract: Gram-negative bacteria resist β-lactam antibiotics primarily by deploying β-lactamase proteins that hydrolytically destroy the antibiotics. In clinical settings, these bacteria are producing variant β-lactamases with "gain-of-activity" mutations that ... ...

    Abstract Gram-negative bacteria resist β-lactam antibiotics primarily by deploying β-lactamase proteins that hydrolytically destroy the antibiotics. In clinical settings, these bacteria are producing variant β-lactamases with "gain-of-activity" mutations that inactivate a broader range of β-lactams. Learning how these mutations broaden substrate activity is important for coping with β-lactam resistance. Here, we investigate a gain of activity mutation in OXA-24/40, a carbapenem-hydrolyzing class D β-lactamase (CHDL) in Acinetobacter baumannii. OXA-24/40 was originally active against penicillin and carbapenem classes of β-lactams, but a clinical variant of OXA-24/40, the single-site substitution mutant P227S, has emerged with expanded activity that now includes advanced cephalosporins and the monobactam aztreonam. Using solution-state nuclear magnetic resonance (NMR) spectroscopy, we have compared the site-specific backbone dynamics of wild-type OXA-24/40 and the P227S variant. P227S changes local backbone flexibility in segments that are important for both binding and hydrolysis of carbapenem and cephalosporin substrates. Our results suggest that mutation-induced changes in sequence-specific dynamics can expand substrate activity and thus highlight the role of protein conformational dynamics in antibiotic resistance. To the best of our knowledge, this is the first NMR study of CHDL conformational dynamics and its impact on the expansion of β-lactam antibiotic resistance.
    MeSH term(s) Acinetobacter baumannii/enzymology ; Acinetobacter baumannii/genetics ; Amino Acid Motifs ; Amino Acid Sequence ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Carbapenems/metabolism ; Carbapenems/pharmacology ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Mutation ; Pliability ; Protein Binding ; Protein Domains ; Protein Structure, Secondary ; Substrate Specificity ; beta-Lactam Resistance/genetics ; beta-Lactamases/chemistry ; beta-Lactamases/genetics ; beta-Lactamases/metabolism ; beta-Lactams/metabolism ; beta-Lactams/pharmacology
    Chemical Substances Bacterial Proteins ; Carbapenems ; beta-Lactams ; beta-lactamase OXA-4 (EC 3.5.2.-) ; beta-Lactamases (EC 3.5.2.6) ; beta-lactamase OXA-24 (EC 3.5.2.6)
    Language English
    Publishing date 2016-11-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1108-3
    ISSN 1520-4995 ; 0006-2960
    ISSN (online) 1520-4995
    ISSN 0006-2960
    DOI 10.1021/acs.biochem.6b00806
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