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Article ; Online: Indirect costs of non-healing diabetic foot wounds in an African origin population in Barbados.

Greenidge, André R / Naitram, Simon / Quimby, Kim R / Anderson, Simon G / Landis, R Clive

Diabetic medicine : a journal of the British Diabetic Association

2022 Volume 39, Issue 9, Page(s) e14888

MeSH term(s)	Barbados/epidemiology ; Costs and Cost Analysis ; Diabetes Mellitus ; Diabetic Foot ; Humans ; Wound Healing
Language	English
Publishing date	2022-05-25
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	605769-x
ISSN	1464-5491 ; 0742-3071 ; 1466-5468
ISSN (online)	1464-5491
ISSN	0742-3071 ; 1466-5468
DOI	10.1111/dme.14888
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Article: 20 Years On: Is It Time to Redefine the Systemic Inflammatory Response to Cardiothoracic Surgery?

Landis, R Clive

The journal of extra-corporeal technology

2015 Volume 47, Issue 1, Page(s) 5–9

Abstract: ... inflammatory response" is also problematic; it is too narrow and might be replaced with host response (the R ... on PIRO could allow these elements of the host Response (R) to be anchored within the context of Premorbid ...

Abstract	The "systemic inflammatory response" has never been defined from a cardiothoracic surgery perspective, but borrowed its definition from the critical care field at a landmark 1992 definition conference on sepsis. It is unclear why the diagnostic criteria for the Systemic Inflammatory Response Syndrome (SIRS) were adopted in isolation, ignoring other potentially more useful definitions for Severe Septic Shock or Secondary Multiple Organ Dysfunction Syndrome. The 1992 SIRS definition for sepsis has since been updated at a conference in 2001 advocating PIRO (Predisposition, Infection, host Response, Organ dysfunction) as a hypothetical model to better link sepsis with clinical outcome. PIRO is readily adaptable to cardiothoracic surgery and provides the precedent and road map for how to update a definition. The need is obvious since the current definition of SIRS is widely disregarded in heart surgery: a dwindling proportion (14%) of articles on the systemic inflammatory response even mention SIRS and 0% monitored SIRS criteria in the past decade in an evidence-based review of anti-inflammatory interventions. The name "inflammatory response" is also problematic; it is too narrow and might be replaced with host response (the R in PIRO) to better convey the wide spectrum of host defensive pathways activated during heart surgery (i.e., complement, coagulation, fibrinolysis, kinins, cytokines, proteases, hemolysis, oxidative stiess). A variant on PIRO could allow these elements of the host Response (R) to be anchored within the context of Premorbid conditions (P) and the inevitable Insult (I) from surgery, to better link risk exposures to Organ dysfunction (O) in heart surgery. The precedent of PIRO suggests the following steps will be required to redefine the systemic inflammatory response: 1) buy-in from the leading societies for cardiothoracic surgery, anesthesia, and perfusion on the need for a re-definition conference, 2) assigning relative risk scores to different premorbid exposures, operative insults, and host response factors on clinical outcome, 3) validation of the risk model in a prospective cohort, and 4) development of algorithms or "apps" to facilitate rapid diagnosis and staging of care at bedside.
MeSH term(s)	Diagnosis, Differential ; Humans ; Multiple Organ Failure/classification ; Multiple Organ Failure/diagnosis ; Multiple Organ Failure/etiology ; Sepsis/classification ; Sepsis/diagnosis ; Sepsis/etiology ; Systemic Inflammatory Response Syndrome/classification ; Systemic Inflammatory Response Syndrome/diagnosis ; Systemic Inflammatory Response Syndrome/etiology ; Terminology as Topic ; Thoracic Surgical Procedures/adverse effects
Language	English
Publishing date	2015-03
Publishing country	United States
Document type	Editorial
ZDB-ID	390977-3
ISSN	0022-1058
ISSN	0022-1058
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Article ; Online: Issue highlights--July 2013.

Landis, R Clive

Cytometry. Part B, Clinical cytometry

2013 Volume 84, Issue 4, Page(s) 205–206

MeSH term(s)	ADP-ribosyl Cyclase 1/genetics ; Biomarkers ; Flow Cytometry ; Genes, bcl-2 ; Humans ; Membrane Glycoproteins/genetics ; Precision Medicine
Chemical Substances	Biomarkers ; Membrane Glycoproteins ; CD38 protein, human (EC 3.2.2.5) ; ADP-ribosyl Cyclase 1 (EC 3.2.2.6)
Language	English
Publishing date	2013-07
Publishing country	United States
Document type	Editorial ; Introductory Journal Article
ZDB-ID	2099657-3
ISSN	1552-4957 ; 1552-4949 ; 0196-4763
ISSN (online)	1552-4957
ISSN	1552-4949 ; 0196-4763
DOI	10.1002/cyto.b.21100
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Article ; Online: Direct healthcare services cost of non-healing diabetic foot wounds in an African origin population in Barbados.

Greenidge, André R / Quimby, Kim R / Rose, Angela M C / Speede, Amy / Hambleton, Ian R / Anderson, Simon G / Landis, R Clive

Diabetic medicine : a journal of the British Diabetic Association

2021 Volume 39, Issue 6, Page(s) e14773

MeSH term(s)	Barbados/epidemiology ; Delivery of Health Care ; Diabetes Mellitus ; Diabetic Foot/epidemiology ; Diabetic Foot/therapy ; Health Services ; Humans ; Wound Healing
Language	English
Publishing date	2021-12-28
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	605769-x
ISSN	1464-5491 ; 0742-3071 ; 1466-5468
ISSN (online)	1464-5491
ISSN	0742-3071 ; 1466-5468
DOI	10.1111/dme.14773
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Article ; Online: M1/M2 Macrophages in Diabetic Nephropathy: Nrf2/HO-1 as Therapeutic Targets.

Landis, Robert Clive / Quimby, Kim R / Greenidge, Andre R

Current pharmaceutical design

2018 Volume 24, Issue 20, Page(s) 2241–2249

Abstract: The process of inflammation is orchestrated by macrophages, according to their state of differentiation: thus, classically activated (M1) macrophages initiate the process by elaborating proinflammatory cytokines and reactive oxygen species, whereas the ... ...

Abstract	The process of inflammation is orchestrated by macrophages, according to their state of differentiation: thus, classically activated (M1) macrophages initiate the process by elaborating proinflammatory cytokines and reactive oxygen species, whereas the latter phase is controlled by alternatively activated macrophages (M2) to resolve inflammation and promote tissue remodelling with the release of growth factors. In a simple human inflammatory response, such as acute crystal arthropathy, macrophages progress linearly through M1 and M2 phases; however, in chronic inflammatory responses, such as atherosclerosis and Diabetic Nephropathy (DN), both M1 and M2 macrophages may coexist, leading to persistent inflammation and fibrosis. A key macrophage receptor that regulates conversion from M1 to M2 is CD163, the hemoglobin scavenger receptor. Scavenging of hemoglobin:haptoglobin (Hb:Hp) complexes via CD163 leads to nuclear translocation of the transcription factor Nrf2 (NF-E2-related factor 2), upregulation of heme oxygenase (HO)-1 cytoprotective protein, and release of interleukin (IL)-10 anti-inflammatory cytokine; IL-10 is then linked in a positive feedback loop to further CD163 expression. The potency of this M1/M2 switching pathway is underscored by the fact that human Hp2 polymorphisms are associated with worsened clinical outcomes for diabetic complications, including DN. Parallel observations in animals show that HO-1 activation by hemin protects against DN in rodent models of diabetes. This review discusses the concept that Nrf2/HO-1 acts as a 'therapeutic funnel' through which a range of natural and synthetic anti-oxidants may drive M1 to M2 switching and improved kidney function in diabetes. We also discuss our observations on the evolution of M1/M2 phenotypes in a human model of wound healing which has presented intriguing potential drug targets for DN, such as eotaxin/CCR3.
MeSH term(s)	Diabetic Nephropathies/drug therapy ; Gene Expression Regulation/drug effects ; Heme Oxygenase-1/metabolism ; Humans ; Macrophages/classification ; Macrophages/drug effects ; Macrophages/physiology ; NF-E2-Related Factor 2/metabolism
Chemical Substances	NF-E2-Related Factor 2 ; NFE2L2 protein, human ; Heme Oxygenase-1 (EC 1.14.14.18)
Language	English
Publishing date	2018-08-10
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/1381612824666180716163845
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Article: Redefining the systemic inflammatory response.

Landis, R Clive

Seminars in cardiothoracic and vascular anesthesia

2009 Volume 13, Issue 2, Page(s) 87–94

Abstract: From the first description of the "systemic inflammatory response" in the early 1990s, it has been recognized that this is a multifaceted response of the body to the combined insult of cardiothoracic surgery with bypass, involving causation by " ... ...

Abstract	From the first description of the "systemic inflammatory response" in the early 1990s, it has been recognized that this is a multifaceted response of the body to the combined insult of cardiothoracic surgery with bypass, involving causation by "activation of complement, coagulation, fibrinolytic, and kallikrein cascades, activation of neutrophils with degranulation and protease enzyme release, oxygen radical production, and the synthesis of various cytokines from mononuclear cells." Yet the intervening 15 years have seen a narrowing of research into individual systems and interventions naively targeted at single pathways without achieving clinically meaningful benefits. The time has come to redefine the systemic inflammatory response so that research can be more productively focused on objectively measuring and interdicting this multisystem disorder. A key concept of this new understanding is that translation into a hard adverse event occurs when the systemic imbalance is combined with a localized trigger. Triggers might be inadvertently provided by transient episodes of ischemia/malperfusion to vulnerable organs or handling trauma to major vessels. Future research should be directed at suppressing systemic activation with combinations of drugs and improved circuit coating, whereas changes in clinical practice and continuous monitoring of perfusion parameters can help eliminate localized triggering events.
MeSH term(s)	Blood Coagulation ; Cardiopulmonary Bypass/adverse effects ; Complement Activation ; Fibrinolysis ; Humans ; Inflammation Mediators/metabolism ; Oxidative Stress ; Postoperative Complications/physiopathology ; Systemic Inflammatory Response Syndrome/classification ; Systemic Inflammatory Response Syndrome/etiology ; Systemic Inflammatory Response Syndrome/physiopathology ; Systemic Inflammatory Response Syndrome/prevention & control
Chemical Substances	Inflammation Mediators
Language	English
Publishing date	2009-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2012371-1
ISSN	1940-5596 ; 1089-2532
ISSN (online)	1940-5596
ISSN	1089-2532
DOI	10.1177/1089253209337743
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Zs.A 5308: Show issues

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Article: The Caribbean: riding the dark horse of HIV/AIDS towards a brighter future.

Landis, R Clive

Cytometry. Part B, Clinical cytometry

2007 Volume 72, Issue 2, Page(s) 153–155

MeSH term(s)	Acquired Immunodeficiency Syndrome/diagnosis ; Acquired Immunodeficiency Syndrome/economics ; CD4-Positive T-Lymphocytes/physiology ; Caribbean Region ; Flow Cytometry/economics ; Forecasting ; HIV Infections/diagnosis ; HIV Infections/economics ; HIV Seroprevalence
Language	English
Publishing date	2007-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2099657-3
ISSN	1552-4957 ; 1552-4949 ; 0196-4763
ISSN (online)	1552-4957
ISSN	1552-4949 ; 0196-4763
DOI	10.1002/cyto.b.20185
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Article: Protease activated receptors: clinical relevance to hemostasis and inflammation.

Landis, R Clive

Hematology/oncology clinics of North America

2007 Volume 21, Issue 1, Page(s) 103–113

Abstract: The protease-activated receptors (PARs) are a unique family of vascular receptors that confer on cells an ability to sense, and respond to, local changes in the proteolytic environment. They are activated by serine proteases of the blood coagulation ... ...

Abstract	The protease-activated receptors (PARs) are a unique family of vascular receptors that confer on cells an ability to sense, and respond to, local changes in the proteolytic environment. They are activated by serine proteases of the blood coagulation cascade, notably thrombin, and are linked to thrombotic and inflammatory effector pathways. In surgery with cardiopulmonary bypass (CPB), thrombin is generated in large quantities in the extracorporeal circuit and can exert systemic effects by way of platelet and endothelial PAR1. Aprotinin (Trasylol), a serine protease inhibitor used in cardiac surgery, preserves platelet function, and attenuates the inflammatory response by protecting the PAR 1 receptor on platelets and endothelium.
MeSH term(s)	Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Aprotinin/pharmacology ; Cardiopulmonary Bypass ; Hemostasis/drug effects ; Hemostasis/physiology ; Humans ; Inflammation/drug therapy ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Aggregation Inhibitors/therapeutic use ; Receptors, Proteinase-Activated/drug effects ; Receptors, Proteinase-Activated/physiology ; Thrombosis/drug therapy
Chemical Substances	Anti-Inflammatory Agents ; Platelet Aggregation Inhibitors ; Receptors, Proteinase-Activated ; Aprotinin (9087-70-1)
Language	English
Publishing date	2007-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	93115-9
ISSN	1558-1977 ; 0889-8588
ISSN (online)	1558-1977
ISSN	0889-8588
DOI	10.1016/j.hoc.2006.11.005
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Article ; Online: Intravenous infusion of haptoglobin for the prevention of adverse clinical outcome in Sickle Cell Disease.

Quimby, Kim R / Hambleton, Ian R / Landis, R Clive

Medical hypotheses

2015 Volume 85, Issue 4, Page(s) 424–432

Abstract: Sickle Cell Disease (SCD) is a genetic condition which manifests as altered hemoglobin (Hb) protein that can aggregate under hypoxic conditions. The resultant sickled erythrocytes experience premature hemolysis, releasing an estimated 10g of free Hb (fHb) ...

Abstract	Sickle Cell Disease (SCD) is a genetic condition which manifests as altered hemoglobin (Hb) protein that can aggregate under hypoxic conditions. The resultant sickled erythrocytes experience premature hemolysis, releasing an estimated 10g of free Hb (fHb) into the intravascular space. FHb participates in redox reactions creating various reactive oxygen species which rapidly and irreversibly scavenge nitric oxide, thereby attenuating its vasodilatory, antithrombotic, and anti-inflammatory properties. FHb also induces endothelial expression of adhesion molecules, triggering leukocyte margination at the vessel wall. These mechanisms participate in diverse SCD-associated clinical events including nephropathy, pulmonary hypertension, chronic leg ulceration, and ischemic events. FHb also exerts a direct reno-toxic effect contributing to albuminuria which is an early, frequent manifestation of glomerular injury. Under normal conditions, fHb is effectively scavenged by the Hb-scavenging mechanism (HSM); this involves binding to haptoglobin (Hp), uptake via the Hb-scavenging receptor (CD163) on monocytes and metabolism by heme-oxygenase-1. This culminates in increased CD163 expression and release of anti-inflammatory by-products e.g. interleukin-10 (IL-10). In SCD, the Hb-binding capacity is overwhelmed by chronic hemolysis; our previous research shows serum Hp as the depleted component. This deficiency could result in the harmful consequences of circulating fHb going unbridled. The hypothesis we explore here is that Hp infusions, in excess of fHb concentration, will allow the HSM to remain functional, and thereby achieve improved clinical outcomes, tracking albuminuria as a sentinel. Albuminuria was selected because of its high prevalence in SCD and its relative ease of diagnosis and monitoring. The hypothesis may be evaluated in four phases: Phase 1 will determine the concentration of Hp needed to trigger the HSM as measured by induction of CD163 and IL-10 and the recovery of hemopexin. Phase 2 will investigate the half-life of HSM induction by analyzing the time-course of CD163 expression and IL-10 and hemopexin serum concentration. Phase 3 will determine patient eligibility for therapy, whether as treatment or prevention. Phase 4 will test the efficacy of Hp transfusions in a randomized control trial as measured by correction of albuminuria. Angiotensin converting enzyme inhibitors (ACEi) are currently the first-line treatment for SCD nephropathy, however hyperkalemia limits its use. Hydroxyurea, which has therapeutic value in many SCD adverse events, has yielded inconsistent effects on albuminuria. We are proposing the addition of an intervention more proximal in the hemolytic cascade. Boosting the exhausted Hb-scavenging capacity via Hp replacement therapy has the potential to modify multiple downstream clinical events.
MeSH term(s)	Albuminuria/diagnosis ; Anemia, Sickle Cell/drug therapy ; Anemia, Sickle Cell/prevention & control ; Anti-Inflammatory Agents ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Biomarkers/metabolism ; Child ; Child, Preschool ; Haptoglobins/administration & dosage ; Haptoglobins/therapeutic use ; Hemoglobins/therapeutic use ; Hemolysis ; Hemopexin/metabolism ; Humans ; Hydroxyurea/therapeutic use ; Infusions, Intravenous ; Interleukin-10/metabolism ; Models, Theoretical ; Reactive Oxygen Species/metabolism ; Receptors, Cell Surface/metabolism ; Treatment Outcome
Chemical Substances	Anti-Inflammatory Agents ; Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; Biomarkers ; CD163 antigen ; Haptoglobins ; Hemoglobins ; IL10 protein, human ; Reactive Oxygen Species ; Receptors, Cell Surface ; Interleukin-10 (130068-27-8) ; Hemopexin (9013-71-2) ; Hydroxyurea (X6Q56QN5QC)
Language	English
Publishing date	2015-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2015.06.023
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Article ; Online: HIV Viral Load Trends in Six Eastern Caribbean Countries Utilizing a Regional Laboratory Referral Service: Implications for Treatment as Prevention.

Landis, R Clive / Carmichael-Simmons, Kelly / Hambleton, Ian R / Best, Anton

PloS one

2015 Volume 10, Issue 4, Page(s) e0125435

Abstract: Objective: Since 2009, seven countries in the Organization of Eastern Caribbean States (OECS), Antigua & Barbuda, Dominica, Grenada, Montserrat, St. Kitts & Nevis, Saint Lucia, and St. Vincent & the Grenadines, have been utilizing a laboratory referral ... ...

Abstract	Objective: Since 2009, seven countries in the Organization of Eastern Caribbean States (OECS), Antigua & Barbuda, Dominica, Grenada, Montserrat, St. Kitts & Nevis, Saint Lucia, and St. Vincent & the Grenadines, have been utilizing a laboratory referral service for HIV-1 viral load (VL) offered by The Ladymeade Reference Unit (LRU) Laboratory, Barbados. The objective of this study was to evaluate 5 year VL trends in the six larger OECS countries participating in this regional referral service. Methods: Blood samples were collected in source countries and transported to Barbados as frozen plasma according to a standardized protocol. Plasma specimens were amplified by RT PCR on a Roche TaqMan 48 analyser (Roche Diagnostics, Panama City, Panama). VL was considered optimally suppressed below a threshold level of < 200 HIV-1 copies/mL of blood. The same threshold was used as a binary indicator in an analysis of the secular change in VL suppression. Montserrat was excluded due to insufficient number of samples. Results: A steady rise in VL referrals from OECS countries was recorded, rising from 312 samples in 2009 to 1,060 samples in 2013. A total of 3,543 samples were tested, with a sample rejection rate (9.2%) mostly due to breaks in the cold chain. Aggregate VL data showed the odds of VL suppression in the Eastern Caribbean improved by 66% for each additional year after 2009 (Odds Ratio 1.66 [95% CI 1.46 to 1.88]; p<0.001). Conclusion: We demonstrate the feasibility of establishing a regional laboratory referral service for HIV VL monitoring in the Eastern Caribbean. Aggregate VL trends showed a significant year-on-year improvement in VL suppression, implying public health benefits through treatment as prevention in the OECS. VL provides a powerful monitoring & evaluation tool for strengthening HIV programs at country level among the small island states participating in this regional referral network.
MeSH term(s)	Clinical Laboratory Techniques ; Female ; HIV Infections/blood ; HIV Infections/epidemiology ; HIV Infections/prevention & control ; Humans ; Male ; RNA, Viral/blood ; Reverse Transcriptase Polymerase Chain Reaction ; Viral Load ; West Indies/epidemiology
Chemical Substances	RNA, Viral
Language	English
Publishing date	2015
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Multicenter Study
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0125435
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