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Article ; Online: Lipoprotein Biology in Sepsis.

Walley, Keith R / Boyd, John H

2020 Volume 48, Issue 10, Page(s) 1547–1549

MeSH term(s)	Biology ; Humans ; Lipoproteins ; Sepsis ; Shock, Septic ; Subtilisins
Chemical Substances	Lipoproteins ; Subtilisins (EC 3.4.21.-)
Language	English
Publishing date	2020-09-13
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0000000000004519
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Article ; Online: Impact of the COVID-19 pandemic on non-COVID-19 community-acquired pneumonia: a retrospective cohort study.

Lee, Terry / Walley, Keith R / Boyd, John H / Cawcutt, Kelly A / Kalil, Andre / Russell, James A

BMJ open respiratory research

2023 Volume 10, Issue 1

Abstract: Background: The COVID-19 pandemic could impact frequency and mortality of non-COVID-19 community-acquired pneumonia (CAP). Changes in frequency, patient mix, treatment and organ dysfunction could cascade together to increase mortality of CAP during ... ...

Abstract	Background: The COVID-19 pandemic could impact frequency and mortality of non-COVID-19 community-acquired pneumonia (CAP). Changes in frequency, patient mix, treatment and organ dysfunction could cascade together to increase mortality of CAP during compared with pre-COVID-19. Methods: Hospitalised CAP patients at St. Paul's Hospital, Vancouver, Canada pre-COVID-19 (fiscal years 2018/2019 and 2019/2020) and during COVID-19 pandemic (2020/2021 and 2021/2022) were evaluated. Results: In 5219 CAP patients, there was no significant difference prepandemic versus during pandemic in mean age, gender and Charlson Comorbidity Score. However, hospital mortality increased significantly from pre-COVID-19 versus during COVID-19 (7.5% vs 12.1% respectively, (95% CI for difference: 3.0% to 6.3%), p<0.001), a 61% relative increase, coincident with increases in ICU admission (18.3% vs 25.5%, respectively, (95% CI for difference: 5.0% to 9.5%) p<0.001, 39% relative increase) and ventilation (12.7% vs 17.5%, respectively, (95% CI for difference: 2.8% to 6.7%) p<0.001, 38% relative increase). Results remained the same after regression adjustment for age, sex and Charlson score. CAP hospital admissions decreased 27% from pre-COVID-19 (n=1349 and 1433, 2018/2019 and 2019/2020, respectively) versus the first COVID-19 pandemic year (n=1047 in 2020/2021) then rose to prepandemic number (n=1390 in 2021/2022). During prepandemic years, CAP admissions peaked in winter; during COVID-19, the CAP admissions peaked every 6 months. Conclusions and relevance: This is the first study to show that the COVID-19 pandemic was associated with increases in hospital mortality, ICU admission and invasive mechanical ventilation rates of non-COVID-19 CAP and a transient, 1-year frequency decrease. There was no winter seasonality of CAP during the COVID-19 pandemic era. These novel findings could be used to guide future pandemic planning for CAP hospital care.
MeSH term(s)	Humans ; Pandemics ; Retrospective Studies ; COVID-19 ; Pneumonia ; Lung ; Community-Acquired Infections/therapy
Language	English
Publishing date	2023-08-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2736454-9
ISSN	2052-4439 ; 2052-4439
ISSN (online)	2052-4439
ISSN	2052-4439
DOI	10.1136/bmjresp-2023-001810
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Article ; Online: Toll-like receptors and opportunities for new sepsis therapeutics.

Boyd, John H

Current infectious disease reports

2012 Volume 14, Issue 5, Page(s) 455–461

Abstract: Serious infection and the patient's response (sepsis) is a serious health problem that, even today, is associated with a mortality rate of 30 %-50 %. The phases of severe sepsis include an early hyperinflammatory response to pathogens and a late ... ...

Abstract	Serious infection and the patient's response (sepsis) is a serious health problem that, even today, is associated with a mortality rate of 30 %-50 %. The phases of severe sepsis include an early hyperinflammatory response to pathogens and a late immunosuppressed phase. Toll-like receptors (TLRs) are a family of transmembrane innate immune receptors that play a major role in both phases of sepsis. Here, their physiology and the therapeutic strategies employed to date are reviewed. Currently, there are no approved therapies targeting TLRs, but it is anticipated that in the future, the less-studied TLRs, such as TLR3, TLR7, and TLR9, will evolve therapeutic targets, perhaps predominantly with agonists, versus the usual antagonist strategies. Furthermore, accurately characterizing the stage of sepsis will be essential to directing appropriate therapeutic choices.
Language	English
Publishing date	2012-07-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2019948-X
ISSN	1534-3146 ; 1523-3847
ISSN (online)	1534-3146
ISSN	1523-3847
DOI	10.1007/s11908-012-0273-5
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Zs.A 5519: Show issues

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Article ; Online: Molecular regulation of plasma lipid levels during systemic inflammation and sepsis.

Trinder, Mark / Boyd, John H / Brunham, Liam R

Current opinion in lipidology

2019 Volume 30, Issue 2, Page(s) 108–116

Abstract: Purpose of review: Sepsis is a common syndrome of multiorgan system dysfunction caused by a dysregulated inflammatory response to an infection and is associated with high rates of mortality. Plasma lipid and lipoprotein levels and composition change ... ...

Abstract	Purpose of review: Sepsis is a common syndrome of multiorgan system dysfunction caused by a dysregulated inflammatory response to an infection and is associated with high rates of mortality. Plasma lipid and lipoprotein levels and composition change profoundly during sepsis and have emerged as both biomarkers and potential therapeutic targets for this condition. The purpose of this article is to review recent progress in the understanding of the molecular regulation of lipid metabolism during sepsis. Recent findings: Patients who experience greater declines in high-density lipoprotein during sepsis are at much greater risk of succumbing to organ failure and death. Although the causality of these findings remains unclear, all lipoprotein classes can sequester and prevent the excessive inflammation caused by pathogen-associated lipids during severe infections such as sepsis. This primordial innate immune function has been best characterized for high-density lipoproteins. Most importantly, results from human genetics and preclinical animal studies have suggested that several lipid treatment strategies, initially designed for atherosclerosis, may hold promise as therapies for sepsis. Summary: Lipid and lipoprotein metabolism undergoes significant changes during sepsis. An improved understanding of the molecular regulation of these changes may lead to new opportunities for the treatment of sepsis.
MeSH term(s)	Animals ; Anticholesteremic Agents/therapeutic use ; Apolipoproteins C/therapeutic use ; Biomarkers/blood ; Cholesterol Ester Transfer Proteins/antagonists & inhibitors ; Cholesterol Ester Transfer Proteins/blood ; Cholesterol Ester Transfer Proteins/genetics ; Cholesterol Ester Transfer Proteins/immunology ; Gene Expression Regulation ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Immunity, Innate ; Lipid Metabolism/drug effects ; Lipid Metabolism/genetics ; Lipid Metabolism/immunology ; Lipoprotein Lipase/blood ; Lipoprotein Lipase/genetics ; Lipoprotein Lipase/immunology ; Lipoproteins, HDL/blood ; Lipoproteins, HDL/genetics ; Lipoproteins, HDL/immunology ; Multiple Organ Failure/blood ; Multiple Organ Failure/genetics ; Multiple Organ Failure/mortality ; Multiple Organ Failure/prevention & control ; Peptide Fragments/therapeutic use ; Proprotein Convertase 9/antagonists & inhibitors ; Proprotein Convertase 9/blood ; Proprotein Convertase 9/genetics ; Proprotein Convertase 9/immunology ; Sepsis/blood ; Sepsis/drug therapy ; Sepsis/genetics ; Sepsis/mortality ; Survival Analysis
Chemical Substances	Anticholesteremic Agents ; Apolipoproteins C ; Biomarkers ; CETP protein, human ; Cholesterol Ester Transfer Proteins ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipoproteins, HDL ; Peptide Fragments ; LPL protein, human (EC 3.1.1.34) ; Lipoprotein Lipase (EC 3.1.1.34) ; PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-)
Language	English
Publishing date	2019-01-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1045394-5
ISSN	1473-6535 ; 0957-9672
ISSN (online)	1473-6535
ISSN	0957-9672
DOI	10.1097/MOL.0000000000000577
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Zs.A 3010: Show issues

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Article ; Online: CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia-associated mortality in mice.

Deng, Haoyu / Liang, Wan Yi / Chen, Le Qi / Yuen, Tin Ho / Sahin, Basak / Vasilescu, Dragoș M / Trinder, Mark / Walley, Keith / Rensen, Patrick C.N. / Boyd, John H / Brunham, Liam R

JCI insight

2024 Volume 9, Issue 8

Abstract: Sepsis is a leading cause of mortality worldwide, and pneumonia is the most common cause of sepsis in humans. Low levels of high-density lipoprotein cholesterol (HDL-C) levels are associated with an increased risk of death from sepsis, and increasing ... ...

Abstract	Sepsis is a leading cause of mortality worldwide, and pneumonia is the most common cause of sepsis in humans. Low levels of high-density lipoprotein cholesterol (HDL-C) levels are associated with an increased risk of death from sepsis, and increasing levels of HDL-C by inhibition of cholesteryl ester transfer protein (CETP) decreases mortality from intraabdominal polymicrobial sepsis in APOE3-Leiden.CETP mice. Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from Streptococcus pneumoniae-induced sepsis in APOE3-Leiden.CETP and APOA1.CETP mice. Mechanistically, CETP inhibition reduced the host proinflammatory response via attenuation of proinflammatory cytokine transcription and release. This effect was dependent on the presence of HDL, leading to attenuation of immune-mediated organ damage. In addition, CETP inhibition promoted monocyte activation in the blood prior to the onset of sepsis, resulting in accelerated macrophage recruitment to the lung and liver. In vitro experiments demonstrated that CETP inhibition significantly promoted the activation of proinflammatory signaling in peripheral blood mononuclear cells and THP1 cells in the absence of HDL; this may represent a mechanism responsible for improved bacterial clearance during sepsis. These findings provide evidence that CETP inhibition represents a potential approach to reduce mortality from pneumosepsis.
MeSH term(s)	Animals ; Female ; Humans ; Mice ; Apolipoprotein E3/metabolism ; Cholesterol Ester Transfer Proteins/antagonists & inhibitors ; Cholesterol Ester Transfer Proteins/metabolism ; Cholesterol, HDL/blood ; Cholesterol, HDL/metabolism ; Disease Models, Animal ; Macrophages/immunology ; Macrophages/metabolism ; Monocytes/immunology ; Monocytes/metabolism ; Pneumonia, Pneumococcal/immunology ; Pneumonia, Pneumococcal/mortality ; Pneumonia, Pneumococcal/metabolism ; Pneumonia, Pneumococcal/microbiology ; Sepsis/immunology ; Sepsis/mortality ; Sepsis/microbiology ; Sepsis/metabolism ; Streptococcus pneumoniae/immunology ; THP-1 Cells
Chemical Substances	Apolipoprotein E3 ; Cholesterol Ester Transfer Proteins ; Cholesterol, HDL ; CETP protein, human
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.173205
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Article ; Online: Globalization of ejection fraction: the pulmonary artery catheter has been outsourced.

Boyd, John H

Critical care medicine

2011 Volume 39, Issue 9, Page(s) 2192

MeSH term(s)	Animals ; Thermodilution ; Ventricular Dysfunction, Left/diagnosis ; Ventricular Dysfunction, Right/diagnosis ; Ventricular Function, Left/physiology ; Ventricular Function, Right/physiology
Language	English
Publishing date	2011-09
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0b013e31821f02d4
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Zs.A 1261: Show issues

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Article ; Online: Assessment of adequacy of volume resuscitation.

Boyd, John H / Sirounis, Demetrios

Current opinion in critical care

2016 Volume 22, Issue 5, Page(s) 424–427

Abstract: Purpose of review: It has recently become evident that administration of intravenous fluids following initial resuscitation has a greater probability of producing tissue edema and hypoxemia than of increasing oxygen delivery. Therefore, it is essential ... ...

Abstract	Purpose of review: It has recently become evident that administration of intravenous fluids following initial resuscitation has a greater probability of producing tissue edema and hypoxemia than of increasing oxygen delivery. Therefore, it is essential to have a rational approach to assess the adequacy of volume resuscitation. Here we review passive leg raising (PLR) and respiratory variation in hemodynamics to assess fluid responsiveness. Recent findings: The use of ultrasound enhances the clinician's ability to detect and predict fluid responsiveness, whereas enthusiasm for this modality must be tempered by recent evidence that it is only reliable in apneic patients. Summary: The best predictor of fluid response for hypotensive patients not on vasopressors is a properly conducted passive leg raise maneuver. For more severely ill patients who are apneic, mechanically ventilated and on vasopressors, point of care echocardiography is the best choice. Increases in vena caval diameter induced by controlled positive pressure breaths are insensitive to arrhythmias and can be performed with relatively brief training. Most challenging are patients who are awake and on vasopressors; we suggest that the best method to discriminate fluid responders is PLR measuring changes in cardiac output.
MeSH term(s)	Cardiac Output/physiology ; Echocardiography/methods ; Fluid Therapy/methods ; Hemodynamics ; Humans ; Hypotension ; Infusions, Intravenous/methods ; Resuscitation ; Stroke Volume
Language	English
Publishing date	2016-07-29
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1235629-3
ISSN	1531-7072 ; 1070-5295
ISSN (online)	1531-7072
ISSN	1070-5295
DOI	10.1097/MCC.0000000000000344
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Zs.A 4999: Show issues

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Article: The social costs and benefits of too-big-to-fail banks

Boyd, John H / Heitz, Amanda

Journal of banking & finance Vol. 68 , p. 251-265

a "bounding" exercise

2016 Volume 68, Page(s) 251–265

Author's details	John H. Boyd, Amanda Heitz
Keywords	Financial crisis ; Financial intermediation ; Banking
Language	English
Publisher	Elsevier
Publishing place	Amsterdam [u.a.]
Document type	Article
ZDB-ID	752905-3 ; 1460614-8
ISSN	1872-6372 ; 0378-4266
ISSN (online)	1872-6372
ISSN	0378-4266
Database	ECONomics Information System

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Article ; Online: Causal Inference for Genetically Determined Levels of High-Density Lipoprotein Cholesterol and Risk of Infectious Disease.

Trinder, Mark / Walley, Keith R / Boyd, John H / Brunham, Liam R

Arteriosclerosis, thrombosis, and vascular biology

2019 Volume 40, Issue 1, Page(s) 267–278

Abstract: Objective: HDL (high-density lipoprotein) cholesterol (HDL-C) and LDL (low-density lipoprotein) cholesterol (LDL-C) are inversely associated with infectious hospitalizations. Whether these represent causal relationships is unknown. Approach and Results: ...

Abstract	Objective: HDL (high-density lipoprotein) cholesterol (HDL-C) and LDL (low-density lipoprotein) cholesterol (LDL-C) are inversely associated with infectious hospitalizations. Whether these represent causal relationships is unknown. Approach and Results: Adults of 40 to 69 years of age were recruited from across the United Kingdom between 2006 and 2010 and followed until March 31, 2016, as part of the UK Biobank. We determined HDL-C, LDL-C, and triglyceride polygenic scores for UK Biobank participants of British white ancestry (n=407 558). We examined the association of lipid levels and polygenic scores with infectious hospitalizations, antibiotic usage, and 28-day sepsis survival using Cox proportional hazards or logistic regression models. Measured levels of HDL-C and LDL-C were inversely associated with risk of infectious hospitalizations, while triglycerides displayed a positive association. A 1-mmol/L increase in genetically determined levels of HDL-C associated with a hazard ratio for infectious disease of 0.84 ([95% CI, 0.75-0.95]; Conclusions: Our results provide causal inference for an inverse relationship between HDL-C, but not LDL-C or triglycerides, and risk of an infectious hospitalization.
MeSH term(s)	Adult ; Aged ; Cholesterol, HDL/blood ; Cholesterol, HDL/genetics ; Female ; Follow-Up Studies ; Genetic Predisposition to Disease ; Hospitalization/trends ; Humans ; Incidence ; Infections/blood ; Infections/epidemiology ; Infections/genetics ; Male ; Mendelian Randomization Analysis ; Middle Aged ; Multifactorial Inheritance ; Polymorphism, Single Nucleotide ; Prospective Studies ; Risk Factors ; United Kingdom/epidemiology
Chemical Substances	Cholesterol, HDL
Language	English
Publishing date	2019-11-07
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.119.313381
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Zs.A 1705: Show issues

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Article ; Online: THE IMPACT OF THE COVID-19 PANDEMIC ON NON-COVID-19 COMMUNITY-ACQUIRED PNEUMONIA, A RETROSPECTIVE COHORT STUDY

Lee, Terry / Walley, Keith R. / Boyd, John H. / Cawcutt, Kelly A. / Kalil, Andre C. / Russell, James A.

medRxiv

Abstract: BACKGROUND The COVID-19 pandemic could impact frequency and mortality of non-COVID-19 community-acquired pneumonia (CAP). Changes in frequency, patient mix, treatment, and organ dysfunction could cascade together to increase mortality of CAP during ... ...

Abstract	BACKGROUND The COVID-19 pandemic could impact frequency and mortality of non-COVID-19 community-acquired pneumonia (CAP). Changes in frequency, patient mix, treatment, and organ dysfunction could cascade together to increase mortality of CAP during compared to pre-COVID-19. METHODS: Hospitalized CAP patients at St. Paul9s Hospital, Vancouver, Canada pre- (fiscal years 2018/2019 and 2019/2020) and during COVID-19 pandemic (2020/2021 and 2021/2022) were evaluated. RESULTS: In 5219 CAP patients, there was no significant difference pre- versus during pandemic in mean age, gender and Charlson co-morbidity score. However, hospital mortality increased significantly from pre- versus during COVID-19 (7.5% versus 12.1% respectively, [95% CI for difference: 3.0-6.3%], p<0.001), a 61% relative increase, coincident with increases in ICU admission (18.3% versus 25.5% respectively, [95% CI for difference: 5.0-9.5%] p<0.001, 39% relative increase) and ventilation (12.7% versus 17.5%, respectively, [95% CI for difference: 2.8-6.7%] p<0.001, 38% relative increase). Results remained the same after regression adjustment for confounders. CAP hospital admissions decreased 27% from pre- (n=1349 and 1433, 2018/2019 and 2019/2020 respectively) versus the first COVID-19 pandemic year (n=1047 in 2020/2021) then rose to pre-pandemic number (n=1390 in 2021/2022). During pre-pandemic years, CAP admissions peaked in winter; during COVID-19, the CAP admissions peaked every six months. CONCLUSIONS AND RELEVANCE: The COVID-19 pandemic was associated with increases in hospital mortality, ICU admission and invasive mechanical ventilation rates of non-COVID-19 CAP and a transient, one year frequency decrease. There was no winter seasonality of CAP during the COVID-19 pandemic era. Future pandemic planning for CAP hospital care is needed.
Keywords	covid19
Language	English
Publishing date	2023-05-05
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.05.04.23289541
Database	COVID19

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