Mervyn Singer
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View article: Exploring the genetic architecture of multiple long-term conditions using a genome-wide association study in the UK Biobank population
Exploring the genetic architecture of multiple long-term conditions using a genome-wide association study in the UK Biobank population Open
The prevalence of multiple long-term conditions (MLTC) is increasing. It is essential to develop strategies to prevent and manage MLTC; however, the biological mechanisms underlying MLTC are not yet clearly understood. We used UK Biobank d…
View article: Does Time to Achieve a Targeted Body Temperature Matter for Survivors of Cardiac Arrest? A Systematic Review and Meta-Analysis
Does Time to Achieve a Targeted Body Temperature Matter for Survivors of Cardiac Arrest? A Systematic Review and Meta-Analysis Open
Objectives: To identify the impact of early hypothermic temperature control (HTC) initiation and achievement on neurologic outcomes after cardiac arrest. Secondary endpoints assessed: 1) overall survival, 2) body temperature at hospital ad…
View article: Development and Validation of the Sequential Organ Failure Assessment (SOFA)-2 Score
Development and Validation of the Sequential Organ Failure Assessment (SOFA)-2 Score Open
Importance Acute dysfunction of vital organs is the hallmark of critical illness. The Sequential Organ Failure Assessment (SOFA) score, the most widely adopted approach to describe organ dysfunction, has not been updated in 30 years and th…
View article: Rationale and Methodological Approach Underlying the Development of the Sequential Organ Failure Assessment (SOFA)–2 Score
Rationale and Methodological Approach Underlying the Development of the Sequential Organ Failure Assessment (SOFA)–2 Score Open
Importance The Sequential Organ Failure Assessment (SOFA) score was published in 1996 to describe organ dysfunction in critically ill adult patients in a readily quantifiable and sequential manner. Considerable changes have occurred over t…
View article: Optimal Cutoffs for the Ratio of Arterial Oxygen Partial Pressure to Inspired Oxygen Fraction in Categorizing Respiratory Impairment Severity in Organ Failure Scores
Optimal Cutoffs for the Ratio of Arterial Oxygen Partial Pressure to Inspired Oxygen Fraction in Categorizing Respiratory Impairment Severity in Organ Failure Scores Open
Background The ratio of arterial oxygen partial pressure to fraction of inspired oxygen (PaO 2 /FiO 2 , hereafter P/F ratio) is a key component of the Sequential Organ Failure Assessment (SOFA) score. It reflects the severity of hypoxaemic…
View article: Peri-Operative Antimicrobial Prophylaxis Modulates CD4+ Lymphocyte Immunophenotype Ex Vivo in High-Risk Patients Undergoing Major Elective Surgery—A Preliminary Observational Study
Peri-Operative Antimicrobial Prophylaxis Modulates CD4+ Lymphocyte Immunophenotype Ex Vivo in High-Risk Patients Undergoing Major Elective Surgery—A Preliminary Observational Study Open
Background: Post-operative infections are a significant cause of morbidity in patients undergoing major elective surgery. Peri-operative antibiotics are used to reduce the risk of infection. Several antibiotics modulate the host immune res…
View article: The amphiregulin- epidermal growth factor receptor axis as a therapeutic target in sepsis
The amphiregulin- epidermal growth factor receptor axis as a therapeutic target in sepsis Open
The Epidermal Growth Factor Receptor (EGFR) and its ligand, amphiregulin (AREG) are critical for epithelial cell proliferation but their important role in inflammation and infection is increasingly described. We recently discovered that th…
View article: Multi‐Omics and ‐Organ Insights into Energy Metabolic Adaptations in Early Sepsis Onset
Multi‐Omics and ‐Organ Insights into Energy Metabolic Adaptations in Early Sepsis Onset Open
Systemic metabolic dysregulation in sepsis critically impacts patient survival. To better understand its onset, untargeted serum metabolomics and lipidomics are analyzed from 152 presymptomatic patients undergoing major elective surgery, a…
View article: Assessing perioperative risks in a mixed elderly surgical population using machine learning: A multi-objective symbolic regression approach to cardiorespiratory fitness derived from cardiopulmonary exercise testing
Assessing perioperative risks in a mixed elderly surgical population using machine learning: A multi-objective symbolic regression approach to cardiorespiratory fitness derived from cardiopulmonary exercise testing Open
Accurate preoperative risk assessment is of great value to both patients and clinical teams. Several risk scores have been developed but are often not calibrated to the local institution, limited in terms of data input into the underlying …
View article: Metabolic Flexibility as a Candidate Mechanism for the Development of Postoperative Morbidity
Metabolic Flexibility as a Candidate Mechanism for the Development of Postoperative Morbidity Open
BACKGROUND: This study investigates the role of metabolic flexibility in determining perioperative outcomes. Metabolic flexibility, a key feature of metabolic health, is the ability to efficiently switch between different fuel sources (pre…
View article: “The NET effect”: Neutrophil extracellular traps—a potential key component of the dysregulated host immune response in sepsis
“The NET effect”: Neutrophil extracellular traps—a potential key component of the dysregulated host immune response in sepsis Open
Neutrophils release neutrophil extracellular traps (NETs) as part of a healthy host immune response. NETs physically trap and kill pathogens as well as activating and facilitating crosstalk between immune cells and complement. Excessive or…
View article: Therapeutic strategies to ameliorate mitochondrial oxidative stress in ischaemia-reperfusion injury: A narrative review
Therapeutic strategies to ameliorate mitochondrial oxidative stress in ischaemia-reperfusion injury: A narrative review Open
Mitochondrial reactive oxygen species (mROS) play a crucial physiological role in intracellular signalling. However, high levels of ROS can overwhelm antioxidant defences and lead to detrimental modifications in protein, lipid and DNA stru…
View article: Building ADMISSION – A research collaborative to transform understanding of multiple long-term conditions for people admitted to hospital
Building ADMISSION – A research collaborative to transform understanding of multiple long-term conditions for people admitted to hospital Open
Background Multiple long-term conditions (MLTCs; commonly referred to as multimorbidity) are highly prevalent among people admitted to hospital and are therefore of critical importance to hospital-based healthcare systems. To date, most re…
View article: The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study
The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study Open
Purpose The landiolol and organ failure in patients with septic shock (STRESS-L study) included a pre-planned sub-study to assess the effect of landiolol treatment on inflammatory and metabolomic markers. Methods Samples collected from 91 …
View article: Mortality prediction after major surgery in a mixed population through machine learning: a multi‐objective symbolic regression approach
Mortality prediction after major surgery in a mixed population through machine learning: a multi‐objective symbolic regression approach Open
Summary Introduction Understanding 1‐year mortality following major surgery offers valuable insights into patient outcomes and the quality of peri‐operative care. Few models exist that predict 1‐year mortality accurately. This study aimed …
View article: Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis
Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis Open
Importance For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these…
View article: Antibiotic-Induced Immunosuppression—A Focus on Cellular Immunity
Antibiotic-Induced Immunosuppression—A Focus on Cellular Immunity Open
Antibiotics are the fundamental treatment for bacterial infections. However, they are associated with numerous side effects. Their adverse effects on the immune system are increasingly recognised, with several mechanisms identified. In thi…
View article: A randomised controlled trial of plasma exchange compared to standard of care in the treatment of severe COVID-19 infection (COVIPLEX)
A randomised controlled trial of plasma exchange compared to standard of care in the treatment of severe COVID-19 infection (COVIPLEX) Open
COVID-19 disease is associated with a hyperinflammatory, pro-thrombotic state and a high mortality. Our primary objective was to assess the change in inflammatory and thrombotic markers associated with PEX, and secondary objectives were to…