
Jon SilversidesQueen's University Belfast | QUB · Centre for Experimental Medicine
Jon Silversides
BSc (Hons), MB BCh BAO (Hons) FRCA MRCP EDIC FFICM PhD
About
50
Publications
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Introduction
Research interests:
-Critical care
-Perioperative medicine
Additional affiliations
May 2015 - October 2019
July 2011 - June 2012
June 2013 - present
Publications
Publications (50)
Background
Proprotein Convertase Subtilisin-Kexin type 9 (PCSK9) is a key regulator of lipid metabolism. Recently, a pro-inflammatory role for PCSK9 has been hypothesised, through reduced bacterial phospholipid clearance. Elevated circulating PCSK9 levels in patients with acute respiratory distress syndrome (ARDS) has been reported in a single coho...
Objective
This article describes the statistical analysis plan for the Biomarker-guided intervention to prevent AKI after major surgery (BigpAK-2) trial.
Design
Adaptive trial design with an interim analysis after enrolment of 618 evaluable patients.
Setting
The BigpAK.-2 trial is an international, prospective, randomised controlled multicentre s...
OBJECTIVES
Near-infrared spectroscopy (NIRS) is a potentially valuable modality to monitor the adequacy of oxygen delivery to the brain and other tissues in critically ill patients, but little is known about the physiologic determinants of NIRS-derived tissue oxygen saturations. The purpose of this study was to assess the contribution of routinely...
Background
Urinary Chemokine (C–C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions.
Methods
Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach cons...
Aims
Fluid accumulation (FA) in critically ill children is associated with poor clinical outcomes. While conservative fluid management has been proposed, evidence to guide practice is scarce. We surveyed paediatric critical care (PCC) physicians worldwide regarding their perceptions of FA, active fluid removal (AFR) practices, safety parameters, an...
Sepsis is a life-threatening condition characterised by endothelial barrier dysfunction and impairment of normal microcirculatory function, resulting in a state of hypoperfusion and tissue oedema. No specific pharmacological therapies are currently used to attenuate microvascular injury. Given the prominent role of endothelial breakdown and microci...
Importance
The efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain.
Objective
To determine whether vitamin C improves outcomes for patients with COVID-19.
Design, Setting, and Participants
Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units...
Rationale:
Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in COVID-19-related Acute Respiratory Distress Syndrome (ARDS).
Objectives:
We investigated safety and efficacy of ORBCEL-C (CD362-enriched, umbilical cord-derived MSCs) in COVID-related ARDS.
Methods:
This multicentre, randomised, double-blind, allocation...
Introduction and Objectives
REALIST-COVID was a UK multicentre, double-blind randomised, allocation concealed, placebo-controlled phase 2 trial, investigating a novel mesenchymal stromal cell (MSC) product (ORBCEL-C cryopreserved, allogeneic, umbilical cord-derived CD362 enriched MSCs) in patients with ARDS due to COVID-19. Here we report follow up...
Background
Mesenchymal stromal cells (MSCs) may be of benefit in ARDS due to immunomodulatory and reparative properties. This trial investigates a novel CD362 enriched umbilical cord derived MSC product (REALIST ORBCEL-C), produced to Good Manufacturing Practice standards, in patients with moderate to severe ARDS due to COVID-19 and ARDS due to oth...
Importance:
The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain.
Objective:
To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19.
Design, setting, and participants:
In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multip...
Purpose:
Fluid overload is common in critical illness and is associated with mortality. This study investigated the feasibility of a randomised trial comparing conservative fluid administration and deresuscitation (active removal of accumulated fluid using diuretics or ultrafiltration) with usual care in critical illness.
Methods:
Open-label, pa...
Background
Mesenchymal stromal cells (MSCs) may be of benefit in acute respiratory distress syndrome (ARDS) due to immunomodulatory, reparative, and antimicrobial actions. ORBCEL-C is a population of CD362 enriched umbilical cord-derived MSCs. The REALIST phase 1 trial investigated the safety and feasibility of ORBCEL-C in patients with moderate to...
Importance:
The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.
Objective:
To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19.
Design, setting, and participants:
The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial f...
Objective
To comprehensively update and survey the current provision of recovery, rehabilitation and follow-up services for adult critical care patients across the UK.
Design
Cross-sectional, self-administered, predominantly closed-question, electronic, online survey.
Setting
Institutions providing adult critical care services identified from nat...
Introduction
Lung cancer is the leading cause of cancer death in Europe. Surgical resection is often the preferred treatment but is associated with morbidity and mortality. Survival with a meaningful quality of life is important; however, the prediction of post-operative dyspnoea (POD) is often difficult and innaccurate.1 The European Society of Th...
PurposeTo study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19).Methods
Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (cont...
Background
The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.
Methods
We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensiv...
Objectives
The primary objective of the study is to assess the safety of a single intravenous infusion of Mesenchymal Stromal Cells (MSCs) in patients with Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Secondary objectives are to determine the effects of MSCs on important clinical outcomes, as described below.
Trial design
REALIST CO...
Background: COVID-19 can result in a severe viral pneumonia, with high reported mortality rates in patients requiring mechanical ventilation. There is controversy as to whether established therapeutic approaches to acute respiratory distress syndrome are optimal in this condition, and numerous novel therapies have been used, often outside the conte...
Accumulation of a positive fluid balance is common in critically ill patients, and is associated with adverse outcomes, including mortality. However, there are few randomised clinical trials to guide clinicians as to the most appropriate fluid strategy following initial resuscitation and on the use of deresuscitation (removal of accumulated fluid u...
The Faculty of Intensive Care Medicine and Intensive Care Society Guideline Development Group have used GRADE methodology to make the following recommendations for the management of adult patients with acute respiratory distress syndrome (ARDS). The British Thoracic Society supports the recommendations in this guideline. Where mechanical ventilatio...
Background: Intravenous fluid administration is a common intervention in critically ill patients. However, this frequently contributes to a positive fluid balance, which is consistently associated with adverse outcomes including mortality. A conservative or deresuscitative (use of diuretics or renal replacement therapies to remove accumulated fluid...
Objectives:
To characterize current practice in fluid administration and deresuscitation (removal of fluid using diuretics or renal replacement therapy), the relationship between fluid balance, deresuscitative measures, and outcomes and to identify risk factors for positive fluid balance in critical illness.
Design:
Retrospective cohort study....
Background
It is unknown whether a conservative approach to fluid administration or deresuscitation (active removal of fluid using diuretics or renal replacement therapy) is beneficial following haemodynamic stabilisation of critically ill patients. PurposeTo evaluate the efficacy and safety of conservative or deresuscitative fluid strategies in ad...
Background:
Fluid administration to critically ill patients remains the subject of considerable controversy. While intravenous fluid given for resuscitation may be life-saving, a positive fluid balance over time is associated with worse outcomes in critical illness. The aim of this systematic review is to summarise the existing evidence regarding...
IntroductionIn this cohort study, we explored the relationship between fluid balance, intradialytic hypotension and outcomes in critically ill patients with acute kidney injury (AKI) who received renal replacement therapy (RRT).Methods
We analysed prospectively collected registry data on patients older than 16 years who received RRT for at least 2...
The clinician tasked with procurement or prescribing of nutritional support for the critically ill patient is faced with a wide and dynamic range of products that can appear bewildering. A sound understanding of the basic components and properties of these products will facilitate informed decision-making and allow for a rational assessment of new...
Fluid overload is associated with mortality in critically ill patients with acute kidney injury (AKI) [1-3]. We explored this relationship in patients with AKI who received renal replacement therapy (RRT) in the ICU to investigate the relationship between fluid balance and intradialytic hypotension with mortality and recovery of renal function.
Phaeochromocytoma is a catecholamine producing tumour and an uncommon cause of hypertension. We present two cases of relatively asymptomatic individuals, in which previously undiagnosed phaeochromocytoma was unmasked by elective nonadrenal surgical procedures, manifesting as postoperative hypertensive crisis and subsequent cardiogenic shock. The in...
Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute inflammatory lung injury with a high short-term mortality rate and significant long-term consequences among survivors. Supportive care, principally with mechanical ventilation, remains the cornerstone of therapy - although the goals of this support have changed in...
Staphylococcal toxic shock syndrome is a rare complication of Staphylococcus aureus infection in which bacterial toxins act as superantigens, activating very large numbers of T cells and generating an overwhelming immune-mediated cytokine avalanche that manifests clinically as fever, rash, shock, and rapidly progressive multiple organ failure, ofte...
We report the case of a patient who presented with coma in the context of baclofen and quetiapine overdose. While the clinical picture was largely in keeping with previous descriptions of baclofen and quetiapine toxicity, the patient went on to exhibit clinical and biochemical features of cranial diabetes insipidus, a finding which has not previous...
Four CTLA4 polymorphisms were investigated in a Northern Irish collection of relapsing-remitting (RR) and primary-progressive (PP) multiple sclerosis (MS) patients. The CTLA4 promoter (-318 C/T), exon 1 (+49 A/G) and intergenic CT60 SNPs, as well as a microsatellite found in the 3' UTR (AT(n)) were analysed in 246 RRMS, 84 PPMS and 158 healthy cont...
Injuries in childhood represent a major public health concern. North and West Belfast is an area in which a high rate of emergency department attendance due to injury has been observed, and in which social deprivation is widespread. We carried out a cross sectional survey of 479 injuries in children aged 0-12 years presenting to four emergency depa...
The CCR5 chemokine receptor has been implicated in the pathogenesis of multiple sclerosis (MS). We carried out an allelic association study using a deletion polymorphism in the coding region of the CCR5 gene in 331 relapsing-remitting (RR) and secondary progressive (SP) MS patients, 108 primary progressive (PP) MS patients and 230 healthy controls....
The aim of this study was to investigate the effects of elevated D-glucose concentrations on vascular smooth muscle cell (VSMC) expression of the platelet-derived growth factor (PDGF)beta receptor and VSMC migratory behavior. Immunoprecipitation, immunofluorescent staining, and RT-PCR of human VSMCs showed that elevated D-glucose induced an increas...