ORCID Profile
0000-0001-7910-0554
Current Organisations
Leeds Teaching Hospitals NHS Trust
,
Royal College of Physicians
,
University of Leeds
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Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.BJA.2019.01.033
Abstract: Chlorhexidine is an antiseptic with a broad spectrum of activity and a persistent effect on skin. Consequently, it has become an ubiquitous antiseptic in healthcare and the community. As use has become widespread, increasing numbers of cases of allergy have been reported in the literature, including cases of anaphylaxis to chlorhexidine gels used on mucous membranes, chlorhexidine-impregnated devices such as central venous catheters, chlorhexidine preparations used on wounds and broken skin, and cases after dental procedures. Numerous governmental warnings have been issued over recent decades to warn of the risk of allergy to chlorhexidine on mucosal surfaces or in medical devices. Whilst the number of published cases likely underestimates the true prevalence of reactions, we retrospectively surveyed clinics with experience in investigating perioperative chlorhexidine allergy. Despite differences in investigation practice before the survey took place, 13 clinics responded which together had diagnosed 252 cases of anaphylaxis to chlorhexidine, and cases of delayed allergy. In eight of 13 clinics, chlorhexidine was within the top four most commonly diagnosed causes of perioperative anaphylaxis. Despite this, the incidence of anaphylaxis to chlorhexidine is low given that patients are very commonly exposed. Sensitisation of healthcare workers can occur, but is uncommon. Before exposing patients to this antiseptic, consideration of the potential risk vs benefit should be undertaken, particularly for higher risk exposures, such as mucosal exposure or i.v. exposure via impregnated lines. Difficulties exist in protecting patients with known allergies from re-exposure to chlorhexidine, which would be improved with uniform labelling and chlorhexidine product registers.
Publisher: Springer Science and Business Media LLC
Date: 24-06-2020
Publisher: Springer Science and Business Media LLC
Date: 06-05-2020
Publisher: Springer Science and Business Media LLC
Date: 17-08-2022
DOI: 10.1038/S41467-022-29931-Z
Abstract: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis -regulatory elements as contributing mechanisms to ICP susceptibility.
Publisher: Elsevier BV
Date: 07-2018
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.BJA.2019.01.026
Abstract: Unsubstantiated penicillin-allergy labels are common in surgical patients, and can lead to significant harm through avoidance of best first-line prophylaxis of surgical site infections and increased infection with resistant bacterial strains. Up to 98% of penicillin-allergy labels are incorrect when tested. Because of the scarcity of trained allergists in all healthcare systems, only a minority of surgical patients have the opportunity to undergo testing and de-labelling before surgery. Testing pathways can be modified and shortened in selected patients. A variety of healthcare professionals can, with appropriate training and in collaboration with allergists, provide testing for selected patients. We review how patients might be assessed, the appropriate testing strategies that can be used, and the minimum standards of safe testing.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.BJA.2019.03.018
Abstract: Suspected perioperative allergic reactions are often severe. To avoid potentially life-threatening re-exposure to the culprit drug, establishing a firm diagnosis and identifying the culprit is crucial. Drug provocation tests are considered the gold standard in drug allergy investigation but have not been recommended in the investigation of perioperative allergy, mainly because of the pharmacological effects of drugs such as induction agents and neuromuscular blocking agents. Some specialised centres have reported benefits of provocation testing in perioperative allergy investigation, but the literature on the subject is limited. Here we provide a status update on the use of drug provocation testing in perioperative allergy, including its use in specific drug groups. This review is based on a literature search and experiences of the authors comprising anaesthesiologists and allergists with experience in perioperative allergy investigation. In addition, 19 participating centres in the International Suspected Perioperative Allergic Reaction Group were surveyed on the use of provocation testing in perioperative allergy investigation. A response was received from 13 centres in eight European countries, New Zealand, and the USA. Also, 21 centres from the Australian and New Zealand Anaesthetic Allergy Group were surveyed. Two centres performed provocation routinely and seven centres performed no provocations at all. Nearly half of the centres reported performing provocations with induction agents and neuromuscular blocking agents. Drug provocation testing is being used in perioperative allergy investigation in specialised centres, but collaborations between relevant specialties and multicentre studies are necessary to determine indications and establish common testing protocols.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.BJA.2019.01.027
Abstract: Suspected perioperative hypersensitivity reactions are rare but contribute significantly to the morbidity and mortality of surgical procedures. Recent publications have highlighted the differences between countries concerning the respective risk of different drugs, and changes in patterns of causal agents and the emergence of new allergens. This review summarises recent information on the epidemiology of perioperative hypersensitivity reactions, with specific consideration of differences between geographic areas for the most frequently involved offending agents.
Publisher: Springer Science and Business Media LLC
Date: 22-01-2018
DOI: 10.1038/S41598-017-14403-Y
Abstract: Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human s les. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype.
Publisher: Elsevier BV
Date: 04-2019
Publisher: American Association for the Advancement of Science (AAAS)
Date: 30-03-2016
DOI: 10.1126/SCITRANSLMED.AAF1471
Abstract: A mutation in pyrin that disrupts regulation leads to autoinflammatory disease.
Publisher: Elsevier BV
Date: 10-2018
Publisher: Elsevier BV
Date: 02-2017
Publisher: Elsevier BV
Date: 2017
Publisher: Oxford University Press (OUP)
Date: 25-05-2018
DOI: 10.1111/CEI.13125
Abstract: This is the second report of the United Kingdom Primary Immunodeficiency (UKPID) registry. The registry will be a decade old in 2018 and, as of August 2017, had recruited 4758 patients encompassing 97% of immunology centres within the United Kingdom. This represents a doubling of recruitment into the registry since we reported on 2229 patients included in our first report of 2013. Minimum PID prevalence in the United Kingdom is currently 5·90/100 000 and an average incidence of PID between 1980 and 2000 of 7·6 cases per 100 000 UK live births. Data are presented on the frequency of diseases recorded, disease prevalence, diagnostic delay and treatment modality, including haematopoietic stem cell transplantation (HSCT) and gene therapy. The registry provides valuable information to clinicians, researchers, service commissioners and industry alike on PID within the United Kingdom, which may not otherwise be available without the existence of a well-established registry.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.BJA.2019.04.044
Abstract: Suspected perioperative allergic reactions are rare but can be life-threatening. The diagnosis is difficult to make in the perioperative setting, but prompt recognition and correct treatment is necessary to ensure a good outcome. A group of 26 international experts in perioperative allergy (anaesthesiologists, allergists, and immunologists) contributed to a modified Delphi consensus process, which covered areas such as differential diagnosis, management during and after anaphylaxis, allergy investigations, and plans for a subsequent anaesthetic. They were asked to rank the appropriateness of statements related to the immediate management of suspected perioperative allergic reactions. Statements were selected to represent areas where there is a lack of consensus in existing guidelines, such as dosing of epinephrine and fluids, the management of impending cardiac arrest, and reactions refractory to standard treatment. The results of the modified Delphi consensus process have been included in the recommendations on the management of suspected perioperative allergic reactions. This paper provides anaesthetists with an overview of relevant knowledge on the immediate and postoperative management of suspected perioperative allergic reactions based on current literature and expert opinion. In addition, it provides practical advice and recommendations in areas where consensus has been lacking in existing guidelines.
Publisher: Elsevier BV
Date: 05-2019
Publisher: Massachusetts Medical Society
Date: 03-10-2019
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.BJA.2019.02.029
Abstract: Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents. We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1-9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated. Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5) these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase. We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.JBC.2022.102624
Abstract: Broadly neutralizing antibodies have huge potential as novel antiviral therapeutics due to their ability to recognize highly conserved epitopes that are seldom mutated in viral variants. A subset of bovine antibodies possess an ultralong complementarity-determining region (CDR)H3 that is highly adept at recognizing such conserved epitopes, but their reactivity against Sarbecovirus Spike proteins has not been explored previously. Here, we use a SARS-naïve library to isolate a broadly reactive bovine CDRH3 that binds the receptor-binding domain of SARS-CoV, SARS-CoV-2, and all SARS-CoV-2 variants. We show further that it neutralizes viruses pseudo-typed with SARS-CoV Spike, but this is not by competition with angiotensin-converting enzyme 2 (ACE2) binding. Instead, using differential hydrogen-deuterium exchange mass spectrometry, we demonstrate that it recognizes the major site of vulnerability of Sarbecoviruses. This glycan-shielded cryptic epitope becomes available only transiently via interdomain movements of the Spike protein such that antibody binding triggers destruction of the prefusion complex. This proof of principle study demonstrates the power of in vitro expressed bovine antibodies with ultralong CDRH3s for the isolation of novel, broadly reactive tools to combat emerging pathogens and to identify key epitopes for vaccine development.
Publisher: Elsevier BV
Date: 10-2020
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Sinisa Savic.