603 results found
U MRA, Shen EY-L, Cartlidge C, et al., 2022, Optimised systematic review tool: Application to candidate biomarkers for the diagnosis of hepatocellular carcinoma., Cancer Epidemiol Biomarkers Prev
This review aims to develop an appropriate review tool for systematically collating metabolites that are dysregulated in disease and applies the method to identify novel diagnostic biomarkers for hepatocellular carcinoma (HCC). Studies that analysed metabolites in blood or urine samples where HCC was compared with comparison groups (healthy, pre-cirrhotic liver disease, cirrhosis) were eligible. Tumour tissue was included to help differentiate primary and secondary biomarkers. Searches were conducted on Medline and EMBASE. A bespoke 'risk-of-bias' tool for metabolomic studies was developed adjusting for analytical quality. Discriminant metabolites for each sample type were ranked using a weighted score accounting for the direction and extent of change and the risk of bias of the reporting publication. A total of 84 eligible studies were included in the review (54 blood, 9 urine and 15 tissue), with six studying multiple sample types. High-ranking metabolites, based on their weighted score, comprised energy metabolites, bile acids, acylcarnitines and lysophosphocholines. This new review tool addresses an unmet need for incorporating quality of study design and analysis to overcome the gaps in standardisation of reporting of metabolomic data. Validation studies, standardised study designs and publications meeting minimal reporting standards are crucial for advancing the field beyond exploratory studies.
Sheridan D, Shawa I, Thomas EL, et al., 2022, Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis, Scientific Reports, Vol: 12, ISSN: 2045-2322
Background: Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis.Aims: We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism.Methods: We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR.Results: HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3.Conclusions: We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol lev
Taylor-Robinson SD, Morgan MY, Spearman CW, et al., 2022, Why SARS-CoV-2 vaccination still matters in Africa, QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, Vol: 115, Pages: 191-192, ISSN: 1460-2725
Dave U, Taylor-Robinson S, 2022, Maintaining resilience in today’s medical environment: personal perspectives on self-care, International Journal of General Medicine, Vol: 2022, Pages: 2475-2478, ISSN: 1178-7074
Background: The practice of medicine is becoming increasingly more stressful, owing to technological development, increased expectations, infrastructure deficiencies, lack of resources and healthcare systems that are struggling to cope in the face of the COVID-19 pandemic around the world.Objective: In this article, we explore ways to reduce stress and improve resilience in the work place in order to enhance wellbeing in the medical profession, but also, ultimately to protect patient safety.Synopsis: We discuss attention to regular mealtimes, protected sleep and daily exercise, together with consideration of mindfulness, gratefulness, self-compassion, self-care and being part of supportive networks as ways to reduce stress.Conclusions: While such techniques are not guaranteed to mitigate stress, psychology studies have shown that awareness of and attention to these components of a healthy lifestyle have the potential to reduce the adverse effects of increasing professional demands.
Edwards C, Suliman AAA, Taylor-Robinson S, et al., 2022, Rebalancing the research equation in Africa: principles and process, BMJ Open, Vol: 12, ISSN: 2044-6055
Background: Many examples of research excellence in Africa have been driven by partnerships led by the global North and have involved localised infrastructure improvements to support the best of international research practice.Objective: In this article, we explore a possible mechanism by which local research networks, appropriately governed, could begin to support national African research programmes by allying research delivery to clinical service.Summary: This article explores the concept that sustainable research effort needs a well-trained and mentored workforce, working to common standards, but which is practically supported by a much developed information technology (IT) infrastructure throughout the continent.Conclusions: The balance of investment and ownership of such a research programme needs to be shared between local and international funding, with the emphasis on developing global South–South collaborations and research strategies which address the environmental impact of medical research activity and mitigate the impact of climate change on African populations. Healthcare must be embedded in the post-COVID-19 approach to research development.
Fertleman M, Pereira C, Dani M, et al., 2022, Cytokine changes in cerebrospinal fluid and plasma post-emergency orthopaedic surgery, Scientific Reports, Vol: 12, ISSN: 2045-2322
Neuroinflammation after surgery and its contribution to peri-operative neurocognitive disorders (PND) is not well understood. Studying the association between central and peripheral cytokines and neuroinflammation is a prelude to the development of treatments for PND. Here, we investigate the hypotheses that there is a greater cytokine response in cerebrospinal fluid (CSF) than plasma after orthopaedic surgery, and that plasma cytokine levels are directly related to CSF cytokine levels, indicating that plasma cytokine levels may have potential as biomarkers of neuroinflammation. Patients admitted with a fractured neck of femur were invited to participate in this study. Participants had a spinal catheter inserted just prior to induction of anaesthesia. Samples of blood and CSF were taken before, immediately after, and on the first day following emergency surgery. The catheter was then removed. Samples were analysed for the presence of ten cytokines by immunoassay. A spinal catheter was successfully inserted in 11 participants during the 18-month study period. Five plasma cytokines (IL-4, IL-6, IL-10, IL-12p70 and IL-13) rose significantly following surgery, whereas all ten CSF cytokines rose significantly (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IFN-γ and TNF-α) (adjusted-p < 0.05). Central (CSF) cytokine levels were consistently higher than their peripheral (plasma) counterparts after surgery, with some patients having a particularly marked neuroinflammatory response. The greatest increases occurred in IL-8 in CSF and IL-6 in plasma. There were significant, strong positive correlations between several of the measured cytokines in the CSF after surgery, but far fewer in plasma. There was no significant correlation between cytokine levels in the plasma and CSF at each of the three time points. To our knowledge, this is the first study to analyse paired samples of plasma and CSF for cytokine levels before and after emerg
Oleribe O, Olawepo O, Ezechi O, et al., 2022, Describing the epidemiology of COVID-19 in Nigeria: an analysis of the first year of the pandemic, Journal of Health Care for the Poor and Underserved, Vol: 33, Pages: 33-46, ISSN: 1049-2089
We report the COVID-19 experience across Nigeria from March 2020 to March 2021. Demographics were obtained from Nigerian Center for Disease Control. By 21 March 2021, 161,737 people were confirmed positive for SARS-COV-2. Overall, testing rates were 0.8% of the population, with positivity rates of 9.6%, complete recovery rates without long-term sequelae of 91.4%, and case fatality rates of 1.3%. Most Nigerian regions contributed to figures for recent cases and deaths in 2021. The picture may change as testing is scaled-up to include community testing. Given so-called “pandemic fatigue” among the general population, various conspiracy theories being prevalent, and the recent introduction of COVID-19 vaccines in Nigeria, we assume that Nigeria is at a pivotal stage of the outbreak. Effort must be made by government to learn successful strategies in other countries to adapt to prevent a rise in case numbers and deaths.
Chowdhury D, Mahmood F, Edwards C, et al., 2021, Five-day outcome of hepatitis E-induced acute liver failure in the ICU, Egyptian Liver Journal, Vol: 11, Pages: 1-9, ISSN: 2090-6226
BackgroundHepatitis E virus (HEV) is an important cause of acute liver failure (ALF) in Bangladesh with pregnant mothers being more vulnerable. As HEV occurs in epidemics, it limits medical capabilities in this resource-poor country. Cerebral oedema, resulting in raised intracranial pressure (ICP), is an important cause of morbidity and mortality. Practical treatments are currently few.To study the baseline characteristics and clinical outcome of HEV-induced ALF in a recent HEV epidemicTo detect raised ICP clinically and observe response to mannitol infusion.This was a prospective cohort study from June until August 2018 of 20 patients admitted to the intensive care unit (ICU) of a major Bangladeshi Referral Hospital with HEV-induced ALF. We diagnosed HEV infection by detecting serum anti-HEV IgM antibody. All were negative for hepatitis B surface antigen and hepatitis A IgM antibody. Data were collected on 5-day outcome after admission to ICU, monitoring all patients for signs of raised ICP. An intravenous bolus of 20% mannitol was administered at a single time point to patients with raised ICP.ResultsTwenty patients were included in the study. Ten (50%) patients, seven (70%) females, received mannitol infusion. HE worsened in eight (40%): seven female and three pregnant. Glasgow Coma scores deteriorated in six (30%): all (100%) females and three pregnant. Consciousness status was not significantly different between pregnant and non-pregnant subjects, nor between those who received mannitol and those who did not. Six patients met King’s College Criteria for liver transplantation.ConclusionsFemale patients had a worse outcome, but pregnancy status was not an additional risk factor in our cohort. Mannitol infusion was also not associated with a significant difference in outcome.
Cordell HJ, Fryett JJ, Ueno K, et al., 2021, Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581], Journal of Hepatology, ISSN: 0168-8278
Oleribe OO, Idigbe IE, Osita-Oleribe P, et al., 2021, Perceptions and opinions of Nigerians to the management and response to COVID-19 in Nigeria., Pan African Medical Journal, Vol: 40, Pages: 1-11, ISSN: 1937-8688
Introduction: we present a qualitative analysis of opinions of the Nigerian general public as to how successful healthcare strategies have been in containing the COVID-19 outbreak. Methods: an online qualitative survey was conducted, consisting of 30 semi-structured questions. Results: four hundred and ninety-five (495) respondents participated, ranging in age from 18 to 59 years. Over 40% of all respondents were critical of public health information. Participants saw provision of social support measures (n = 83), lack of economic, financial and social support (n = 65), enforcement of restrictions on movement outside the home, availability of face-masks and social distancing (n = 53) and provision of COVID-19 testing (n = 48) as the major things that were handled poorly by the government and health authorities. Conclusion: we advocate coordinated forward planning for public safety until vaccines are widely available; while social distancing should continue. Policymakers need to be adaptable to changing conditions, given fluctuating case numbers and fatality rates.
Oleribe O, Suliman A, Taylor-Robinson S, et al., 2021, Possible reasons why Sub-Saharan Africa experienced a less severe COVID-19 Pandemic in 2020, Journal of Multidisciplinary Healthcare, Vol: 2021, Pages: 3267-3271, ISSN: 1178-2390
Both scientific authorities and governments of nations worldwide were found lacking in their COVID-19 response and management, resulting in significant distrust by the gen-eral public in 2020. Scientific and medical bodies often failed to give the right counsel on the appropriate course of action on COVID-19, because proven steps were not known, while many governments around the world took ineffective, late or inappropriate COVID-19 control and containment strategies. If the 2020 COVID-19 incidence rates are to be believed, much of sub-Saharan Africa had a lower disease prevalence than expected. We put forwards six factors peculiar to much of sub-Saharan Africa that may have accounted for the pandemic landscape there in 2020. We also discuss why the situation has become more serious in 2021.
Taylor-Robinson S, Trovato G, 2021, Semi-elective cervical disc replacements for cervical myelopathy: a qualitative study, Patient Preference and Adherence, Vol: 2021, Pages: 2455-2458, ISSN: 1177-889X
Cervical disc prolapse can be accompanied by severe pain, numbness, paraesthesiae and muscle weakness. The choice lies between a conservative approach with physiotherapy and pain modulating drugs, such as gabapentin, or a more active surgical approach, ranging from nerve decompression through vertebral foraminotomy through to cervical disc replacement. We relate the experience of a medically qualified patient in having disc prolapse at three cervical levels and what it was like to experience a lonely and difficult post-surgical recovery. Despite this, the patient would still choose active surgical decompression over a non-interventional approach. The reasons for this are discussed from the patient perspective, of which there is little directly in the medical literature.
Taylor-Robinson S, De Souza Lopes P, Zdravkov J, et al., 2021, Should commercial sex workers have unrestricted healthcare access across the world?, International Journal for Equity in Health, Vol: 20, Pages: 1-5, ISSN: 1475-9276
We argue commercial sex workers have rights to healthcare and psychosocial support. While decriminalization is not legally enacted in most countries, we would suggest these workers rights include freedom from harassment and opportunities to lead healthy lives. The need for healthcare access for all is heightened in the COVID-19 pandemic where some people flout rules on lockdown by engaging with commercial sex workers and may unwittingly spread SARS-CoV-2 in so doing. Unrestricted healthcare access without stigma for commercial sex workers protects them, and has a beneficial societal effect on those who engage with them and on their contacts.
Alsaleh M, Leftley Z, OConnor T, et al., 2021, Mapping of population disparities in the cholangiocarcinoma urinary metabolome, Scientific Reports, Vol: 11, Pages: 1-12, ISSN: 2045-2322
Phenotypic diversity in urinary metabolomes of different geographical populations has been recognized recently. In this study, urinary metabolic signatures from Western (United Kingdom) and South-East Asian (Thai) cholangiocarcinoma patients were characterized to understand spectral variability due to host carcinogenic processes and/or exogenous differences (nutritional, environmental and pharmaceutical). Urinary liquid chromatography mass spectroscopy (LC–MS) spectral profiles from Thai (healthy = 20 and cholangiocarcinoma = 14) and UK cohorts (healthy = 22 and cholangiocarcinoma = 10) were obtained and modelled using chemometric data analysis. Healthy metabolome disparities between the two distinct populations were primarily related to differences in dietary practices and body composition. Metabolites excreted due to drug treatment were dominant in urine specimens from cholangiocarcinoma patients, particularly in Western individuals. Urine from participants with sporadic (UK) cholangiocarcinoma contained greater levels of a nucleotide metabolite (uridine/pseudouridine). Higher relative concentrations of 7-methylguanine were observed in urine specimens from Thai cholangiocarcinoma patients. The urinary excretion of hippurate and methyladenine (gut microbial-host co-metabolites) showed a similar pattern of lower levels in patients with malignant biliary tumours from both countries. Intrinsic (body weight and body composition) and extrinsic (xenobiotic metabolism) factors were the main causes of disparities between the two populations. Regardless of the underlying aetiology, biological perturbations associated with cholangiocarcinoma urine metabolome signatures appeared to be influenced by gut microbial community metabolism. Dysregulation in nucleotide metabolism was associated with sporadic cholangiocarcinoma, possibly indicating differences in mitochondrial energy production pathways between cholangiocar
Alfadda A, Sherbeeni SM, Alqutub AN, et al., 2021, THE PREVALENCE OF STEATOSIS AND FIBROSIS IN A SAUDI TYPE 2 DIABETES POPULATION: EVIDENCE FROM THE CORDIAL STUDY, Publisher: WILEY, Pages: 1126A-1127A, ISSN: 0270-9139
Taylor-Robinson SD, 2021, Covid-19 dysphonia-unconscious bias and the Central role of speech and language therapists., QJM: an international journal of medicine, Vol: 114, Pages: 762-763, ISSN: 1460-2393
Cholangiocarcinoma (CCA) is a highly lethal adenocarcinoma of the hepatobiliary system, which can be classified as intrahepatic, perihilar and distal. Each anatomic subtype has distinct genetic aberrations, clinical presentations and therapeutic approaches. In endemic regions, liver fluke infection is associated with CCA, owing to the oncogenic effect of the associated chronic biliary tract inflammation. In other regions, CCA can be associated with chronic biliary tract inflammation owing to choledocholithiasis, cholelithiasis, or primary sclerosing cholangitis, but most CCAs have no identifiable cause. Administration of the anthelmintic drug praziquantel decreases the risk of CCA from liver flukes, but reinfection is common and future vaccination strategies may be more effective. Some patients with CCA are eligible for potentially curative surgical options, such as resection or liver transplantation. Genetic studies have provided new insights into the pathogenesis of CCA, and two aberrations that drive the pathogenesis of non-fluke-associated intrahepatic CCA, fibroblast growth factor receptor 2 fusions and isocitrate dehydrogenase gain-of-function mutations, can be therapeutically targeted. CCA is a highly desmoplastic cancer and targeting the tumour immune microenvironment might be a promising therapeutic approach. CCA remains a highly lethal disease and further scientific and clinical insights are needed to improve patient outcomes.
Cordell HJ, Fryett JJ, Ueno K, et al., 2021, An international genome-wide meta-analysis of primary biliary cholangitis: novel risk loci and candidate drugs, Journal of Hepatology, Vol: 75, Pages: 572-581, ISSN: 0168-8278
Backgrounds & AimsPrimary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening.MethodsWe combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts.ResultsWe identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (TH)1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders.ConclusionsThis study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders.Lay summaryPrimary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan
Taylor-Robinson SD, 2021, Reply to Is retirement wasted on the old? A paraphrase of George Bernard Shaw, QJM: an international journal of medicine, Vol: 114, Pages: 680-680, ISSN: 1460-2393
Chowdhury D, Mahmood F, Edwards C, et al., 2021, 5 Day outcome of hepatitis E virus induced acute liver failure in the ICU, Publisher: WILEY, Pages: 75-75, ISSN: 0815-9319
Oleribe O, Miller R, Wadzeck M, et al., 2021, Klamath Tribal response to the pandemic of COVID-19 among Klamath Tribal Community in Oregon, USA, Global advances in health and medicine : improving healthcare outcomes worldwide, Vol: 10, Pages: 1-7, ISSN: 2164-9561
IntroductionSocially-disadvantaged populations are more at risk of contracting COVID-19 than those with access to better medical facilities. We looked at responses of Klamath Tribes in Oregon, USA to mitigate spread of COVID-19 in a community with a higher incidence of obesity, diabetes and coronary heart disease, compared to the general US population. This study reports on Klamath Tribes response to COVID-19 March -September 2020.MethodsKlamath Tribes Tribal Health and Family Services established a COVID-19 Incident Management Team (IMT), instituting creative programs including a Walk-In Testing Center, implementing strict infection control protocols and regular sharing of information on the pandemic and prevalence of COVID-19 amongst Klamath Tribes. All COVID-19 tests were documented with positive cases isolated and people with high risk exposures quarantined and provided with wrap-around medical and social services until recovered or past quarantine time period.ResultsA total of 888 (12%) tribal members were tested for COVID1-19 between March to September 2020; 50 were found positive for COVID-19, giving a test positivity rate of 5.6% (Male – 6.3%; Female – 5.2%). No deaths have been reported amongst the local Klamath Tribes and other American Indians/Alaska Native (AI/AN) population served by the tribe.ConclusionDespite the fact that structural inequities including income disparities have shaped racial and ethnic impact of epidemics around the world, the timely response, establishment of partnerships and proactive control of the epidemic resulted in minimal impact among the Klamath Tribal and other AI/AN populations served by the tribal facilities.
Taylor-Robinson S, Rhodes-Kendler O, Parker R, 2021, The Antiviral Diet, Publisher: Europe Books, ISBN: 9791220109789
Agyei-Nkansah A, Taylor-Robinson S, 2021, The state of Ghanaian liver medicine, Pan African Medical Journal, Vol: 39, Pages: 1-7, ISSN: 1937-8688
This paper aims to highlight the challenges in managing liver diseases in Ghana and the efforts needed to improve services to help curb the high rate of liver mortality in the young adults. Ghana is a rising, middle-income West African country with well-established administrative systems for healthcare, albeit with hospitals lacking modern equipment and being devoid of infrastructure for sophisticated interventional procedures. Although liver disease is common, due to the high prevalence of chronic viral hepatitis B and C infection, antiviral drugs are commonly unavailable, even in the rare instances where they can be afforded. Hospital wards and outpatient clinics are usually over-crowded with long waiting times and limited doctor-patient time interaction. Treatment for end-stage liver disease can be a challenge, with limited endoscopic services, which are centered in the big cities and with expertise which is not widespread. The training program in endoscopic therapies by the Mayo Clinic (Rochester, Minnesota, USA), with faculty coming to Ghana to disseminate practical skills during a “training of trainers” program has gone a long way spreading the knowledge of managing life-threatening complications, such as variceal hemorrhage, albeit on a small scale in national terms. Collaboration between institutions from well-resourced and poorly-resourced countries exemplifies how such partnerships can go a long way in helping to support local training needs and the development of transferrable skills. Such partnerships may effectively provide healthcare workers with adequate training, with hepatology treatment protocols that are adapted to the local environment and thus allowing contextualisation of generic guidelines from the developed world and making them applicable to local settings.
Taylor-Robinson SD, Spearman CW, Suliman AAA, 2021, Why is there a paucity of clinical trials in Africa?, QJM: an international journal of medicine, Vol: 114, Pages: 357-358, ISSN: 1460-2393
Disproportionately few clinical trials are undertaken on the African continent, in part due to lingering neocolonial attitudes in the Global North which keep research activity primarily in developing countries, while being skeptical of the abilities of those in the Global South to undertake organized clinical studies. In the era of the COVID-19 pandemic, applicable research and clinical trials should be undertaken in relevant populations in order to extrapolate to a population level. This is all the more important in Africa, which has a rich genetic diversity. We suggest that a lack of organized research ethics committees across the continent and a deficiency of appropriate training are responsible in part for the reluctance of clinical trial organizers in the developed countries of the Global North to engage with medical leadership in Africa. We consider ways of alleviating this problem, including suggesting a pan-continental surveillance of ethics committee agendas and of training, either through the auspices of the African Union or the World Health Organization. In addition, medical leadership in African nations must be encouraged to take ownership of their medical ethics agendas to facilitate decent international clinical trial participation for the good of the continent as a whole.
Asselta R, Paraboschi EM, Gerussi A, et al., 2021, X chromosome contribution to the genetic architecture of primary biliary cholangitis., Gastroenterology, Vol: 160, Pages: 2483-2495.e26, ISSN: 0016-5085
BACKGROUND & AIMS: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. METHODS: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). RESULTS: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P = 9.93 × 10-8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10-9; OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). CONCLUSIONS: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.
Omotunde SM, Oleribe OO, Taylor-Robinson S, 2021, Community psychiatry care: an urgent need in Nigeria, Journal of Multidisciplinary Healthcare, Vol: 14, Pages: 1145-1148, ISSN: 1178-2390
Nigeria’s mental health policy was formulated in 1991, but it did not make adequate provision for community-based psychiatric care. Since there are only seven government-owned psychiatry facilities in Nigeria and these are always overwhelmed, there is the need to overhaul the existing policy and emphasise the urgency of a shift from inpatient psychiatric mental healthcare towards a community-based multidisciplinary psychiatric healthcare system.
Taylor-Robinson SD, 2021, Retirement - a time to dread or to cherish?, QJM: an international journal of medicine, Vol: 114, Pages: 296-297, ISSN: 1460-2393
Retirement is often a taboo subject amongst medical professionals. Many have dedicated a major part of their lives to the practice of medicine to the exclusion of anything else. The thought of empty days or lack of externally driven purpose is something that unsettles many who are approaching pensionable age. In reality such fears rarely materialise. The challenge of transition to a new phase of life is all the more poignant if ill health intervenes early, causing premature cessation of work.
Taylor-Robinson SD, 2021, Personal perspectives: Having a series of cardiac events, QJM: an international journal of medicine, Vol: 114, Pages: 291-292, ISSN: 1460-2393
It has never been clear to me whether being a medically-qualified patient has positive or negative associations. In 2019, after a prostatectomy, where I had extended bleeding per urethra, I suffered two myocardial infarctions, underwent three coronary angiograms and eventually coronary stenting. Junior doctors never examined me at any point, while senior ones worried over the risk of stent placement in an actively bleeding patient. I report my views on how this seemed as a largely passive, but still actively thinking patient.
Taylor-Robinson SD, 2021, COVID hypoxia—personal reflections, QJM: an international journal of medicine, Vol: 114, Pages: 343-343, ISSN: 1460-2393
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