Publications
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Taylor-Robinson SD, 2021, Personal perspectives: having the time to observe the patient, Journal of Medical Ethics, Vol: 48, Pages: 215-216, ISSN: 0306-6800
Being a medically qualified patient can be an unpleasant experience for a person who is used to making decisions. For the most part, this applies to the vast majority of doctors and other healthcare professionals. Becoming passive and surrendering the decision-making process to others is alien to the medical culture we were taught. However, when as a hospitalised medically qualified patient, one sees fellow patients in difficulty, or deteriorating clinically, unnoticed by medical staff, the question of whether it is ethical to intervene arises. I report my views on this as a largely passive, but still actively thinking patient.
Ohihoin AG, Ohihoin EN, Bakare A, et al., 2021, The effect of first line anti-retroviral drugs on the menstrual cycle of HIV positive patients, Annals of Medical and Health Sciences Research, Vol: 11, Pages: 1328-1331, ISSN: 2141-9248
Background: The quality of life and life expectancy of individuals living with HIV has improved significantly. This improvement is largely due to the use of Highly Active Anti-Retroviral Therapy (HAART). The effect of prolonged usage of this therapy on the menstrual function of the females within the reproductive age range is poorly understood.Methodology: A cross-sectional comparative study that involved women within the reproductive age range of 15-45 years. The women were grouped into A, B and C categories. Group A had HIV positive women already on Anti-Retroviral (ARV) therapy. Group B were HIV positive women naïve to anti-retroviral drugs at the time of recruitment. Group C comprised of HIV negative women within the reproductive age range not being managed for infertility.Results: The mean age of the participants across the study groups were respectively 32 years, 33.4 years and 37.58 years. The average weight among participants in the study was 66.38 kg, with a range of 53- 94 kg. The average duration of use of ARVs was 81.12 months (6.7 years). The mean CD4 values across the study population who were HIV positive were 725 and the average viral load was 20 copies per ml. The commonest menstrual abnormality was oligomenorrhea, occurring in close to 25% of respondent who were HIV positive and on ARVs. Menstrual abnormality was more in the HIV positive women receiving antiretroviral drugs than in the other two cohorts. (p=0.007).Conclusion: Long term usage of some first line highly active anti-retroviral therapy is associated with increased menstrual abnormality.
Taylor-Robinson SD, 2021, COVID hypoxia - promoting the use of hand-held pulse oximeters to save lives, QJM: an international journal of medicine, ISSN: 1460-2393
Chatzimichail S, Rahimi F, Saifuddin A, et al., 2021, Hand-portable HPLC with broadband spectral detection enables analysis of complex polycyclic aromatic hydrocarbon mixtures, Communications Chemistry, Vol: 4, ISSN: 2399-3669
Polycyclic aromatic hydrocarbons (PAHs) are considered priority hazardous substances due to their carcinogenic activity and risk to public health. Strict regulations are in place limiting their release into the environment, but enforcement is hampered by a lack of adequate field-testing procedure, instead relying on sending samples to centralised analytical facilities. Reliably monitoring levels of PAHs in the field is a challenge, owing to the lack of field-deployable analytical methods able to separate, identify, and quantify the complex mixtures in which PAHs are typically observed. Here, we report the development of a hand-portable system based on high-performance liquid chromatography incorporating a spectrally wide absorption detector, capable of fingerprinting PAHs based on their characteristic spectral absorption profiles: identifying 100% of the 24 PAHs tested, including full coverage of the United States Environmental Protection Agency priority pollutant list. We report unsupervised methods to exploit these new capabilities for feature detection and identification, robust enough to detect and classify co-eluting and hidden peaks. Identification is fully independent of their characteristic retention times, mitigating matrix effects which can preclude reliable determination of these analytes in challenging samples. We anticipate the platform to enable more sophisticated analytical measurements, supporting real-time decision making in the field.
Taylor-Robinson S, de Souza Lopes PA, Zdravkov J, et al., 2021, A Personal Perspective: Is Bullying Still a Problem in Medicine?, Advances in Medical Education and Practice, Vol: 12, Pages: 141-145, ISSN: 1179-7258
Bullying of whatever form should have no place in the Medical Profession. Reforms to junior doctor training and reduction in working hours have helped to control most of the individual bullying which may have existed in the past. However, the complexities of institutional bullying still exist. In the United Kingdom, centralised monitoring systems, such as Athena SWAN, are designed to reward academic and medical institutions for positive steps to introduce equality and mitigate bullying. However, the reality is that such processes may be conducted in healthcare or educational establishments that have little intention to address the problem thoroughly. We report the personal experience of both individual and institutional bullying in the medical career of a medically-qualified interviewee and reflect on ways to mitigate the problem. We also consider whether unconscious bias affects our relationships with patients. In a caring medical profession, there should be no room for intolerance, unconscious bias or bullying.
Oleribe OO, Oskouipour P, Nwanyanwu O, et al., 2021, The Covid-19 era: the view from Nigeria, QJM: an international journal of medicine, Vol: 114, Pages: 13-15, ISSN: 1460-2393
If we were told that one day the entire world would take its guidance for managing a health crisis from empirical thought, nobody would have believed it. However, with the December 2019 arrival of COVID-19 in China, the world subsequently went into a frenzied state that resulted in widespread adoption of untested strategies or potential cures; circumstantial evidence provided without randomized control trials (RCTs) was published rapidly and widely considered the gold standard in medical research and therapeutics. Nigeria and much of the rest of the world blindly adopted treatments like chloroquine or hydroxychloroquine and various prevention strategies, often without monitoring the efficacy of these treatment and social control strategies. COVID-19 provided Nigeria a critical opportunity to create or strengthen its national laboratory system by building up its Level 3 laboratories in all parts of the country with the capability to perform PCR tests and viral isolation. There was also an opportunity to establish hospitals in every region of a sufficient standard to reduce the numbers of Nigerians travelling abroad to seek medical treatment; to invest in building capacity to develop antiviral medications and vaccines in Nigeria, and to ensure better international health policies. Rather, Nigerian leaders, government, and health managers decided (like most other nations of the world) to shut down society using isolationist policies that were not necessarily tailored to local needs. Despite adopting these methods, COVID-19 cases continued to skyrocket in Nigeria. In the future, before adopting such broad sweeping policies, there should be local tailoring to assess their effectiveness in different communities. Given that the country has much experience in controlling Lassa and Marburg Fever outbreaks, Nigeria should lead by developing new strategies, new protocols, and new local guidelines, based on validated and reproducible studies to ensure that the public health aut
Larsson E, Mawkin M, Taylor-Robinson S, et al., 2020, Implementing Innovative Approaches to Healthcare in a Lower-Middle Income Country: Perspectives from Malawi, International Journal of General Medicine, Vol: 2020, Pages: 1723-1730, ISSN: 1178-7074
Middle Income Country: Perspectives from Malawi AbstractFulltextMetricsGet PermissionCite this articleAuthors Larsson E, Mawkin M, Taylor-Robinson SD, Harrington P, Gondwe H, Watson C, Gallagher J, Ledwidge M, Chirambo GB, O'Donoghue JReceived 3 October 2020Accepted for publication 2 December 2020Published 31 December 2020 Volume 2020:13 Pages 1723—1730DOI https://doi.org/10.2147/IJGM.S285130Checked for plagiarism YesReview by Single anonymous peer reviewPeer reviewer comments 2Editor who approved publication: Dr Scott FraserArticle has an altmetric score of 5Emma Larsson,1 Mala Mawkin,1 Simon D Taylor-Robinson,1 Peter Harrington,2 Hastings Gondwe,3 Chris Watson,2,4 Joseph Gallagher,2 Mark Ledwidge,2 Griphin Baxter Chirambo,5,6 John O’Donoghue2,6,71Imperial College London, South Kensington, London SW7 2BX, UK; 2gHealth Research Group, University College Dublin, Dublin, Ireland; 3St John’s Hospital, Mzuzu, Malawi; 4Wellcome-Wolfson Institute for Experimental Medicine, Queens University Belfast, Belfast, Northern Ireland; 5Mzuzu University, Mzuzu, Malawi; 6Malawi eHealth Research Centre, University College Cork, Cork, Ireland; 7ASSERT Research Centre, University College Cork, Cork, IrelandCorrespondence: John O’DonoghueASSERT Research Centre, University College Cork, College Road, Cork T12 K8AF, IrelandTel +353 21 420 5616Email john.odonoghue@ucc.ieIntroduction: Safe, reliable, and effective healthcare systems are essential for all nations to ensure the health and wellbeing of their citizens. However, this is not always achievable with clinical therapies constantly evolving, resulting in a domino effect of structural, policy and training changes. For low- and middle-income countries (LMICs), implementing change is restricted. It is essential that innovative and realistic solutions are developed, so that effective change can be realised in LMICs.Materials and Methods: In this report of a global health conference held in July 2019, six pe
Rose CF, Amodio P, Bajaj JS, et al., 2020, Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy, Journal of Hepatology, Vol: 73, Pages: 1526-1547, ISSN: 0168-8278
Hepatic encephalopathy (HE) is a frequent and serious complication of both chronic liver disease and acute liver failure. HE manifests as a wide spectrum of neuropsychiatric abnormalities, from subclinical changes (mild cognitive impairment) to marked disorientation, confusion and coma. The clinical and economic burden of HE is considerable, and it contributes greatly to impaired quality of life, morbidity and mortality. This review will critically discuss the latest classification of HE, as well as the pathogenesis and pathophysiological pathways underlying the neurological decline in patients with end-stage liver disease. In addition, management strategies, diagnostic approaches, currently available therapeutic options and novel treatment strategies are discussed.
Ahmad A, Atzori S, Maurice J, et al., 2020, Non-invasive splenic parameters of portal hypertension: Assessment and utility, World Journal of Hepatology, Vol: 12, Pages: 1055-1066, ISSN: 1948-5182
BACKGROUNDPortal hypertension is a major complication of cirrhosis that is associated with significant morbidity and mortality. The present gold-standard method to risk stratify and observe cirrhosis patients with portal hypertension is hepatic venous pressure gradient measurement or esophagogastroduodenoscopy. However, these methods are invasive, carry a risk of complications and are associated with significant patient discomfort. Therefore, non-invasive splenic parameters are of clinical interest as potential useful markers in determining the presence of portal hypertension. However, diagnostic accuracy and reproducibility remains unvalidated.AIMTo assess the diagnostic accuracy of spleen stiffness, area and diameter in predicting the presence of portal hypertension.METHODSOf 50 patients with varying liver disease pathologies were prospectively recruited from the St. Mary’s Hospital Liver Unit in London; 25 with evidence of portal hypertension and 25 with no evidence of portal hypertension. Liver stiffness, spleen stiffness, spleen diameter and spleen area were measured using the Philips Affiniti 70 elastography point quantification point shear wave elastography system. The aspartate aminotransferase-to-platelet-ratio-index (APRI) score was also calculated. Performance measures, univariate and multivariate logistic regression were used to evaluate demographic, clinical and elastography variables. Interclass correlation coefficient was used to determine the reproducibility of splenic area and diameter.RESULTSOn univariate and individual performance, platelet count [area under the receiver operating characteristic (AUROC) 0.846, P value < 0.001], spleen area (AUROC 0.828, P value = 0.002) and APRI score (AUROC 0.827, P value < 0.001) were the most accurate variables in identifying the presence of portal hypertension. On multivariate logistic regression models constructed, the combination of spleen area greater than 57.90 cm2 and platelet count less than
Dave U, Dave A, Taylor-Robinson S, 2020, Mindfulness in gastroenterology training and practice: a personal perspective, Clinical and Experimental Gastroenterology, Vol: 13, Pages: 497-502, ISSN: 1178-7023
Background: Work-related stress is becoming an increasingly recognised occupational hazard that can have detrimental effects on the health of both patient and doctor. The practice of gastroenterology not only includes the demands of clinics and in-patient work faced by other medical specialities but also the additional burden of complex, and often high-risk, endoscopic interventions. Mindfulness, a secular form of meditation, can relieve stress, even if only practiced for a few minutes a day.Methods and Results: We present a personal perspective of the burnout experienced in stressful gastroenterology careers and the personal use of mindfulness in the daily routine to provide a source of calm when surrounded by many different pressures. We review some of the literature exploring the role of mindfulness in clinical practice with an emphasis on gastroenterology. While the practice of mindfulness is not designed to obviate immediacy and quick decisions in a rapidly changing clinical environment, it has been held widely useful to mitigate the stress involved in making those decisions.Conclusion: Practicing mindfulness, meditation and mindful living offers many advantages to gastroenterologists’ wellbeing as well improved patient care. We advocate its teaching to both gastroenterology trainees and consultants who are not familiar with the technique.
Taylor-Robinson SD, Dykes K, Hawkes B, 2020, Personal perspectives: having a prostatectomy and the role of the cancer specialist nurse, International Journal of General Medicine, Vol: 13, Pages: 897-901, ISSN: 1178-7074
Background: Doctors are often ill-prepared to become patients, despite knowing the technicalities of surgical procedures and the day-to-day workings of hospital life intimately. Surrendering the decision-making process to other healthcare professionals can be an unnerving process for many of those who are medically qualified. Aim: Although the sequelae of prostatectomy have often been written about, little is in the literature from medically qualified patients about their personal experiences of the procedure. We aimed to highlight areas where communication between medically qualified patients and their carers may be strengthened. Methods and Results: We present a personal perspective of the emotional issues surrounding a potential cancer diagnosis, the experience of having a prostatectomy and what the hospital encounters were like in reality with a viewpoint of informing the medical profession in providing better patient information when they ask "what will it be like?". From this perspective, the critical role of the cancer specialist nurse is highlighted as the lynch pin in providing a continuing source of information to medically qualified patients and in not treating them as omniscient, simply because of a medical degree. Conclusion: Prostatectomy is a common procedure, but often questions about recovery after the procedure including impotence and incontinence are left unanswered in dealing with medically qualified colleagues when they are patients. Human behaviour is predictable, and medically qualified patients are just as apt to forget what is said to them as anyone else. However, the central role of the cancer specialist nurse as the bridge between the medical team and the patient should not be underestimated.
Oleribe O, Ezechi O, Osita-Oliberi P, et al., 2020, Public perception of COVID-19 management and response in Nigeria: a cross-sectional survey, BMJ Open, Vol: 10, Pages: 1-7, ISSN: 2044-6055
Objectives: A study designed to assess the public perception of the response of government and its institutions to the COVID-19 pandemic in Nigeria. Setting: Self-selecting participants throughout Nigeria completed a self-administered questionnaire through an online cross-sectional survey. Participants: 495 Results: The majority of respondents were married (76.6%), were males (61.8%), had tertiary level education (91.0%), were public servants (36.8%), Christians (82.6%), and resident either in the Federal Capital Territory (Abuja) (49.1%) or in the South-East Region of Nigeria (36.6%). Over 95% of the respondents had heard of COVID-19 (98.8%) and knew it is a viral disease (95.4%). The government and its institutions response to the pandemic were rated as poor, with the largest rating as poor for Federal President’s Office (57.5%). Communication (50.0%) and prevention messages (43.7%) received the highest perception good rating. Female respondents and those less than 40 years generally rated the governmental responses as poor. Conclusions/Recommendations: It is recommended that as a public-private partnership approached was efficiently used to more effectively disseminate public health communication and prevention messages, the Nigerian Government should expand this collaboration to improve the quality of services provided in other areas of COVID-19 outbreak management.
Trovato G, Taylor-Robinson S, 2020, Synergy or overlap: non-alcoholic fatty liver disease and coronary heart disease a plea for computational epidemiology and multi-omics approaches, Sudan Heart Journal, Vol: 8, Pages: 33-33
Non-alcoholic fatty liver disease (NAFLD) is increasing in prevalence around the world. It is associated with the metabolic syndrome with cardiovascular disease the most usual cause of death. Clinical methods used to screen for NAFLD on a preliminary basis include the use of multiple algorithms, based on non-invasive serum biomarkers. The presence of NAFLD has been linked to surrogate markers of cardiovascular disease such as carotid intima-media thickness, the presence of carotid plaque, brachial artery vasodilatory responsiveness and CT coronary artery calcification scores. The issue of whether NAFLD is a cardiovascular risk factor itself needs to be fully determined, but it frequently coexists with insulin resistance, the metabolic syndrome and type 2 diabetes.There is no specific medical treatment for NAFLD and the evidence is incomplete with respect to the efficacy of interventions that reduce cardiovascular risk. Management of patients with NAFLD should involve identification of risk factors with key points being lifestyle change and the treatment of underlying diabetes, dyslipidemia and hypertension. Managing big data - which must be achieved and validated in advance as much as possible – should be processed by comprehensive computational epidemiology and “-omics” approaches, taking into account advanced research challenging heterogeneity. Validation and replication are mandatory before utilizing “-omic” biomarkers in diagnostics to identify patients at risk of advanced disease, including coronary heart disease.
Rahimi F, Chatzimichail S, Saifuddin A, et al., 2020, A review of portable high-performance liquid chromatography: the future of the field?, Chromatographia, Vol: 83, Pages: 1165-1195, ISSN: 0009-5893
There is a growing need for chemical analyses to be performed in the field, at the point of need. Tools and techniques often found in analytical chemistry laboratories are necessary in performing these analyses, yet have, historically, been unable to do so owing to their size, cost and complexity. Technical advances in miniaturisation and liquid chromatography are enabling the translation of these techniques out of the laboratory, and into the field. Here we examine the advances that are enabling portable liquid chromatography (LC). We explore the evolution of portable instrumentation from its inception to the most recent advances, highlighting the trends in the field and discussing the necessary criteria for developing in-field solutions. While instrumentation is becoming more capable it has yet to find adoption outside of research.
Oleribe O, Osita-Oleribe P, Salako B, et al., 2020, COVID-19 Experience: Taking the right steps at the right time to prevent avoidable morbidity and mortality in Nigeria and other nations of the world, International Journal of General Medicine, Vol: 2020, Pages: 491-195, ISSN: 1178-7074
The 2020 Coronavirus pandemic has caused countless governmental and societal challenges around the world. Nigeria, Africa’s most populous nation, has been exposed in recent years to a series of epidemics including Ebola and Lassa Fever. In this paper we document our perception of the national response to COVID-19 in Nigeria. The response to the pandemic is with a healthcare system that has changed as a result of previous infectious disease outbreaks but in the context of scarce resources typical of many low-middle income countries. We make recommendations regarding what measures should be in place for future epidemics.
Syms R, Khuntikeo N, Titapun A, et al., 2020, In vitro intraductal MRI and T2 mapping of cholangiocarcinoma using catheter coils, Hepatic Medicine : Evidence and Research, Vol: 2020, Pages: 107-114, ISSN: 1179-1535
Aim: Diagnostic imaging of early-stage cholangiocarcinoma is challenging. A previous in vitro study of fixed-tissue liver resection specimens investigated T2 mapping as a method of exploiting the locally increased signal-to-noise ratio (SNR) of duodenoscope coils for improved quantitative magnetic resonance imaging (MRI), despite their non-uniform sensitivity. This work applies similar methods to unfixed liver specimens using catheter-based receivers.Methods: Ex vivo intraductal MRI and T2 mapping were carried out at 3T on unfixed resection specimens obtained from cholangiocarcinoma patients immediately after surgery using a catheter coil based on a thin-film magneto-inductive waveguide, inserted directly into an intrahepatic duct.Results: Polypoid intraductal cholangiocarcinoma was imaged using fast spin echo sequences. High resolution T2 maps were extracted by fitting of data obtained at different echo times to mono-exponential models, and disease-induced changes were correlated with histopathology. An increase in T2 was found compared with fixed specimens and differences in T2 allowed the resolution of tumour tissue and malignant features such as polypoid morphology.Conclusions: Despite their limited field of view, useful data can be obtained using catheter coils, and T2 mapping offers an effective method of exploiting their local SNR advantage without the need for image correction.
Sonderup MW, Dusheiko G, Desalegn H, et al., 2020, Hepatitis B in sub-Saharan Africa-How many patients need therapy?, Journal of Viral Hepatitis, Vol: 27, Pages: 560-567, ISSN: 1345-2533
Hepatitis B is endemic in sub‐Saharan Africa with ~60 million people chronically infected. While prevention, through vaccination, is central to elimination strategies, only 11 countries have birth dose vaccination and full vaccine coverage remains at suboptimal levels. Furthermore, to fully realize elimination, those chronically infected need to be identified, assessed for therapy and then linked to care. Given current treatment criteria, the precise quantum of people warranting therapy, according to criteria, is essentially unknown. The issue is further complicated by data to suggest differences in the numbers of people requiring treatment when applying WHO as compared to European Association for the Study of the Liver, EASL, criteria. Optimal determination of treatment eligibility is further hindered by the lack of available tools to adequately assess individual patients. It is conceivable that accurately determining the number of those requiring treatment, given the heterogeneity of hepatitis B in Africa, is difficult. Better studies and data are required. More signifcantly, improved access and availability to the diagnostic tools needed to assess patients in additon to access to drugs are as, if not more important, to achieve elimination.
Rahman MM, Ghoshal UC, Ragunath K, et al., 2020, Biomedical research in developing countries: Opportunities, methods, and challenges, Indian Journal of Gastroenterology, Vol: 39, Pages: 292-302, ISSN: 0254-8860
Health research is essential for improving global health, health equity, and economic development. There are vast differences in the disease burden, research budget allocation, and scientific publications between the developed and the low-middle-income countries, which are the homes of 85% of the world's population. There are multiple challenges, as well as opportunities for health research in developing countries. One of the primary reasons for reduced research output from the developing countries is the lack of research capacity. Many developing countries are striving to build their research capacity. They are trying to understand their needs and goals to solve their fundamental health problems, but the opportunity for research education and training remains low. The first joint research meeting of the Bangladesh Gastroenterology Society and the British Society of Gastroenterology took place in February 2020 at the Bangabandhu Sheikh Mujib Medical University in Dhaka, Bangladesh, aimed at providing an overview of medical research for young, aspiring medical researchers. This review article provides an outline of the research day and covers a number of useful topics. This review aims to provide a basic guide for early career researchers, both within the field of gastroenterology and, more generally, to all spheres of medical research.
Hoogenboom TCH, Patel N, Cook NA, et al., 2020, The effect of aloe vera juice on liver enzymes and hepatic structure in a healthy population., Integr Med (Encinitas), Vol: 19, Pages: 30-34, ISSN: 1546-993X
Background: There have been isolated reports of Aloe vera hepatotoxicity, usually manifested by transient liver function test abnormalities. While the European Food Safety Authority has recommended that whole leaf products containing the rind of the Aloe vera plant should not be used for human oral consumption, those Aloe vera gels made of the treated plant pulp alone are considered safe for daily consumption, provided recommended quantities are not exceeded. We aimed to assess hepatic function in healthy volunteers consuming the purified plant pulp Aloe vera gel over a 60 day period. Methods: 35 healthy volunteers consumed the maximum recommended daily dose of 2 oz (57 mL) of Aloe vera gel twice daily for a total of 60 days. The participants attended an initial baseline visit where biochemical measurements of hepatic synthetic function were obtained, and each volunteer underwent hepatic ultrasound with elastography, superb microvascular imaging and image quantification. Further visits were undertaken at days 30 and 60 to undergo the same biochemical and imaging measurements of liver function to monitor if there were any changes in the parameters measured. Results: Seven volunteers failed to complete the study, citing unspecified gastrointestinal upset and/or an inability to tolerate the taste of the Aloe vera gel. None of these individuals had disturbance of biochemical or imaging parameters of hepatic function. Of the remaining 27 healthy volunteers, none had a change in either biochemical indices of liver function, or of ultrasound markers of hepatic blood flow or liver tissue elasticity after 60 days of Aloe vera gel consumption. However, there was a non-significant reduction in serum homocysteine levels as the only detectable change in the cohort. Conclusions: Despite reports of potential hepatotoxicity with some Aloe vera products, in this healthy cohort, extended consumption of purified plant-pulp Aloe vera gel did not have any detectable effects on hepatic f
Bassendine M, Taylor-Robinson S, Fertleman M, et al., 2020, Is Alzheimer's Disease a liver disease of the brain?, Journal of Alzheimer's Disease, Vol: 75, Pages: 1-14, ISSN: 1387-2877
Clinical specialization is not only a force for progress, but it has also led to the fragmentation of medical knowledge. The focus of research in the field of Alzheimer’s disease (AD) is neurobiology, while hepatologists focus on liver diseases and lipid specialists on atherosclerosis. This article on AD focuses on the role of the liver and lipid homeostasis in the development of AD. Amyloid-β (Aβ) deposits accumulate as plaques in the brain of an AD patient long before cognitive decline is evident. Aβ generation is a normal physiological process; the steady-state level of Aβ in the brain is determined by balance between Aβ production and its clearance. We present evidence suggesting that the liver is the origin of brain Aβ deposits and that it is involved in peripheral clearance of circulating Aβ in the blood. Hence the liver could be targeted to decrease Aβ production or increase peripheral clearance.
Khuntikeo N, Titapun A, Chamadol N, et al., 2020, Improving the detection of cholangiocarcinoma: in vitro MRI-based study using local coils and T2 mapping, Hepatic Medicine : Evidence and Research, Vol: 12, Pages: 29-39, ISSN: 1179-1535
Aim: Cholangiocarcinoma is endemic in southeast Asia, generally developing from liver fluke infestation. However, diagnostic imaging of early-stage disease is challenging. The aim of this work is to investigate relaxometry (specifically, T2 mapping) as a method of exploiting the higher signal-to-noise ratio (SNR) of internal coils for improved reception of magnetic resonance signals, despite their non-uniform sensitivity.Methods: Ex vivo T2 mapping was carried out at 3T on fixed resection specimens from Thai cholangiocarcinoma patients using an mGRASE sequence and an endoscope coil based on a thin-film magneto-inductive waveguide and designed ultimately for internal use.Results: Disease-induced changes including granulomatous inflammation, intraepithelial neoplasia and intraductal tumours were correlated with histopathology, and relaxation data were compared with mono- and bi-exponential models of T2 relaxation. An approximately 10-fold local advantage in SNR compared to a 16-element torso coil was demonstrated using the endoscope coil, and improved tissue differentiation was obtained without contrast agents.Conclusion: The performance advantage above follows directly from the inverse relation between the component of the standard deviation of T2 due to thermal noise and the SNR, and offers an effective method of exploiting the SNR advantage of internal coils. No correction is required, avoiding the need for tracking, relaxing constraints on coil and slice orientation and providing rapid visualization.
Mohamed Z, Mbwambo J, Rwegasha J, et al., 2020, In-field evaluation of Xpert® HCV viral load fingerstick assay in people who inject drugs in Tanzania, Liver International, Vol: 40, Pages: 514-521, ISSN: 1478-3223
BackgroundAlthough novel hepatitis C (HCV) RNA point-of-care technology has the potential to enhance diagnosis in resource-limited settings, very little real-world validation of their utility exists. We evaluate the performance of HCV RNA quantification using the Xpert® HCV Viral Load Fingerstick assay (Xpert® HCV VL Fingerstick assay) as compared to the WHO pre-qualified plasma Xpert® HCV viral load assay among people who inject drugs (PWID) attending an opioid agonist therapy (OAT) clinic in Dar-es-Salaam, Tanzania. MethodsBetween December 2018 and February 2019 consecutive HCV seropositive PWID attending the OAT clinic provided paired venous and finger-stick samples for HCV RNA quantification. These were processed on-site using the GeneXpert® platform located at the Central tuberculosis reference laboratory. ResultsA total of 208 out of 220 anti-HCV positive participants recruited (94.5%) had a valid Xpert® HCV VL result available; 126 (61%; (95% CI 53.8-67.0) had detectable and quantifiable HCV RNA. 188 (85%) had paired plasma and finger-stick whole blood samples; the sensitivity and specificity for the quantification of HCV RNA levels were 99.1% and 98.7% respectively. There was an excellent correlation (R2=0.95) and concordance (mean difference 0.13 IU/mL, (95% CI -0.9 to 0.16 IU/mL) in HCV RNA levels between plasma samples and finger-stick samples.ConclusionThis study found excellent performance of the Xpert® HCV VL Fingerstick assay for HCV RNA detection and quantification in an African-field setting. Its clinical utility represents an important watershed in overcoming existing challenges to HCV diagnosis, which should play a crucial role in HCV elimination in Africa.
Cox IJ, Idiliman R, Fagan A, et al., 2020, Metabolomics and microbial composition increase insight into the impact of dietary differences in cirrhosis., Liver International, Vol: 40, Pages: 416-427, ISSN: 1478-3223
BACKGROUND & AIMS: Dietary changes can modulate gut microbiota and interact with cirrhosis. Our prior study demonstrated that microbial diversity was higher in Turkish versus USA cirrhotics, which was associated with lower risk of 90-day hospitalizations. We aimed to define gut microbial functional and metabolomic changes to increase insight into benefits of the Mediterranean compared to Western diets. METHODS: 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied. Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake while Americans consumed a Western diet. Predicted gut microbial functionalities and plasma metabolomics were compared between/within countries. Correlation network differences between microbiota and metabolites in cirrhotics from Turkey versus USA were evaluated. RESULTS: Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in Turkey compared to USA cirrhotics. Plasma metabolomics demonstrated higher relative lactate levels in Turkey versus USA. The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and USA, with reduced lipids and phosphocholines. Phosphocholines were significantly lower in patients hospitalized in 90 days (p=0.03). Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients. CONCLUSIONS: A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis. These altered diet-microbial interactions could potentially affect the 90-day hospitalization risk.
Dumenci O, U AMR, Khan S, et al., 2020, Exploring metabolic consequences of CPS1 and CAD dysregulation in hepatocellular carcinoma by network reconstruction, Journal of Hepatocellular Carcinoma, Vol: 7, Pages: 1-9, ISSN: 2253-5969
Purpose: Hepatocellular carcinoma (HCC) is the fourth commonest cause of cancer-related mortality; it is associated with various genetic alterations, some involved in metabolic reprogramming. This study aimed to explore the potential metabolic impact of Carbamoyl Phosphate Synthase I (CPS1) and carbamoyl phosphate synthetase/aspartate transcarbamoylase/dihydroorotase (CAD) dysregulation through the reconstruction of a network that integrates information from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, Human Metabolome Database (HMDB) and Human Protein Atlas (HPA). Methods and Results: Existing literature was used to determine the roles of CPS1 and CAD in HCC. CPS1 downregulation is thought to play a role in hepatocarcinogenesis through an increased glutamine availability for de novo pyrimidine biosynthesis, which CAD catalyzes the first three steps for. KEGG, HMDB and HPA were used to reconstruct a network of relevant pathways, demonstrating the relationships between genes and metabolites using the MetaboSignal package in R. The network was filtered to exclude any duplicates, and those greater than three steps away from CPS1 or CAD. Consequently, a network of 18 metabolites, 28 metabolic genes and 1 signaling gene was obtained, which indicated expression profiles and prognostic information of each gene in the network.Conclusion: Information from different databases was collated to form an informative network that integrated different ‘-omics’ approaches, demonstrating the relationships between genetic and metabolic components of urea cycle and the de novo pyrimidine biosynthesis pathway. This study paves the way for further research by acting as a template to investigate the relationships between genes and metabolites, explore their potential roles in various diseases and aid the development of new screening and treatment methods through network reconstruction.
Clements O, Eliahoo J, Kim JU, et al., 2020, Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: A systematic review and meta-analysis, Journal of Hepatology, Vol: 72, Pages: 95-103, ISSN: 0168-8278
Background & AimsCholangiocarcinoma (CCA) carries a poor prognosis, is increasing in incidence and its causes are poorly understood. Although some risk factors are known, they vary globally and collectively account for a minority of cases. The aim of this study was to perform a comprehensive meta-analysis of risk factors for intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA), from Eastern and Western world studies.MethodsA literature search of case-control studies was performed to identify potential risk factors for iCCA and eCCA. Pooled odds ratios (ORs) with 95% CIs and heterogeneity were calculated. Funnel plots were used to assess publication bias, and meta-regression was used to select risk factors for comparison between Eastern and Western studies.ResultsA total of 13 risk factors were selected from 25 case-control studies in 7 geographically diverse countries. The strongest risk factors for both iCCA and eCCA were biliary cysts and stones, cirrhosis, hepatitis B and hepatitis C. Choledochal cysts conferred the greatest risk of both iCCA and eCCA with pooled ORs of 26.71 (95% CI 15.80–45.16) and 34.94 (24.36–50.12), respectively. No significant associations were found between hypertension and obesity for either iCCA or eCCA. Comparing Eastern and Western populations, there was a difference for the association of hepatitis B with iCCA (coefficient = −0.15195; 95% CI −0.278 to −0.025; p = 0.022).ConclusionThis is the most comprehensive meta-analysis of CCA risk factors to date. Some risk factors, such as diabetes, although less strong, are increasing globally and may be contributing to rising rates of this cancer.
Alsaleh M, Leftley Z, Barbera TA, et al., 2020, Characterisation of the serum metabolic signature of cholangiocarcinoma in a United Kingdom cohort, Journal of Clinical and Experimental Hepatology, Vol: 10, Pages: 17-29, ISSN: 0973-6883
BackgroundA distinct serum metabonomic pattern has been previously revealed to be associated with various forms of liver disease. Here, we aimed to apply mass spectrometry to obtain serum metabolomic profiles from individuals with cholangiocarcinoma and benign hepatobiliary diseases to gain an insight into pathogenesis and search for potential early-disease biomarkers.MethodsSerum samples were profiled using a hydrophilic interaction liquid chromatography platform, coupled to a mass spectrometer. A total of 47 serum specimens from 8 cholangiocarcinoma cases, 20 healthy controls, 8 benign disease controls (bile duct strictures) and 11 patients with hepatocellular carcinoma (as malignant disease controls) were included. Data analysis was performed using univariate and multivariate statistics.ResultsThe serum metabolome disparities between the metabolite profiles from healthy controls and patients with hepatobiliary disease were predominantly related to changes in lipid and lipid-derived compounds (phospholipids, bile acids and steroids) and amino acid metabolites (phenylalanine). A metabolic pattern indicative of inflammatory response due to cirrhosis and cholestasis was associated with the disease groups. The abundance of phospholipid metabolites was altered in individuals with liver disease, particularly cholangiocarcinoma, but no significant difference was seen between profiles from patients with benign biliary strictures and cholangiocarcinoma.ConclusionThe serum metabolome in cholangiocarcinoma exhibited changes in metabolites related to inflammation, altered energy production and phospholipid metabolism. This study serves to highlight future avenues for biomarker research in large-scale studies.
Bajaj JS, Salzman N, Acharya C, et al., 2019, Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis, JCI insight, Vol: 4, Pages: 1-11, ISSN: 2379-3708
BACKGROUND. Hepatic encephalopathy (HE) is associated with poor outcomes. A prior randomized, pilot trial demonstrated safety after oral capsular fecal microbial transplant (FMT) in HE, with favorable changes in microbial composition and cognition. However, microbial functional changes are unclear. The aim of this study was to determine the effect of FMT on the gut-brain axis compared with placebo, using microbial function based on bile acids (BAs), inflammation (serum IL-6, LPS-binding protein [LBP]), and their association with EncephalApp.METHODS. Twenty cirrhotic patients were randomized 1:1 into groups that received 1-time FMT capsules from a donor enriched in Lachnospiraceae and Ruminococcaceae or placebo capsules, with 5-month follow-up for safety outcomes. Stool microbiota and BA; serum IL-6, BA, and LBP; and EncephalApp were analyzed at baseline and 4 weeks after FMT/placebo. Correlation networks among microbiota, BAs, EncephalApp, IL-6, and LBP were performed before/after FMT.RESULTS. FMT-assigned participants had 1 HE recurrence and 2 unrelated infections. Six placebo-assigned participants developed negative outcomes. FMT, but not placebo, was associated with reduced serum IL-6 and LBP and improved EncephalApp. FMT-assigned participants demonstrated higher deconjugation and secondary BA formation in feces and serum compared with baseline. No change was seen in placebo. Correlation networks showed greater complexity after FMT compared with baseline. Beneficial taxa, such as Ruminococcaceae, Verrucomicrobiaceae, and Lachnospiraceae, were correlated with cognitive improvement and decrease in inflammation after FMT. Fecal/serum secondary/primary ratios and PiCRUST secondary BA pathways did not increase in participants who developed poor outcomes.CONCLUSION. Gut microbial function in cirrhosis is beneficially affected by capsular FMT, with improved inflammation and cognition. Lower secondary BAs in FMT recipients could select for participants who develop negati
Oleribe OO, Momoh J, Uzochukwu BSC, et al., 2019, Identifying key challenges facing healthcare systems in Africa and potential solutions, International Journal of General Medicine, Vol: 2019, Pages: 395-403, ISSN: 1178-7074
Introduction: Healthcare systems in Africa suffer from neglect and underfunding, leading to severe challenges across the six World Health Organization (WHO) pillars of healthcare delivery. We conducted this study to identify the principal challenges in the health sector in Africa and their solutions for evidence-based decisions, policy development and program prioritization. Methods: The study was conducted as part of a recent African Epidemiological Association Meeting in Maputo, Mozambique with participants drawn from 11 African countries, Cuba, Portugal and the United Kingdom. Participants were divided into ten groups, consisting of 7 to 10 persons each. Brainstorming approaches were used in a structured, modified nominal group process exercise to identify key challenges and strategies to mitigate healthcare service challenges in Africa. Identified challenges and solutions were prioritised by ranking 1-5, with 1 most important and 5 being least important. Results: The first three challenges identified were inadequate human resources (34.29%), inadequate budgetary allocation to health (30%) and poor leadership and management (8.45%). The leading solutions suggested included training and capacity building for health workers (29.69%), increase budgetary allocation to health (20.31%) and advocacy for political support and commitment (12.31%). Conclusion: The underdeveloped healthcare systems in Africa need radical solutions with innovative thought to break the current impasse in service delivery. For example, public-private initiatives should be sought, where multinational companies extracting resources from Africa might be encouraged to plough some of the profits back into healthcare for the communities providing the workforce for their commercial activities. Most problems and their solutions lie within human resources, budget allocation and management. These should be accorded the highest priority for better health outcomes.
Youssaf A, Kim J, Eliahoo J, et al., 2019, Ablative therapy for unresectable intrahepatic cholangiocarcinoma: A systematic review and meta-analysis, Journal of Clinical and Experimental Hepatology, Vol: 9, Pages: 740-748, ISSN: 0973-6883
Background: Intrahepatic cholangiocarcinoma (iCCA) is usually a fatal malignancy with rising incidence globally. Surgical resection currently remains the only curative treatment. However, as only a minority of iCCA are amenable to resection, new therapeutic modalities are needed. Aims: Our aims were to systematically review and perform a meta-analysis on the existing literature regarding the use of ablative therapies in iCCA; and to assess their efficacy as a treatment modality by calculating pooled survival results and investigate associations between prognostic factors and survival. Methods: A comprehensive search of the PubMed database for relevant articles was performed. Studies assessing survival in patients with iCCA undergoing ablation were included. Data were extracted on patient, tumour and treatment characteristics and survival. Random effects meta-analysis was used to pool the data. Galbraith plots were used to investigate heterogeneity; bubble plots were formulated using regression-based meta-analysis. Results: 10 studies were included in the final analysis, yielding an aggregate of 206 patients (69.5% male, median age 51.2-72.5) and 320 tumours. 70.4% of patients were recurrent cases of iCCA and 29.6% primary iCCA. Median overall survival ranged from 8.7 to 52.4 months. Pooled survival rates for 1, 3 and 5-year survival were 76% (95% CI: 68-83%), 33% (21-44%) and 16% (7-26%), respectively. No significant association was found between the median age, number of tumours or median tumour size and 1-year survival. Conclusion: Ablative therapies display promising potential as treatment modalities for iCCA. However, further research is necessary to validate these findings.
Ahmad A, Atzori S, Taylor-Robinson S, et al., 2019, Spleen stiffness measurements using point shear wave elastography detects noncirrhotic portal hypertension in human immunodeficiency virus, Medicine, Vol: 98, ISSN: 0025-7974
Objectives:To assess the utility of spleen stiffness as a diagnostic tool inindividuals withHIV andnon-cirrhotic portal hypertension(NCPH).Design:The Philips EPIQ7TM, a newpoint shearwave elastography (pSWE) technique, was used to assess liver and spleen stiffnessin3 patient groups. Group1:HIV and NCPH(n=11); Group 2: HIV withpast didanosine(ddI) exposure without known liver disease or NCPH(n=5), Group 3: HIV without known liver disease or ddI exposure(n=9). Methods:Groups were matched for age, HIV chronicity and antiretroviral treatment (including cumulative ddI exposure in Groups 1 and 2). Differences in liver and spleen stiffness (in kPa) between groups were analysed using the Mann-Whiney U test.Results:Liver and spleen stiffness were both significantly higher in NCPH vs ddI-exposed (p=0.019 and p=0.006) and ddI-unexposed controls (p=0.038 and p<0.001). Spleen stiffness was more effective than liver stiffness at predicting NCPH, AUROC 0.812 vs 0.948. Combining the two variables improved the diagnostic performance, AUROC 0.961. The optimal cut-off for predicting NCPH using splenic stiffness was 25.4kPa, with sensitivity 91%, specificity 93%, PPV 91%, NPV 93%, positive likelihood ratio 12.73, negative likelihood ratio 0.10. Spleen and liver stiffness scores were strongly correlated (p=0.0004 95%CI 18,59). Conclusions:Elevated spleen stiffness is observed in HIV with NCPH and can be quantified easily using pSWE with high diagnostic accuracy. Novel strategies such as pSWE for longitudinal monitoring of patients with HIV and NCPH should be considered.
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