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Background: Donor hepatitis-C (HCV) infection has historically represented a barrier to kidney transplantation (KT). However, direct-acting antiviral (DAA) medications have revolutionised treatment of chronic HCV infection. Recent American studies have demonstrated that DAA regimes can be used safely peri-operatively in KT to mitigate HCV transmission risk. Methods: To formulate this narrative review, a comprehensive literature search was performed to analyse results of existing clinical trials examining KT from HCV-positive donors to HCV-negative recipients with peri-operative DAA regimes. Results: 13 studies were reviewed (11 single centre, four retrospective). Outcomes for 315 recipients were available across these studies. A sustained virological response at 12 weeks (SVR12) of 100% was achieved in 11 studies. One study employed an ultrashort DAA regime and achieved an SVR12 of 98%, while another achieved SVR12 of 96% due to treatment of a missed mixed genotype. Conclusion: HCV+ KT is safe and may allow increased utilisation of organs for transplantation from HCV+ donors, who often have other favourable characteristics for successful donation. Findings from US clinical trials can be applied to the United Kingdom transplant framework to improve organ utilisation as suggested by the NHSBT vision strategy "Organ Donation and Transplantation 2030: meeting the need?. [ABSTRACT FROM AUTHOR]

• Elexacaftor/tezacaftor/ivacaftor (E/T/I) does not worsen liver fibrosis in CF. • In those with elevated liver stiffness at baseline, this reduced following E/T/I. • Liver fibrosis markers did not change in those with CF liver disease on E/T/I. There are limited studies to date on the effects of elexacaftor/tezacaftor/ivacaftor (E/T/I) on markers of liver fibrosis in adults with cystic fibrosis (CF). This study aims to analyse changes in makers of liver fibrosis before and after initiation of E/T/I in CF adults. Outcome measures of liver fibrosis, including liver stiffness measurement (LSM) using FibroScan, AST-to-platelet-ratio index (APRI) and gamma-GT-to-platelet-ratio (GPR) were available in 74 CF adults following initiation of E/T/I. This was compared to historical data collected in 2018 prior to UK availability of E/T/I. The median duration of E/T/I therapy at the time liver fibrosis markers were repeated was 21 (IQR: 17–25) months. There was an increase in APRI from historical measurement to follow-up but no change in LSM or GPR. There were no differences in change in fibrosis markers according to CF liver disease (CFLD) status, although those with a raised LSM at baseline (>6.8 kPa) (n = 14) had a significant reduction in LSM from historical measurement to follow-up versus those with a normal historical value (-3.3 kPa vs 0.25 kPa, p < 0.01). Apart from APRI, we found no changes in liver fibrosis outcomes after initiation of E/T/I in adults with CF. Those with a historical diagnosis of CFLD had no significant worsening or improvement of liver fibrosis markers. We did observe a reduction in LSM in those with liver nodularity, with an initial highest result suggesting a potential positive treatment effect of E/T/I in this category of those with severe CFLD. [ABSTRACT FROM AUTHOR]

Introduction: Whilst disease-modifying therapies are the cornerstone for treatment of multiple sclerosis (MS), there is a need to develop novel therapeutics for the symptomatic sequalae of the disease. Cannabis-based medicinal products (CBMPs) have been suggested as a potential therapy for the associated pain, spasticity, and mental health disorders. However, there is a paucity of clinical evidence on CBMPs in MS. The aim of this study is to assess changes in MS-specific and general health-related quality of life (HRQoL) outcomes alongside adverse event incidence in patients prescribed CBMPs for MS from the UK Medical Cannabis Registry (UKMCR)., Method: Patients prescribed CBMPs for MS symptoms for longer than one month were identified from the UKMCR. The primary outcomes were changes from baseline in MS Quality of Life-54 (MSQoL-54), Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L scales at one month, three months and six months. p < 0.050 was defined as statistically significant., Results: 141 patients met the inclusion criteria for the study. There was an improvement in the following subscales of the MSQoL-54 at 6 months: change in health scale, cognitive function, mental health composition, physical health, role limitations due to physical limitation and due to emotional problems, as well as social and sexual function (p < 0.050). There were also improvements in the EQ-5D-5L index value, GAD-7 and SQS (p < 0.050). 146 (103.55 %) adverse events were reported in total. Most were considered mild (n = 47; 33.33 %) and moderate (n = 72; 51.06 %)., Conclusions: This preliminary analysis demonstrates a possible association with improved general health-related quality of life in those prescribed CBMPs for MS. Moreover, the results suggest that CBMPs are well-tolerated in the first 6 months of treatment. However, this must be interpreted with caution considering the limitations of the observational study design., Competing Interests: Declaration of competing interest Coauthor: Name: Mr Matthew Murphy Disclosure: Matthew Murphy is a biomedical sciences student at Imperial College London. Matthew Murphy has no shareholdings in pharmaceutical companies. Coauthor: Name: Ms Varinder Kaur Disclosure: Varinder Kaur is a biomedical sciences student at Imperial College London. Varinder Kaur has no shareholdings in pharmaceutical companies. Coauthor: Name: Ms Hahn Lan Bui Disclosure: Hanh Lan Bui is a biomedical sciences student at Imperial College London. Hanh Lan Bui has no shareholdings in pharmaceutical companies. Coauthor: Name: Mr Toby Yang Disclosure: Toby Yang is a biomedical sciences student at Imperial College London. Toby Yang has no shareholdings in pharmaceutical companies. Coauthor: Name: Dr Simon Erridge Disclosure: Simon Erridge is a junior doctor and is the Head of Research at Curaleaf Clinic. Simon Erridge is an honorary clinical research fellow at Imperial College London. The views expressed are those of the author(s) and not necessarily those of the NHS. Simon Erridge has no shareholdings in pharmaceutical companies. … Coauthor: Name: Mr Carl Holvey Disclosure: Carl Holvey is Chief Clinical Pharmacist at Curaleaf Clinic. Carl Holvey has no shareholdings in pharmaceutical companies. Coauthor: Name: Dr Ross Coomber Disclosure: Ross Coomber is a consultant orthopaedic surgeon, Operations Director at Curaleaf Clinic and a consultant at St George's Hospital, London. The views expressed are those of the author(s) and not necessarily those of the NHS. Ross Coomber has no shareholdings in pharmaceutical companies. Coauthor: Name: Dr James J Rucker Disclosure: James Rucker is a consultant psychiatrist and a former director at Curaleaf Clinic. James Rucker is an honorary consultant psychiatrist at The South London & Maudsley NHS Foundation Trust, and an NIHR Clinician Scientist Fellow at the Centre for Affective Disorders at King's College London. James Rucker is funded by a fellowship (CS-2017-17-007) from the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. James Rucker has no shareholdings in pharmaceutical companies. James Rucker reviewed this article and made comments. Coauthor: Name: Dr Mark W Weatherall. Disclosure: Mark Weatherall is a consultant in neurology and a former director at Curaleaf Clinic. The views expressed are those of the author(s) and not necessarily those of the NHS. Mark Weatherall has no shareholdings in pharmaceutical companies. Corresponding author: Name: Mr Mikael H Sodergren Disclosure: Mikael Sodergren is a consultant hepatopancreatobiliary surgeon, the managing director at Curaleaf Clinic and a consultant at Imperial College NHS Trust, London. He is senior clinical lecturer at Imperial College London and Chief Medical Officer at Curaleaf International. The views expressed are those of the author(s) and not necessarily those of the NHS., (Copyright © 2024. Published by Elsevier B.V.)

Background: Long-term outcome after subarachnoid hemorrhage, beyond the first few months, is difficult to predict, but has critical relevance to patients, their families, and carers., Objective: To assess the performance of the Subarachnoid Hemorrhage International Trialists (SAHIT) prediction models, which were initially designed to predict short-term (90 d) outcome, as predictors of long-term (2 yr) functional outcome after aneurysmal subarachnoid hemorrhage (aSAH)., Methods: We included 1545 patients with angiographically-proven aSAH from the Genetic and Observational Subarachnoid Haemorrhage (GOSH) study recruited at 22 hospitals between 2011 and 2014. We collected data on age, WNFS grade on admission, history of hypertension, Fisher grade, aneurysm size and location, as well as treatment modality. Functional outcome was measured by the Glasgow Outcome Scale (GOS) with GOS 1 to 3 corresponding to unfavorable and 4 to 5 to favorable functional outcome, according to the SAHIT models. The SAHIT models were assessed for long-term outcome prediction by estimating measures of calibration (calibration slope) and discrimination (area under the receiver-operating characteristic curve [AUC]) in relation to poor clinical outcome., Results: Follow-up was standardized to 2 yr using imputation methods. All 3 SAHIT models demonstrated acceptable predictive performance for long-term functional outcome. The estimated AUC was 0.71 (95% CI: 0.65-0.76), 0.73 (95% CI: 0.68-0.77), and 0.74 (95% CI: 0.69-0.79) for the core, neuroimaging, and full models, respectively; the calibration slopes were 0.86, 0.84, and 0.89, indicating good calibration., Conclusion: The SAHIT prediction models, incorporating simple factors available on hospital admission, show good predictive performance for long-term functional outcome after aSAH., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Background: Near-infrared spectroscopy (NIRS) intravascular ultrasound imaging can detect lipid-rich plaques (LRPs). LRPs are associated with acute coronary syndromes or myocardial infarction, which can result in revascularisation or cardiac death. In this study, we aimed to establish the relationship between LRPs detected by NIRS-intravascular ultrasound imaging at unstented sites and subsequent coronary events from new culprit lesions., Methods: In this prospective, cohort study (LRP), patients from 44 medical centres were enrolled in Italy, Latvia, Netherlands, Slovakia, UK, and the USA. Patients with suspected coronary artery disease who underwent cardiac catheterisation with possible ad hoc percutaneous coronary intervention were eligible to be enrolled. Enrolled patients underwent scanning of non-culprit segments using NIRS-intravascular ultrasound imaging. The study had two hierarchal primary hypotheses, patient and plaque, each testing the association between maximum 4 mm Lipid Core Burden Index (maxLCBI 4mm ) and non-culprit major adverse cardiovascular events (NC-MACE). Enrolled patients with large LRPs (≥250 maxLCBI 4mm ) and a randomly selected half of patients with small LRPs (<250 maxLCBI 4mm ) were followed up for 24 months. This study is registered with ClinicalTrials.gov, NCT02033694., Findings: Between Feb 21, 2014, and March 30, 2016, 1563 patients were enrolled. NIRS-intravascular ultrasound device-related events were seen in six (0·4%) patients. 1271 patients (mean age 64 years, SD 10, 883 [69%] men, 388 [31%]women) with analysable maxLCBI 4mm were allocated to follow-up. The 2-year cumulative incidence of NC-MACE was 9% (n=103). Both hierarchical primary hypotheses were met. On a patient level, the unadjusted hazard ratio (HR) for NC-MACE was 1·21 (95% CI 1·09-1·35; p=0·0004) for each 100-unit increase maxLCBI 4mm ) and adjusted HR 1·18 (1·05-1·32; p=0·0043). In patients with a maxLCBI 4mm more than 400, the unadjusted HR for NC-MACE was 2·18 (1·48-3·22; p<0·0001) and adjusted HR was 1·89 (1·26-2·83; p=0·0021). At the plaque level, the unadjusted HR was 1·45 (1·30-1·60; p<0·0001) for each 100-unit increase in maxLCBI 4mm . For segments with a maxLCBI 4mm more than 400, the unadjusted HR for NC-MACE was 4·22 (2·39-7·45; p<0·0001) and adjusted HR was 3·39 (1·85-6·20; p<0·0001)., Interpretation: NIRS imaging of non-obstructive territories in patients undergoing cardiac catheterisation and possible percutaneous coronary intervention was safe and can aid in identifying patients and segments at higher risk for subsequent NC-MACE. NIRS-intravascular ultrasound imaging adds to the armamentarium as the first diagnostic tool able to detect vulnerable patients and plaques in clinical practice., Funding: Infraredx., (Copyright © 2019 Elsevier Ltd. All rights reserved.)