Search

Objectives: IgA vasculitis (IgAV) in adults has been relatively under-investigated. Since outcomes are worse in other forms of vasculitis with increasing age, we investigated the outcomes of IgAV comparing younger adults (18-34), middle-aged adults (35-64) and elderly patients (≥64 years) focusing on kidney outcomes., Methods: We identified patients with renal biopsy-confirmed IgAV nephritis and collected data regarding clinical features and progression to end stage kidney disease (ESKD). The relationship between patient factors and ESKD was analysed by regression., Results: We identified 202 cases, 34% aged 18-34, 43% aged 35-64 and 23% elderly (>64 years). Median follow-up was 44 months. Elderly patients were more likely to present with ESKD (23.9%) compared with middle-aged (13.7%) and younger adults (2.9%) (χ2 11.6, P = 0.002). In patients with independent kidney function at biopsy, there was no difference in outcomes between age groups. Male gender, Black ethnicity, diabetes, histological evidence of chronic renal damage and estimated glomerular filtration rate < 30 ml/min were risk factors for development of ESKD. In this observational study 68.3% of patients received glucocorticoids and 56.9% additional immunosuppression., Conclusion: Elderly patients with IgAV are more likely to have ESKD at presentation, but there is no difference in renal survival between age groups, among those presenting with independent renal function. Renal impairment at biopsy is an independent risk factor for subsequent development of ESKD. There is significant variability in the timing of kidney biopsy and management of these patients among specialist centres. Young adults have outcomes more in keeping with childhood IgAV., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In recent years, major advances in our understanding of risk factors implicated in the development of cardiovascular disease (CVD), in available tools for early detection of CVD, and in effective interventions to prevent subclinical or clinically manifest disease, have led to an increasing appreciation of prevention as a major pillar of cardiovascular (CV) medicine. Preventive Cardiology has evolved into a dynamic sub-speciality focused on the promotion of CV health through all stages of life, and on the management of individuals at risk of developing CVD or experiencing recurrent CV events, through interdisciplinary care in different settings. As the level of knowledge, specialized skills, experience, and committed attitudes related to CV prevention has exceeded core cardiology training, the European Association of Preventive Cardiology (EAPC) has placed major emphasis on continuous education and training of physicians and allied professionals involved in CV prevention, with the aim of setting standards for practice and improving quality of care. The EAPC recognizes the need for a comprehensive educational offer across different levels of training (from core cardiology to sub-speciality to expert training) as well as the need for interdisciplinary approaches that will promote synergies among allied professionals involved in CV prevention. This statement by the EAPC aims to highlight current gaps and unmet needs and to describe the framework to help standardize, structure, and deliver comprehensive, up-to-date, interactive, and high-quality education using a combination of traditional and novel educational tools. The document aims to form the basis for ongoing refinements of the EAPC educational offer, with the ultimate goal of ensuring that new evidence in the field will translate to better CV practice and improved outcomes for our patients., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Patients with Gorlin (basal cell nevus) syndrome (GS) have numerous phenotypic abnormalities due to over-activity of the hedgehog (HH) signaling pathway, most commonly due to a heritable mutation in the PTCH1 gene, which encodes a major inhibitor of this pathway. HH inhibitors (HHi) taken orally can reverse some of the manifestations, most prominent of which is the development of numerous cutaneous basal cell carcinomas (BCCs). In order to improve the benefit:risk ratio, we have developed a gel containing a small cyclopamine-derived molecule that can be applied topically in expectation that this mode of delivery can reduce the burden of BCCs without producing the systemic adverse effects that cause patients to stop treatment with oral HHis., Objectives: This study attempts to determine whether or not Patidegib Topical Gel, 2% or 4%, can accumulate in high enough concentrations to have local anti-BCC efficacy but not so high that systemic drug levels produce the adverse effects that are typical of oral HHi treatment., Methods: We conducted a small, randomized, double blinded Phase 2A trial at two sites in the United Kingdom to assess the clinical and molecular efficacy and adverse effects of 6 months of twice daily application of Patidegib Topical Gel to the entire face as well as to treatment-targeted surgically-eligible BCCs at other anatomical sites., Results: Post hoc analyses suggested that Patidegib Topical Gel reduced the number of new surgically-eligible BCCs and the level of HH signaling with minimal adverse effects., Conclusions: Patidegib Topical Gel warrants further clinical development., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Chimeric antigen receptor T cell (CAR-T) therapy, an innovative immune cell therapy, has revolutionized the treatment landscape of haematological malignancies. The past 2 years has witnessed the successful application of CD19-targeting CAR constructs in refractory cases of autoimmune rheumatic diseases, including systemic lupus erythematosus, systemic sclerosis and anti-synthetase syndrome. In comparison with existing B cell depletion therapies, targeting CD19 has demonstrated a more rapid and profound therapeutic effect, enabling drug-free remission with manageable adverse events. These promising results necessitate validation through long-term, large-sample randomized controlled studies. Corroborating the role of CAR-T therapy in refractory rheumatological disorders and affirming safety, efficacy and durability of responses are the aims of future clinical studies. Optimizing the engineering strategies and better patient selection are also critical to further refining the successful clinical implementation of CAR-T therapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency (21HD) can affect the in utero development of the genital anatomy of people with the 46XX karyotype. Health professionals engage parents in decision-making regarding managing genitals with this difference, including genital surgery options and patient communication., Aim: We sought to investigate parental communication with their daughters regarding clitoral size variation related to neonatal CAH., Methods: Semistructured in-person interviews of 24 parents of chromosomal XX children with clitoral size variation attributable to a neonatal CAH diagnosis comprised 3 management categories: (1) clitoral reduction surgery (RS) (7 parents, 9 children), (2) clitoral concealment surgery (CS) (8 parents, 8 children), and no surgery on or around the clitoris (NS) (9 parents, 7 children)., Outcomes: Four representative themes, Obvious Choice, Still Different, Parental Burden, and Ignorance Is Bliss, were common across all 3 treatment groups., Results: For most parents, none of the 3 options of genital appearance alteration via clitoral reduction, clitoral concealment surgery, or avoidance of clitoral surgery ameliorated concerns, with most parents expressing an aversion to educating their child on the topic of genital differences, past treatment, or future function., Clinical Implications: Reliance on surgical treatment pathways to manage this psychosocial concern is ineffective in alleviating parental uncertainty without the application of psychosocial interventions., Strengths and Limitations: This was a qualitative study but was limited to parents of children with a specific genital difference, without direct exploration of parental values regarding the clitoris or the application of adequate psychosocial care., Conclusion: Healthcare services must have an impact on parental ability to engage in essential communication with their children in cases such as clitoral size variation related to neonatal CAH. Improved communication skills allow parents to engage in more genuine decision-making and adapt to enduring genital reality, including possible future sexual challenges for their adult child, without resorting to burdensome strategies focused on attempts to perpetuate a benevolent ignorance., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Nonalcoholic fatty liver disease (NAFLD) is prevalent in 25-30% of British and European populations, representing a potential global public health crisis. Marine omega-3 (n-3) polyunsaturated fatty acids offer well-evidenced benefits to NAFLD biomarkers; however, the effect of plant-based n-3 has not been evaluated with a systematic review and meta-analysis., Objective: The review aimed to systematically evaluate the effect of plant-based n-3 supplementation on NAFLD surrogate biomarkers and parameters., Data Sources: Medline (EBSCO), PubMed, CINAHL (EBSCO), Cochrane Central Register of Controlled Trials, the International Clinical Trials Registry Platform, and Google Scholar databases were searched to identify randomized controlled trials published between January 1970 and March 2022 evaluating the impact of plant-based n-3 interventions on diagnosed NAFLD. The review followed the PRISMA checklist and is PROSPERO registered (CRD42021251980)., Data Extraction: A random-effects model and generic inverse variance methods synthesized quantitative data, followed by a leave-one-out method for sensitivity analysis. We identified 986 articles; after the application of selection criteria, six studies remained with 362 patients with NAFLD., Results: The meta-analysis showed that plant-based n-3 fatty acid supplementation significantly reduced alanine aminotransferase (ALT) (mean difference: 8.04 IU/L; 95% confidence interval: 14.70, 1.38; I2 = 48.61%) and plasma/serum triglycerides (44.51 mg/dL; 95% confidence interval: -76.93, -12.08; I2 = 69.93%), alongside body-composition markers in patients with NAFLD (P < 0.05)., Conclusion: Plant-based n-3 fatty acid supplementation improves ALT enzyme biomarkers, triglycerides, body mass index, waist circumference, and weight loss when combined with lifestyle interventions to increase physical activity and a calorie-controlled diet. Further research is needed to identify the most effective plant-based n-3 sources in larger numbers of patients with NAFLD over longer study durations., Systematic Review Registration: PROSPERO registration no. CRD42021251980., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Objectives: The National Health Service in England funds 12 months of weekly subcutaneous tocilizumab (qwTCZ) for patients with relapsing or refractory giant cell arteritis (GCA). During the COVID-19 pandemic, some patients were allowed longer treatment. We sought to describe what happened to patients after cessation of qwTCZ., Methods: Multicentre service evaluation of relapse after stopping qwTCZ for GCA. The log-rank test was used to identify significant differences in time to relapse., Results: 336 GCA patients were analysed from 40 centres, treated with qwTCZ for a median (interquartile range, IQR) of 12 (12-17) months. At time of stopping qwTCZ, median (IQR) prednisolone dose was 2 (0-5) mg/day. By 6, 12 and 24 months after stopping qwTCZ, 21.4%, 35.4% and 48.6% respectively had relapsed, requiring an increase in prednisolone dose to a median (IQR) of 20 (10-40) mg/day. 33.6% of relapsers had a major relapse as defined by EULAR. Time to relapse was shorter in those that had previously also relapsed during qwTCZ treatment (P = 0.0017); in those not in remission at qwTCZ cessation (P = 0.0036); and in those with large vessel involvement on imaging (P = 0.0296). Age ≥65, gender, GCA-related sight loss, qwTCZ treatment duration, TCZ taper, prednisolone dosing, and conventional synthetic DMARD use were not associated with time to relapse., Conclusion: Up to half our patients with GCA relapsed after stopping qwTCZ, often requiring a substantial increase in prednisolone dose. One third of relapsers had a major relapse. Extended use of TCZ or repeat treatment for relapse should be considered for these patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Emergency department (ED) crowding is a worsening global problem caused by hospital capacity and other health system challenges. While patients across a broad spectrum of illnesses may be affected by crowding in the ED, patients with cardiovascular emergencies-such as acute coronary syndrome, malignant arrhythmias, pulmonary embolism, acute aortic syndrome, and cardiac tamponade-are particularly vulnerable. Because of crowding, patients with dangerous and time-sensitive conditions may either avoid the ED due to anticipation of extended waits, leave before their treatment is completed, or experience delays in receiving care. In this educational paper, we present the underlying causes of crowding and its impact on common cardiovascular emergencies using the input-throughput-output process framework for patient flow. In addition, we review current solutions and potential innovations to mitigate the negative effect of ED crowding on patient outcomes., Competing Interests: Conflict of interest: C.W.B. is a paid speaker and Advisory Board member for Roche Diagnostics. He has received research funding from Abbott Laboratories and Visby Medical. He is an Advisory Board member and consultant for AstraZeneca and InCarda Therapeutics. He is an advisor to Lucia Health Guidelines.., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Bilobar liver metastases from colorectal cancer pose a challenge for obtaining a satisfactory oncological outcome with an adequate future liver remnant. This study aimed to assess the clinical and pathological determinants of overall survival and recurrence-free survival among patients undergoing surgical clearance of bilobar liver metastases from colorectal cancer., Methods: A retrospective international multicentre study of patients who underwent surgery for bilobar liver metastases from colorectal cancer between January 2012 and December 2018 was conducted. Overall survival and recurrence-free survival at 1, 2, 3 and 5 years after surgery were the primary outcomes evaluated. The secondary outcomes were duration of postoperative hospital stay, and 90-day major morbidity and mortality rates. A prognostic nomogram was developed using covariates selected from a Cox proportional hazards regression model, and internally validated using a 3:1 random partition into derivation and validation cohorts., Results: A total of 1236 patients were included from 70 centres. The majority (88 per cent) of the patients had synchronous liver metastases. Overall survival at 1, 2, 3 and 5 years was 86.4 per cent, 67.5 per cent, 52.6 per cent and 33.8 per cent, and the recurrence-free survival rates were 48.7 per cent, 26.6 per cent, 19.2 per cent and 10.5 per cent respectively. A total of 25 per cent of patients had recurrent disease within 6 months. Margin positivity and progressive disease at liver resection were poor prognostic factors, while adjuvant chemotherapy in margin-positive resections improved overall survival. The bilobar liver metastases from colorectal cancer-overall survival nomogram was developed from the derivation cohort based on pre- and postoperative factors. The nomogram's ability to forecast overall survival at 1, 2, 3 and 5 years was subsequently validated on the validation cohort and showed high accuracy (overall C-index = 0.742)., Conclusion: Despite the high recurrence rates, overall survival of patients undergoing surgical resection for bilobar liver metastases from colorectal cancer is encouraging. The novel bilobar liver metastases from colorectal cancer-overall survival nomogram helps in counselling and informed decision-making of patients planned for treatment of bilobar liver metastases from colorectal cancer., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Acute mesenteric haematoma (AMH) is a rare condition and established causes include blunt trauma, aneurysmal rupture, acute pancreatitis and anticoagulant use. A male patient in his 50s presented with abdominal pain and loss of consciousness that was immediately preceded by a prolonged coughing episode. A computed tomography (CT) abdomen-pelvis revealed two acute mesenteric haematomas and haematoperitoneum and admission swabs diagnosed coronavirus disease 2019 (COVID-19). The patient had no other acute clinical issues and was not taking anticoagulants. The haematomas were managed conservatively and a follow up computed tomography (CT) 4 weeks post-discharge revealed significant improvement. No clear vessel was identified as the source of the bleed in any of the investigations. This case represents a rare instance of AMH and haematoperitoneum with no established cause. We theorize that the combination of the patient's systemic response to COVID-19 and raised intra-abdominal pressure caused by coughing contributed to the bleeding., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2023.)

Vestibular schwannomas are benign nerve sheath tumours that arise on the vestibulocochlear nerves. Vestibular schwannomas are known to occur in the context of tumour predisposition syndromes NF2-related and LZTR1-related schwannomatosis. However, the majority of vestibular schwannomas present sporadically without identification of germline pathogenic variants. To identify novel genetic associations with risk of vestibular schwannoma development, we conducted a genome-wide association study in a cohort of 911 sporadic vestibular schwannoma cases collated from the neurofibromatosis type 2 genetic testing service in the north-west of England, UK and 5500 control samples from the UK Biobank resource. One risk locus reached genome-wide significance in our association analysis (9p21.3, rs1556516, P = 1.47 × 10-13, odds ratio = 0.67, allele frequency = 0.52). 9p21.3 is a genome-wide association study association hotspot, and a number of genes are localized to this region, notably CDKN2B-AS1 and CDKN2A/B, also referred to as the INK4 locus. Dysregulation of gene products within the INK4 locus have been associated with multiple pathologies and the genes in this region have been observed to directly impact the expression of one another. Recurrent associations of the INK4 locus with components of well-described oncogenic pathways provides compelling evidence that the 9p21.3 region is truly associated with risk of vestibular schwannoma tumorigenesis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objectives: Interventions aimed at increasing TNF-α inhibitor serum drug levels (SDLs) may improve treatment response; however, previous studies suggesting SDL cut-offs have not accounted for treatment adherence. The aim of this study was to establish the relationship between adalimumab/certolizumab SDLs and EULAR good vs non-/moderate response and to define SDL cut-offs associated with good response in fully adherent patients., Methods: In a prospective observational study, 475 patients with RA were treated with certolizumab (n = 192) or adalimumab (n = 283). At baseline and 3, 6 and 12 months, patients had 28-joint DAS, self-reported treatment adherence and SDLs measured. Fully adherent patients were analysed as a subgroup. Follow-up data at 3, 6 and 12 months were analysed separately. Median SDLs were compared in good vs non-/moderate response patients and receiver operating characteristics (ROC) curves were used to establish cut-off SDLs., Results: Fully adherent good responders had significantly higher median adalimumab/certolizumab SDLs compared with non-/moderate responders (P = 0.04 and P = 0.0005, respectively). ROC analysis reported 3 month non-trough adalimumab SDLs discriminated good vs non-/moderate response with an area under the curve (AUC) of 0.63 (95% CI 0.52, 0.75), with a cut-off of 7.5 mg/l being 39.1% specific and 80.9% sensitive. Similarly, 3 month non-trough certolizumab SDLs discriminated good vs non-/moderate response with an AUC of 0.65 (95% CI 0.51, 0.78), with a cut-off of 26.0 mg/l being 43.9% specific and 77.8% sensitive., Conclusion: In fully adherent patients, higher SDLs are detected in good responders, suggesting that interventions to improve SDLs, such as encouraging adherence, could improve treatment response. The 3 month non-trough SDL cut-offs of 7.5 mg/l for adalimumab and 26.0 mg/l for certolizumab may be useful in clinical practice., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Compared with other mental health conditions or psychiatric presentations, such as self-harm, which may be seen in emergency departments, eating disorders can seem relatively rare. However, they have the highest mortality across the spectrum of mental health, with high rates of medical complications and risk, ranging from hypoglycaemia and electrolyte disturbances to cardiac abnormalities. People with eating disorders may not disclose their diagnosis when they see healthcare professionals. This can be due to denial of the condition itself, a wish to avoid treatment for a condition which may be valued, or because of the stigma attached to mental health. As a result their diagnosis can be easily missed by healthcare professionals and thus the prevalence is underappreciated. This article presents eating disorders to emergency and acute medicine practitioners from a new perspective using the combined emergency, psychiatric, nutrition and psychology lens. It focuses on the most serious acute pathology which can develop from the more common presentations; highlights indicators of hidden disease; discusses screening; suggests key acute management considerations and explores the challenge of mental capacity in a group of high-risk patients who, with the right treatment, can make a good recovery., (© The Author(s) 2021. Published by Oxford University Press on behalf of Postgraduate Medical Journal.)

The term "psychologically informed health care" refers to the comprehensive integration of psychological principles into health care. Psychologically informed health care has the potential to lead to a transformation of care, resulting in truly transdisciplinary care. To facilitate its future development, we discuss key characteristics of this approach. These include the direct mode (psychologists assessing and treating patients themselves) and indirect mode (psychologists working through other health care providers) of integrating psychological principles into healthcare; the range of health domains targeted using this approach; transdisciplinary care, transcending traditional disciplinary boundaries; and the positioning of care. We describe a framework for transdisciplinary care, which we refer to as the Framework for Catalytic Collaboration. This framework comprises six dimensions: setting, disciplines, patients/clients, mode of psychological care, primary components of care, and primary targets of care. We also provide four brief illustrations of psychologically informed health care. Finally, we discuss future directions, including the need for professional recognition of the indirect mode, financing of the indirect mode, cross-disciplinary training and trans-disciplinary research., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

Objectives: This study aimed to measure (1) the proportion of children who continue to receive specialist care (rheumatology/ophthalmology) as adults, (2) the characteristics associated with continuing specialist care, and (3) the frequency of specialist care appointments in both paediatric and adult services., Methods: A retrospective cohort of young people with JIA was identified from UK primary care electronic health records (Clinical Practice Research Datalink) between 1 April 2003 and 31 December 2018. To be included in the study, cases needed to have at least 1 year of registration at their general practice beyond age 18 and linkage to Hospital Episodes Statistics data for secondary care information. All specialist care outpatient visits were identified from Hospital Episodes Statistics outpatient data., Results: There were 666 young people included in the study. Of these, 427 (64%) received specialist care beyond age 18, 90 (13%) had their last recorded contact at 16-17 years and 149 (22%) did not continue after 16 years. Older age at diagnosis, female gender, less deprivation and a childhood diagnosis of uveitis were associated with continuing specialist care beyond age 18. Of those continuing beyond 18, 35% (n = 153) were subsequently discharged by the study end date. Of all those discharged, 32% had a missed appointment recorded after the last attended visit, suggesting failure to attend., Conclusions: Two-thirds of young people with JIA continue to receive specialist care beyond age 18. This is useful information for children and young people with JIA and their families planning for their future, and for clinicians planning health-care services., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Currently, no authoritative guidelines exist recommending the analytical performance specification (APS) of blood beta-hydroxybutyrate (BOHB) testing in order to meet the clinical needs of patients. This study has applied existing diabetic ketoacidosis (DKA) BOHB diagnostic thresholds and the recommended rates of fall in BOHB concentrations during DKA treatment to establish pragmatic APSs for BOHB testing., Methods: Required analytical performance was based on 2 clinical requirements: (a) to reliably distinguish between non-adjacent DKA BOHB diagnostic categories of <0.6, 0.6 to 1.5, 1.6 to 2.9, and ≥3 mmol/L, and (b) to be assured that a measured 0.5 mmol/L reduction in BOHB indicates the true concentration is at least falling (meaning >0 mmol/L decline)., Results: An analytical coefficient of variation (CV) of <21.5% could reliably distinguish all non-adjacent diagnostic categories with >99% certainty, assuming zero bias. In contrast, within-day CVs of 4.9%, 7.0%, and 9.1% at 3 mmol/L BOHB were required to assure truly falling ketone concentrations with 99% (optimal), 95% (desirable), and 90% (minimal) probability, respectively. These CVs are larger at lower BOHB concentrations and smaller at higher concentrations., Conclusions: Reliable tracking of changes in BOHB during DKA treatment largely drives the requirement for analytical performance. These data can be used to guide minimal, desirable, and optimal performance targets for BOHB meters and laboratory assays., (© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Compared with other mental health conditions or psychiatric presentations, such as self-harm, which may be seen in emergency departments, eating disorders can seem relatively rare. However, they have the highest mortality across the spectrum of mental health, with high rates of medical complications and risk, ranging from hypoglycaemia and electrolyte disturbances to cardiac abnormalities. People with eating disorders may not disclose their diagnosis when they see healthcare professionals. This can be due to denial of the condition itself, a wish to avoid treatment for a condition which may be valued, or because of the stigma attached to mental health. As a result their diagnosis can be easily missed by healthcare professionals and thus the prevalence is underappreciated. This article presents eating disorders to emergency and acute medicine practitioners from a new perspective using the combined emergency, psychiatric, nutrition and psychology lens. It focuses on the most serious acute pathology which can develop from the more common presentations; highlights indicators of hidden disease; discusses screening; suggests key acute management considerations and explores the challenge of mental capacity in a group of high-risk patients who, with the right treatment, can make a good recovery., (© The Author(s) 2021. Published by Oxford University Press on behalf of Postgraduate Medical Journal.)

Successful pancreas or islet transplantation is currently the only cure for type 1 diabetes mellitus. Since the first pancreas transplant in 1966, there have been various refinements of surgical technique along with improved immunosuppressive regimens, resulting in significantly improved outcomes, with contemporary research into graft monitoring and newer biomarkers, potentially lengthening graft survival rates further. Patients with insulin-dependent diabetes mellitus who are eligible for pancreas or islet transplantation represent a select group, the tip of the iceberg for a significant global diabetes disease burden. In the last 50 years, there have been quantum advances in alternative technologies in diabetes therapy, both experimental and translational. Further development and improved access are required to treat the larger proportion of people suffering from diabetes. Emerging stem cell therapy is still experimental whereas alternatives including automated insulin delivery systems and islet cell transplantation are already used in some countries. Whilst automated insulin delivery systems have increased in efficacy, they still do not achieve the near physiological control of blood sugar, which can be achieved by successful pancreas or islet transplantation. This state-of-the-art review provides a summary of pancreas and islet transplantation to its current place in diabetes therapy, along with alternative and future therapies, including the obstacles associated with the dissemination of these new therapies. With the advent of these modern cellular and technological advances, this review addresses the question: are we entering an era where whole organ pancreas transplantation could be replaced entirely by modern technological advances in diabetes therapy?, Competing Interests: Conflicts of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Objective: This paper describes the co-production of a training video to support people with RA to self-examine for tender and swollen joints., Methods: The patient and public involvement and engagement (PPIE) group supporting a remote monitoring study elected to develop a video to train people with RA how to self-examine for tender and swollen joints, because nothing appropriate was publicly available to fulfil their needs. A core team of PPIE group members and clinicians developed the video, with input from conception to dissemination from the PPIE group. The video was posted, open access, on a YouTube website in February 2021, alongside supporting materials. The number of monthly hits was tracked and a survey developed to ascertain feedback., Results: The video received 1000 hits in the first week, and >40 000 at 10 months. The top three countries viewing the video were India, the USA and the UK, with a range of ages and gender profile broadly corresponding to those of RA patients. Forty-eight survey responses were received (26 patients and 22 clinicians). Patients reported an improvement in their ability to self-examine after watching this video. Eighty-six per cent of patients and 71% of clinicians would recommend the video. It has been used and disseminated by a number of national organizations within the UK., Conclusion: This co-produced, open-access training video for people with RA, originally intended to support a research study into remote monitoring, has been well received, reflecting an international interest in self-examination., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Vascular dysfunction is a significant contributor to the pathophysiology of psoriasis. Some individuals have variation within the gene for vascular endothelial growth factor-A (VEGF-A), which confers an increased risk of developing psoriasis and having a severe disease phenotype, and may determine responsiveness to treatment., Aim: To determine whether patients with psoriasis have alterations in cutaneous microvascular anatomy and physiology due to expression of VEGF and whether laser Doppler imaging has utility in the assessment of this., Methods: Twelve adult volunteers with Type 1 chronic plaque psoriasis underwent laser Doppler imaging of plaque and uninvolved skin. Skin biopsies were taken from the areas imaged for immunohistochemistry, including blood and lymphatic vessel markers, and VEGF-A isotype analysis (VEGF-A121, VEGF-A165 and VEGF-D). Venous blood was collected for DNA extraction, VEGF-A genotyping and peripheral blood mononuclear cell culture., Results: Mean blood vessel area (P < 0·01), number of blood vessels (P < 0·001), number of lymphatic vessels (P < 0·001) and blood flow (P < 0·001) was significantly increased in psoriasis plaques, as was expression of VEGF-A121 (P < 0·01), VEGF-A165 (P < 0·04) and VEGF-D (P < 0·01). Blood flow within psoriasis plaques was independent of their increased vascularity (P < 0·01) and may be associated with baseline productivity of VEGF. The number of blood vessels within uninvolved skin in patients with psoriasis was associated with the VEGF-A (rs833061) genotype (P = 0·01), in a relationship suggesting an allele dosing effect., Conclusion: Noninvasive imaging of blood flow may help determine the cutaneous vascular signature for individual patients. This may be a useful prognostic indicator of psoriasis susceptibility and severity, and thus support selection of treatments., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest. AK-A was a work-experience student., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alterations that take place before the onset of clinically overt CVD. CMR allows for detailed evaluation of biventricular function together with tissue characterization of vessels/myocardium in the same examination, yielding a reliable assessment of disease activity that might not be mirrored by blood biomarkers and other imaging modalities. Therefore, CMR provides diagnostic information that enables timely clinical decision-making and facilitates the tailoring of treatment to individual patients. Here we review the role of CMR in the early and accurate diagnosis of CVD in patients with ARDs compared with other non-invasive imaging modalities. Furthermore, we present a consensus-based decision algorithm for when a CMR study could be considered in patients with ARDs, together with a standardized study protocol. Lastly, we discuss the clinical implications of findings from a CMR examination., Competing Interests: Conflict of interest: E.D. has received speaker fees or honoraria from Astra Zeneca, Pfizer, Bristol Myers Squibb, General Electric, and Abbott Vascular, and research funding from GE Healthcare. L.G. has received speaker fees or honoraria from GE Healthcare, Caption Health, Philips Healthcare, and EchoNous. J.A.C. Lima has received honoraria from Astra Zeneca. N.A.-M. has received speaker fees or honoraria from GE Healthcare and Abbott Vascular. M.M.-C. has received research funding from MSD. M.M. has received research funding from the National Scleroderma Foundation. R.N. has received speaker fees from Sanofi Genzyme, Bayer, and Boehringer-Ingelheim, and unrestricted research funding from Philips Volcano and Biotronik. N.A.B.N. has received speaker fees or honoraria from Novo Nordisk and Servier, research funding from GlaxoSmithKline, and royalties for intellectual property from UpToDate. S.E.P. provides consultancy to and is stockowner of Circle Cardiovascular Imaging. L.E.S. has received speaker fees or honoraria from Pfizer and Janssen. J.S. has received unrestricted research grant from Bayer. P.S. has received speaker fees or honoraria from Astra Zeneca, Boehringer-Ingelheim, Medtronic, Novartis, Servier, and Respicardia. L.M.S.-G. has received speaker fees or honoraria from Amgen. J.W. has received speaker fees or honoraria from Abbott Vascular and research funding form GE Healthcare., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Accurate quality of life (QoL) data and functional results after cancer surgery are lacking for older patients. The international, multicenter Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery (GOSAFE) Study compares QoL before and after surgery and identifies predictors of decline in QoL., Methods: GOSAFE prospectively collected data before and after major elective cancer surgery on older adults (≥70 years). Frailty assessment was performed and postoperative outcomes recorded (30, 90, and 180 days postoperatively) together with QoL data by means of the three-level version of the EuroQol five-dimensional questionnaire (EQ-5D-3L), including 2 components: an index (range = 0-1) generated by 5 domains (mobility, self-care, ability to perform the usual activities, pain or discomfort, anxiety or depression) and a visual analog scale., Results: Data from 26 centers were collected (February 2017-March 2019). Complete data were available for 942/1005 consecutive patients (94.0%): 492 male (52.2%), median age 78 years (range = 70-95 years), and primary tumor was colorectal in 67.8%. A total 61.2% of all surgeries were via a minimally invasive approach. The 30-, 90-, and 180-day mortality was 3.7%, 6.3%, and 9%, respectively. At 30 and 180 days, postoperative morbidity was 39.2% and 52.4%, respectively, and Clavien-Dindo III-IV complications were 13.5% and 18.7%, respectively. The mean EQ-5D-3L index was similar before vs 3 months but improved at 6 months (0.79 vs 0.82; P < .001). Domains showing improvement were pain and anxiety or depression. A Flemish Triage Risk Screening Tool score greater than or equal to 2 (odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.13 to 2.21, P = .007), palliative surgery (OR = 2.14, 95% CI = 1.01 to 4.52, P = .046), postoperative complications (OR = 1.95, 95% CI = 1.19 to 3.18, P = .007) correlated with worsening QoL., Conclusions: GOSAFE shows that older adults' preoperative QoL is preserved 3 months after cancer surgery, independent of their age. Frailty screening tools, patient-reported outcomes, and goals-of-care discussions can guide decisions to pursue surgery and direct patients' expectations., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The incidence and prevalence of JIA was last estimated in the UK in 1994. Since then the disease has been reclassified, the specialty of paediatric rheumatology has evolved and there has been a significant shift in disease management with new advanced therapies. This study aimed to provide up-to-date national estimates of this disease., Methods: Children and young people (CYP) with JIA were identified in the Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases, which source data from the two most commonly used primary care electronic health record systems in the UK. These databases were combined and the cohort was identified (2000-18) using predefined code lists. Validation was performed through linkage to the England Hospital Episode Statistics. Annual incidence and prevalence rates were calculated and stratified by gender, age group and nation of the UK. Direct standardization to the UK population was performed and 5 year incidence rates were calculated between 2003 and 2018., Results: The age-standardized incidence rate was 5.61 per 100 000 population. The age-standardized prevalence rate in 2018 was 43.5 per 100 000. Rates were higher in Scotland compared with England: incidence rate ratio 1.27 (95% CI 1.11, 1.46). The 5 year incidence rates did not change significantly over time., Conclusions: This study has provided the first contemporaneous estimates of occurrence of JIA in the UK in 25 years. These data provide important estimates to inform resource allocation and health service development for management of JIA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Aims: The SYNTAX II study evaluated the impact of advances in percutaneous coronary intervention (PCI), integrated into a single revascularization strategy, on outcomes of patients with de novo three-vessel disease. The study employed decision-making utilizing the SYNTAX score II, use of coronary physiology, thin-strut biodegradable polymer drug-eluting stents, intravascular ultrasound, enhanced treatments of chronic total occlusions, and optimized medical therapy. Patients treated with this approach were compared with predefined patients from the SYNTAX I trial., Methods and Results: SYNTAX II was a multicentre, single-arm, open-label study of patients requiring revascularization who demonstrated clinical equipoise for treatment with either coronary artery bypass grafting (CABG) or PCI, predicted by the SYNTAX score II. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which included any revascularization. The comparators were a matched PCI cohort trial and a matched CABG cohort, both from the SYNTAX I trial. At 5 years, MACCE rate in SYNTAX II was significantly lower than in the SYNTAX I PCI cohort (21.5% vs. 36.4%, P < 0.001). This reflected lower rates of revascularization (13.8% vs. 23.8%, P < 0.001), and myocardial infarction (MI) (2.7% vs. 10.4%, P < 0.001), consisting of both procedural MI (0.2% vs. 3.8%, P < 0.001) and spontaneous MI (2.3% vs. 6.9%, P = 0.004). All-cause mortality was lower in SYNTAX II (8.1% vs. 13.8%, P = 0.013) reflecting a lower rate of cardiac death (2.8% vs. 8.4%, P < 0.001). Major adverse cardiac and cerebrovascular events' outcomes at 5 years among patients in SYNTAX II and predefined patients in the SYNTAX I CABG cohort were similar (21.5% vs. 24.6%, P = 0.35)., Conclusions: Use of the SYNTAX II PCI strategy in patients with de novo three-vessel disease led to improved and durable clinical results when compared to predefined patients treated with PCI in the original SYNTAX I trial. A predefined exploratory analysis found no significant difference in MACCE between SYNTAX II PCI and matched SYNTAX I CABG patients at 5-year follow-up., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: The purpose of this study was to describe the maternal and fetal outcomes in patients with inflammatory rheumatic diseases attending a joint rheumatology and obstetric clinic in the UK., Methods: Electronic records of 98 patients attending the joint rheumatology and obstetric clinic between January 2018 and January 2020 were analysed. Data on patient demographics, characteristics (including age, ethnicity, diagnosis, and medications taken during pregnancy), pregnancy outcomes (miscarriage, stillbirth or live birth), maternal complications [infection, post-partum haemorrhage (PPH) or pre-eclampsia] and fetal complications (sepsis, congenital heart block, prematurity and low birth weight) were tabulated. Subgroups of patients based on maternal diagnosis, medications and Ro/La antibody status were described in a similar manner., Results: The cohort was found to be predominantly Caucasian women >30 years of age, diagnosed with a CTD. Of 98 pregnancies, 97% ( n  = 95) resulted in a live birth, with only 2% resulting in miscarriage ( n  = 2) and 1% in stillbirth ( n  = 1). The median duration of gestation was 38 (interquartile range 37-39) weeks, and the majority of patients had a normal vaginal delivery (35%, n  = 34), whereas 30% had emergency Caesarean sections ( n  = 29). The median birth weight was 3120 (interquartile range 2690-3410) g. The most common maternal complications were PPH (56%, n  = 54) and infection (22%, n  = 21). The most common fetal complications were prematurity (23%, n  = 22) and low birth weight (17%, n  = 16)., Conclusion: We report favourable outcomes from this service model, including a high live birth rate, a low miscarriage rate and a high median birth weight. With limited reported data of pregnancy outcomes from joint obstetric/rheumatology clinics, this service model might be beneficial in other centres., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Aims: Operability of type A acute aortic dissections (TAAAD) is currently based on non-standardized decision-making process, and it lacks a disease-specific risk evaluation model that can predict mortality. We investigated patient, intraoperative data, surgeon, and centre-related variables for patients who underwent TAAAD in the UK., Methods and Results: We identified 4203 patients undergoing TAAAD surgery in the UK (2009-18), who were enrolled into the UK National Adult Cardiac Surgical Audit dataset. The primary outcome was operative mortality. A multivariable logistic regression analysis was performed with fast backward elimination of variables and the bootstrap-based optimism-correction was adopted to assess model performance. Variation related to hospital or surgeon effects were quantified by a generalized mixed linear model and risk-adjusted funnel plots by displaying the individual standardized mortality ratio against expected deaths. Final variables retained in the model were: age [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.02-1.03; P < 0.001]; malperfusion (OR 1.79, 95% CI 1.51-2.12; P < 0.001); left ventricular ejection fraction (moderate: OR 1.40, 95% CI 1.14-1.71; P = 0.001; poor: OR 2.83, 95% CI 1.90-4.21; P < 0.001); previous cardiac surgery (OR 2.29, 95% CI 1.71-3.07; P < 0.001); preoperative mechanical ventilation (OR 2.76, 95% CI 2.00-3.80; P < 0.001); preoperative resuscitation (OR 3.36, 95% CI 1.14-9.87; P = 0.028); and concomitant coronary artery bypass grafting (OR 2.29, 95% CI 1.86-2.83; P < 0.001). We found a significant inverse relationship between surgeons but not centre annual volume with outcomes., Conclusions: Patient characteristics, intraoperative factors, cardiac centre, and high-volume surgeons are strong determinants of outcomes following TAAAD surgery. These findings may help refining clinical decision-making, supporting patient counselling and be used by policy makers for quality assurance and service provision improvement., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Renal transplantation has become the gold-standard treatment for the majority of patients with established renal failure. Recent decades have seen significant progress in immunosuppressive therapies and advances in post-transplant management of recipients, resulting in improved graft and patient outcomes. However, the open technique of allograft implantation has stood the test of time, remaining largely unchanged. In a world where major advances in surgery have been facilitated by innovations in the fields of biotechnology and medical instrumentation, minimally invasive options have been introduced for the recipient undergoing kidney transplantation. In this review we present the evolution of minimally invasive kidney transplantation, with a specific focus on robot-assisted kidney transplant and the benefits it offers to specific patient groups. We also discuss the ethical concerns that must be addressed by transplant teams considering developing or referring to robotic programs., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Background: 4CMenB is a protein-based meningococcal B vaccine, but the vaccine antigens may be present on non-group B meningococci. In September 2015, the UK implemented 4CMenB into the national infant immunization program, alongside an emergency adolescent meningococcal ACWY (MenACWY) program to control a national outbreak of group W (MenW) disease caused by a hypervirulent strain belonging to the ST-11 clonal complex. The adolescent program aimed to provide direct protection for adolescents and indirect protection across the population., Methods: Public Health England conducts meningococcal disease surveillance in England. MenW cases confirmed during 4 years before and 4 years after implementation of both vaccines were analyzed. Poisson models were constructed to estimate direct protection against MenW disease offered by the infant 4CMenB program along with the indirect impact of the adolescent MenACWY program in children eligible for 4CMenB but not MenACWY., Results: Model estimates showed 69% (adjusted incidence rate ratio [aIRR], .31; 95% CI, .20-.67) and 52% (aIRR, .48; 95% CI, .28-.81) fewer MenW cases than predicted among age-cohorts that were fully- and partly-eligible for 4CMenB, respectively. There were 138 MenW cases in <5-year-olds. 4CMenB directly prevented 98 (95% CI, 34-201) cases, while the MenACWY program indirectly prevented an additional 114 (conservative) to 899 (extreme) cases over 4 years. Disease severity was similar in 4CMenB-immunized and unimmunized children., Conclusions: This is the first real-world evidence of direct protection afforded by 4CMenB against MenW:cc11 disease. 4CMenB has the potential to provide some protection against all meningococcal serogroups., (© Crown copyright 2020.)

Objectives: To determine the prevalence of 16S rRNA methyltransferase- (16S RMTase-) producing Gram-negative bacteria in patients in the UK and to identify potential risk factors for their acquisition., Methods: A 6 month prospective surveillance study was conducted from 1 May to 31 October 2016, wherein 14 hospital laboratories submitted Acinetobacter baumannii, Enterobacterales and Pseudomonas aeruginosa isolates that displayed high-level amikacin resistance according to their testing methods, e.g. no zone of inhibition with amikacin discs. Isolates were linked to patient travel history, medical care abroad, and previous antibiotic exposure using a surveillance questionnaire. In the reference laboratory, isolates confirmed to grow on Mueller-Hinton agar supplemented with 256 mg/L amikacin were screened by PCR for 16S RMTase genes armA, rmtA-rmtH and npmA, and carbapenemase genes (blaKPC, blaNDM, blaOXA-48-like and blaVIM). STs and total antibiotic resistance gene complement were determined via WGS. Prevalence was determined using denominators for each bacterial species provided by participating hospital laboratories., Results: Eighty-four isolates (44.7%), among 188 submitted isolates, exhibited high-level amikacin resistance (MIC >256 mg/L), and 79 (94.0%) of these harboured 16S RMTase genes. armA (54.4%, 43/79) was the most common, followed by rmtB (17.7%, 14/79), rmtF (13.9%, 11/79), rmtC (12.7%, 10/79) and armA + rmtF (1.3%, 1/79). The overall period prevalence of 16S RMTase-producing Gram-negative bacteria was 0.1% (79/71 063). Potential risk factors identified through multivariate statistical analysis included being male and polymyxin use., Conclusions: The UK prevalence of 16S RMTase-producing Gram-negative bacteria is low, but continued surveillance is needed to monitor their spread and inform intervention strategies., (© Crown copyright 2021.)

Aims: None of the existing studies on adherence have directly measured levels of all medications (or their metabolites) in patients with heart failure (HF)., Methods and Results: We used liquid chromatography-tandem mass spectrometry to measure the presence of prescribed drugs (diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists) in the urine of patients reviewed 4-6 weeks after hospitalization with HF. Patients were unaware that adherence was being assessed. Of the 341 patients studied, 281 (82.4%) were adherent, i.e. had all prescribed drugs of interest detectable in their urine. Conversely, 60 patients (17.6%) were partially or completely non-adherent. Notably, 24 of the 60 were non-adherent to only diuretic therapy and only seven out of all 341 patients studied (2.1%) were completely non-adherent to all prescribed HF drugs. There were no major differences in baseline characteristics between adherent and non-adherent patients., Conclusion: Non-adherence, assessed using a single spot urine measurement of drug levels, was confirmed in one of five patients evaluated 4-6 weeks after hospitalization with HF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: The use of transvenous pacing leads is associated with the risk of developing tricuspid valve (TV) dysfunction. This develops through several mechanisms including the failure of leaflet coaptation or direct damage to the TV or to its sub-valvular apparatus and can result in significant tricuspid regurgitation (TR). Multiple approaches to pacemaker implantation after transvenous lead extraction (TLE) or surgical TV repair have been described. Placement of pacing leads across the TV is generally avoided in such circumstances., Case Summary: A 66-year-old woman presented with a year-long history of exertional dyspnoea, peripheral oedema, and postural neck pulsations. Her medical history included a dual-chamber pacemaker implantation for sinus node dysfunction 14 years ago. Echocardiography revealed severe lead-related TR. Her case was discussed in our multi-disciplinary team meeting. A decision was made to perform a TLE and implant a leadless pacemaker in an attempt to avoid open-heart surgery if possible. This was reserved as an option in the event of persistent severe TR. Transvenous extraction of the right ventricular lead was performed. The atrial lead was preserved and connected to and AAI device. A Micra AV was implanted allowing for atrioventricular (AV) synchronous pacing., Discussion: We present the first case of successful implementation of AV sequential pacing using a dual-pacemaker approach involving the use of an AAI pacemaker and a Micra AV device. This was performed after TLE for severe lead-related TR., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS)., Method: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS., Results: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30)., Conclusion: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Few data have looked at the occurrence and clinical correlates of self-reported shorter than desired ejaculation latency (rapid ejaculation, RE) and its related distress in the general population., Aim: To determine the prevalence and clinical correlates of self-reported RE and RE- related distress in middle age and older European men., Methods: Subjects were recruited from population samples of men aged 40-79 years across 8 European centers., Outcomes: Self-reported RE and its related distress were derived from the European male Aging Study (EMAS) sexual function questionnaire (EMAS-SFQ). Beck's depression Inventory (BDI) was used for the quantification of depressive symptoms, the Short Form 36 health survey (SF-36) for the assessment of the quality of life, the International Prostate Symptom Score (IPSS) for the evaluation of lower urinary tract symptoms., Results: About 2,888 community dwelling men aged 40-79 years old (mean 58.9 ± 10.8 years) were included in the analysis. Among the subjects included, 889 (30.8%) self-reported RE. Among them, 211 (7.3%) claimed to be distressed (5.9% and 1.4% reported mild or moderate-severe distress, respectively). Increasing levels of RE-related distress were associated with a progressive worse sexual functioning, higher risk of ED and with couple impairment, along with a higher prevalence of depressive symptoms (all P < 0.05). Furthermore, a worse quality of life and higher IPSS score were associated with RE-related distress (all P < 0.05). The aforementioned results were confirmed even when patients using drugs possibly interfering with ejaculation or those without a stable relationship were excluded from the analysis., Clinical Implications: RE is a frequent condition in men from the general population; however, its related distress is relatively modest. Nonetheless, men with any degree of self-reported RE show increasing levels of depression, worse quality of life and worse couple satisfaction., Strengths & Limitations: This is the first study estimating the prevalence of self-reported RE and its related distress, along with their biological and psychological correlates, in a population sample of European middle age and older men. However, is should be recognized that the diagnosis of RE was derived from patient reports and not supported by Intra-ejaculatory-Latency-Time (IELT) measurements., Conclusion: Self-reported RE is relatively common in European men aged more than 40 years. The reported limited RE-related distress may explain the relatively low number of medical consultations for RE. RE-related distress is associated with worse sexual function, couple impairment, and more LUTS resulting in a worse quality of life and mood disturbances. Corona G, Rastrelli G, Bartfai G, et al. Self-Reported Shorter Than Desired Ejaculation Latency and Related Distress-Prevalence and Clinical Correlates: Results From the European Male Ageing Study. J Sex Med Rev 2021;18:908-919., (Copyright © 2021. Published by Elsevier Inc.)

Background: We assessed the accuracy and clinical effectiveness of high-sensitivity cardiac troponin (hs-cTn) assays for early rule-out of non-ST-segment elevation myocardial infarction (NSTEMI) in adults presenting with acute chest pain., Methods: Sixteen databases were searched to September 2019. Review methods followed published guidelines. The bivariate model was used to estimate summary sensitivity and specificity with 95% confidence intervals for meta-analyses involving 4 or more studies, otherwise random-effects logistic regression was used., Results: Thirty-seven studies (124 publications) were included in the review. The hs-cTn test strategies evaluated in the included studies were defined by the combination of 4 factors (assay, number of tests, timing of tests, and threshold concentration or change in concentration between tests). Clinical opinion indicated a minimum acceptable sensitivity of 97%. A single test at presentation using a threshold at or near the assay limit of detection could reliably rule-out NSTEMI for a range of hs-cTn assays. Serial testing strategies, which include an immediate rule-out step, increased the proportion ruled out without loss of sensitivity. Finally, serial testing strategies without an immediate rule-out step had excellent sensitivity and specificity, but at the expense of the option for immediate patient discharge., Conclusion: Test strategies that comprise an initial rule-out step, based on low hs-cTn concentrations at presentation and a minimum symptom duration, and a second step for those not ruled-out that incorporates a small absolute change in hs-cTn at 1, 2, or 3 hours, produce the highest rule-out rates with a very low risk of missed NSTEMI., Prospero Registration: CRD42019154716., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing but relatively intact activities of daily living. MCI is a risk state for further cognitive and functional decline with 5-15% of people developing dementia per year. However, ~50% remain stable at 5 years and in a minority, symptoms resolve over time. There is considerable debate about whether MCI is a useful clinical diagnosis, or whether the use of the term prevents proper inquiry (by history, examination and investigations) into underlying causes of cognitive symptoms, which can include prodromal neurodegenerative disease, other physical or psychiatric illness, or combinations thereof. Cognitive testing, neuroimaging and fluid biomarkers can improve the sensitivity and specificity of aetiological diagnosis, with growing evidence that these may also help guide prognosis. Diagnostic criteria allow for a diagnosis of Alzheimer's disease to be made where MCI is accompanied by appropriate biomarker changes, but in practice, such biomarkers are not available in routine clinical practice in the UK. This would change if disease-modifying therapies became available and required a definitive diagnosis but would present major challenges to the National Health Service and similar health systems. Significantly increased investment would be required in training, infrastructure and provision of fluid biomarkers and neuroimaging. Statistical techniques combining markers may provide greater sensitivity and specificity than any single disease marker but their practical usefulness will depend on large-scale studies to ensure ecological validity and that multiple measures, e.g. both cognitive tests and biomarkers, are widely available for clinical use. To perform such large studies, we must increase research participation amongst those with MCI., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society.)