Search

Introduction: Pulsed-field ablation (PFA) is a novel modality for pulmonary vein isolation in patients with atrial fibrillation (AF). We describe the initial uptake and experience of PFA using a pentaspline catheter across selected National Health Service England (NHSE) centres., Methods: Data collected by NHSE Specialised Services Development Programme regarding AF ablation procedures using a single-shot, pentaspline, multielectrode PFA catheter (FARAWAVE, Boston Scientific) between June 2022 and August 2024 were aggregated and analysed to examine procedural metrics, acute efficacy and safety outcomes over 3-month follow-up., Results: 1034 procedures were submitted. The patients were 32.1% female, mean age 63.8±10.7 years, 53.1% paroxysmal AF and 89.7% first-time AF ablation. Procedures were performed by 48 consultant operators at nine NHSE centres, with a mean of 115 procedures per centre (range 25-264). 93.7% of procedures were performed under general anaesthesia. Median skin-to-skin procedure time was 74 min (IQR 55-96 min) and fluoroscopy time 20 min (IQR 15-27 min). Electroanatomical mapping was used in 15.3%. In first-time ablation cases, acute isolation of all pulmonary veins was achieved in 99.5% of patients. Left atrial (LA) posterior wall ablation using the PFA catheter was performed in 11.0% of cases; additional LA radiofrequency ablation was performed in 0.6%. The major and minor acute procedural complication rates were, respectively, 1.3% and 3.1%, with no reports of periprocedural death or atrio-oesophageal fistula. 63.8% of patients were discharged on the day of procedure. Follow-up data were available for 870 procedures (84.1%). In the 3 months following ablation, hospitalisation for arrhythmia occurred in 3.2%, with 0.9% rehospitalised for procedural-related complications., Conclusion: In this real-world, nationwide registry of a pentaspline PFA catheter, efficacy, safety and efficiency outcomes were comparable to those from previous PFA studies in patients with AF., Competing Interests: Competing interests: FM reports: Steering Committee, consulting and speaker fees for Medtronic; Steering Committee, Boston Scientific. VL reports: support from UK National Institute for Health Research scholarship award, speaker for Boston Scientific and Biosense Webster, research grants from Biosense Webster. DG reports: institutional research grants from Boston Scientific and Medtronic and speaker fees from Boston Scientific. CAM reports: research grants from Boston Scientific, Consulting fees from Boston Scientific, Medtronic, Biosense Webster, Advisory Board Committee member for Boston Scientific, Medtronic. SZ reports: research grants from Boston Scientific. SG reports: speaker fees from Boston Scientific. SHC reports: research grant and speaker fees from Abbott Medical; educational grant and consulting fees from Boston Scientific; consulting fees from Medtronic. DT reports: speaker fees from Boston Scientific and Abbott Medical. The other authors report no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ Group.)

Background & Aims: Interventional clinical trials in ASUC are characterised by substantial heterogeneity due to a lack of consensus in several key areas of trial design - this impedes clinical research efforts to identify novel therapies. The objective of this initiative was to achieve the first consensus and provide clear position statements on ASUC trial design., Methods: A modified Delphi consensus approach was employed with a panel of twenty clinicians with international representation and expertise in ASUC trial design and delivery. Agreement was defined as at least 75% of participants voting as 'agree' with each statement., Results: In total, thirty statements achieved consensus and were approved. Statements centred on proposing suitable eligibility criteria (disease extent, disease severity, prior therapy exposure), optimising trial design (randomisation, stratification, corticosteroid handling, timing of assessments), and recommending primary and secondary endpoints alongside defining key efficacy outcomes (clinical and endoscopic reponse and remission, treatment failure, quality of life)., Conclusions: The expansion of drugs to treat moderate-severe UC over the past decade, particularly the rapidly acting Janus kinase inhibitors, is promising and has reignited the interest in identifying suitable therapeutic candidates for ASUC. Clinical trials in this high-risk population are challenging to conduct and this consensus provides a framework for future trials to advance drug development., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Women identified at risk for preterm may be vulnerable to developing mental health difficulties due to the increased likelihood of poor pregnancy outcome and uncertainty surrounding their delivery. Formal assessment of mental wellbeing in specialist preterm birth clinics is not routinely offered, but may offer the opportunity for early intervention., Methods: We aimed to investigate if demographic characteristics and obstetric risk factors were associated with psychological wellbeing in women at risk of preterm birth. We explored associations between mental wellbeing and risk factors for preterm birth using hierarchical regression analyses., Results: When demographic variables were considered alone, high body mass index (BMI) was significantly associated with anxiety ( p  = .026), however became non-significant when obstetric risk factors were also considered. Previous late miscarriage was associated with high anxiety ( p  = .049). Lower maternal age at estimated date of delivery ( p  = .019) and non-European ethnic heritage ( p  = .029) were significantly associated with depression. High maternal BMI ( p  < .001), being of any other non-European ethnic heritage ( p  = .043), currently smoking ( p  = .002), and previous spontaneous preterm birth ( p  = .017) were associated with lower perceived wellbeing., Discussion: The results of this study highlight the importance of routinely monitoring mental health in women with relevant risk factors, particularly if they are already at risk of preterm birth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Worrall, Christiansen, Carlisle, Fallon, Khalil, Shennan, Tribe, Carter, Silverio and The UK Preterm Clinical Network.)

Background: Inflammatory bowel disease (IBD) causes fatigue, pain and faecal urgency/incontinence symptoms. Identifying symptom profile subgroups and related psychological correlates might enable earlier intervention and more effective tailored treatment pathways., Methods: This study was nested within a randomised controlled trial of a digital symptom intervention for people with IBD (n=780). Latent profile analysis (LPA) was conducted on pre-randomisation baseline measures of fatigue, pain, and faecal incontinence. Multinominal logistic regression examined associations between profile membership and clinical, demographic and psychological factors., Results: LPA determined a three-profile model: Moderate (50%), High (40%) and Severe symptoms (10%). Diagnosis and faecal calprotectin were not associated with profile membership, but female gender, comorbidity, time since diagnosis and IBS-type symptoms were associated with High and Severe symptoms profiles. Depression, anxiety, negative symptom perceptions, all-or-nothing and avoidance behaviours significantly increased the relative risk of High and Severe symptoms profile membership., Conclusions: Many participants experienced symptoms even when deemed to be in clinical remission. After controlling for clinical, inflammatory, and demographic factors, the relative risk of High or Severe symptom profile membership was associated with potentially modifiable cognitive behavioural factors. These factors were also associated with IBS-type symptoms. Recognising the potential impact of cognitive behavioural factors in exacerbating symptoms can lead to earlier identification of patients who require support and allows treatment plans to be tailored more precisely. The findings from this study promote a more integrated approach to IBD management, combining medical treatment with cognitive behavioural interventions to enhance patient care and improve outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Consistently engaging with client distress can negatively impact mental health workers (MHWs). This has been described by the concept of empathy-based stress (EBS) (which encompasses burnout; secondary traumatic stress; compassion fatigue and vicarious trauma). Previous reviews of interventions to reduce EBS have not addressed MHWs as a distinct group, despite evidence suggesting they are particularly vulnerable to it. In the context of rising demand for mental health services, it is especially important to understand how to mitigate the impact of EBS on MHWS. This scoping review therefore aimed to identify and describe available interventions to reduce or prevent EBS in MHWs. A systematic scoping review of the literature between 1970 and 2022 was undertaken using five electronic databases. A total of 51 studies were included, which varied significantly with regards to: interventions used; study methodology and theoretical underpinnings. Studies were grouped according to the level at which they aimed to intervene, namely: individual; team or organisational. The review concluded that most studies intervened at the level of the individual, despite the proposed causes of EBS being predominantly organisational. Furthermore, theoretical links to the origins of EBS were largely unclear. This suggests a lack of empirical evidence from which organisations employing MHWs can draw, to meaningfully prevent or reduce EBS in their staff. A dedicated research agenda is outlined to address this, and, other pertinent issues in the field and signifies a call for more theoretically grounded research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 May et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Conflict of interest: none declared.

In the modern era, cardiologists managing patients and families with cardiomyopathies need to be familiar with every stage of the diagnostic pathway from clinical phenotyping to the prescription and interpretation of genetic tests. This clinical consensus statement from the ESC Council for Cardiovascular Genomics aims to promote the integration of genetic testing into routine cardiac care of patients with cardiomyopathies, as recommended in the 2023 ESC guidelines for cardiomyopathies. The document describes the types of genetic tests currently available and provides advice on their prescription and for counselling after the return of genetic findings, including the approach in patients and families with variants of unknown significance., (© 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.)

Purpose: There are limited data about the outcome of old intensive care (ICU) patients suffering from Covid-19 in the post-vaccination era. This study distinguishes the pre- and post-acute illness living conditions of ICU survivors from non-survivors., Methods: This prospective international multicenter study included 642 old (≥ 70 years) ICU patients, including data ranging from pre-illness condition to functional 90-days follow-up. The primary endpoint was the difference of living conditions of ICU-survivors before ICU admission and 90-days after ICU discharge. Secondary outcomes were 90-days mortality, and quality of life., Results: A total of 642 patients were included. Significantly more ICU survivors lived at their own homes without support before ICU admission than non-survivors (p = 0.016), while more non-survivors resided in nursing homes (p = 0.016). ICU mortality was 39 %, 30-days and 90 days mortality were 47 %and 55 %. After 90 days, only 22 % maintained the same living conditions. Surviving patients viewed ICU admission positively after 90 days, while relatives were more uncertain. Quality of life indicated a self-reported average score of 60 (50-75)., Conclusion: Living conditions influence the outcome of critically ill old patients suffering from Covid-19. Only a minority returned to their initial habitat after ICU survival. Trial registration numberNCT04321265., Competing Interests: Declaration of competing interest SJS received grants and non-financial support from Reactive Robotics GmbH (Munich, Germany), ASP GmbH (Attendorn, Germany), STIMIT AG (Biel, Switzerland), ESICM (Geneva, Switzerland), grants, personal fees, and non-financial support from Fresenius Kabi Deutschland GmbH (Bad Homburg, Germany), grants from the Innovationsfond of The Federal Joint Committee (G-BA), personal fees from Springer Verlag GmbH (Vienna, Austria) for educational purposes and Advanz Pharma GmbH (Bielefeld, Germany), non-financial support from national and international societies (and their congress organisers) in the field of anesthesiology and intensive care medicine, outside the submitted work. Dr. Schaller holds stocks in small amounts from Alphabet Inc., Bayer AG, and Siemens AG; these holdings have not affected any decisions regarding his research or this study. All other authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: Little is known about the distribution and clinical course of patients with inherited arrhythmia syndrome (IAS) and concomitant atrial arrhythmias (AAs). The aim of the study is (i) to characterize the distribution of AAs in patients with IAS and (ii) evaluate the long-term clinical course of these patients., Methods and Results: An international multicentre study was performed and involved 28 centres in 16 countries. Inclusion criteria were (i) IAS and (ii) electrocardiographic documentation of AAs. The primary endpoint was a composite of sudden cardiac death, sustained ventricular arrhythmias (VAs), or appropriate implantable cardioverter defibrillator (ICD) interventions. Strokes, inappropriate ICD shocks due to AAs, and the occurrence of sinus node dysfunction were assessed. A total of 522 patients with IAS and AAs were included. Most patients were diagnosed with Brugada syndrome (n = 355, 68%) and long QT syndrome (n = 93, 18%). The remaining patients (n = 71, 14%) presented with short QT syndrome, early repolarization syndrome, catecholaminergic polymorphic ventricular tachycardia, progressive cardiac conduction diseases, or idiopathic ventricular fibrillation. Atrial fibrillation was the most prevalent AA (82%), followed by atrial flutter (9%) and atrial tachycardia (9%). Atrial arrhythmia was the first clinical manifestation of IAS in 52% of patients. More than one type of AA was documented in 23% of patients. Nine patients (3%) experienced VA before the diagnosis of IAS due the use of anti-arrhythmic medications taken for the AA. The incidence of the primary endpoint was 1.4% per year, with a two-fold increase in patients who experienced their first AA before the age of 20 (odds ratio 2.2, P = 0.043). This was consistent across the different forms of IAS. Inappropriate ICD shock due to AAs was reported in 2.8% of patients, strokes in 4.4%, and sinus node dysfunction in 9.6%., Conclusion: Among patients with IAS and AAs, AA is the first clinical manifestation in about half of the cases, with more than one form of AAs present in one-fourth of the patients. The occurrence of AA earlier in life may be associated with a higher risk of VAs. The occurrence of stroke and sinus node dysfunction is not infrequently in this cohort., Competing Interests: Conflict of interest: G.C. has received honoraria from Bristol-Myers Squibb SA. Microport CRM, Biosense Webster, research grants from Boston Scientific Inc. J.T.-H. has been a consultant for Johnson and Johnson, Boston, MicroPort, Solid Bioscience, Cytokinetics, and Leo Pharma. All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Concerns exist about the possible detrimental effects of exercise training on aortic size and valve function in individuals with bicuspid aortic valve (BAV). This multicentre international study aimed to determine the characteristics of aortic size and valve function in athletes versus non-athletes with BAV and athletes with tricuspid aortic valve (TAV)., Methods: We enrolled competitive athletes with BAV and age- and sex-matched athletes with TAV and non-athletes with BAV. We assessed valve function, aortic size and biventricular measures using echocardiography. Individuals with established moderate-severe AV stenosis, regurgitation or significant aortic dilation were excluded from the study., Results: The study population comprised 504 participants: 186 competitive athletes with BAV (84% males; age 30±11 years), 193 competitive athletes with TAV and 125 non-athletes with BAV. The aortic annulus was greater in athletes with BAV than athletes with TAV and non-athletes with BAV (p<0.001). Both athletic and non-athletic individuals with BAV had greater sinuses of Valsalva, sino-tubular junction and ascending aorta diameters than athletes with TAV (p<0.001). However, no significant differences were found between athletes and non-athletes with BAV. Left ventricular index volumes and mass were greater in athletes with BAV than in the other two groups (p<0.001). Individuals with BAV (athletes and non-athletes) had greater mean gradients than TAV athletes., Conclusion: This multicentre international study demonstrates no differences between athletes with BAV and non-athletes with BAV regarding aortic valve function or aortic dimensions. However, athletes with BAV have larger aortic diameters and a relatively worse valvular function than athletes with TAV., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The effects of triathlon exercise on cardiac function are well documented. While Olympic triathlon (swim-bike-run) remains the standard format, increasing concerns about water quality in natural waterways present ongoing challenges for open-water swimming events, highlighting the potential need to consider alternative formats such as duathlon (run-bike-run) in some circumstances. An additional run may increase the overall metabolic and cardiovascular demand compared with the swim in triathlon, leading to reduced future performance. Conversely, the majority of EICF research reports reversal of post-exercise perturbations within 24-7 days of recovery but duathlon has not yet been studied in this context. Therefore, this study aimed to investigate the cardiac, autonomic, haemodynamic and biomarker responses during and following two Olympic distance (OD) duathlon separated by 7 days of recovery. Highly-trained (V O 2max >60 mL·kg -1 ·min -1 ) male participants (n = 10) completed two lab-based OD duathlons, either continuous (BD) or with functional measurements after each leg (UD), separated by 7 days of rest. Conventional echocardiography recorded standard and tissue Doppler measures of left ventricular (LV) structure and function. Speckle tracking echocardiography was used to measure global longitudinal strain (GLS). Time and frequency domain analysis of HRV, as well as plasma high sensitivity cardiac troponin T (hs-cTnT) were measured pre and post exercise. In the broken duathlon trial (BD) cardiac measurements and blood samples were also taken between each leg. In the unbroken duathlon (UD) participants performed each leg sequentially. Duathlon exercise resulted in similar cardiac functional and biomarker alterations as previously reported in triathlon and standalone running and cycling exercise. Cardiac troponins were still elevated following 24 h -1 of recovery. However, functional changes were resolved within 24 h -1 of passive recovery and did not impair subsequent duathlon performance, or pre-exercise measurements 7 days after the first trial. Whether or not elite or recreational athletes experience the same magnitude and reversibility of these changes remains to be elucidated further., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Inappropriate therapy (IAT) is an undesirable side effect of implantable cardiac defibrillator (ICD) therapy. Early studies with the subcutaneous ICD (S-ICD) showed relatively high inappropriate shock (IAS) rates. The PRAETORIAN (Prospective Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy) trial demonstrated that the S-ICD is noninferior to the transvenous ICD (TV-ICD) with regard to the combined end point of IAS and complications. This secondary analyses evaluates all IAT in the PRAETORIAN trial., Methods: This international, multicenter trial randomized 849 patients with an indication for ICD therapy between S-ICD (n=426) and TV-ICD therapy (n=423). ICD programming was mandated by protocol. All analysis were performed in the modified intention-to-treat population., Results: In both groups 42 patients experienced IAT (48-month Kaplan-Meier estimated cumulative incidence, 9.9% and 10.1%, respectively; hazard ratio (HR), 0.99 [95% CI, 0.65-1.52]; P =0.97). There was no significant difference in patients experiencing IAS between both groups ( P =0.14). In the S-ICD group, 81 IAT episodes with 124 IAS and 1 inappropriate antitachycardia pacing occurred versus 89 IAT episodes with 130 IAS and 124 inappropriate antitachycardia pacing in the TV-ICD group. IAT episodes were most frequently caused by supraventricular tachycardias in the TV-ICD group (n=83/89) versus cardiac oversensing in the S-ICD group (n=40/81). In the TV-ICD group, a baseline heart rate >80 bpm (HR, 1.99 [95% CI, 1.05-3.76]; P =0.03), a history of atrial fibrillation (HR, 2.66 [95% CI, 1.41-5.02]; P =0.003), and smoking (HR, 2.46 [95% CI, 1.31-4.09]; P =0.005) were independent predictors for IAT. A QRS duration >120 ms was an independent predictor for IAT caused by cardiac oversensing in the S-ICD group (HR, 3.13 [95% CI, 1.34-7.31]; P =0.008). Post-IAS interventions significantly reduced IAS recurrence in both groups ( P =0.046)., Conclusions: There was no significant difference in IAT and IAS rates between the S-ICD and TV-ICD in a conventional ICD population, but causes and predictors for IAT differed between the devices. After the first IAS, an intervention significantly reduced the recurrence rate of IAS., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01296022., Competing Interests: Dr Knops reports consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cardiac, and has stock options from AtaCor Medical, Inc. Dr El Chami reports consultancy fees from Boston Scientific and Medtronic. Dr Mittal reports consultancy fees from Boston Scientific and Medtronic.Dr Neuzil reports modest speaker honoraria from Biotronik, Boston Scientific, and Medtronic. K.M. Kooiman reports consultancy fees from Boston Scientific. Dr Lambiase reports educational and research grants from and is in the research board of Boston Scientific, and reports research grants from Abbott. Dr Vernooy reports consultancy fees from Medtronic and Abbott. M.C. Burke is a consultant, receives honoraria, as well as research grants from Boston Scientific and has equity in and is chief medical officer for AtaCor Medical, Inc. Dr Wright has consultancy arrangements with Boston Scientific and Medtronic and a research grant from Boston Scientific. Dr Nordbeck reports modest speaker honoraria from Biotronik, Boston Scientific, and Medtronic. Dr Miller reports consultancy fees from Boston Scientific. Dr Whinnett is an advisor for Boston Scientific, on the advisory board for Medtronic and Abbot, and reports speaker fees from Medtronic. The other authors report no conflicts.

Therapeutics of neuroinflammatory disorders including multiple sclerosis is one of the fastest growing areas in neurology. However, pressures on higher specialty training in neurology together with an expanding curriculum have led to challenges in adequately preparing trainees for a subspecialist career. In this study we set out to understand current perceptions and barriers to training in neuroinflammatory disorders among neurology trainees in the UK. A structured questionnaire was used to assess trainees' perspectives on training opportunities and career aspirations. Findings reveal significant gaps in training, including insufficient training opportunities, lack of mentorship, and concerns about managing complex treatment regimes. We used these findings to develop structured action points with aim of improving training and retention in this subspecialty. These include early exposure to subspecialty experiences, enhanced mentorship, and equal access to training opportunities regardless of geographical location. Our findings underscore the need for further curriculum development in neurology training, potentially combining early support with dedicated fellowships later in training, in order to ensure sustainability of neuroinflammation as a subspecialty and to meet the growing demand for expertise in MS and related conditions., Competing Interests: Declaration of competing interest TA has received honoraria or consulting fees for participating in advisory boards related to trial steering committees and data and safety monitoring committees, speaker fees & research grants from Janssen, Merck, Novartis, Roche and Sanofi-Genzyme NR has received honoraria and/or support to attend educational meetings from: Biogen, Novartis, Sanofi, TG therapeutics, Genzyme and Bayer. His institution has also received support for research from Biogen, Genzyme, Sanofi and Novartis. KS has received honoraria/support from Biogen, Merck KGaA, and Novartis, Roche and Sanofi-Genzyme, speaking honoraria from, and/or served in an advisory role for, Biogen, EMD Serono, IGES UK, Merck KGaA, Novartis, Roche, and Sanofi-Genzyme and Teva; and remuneration for teaching activities from AcadeMe and Medscape. RD received honoraria for speaking and/or traveling from Biogen, Merck, Roche, Teva, Janssen, and Sanofi. She served on advisory board of Roche, Biogen, Janssen, Sandoz and Merck. All honoraria for speaking, travelling and advisory boards were paid into an institutional account and used to support research, open access publications, and training for group members. She has received grant support from Biogen, Merck, Celgene. SH has received unrestricted educational grants or speaking honoraria from Biogen, Merck Serono, Novartis, Roche and Sanofi Genzyme. In the last 3 years, JC has received support from the Health Technology Assessment (HTA) Programme (National Institute for Health Research, NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust. He is supported in part by the NIHR University College London Hospitals (UCLH) Biomedical Research Centre, London, UK. He has been a local principal investigator for a trial in MS funded by MS Canada. A local principal investigator for commercial trials funded by: Ionis and Roche; and has taken part in advisory boards/consultancy for Biogen, Janssen, Lucid, Merck, NervGen, Novartis and Roche. ET reports honoraria and support to attend educational meetings from Merck and Novartis, support to attend educational meetings from Biogen, and salary as a UK MS Register fellow from Biogen outside the submitted work KM reports honoraria for advisory boards/educational activities from Biogen, Roche, Merck, Teva, Novartis, Sanofi. ORP has received honoraria for advisory boards and/or educational activities from Biogen, Teva, Sanofi, Merck, Janssen, Novartis, and Roche HLF has received support from the Health Technology Assessment Programme (NIHR) and the UK MS Society. In the past 3 years, HLF has been a local principal investigator for trials in MS funded by Novartis, Roche and Biogen Idec and has taken part in advisory boards and consultancy for Merck, Teva, Biogen, and Novartis ADS received honoraria or consulting fees for participating in advisory boards and speaker fees from, Merck, Novartis, Roche NMD received honoraria or consulting fees for participating in advisory boards, speaker fees & educational support from Merck, Novartis, Roche, Biogen, Moderna and Sanofi-Genzyme, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: It has been observed that 5-8% of primary bariatric procedures result in inadequate treatment response, necessitating the need for revisional surgery. In this systematic review and meta-analysis, we aim to compare the effectiveness of single anastomosis duodeno-ileal bypass (SADI) and one anastomosis gastric bypass (OAGB) in addressing weight recurrence following sleeve gastrectomy., Methods: We systematically searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. Studies were considered eligible if they compared SADI with OAGB as revisional surgeries following sleeve gastrectomy., Results: Our search strategy yielded four articles with a total of 309 patients. Regarding weight loss at 1 year of follow-up, SADI was favorable based on excess weight loss percentage (EWL%) and total weight loss percentage (TWL%). At 2 years of follow-up, EWL% did not show a statistically significant difference between the two operations although TWL% was higher in SADI group. Regarding postoperative bile reflux, the OAGB group had a significantly higher incidence of biliary reflux (OR 0.15; 95% CI 0.04 to 0.53; P = 0.003). Patients enrolled in SADI did not develop anastomotic ulcers according to the four studies included in the analysis. In contrast, seven patients in the OAGB group did develop anastomotic ulcers, but the difference was not statistically significant (OR 0.23; 95% CI 0.05 to 1.10; P = 0.07)., Conclusion: ADI is a feasible procedure with a favorable outcome compared to OAGB as a revisional surgery following sleeve gastrectomy regarding weight loss at 1 year with a lower incidence of postoperative biliary reflux., Competing Interests: Declarations. Ethics Approval and Consent to Participate: This meta-analysis paper is based on previously published studies and does not involve any direct participation of human or animal subjects, and for this type of study, formal consent is not required. Conflict of Interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Quantified small bowel motility assessment using cine magnetic resonance enterography (MRE) has shown promise as a biomarker in adult inflammatory bowel disease. Whether quantified motility corresponds to treatment response in paediatric inflammatory bowel disease is unknown., Objective: To test whether changes in motility reflect response., Materials and Methods: Local ethics approval was granted for this single-institution, retrospective study. All children < 18 years with confirmed inflammatory bowel disease, who had more than one MRE between Jan 2011-Jan 2022, were included. Simplified MaRIA (sMaRIA) and motility index (quantified motility) at all terminal ileum and diseased non-terminal ileum segments were independently assessed by two radiologists each with ≥ 9 years' experience. Change in (Δ) motility index was compared to clinical (gastroenterologist physician's global assessment) and consensus radiological reference standard (response = decrease in sMaRIA of more than or equal to 2 points) in responders versus non-responders using the Mann-Whitney test. Sensitivity and specificity of Δ motility index more than zero were compared to decrease in sMaRIA of 2 or more points for identifying clinical response., Results: Of 64 children aged 5-16, 21 out of 64 (33%) were responders, 37 out of 64 (58%) were non-responders and 6 out of 64 (9%) had inactive disease according to clinical reference standard. Δ Motility index by both radiologists was higher in responders (+ 16, + 39) than non-responders (-43, -44), P = 0.04, P = 0.01 each radiologist, respectively. Motility index was more sensitive (57% versus 24%), but less specific (67% versus 93%) than sMaRIA in identifying clinical response., Conclusion: Motility index on cine MRE corresponds to clinical response, and is more sensitive at detecting response compared to sMaRIA in paediatric inflammatory bowel disease., Competing Interests: Declarations. Conflicts of interest: The authors of this manuscript declare relationships with the following companies: Motilent Ltd as follows: HEF – previous internship. SAT – Holds share options., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Respiratory syncytial virus (RSV) is a common cause of severe respiratory tract infection at the extremes of age and in vulnerable populations. However, it is difficult to predict the clinical course and most infants who develop severe disease have no pre-existing risk factors. With the recent licencing of RSV vaccines and monoclonal antibodies, it is important to identify high-risk individuals in order to prioritise those who will most benefit from prophylaxis. The immune response to RSV and the mechanisms by which the virus prevents the establishment of immunological memory have been extensively investigated but remain incompletely characterised. In animal models, beneficial and harmful immune responses have both been demonstrated. While only chimpanzees are fully permissive for human RSV replication, most research has been conducted in rodents, or in calves infected with bovine RSV. Based on these studies, components of innate and adaptive immune systems, cytokines, chemokines and metabolites, and specific genetic and transcriptomic signatures are identified as potential predictive indicators of RSV disease severity. These findings may inform the development of future human studies and contribute to the early identification of patients at high risk of severe infection. This narrative review summarises the factors involved in the immune response to RSV infection in these models and highlights the relationship between potential biomarkers and disease severity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jeroen Aerssens reports a relationship with Janssen Pharmaceutica NV that includes: employment. Jeroen Aerssens reports a relationship with Johnson and Johnson Ltd that includes: equity or stocks. Deniz Oner reports a relationship with Janssen Pharmaceutica NV that includes: employment. SBD has previously received honoraria from Sanofi for taking part in RSV advisory boards and has provided consultancy and/or investigator roles in relation to product development for Janssen, AstraZeneca, Pfizer, Moderna, Valneva, MSD, iLiAD, MundiPharma and Sanofi with fees paid to my institution. SBD is a member of the UK Department of Health and Social Care's (DHSC) Joint Committee on Vaccination and Immunisation (JCVI) RSV subcommittee and Medicines and Healthcare products Regulatory Agency's (MHRA) Paediatric Medicine Expert Advisory Group (PMEAG), but the reviews expressed herein do not necessarily represent those of DHSC, JCVI, MHRA or PMEAG. AJP is chair of DHSC's Joint Committee on Vaccination and Immunisation and has been funded on RSV vaccines by the EC IMI programme. RST has received honoraria for internal presentations at AstraZeneca, GSK and Sanofi. PJMO has consulted for GSK, Moderna, Janssen, Seqirus, Pfizer, AstraZeneca, Shionogi, BioNet Asia and Sanofi. DO was an employee of Janssen Pharmaceutica NV JA was an employee of Janssen Pharmaceutica NV and is a shareholder of Johnson & Johnson. DT, JP, CM, JM have no conflicts to declare. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The South West Thames Centre for Genomics implemented a wider diagnostic Next Generation Sequencing (NGS) gene panel for eligible cancer patients undergoing diagnostic testing whilst restricting data analysis and reporting for BRCA1/BRCA2/PALB2/CHEK2 1100delC only as per contemporaneous guidelines. This study investigated the cost-utility of reanalyzing existing diagnostic grade extended panel data for truncating germline pathogenic variants (GPVs) in known moderate risk cancer susceptibility genes (CSGs) and performing follow-up genetic testing for first-degree relatives if patients have an identified CSG allele., Methods: Reanalysis of existing NGS data was undertaken in 889 samples from cancer patients contemporaneously eligible through the NHS England National Genomic Test Directory (NGTD) codes R207 (ovarian) or R208 (breast) who had tested negative for BRCA1/BRCA2/PALB2 and CHEK2 1100delC founder variant. We modeled the cost and health outcomes for comparisons between: 1. Extending reanalysis to ATM truncating GPVs (partial extended testing) versus historical genetic testing, and 2. Extending analysis to ATM truncating GPV/BRIP1 truncating GPV/CHEK2 truncating GPV excluding CHEK2 1100delC/RAD51C truncating GPV/RAD51D truncating GPV (full extended testing) versus historical genetic testing., Results: For partial extended testing, the ICER compared with historical genetic testing was UK£49,671/QALY. For full extended testing, the ICER compared with historical genetic testing of historical genetic testing was UK£5716/QALY. The full extended testing remained cost-effective with a 30% increase in genetic testing cost., Conclusion: Where existing NGS data for cancer susceptibility genes is stored to diagnostic standard in UK laboratories, this study suggests it is cost-effective to analyze, report and clinically manage patients and relatives by extended analysis to an 8-gene panel compared to the historical genetic testing., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Unicompartmental knee replacements (UKRs) have become an increasingly attractive option for end-stage single-compartment knee osteoarthritis (OA). However, there remains controversy in patient selection. Natural language processing (NLP) is a form of artificial intelligence (AI). We aimed to determine whether general-purpose open-source natural language programs can make decisions regarding a patient's suitability for a total knee replacement (TKR) or a UKR and how confident AI NLP programs are in surgical decision making., Methods: We conducted a case-based cohort study using data from a separate study, where participants (73 surgeons and AI NLP programs) were presented with 32 fictitious clinical case scenarios that simulated patients with predominantly medial knee OA who would require surgery. Using the overall UKR/TKR judgments of the 73 experienced knee surgeons as the gold standard reference, we calculated the sensitivity, specificity, and positive predictive value of AI NLP programs to identify whether a patient should undergo UKR., Results: There was disagreement between the surgeons and ChatGPT in only five scenarios (15.6%). With the 73 surgeons' decision as the gold standard, the sensitivity of ChatGPT in determining whether a patient should undergo UKR was 0.91 (95% confidence interval (CI): 0.71 to 0.98). The positive predictive value for ChatGPT was 0.87 (95% CI: 0.72 to 0.94). ChatGPT was more confident in its UKR decision making (surgeon mean confidence = 1.7, ChatGPT mean confidence = 2.4)., Conclusions: It has been demonstrated that ChatGPT can make surgical decisions, and exceeded the confidence of experienced knee surgeons with substantial inter-rater agreement when deciding whether a patient was most appropriate for a UKR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 IMPERIAL COLLEGE LONDON. Published by Elsevier B.V. All rights reserved.)

Background/purpose: Amidst the emergence of new therapeutic options, traditional therapeutic plasmapheresis (TPE) used in diseases involving a toxic substance in the plasma, remains a viable alternative for cases of recalcitrant solar urticaria (SU). We emphasize the importance of documenting successful experience with repeated plasmapheresis to increase awareness amongst physicians and dermatologists regarding this effective treatment option., Material and Method: We reported a case of recalcitrant SU that had not responded to a combination of H1-antihistamines, immunosuppressants, omalizumab and intravenous immunoglobulin. We introduced serial TPE, which involved two consecutive days of procedures for each course was introduced. We detailed the regimen and highlighted the clinical and objective benefits observed with multiple treatments. Additionally, we compared this to other plasmapheresis regimens and their treatment responses previously reported for solar urticaria., Results: Our patient underwent serial TPE, totaling 42 procedures over five years. Following the last TPE session, phototesting showed a sustained prolongation of minimal urticating doses (MUDS), which exceeded the maximum tested doses across nearly all ultraviolet (UV) and visible light ranges, with the exception of the two short ultraviolet B (UVB) wavelengths. MUDs increased to 25 from 6 mj/cm2 at 307.5± 5nm, and to 500 from 15 mj/cm2 at 320 ± 10nm, before the initial TPE. In our review, we included five articles covering eight SU patients who received TPE. Of these, the five patients with positive intradermal tests responded particularly well immediately after treatment. However, the condition relapsed within two weeks in one patient and within two months in another. In contrast, the other three patients with negative intradermal tests, showed no significant benefits from the treatment. No serious side effects from TPE were reported amongst the patients., Conclusions: This review underscores the efficacy of serial plasmapheresis procedures in treating refractory cases of SU, high3lighting the robust results observed.

Schizophrenia presents significant diagnostic and treatment challenges, particularly in distinguishing between treatment-resistant (TRS) and non-treatment-resistant schizophrenia (NTRS). This cross-sectional study analyzed routine laboratory parameters as potential biomarkers to differentiate TRS, NTRS, and healthy individuals within a Qatari cohort. The study included 31 TRS and 38 NTRS patients diagnosed with schizophrenia, alongside 30 control subjects from the Qatar Biobank. Key measurements included complete blood count, lipid panel, HbA1c, and ferritin levels. Our findings indicated elevated body mass index (BMI) and triglyceride (TG) levels in both patient groups compared to controls. The NTRS group also showed higher HbA1c levels. Variations in inflammatory markers were noted, with the NTRS group exhibiting a higher platelet/lymphocyte ratio (PLR). Multivariate analysis highlighted significant differences in platelet count, mean platelet volume (MPV), TG, HbA1c, BMI, neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), and ferritin among the groups. Linear regression analysis revealed that MLR and clozapine treatment were significantly correlated with the severity of schizophrenia symptoms. The Random Forest model, a supervised machine learning algorithm, efficiently differentiated between cases and controls and between TRS and NTRS, with accuracies of 86.87 % and 88.41 %, respectively. However, removing PANSS scores notably decreased the model's diagnostic effectiveness. These results suggest that accessible peripheral laboratory parameters can serve as useful biomarkers for schizophrenia, potentially aiding in the early identification of TRS, enhancing personalized treatment strategies, and contributing to precision psychiatry. Future longitudinal studies are necessary to confirm these findings and further explore the role of inflammation in schizophrenia pathophysiology and treatment response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Legg-Calve-Perthes disease (LCPD) is a developmental disorder causing avascular necrosis of the femoral head in children, with long-term consequences that can extend into adulthood. Early diagnosis and management in primary care are crucial but challenging., Aim: This review aims to provide a concise overview of the presentation, differential diagnosis and management of LCPD, offering practical guidance for primary healthcare professionals., Method: Recent literature and expert opinions were reviewed to summarise the epidemiology, diagnosis and current management of LCPD., Results: LCPD commonly presents as a painless limp in children aged between 2 and 14 years, with the diagnosis based on the clinical features and radiographic abnormalities. Management is individualised and includes non-operative care to surgery, which attempts to correct anatomical abnormalities and therefore delay the onset of osteoarthritis. The review highlights the importance of primary care in early detection, appropriate referral and interim management., Conclusion: LCPD is a rare condition that can lead to long-term disability, affecting a child's physical, mental and social development, often presenting as a painless limp. Diagnosis typically involves plain radiographs, with MRI or hip joint arthrography providing additional details for management, which may include both non-surgical (eg, physiotherapy) and surgical options. Early recognition by primary care providers is crucial for timely referral to orthopaedic services, along with interim support through physiotherapy, pain management and access to mental health and educational resources., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To propose a standardized method of subjectively and objectively evaluating outcomes of sclerotherapy in treating low flow vascular malformations., Materials and Methods: Sixty-six patients with low flow vascular malformations (venous, lymphatic, or combined) were treated with percutaneous sclerotherapy using bleomycin, doxycycline, or sodium tetradecyl sulphate. Each lesion required between 2-5 sessions of sclerotherapy with 8-week intervals in between. The success of sclerotherapy was evaluated subjectively and objectively. The subjective response was based on the degree of patient satisfaction, by recording improvement of their symptoms and quality of life. The objective response was based on the changes in lesion characteristics after treatment, by recording changes in size, sonographic features, number of cystic spaces, and development of phleboliths., Results: 91% of our patients were satisfied with the treatment and reported improvement of symptoms and quality of life. Radiologically, 62% (41/66) of the patients had a reduction in lesion size, 77% (51/66) had a change in echogenicity, 84% (51/61) had a reduction in cystic spaces, and 68% (30/44) developed phleboliths. Of the patients reporting significant improvement, 94% displayed reduction in cystic spaces, 89% displayed change in the echogenicity and 71% showed changes in the size of the lesions, representing a linear correlation., Conclusion: Evaluating the outcomes of percutaneous sclerotherapy for treating vascular malformations is a recognized challenge. Creating a questionnaire with defined parameters to apply before and after treatment allows objective measurement of outcomes. This will enable improved treatment pathways and treatment choice for patients, informed consent, and enable outcome comparison with other centers., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: None., (© 2024. The Author(s).)

Background: Bleomycin ElectroScleroTherapy (BEST) is a new approach in the treatment of vascular malformations. After bleomycin is administered to the malformation, electric pulses are applied to the target area to enhance the effectiveness of bleomycin. The mode of action is comparable to the effect of electrochemotherapy on tumour vasculature. For the wider and safer use of BEST in the clinical treatment of low-flow vascular malformations, this Current Operating Procedure (COP) is being prepared. It is a proposal for the clinical standardisation of BEST using the Cliniporator ® as the electrical pulse generator with its associated electrodes. The electrical parameters considered in this protocol are those validated by the European Standard Operating Procedures for Electrochemotherapy (ESOPE) with the Cliniporator ® ., Conclusions: General requirements are proposed, and, depending on the type of lesion, local skills and the availability of radiological equipment, two technical approaches of BEST are described based on ultrasound guided intervention or combined ultrasound and fluoroscopic guided intervention., (© 2024 Tobian Muir et al., published by Sciendo.)

Introduction: medial patellofemoral ligament reconstruction (MPFLr) is a common surgical procedure for treating patellar instability. Grafts can be fixed to the femur using a bone-tunnel technique with an interference screw. However, this may lead to femoral tunnel enlargement (FTE) post-operatively. The aim of this study was to assess the correlation between time after MPFLr and FTE, to evaluate factors that might influence FTE and to determine if FTE can be reliably evaluated with plain radiographs., Methods: we conducted a single-surgeon series, retrospective review of 70 MPFLr (52 female; 18 male) between 2014 and 2022. We assessed change in femoral tunnel area compared with original tunnel area (TP0), on lateral radiographs at two time points. Time point one (TP1): mean 34 days (standard deviation (SD): 25); and Time Point 2 (TP2): mean 490 days (SD: 333). We analysed the relationship between surgical characteristics to FTE, and assessed inter- and intra-rater reliability of FTE., Results: tunnel area significantly increased from TP0 to TP1 and TP2 (p < 0.001). Mean percentage increase in cross-sectional tunnel area (CTA) between TP0 and TP1 was 113 % (SD: 49 %). Mean percentage increase in CTA between TP0 and TP2 was 139 % (SD: 64 %). There were 25 cases (36 %) of tunnel malposition. There was no significant correlation between distance from the isometric point and FTE at TP1 (r = 0.05; 95 % confidence intervals (CI): -0.19 to 0.29) or TP2 (r = 0.17: 95 % CI: -0.068 to 0.39). There were no other significant correlations with FTE. Inter-rater reliability for FTE at TP1 was moderate (Inter-Class Coefficient (ICC): 0.67; 95 % CI: 0.47 to 0.80; p < 0.001), with intra-rater reliability being excellent (ICC: 0.94; 95 % CI: 0.90 to 0.96; p < 0.001)., Conclusion: FTE after MPFLr is common. Plain radiographs can be used reliably to monitor tunnel enlargement in clinical practice., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024 All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: While people with type 2 diabetes (T2D) are more susceptible to infections, studies potentially underestimate the true burden of infection-related mortality since they rely on clinical coding systems primarily structured by body system, and by only focusing on underlying cause. This study examined cause-specific mortality in people with T2D compared to the general population during 2015-2019, focusing on infections., Methods: 509,403 people aged 41-90 years with T2D alive on 1/1/2015 in Clinical Practice Research Datalink were matched to 976,431 without diabetes on age, sex, and ethnicity. Recorded underlying cause of death was identified through national linked mortality data; infection-related deaths were counted across all ICD-10 (10th revision of the International Classification of Diseases) chapters, not just infection chapters A00-B99. All-cause and cause-specific hazard ratios (HR) for mortality during 2015-2019 compared people with T2D to people without diabetes and were estimated using Cox models adjusting for region. Additional analyses for sepsis related mortality considered the impact of including any mention of sepsis on the death certificate., Findings: 85,367/509,403 (16.8%) people with T2D died during 2015-2019 compared to 106,824/976,431 (10.9%) of people without diabetes of the same sex, age and ethnicity. All infections (11,128/85,367 = 13.0%) represented the third highest underlying cause of death among people with T2D after cardiovascular disease and cancer; a much higher contribution than counting only from specific infection chapters (1046/85,367 = 1.2%). The HR for people with T2D vs non-diabetes for all infection mortality (1.82, 95% CI 1.78-1.86) was higher than that estimated for all-cause (HR = 1.65, 95% CI 1.64-1.66). The estimated mortality rate associated with sepsis among people with T2D was highly dependent on whether any mention was included (2.2 per 1000 person-years) or only underlying cause (0.2 per 1000 person-years); but the HR for people with T2D vs non-diabetes was similar (any mention HR = 2.26, 95% CI 2.19-2.34 vs underlying cause only HR = 2.52, 95% CI 2.27-2.80)., Interpretation: People with T2D die from infections at a higher rate than similar people without diabetes, and the overall burden is greater than previously reported. Routine statistics concentrating on underlying cause of death may somewhat under-estimate the importance of infections as causes of death among people with T2D. These findings emphasise the potential importance of awareness, earlier diagnosis and treatment of infections to prevent premature deaths., Funding: National Institute for Health and Care Research., Competing Interests: NS has consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics outside the submitted work., (© 2024 The Author(s).)

Background: For female patients with Lynch syndrome (LS), endometrial cancer (EC) is often their first cancer diagnosis. A testing pathway of somatic tumour testing triage followed by germline mismatch repair (MMR) gene testing is an effective way of identifying the estimated 3% of EC caused by LS., Methods: A retrospective national population-based observational study was conducted using comprehensive national data collections of functional, somatic and germline MMR tests available via the English National Cancer Registration Dataset. For all EC diagnosed in 2019, the proportion tested, median time to test, yield of abnormal results and factors influencing testing pathway initiation were examined., Results: There was an immunohistochemistry (IHC) or microsatellite instability (MSI) test recorded for 17.8% (1408/7928) of patients diagnosed with EC in 2019. Proportions tested varied by Cancer Alliance and age. There was an MLH1 promoter hypermethylation test recorded for 43.1% (149/346) of patients with MLH1 protein IHC loss or MSI. Of patients with EC eligible from tumour-testing, 25% (26/104) had a germline MMR test recorded. Median time from cancer diagnosis to germline MMR test was 315 days (IQR 222-486)., Conclusion: This analysis highlights the regional variation in recorded testing, patient attrition, delays and missed opportunities to diagnose LS, providing an informative baseline for measuring the impact of the national guidance from the National Institute for Health and Care Excellence on universal reflex LS testing in EC, implemented in 2020., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Gene therapy has recently become a reality in the treatment of cardiovascular diseases. Strategies to modulate gene expression using antisense oligonucleotides or small interfering RNA are proving to be safe and effective in the clinic. Adeno-associated viral vector-based gene delivery and CRISPR-Cas9-based genome editing have emerged as efficient strategies for gene delivery and repair in humans. Overall, gene therapy holds the promise not only of expanding current treatment options, but also of intervening in previously untackled causal disease mechanisms with little side effects. This scientific statement provides a comprehensive overview of the various modalities of gene therapy used to treat heart failure and some of its risk factors, and their application in the clinical setting. It discusses specifically the possibilities of gene therapy for hereditary heart diseases and (non)-genetic heart failure. Furthermore, it addresses safety and clinical trial design issues and challenges for future regulatory strategies., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Health literacy is defined as an individual's ability to access, understand and use information to make informed decisions. This study aimed to assess health literacy levels and explore the relationship between health literacy and chronic obstructive pulmonary disease (COPD) severity. A cross-sectional study of health literacy in patients with COPD used the Health Literacy Questionnaire (HLQ) and the Medical Research Council Breathlessness Scale to assess COPD severity. HLQ domains of 'having sufficient information to manage my health', 'actively managing health', and 'understanding health information' scored most highly. Patients with the greatest COPD severity had lower scores in the domain 'having sufficient information to manage my health', but indicated an improved ability to appraise health information. Patients with increased COPD severity have greater self-reported skills in appraising health information, but they report reduced confidence in having sufficient information to manage their health. This study highlights the importance of considering health literacy levels, as this could be a barrier to successful self-management.

Trauma remains a significant cause of mortality and morbidity. Non-compressible torso haemorrhage is one of the key drives of these mortality data. Our contemporary management has focused on damage control resuscitation, with a focus on haemorrhage control, haemostatic resuscitation and permissive hypotension. The evidence for permissive hypotension lacks the robustness as other treatments, such as tranexamic acid. Despite this clinicians still target arbitrary systolic blood pressure cutoffs as both goals and ceilings of therapy. In this paper, we suggest that perhaps more consideration should be given to the diastolic blood pressure in bleeding trauma patients. The diastolic blood pressure is critical for coronary perfusion, and in turn the cardiac output responsible for cerebral blood flow. We suggest that a move to reframing resuscitation in terms of physiology may change the way that we resuscitate these patients and allow for more nuanced treatment strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

During pregnancy, the maternal cardiovascular (CV) system undergoes major haemodynamic alterations ensuring adequate placental perfusion and a healthy pregnancy course. Hypertensive disorders of pregnancy (HDP) occur in almost 10% of gestations and preeclampsia, a more severe form, in 3-4%. Women with HDP demonstrated impaired myocardial function, biventricular chamber dysfunction and adverse biventricular remodelling. Shortly after delivery, women who experienced HDP express increased risk of classic CV risk factors such as hypertension, renal disease, abnormal lipid profile, and diabetes. Within the first two decades following a HDP, women experience increased rates of heart failure, chronic hypertension, ischaemic heart and cerebral disease. The mechanism underlying the relationship between HDP in younger women and CV disease later in life could be explained by sharing pre-pregnancy CV risk factors or due to a direct impact of HDP on the maternal CV system conferring a state of increased susceptibility to future metabolic or haemodynamic insults. Racial disparities in CV risk and social determinants of health also play an important role in their remote CV risk. Although there is general agreement that women who suffered from HDP should undertake early CV screening to allow appropriate prevention and timely treatment, a screening and intervention protocol has not been standardized due to limited available evidence. In this review, we discuss why women with hypertensive pregnancy may be disproportionately affected by heart failure with preserved ejection fraction and how cardiac remodelling during or after pregnancy may influence its development., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Deep brain stimulation is a treatment for advanced Parkinson's disease and currently tuned to target motor symptoms during daytime. Parkinson's disease is associated with multiple nocturnal symptoms such as akinesia, insomnia, and sleep fragmentation, which may require adjustments of stimulation during sleep for best treatment outcome., Objectives: There is a need for a robust biomarker to guide stimulation titration across sleep stages. This study aimed to investigate whether evoked resonant neural activity (ERNA) is modulated by sleep., Methods: We recorded local field potentials from the subthalamic nucleus of four Parkinson's patients with externalized electrodes while applying single stimulation pulses to investigate the effect of sleep on ERNA., Results: We found that ERNA features change with wakefulness and sleep stages and are correlated with canonical frequency bands and heart rate., Conclusions: Given that ERNA modulates with sleep, it could be used as a robust marker for automatic stimulation titration during sleep. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Distal radius fractures (DRFs) are a common orthopaedic injury, often requiring surgical intervention. Routine postoperative radiographs are frequently obtained after surgical fixation to ensure adequacy of fixation and rule out early complications, yet their necessity remains unclear. Through this study, we tried to evaluate the impact of routine postoperative radiographs on the management of DRFs. The objective was to determine whether routine postoperative radiographs are necessary for the effective management of patients following surgical fixation of DRFs using volar locking plates., Methods: A review of 176 patients who underwent distal radius open reduction and internal fixation with volar locking plates at a UK district general hospital was conducted over a period of two years. Data on patient demographics, fracture characteristics, postoperative imaging new findings, and management changes were collected and analysed. The primary outcome measure was the rate of reoperation based on new findings in the routine postoperative radiographs., Results: Routine postoperative radiographs were obtained in all the cases, with only 1% (one patient) requiring reoperation based on the presence of new findings on the postoperative radiographs. Approximately 8% (12 patients) experienced a change in their management in the form of prolonged cast immobilization., Conclusion: Routine postoperative radiographs for DRFs with open reduction internal fixation may have limited impact on management decisions. The study highlights the potential overutilization of postoperative radiographs, leading to increased healthcare costs and radiation exposure. Based on the study's findings, a case-by-case approach, considering fracture type, associated injuries, and clinical indications, is advocated. Reducing the use of routine radiographs could save resources and reduce unnecessary radiation exposure without compromising patient care., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Audit Department, Buckinghamshire Healthcare NHS Trust issued approval n/a. This study was registered as an audit with the audit department at Buckinghamshire Healthcare NHS Trust and presented locally in the trauma and orthopaedic department monthly audit meeting. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tayyem et al.)

Competing Interests: Competing interests: None declared.

Background: Guidance and outcomes of coronary ischemia assessment (IA) in those with structural heart disease (SHD), presenting with monomorphic ventricular tachycardia (MMVT) is unclear., Objectives: To assess the impact of IA on arrhythmic and non-arrhythmic outcomes in those with SHD., Methods: Patients presenting with MMVT over a 6-year period to a tertiary center were retrospectively analyzed. Propensity score-matched analysis was performed comparing those undergoing IA to those who did not. The primary endpoint was a composite of VT recurrence, appropriate ICD therapy, heart failure hospitalization, and death. Secondary analysis of the individual components of the composite was performed. Kaplan-Meier, univariate and multivariate analysis was performed to compare the two groups and derive predictors of poor outcomes., Results: Two hundred and seventeen patients (57.6% ICM) were analyzed. 55.8% underwent IA. Following propensity score-matching, 120 patients remained. At 12 months, freedom from the primary endpoint was 68.3% of those undergoing IA versus 43.3% who did not, p < 0.001, multivariate HR 0.56 (0.34-0.92). This was driven by a reduction in all-cause mortality, with a 12-month survival of 98.3% in those undergoing IA versus 86.5% in those not undergoing IA (p < 0.01). Coronary intervention was associated with a significantly higher event-free 12-month survival compared to those who did not undergo intervention (82.4% vs 51.5%, respectively, p = 0.01)., Conclusions: Patients with SHD presenting MMVT who undergo an IA have significantly improved freedom from VT recurrence, appropriate ICD therapies, HF hospitalization, and death compared to those who do not, driven by a reduction in mortality., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Physical activity (PA) is established as a cornerstone of cardiovascular health, however, disparities in participation exist across sociocultural groups, which in turn affect cardiovascular outcomes. Evidence suggests that although the positive cardiovascular effects of exercise are consistent across populations, notable differences in the magnitude of these benefits exist for racial and ethnic minorities and the female sex. Women derive greater protection from PA compared with men, with reduced rates of sudden cardiac death. In this review we examine the complex interplay of race and/or ethnicity and sex on the cardiovascular benefits associated with PA and exercise, cardiovascular adaptations to exercise, risks of sudden cardiac death, and "excessive" volume of exercise. Understanding these factors is crucial for developing targeted interventions to promote cardiovascular health and offset disparities., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Stress echocardiography is widely used to assess patients with chest pain. The clinical value of a positive or negative test result to inform on likely longer-term outcomes when applied in real world practice across a healthcare system has not been previously reported., Methods and Results: 5503 patients recruited across 32 UK NHS hospitals between 2018 and 2022, participating in the EVAREST/BSE-NSTEP prospective cohort study, with data on medical outcomes up to 2023 available from NHS England were included in analysis. Stress echocardiography results were related to outcomes, including death, procedures, hospital admissions and relevant cardiovascular diagnoses, based on Kaplan-Meier analysis and Cox proportional hazard ratios. Median follow-up was 829 days (IQR 224-1434). A positive stress echocardiogram was associated with a greater risk of myocardial infarction (HR 2.71, 95% CI 1.73-4.24, P<0.001), and a composite endpoint of cardiac-related mortality and myocardial infarction (HR 2.03, 95% CI 1.41-2.93, P<0.001). Hazard ratios increased with ischaemic burden. A negative stress echocardiogram identified an event-free 'warranty period' of at least five years in patients with no prior history of coronary artery disease, and four years for those with disease., Conclusions: In real-world practice, the degree of myocardial ischaemia recorded by clinicians at stress echocardiography correctly categorises risk of future events over the next five years. Reporting a stress echocardiogram as negative correctly identifies patients with no greater than a background risk of cardiovascular events over a similar time period., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The recent pandemic was caused by the emergence of a new human pathogen, SARS-CoV-2. While the rapid development of many vaccines provided an end to the immediate crisis, there remains an urgent need to understand more about this new virus and what constitutes a beneficial immune response in terms of successful resolution of infection. Indeed, this is key for development of vaccines that provide long lasting protective immunity. The interferon lambda (IFNL) family of cytokines are produced early in response to infection and are generally considered anti-viral and beneficial. However, data regarding production of IFNL cytokines in coronavirus disease 2019 (COVID-19) patients is highly variable, and generally from underpowered studies. In this study, we measured all three IFNL1, IFNL2, and IFNL3 cytokines in plasma from a well characterized, large COVID-19 cohort (n = 399) that included good representation from patients with a more indolent disease progression, and hence a beneficial immune response. While all three cytokines were produced, they differed in both the frequency of expression in patients, and the levels produced. IFNL3 was produced in almost all patients but neither protein level nor IFNL3/IFNL4 single nucleotide polymorphisms were associated with clinical outcome. In contrast, both IFNL1 and IFNL2 levels were significantly lower, or absent, in plasma of patients that had a more severe disease outcome. These data are consistent with the concept that early IFNL1 and IFNL2 cytokine production is protective against SARS-CoV-2 infection., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology.)

The Association of British Neurologists last published guidelines on disease-modifying treatment (DMT) in multiple sclerosis (MS) in 2015. Since then, additional DMTs have been licensed and approved for prescribing within the National Health Service for relapsing-remitting MS, early primary progressive MS and active secondary progressive MS. This updated guidance provides a consensus-based approach to using DMTs. We provide recommendations for eligibility, starting, monitoring, switching and stopping of DMTs; pregnancy; equitable access to DMT; autologous haemopoietic stem-cell transplantation; and use of generics. We highlight best practice where it exists and discuss future priorities., Competing Interests: Competing interests: TA has received honoraria or consulting fees for participating in advisory boards related to trial steering committees and data and safety monitoring committees, speaker fees and research grants from Janssen, Merck, Novartis, Roche and Sanofi-Genzyme. She holds a research grant from Merck Serono towards a study looking longer term outcomes with Cladribine. TA is funded by the NIHR on a 60-month SCRPA award (2024–2029) ref NIHR304536. TR twitter/X handle is @tarunyaarun. HLF has received research support from the Health Technology Assessment Programme (NIHR), EME Programme, the UK MS Society and the Horne Family Foundation. In the past 3 years, HLF has been a local principal investigator for trials in MS funded by Novartis, Roche and Biogen Idec and has taken part in advisory boards and consultancy for Merck, Novartis and Roche. In the last 5 years, SML has received speaker fees from Merck Serono and Novartis, and sponsorship to attend educational meetings from Roche and Sanofi-Genzyme. SJ has served as a Chief/Principal Investigator for Clinical Trials or has been an international advisory board member for Alexion, Alnylam, Argenx, Immunovant, Janssen, Merck, Novartis, Regeneron and UCB Pharma; is currently an expert panel member of the Myasthenia Gravis consortium for Argenx; and has received speaker fees from Eisai, Terumo BCT and UCB Pharmaceuticals. RD received honoraria for speaking and/or travelling from Biogen, Merck, Teva, Roche, Novartis, Janssen and Sanofi. She served on advisory boards for Roche, Biogen, Janssen, Novartis, Sandoz and Merck. She has received grant support from Biogen, Merck, Celgene. RD twitter is @drruthdobson. Disclosures: JH, or affiliated institutions have received either consulting fees, honoraria, support to attend meetings, clinical service support or research support from Biogen, F. Hoffmann-La Roche, Sanofi Genzyme, Merck Serono, Novartis, Oxford Health Policy Forum. KM: no competing interests relevant to the guidelines (and no twitter account). OC has received honoraria or consultation fees from Neurology Journal, Novartis, Biogen, Merck. JP has received support for scientific meetings and honorariums for advisory work from Merck Serono, Novartis, Chugai, Alexion, Roche, Medimmune, Amgen, Vitaccess, UCB, Mitsubishi, Amplo, Janssen. Grants from Alexion, Argenx, Clene, Roche, Medimmune, Amplobio technology. Patent ref P37347WO and licence agreement Numares multimarker MS diagnostics Shares in AstraZenica. Her group has been awarded an ECTRIMS fellowship and a Sumaira Foundation grant to start later this year. A Charcot fellow worked in Oxford 2019–2021. She acknowledges partial funding to the trust by highly specialised services NHS England. She is on the medical advisory boards of the Sumaira Foundation and MOG project charities, is a member of the Guthy Jackon Foundation Charity and is on the Board of the European Charcot Foundation and the steering committee of MAGNIMS and the UK NHSE IVIG Committee and chairman of the NHSE neuroimmunology patient pathway and ECTRIMS Council member on the educational committee since June 2023. On the ABN advisory groups for MS and neuroinflammation and neuromuscular diseases. AD: no competing interests. PAM reports no conflict of interest. He discloses travel support and speaker honoraria from unrestricted educational activities organised by Novartis, Bayer Health Care, Bayer Pharma, Biogen Idec, Merck-Serono and Sanofi Aventis. He discloses consulting to Magenta Therapeutics, Jasper Therapeutics and Cellerys AG. He reports grants from NIHR-EME and the Benaroya Research Institute and discloses consulting to Magenta Therapeutics, Jasper Therapeutics and Cellerys AG. WR in the last 5 years has received speaking fees and/or served on advisory boards from Biogen, Roche, Novartis, Janssen, Merck Serono, Sandoz, Sanofi and Celgene., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/objectives: An air-bone gap (ABG) on audiometry is usually secondary to a conductive hearing loss. However, persistent and repeatable ABGs on audiometry in the absence of external or middle ear pathology is thought to arise from inner ear disorders including Meniere's Disease (MD). In this paper, we aim to showcase this interesting finding occurring in MD with an associated literature review., Methods: Using retrospective review and analysis of case notes, we describe eight cases of persistent ABG on audiometry in MD. All other causes for the ABG were explored and excluded with the aid of objective audiological testing., Results: ABG can occur in a small sub-set of the MD population. In our case series, the ABG was typically found to affect the low frequencies. Higher frequencies appear to be spared. However, a detailed history, examination and battery of objective tests are required to ensure that all other causes of the ABG are reliably considered and excluded prior to attributing it to the inner ear. The finding of an ABG in MD may be dependent on the stage of the disease. Further research is required to determine the underlying cause of the ABG and its potential applications to help guide treatment.

Aims: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are prevalent comorbidities associated with significant morbidity/mortality. We assessed prevalence of, patient profiles and outcomes associated with COPD across the ejection fraction (EF) spectrum., Methods: HF patients enrolled in the Swedish HF registry between 2005 and 2021 were considered. Multivariable logistic regression models were fitted to assess patient characteristics independently associated with COPD and Cox regression models for investigating the associations between COPD and outcomes, that is, morbidity/mortality., Results: Among 97 904 HF patients, COPD prevalence was 13%, highest in HF with preserved EF [HFpEF: 16%, HF with mildly reduced EF (HFmrEF): 12%, HF with reduced EF (HFrEF): 11%]. Key patient characteristics independently associated with a diagnosis of COPD included higher EF, female sex, smoking, obstructive sleep disorder, peripheral artery disease, a lower educational level, more severe HF, more likely mineralocorticoid receptor antagonist and diuretic use but less likely use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin-receptor-neprilysin inhibitors (not in HFrEF), beta-blockers, HF device therapies, and follow-up in HF nurse-led clinics. COPD was independently associated with a 15% higher risk of cardiovascular (CV) death/HF hospitalization [hazard ratio: 1.15 (95% confidence interval: 1.11-1.18)], CV death, non-CV death, all-cause death and HF hospitalizations, regardless of EF., Conclusions: COPD was present in every eight patient with HF, and more common with preserved EF. Patients with COPD had more severe HF, heavier comorbidity burden and worse morbidity/mortality regardless of EF. Our results call for improved diagnostic and management strategies in patients with HF and COPD., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Obesity and underweight are a growing health problem worldwide and a challenge for clinicians concerning antithrombotic therapy, due to the associated risks of thrombosis and/or bleeding. This clinical consensus statement updates a previous one published in 2018, by reviewing the most recent evidence on antithrombotic drugs based on body size categories according to the World Health Organization classification. The document focuses mostly on individuals at the extremes of body weight, i.e. underweight and moderate-to-morbid obesity, who require antithrombotic drugs, according to current guidelines, for the treatment or prevention of cardiovascular diseases or venous thromboembolism. Managing antithrombotic therapy or thromboprophylaxis in these individuals is challenging, due to profound changes in body composition, metabolism and organ function, and altered drug pharmacokinetics and pharmacodynamics, as well as weak or no evidence from clinical trials. The document also includes artificial intelligence simulations derived from in silico pharmacokinetic/pharmacodynamic models, which can mimic the pharmacokinetic changes and help identify optimal regimens of antithrombotic drugs for severely underweight or severely obese individuals. Further, bariatric surgery in morbidly obese subjects is frequently performed worldwide. Bariatric surgery causes specific and additional changes in metabolism and gastrointestinal anatomy, depending on the type of the procedure, which can also impact the pharmacokinetics of antithrombotic drugs and their management. Based on existing literature, the document provides consensus statements on optimizing antithrombotic drug management for underweight and all classes of obese patients, while highlighting the current gaps in knowledge in these complex clinical settings, which require personalized medicine and precision pharmacology., (© 2024 the European Society of Cardiology.)

A female patient in her 70s presented with mild slurred speech. Clinical assessment revealed only minor dysarthria. A stroke protocol CT study was performed comprising a non-contrast CT head, CT angiogram (CTA) and CT perfusion (CTP) imaging. Despite a normal non-contrast CT head, CTP imaging demonstrated a large left anterior circulation territory abnormality compatible with core infarct. The CTA displayed absent left middle cerebral artery opacification and an abnormal pattern of thalamic and posterior fossa structure enhancement. Following a neuroradiology review, it was identified that the contrast bolus had been administered into the right brachial artery causing direct arterial opacification of the right vertebral/carotid arteries and their distal branches. No contrast was present in the left carotids or distal left intracranial anterior circulation giving the false impression of a large vessel occlusion. The patient was subsequently discharged without receiving inappropriate reperfusion therapy. This case highlights the role of technical factors influencing CT interpretation, particularly when performed by artificial intelligence/automated analysis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)