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Pembrolizumab has received approval in the UK as first-line monotherapy for recurrent and/or metastatic HNSCC (R/M HNSCC) following the results of the KEYNOTE-048 trial, which demonstrated a longer overall survival (OS) in comparison to the EXTREME chemotherapy regimen in patients with a combined positive score (CPS) ≥1. In this article, we provide retrospective real-world data on the role of pembrolizumab monotherapy as first-line systemic therapy for HNSCC across 18 centers in the UK from March 20, 2020 to May 31, 2021. 211 patients were included, and in the efficacy analysis, the objective response rate (ORR) was 24.7%, the median progression-free survival (PFS) was 4.8 months (95% confidence interval [CI]: 3.6-6.1), and the median OS was 10.8 months (95% CI 9.0-12.5). Pembrolizumab monotherapy was well tolerated, with 18 patients having to stop treatment owing to immune-related adverse events (irAEs). 53 patients proceeded to second-line treatment with a median PFS2 of 10.2 months (95% CI: 8.8-11.5). Moreover, patients with documented irAEs had a statistically significant longer median PFS (11.3 vs. 3.3 months; log-rank p value = <.001) and median OS (18.8 vs. 8.9 months; log-rank p value <.001). The efficacy and safety of pembrolizumab first-line monotherapy for HNSCC has been validated using real-world data., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Myocardial fibrosis (MF) forms part of the arrhythmic substrate for ventricular arrhythmias (VAs)., Objectives: This study sought to determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmias in patients with nonischemic cardiomyopathy (NICM)., Methods: Patients with NICM in a derivation cohort (n = 866) and a validation cohort (n = 848) underwent quantification of TF and GZF. The primary composite endpoint was sudden cardiac death or VAs (ventricular fibrillation or ventricular tachycardia)., Results: The primary endpoint was met by 52 of 866 (6.0%) patients in the derivation cohort (median follow-up: 7.5 years; Q1-Q3: 5.2-9.3 years). In competing-risks analyses, MF on visual assessment (MF VA ) predicted the primary endpoint (HR: 5.83; 95% CI: 3.15-10.8). Quantified MF measures permitted categorization into 3 risk groups: a TF of >0 g and ≤10 g was associated with an intermediate risk (HR: 4.03; 95% CI: 1.99-8.16), and a TF of >10 g was associated with the highest risk (HR: 9.17; 95% CI: 4.64-18.1) compared to patients with no MF VA (lowest risk). Similar trends were observed in the validation cohort. Categorization into these 3 risk groups was achievable using TF or GZF in combination or in isolation. In contrast, LVEF of <35% was a poor predictor of the primary endpoint (validation cohort HR: 1.99; 95% CI: 0.99-4.01)., Conclusions: MF VA is a strong predictor of sudden cardiac death and VAs in NICM. TF and GZF mass added incremental value to MF VA . In contrast, LVEF was a poor discriminator of arrhythmic risk., Competing Interests: Funding Support and Author Disclosures This work was supported by a National Heart and Lung Institute Foundation grant awarded to Drs Prasad, Hammersley, Jones, Tayal, and Halliday as well as a British Society for Heart Failure Research Fellowship and a British Heart Foundation Clinical Research Training Fellowship (FS/CRTF/23/24444) awarded to Dr Mach. Additionally, the study was supported by Rosetrees Trust, the Alexander Jansons Myocarditis UK Foundation, a BHF Intermediate Clinical Research Fellowship awarded to Dr Halliday (FS/ICRF/21/26019), and an MRC Fellowship awarded to Dr Tayal (MRC MR/W023830/1). This work was additionally supported by The British Heart Foundation (RE/18/4/34215; SP/17/11/32885), Royston Centre for Cardiomyopathy Research, Sir Jules Thorn Charitable Trust (21JTA), Medical Research Council (UK), National Institute for Health Research, Royal Brompton Cardiovascular Biomedical Research Unit, and National Institute for Health Research Imperial College Biomedical Research Centre. Medtronic Plc provided funding for the salary as a research fellow for Dr Zegard. Boston Scientific provided funding for Dr Qiu (statistician). These companies had no participation whatsoever in the study. The views expressed in this work are those of the authors and not necessarily those of the funders. Dr Hammersley has received research funding from Siemens. Dr Baruah is an employee of AstraZeneca. Dr Guha has received honoraria from Bayer, Pfizer, Novartis, AstraZeneca, and Servier Laboratories; has received an unrestricted educational grant from Biotronik; and has received travel assistance from Abbott Laboratories, Medtronic, Biotronik, and Boston Scientific. Dr Ware has acted as a consultant for MyoKardia, Foresite Labs, Pfizer, and Health Lumen. Dr Halliday has received honoraria from AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Forecasting the need for Renal Replacement Therapy (RRT) in intensive care units (ICUs) at an early stage can enhance patient outcomes and optimize resource allocation. The study aimed to develop a model for early prediction of Renal Replacement Therapy (RRT) requirement within 24 hours of ICU admission, utilizing machine learning techniques and SHapley Additive exPlanations (SHAP). It assessed various models including Random Forest (RF), Neural Network (NN), and XGBoost, using data from 34,000 ICU admissions. XGBoost showed superior performance in terms of AUPRC, while RF performed better in AUC-ROC. Results were consistent before and after Principal Component Analysis (PCA) and feature evaluation analysis. The top 10 feature models outperformed the PCA model while using fewer inputs. These findings suggest the potential utility of the developed models in accurately predicting RRT requirement within 24 hours of ICU admission, aiding in efficient critical care delivery.

Background: The airway microbiome in severe asthma has not been characterised at species-level by metagenomic sequencing, nor have the relationships between specific species and mucosal immune responses in 'type-2 low', neutrophilic asthma been defined. We performed an integrated species-level metagenomic data with inflammatory mediators to characterise prevalence of dominant potentially pathogenic organisms and host immune responses., Methods: Sputum and nasal lavage samples were analysed using long-read metagenomic sequencing with Nanopore and qPCR in two cross-sectional adult severe asthma cohorts, Wessex (n = 66) and Oxford (n = 30). We integrated species-level data with clinical parameters and 39 selected airway proteins measured by immunoassay and O-link., Results: The sputum microbiome in health and mild asthma displayed comparable microbial diversity. By contrast, 23% (19/81) of severe asthma microbiomes were dominated by a single respiratory pathogen, namely H. influenzae (n = 10), M. catarrhalis (n = 4), S. pneumoniae (n = 4) and P. aeruginosa (n = 1). Neutrophilic asthma was associated with H. influenzae, M. catarrhalis, S. pneumoniae and T. whipplei with elevated type-1 cytokines and proteases; eosinophilic asthma with higher M. catarrhalis, but lower H. influenzae, and S. pneumoniae abundance. H. influenzae load correlated with Eosinophil Cationic Protein, elastase and IL-10. R. mucilaginosa associated positively with IL-6 and negatively with FGF. Bayesian network analysis also revealed close and distinct relationships of H. influenzae and M. catarrhalis with type-1 airway inflammation. The microbiomes and cytokine milieu were distinct between upper and lower airways., Conclusions: This species-level integrated analysis reveals central, but distinct associations between potentially pathogenic bacteria and airways inflammation in severe asthma., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objective/background: Various anastomotic and reconstruction techniques are used for minimally invasive total (miTG) and distal gastrectomy (miDG). Their effects on postoperative morbidity have not been extensively studied., Methods: MiTG and miDG patients were selected from 9356 oncological gastrectomies performed 2017-2021 in 44 centers. Endpoints included anastomotic leakage (AL) rate and postoperative morbidity tested by multivariable analysis., Results: Three major anastomotic techniques (circular stapled (CS); linear stapled (LS); hand sewn (HS)), and three major bowel reconstruction types (Roux (RX); Billroth I (BI); Billroth II (BII)) were identified in miTG (n=878) and miDG (n=3334). Postoperative complications including AL (5.2% vs. 1.1%), overall (28.7% vs. 16.3%) and major morbidity (15.7% vs. 8.2%), as well as 90-day mortality (1.6% vs. 0.5%) were higher after miTG compared with miDG. After miTG, AL rate was higher after CS (4.3%) and HS (7.9%) compared with LS (3.4%). Similarly, major complications (LS: 9.7%, CS: 16.2%, HS: 12.7%) were lowest after LS. Multivariate analysis confirmed anastomotic technique as predictive factor for AL, overall and major complications. In miDG, AL rate (BI: 1.4%, BII 0.8%, RX 1.2%), overall (BI: 14.5%, BII: 15.0%, RX: 18.7%,) and major morbidity (BI: 7.9%, BII: 9.1%, RX: 7.2%), and mortality (BI: 0%, BII: 0.1%, RY: 1.1%%) were not affected by bowel reconstruction., Conclusion: In oncologically suitable situations, miDG should be preferred to miTG, as postoperative morbidity is significantly lower. LS should be a preferred anastomotic technique for miTG in Western Centers. Conversely, bowel reconstruction in DG may be chosen according to surgeon's preference., Competing Interests: Sources of Funding/Support/Conflicts of Interest: The authors declare no conflict of interest. No third-party financial funds or materials were accepted or necessary for execution of this research project., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Type 2 diabetes is a common chronic disease that continues to increase in prevalence globally and is a major healthcare burden. Diabetes and hypertension frequently occur concurrently, and the use of antihypertensive agents is common in diabetic patients. One antihypertensive agent, verapamil, has tentatively shown potentially positive effects on glycemic control in assorted pre-clinical models., Aim: To evaluate the effect of verapamil on glycemic control in hypertensive type 2 diabetic patients., Methods: Type 2 diabetic hypertensive patients were recruited from King Fahad Medical City, Riyadh, KSA, to receive oral verapamil therapy. Blood pressure and glycometabolic parameters, including fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), C-peptide, and homeostatic model assessment insulin resistance (HOMA-IR), were monitored at baseline and after 6 months of verapamil therapy., Results: Thirty-five patients (16 male, 19 female) with a mean age of 57.2 years were recruited. The use of verapamil was associated with non-significant decreases in HbA1c, FPG, C-peptide, and HOMA-IR. However, a sub-group of 17 participants showed a decrease in HbA1c that was ≥0.5%. Univariate logistic regression showed that baseline BMI, HOMA-IR, and C-peptide were significantly (P < 0.05) associated with HbA1c reductions of ≥0.5%., Conclusion: Verapamil is metabolically neutral and allows the stabilization of glycometabolic parameters in type 2 diabetic individuals. Additional research exploring the mechanism behind the variable response to verapamil therapy is warranted., (Copyright © 2024 Copyright: © 2024 Nigerian Journal of Clinical Practice.)

Favourable outcomes with CPX-351 versus conventional 7 + 3 were demonstrated in the pivotal phase III trial in adults aged 60-75 years with newly diagnosed, highrisk/secondary acute myeloid leukaemia (AML). As a complement to the clinical trial and to address important data gaps, the CPX-351 Real-World Effectiveness and SafeTy (CREST-UK; NCT05169307) study evaluated the use of CPX-351 in routine clinical practice in the UK, in 147 patients with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. Best response of complete remission or complete remission with incomplete platelet or neutrophil recovery was achieved by 53% of evaluable patients. Kaplan-Meier median overall survival (OS) was 12.8 months (95% confidence interval 9.2-15.3). Fifty (34%) patients proceeded to haematopoietic cell transplantation (HCT); median OS landmarked from the HCT date was not reached. There were no new safety concerns with CPX-351 identified in CREST-UK. Patients treated with CPX-351 in the outpatient setting spent an average of 24.4, 16.7, 28.2, and 27.7 fewer days on the ward compared with inpatients during first induction, second induction, first consolidation, and second consolidation, respectively. The results from CREST-UK provide valuable insights into the effectiveness, safety, and outpatient delivery of CPX-351 in routine clinical practice in the UK., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Hemostatic powders are used as second-line treatment in acute gastrointestinal (GI) bleeding (AGIB). Increasing evidence supports the use of TC-325 as monotherapy in specific scenarios. This prospective, multicenter study evaluated the performance of TC-325 as monotherapy for AGIB., Methods: Eighteen centers across Europe and USA contributed to a registry between 2016 and 2022. Adults with AGIB were eligible, unless TC-325 was part of combined hemostasis. The primary endpoint was immediate hemostasis. Secondary outcomes were rebleeding and mortality. Associations with risk factors were investigated (statistical significance at P≤0.05)., Results: One hundred ninety patients were included (age 51-81 years, male: female 2:1), with peptic ulcer (n=48), upper GI malignancy (n=79), post-endoscopic treatment hemorrhage (n=37), and lower GI lesions (n=26). The primary outcome was recorded in 96.3% (95% confidence interval [CI]: 92.6-98.5) with rebleeding in 17.4% (95%CI 11.9-24.1); 9.9% (95%CI 5.8-15.6) died within 7 days, and 21.7% (95%CI 15.6-28.9) within 30 days. Regarding peptic ulcer, immediate hemostasis was achieved in 88% (95%CI 75-95), while 26% (95%CI 13-43) rebled. Higher ASA score was associated with mortality (OR 23.5, 95%CI 1.60-345; P=0.02). Immediate hemostasis was achieved in 100% of cases with malignancy and post-intervention bleeding, with rebleeding in 17% and 3.1%, respectively. Twenty-six patients received TC-325 for lower GI bleeding, and in all but one the primary outcome was achieved., Conclusions: TC-325 monotherapy is safe and effective, especially in malignancy or post-endoscopic intervention bleeding. In patients with peptic ulcer, it could be helpful when the primary treatment is unfeasible, as bridge to definite therapy., Competing Interests: Conflict of Interest: Rehan J. Haidry declares: Pentax Medical, Apollo Endosurgery, Medtronic, Odin Vision, Cook Endoscopy, Fractyl Limited, Endogastric Solutions; Enrique Rodríguez de Santiago declares: Olympus, Norgine and Apollo Endosurgery (Educational activities) Adacyte therapeuthics (Advisory); Seth A. Gross declares: Cook, Medtronic, Olympus, Microtech. The other authors have nothing to declare, (Copyright: © 2024 Hellenic Society of Gastroenterology.)

This study aimed to use a musculoskeletal model to predict changes in spinal moments following simulated breast surgery. A female full body musculoskeletal model with a fully articulated thoracolumbar spine and independent moveable breast segments was customised for this study. Key findings suggest that the simulated removal of breast tissue (750 g to 1501 g) can reduce the magnitude of lumbar spine extensor moments by >0.05 Nm/kg during walking and jogging. A customised female whole-body musculoskeletal model is capable of providing a first approximation of changes in spinal loading following simulated breast surgery.

Early kidney injury may be detected by urinary markers, such as beta-2 microglobulin (B2M), tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), kidney injury molecule-1 (KIM-1) and/or neutrophil gelatinase-associated lipocalin (NGAL). Of these biomarkers information on pathophysiology and reference ranges in both healthy and diseased populations are scarce. Differences in urinary levels of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL were compared 24 h before and after nephrectomy in 38 living kidney donors from the REnal Protection Against Ischaemia-Reperfusion in transplantation study. Linear regression was used to assess the relation between baseline biomarker concentration and kidney function 1 year after nephrectomy. Median levels of urinary creatinine and creatinine standardized B2M, TIMP-2, IGFBP7, KIM-1, NGAL, and albumin 24 h before nephrectomy in donors were 9.4 mmol/L, 14 μg/mmol, 16 pmol/mmol, 99 pmol/mmol, 63 ng/mmol, 1390 ng/mmol and 0.7 mg/mmol, with median differences 24 h after nephrectomy of - 0.9, + 1906, - 7.1, - 38.3, - 6.9, + 2378 and + 1.2, respectively. The change of donor eGFR after 12 months per SD increment at baseline of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL was: - 1.1, - 2.3, - 0.7, - 1.6 and - 2.8, respectively. Urinary TIMP-2 and IGFBP7 excretion halved after nephrectomy, similar to urinary creatinine, suggesting these markers predominantly reflect glomerular filtration. B2M and NGAL excretion increased significantly, similar to albumin, indicating decreased proximal tubular reabsorption following nephrectomy. KIM-1 did not change considerably after nephrectomy. Even though none of these biomarkers showed a strong relation with long-term donor eGFR, these results provide valuable insight into the pathophysiology of these urinary biomarkers., (© 2024. The Author(s).)

Objectives: To evaluate the additional diagnostic benefit of diffusion weighted imaging (DWI) and contrast enhanced (CE) images during MR enterography (MRE) of Crohn's disease., Methods: Datasets from 73 patients (mean age 32; 40 male) (28 new-diagnosis, 45 relapsed) were read independently by two radiologists selected from a pool of 13. Radiologists interpreted datasets using three sequential sequence blocks: (1) T2 weighted and steady state free precession gradient echo (SSFP) images alone (T2^); (2) T2 weighted and SSFP images with DWI (T2 + DWI^) and; (3) T2 weighted images, SSFP, DWI and post-contrast enhanced (CE) T1 images (T2 + DWI + CE^), documenting presence, location, and activity of small bowel disease. For each sequence block, sensitivity and specificity (readers combined) was calculated against an outcome-based construct reference standard., Results: 59/73 patients had small bowel disease. Per-patient sensitivity for disease detection was essentially identical (80 % [95 % CI 72, 86], 81 % [73,87], and 79 % [71,86] for T2^, T2 + DWI^and T2 + DWI + CE^respectively). Specificity was identical (82 % [64 to 92]). Per patient sensitivity for disease extent was 56 % (47,65), 56 % (47,65) and 52 % (43 to 61) respectively, and specificity was 82 % (64 to 92) for all blocks. Sensitivity for active disease was 97 % (90,99), 97 % (90,99) and 98 % (92,99), and specificity was also comparable between all sequence combination reads. Results were consistent across segments and newly diagnosed/relapse patients., Conclusion: There is no additional diagnostic benefit of adding either DWI or CE to T2 FSE and SSFP sequences for evaluating small bowel Crohn's disease, suggesting MRE protocols can be simplified safely., 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. STaylor has shares in Motilent, research support from Takeda and research consultant to Aztrazeneca., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Barrett's oesophagus is the only known precursor to oesophageal adenocarcinoma, a cancer with very poor prognosis. The main risk factors for Barrett's oesophagus are a history of gastro-oesophageal acid reflux symptoms and obesity. Men, smokers and those with a family history are also at increased risk. Progression from Barrett's oesophagus to cancer occurs via an intermediate stage, known as dysplasia. However, dysplasia and early cancer usually develop without any clinical signs, often in individuals whose symptoms are well controlled by acid suppressant medications; therefore, endoscopic surveillance is recommended to allow for early diagnosis and timely clinical intervention. Individuals with Barrett's oesophagus need to be fully informed about the implications of this diagnosis and the benefits and risks of monitoring strategies. Pharmacological treatments are recommended for control of symptoms, but not for chemoprevention. Dysplasia and stage 1 oesophageal adenocarcinoma have excellent prognoses, since they can be cured with endoscopic or surgical therapies. Endoscopic resection is the most accurate staging technique for early Barrett's-related oesophageal adenocarcinoma. Endoscopic ablation is effective and indicated to eradicate Barrett's oesophagus in patients with dysplasia. Future research should focus on improved accuracy for dysplasia detection via new technologies and providing more robust evidence to support pathways for follow-up and treatment., Competing Interests: Competing interests: MdP participated in the BEST3 screening trial and received consultant fees from Medtronic. JNP was chair of the trial Steering committee of the AspECT trial. NJT participated in the AspECT trial., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Recent discourse around the implementation of medical associate professions (MAPs) into medical specialties has proven divisive and controversial. These roles could benefit oral and maxillofacial surgery (OMFS) departments and grant trainees increased operating experience, but their implementation could prove detrimental to training. We discuss the potential impact in OMFS., (Copyright © 2023 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: In liver cirrhosis, acute variceal bleeding (AVB) is associated with a 1-year mortality rate of up to 40%. Data on early or pre-emptive transjugular intrahepatic portosystemic stent-shunt (TIPSS) in AVB is inconclusive and may not reflect current management strategies. Randomised controlled trial of EArly transjugular intrahepatiC porTosystemic stent-shunt in AVB (REACT-AVB) aims to investigate the clinical and cost-effectiveness of early TIPSS in patients with cirrhosis and AVB after initial bleeding control., Methods and Analysis: REACT-AVB is a multicentre, randomised controlled, open-label, superiority, two-arm, parallel-group trial with an internal pilot. The two interventions allocated randomly 1:1 are early TIPSS within 4 days of diagnostic endoscopy or secondary prophylaxis with endoscopic therapy in combination with non-selective beta blockers. Patients aged ≥18 years with cirrhosis and Child-Pugh Score 7-13 presenting with AVB with endoscopic haemostasis are eligible for inclusion. The primary outcome is transplant-free survival at 1 year post randomisation. Secondary endpoints include transplant-free survival at 6 weeks, rebleeding, serious adverse events, other complications of cirrhosis, Child-Pugh and Model For End-Stage Liver Disease (MELD) scores at 6 and 12 months, health-related quality of life, use of healthcare resources, cost-effectiveness and use of cross-over therapies. The sample size is 294 patients over a 4-year recruitment period, across 30 hospitals in the UK., Ethics and Dissemination: Research ethics committee of National Health Service has approved REACT-AVB (reference number: 23/WM/0085). The results will be submitted for publication in a peer-reviewed journal. A lay summary will also be emailed or posted to participants before publication., Trial Registration Number: ISRCTN85274829; protocol version 3.0, 1 July 2023., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Aims: To compare the association between measures of left atrial (LA) structure and function, derived from cardiovascular magnetic resonance (CMR), with cardiovascular (CV) death or non-fatal heart failure (HF) events in patients with non-ischaemic dilated cardiomyopathy (DCM)., Methods and Results: CMR studies of 580 prospectively recruited patients with DCM in sinus rhythm (median age 54 [interquartile range 44-64] years, 61% men, median LVEF 42% [30-51%]) were analysed for measures of LA structure (left atrial maximum volume index [LAVImax], left atrial minimum volume index [LAVImin]) and function (left atrial emptying fraction [LAEF], left atrial reservoir strain [LARS], left atrial conduit strain [LACS] and left atrial booster strain [LABS]). Over median follow-up of 7.4 years, 103 patients (18%) met the primary endpoint. Apart from LACS, each measure of LA structure and function was associated with the primary endpoint after adjusting for other important prognostic variables. The addition of each LA metric to a baseline model containing the same important prognostic covariates improved model discrimination, with LAVImin providing the greatest improvement (C-statistic improvement: 0.702 to 0.738; χ2 test comparing likelihood ratio p < 0.0001; categorical net reclassification index: 0.210 (95% CI 0.023-0.392)). Patients in the highest tercile of LAVImin had similar event rates to those with persistent atrial fibrillation. Measures of LA strain did not enhance model discrimination above LA volumetric measures., Conclusion: Measure of left atrial structure and function offer important prognostic information in patients with DCM and enhance prediction of adverse outcomes. LA strain was not incremental to volumetric analysis for risk prediction., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The adoption of robotic platforms in upper gastrointestinal (GI) surgery is expanding rapidly. The absence of centralised guidance and governance in adoption of new surgical technologies may lead to an increased risk of patient harm., Methods: Surgeon stakeholders participated in a Delphi consensus process following a national open-invitation in-person meeting on the adoption of robotic upper GI surgery. Consensus agreement was deemed met if >80% agreement was achieved., Results: Following two rounds of Delphi voting, 25 statements were agreed on covering the training process, governance and good practice for surgeons' adoption in upper GI surgery. One statement failed to achieve consensus., Conclusions: These recommendations are intended to support surgeons, patients and health systems in the adoption of robotics in upper GI surgery.

Background: Standardisation of referral pathways and the transfer of patients with acute aortic syndromes (AAS) to regional centres are recommended by NHS England in the Acute Aortic Dissection Toolkit. The aim of the Transfer of Thoracic Aortic Vascular Emergencies to Regional Specialist INstitutes Group study was to establish an interdisciplinary consensus on the interhospital transfer of patients with AAS to specialist high-volume aortic centres., Methods: Consensus on the key aspects of interhospital transfer of patients with AAS was established using the Delphi method, in line with Conducting and Reporting of Delphi Studies guidelines. A national patient charity for aortic dissection was involved in the design of the Delphi study. Vascular and cardiothoracic surgeons, emergency physicians, interventional radiologists, cardiologists, intensivists and anaesthetists in the United Kingdom were invited to participate via their respective professional societies., Results: Three consecutive rounds of an electronic Delphi survey were completed by 212, 101 and 58 respondents, respectively. Using predefined consensus criteria, 60 out of 117 (51%) statements from the survey were included in the consensus statement. The study concluded that patients can be taken directly to a specialist aortic centre if they have typical symptoms of AAS on the background of known aortic disease or previous aortic intervention. Accepted patients should be transferred in a category 2 ambulance (response time <18 min), ideally accompanied by transfer-trained personnel or Adult Critical Care Transfer Services. A clear plan should be agreed in case of a cardiac arrest occurring during the transfer. Patients should reach the aortic centre within 4 hours of the initial referral from their local hospital., Conclusions: This consensus statement is the first set of national interdisciplinary recommendations on the interhospital transfer of patients with AAS. Its implementation is likely to contribute to safer and more standardised emergency referral pathways to regional high-volume specialist aortic units., 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.)

Objectives: The simple ultrasound activity score for Crohn's disease (SUS-CD) and bowel ultrasound score (BUSS) are promising intestinal ultrasound (IUS) indices of CD, but studied mainly in small settings with few sonographers. We compared SUS-CD and BUSS against histological and magnetic resonance enterography (MRE) reference standards in a post hoc analysis of a prospective multicentre, multireader trial., Methods: Participants recruited to the METRIC trial (ISRCTN03982913) were studied, including those with available terminal ileal (TI) biopsies. Sensitivity and specificity of SUS-CD and BUSS for TI CD activity were calculated with 95% confidence intervals (CI), from the prospective observations of the original METRIC trial sonographers against the histological activity index (HAI) and the simplified magnetic resonance index of activity (sMARIA)., Results: We included 284 patients (median 31.5 years, IQR 23-46) from 8 centres, who underwent IUS and MRE. Of these, 111 patients had available terminal ileal biopsies with HAI scoring. Against histology, sensitivity and specificity for active disease were 79% (95% CI 69-86%) and 50% (31-69%) for SUS-CD, and 66% (56-75%) and 68% (47-84%) for BUSS, respectively. Compared to sMARIA, the sensitivity and specificity for active CD were 81% (74-86%) and 75% (66-83%) for SUS-CD, and 68% (61-74%) and 85% (76-91%) for BUSS, respectively. The sensitivity of SUS-CD was significantly greater than that of BUSS against HAI and sMARIA (p < 0.001), but its specificity was significantly lower than of BUSS against the MRE reference standard (p = 0.003)., Conclusions: Particularly when compared to MRE activity scoring, SUS-CD and BUSS are promising tools in a real-world clinical setting., Clinical Relevance Statement: When tested using data from a multicentre, multireader diagnostic accuracy trial, the simple ultrasound activity score for Crohn's disease (SUS-CD) and bowel ultrasound score (BUSS) were clinically viable intestinal ultrasound indices that were reasonably sensitive and specific for terminal ileal Crohn's disease, especially when compared to a magnetic resonance reference standard., Key Points: The simple ultrasound activity score for Crohn's disease and bowel ultrasound score are promising intestinal ultrasound indices of Crohn's disease but to date studied mainly in small settings with few sonographers. Compared to histology and the magnetic resonance reference standard in a multicentre, multireader setting, the sensitivity of simple ultrasound activity score for Crohn's disease is significantly greater than that of bowel ultrasound score. The specificity of simple ultrasound activity score for Crohn's disease was significantly lower than that of bowel ultrasound score compared to the magnetic resonance enterography reference standard. The specificity of both indices was numerically higher when the magnetic resonance enterography reference standard was adopted., (© 2023. The Author(s).)

Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Rationale: Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized controlled trial (RCT). Objectives: To establish the feasibility of randomization in a surgery-versus-nonsurgery trial as well as the key outcome measures that are important to identify relevant patient-centered outcomes in a subsequent RCT. Methods: The MIST-3 (third Multicenter Intrapleural Sepsis Trial) was a prospective multicenter RCT involving eight U.K. centers combining on-site and off-site surgical services. The study enrolled all patients with a confirmed diagnosis of pleural infection and randomized those with ongoing pleural sepsis after an initial period (as long as 24 h) of standard care to one of three treatment arms: continued standard care, early IET, or a surgical opinion with regard to early VATS. The primary outcome was feasibility based on >50% of eligible patients being successfully randomized, >95% of randomized participants retained to discharge, and >80% of randomized participants retained to 2 weeks of follow-up. The analysis was performed per intention to treat. Measurements and Main Results: Of 97 eligible patients, 60 (62%) were randomized, with 100% retained to discharge and 84% retained to 2 weeks. Baseline demographic, clinical, and microbiological characteristics of the patients were similar across groups. Median times to intervention were 1.0 and 3.5 days in the IET and surgery groups, respectively ( P  = 0.02). Despite the difference in time to intervention, length of stay (from randomization to discharge) was similar in both intervention arms (7 d) compared with standard care (10 d) ( P  = 0.70). There were no significant intergroup differences in 2-month readmission and further intervention, although the study was not adequately powered for this outcome. Compared with VATS, IET demonstrated a larger improvement in mean EuroQol five-dimension health utility index (five-level edition) from baseline (0.35) to 2 months (0.83) ( P  = 0.023). One serious adverse event was reported in the VATS arm. Conclusions: This is the first multicenter RCT of early IET versus early surgery in pleural infection. Despite the logistical challenges posed by the coronavirus disease (COVID-19) pandemic, the study met its predefined feasibility criteria, demonstrated potential shortening of length of stay with early surgery, and signals toward earlier resolution of pain and a shortened recovery with IET. The study findings suggest that a definitive phase III study is feasible but highlights important considerations and significant modifications to the design that would be required to adequately assess optimal initial management in pleural infection.The trial was registered on ISRCTN (number 18,192,121).

Background: Novel biologic therapies have revolutionised the management of severe asthma with more ambitious treatment aims. Here we analyse the definition of clinical remission as a suggested treatment goal and consider the characteristics associated with clinical remission in a large, real-world severe asthma cohort., Methods: This was a retrospective analysis of severe asthma patients registered in the UK Severe Asthma Registry (UKSAR) who met strict national access criteria for biologics. Patients had a pre-biologics baseline assessment and annual review. The primary definition of clinical remission applied included Asthma Control Questionnaire (ACQ)-5 <1.5 and no oral corticosteroids for disease control and forced expiratory volume in 1 s above lower limit of normal or no more than 100 mL less than baseline., Results: 18.3% of patients achieved the primary definition of remission. The adjusted odds of remission on biologic therapy were 7.44 (95% CI 1.73-31.95)-fold higher in patients with type 2 (T2)-high biomarkers. The adjusted odds of remission were lower in patients who were female (OR 0.61, 95% CI 0.45-0.93), obese (OR 0.49, 95% CI 0.24-0.65) or had ACQ-5 ≥1.5 (OR 0.19, 95% CI 0.12-0.31) pre-biologic therapy. The likelihood of remission reduced by 14% (95% CI 0.76-0.97) for every 10-year increase in disease duration. 12-21% of the cohort attained clinical remission depending on the definition applied; most of those who did not achieve remission failed to meet multiple criteria., Conclusions: 18.3% of patients achieved the primary definition of clinical remission. Remission was more likely in T2-high biomarker patients with shorter duration of disease and less comorbidity. Further research on the optimum time to commence biologics in severe asthma is required., Competing Interests: Conflict of interest: The UK Severe Asthma Registry (UKSAR) does not receive any monetary benefits or benefits-in-kind from any pharmaceutical entity; UKSAR does make limited data contributions to the International Severe Asthma Registry (ISAR) and the European Respiratory Society Clinical Research Collaborative (SHARP), which do receive pharmaceutical funding. P.J. McDowell reports speaker fees from GlaxoSmithKline and scientific meeting support from Chiesi. R. McDowell and M. Patel have no conflicts of interest to declare. M.C. Eastwood reports support to attend meetings from GlaxoSmithKline. J. Busby reports grants from AstraZeneca and personal fees from Nuvoair. P.H. Patel received advisory board fees and lecture fees from AstraZeneca, GlaxoSmithKline, Novartis and Sanofi. D.J. Jackson has received speaker fees and consultancy fees from AstraZeneca, GlaxoSmithKline and Sanofi Regeneron. A. Mansur declares personal and to institution payment for talks, advisory board meetings and sponsorship to attend conferences from AstraZeneca, GlaxoSmithKline, Teva, Sanofi, Novartis and Boehringer Ingelheim; he also declares research grants from GlaxoSmithKline. H. Burhan reports fees for advisory board meetings from AstraZeneca and Novartis, honoraria for lectures from AstraZeneca, Chiesi, GSK and Sanofi, and support for attending conferences from AstraZeneca, Chiesi and GSK. S. Doe has participated on advisory boards for Vertex, Gilead and Novartis, and has received support for travel to meetings from GlaxoSmithKline, AstraZeneca, Gilead, Teva; Sanofi, Chiesi and Forest, and fees for lectures from GlaxoSmithKline, AstraZeneca and Sanofi. R. Chaudhuri has received lecture fees from GlaxoSmithKline, AstraZeneca, Teva, Chiesi, Sanofi and Novartis, honoraria for advisory board meetings from GlaxoSmithKline and AstraZeneca, sponsorship to attend international scientific meetings from Chiesi, Sanofi and GlaxoSmithKline, and a research grant (paid to institute) from AstraZeneca for a UK multicentre study. R. Gore has received fees for lecturing from AstraZeneca, Novartis, Sanofi and GlaxoSmithKline. J.W. Dodd declares he has received honoraria for participating in advisory boards and given lectures at meetings supported by GlaxoSmithKline, Boehringer Ingelheim, Chiesi, AstraZeneca, Fisher & Paykel and Aerogen; he has received sponsorship for attending international scientific meetings from Chiesi; he has also taken part in asthma clinical trials sponsored by Sanofi, AstraZeneca and Chiesi, for which his institution received remuneration; his institution has received funding for research from the MRC, NIHR, SBRI, NHSx, Templeton Foundation and Southmead Hospital research charity. T. Brown has received fees as an external expert from AstraZeneca, speaker fees from AstraZeneca, GlaxoSmithKline, Sanofi, Teva, Novartis and Chiesi, honoraria for advisory board attendance from AstraZeneca, Sanofi and Teva, and sponsorship to attend international scientific meetings from Sanofi, GlaxoSmithKline, Teva, Chiesi and Napp Pharmaceuticals. D. Subramanian is part of the AstraZeneca Precision National Working group and has received speaker fees from Chiesi. L.G. Heaney is academic lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma, which involves industrial partnerships with a number of pharmaceutical companies., (Copyright ©The authors 2023.)

Background and Aims: Patients often first present with symptoms of trigeminal neuralgia (TN) to primary care. However, there has been little research to determine whether the diagnosis and management of this condition is carried out according to current guidelines. Furthermore, there is little up-to-date information regarding the prevalence of TN in the UK. The aim is to estimate the prevalence of TN and to audit the diagnosis and management process of TN in primary care., Methods: Between 2019 and 2020 a search was made at five UK GP practices with a total patient population of 55,842 using EMIS and SystmOne patient record systems to review patient consultations to identify patients coded with TN or facial pain (FP). These records were reviewed to ascertain the basis for diagnosis, management in primary care and referral to secondary care., Results: 157 patients were identified; 54 coded with FP and 103 with TN. These results indicate a prevalence of 22.3 in 10,000. There was no difference in documented symptoms between the two groups. Seven patients had all ICDH3 criteria recorded, with two meeting the requirements for TN diagnosis. 58.8% of patients with TN were started on carbamazepine, the current gold standard treatment, compared with 16.7% in the FP group. 38.2% of TN patients were referred to a range of different specialities., Conclusion: The prevalence of TN may be higher than previously thought. Key diagnostic criteria are often omitted, leading to potential misdiagnosis or delays in diagnosis. Relatively few referrals are made, though all patients should be considered for imaging., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background Coronaviruses are viral agents that commonly infect animals, but have the ability to cause respiratory illness in humans, exemplified by the ongoing novel coronavirus outbreak (COVID-19). Due to the sparse literature on the effects of COVID-19 on the respiratory system, and the possible development of persistent asthma-like symptoms after infection, this cross-sectional analysis was performed in order to compare the clinical and investigative parameters between post-COVID patients and asthmatic patients. Methods A retrospective cross-sectional study was conducted on patients with prior history of COVID-19 infection that presented to the pulmonology or respiratory outpatient clinics with asthma-like symptoms and were subsequently compared to known asthmatic patients with absent history of prior COVID-19 infection, in order to evaluate the degree of similarity between both cohorts. In this study, asthma-like symptoms were defined as: (i) cough, (ii) wheezing, (iii) chest tightness, and (iv) shortness of breath. Moreover, comparisons of investigative parameters were also performed, including (i) fractional exhaled nitric oxide (FeNO), (ii) serum immunoglobulin E (IgE), (iii) absolute eosinophil counts, and (iv) qualitative spirometry results. All statistical analyses were conducted via chi-squared testing for categorical variables, and independent t-test for continuous variables. Results In this study, there were a total of 76 patients included that conformed to the eligibility criteria, including 39 patients with post-COVID symptoms with absent history of asthma or other respiratory illnesses, and 37 patients with known asthma with absent history of prior COVID-19 infection or other respiratory illnesses. Overall, this study revealed the similarities between both cohorts with respect to the incidence of cough, chest tightness, and shortness of breath. Moreover, there were similarities between the serum IgE and spirometry results. However, there were differences within the complaint of wheeze, FeNO values, and eosinophil counts between both cohorts. The placement of post-COVID patients on bronchodilator therapy involving inhaled corticosteroids and long-acting beta-agonists revealed improvement in all follow-up patients. Conclusion In conclusion, there was considerable similarity in the complaint of asthma-like symptoms after COVID-19 infection, associated with an improvement after the use of bronchodilator therapy, indicating the potential role of anti-asthma therapy (e.g., bronchodilator therapy) in managing post-COVID asthma-like symptoms. In order to validate our conclusion, further comprehensive studies with robust methodologies and larger sample populations are encouraged., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Husain et al.)

Aims: To characterize the phenotype, clinical outcomes and rate of disease progression in patients with early-stage non-ischaemic cardiomyopathy (early-NICM)., Methods and Results: We conducted a prospective observational cohort study of patients with early-NICM assessed by late gadolinium enhancement cardiovascular magnetic resonance (CMR). Cases were classified into the following subgroups: isolated left ventricular dilatation (early-NICM H-/D+), non-dilated left ventricular cardiomyopathy (early-NICM H+/D-), or early dilated cardiomyopathy (early-NICM H+/D+). Clinical follow-up for major adverse cardiovascular events (MACE) included non-fatal life-threatening arrhythmia, unplanned cardiovascular hospitalization or cardiovascular death. A subset of patients (n = 119) underwent a second CMR to assess changes in cardiac structure and function. Of 254 patients with early-NICM (median age 46 years [interquartile range 36-58], 94 [37%] women, median left ventricular ejection fraction [LVEF] 55% [52-59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis between subgroups (p = 0.90), however fibrosis mass was lowest in early-NICM H-/D+, higher in early-NICM H+/D- and highest in early-NICM H+/D+ (p = 0.03). Over a median follow-up of 7.9 (5.5-10.0) years, 28 patients (11%) experienced MACE. Non-sustained ventricular tachycardia (hazard ratio [HR] 5.1, 95% confidence interval [CI] 2.36-11.00, p < 0.001), myocardial fibrosis (HR 3.77, 95% CI 1.73-8.20, p < 0.001) and diabetes mellitus (HR 5.12, 95% CI 1.73-15.18, p = 0.003) were associated with MACE in a multivariable model. Only 8% of patients progressed from early-NICM to dilated cardiomyopathy with LVEF <50% over a median of 16 (11-34) months., Conclusion: Early-NICM is not benign. Fibrosis develops early in the phenotypic course. In-depth characterization enhances risk stratification and might aid clinical management., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: Alcohol-related liver disease (ALD) is the most common cause of liver-related ill health and liver-related deaths in the UK, and deaths from ALD have doubled in the last decade. The management of ALD requires treatment of both liver disease and alcohol use; this necessitates effective and constructive multidisciplinary working. To support this, we have developed quality standard recommendations for the management of ALD, based on evidence and consensus expert opinion, with the aim of improving patient care., Design: A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology ALD Special Interest Group developed the quality standards, with input from the British Liver Trust and patient representatives., Results: The standards cover three broad themes: the recognition and diagnosis of people with ALD in primary care and the liver outpatient clinic; the management of acutely decompensated ALD including acute alcohol-related hepatitis and the posthospital care of people with advanced liver disease due to ALD. Draft quality standards were initially developed by smaller working groups and then an anonymous modified Delphi voting process was conducted by the entire group to assess the level of agreement with each statement. Statements were included when agreement was 85% or greater. Twenty-four quality standards were produced from this process which support best practice. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice and an audit tool provided., Conclusion: It is hoped that services will review their practice against these recommendations and key performance indicators and institute service development where needed to improve the care of patients with ALD., Competing Interests: Competing interests: RP: research support from NIHR and LEeds Hospital Charity. Consulting fees from Durect. Fees for speaking from Norgine Pharmaceuticals. Advisory board fees from Novo Nordisk. LC: consulting fees from Novo Nordisk relating to non-alcohol-related fatty liver disease. TP: research grant support from NIHR, Society for the Study of Addiction, Office of Police and Crime Commissioner. SMorgan: research support from NIHR. Consulting fees from Norgine Pharmaceuticals, Payment or honoraria from Sandoz UK and Dr Falk. LEadership roles with BRitish Society of Gastroenterology, Alcohol HEalth Alliance, Medical Council on Alcohol.These authors declare no conflicts of interest: SA, MA, RA, SB, VB, RB, ID, AD, PD, RGailer, EForrest, EForster, RGoldin, VH, AJ, VL, DL, JMcDonagh, JMaurice, SMasson, TN, EO, GP, NRajoriya, NRainford, PR, JR, JS, MS, AS, ES, JT, RV, IW and AW., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Colon cancer in ulcerative colitis patients with liver transplant (UCCOLT) due to primary sclerosing cholangitis carries significant treatment challenges. Aim of this literature search is to review management strategies and provide a framework to facilitate the decisional process in this clinical setting., Methods: PRISMA-compliant systematic search was followed by critical expert commentary of the results and development of a surgical management algorithm. Endpoints included surgical management, operative strategies, functional and survival outcomes. Technical and strategics aspects with particular regard to the choice of reconstruction were evaluated to tentatively develop an integrated algorithm., Results: Ten studies reporting treatment of 20 UCCOLT patients were identified after screening. Nine patients underwent proctocolectomy and end-ileostomy (PC) and eleven had restorative ileal pouch-anal anastomosis (IPAA). Reported results for perioperative outcomes, oncological outcomes, and graft loss were comparable for both procedures. There were no reports of subtotal colectomies and ileo-rectal anastomosis (IRA)., Conclusions: Literature in the field is scarce and decision-making is particularly complex. PC and IPAA have been reported with good results. Nevertheless, IRA may also be considered in UCCOLT patients in selected cases, reducing the risks of sepsis, OLT and pouch failure; furthermore, in young patients, it has the advantage of preserving fertility or sexual function. The proposed treatment algorithm may represent a valuable support in guiding surgical strategy., Competing Interests: Declaration of competing interest The authors have no conflict of interest or financial disclosures., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Patients with FLT3-mutated AML have a high relapse rate and suboptimal outcomes. Many have co-mutations suitable for measurable residual disease (MRD) monitoring by RT-qPCR and those destined to relapse can be identified by high or rising levels of MRD, called molecular failure.  This provides a window for pre-emptive intervention, but there is little evidence to guide treatment. The use of FLT3 inhibitors (FLT3i) appears attractive but their use has not yet been evaluated.  We identified 56 patients treated with FLT3i at molecular failure.  The FLT3 mutation was an ITD in 52, TKD in 7 and both in 3. Over half of patients had previously received midostaurin. Molecular failure occurred at a median 9.2 months from diagnosis and was treated with gilteritinib (n = 38), quizartinib (n = 7) or sorafenib (n = 11). 60% achieved a molecular response, with 45% reaching MRD negativity. Haematological toxicity was low, and 22 patients were bridged directly to allogeneic transplant with another 6 to donor lymphocyte infusion. 2-year overall survival was 80% (95%CI 69-93) and molecular event-free survival 56% (95%CI 44-72). High-sensitivity next-generation sequencing for FLT3-ITD at molecular failure identified patients more likely to benefit. FLT3i monotherapy for molecular failure is a promising strategy which merits evaluation in prospective studies., (© 2023. The Author(s).)

Competing Interests: Competing interests: GM is on the editorial board for BMJ Heart.

Background: Patients often ask about the time taken to return to activities of daily living (ADLs) after breast surgery, but there is a lack of data to give accurate guidance. We aimed to assess the feasibility of a study to determine the time taken to return to ADLs after mastectomy with or without breast reconstruction., Materials and Methods: A prospective multicentre, self-reported questionnaire-based feasibility study of women who had undergone mastectomy ± reconstruction was performed, between Jan 2017 and Dec 2019. Women were asked to self-report when they returned to 15 ADLs with a 5-option time scale for "return to activity.", Results: The questionnaire was returned by 42 patients (median [range] age: 64 [31-84]). Of these, 22 had simple mastectomy, seven mastectomy and implant reconstruction, seven mastectomy and autologous reconstruction (DIEP), and six did not specify. Overall, over 90% could manage stairs and brush hair by two weeks and 84% could get in and out of the bath by four weeks. By 1-2 months, 92% could do their own shopping and 86% could drive. 68% of women employed returned to work within four months. Compared to simple mastectomy, patients undergoing reconstruction took a longer time to return to getting in/out of bath (<2 vs. 2-4 weeks), vacuuming (2-4 weeks vs. 1-2 months), and fitness (1-2 vs. 3-4 months). There was a slower return to shopping (1-2 months vs. 2-4 weeks), driving and work (both 3-4 vs. 1-2 months), and sports (3-4 vs. 1-2 months) in autologous reconstruction compared to implant reconstruction., Conclusion: This study is feasible. It highlights slower return to specific activities (particularly strength-based) in reconstruction patients, slower in autologous compared with implant reconstruction. The impact on return to ADLs should be discussed as part of the preoperative counselling as it will inform patients and help guide their decision making. A larger study is required to confirm these results., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 L. Ballance et al.)

With the increased availability of genomic sequencing technologies, the molecular bases for kidney diseases such as nephronophthisis and mitochondrially inherited and autosomal-dominant tubulointerstitial kidney diseases (ADTKD) has become increasingly apparent. These tubulointerstitial kidney diseases (TKD) are monogenic diseases of the tubulointerstitium and result in interstitial fibrosis and tubular atrophy (IF/TA). However, monogenic inheritance alone does not adequately explain the highly variable onset of kidney failure and extra-renal manifestations. Phenotypes vary considerably between individuals harbouring the same pathogenic variant in the same putative monogenic gene, even within families sharing common environmental factors. While the extreme end of the disease spectrum may have dramatic syndromic manifestations typically diagnosed in childhood, many patients present a more subtle phenotype with little to differentiate them from many other common forms of non-proteinuric chronic kidney disease (CKD). This review summarises the expanding repertoire of genes underpinning TKD and their known phenotypic manifestations. Furthermore, we collate the growing evidence for a role of modifier genes and discuss the extent to which these data bridge the historical gap between apparently rare monogenic TKD and polygenic non-proteinuric CKD (excluding polycystic kidney disease).

Background: Annual national diabetes audit data consistently shows most people with diabetes do not consistently achieve blood glucose targets for optimal health, despite the large range of treatment options available., Aim: To explore the efficacy of a novel clinical intervention to address physical and mental health needs within routine diabetes consultations across health care settings., Methods: A multicenter, parallel group, individually randomized trial comparing consultation duration in adults diagnosed with T1D or T2D for ≥6 months using the Spotlight-AQ platform versus usual care. Secondary outcomes were HbA1c, depression, diabetes distress, anxiety, functional health status, and healthcare professional burnout. Machine learning models were utilized to analyze the data collected from the Spotlight-AQ platform to validate the reliability of question-concern association; as well as to identify key features that distinguish people with type 1 and type 2 diabetes, as well as important features that distinguish different levels of HbA1c., Results: n = 98 adults with T1D or T2D; any HbA1c and receiving any diabetes treatment participated ( n = 49 intervention). Consultation duration for intervention participants was reduced in intervention consultations by 0.5 to 4.1 minutes (3%-14%) versus no change in the control group (-0.9 to +1.28 minutes). HbA1c improved in the intervention group by 6 mmol/mol (range 0-30) versus control group 3 mmol/mol (range 0-8). Moderate improvements in psychosocial outcomes were seen in the intervention group for functional health status; reduced anxiety, depression, and diabetes distress and improved well-being. None were statistically significant. HCPs reported improved communication and greater focus on patient priorities in consultations. Artificial Intelligence examination highlighted therapy and psychological burden were most important in predicting HbA1c levels. The Natural Language Processing semantic analysis confirmed the mapping relationship between questions and their corresponding concerns. Machine learning model revealed type 1 and type 2 patients have different concerns regarding psychological burden and knowledge. Moreover, the machine learning model emphasized that individuals with varying levels of HbA1c exhibit diverse levels of psychological burden and therapy-related concerns., Conclusion: Spotlight-AQ was associated with shorter, more useful consultations; with improved HbA1c and moderate benefits on psychosocial outcomes. Results reflect the importance of a biopsychosocial approach to routine care visits. Spotlight-AQ is viable across health care settings for improved outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Spotlight-AQ owns the preclinic assessment platform. RCK and KBK are founders and shareholders in Spotlight-AQ. All other authors have no financial or other competing interests.

Introduction: Robotic-assisted knee replacement systems have been introduced to healthcare services worldwide in an effort to improve clinical outcomes for people, although high-quality evidence that they are clinically, or cost-effective remains sparse. Robotic-arm systems may improve surgical accuracy and could contribute to reduced pain, improved function and lower overall cost of total knee replacement (TKR) surgery. However, TKR with conventional instruments may be just as effective and may be quicker and cheaper. There is a need for a robust evaluation of this technology, including cost-effectiveness analyses using both within-trial and modelling approaches. This trial will compare robotic-assisted against conventional TKR to provide high-quality evidence on whether robotic-assisted knee replacement is beneficial to patients and cost-effective for healthcare systems., Methods and Analysis: The Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial-Knee is a multicentre, participant-assessor blinded, randomised controlled trial to evaluate the clinical and cost-effectiveness of robotic-assisted TKR compared with TKR using conventional instruments. A total of 332 participants will be randomised (1:1) to provide 90% power for a 12-point difference in the primary outcome measure; the Forgotten Joint Score at 12 months postrandomisation. Allocation concealment will be achieved using computer-based randomisation performed on the day of surgery and methods for blinding will include sham incisions for marker clusters and blinded operation notes. The primary analysis will adhere to the intention-to-treat principle. Results will be reported in line with the Consolidated Standards of Reporting Trials statement. A parallel study will collect data on the learning effects associated with robotic-arm systems., Ethics and Dissemination: The trial has been approved by an ethics committee for patient participation (East Midlands-Nottingham 2 Research Ethics Committee, 29 July 2020. NRES number: 20/EM/0159). All results from the study will be disseminated using peer-reviewed publications, presentations at international conferences, lay summaries and social media as appropriate., Trial Registration Number: ISRCTN27624068., Competing Interests: Competing interests: Stryker is providing funding for consumables, preoperative CT costs and 10 min of theatre time, according to contractual arrangements. They also fund some postoperative CT costs in the learning effects study. Appropriate contracts are in place to ensure the independence of the trial team with regard to study design, data collection, management, analysis and interpretation in line with NIHR reporting standards. Multiple investigators are investigators on two other NIHR-funded studies receiving additional support for treatment costs from Stryker, START:REACTS (16/61/18) (AM, HP, CEH, JM and MU) and RACER-Hip (NIHR131407) (AM, ETD, HP, SR, CEH, DRE, JM, FSH, JAS and MU). The full independence of the investigators of these related studies are protected by legal agreements, similar to this study. FSH receives funding from Stryker to run clinical studies. Multiple authors report other unrelated research grants from NIHR during the conduct of the study. DRE, HP and JG are supported from NIHR Research Capability Funding via University Hospitals Coventry and Warwickshire. MU is chief investigator or coinvestigator on multiple previous and current research grants from the UK National Institute for Health Research, Arthritis Research UK and is a coinvestigator on grants funded by the Australian NHMRC and Norwegian MRC. He was an NIHR Senior Investigator until March 2021. He has received travel expenses for speaking at conferences from the professional organisations hosting the conferences. He is a director and shareholder of Clinvivo that provides electronic data collection for health services research. He is part of an academic partnership with Serco Ltd, funded by the European Social Fund, related to return to work initiatives. Until March 2020 he was an editor of the NIHR journal series, and a member of the NIHR Journal Editors Group, for which he received a fee., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Health technology assessments (HTAs) of robotic assisted surgery (RAS) face several challenges in assessing the value of robotic surgical platforms. As a result of using different assessment methods, previous HTAs have reached different conclusions when evaluating RAS. While the number of available systems and surgical procedures is rapidly growing, existing frameworks for assessing MedTech provide a starting point, but specific considerations are needed for HTAs of RAS to ensure consistent results. This work aimed to discuss different approaches and produce guidance on evaluating RAS., Methods: A consensus conference research methodology was adopted. A panel of 14 experts was assembled with international experience and representing relevant stakeholders: clinicians, health economists, HTA practitioners, policy makers, and industry. A review of previous HTAs was performed and seven key themes were extracted from the literature for consideration. Over five meetings, the panel discussed the key themes and formulated consensus statements., Results: A total of ninety-eight previous HTAs were identified from twenty-five total countries. The seven key themes were evidence inclusion and exclusion, patient- and clinician-reported outcomes, the learning curve, allocation of costs, appropriate time horizons, economic analysis methods, and robotic ecosystem/wider benefits., Conclusions: Robotic surgical platforms are tools, not therapies. Their value varies according to context and should be considered across therapeutic areas and stakeholders. The principles set out in this paper should help HTA bodies at all levels to evaluate RAS. This work may serve as a case study for rapidly developing areas in MedTech that require particular consideration for HTAs.