Aging towards walkable futures: insights from a multidisciplinary workshop held in Barcelona, Spain.

Background: The aging of the world's population and the increase in sedentary lifestyles are leading to an increase in walking impairments at older ages. Here, we aimed to comprehensively discuss walking in the context of an aging population; and identify and agree on a list of future research priorities and policy actions.

Methods: We followed a participatory approach and held a multidisciplinary two-day workshop on October, 2023 in Barcelona, Spain, with experts in the fields of aging and walking, and participants from the general public.

Large-scale evaluation of outcomes after a genetic diagnosis in children with severe developmental disorders.

Purpose: We sought to evaluate outcomes for clinical management after a genetic diagnosis from the Deciphering Developmental Disorders study.

Methods: Individuals in the Deciphering Developmental Disorders study who had a pathogenic/likely pathogenic genotype in the DECIPHER database were selected for inclusion ( = 5010). Clinical notes from regional clinical genetics services notes were reviewed to assess predefined clinical outcomes relating to interventions, prenatal choices, and information provision.

Thrombolysis for aneurysmal subarachnoid haemorrhage.

Background: Aneurysmal subarachnoid haemorrhage continues to cause a significant burden of morbidity and mortality despite advances in care. Trials investigating local administration of thrombolytics have reported promising results.

Objectives: - To assess the effect of thrombolysis on improving functional outcome and case fatality following aneurysmal subarachnoid haemorrhage - To determine the effect of thrombolysis on the risk of cerebral artery vasospasm, delayed cerebral ischaemia, and hydrocephalus following subarachnoid haemorrhage - To determine the risk of complications of local thrombolysis in aneurysmal subarachnoid haemorrhage SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (last searched 9 March 2023), MEDLINE Ovid (1946 to 9 March 2023), and Embase Ovid (1974 to 9 March 2023).

Benefit and Harms of Radical Nephroureterectomy as Part of a Multimodal Treatment Strategy for Upper Tract Urothelial Carcinoma Patients Presenting with Clinical Evidence of Regional Lymph Node Metastasis: A Systematic Review and Meta-analysis by the European Association of Urology Guidelines.

Background And Objective: Given the uncertainty regarding the role of radical nephroureterectomy (RNU) as part of a multimodal treatment strategy for upper tract urothelial carcinoma (UTUC) patients with cN+ disease, we aimed to perform a systematic review and meta-analysis of the corresponding literature.

Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we identified 17 observational comparative and noncomparative studies, published between January 2000 and September 2024, evaluating UTUC patients with cTanyN+M0 disease (P) who received RNU as part of a multimodal treatment strategy (I), as compared with any treatment strategy if applicable (C), to assess oncological or postoperative outcomes (O). Meta-analyses were further performed, as appropriate.

Assessment and management of late radiation-associated dysphagia after treatment for head and neck cancer: A scoping review and survey of UK speech and language therapists.

Background: Late side effects of head and neck cancer treatment commonly affect swallowing function. Late radiation-associated dysphagia (late-RAD) often presents years post-treatment when patients have been discharged from their multidisciplinary team. Timely symptom management may provide important physical and emotional support, potentially reducing the overall healthcare burden.

Clinical Spectrum and Prognosis of Atypical Autosomal Dominant Polycystic Kidney Disease Caused by Monoallelic Pathogenic Variants of IFT140.

Rationale & Objective: Monoallelic predicted Loss-of-Function (pLoF) variants in IFT140 have recently been associated with an autosomal dominant polycystic kidney disease (ADPKD)-like phenotype. This study sought to enhance the characterization of this phenotype.

Study Design: Case series.

Enhancing lung transplantation with ECMO: a comprehensive review of mechanisms, outcomes, and future considerations.

Background: Lung transplantation (LTx) is a critical intervention for patients with end-stage lung disease. However, challenges such as donor organ scarcity and post-transplant complications significantly affect its success. Recent advancements in Extracorporeal Membrane Oxygenation (ECMO) have shown promise in improving the outcomes and expanding eligibility for LTx.

Hydroxychloroquine in combination with platinum doublet chemotherapy as first-line treatment for extensive-stage small cell lung cancer (Study 15): A randomised phase II multicentre trial.

Background: Most patients with small-cell lung cancer (SCLC) present with extensive-stage (ES) disease and have a poor prognosis despite achieving high initial response rates to platinum-based doublet chemotherapy. This study evaluated whether adding hydroxychloroquine (HCQ) to chemotherapy could improve outcomes.

Methods: This was a randomised multicentre phase II trial.

The DLEU2-miR-15a-16-1 Cluster Is a Determinant of Bone Microarchitecture and Strength in Postmenopausal Women and Mice.

This study explores how select microRNAs (miRNAs) influence bone structure in humans and in transgenic mice. In trabecular bone biopsies from 84 postmenopausal women (healthy, osteopenic, and osteoporotic), we demonstrate that (deleted in lymphocytic leukemia 2)-encoded is strongly positively associated with bone mineral density (BMD) at different skeletal sites. In bone transcriptome analyses, levels correlated positively with the osteocyte characteristic transcripts (encoding sclerostin) and (Matrix Extracellular Phosphoglycoprotein), while the related showed a negative association with BMD and osteoblast markers.

Fatal Tension Gastrothorax: Two Case Reports.

Tension gastrothorax is a rare and potentially fatal complication of a diaphragmatic hernia, in which a massively dilated, intrathoracic stomach compresses the lungs and mediastinum, causing cardiorespiratory compromise, in a mechanism akin to tension pneumothorax. Although it is very rare, tension gastrothorax has been reported in the literature; however, such reports are almost exclusively restricted to its clinical presentation and treatment in emergency departments. To the best of our knowledge, no adult autopsy case reports of tension gastrothorax have been reported in the literature.

Report on an audit of two decades' activities of a clinical ethics committee: the Newcastle upon Tyne Hospitals NHS Foundation Trust Clinical Ethics Advisory Group (CEAG).

Background: 'The Clinical Ethics Advisory Group' (CEAG) is the clinical ethics support body for Newcastle upon Tyne Hospitals National Health Service Foundation Trust. A significant change in CEAG's way of working occurred over the past 5 years as a result of Court decisions, increasing public expectations and an increase in CEAG's paediatric case flow.

Purpose: Review historical data: (a) as a useful benchmark to look for the early impact of significant service changes and (b) to seek possible reference ('sentinel') cases for use with a posited practical (casuistic) case-based reasoning model.

UKHCDO gene therapy taskforce: Guidance for implementation of haemophilia gene therapy into routine clinical practice for adults.

Introduction: 2022 was a landmark year with two adeno-associated viral vectors (AAVs) receiving conditional marketing authorization from EMA for the treatment of persons with severe haemophilia A and severe to moderately severe haemophilia B and a third in 2024. Gene therapy is a transformative, irreversible treatment with long-lasting effects, necessitating development of new clinical pathways to ensure optimal outcomes.

Aim: To develop a consensus framework and service specification for delivery of AAV gene therapy for haemophilia in adults within the UK using the hub-and-spoke model proposed by the European Association of Haemophilia and Allied Disorders and the European Haemophilia Consortium.

ATMP clinical trials in the UK.

Aims: The UK advanced therapy medicinal product (ATMP) clinical trials database, produced annually by CGT Catapult, aims to assess the progress and state of the UK ATMP clinical development landscape. The aim of this article is to highlight key findings from the database and put them into context within the global landscape and various initiatives intended to attract ATMP developers to the UK.

Method: A targeted search of GlobalData's clinical trial database was performed, followed by refinement so that only trials investigating products meeting ATMP definitions were included, and that each trial was only counted once in the analysis.

Avoiding "a piece of paper on the wall that everyone ignores": A qualitative study on the barriers for implementing open fracture guidelines.

Background: Ortho-plastic evidence-based clinical guidelines for open fractures have demonstrated to standardise care and improve outcomes for patients admitted following lower extremity trauma. Despite its benefits, very few countries have introduced such guidance. The aim of this study was to explore the attitudes, barriers and limitations to the development and implementation of guidelines for lower limb open fractures METHODS: Twelve renowned orthopaedic and plastic surgeons, based in countries with no guidelines at present, underwent semi-structured interviews.

Management of adult mechanically ventilated patients: A UK-wide survey.

Background: Mechanical ventilation is a common and often lifesaving intervention that is utilised in intensive care. However, the practices can vary between centres. Through this national survey we aim to gain more information about different strategies adopted across the UK.

The abscopal effects of sonodynamic therapy in cancer.

The abscopal effect is a phenomenon wherein localised therapy on the primary tumour leads to regression of distal metastatic growths. Interestingly, various pre-clinical studies utilising sonodynamic therapy (SDT) have reported significant abscopal effects, however, the mechanism remains largely enigmatic. SDT is an emerging non-invasive cancer treatment that uses focussed ultrasound (FUS) and a sonosensitiser to induce tumour cell death.

Variation in surgery postponement rates in the NHS in England.

Introduction: Postponement of surgery at preoperative assessment in the days or weeks before the patient is admitted for surgery, as distinct from cancellation on the planned day of surgery, can be devastating for patients and an inefficient use of finite resources. However, postponements are often poorly recorded. The primary aim of this pilot study was to investigate elective surgical postponement rates during or after preoperative assessment across England, and the reasons for postponement for patients on an elective surgical pathway.

TRBC1-CAR T cell therapy in peripheral T cell lymphoma: a phase 1/2 trial.

Relapsed/refractory peripheral T cell lymphomas (PTCLs) are aggressive tumors with a poor prognosis. Unlike B cell lymphomas, treatment of PTCL has not benefited from advances in immunotherapy. This is largely due to a lack of suitable target antigens that discriminate malignant from normal T cells, thus avoiding severe immunosuppression consequent to depletion of the entire T cell compartment.