Pelvis Or Involved Node Treatment: Eradicating Recurrence in Prostate Cancer (POINTER-PC) - study protocol paper for a phase III multicentre, open-label randomised controlled trial.

Introduction: Prostate cancer (PCa) is the most common cancer in men. Recurrence may occur in up to half of patients initially treated with curative intent for high-risk localised/locally advanced PCa. Pelvic nodal recurrence is common in this setting, but no clear standard of care exists for these patients, with potential therapeutic approaches including stereotactic body radiotherapy (SBRT) to the involved node(s) alone, extended nodal irradiation (ENI) to treat sites of potential micrometastatic spread in addition to involved node(s) and androgen deprivation therapy with or without additional systemic anticancer therapies.

Delays to Revascularisation and Outcomes of Non-elective Admissions for Chronic Limb Threatening Ischaemia: a UK Population Based Cohort Study.

Objective: Major amputation and death are significant outcomes after lower limb revascularisation for chronic limb threatening ischaemia (CLTI), but there is limited evidence on their association with the timing of revascularisation. The aim of this study was to examine the relationship between time from non-elective admission to revascularisation and one year outcomes for patients with CLTI.

Methods: This was an observational, population based cohort study of patients aged ≥ 50 years with CLTI admitted non-electively for infra-inguinal revascularisation procedures in English NHS hospitals from January 2017 to December 2019 recorded in the Hospital Episode Statistics database.

Breast cancer outcomes in women with ovarian cancer and a pathogenic germline BRCA mutation.

Background: Women with ovarian cancer (OC) and a pathogenic variant in the BRCA1 or BRCA2 genes are at increased risk of developing breast cancer (BC). Evidence for long term outcomes in these patients who undergo bilateral risk reduction mastectomy (RRM) after ovarian cancer is sparse. The aim of this study was to analyse the long-term breast cancer-related outcomes of patients who have been diagnosed with ovarian cancer and found to have BRCA1 or 2 pathogenic variants.

Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach.

There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health.

Ultrastructural imaging biomarkers in diabetic macular edema: A major review.

Diabetic macular edema (DME) is a vision-threatening complication of diabetic retinopathy and causes significant morbidity in patients. Anti-vascular endothelial growth factor (VEGF) agents are the mainstay of treatment for DME, with steroid implants being used for the treatment of anti-VEGF resistant eyes. Over the years, several classification systems have been devised to describe the patterns of DME using optical coherence tomography (OCT).

Endothelial dysfunction in adults with congenital heart disease: A systematic review and meta-analysis.

Background: Adults with congenital heart disease (ACHD) can face a lifelong risk of premature cardiovascular events. Endothelial dysfunction and arterial stiffness may be some of the key mechanisms involved. Early identification of endothelial damage in ACHD could be crucial to mitigate the adverse events.

Sleep quality in children with hepatic glycogen storage diseases, a prospective observational pilot study.

Background: Hepatic glycogen storage diseases (GSDs) are characterised by enzyme defects affecting liver glycogen metabolism, where carbohydrate supplementation to prevent overnight hypoglycaemia is common. Concerns around sleep quality in hepatic GSDs relate to emerging evidence that overnight dysglycaemia impacts sleep quality.

Methods: This prospective observational study reported sleep quality and duration in children with hepatic GSDs over 7 days utilising: actigraphy (Actiwatch 2 by Phillips Respironics), sleep diaries, proxy reported age-appropriate sleep and quality-of-life (QoL) questionnaires, in the context of nocturnal glycaemic profiles continuous glucose monitor (CGM, Dexcom G6) and nocturnal dietary management strategies.

Primary thyroid B-cell lymphoma: molecular insights into its clonal evolution and relapse.

Primary thyroid lymphomas comprise largely extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL) and diffuse large B-cell lymphoma (DLBCL), followed by follicular lymphoma (FL). They commonly develop from a background of Hashimoto's thyroiditis (HT), where dysregulated immune responses trigger autoreactive infiltrates and drive clonal B-cell evolution. To understand how these lymphomas and their relapse evolve, we investigated 10 cases by mutation profiling, including five with metachronous lymphomas [primary lymphoma (EMZL = 4, DLBCL = 1) with local relapse (EMZL = 3, DLBCL = 2)], one composite EMZL and Epstein-Barr virus (EBV)-positive DLBCL, and four lymphomas (EMZL = 3, FL = 1) with prior or subsequent biopsy showing HT.

Conserve or Reverse? Outcomes of Conservative treatment versus Reverse Shoulder Arthroplasty in displaced 3- & 4-part proximal humeral fractures in patients over 60 years.

Background: The optimal treatment of 3- and 4-part proximal humeral fractures in older adults remains controversial. This aim of this study was compare patient reported outcomes following reverse shoulder arthroplasty (RSA) or non-operative management in patients over 60 years old.

Methods: A retrospective review was undertaken of patients following 3- or 4-part proximal humeral fractures treated with RSA or non-operative treatment with minimum 2-year follow-up.

A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.

Background And Objectives: The pharmacokinetics (PK) of piperacillin/tazobactam (PIP/TAZ) is highly variable across different patient populations and there are controversies regarding non-linear elimination as well as the fraction unbound of PIP (f). This has led to a plethora of subgroup-specific models, increasing the risk of misusing published models when optimising dosing regimens. In this study, we aimed to develop a single model to simultaneously describe the PK of PIP/TAZ in diverse patient populations and evaluate the current dosing recommendations by predicting the PK/pharmacodynamics (PD) target attainment throughout life.

Perinatal emotional skills groups for women and birthing people with borderline personality disorder: outcomes from a feasibility randomised controlled trial.

Background: There is no clear evidence about how to support people with borderline personality disorder (BPD) during the perinatal period. Perinatal emotional skills groups (ESGs) may be helpful, but their efficacy has not been tested.

Aims: To test the feasibility of conducting a randomised controlled trial (RCT) of perinatal ESGs for women and birthing people with BPD.

How do patients determine when their inhaler is empty? Insights from an analysis of returned inhalers and a patient survey.

Background: Inhalers are widely used for the management of asthma and chronic obstructive pulmonary disease. However, there is little knowledge about the extent to which an inhaler is used and when it is disposed of, despite the implications for an individual's health (when used beyond the recommended number of doses (overused)), and medicine wastage, healthcare costs and the environment (when discarded with remaining doses (underused)). To explore inhaler use, we assessed the number of doses remaining in pressurised metered-dose inhalers (pMDIs) returned via a Chiesi Inhaler Recycling scheme.

'Making abortion safe': abortion and post-abortion care providers' experiences of stigma in Rwanda, Zimbabwe, Sierra Leone and Nigeria.

Background: Social stigma and the marginalisation of abortion care within medical settings can negatively affect abortion providers. While some research has evaluated stigma interventions in legally restrictive settings, little work has explored the experiences of healthcare professionals (HCPs) providing abortion and post-abortion care (PAC) outside the USA. This study, part of the Royal College of Obstetricians and Gynaecologists' 'Making Abortion Safe' programme, aimed to understand providers' experiences of abortion stigma in four African countries with restrictive legislation.

The efficacy of cellulose dressings in burn wound management: a systematic review and meta-analysis.

Introduction: Burn wound management is challenging, especially in paediatric patients when optimising outcomes. Superficial burns are generally managed conservatively with dressings; however, frequent dressing changes can be a source of pain and discomfort. Cellulose dressings mitigate these problems, and current reports in the literature have demonstrated positive outcomes when compared against routine dressing types.

"ICODE Hip US Calculator": a mobile phone aid for screening with Graf's sonographic technique.

Aim: Aiming to offer a diagnostic tool to aid examiners with correct hip typing and decision-making about patient management, members of the Board of the International Interdisciplinary Consensus Committee on DDH Evaluation (ICODE - https://www.icode.expert), introduced the cross-platform mobile application (Android and iOS) called "ICODE Hip US Calculator".

International consensus to define outcomes for trials of chemoradiotherapy for anal cancer (CORMAC-2): defining the outcomes from the CORMAC core outcome set.

Variation in outcomes definitions and reporting limit the utility of clinical trial results. The Core Outcome Research Measures in Anal Cancer (CORMAC) project developed a core outcome set (COS) for chemoradiotherapy trials for anal squamous cell carcinoma (ASCC) through an international healthcare professional and patient consensus process. The CORMAC-COS comprises 19 outcomes across 4 domains (disease activity, survival, toxicity, life impact).

Limb Salvage Versus Amputation: A Review of Variables Influencing the Assessment and Decision-Making in Complex Limb Fracture Management.

Complex limb injuries are combination injuries that involve all components of a limb's tissue, such as skin, bone with its surrounding soft tissue cover, and neurovascular elements. Complex limb trauma often has a background of a significant mechanism of injuries such as high-velocity road traffic accidents, ballistic injuries, industrial accidents, and other major mechanisms of injuries which involve high amounts of energy transfer through these tissue layers. These injuries pose a major challenge to trauma and orthopaedic surgeons.

Pure Yolk Sac Testicular Tumour in an Adult: A Diagnostic Dilemma.

A rare case of a pure yolk sac testicular tumour presenting in an adult with learning difficulties is presented. Pure yolk sac tumours are much more common in children, but when they do occur in adults, onset can be both insidious and aggressive. The best practice for identification involves the precise use of ultrasound, blood tests for tumour markers and FDG-PET/CT imaging for staging.

2-year results from an observational study of proactive treatment regimens with intravitreal aflibercept 2 mg in patients with nAMD in clinical practice: XTEND study UK cohort.

Objectives: The 36-month XTEND (NCT03939767) multicentre, observational, prospective study examined the effectiveness of proactive treatment regimens of intravitreal aflibercept (IVT-AFL) 2 mg in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice. The 12- and 24-month outcomes from the XTEND UK cohort are reported.

Methods: Patients aged ≥50 years with nAMD planned to receive IVT-AFL 2 mg were eligible.

Primary Versus Secondary Immune Thrombocytopenia (ITP): A Meeting Report from the 2023 McMaster ITP Summit.

The McMaster Immune Thrombocytopenia (ITP) Summit was an educational seminar from leading experts in immune thrombocytopenia and related disorders geared towards hematologists, internists, immunologists, and clinical and translational scientists. The focus of the Summit was to review the mechanisms, diagnosis and treatment of primary versus secondary ITP. Specific objectives were to describe the unique features of secondary ITP, and to review its mechanisms in the context of autoimmune disease and infection.

The Surgical Management of the Eye in Facial Palsy.

The surgical management of the periocular region in facial palsy is a critical aspect of addressing the ocular morbidity associated with facial paralysis. The reconstruction around the eye in facial palsy should take into account the duration of the facial palsy and underlying ocular pathologies. Exposure keratopathy can develop secondary to lagophthalmos, ectropion, and brow ptosis.

Clinical and patient-reported outcomes in women offered oncoplastic breast-conserving surgery as an alternative to mastectomy: ANTHEM multicentre prospective cohort study.

Background: Oncoplastic breast-conserving surgery may be a better option than mastectomy, but high-quality comparative evidence is lacking. The aim of the ANTHEM study (ISRCTN18238549) was to explore clinical and patient-reported outcomes in a multicentre cohort of women offered oncoplastic breast-conserving surgery as an alternative to mastectomy with or without immediate breast reconstruction.

Methods: Women with invasive/pre-invasive breast cancer who were offered oncoplastic breast-conserving surgery with volume replacement or displacement techniques to avoid mastectomy were recruited prospectively.

The genome of the solitary bee Tetrapedia diversipes (Hymenoptera, Apidae).

Tetrapedia diversipes is a Neotropical solitary bee commonly found in trap-nests, known for its morphological adaptations for floral oil collection and prepupal diapause during the cold and dry season. Here, we present the genome assembly of T. diversipes (332 Mbp), comprising 2,575 scaffolds, with 15,028 predicted protein-coding genes.

Next generation brain health: transforming global research and public health to promote prevention of dementia and reduce its risk in young adult populations.

Efforts to prevent dementia can benefit from precision interventions delivered to the right population at the right time; that is, when the potential to reduce risk is the highest. Young adults (aged 18-39 years) are a neglected population in dementia research and policy making despite being highly exposed to several known modifiable risk factors. The risk and protective factors that have the biggest effect on dementia outcomes in young adulthood, and how these associations differ across regions and groups, still remain unclear.

Building global collaborative research networks in paediatric critical care: a roadmap.

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups.