Clinical experience with the AKT1 inhibitor miransertib in two children with PIK3CA-related overgrowth syndrome.

Background: PIK3CA-related overgrowth spectrum (PROS) refers to a group of rare disorders, caused by somatic activating mutations in PIK3CA, resulting in abnormal PI3K-AKT-mTOR pathway signalling. Significant associated morbidity is frequently observed, and approved treatments are lacking. Miransertib (ARQ 092) is a novel, orally available, selective pan-AKT inhibitor with proven in vitro efficacy.

Simoctocog Alfa (Nuwiq) in Previously Untreated Patients with Severe Haemophilia A: Final Results of the NuProtect Study.

Introduction:  FVIII inhibitor development is the most serious contemporary treatment complication in haemophilia A, particularly in previously untreated patients (PUPs). No inhibitors developed in clinical trials in previously treated patients treated with simoctocog alfa (Nuwiq), a fourth-generation recombinant FVIII produced in a human cell line.

Methods:  The NuProtect study investigated the immunogenicity of simoctocog alfa in PUPs.

Treatment Outcomes for Small Cell Carcinoma of the Bladder: Results From a UK Patient Retrospective Cohort Study.

Purpose: Small cell carcinoma of the bladder (SCCB) is rare, accounting for less than 1% of all bladder carcinomas. It is aggressive, and outcomes are poor as a result of its early metastatic spread. Owing to its rarity, there are limitations on data to propose standardized management pathways.

Why, when and how do secondary-care clinicians have emergency care and treatment planning conversations? Qualitative findings from the ReSPECT Evaluation study.

Background: The Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) is an emergency care and treatment planning (ECTP) process, developed to offer a patient-centred approach to deciding about and recording treatment recommendations. Conversations between clinicians and patients or their representatives are central to the ReSPECT process. This study aims to understand why, when, and how ReSPECT conversations unfold in practice.

Factors associated with secondary traumatic stress and burnout in neonatal care staff: A cross-sectional survey study.

Introduction: High rates of secondary traumatic stress and burnout have been found across nursing populations. However, few studies have focused on neonatal staff.

Objective: The objectives of this article are to explore the prevalence and severity of secondary traumatic stress (STS) and burnout in neonatal staff, and identify risk factors and protective factors for STS and burnout within this population with the aim of informing future staff support.

A novel CASR variant in a family with familial hypocalciuric hypercalcaemia and primary hyperparathyroidism.

Summary: Familial hypocalciuric hypercalcaemia (FHH) is a dominantly inherited, lifelong benign disorder characterised by asymptomatic hypercalcaemia, relative hypocalciuria and variable parathyroid hormone levels. It is caused by loss-of-function pathogenic variants in the calcium-sensing receptor (CASR) gene. Primary hyperparathyroidism (PHPT) is characterised by variable hypercalcaemia in the context of non-suppressed parathyroid hormone levels.

Germline APOBEC3B deletion increases somatic hypermutation in Asian breast cancer that is associated with Her2 subtype, PIK3CA mutations and immune activation.

A 30-kb deletion that eliminates the coding region of APOBEC3B (A3B) is >5 times more common in women of Asian descent compared to European descent. This polymorphism creates a chimera with the APOBEC3A (A3A) coding region and A3B 3'UTR, and it is associated with an increased risk for breast cancer in Asian women. Here, we explored the relationship between the A3B deletion polymorphism with tumour characteristics in Asian women.

Guidelines for Best Practice in the Audiological Management of Adults with Severe and Profound Hearing Loss.

Individuals with severe to profound hearing loss are likely to present with complex listening needs that require evidence-based solutions. This document is intended to inform the practice of hearing care professionals who are involved in the audiological management of adults with a severe to profound degree of hearing loss and will highlight the special considerations and practices required to optimize outcomes for these individuals.

The Impact of COVID-19 Pandemic on Adult and Pediatric Allergy & Immunology Services in the UK National Health Service.

Background: The coronavirus disease 2019 pandemic imposed multiple restrictions on health care services.

Objective: To investigate the impact of the pandemic on Allergy & Immunology (A&I) services in the United Kingdom.

Methods: A national survey of all A&I services registered with the Royal College of Physicians and/or the British Society for Allergy and Clinical Immunology was carried out.

Mononeuritis multiplex: an unexpectedly frequent feature of severe COVID-19.

The prolonged mechanical ventilation that is often required by patients with severe COVID-19 is expected to result in significant intensive care unit-acquired weakness (ICUAW) in many of the survivors. However, in our post-COVID-19 follow-up clinic we have found that, as well as the anticipated global weakness related to loss of muscle mass, a significant proportion of these patients also have disabling focal neurological deficits relating to multiple axonal mononeuropathies. Amongst the 69 patients with severe COVID-19 that have been discharged from the intensive care units in our hospital, we have seen 11 individuals (16%) with such a mononeuritis multiplex.

The Effect of Temperature Increases on Brain Tissue Oxygen Tension in Patients with Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Substudy.

Fever may aggravate secondary brain injury after traumatic brain injury (TBI). The aim of this study was to identify episodes of temperature increases through visual plot analysis and algorithm supported detection, and to describe associated patterns of changes in on brain tissue oxygen tension (PO). Data derive from the high-resolution cohort of the multicenter prospective Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study.

Real-world experience with caplacizumab in the management of acute TTP.

The cornerstone of life-saving therapy in immune-mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti-von Willebrand factor nanobody trialed in 2 multicenter randomized controlled trials (RCTs) leading to European Union and US Food and Drug Administration approval, has been available in the United Kingdom (UK) through a patient access scheme. Data were collected retrospectively from 2018 to 2020 for 85 patients (4 children) receiving caplacizumab from 22 UK hospitals.

The anesthetist as cardiologist: a case of heart block identified in the peripartum period.

We describe a case of undiagnosed heart block which was detected during the postpartum surgical repair of a vaginal tear, and the subsequent investigations that confirmed diagnosis of atrio-ventricular heart block.

Changes in muscle strength and physical function in older patients during and after hospitalisation: a prospective repeated-measures cohort study.

Aim: to investigate changes in knee-extension strength and physical function in older adults during and after acute hospital admission, and the contributions of illness severity, frailty and sedentary activity to changes in knee-extension strength.

Methods: prospective repeated-measures cohort study on a sample of participants aged ≥75 recruited within 24 hours of acute hospital admission. Knee-extension, grip strength and functional mobility (de Morton Mobility Index, DEMMI) were measured at recruitment, day 7 (or discharge if earlier), and at follow-up 4-6 weeks later.

Bouveret Syndrome: A Systematic Review of Endoscopic Therapy and a Novel Predictive Tool to Aid in Management.

Background And Goals: Bouveret syndrome is characterized by gastroduodenal obstruction caused by an impacted gallstone. Current literature recommends endoscopic therapy as the first line of intervention despite significantly lower success rates compared with surgery. The lack of treatment efficacy studies and the paucity of clinical guidelines contribute to current practices being arbitrary.

Understanding Fatigue in Primary Biliary Cholangitis.

Background: Fatigue affects 50% of primary biliary cholangitis patients and is severe in approximately 20%, significantly affecting quality of life. The pathogenesis of fatigue in primary biliary cholangitis is poorly understood. This study aimed to explore subgroups of fatigue to support targeting of selected groups in future clinical trials.

How can we meet the support needs of LGBT cancer patients in oncology? A systematic review.

Objectives: Approximately 3.6 million people in the UK identify as lesbian, gay, bisexual and transgender (LGBT). Fear of discrimination and lack of sexual orientation and gender identity recording suggests LGBT people are invisible to health services.

A multicentre cross-sectional observational study of cancer multidisciplinary teams: Analysis of team decision making.

Background: Multidisciplinary teams (MDT) formulate expert informed treatment recommendations for people with cancer. We set out to examine how the factors proposed by the functional perspective of group decision making (DM), that is, interaction process, internal factors (factors emanating from within the group such as group size), external circumstances (factors coming from the outside of the team), and case-complexity affect the quality of MDT decision making.

Methods: This was a cross-sectional observational study.

Landscape of G-quadruplex DNA structural regions in breast cancer.

Response and resistance to anticancer therapies vary due to intertumor and intratumor heterogeneity. Here, we map differentially enriched G-quadruplex (G4) DNA structure-forming regions (∆G4Rs) in 22 breast cancer patient-derived tumor xenograft (PDTX) models. ∆G4Rs are associated with the promoters of highly amplified genes showing high expression, and with somatic single-nucleotide variants.

Tracheal intubation in traumatic brain injury: a multicentre prospective observational study.

Background: We aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity.

Methods: Data from the international prospective pan-European cohort study, Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI), were used (n=4509). For prehospital intubation, we excluded self-presenters.

Stem Cell Transplantation and Vinblastine Monotherapy for Relapsed Pediatric Anaplastic Large Cell Lymphoma: Results of the International, Prospective ALCL-Relapse Trial.

Purpose: To analyze the efficacy of a risk-stratified treatment of children with relapsed anaplastic large cell lymphoma (ALCL). The ALCL-Relapse trial (ClinicalTrials.gov identifier: NCT00317408) stratified patients according to the time of relapse and CD3 expression to prospectively test reinduction approaches combined with consolidation by allogeneic or autologous hematopoietic stem cell transplantation (SCT) and vinblastine monotherapy.