Myocardial ischaemia following COVID-19: a cardiovascular magnetic resonance study.

The pathophysiology of myocardial injury following COVID-19 remains uncertain. COVID-HEART was a prospective, multicentre study utilising cardiovascular magnetic resonance (CMR) to characterise COVID-related myocardial injury. In this pre-specified analysis, the objectives were to examine (1) the frequency of myocardial ischaemia following COVID-19, and (2) the association between ischaemia and myocardial injury.

C286, an orally available retinoic acid receptor β agonist drug, regulates multiple pathways to achieve spinal cord injury repair.

Retinoic acid receptor β2 (RARβ2) is an emerging therapeutic target for spinal cord injuries (SCIs) with a unique multimodal regenerative effect. We have developed a first-in-class RARβ agonist drug, C286, that modulates neuron-glial pathways to induce functional recovery in a rodent model of sensory root avulsion. Here, using genome-wide and pathway enrichment analysis of avulsed rats' spinal cords, we show that C286 also influences the extracellular milieu (ECM).

Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamic results of KCL-286, a novel retinoic acid receptor-β agonist for treatment of spinal cord injury, in male healthy participants.

Aims: KCL-286 is an orally available agonist that activates the retinoic acid receptor (RAR) β2, a transcription factor which stimulates axonal outgrowth. The investigational medicinal product is being developed for treatment of spinal cord injury (SCI). This adaptive dose escalation study evaluated the tolerability, safety and pharmacokinetics and pharmacodynamic activity of KCL-286 in male healthy volunteers to establish dosing to be used in the SCI patient population.

A randomized comparison of CPX-351 and FLAG-Ida in adverse karyotype AML and high-risk MDS: the UK NCRI AML19 trial.

Liposomal daunorubicin and cytarabine (CPX-351) improved overall survival (OS) compared with 7+3 chemotherapy in older patients with secondary acute myeloid leukemia (AML); to date, there have been no randomized studies in younger patients. The high-risk cohort of the UK NCRI AML19 trial (ISRCTN78449203) compared CPX-351 with FLAG-Ida in younger adults with newly diagnosed adverse cytogenetic AML or high-risk myelodysplastic syndromes (MDS). A total of 189 patients were randomized (median age, 56 years).

Myocardial Involvement After Hospitalization for COVID-19 Complicated by Troponin Elevation: A Prospective, Multicenter, Observational Study.

Background: Acute myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) has a poor prognosis. Its associations and pathogenesis are unclear. Our aim was to assess the presence, nature, and extent of myocardial damage in hospitalized patients with troponin elevation.

Physical activity and liver disease affect the fat-free mass in adolescents with cystic fibrosis.

Unlabelled: Cystic fibrosis (CF) is predominantly a lung disease but is also characterised by impaired skeletal muscularity and a reduction in fat-free mass. We aimed to test the hypothesis that clinical and anthropometric parameters would determine fat-free mass impairment in adolescents with CF. We measured the fat-free mass index (FFMI) using bioelectrical impedance, the lung function using spirometry, the number of shuttles as a measure of exercise tolerance and the reported physical activity in children and young people with CF in a tertiary centre at King's College Hospital, London, UK.

Cellular and molecular mechanisms of IMMunE dysfunction and Recovery from SEpsis-related critical illness in adults: An observational cohort study (IMMERSE) protocol paper.

Sepsis is a common illness. Immune responses are considered major drivers of sepsis illness and outcomes. However, there are no proven immunomodulator therapies in sepsis.

Mortality after 36 weeks postmenstrual age of extremely preterm infants in neonatal care: The impact of growth impairment and bronchopulmonary dysplasia.

Background: A small group of extremely preterm infants survive to 36 weeks postmenstrual age (PMA), but die before discharge from neonatal care.

Aims: To investigate which epidemiological and clinical parameters were related to death after 36 weeks PMA in extremely preterm infants.

Study Design: Retrospective whole-population study.

Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial.

Background: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care.

The organization and impacts of clinical research delivery workforce redeployment during the COVID-19 pandemic: a qualitative case study of one research-intensive acute hospital trust.

Background: COVID-19 has tested healthcare and research systems around the world, forcing the large-scale reorganization of hospitals, research infrastructure and resources. The United Kingdom has been singled out for the speed and scale of its research response. The efficiency of the United Kingdom's research mobilization was in large part predicated on the pre-existing embeddedness of the clinical research system within the National Health Service (NHS), a public, free-at-point-of-delivery healthcare system.

Does closed-loop automated oxygen control reduce the duration of mechanical ventilation? A randomised controlled trial in ventilated preterm infants.

Background: Many preterm infants require supplemental oxygen in the newborn period but experience frequent fluctuations of their oxygen saturation levels. Intermittent episodes of hypoxia or hyperoxia increase the risk of complications. Compliance with achievement of oxygen saturation targets is variable, and the need for frequent adjustments of the inspired oxygen concentration increases workload.

Disrupted Peyer's Patch Microanatomy in COVID-19 Including Germinal Centre Atrophy Independent of Local Virus.

Confirmed SARS-coronavirus-2 infection with gastrointestinal symptoms and changes in microbiota associated with coronavirus disease 2019 (COVID-19) severity have been previously reported, but the disease impact on the architecture and cellularity of ileal Peyer's patches (PP) remains unknown. Here we analysed tissues from throughout the gastrointestinal (GI) tract of patients who died with COVID-19. When virus was detected by PCR in the GI tract, immunohistochemistry identified virus in epithelium and lamina propria macrophages, but not in lymphoid tissues.

Neurally Adjusted Ventilatory Assist in Very Prematurely Born Infants with Evolving/Established Bronchopulmonary Dysplasia.

 During neurally adjusted ventilatory assist (NAVA)/noninvasive (NIV) NAVA, a modified nasogastric feeding tube with electrodes monitors the electrical activity of the diaphragm (Edi). The Edi waveform determines the delivered pressure from the ventilator.  Our objective was to determine whether NAVA/NIV-NAVA has advantages in infants with evolving/established bronchopulmonary dysplasia (BPD).

Epilepsy and mortality: a retrospective cohort analysis with a nested case-control study identifying causes and risk factors from primary care and linkage-derived data.

Objectives: People with epilepsy (PWE) have a higher mortality rate than the general population. Epilepsy-related deaths have increased despite all-cause mortality decreasing in the general population pre-COVID-19. We hypothesised that clinical and lifestyle factors may identify people more at risk.

Less Invasive Surfactant Administration in Very Prematurely Born Infants.

 Less invasive surfactant administration (LISA) is the preferred mode of surfactant administration for spontaneously breathing preterm babies supported by noninvasive ventilation (NIV).  The aim of this study was to determine whether LISA on the neonatal unit or in the delivery suite was associated with reduced rates of bronchopulmonary dysplasia (BPD) or the need for intubation, or lower durations of invasive ventilation and length of hospital stay (LOS).  A historical comparison was undertaken.

Development and Validation of a Good Manufacturing Process for IL-4-Driven Expansion of Chimeric Cytokine Receptor-Expressing CAR T-Cells.

Adoptive cancer immunotherapy using chimeric antigen receptor (CAR) engineered T-cells holds great promise, although several obstacles hinder the efficient generation of cell products under good manufacturing practice (GMP). Patients are often immune compromised, rendering it challenging to produce sufficient numbers of gene-modified cells. Manufacturing protocols are labour intensive and frequently involve one or more open processing steps, leading to increased risk of contamination.

A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex.

There is increasing evidence that endogenous retroviruses (ERVs) play a significant role in central nervous system diseases, including amyotrophic lateral sclerosis (ALS). Studies of ALS have consistently identified retroviral enzyme reverse transcriptase activity in patients. Evidence indicates that ERVs are the cause of reverse transcriptase activity in ALS, but it is currently unclear whether this is due to a specific ERV locus or a family of ERVs.

Demographic, multi-morbidity and genetic impact on myocardial involvement and its recovery from COVID-19: protocol design of COVID-HEART-a UK, multicentre, observational study.

Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, myocardial injury is increasingly reported and associated with adverse outcomes. However, the pathophysiology, extent of myocardial injury and clinical significance remains unclear.

Methods: COVID-HEART is a UK, multicentre, prospective, observational, longitudinal cohort study of patients with confirmed COVID-19 and elevated troponin (sex-specific > 99th centile).

Non-invasive assessment of intrapulmonary shunt and ventilation to perfusion ratio in children with hepatopulmonary syndrome before and after liver transplantation.

Objectives: To use the oxyhaemoglobin dissociation curve (ODC) to non-invasively measure the ventilation perfusion ratio (V/Q) and right-to-left intrapulmonary vascular shunt before and after liver transplantation (LT) in children with hepatopulmonary syndrome (HPS). To investigate whether the right-to-left shunt derived by ODC correlated with the shunt derived by technetium-99 labelled macroaggregated albumin lung perfusion scan (MAA).

Methods: A retrospective cohort study at King's College Hospital NHS Foundation Trust, London, UK was performed between 1998 and 2016.

Using electronic patient records to assess the effect of a complex antenatal intervention in a cluster randomised controlled trial-data management experience from the DESiGN Trial team.

Background: The use of electronic patient records for assessing outcomes in clinical trials is a methodological strategy intended to drive faster and more cost-efficient acquisition of results. The aim of this manuscript was to outline the data collection and management considerations of a maternity and perinatal clinical trial using data from electronic patient records, exemplifying the DESiGN Trial as a case study.

Methods: The DESiGN Trial is a cluster randomised control trial assessing the effect of a complex intervention versus standard care for identifying small for gestational age foetuses.