Development of a multivariable gene-expression signature targeting T-cell-mediated rejection in peripheral blood of kidney transplant recipients validated in cross-sectional and longitudinal samples.

Background: Acute T-cell mediated rejection (TCMR) is usually indicated by alteration in serum-creatinine measurements when considerable transplant damage has already occurred. There is, therefore, a need for non-invasive early detection of immune signals that would precede the onset of rejection, prior to transplant damage.

Methods: We examined the RT-qPCR expression of 22 literature-based genes in peripheral blood samples from 248 patients in the Kidney Allograft Immune Biomarkers of Rejection Episodes (KALIBRE) study.

Sustained inflations during delivery suite stabilisation in prematurely-born infants - A randomised trial.

Background: Sustained inflations at initial stabilisation in the delivery suite may reduce the need for intubation and result in a shorter duration of initial ventilation, but have not been compared to routine UK practice.

Aims: To compare the early efficacy of sustained inflation during stabilisation after delivery to UK practice.

Study Design: A randomised trial was performed of a fifteen second sustained inflation compared to five inflations lasting 2 to 3 s, each intervention could be repeated once if no chest rise was apparent.

Replacing hospital-based epilepsy clinics with rural epilepsy clinics and education in Uganda: impact on attendance.

: A high proportion of the Ugandan population with epilepsy receive no treatment. : To determine whether introduction of an agreed multidisciplinary guideline and establishment of a local clinic outside the hospital and four rural satellite clinics improved attendance and follow-up by children with epilepsy in Western Uganda. : A multidisciplinary team from Kagando Hospital, Kasese, south-west Uganda created a guideline for the management of epilepsy.

Human retinoic acid-regulated CD161 regulatory T cells support wound repair in intestinal mucosa.

Repair of tissue damaged during inflammatory processes is key to the return of local homeostasis and restoration of epithelial integrity. Here we describe CD161 regulatory T (T) cells as a distinct, highly suppressive population of T cells that mediate wound healing. These T cells were enriched in intestinal lamina propria, particularly in Crohn's disease.

UK neonatal resuscitation survey.

Background: Previous surveys have demonstrated that neonatal resuscitation practices on the delivery suite vary between UK units, particularly according to the hospital's neonatal unit's level. Our aim was to determine if recent changes to the Resuscitation Council guidelines had influenced clinical practice.

Methods: Surveys of resuscitation practices at UK delivery units carried out in 2012 and 2017 were compared.

Methemoglobinemia during the Use of Glyceryl Trinitrate Patches in Neonates: Two Case Reports.

Methemoglobinemia can result in severe hypoxia. It has been frequently reported during the use of inhaled nitric oxide, but can occur where nitrate containing medications are used. Glyceryl trinitrate (GTN) patches have been used in the treatment of digital and limb ischemia in prematurely born infants.

Infection control and treatment guidelines and neonatal mortality in a rural hospital in Uganda.

: The neonatal mortality rate in Uganda has been 24-27/1000 live births for the last 14 years. : To determine the impact on neonatal mortality of the introduction of infection prevention and treatment guidelines in a resource-poor setting. : A prospective study was undertaken in Kagando Hospital, a rural hospital in Western Uganda of infants live-born in hospital and those admitted from the community or other hospitals between 2013 and 2017.

Nutritional status and pulmonary outcome in children and young people with cystic fibrosis.

Background: Nutrition is closely related to mortality and pulmonary and respiratory muscle function in cystic fibrosis (CF) patients. We initially validated results from a bioelectrical impedance device against dual energy x-ray absorptiometry (DEXA). We then determined whether fat free mass assessed by a portable impedance device rather than body mass index (BMI) better correlated with pulmonary function, respiratory muscle strength and exercise capacity in CF patients.

Relationship of resuscitation, respiratory function monitoring data and outcomes in preterm infants.

Intraventricular haemorrhage (IVH) and bronchopulmonary dysplasia (BPD) are major complications of premature birth. We tested the hypotheses that prematurely born infants who developed an IVH or BPD would have high expiratory tidal volumes (V) (V > 6 ml/kg) and/or low-end tidal carbon dioxide (ETCO) levels (ETCO levels < 4.5 kPa) as recorded by respiratory function monitoring or hyperoxia (oxygen saturation (SaO) > 95%) during resuscitation in the delivery suite.

Optimized Peptide-MHC Multimer Protocols for Detection and Isolation of Autoimmune T-Cells.

Peptide-MHC (pMHC) multimers have become the "gold standard" for the detection and isolation of antigen-specific T-cells but recent evidence shows that normal use of these reagents can miss fully functional T-cells that bear T-cell receptors (TCRs) with low affinity for cognate antigen. This issue is particularly pronounced for anticancer and autoimmune T-cells as self-reactive T-cell populations are enriched for low-affinity TCRs due to the removal of cells with higher affinity receptors by immune tolerance mechanisms. Here, we stained a wide variety of self-reactive human T-cells using regular pMHC staining and an optimized technique that included: (i) protein kinase inhibitor (PKI), to prevent TCR triggering and internalization, and (ii) anti-fluorochrome antibody, to reduce reagent dissociation during washing steps.

Effect of dexamethasone exposure on the neonatal unit on the school age lung function of children born very prematurely.

The objective of this study was to determine the impact of postnatal dexamethasone treatment on the neonatal unit on the school age lung function of very prematurely born children. Children born prior to 29 weeks of gestational age had been entered into a randomised trial of two methods of neonatal ventilation (United Kingdom Oscillation Study). They had comprehensive lung function measurements at 11 to 14 years of age.

The effects of sleeping position, maternal smoking and substance misuse on the ventilatory response to hypoxia in the newborn period.

Background: Maternal smoking, substance misuse in pregnancy and prone sleeping increase the risk of sudden infant death syndrome (SIDS). We examined the effect of maternal smoking, substance misuse and sleeping position on the newborn response to hypoxia.

Methods: Infants born between 36 and 42 weeks of gestational age underwent respiratory monitoring in the prone and supine sleeping position before and during a hypoxic challenge.

Positive airway pressure devices for the management of breathlessness.

Purpose Of Review: Breathlessness is a common symptom in many chronic diseases and may be refractory to pharmacotherapy. In this review, we discuss the pathophysiology of breathlessness and the role of positive airway pressure (PAP) devices to ameliorate it.

Recent Findings: Breathlessness is directly related to neural respiratory drive, which can be modified by addressing the imbalance between respiratory muscle load and capacity.

A randomized phase 2B trial of vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations - results of a prematurely terminated study.

Background: Studies have suggested the reduced effectiveness of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections with high vancomycin minimum inhibitory concentrations. Alternative agents such as daptomycin may be considered. We conducted a randomized controlled study comparing daptomycin against vancomycin in the treatment of MRSA bloodstream infections with high vancomycin minimum inhibitory concentrations.

Evaluation of eLearning for the teaching of undergraduate ophthalmology at medical school: a randomised controlled crossover study.

Aim: To compare ophthalmology teaching delivered by eLearning with traditional lectures, in terms of undergraduate performance and satisfaction.

Methods: Randomised controlled crossover study at King's College London Medical School with 245 third year medical students. The ophthalmology syllabus was divided into ten topics.

Antidepressant utilisation and incidence of weight gain during 10 years' follow-up: population based cohort study.

Objective: To evaluate the long term association between antidepressant prescribing and body weight.

Design: Population based cohort study.

Setting: General practices contributing to the UK Clinical Practice Research Datalink, 2004-14.

Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer.

Hyperactivation of Wnt and Ras-MAPK signalling are common events in development of colorectal adenomas. Further progression from adenoma-to-carcinoma is frequently associated with 20q gain and overexpression of Aurora kinase A (AURKA). Interestingly, AURKA has been shown to further enhance Wnt and Ras-MAPK signalling.

Association between depressive symptoms and objectively measured daily step count in individuals at high risk of cardiovascular disease in South London, UK: a cross-sectional study.

Objectives: Depressive symptoms are common but rarely considered a risk factor for unhealthy lifestyles associated with cardiovascular disease (CVD). This study investigates whether depressive symptoms are associated with reduced physical activity (PA) in individuals at high risk of developing CVD.

Design: Secondary analysis of the cross-sectional baseline data from a randomised controlled trial of an intensive lifestyle intervention.

Long-term trends in antithrombotic drug prescriptions among adults aged 80 years and over from primary care: a temporal trends analysis using electronic health records.

Purpose: This study aimed to estimate trends in antithrombotic prescriptions from 2001 to 2015 among people aged 80 years and over within clinical indications.

Methods: A prospective cohort study with 215,559 participants registered with the UK Clinical Practice Research Datalink from 2001 to 2015 was included in the analyses. The prevalence and incidence of antiplatelet and anticoagulant drugs were estimated for each year and by five clinical indications.

Paediatric outcomes and timing of admission.

Studies of adult patients have demonstrated that weekend admissions compared with weekday admissions had a significantly higher hospital mortality rate. We have reviewed the literature to determine if the timing of admission, for example, weekend or weekday, influenced mortality and morbidity in children. Seventeen studies reported the effect of timing of admission on mortality, and only four studies demonstrated an increase in those admitted at the weekend.

Cell Therapy in Organ Transplantation: Our Experience on the Clinical Translation of Regulatory T Cells.

Solid organ transplantation is the treatment of choice for patients with end-stage organ dysfunction. Despite improvements in short-term outcome, long-term outcome is suboptimal due to the increased morbidity and mortality associated with the toxicity of immunosuppressive regimens and chronic rejection (1-5). As such, the attention of the transplant community has focused on the development of novel therapeutic strategies to achieve allograft tolerance, a state whereby the immune system of the recipient can be re-educated to accept the allograft, averting the need for long-term immunosuppression.

Update: non-invasive ventilation in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) remains a common cause of morbidity and mortality worldwide. Patients with COPD and respiratory failure, whether acute or chronic have a poorer prognosis than patients without respiratory failure. Non-invasive ventilation (NIV) has been shown to be a useful tool in both the acute hospital and chronic home care setting.