Tranexamic acid for significant traumatic brain injury (The CRASH-3 trial): Statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial.

Worldwide, traumatic brain injury (TBI) kills or hospitalises over 10 million people each year. Early intracranial bleeding is common after TBI, increasing the risk of death and disability. Tranexamic acid reduces blood loss in surgery and death due to bleeding in trauma patients with extra-cranial injury.

Relationship between renal CD68 infiltrates and the Oxford Classification of IgA nephropathy.

Aims: The Oxford Classification E score (endocapillary hypercellularity) predicts renal functional decline in IgA nephropathy (IgAN) patients free from steroid/immunosuppressive (IS) therapy, but is poorly reproducible. We hypothesise that endocapillary hypercellularity reflects glomerular inflammation and that the presence of CD68-positive cells is a more robust marker of E score.

Methods And Results: CD68-positive cells were quantified in glomeruli and tubulointerstitium in biopsies from 118 IgAN patients, and cell counts were correlated with the criteria of the Oxford Classification, assigned on PAS-stained serial sections.

Outcome measures in clinical trials of treatments for acute severe haemorrhage.

Background: Acute severe haemorrhage is a common complication of injury, childbirth, surgery, gastrointestinal pathologies and other medical conditions. Bleeding is a major cause of death, but patients also die from non-bleeding causes, the frequency of which varies by the site of haemorrhage and between populations. Because patients can bleed to death within hours, established interventions inevitably take priority over randomisation into a trial.

Histologic Classification of IgA Nephropathy: Past, Present, and Future.

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Since its description in 1968, a number of histologic descriptions and classification systems have emerged, the most recent of which is the Oxford Classification of IgAN. We present a historical panorama of histologic classifications of IgAN and discuss the most recent developments, updates, and future challenges of the Oxford Classification of IgAN.

Understanding and predicting disease relationships through similarity fusion.

Motivation: Combining disease relationships across multiple biological levels could aid our understanding of common processes taking place in disease, potentially indicating opportunities for drug sharing. Here, we propose a similarity fusion approach which accounts for differences in information content between different data types, allowing combination of each data type in a balanced manner.

Results: We apply this method to six different types of biological data (ontological, phenotypic, literature co-occurrence, genetic association, gene expression and drug indication data) for 84 diseases to create a 'disease map': a network of diseases connected at one or more biological levels.

Colloids versus crystalloids for fluid resuscitation in critically ill people.

Background: Critically ill people may lose fluid because of serious conditions, infections (e.g. sepsis), trauma, or burns, and need additional fluids urgently to prevent dehydration or kidney failure.

Release of cell wall phenolic esters during hydrothermal pretreatment of rice husk and rice straw.

Background: Rice husk and rice straw represent promising sources of biomass for production of renewable fuels and chemicals. For efficient utilisation, lignocellulosic components must first be pretreated to enable efficient enzymatic saccharification and subsequent fermentation. Existing pretreatments create breakdown products such as sugar-derived furans, and lignin-derived phenolics that inhibit enzymes and fermenting organisms.

Eavesdropping and crosstalk between secreted quorum sensing peptide signals that regulate bacteriocin production in Streptococcus pneumoniae.

Quorum sensing (QS), where bacteria secrete and respond to chemical signals to coordinate population-wide behaviors, has revealed that bacteria are highly social. Here, we investigate how diversity in QS signals and receptors can modify social interactions controlled by the QS system regulating bacteriocin secretion in Streptococcus pneumoniae, encoded by the blp operon (bacteriocin-like peptide). Analysis of 4096 pneumococcal genomes detected nine blp QS signals (BlpC) and five QS receptor groups (BlpH).

The impact of early outcome events on the effect of tranexamic acid in post-partum haemorrhage: an exploratory subgroup analysis of the WOMAN trial.

Background: In severe post-partum haemorrhage, death can occur within hours of bleeding onset so interventions to control the bleeding must be given immediately. In clinical trials of treatments for life-threatening bleeding, established treatments are given priority and the trial treatment is usually given last. However, enrolling patients in whom severe maternal morbidity or death is imminent or inevitable at the time of randomisation may dilute the effects of a trial treatment.

Risk factors for peripartum hysterectomy among women with postpartum haemorrhage: analysis of data from the WOMAN trial.

Background: Peripartum hysterectomy can cause significant morbidity and mortality. Most studies of peripartum hysterectomy are from high income countries. This cohort study examined risk factors for peripartum hysterectomy using data from Africa, Asia, Europe and the Americas.

Neonatal leukaemia.

Neonatal leukaemia is defined as occurring within the first 28 days of life and most, if not all, cases are congenital. With the exception of Down syndrome-associated transient abnormal myelopoiesis, which is not considered here, neonatal leukaemias are rare. In two-thirds of patients the disease manifests as an acute myeloid leukaemia, frequently with monocytic/monoblastic characteristics.

Repurposing available drugs for neurodevelopmental disorders: The fragile X experience.

Many available drugs have been repurposed as treatments for neurodevelopmental disorders. In the specific case of fragile X syndrome, many clinical trials of available drugs have been conducted with the goal of disease modification. In some cases, detailed understanding of basic disease mechanisms has guided the choice of drugs for clinical trials, and several notable successes in fragile X clinical trials have led to common use of drugs such as minocycline in routine medical practice.

Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial.

Background: Tranexamic acid can prevent death due to bleeding after trauma and post-partum haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in adults with stroke due to intracerebral haemorrhage.

Methods: We did an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage from acute stroke units at 124 hospital sites in 12 countries.

Twenty-four-hour normothermic perfusion of discarded human kidneys with urine recirculation.

Transportable normothermic kidney perfusion for 24 hours or longer could enable viability assessment of marginal grafts, increased organ use, and improved transplant logistics. Eleven clinically declined kidneys were perfused normothermically, with 6 being from donors after brain death (median cold ischemia time 33 ± 36.9 hours) and 5 being from donors after circulatory death (36.

Haematological and fibrinolytic status of Nigerian women with post-partum haemorrhage.

Background: Early treatment with tranexamic acid reduces deaths due to bleeding after post-partum haemorrhage. We report the prevalence of haematological, coagulation and fibrinolytic abnormalities in Nigerian women with postpartum haemorrhage.

Methods: We performed a secondary analysis of the WOMAN trial to assess laboratory data and rotational thromboelastometry (ROTEM) parameters in 167 women with postpartum haemorrhage treated at University College Hospital, Ibadan, Nigeria.

Effect of emotional content on online video sharing among health care professionals and researchers (DIFFUSION): results and lessons learnt from a randomised controlled trial.

Objectives: We assessed the effect of emotional content on the extent to which online videos are shared among health professionals.

Setting: We conducted a two-arm randomised controlled trial. We sent a link to one of two videos by email to participants asking them to watch the video and forward it to their colleagues.

Manipulation of host and parasite microbiotas: Survival strategies during chronic nematode infection.

Intestinal dwelling parasites have evolved closely with the complex intestinal microbiota of their host, but the significance of the host microbiota for metazoan pathogens and the role of their own intestinal microbiota are still not fully known. We have found that the parasitic nematode acquired a distinct intestinal microbiota from its host, which was required for nematode fitness. Infection of germ-free mice and mice monocolonized with demonstrated that successful infections require a host microbiota.

Optimising conditions for bioethanol production from rice husk and rice straw: effects of pre-treatment on liquor composition and fermentation inhibitors.

Background: Rice straw and husk are globally significant sources of cellulose-rich biomass and there is great interest in converting them to bioethanol. However, rice husk is reportedly much more recalcitrant than rice straw and produces larger quantities of fermentation inhibitors. The aim of this study was to explore the underlying differences between rice straw and rice husk with reference to the composition of the pre-treatment liquors and their impacts on saccharification and fermentation.

Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices.

We present a consensus report pertaining to the improved clarity of definitions and classification of glomerular lesions in lupus nephritis that derived from a meeting of 18 members of an international nephropathology working group in Leiden, Netherlands, in 2016. Here we report detailed recommendations on issues for which we can propose adjustments based on existing evidence and current consensus opinion (phase 1). New definitions are provided for mesangial hypercellularity and for cellular, fibrocellular, and fibrous crescents.

Does tranexamic acid lead to changes in MRI measures of brain tissue health in patients with spontaneous intracerebral haemorrhage? Protocol for a MRI substudy nested within the double-blind randomised controlled TICH-2 trial.

Objectives: To test whether administration of the antifibrinolytic drug tranexamic acid (TXA) in patients with spontaneous intracerebral haemorrhage (SICH) leads to increased prevalence of diffusion-weighted MRI-defined hyperintense ischaemic lesions (primary hypothesis) or reduced perihaematomal oedema volume, perihaematomal diffusion restriction and residual MRI-defined SICH-related tissue damage (secondary hypotheses).

Design: MRI substudy nested within the double-blind randomised controlled Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 trial (ISRCTN93732214).

Setting: International multicentre hospital-based study.