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T-follicular helper (Tfh) cells are key drivers of antibodies that protect from malaria. However, little is known regarding the host and parasite factors that influence Tfh and functional antibody development. Here, we use samples from a large cross-sectional study of children residing in an area of high malaria transmission in Uganda to characterize Tfh cells and functional antibodies to multiple parasites stages. We identify a dramatic re-distribution of the Tfh cell compartment with age that is independent of malaria exposure, with Th2-Tfh cells predominating in early childhood, while Th1-Tfh cell gradually increase to adult levels over the first decade of life. Functional antibody acquisition is age-dependent and hierarchical acquired based on parasite stage, with merozoite responses followed by sporozoite and gametocyte antibodies. Antibodies are boosted in children with current infection, and are higher in females. The children with the very highest antibody levels have increased Tfh cell activation and proliferation, consistent with a key role of Tfh cells in antibody development. Together, these data reveal a complex relationship between the circulating Tfh compartment, antibody development and protection from malaria.

Summary: Background: An episode of acute ulcerative colitis (UC) represents an important watershed moment in a patient's disease course. Aims: To derive a personalised algorithm for identifying patients at high risk of corticosteroid non‐response from variables available at hospital presentation using a large prospectively collected acute UC patient database and machine learning‐based techniques. Methods: We analysed data from 682 consecutive presentations of acute UC. We used an Akaike information criterion‐based elastic net model to select variables based on the 419 earliest presentations of acute UC (1996–2017). We constructed two risk‐scoring algorithms, with and without utilising additional endoscopic variables, using logistic regression models. We validated these risk scores on separate cohorts of 181 (2018–2022) and 82 (2015–2022) acute UC presentations. Results: The partial risk of rescue (ROR) score included the admission indices of oral corticosteroid treatment, bowel frequency ≥6/24 h, albumin, CRP ≥12 mg/mL and log10CRP. The full ROR score incorporates the same variables with the addition of the Mayo endoscopic subscore and disease extent. The AUCs in the main validation cohort were 0.76 (95% CI: 0.69–0.83) and 0.78 (95% CI: 0.71–0.85) for the partial and full ROR scores, respectively. Conclusions: These pragmatic personalised risk scores (available at www.severecolitis.com) have comparably strong performance characteristics and usability enabling the identification of individuals at high risk of corticosteroid non‐response before or after endoscopic assessment. The ROR scores have the potential to challenge conventional acute UC treatment paradigms by identifying patients who may benefit from early rescue therapy or participation in relevant clinical trials. [ABSTRACT FROM AUTHOR]

Objective: The 'Red Blanket' protocol fast tracks trauma patients with severe blood loss to the designated trauma operating theatre directly from the hospital helipad or Emergency Department. This study aimed to assess the impact of patient blood management (PBM) strategies on severely injured trauma patients treated under the 'Red Blanket' protocol at a quaternary referral hospital. Methods: This retrospective review was conducted on all urgent trauma cases that were treated under the 'Red Blanket' protocol in a ten-year period between January 2007 and December 2017. The use of blood products and patient outcomes was compared between the 3.5-year periods pre- and post-ROTEM® implementation on 30th June 2014 (Jan 2011-June 2014 versus July 2014-Dec 2017). Results: During the study period, 120 trauma patients were treated under the 'Red Blanket' protocol at our institution. Intention to treat analysis showed a reduction in fresh frozen plasma usage following the introduction of ROTEM®-guided transfusion. Furthermore, subgroup analysis suggested reduced blood product usage in patients who survived. Conclusions: Patient blood management is a coordinated package of systems and tools, including education, patient logistics, anaemia management, intraoperative cell salvage, rotational thromboelastometry and massive transfusion protocols that together conserve blood products and improve outcomes. The implementation of ROTEM®-guided transfusion demonstrated a reduction in fresh frozen plasma usage. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in the liver as a consequence of metabolic perturbations associated with obesity, type 2 diabetes, dyslipidemia, and insulin resistance. People with NAFLD may develop metabolic and cardiovascular complications and/or liver-related complications, especially fibrosis and hepatocellular carcinoma, associated with high morbidity and mortality. Due to the high and increasing prevalence of NAFLD, there is an urgent need to identify people at risk of developing liver fibrosis and complications. CC-chemokine ligand 2 (CCL2) is chemokine that attracts inflammatory monocytes to stressed or injured tissues. Infiltrating inflammatory monocytes and CCL2 are strongly implicated in the pathogenesis of liver disease in animal models; however, evidence in patient cohorts is conflicting. Methods: We investigated associations between circulating CCL2 and clinical parameters, including fibrosis assessed by liver stiffness measurement, in a cohort of 250 NAFLD patients. We also measured fatty acid binding protein 2 (FABP2), a putative biomarker of intestinal permeability in patients with liver disease, since pro-inflammatory gut-derived microbial products may induce inflammatory chemokines such as CCL2. Results: Serum CCL2 levels were weakly associated with liver stiffness, but the association was no longer significant after accounting for age, diabetes, and BMI in a multivariable model. Consistent with this, girth and BMI were the strongest predictors of elevated circulating CCL2. Serum FABP2 was weakly, but significantly, correlated with CCL2, and negatively correlated with estimated glomerular filtration rate. Conclusion: Circulating CCL2 and FABP2 are associated with NAFLD comorbidities but not liver disease progression in patients with NAFLD. [ABSTRACT FROM AUTHOR]

Background: Hyperglycaemia occurs frequently in the critically ill. Dietary intake of advanced glycation end‐products (AGEs), specifically Nε‐(carboxymethyl)lysine (CML), may exacerbate hyperglycaemia through perturbation of insulin sensitivity. The present study aimed to determine whether the use of nutritional formulae, with varying AGE loads, affects the amount of insulin administered and inflammation. Methods: Exclusively tube fed patients (n = 35) were randomised to receive Nutrison Protein Plus Multifibre®, Diason® or Glucerna Select®. Insulin administration was standardised according to protocol based on blood glucose (<10 mmol L–1). Samples were obtained at randomisation and 48 h later. AGEs in nutritional formula, plasma and urine were measured using mass spectrometry. Plasma inflammatory markers were measured using an enzyme‐linked immunosorbent assay and multiplex bead‐based assays. Results: AGE concentrations of CML in nutritional formulae were greatest with delivery of Nutrison Protein Plus® (mean [SD]; 6335 pmol mol–1 [2436]) compared to Diason® (4836 pmol mol–1 [1849]) and Glucerna Select® (4493 pmol mol–1 [1829 pmol mol–1]) despite patients receiving similar amounts of energy (median [interquartile range]; 12 MJ [8.2–13.7 MJ], 11.5 MJ [8.3–14.5 MJ], 11.5 MJ [8.3–14.5 MJ]). More insulin was administered with Nutrison Protein Plus® (2.47 units h–1 [95% confidence interval (CI) = 1.57–3.37 units h–1]) compared to Diason® (1.06 units h–1 [95% CI = 0.24–1.89 units h–1]) or Glucerna Select® (1.11 units h–1 [95% CI = 0.25–1.97 units h–1]; p = 0.04). Blood glucose concentrations were similar. There were associations between greater insulin administration and reductions in circulating interleukin‐6 (r = –0.46, p < 0.01), tumour necrosis factor‐α (r = −0.44, p < 0.05), high sensitivity C‐reactive protein (r = −0.42, p < 0.05) and soluble receptor for advanced glycation end‐products (r = −0.45, p < 0.01) concentrations. Conclusions: The administration of greater AGE load in nutritional formula potentially increases the amount of insulin required to maintain blood glucose within a normal range during critical illness. There was an inverse relationship between exogenous insulin and plasma inflammatory markers. Key points: Enteral nutrition formula comprise varying amounts of advanced glycation end‐products, specifically Nε‐(carboxymethyl)lysine (CML), which has the potential to exacerbate hyperglycaemia as seen in the healthy population.Patients in the control arm, receiving the highest carbohydrate and CML quantity, had a higher exogenous insulin requirement compared to the two interventional formulae.Our findings also showed an association between increasing doses of insulin and a reduction in inflammatory markers (interleukin‐6, tumour necrosis factor‐α and high sensitivity C‐reactive protein).Further research is required to determine whether manipulation of AGEs in enteral nutrition formula impacts insulin sensitivity and inflammation. [ABSTRACT FROM AUTHOR]

Background: Queensland introduced a colour‐coded cardiotocograph (CTG) classification system (green, blue, yellow and red) to complement the Royal Australian and New Zealand College of Obstetricians and Gynaecologists prose‐based classification system of 'low, unlikely, maybe or likely' fetal compromise. Aims: The aim of the study was to determine the clinical impact of the introduction of the colour‐coded CTG classification system compared to the prose‐based system. We hypothesised there would be no change in the rate of operative delivery for intrapartum fetal compromise (OD‐IFC). Materials and methods: This retrospective non‐inferiority study from November 2014 to May 2018 used routinely collected data from the Mater Mother's Hospital. Non‐insured women with a singleton, non‐anomalous, cephalic fetus at term, attempting a vaginal birth with continuous intrapartum CTG were included. The primary outcome was OD‐IFC. Secondary outcomes included various obstetric and perinatal outcomes. Non‐inferiority analysis was performed with a pre‐specified non‐inferiority margin of 2% risk difference. Results: Eleven thousand seven hundred and twenty‐seven participants were included. The OD‐IFC rate was similar across the study groups (prose‐based 15.1% vs colour‐coded 15.3%, adjusted odds ratio (aOR) 1.02, 95% CI 0.93–1.13) with the adjusted risk difference of 0.29% (95% CI −0.98 to 1.56), which did not exceed the inferiority margin. There were more spontaneous (aOR 1.11, 95% CI 1.04–1.19) and fewer instrumental (aOR 0.87, 95% CI 0.80–0.95) vaginal births in the colour‐coded cohort. There were no differences in neonatal outcomes. Conclusions: Reassuringly, the colour‐coded CTG classification system was non‐inferior to the prose‐based system, did not influence OD‐IFC but was associated with more spontaneous vaginal deliveries. [ABSTRACT FROM AUTHOR]