Therapeutic interventions targeting enteropathy in severe acute malnutrition modulate systemic and vascular inflammation and epithelial regeneration

Sturgeon JP, Mutasa K, Bwakura-Dangarembizi M, Amadi B, Ngosa D, Dzikiti A, Chandwe K, Besa E, Mutasa B, Murch SH, Hill S, Playford RJ, VanBuskirk K, Kelly P, Prendergast AJ, TAME Trial Team.
eBiomedicine 2025

This is an analysis of the tertiary outcomes of the TAME trial, looking at interventions in children with severe acute malnutrition. We showed that:

• Both budesonide and colostrum reduced systemic inflammation
• Children receiving colostrum had higher GLP2 and angiopoietin, and lower LPS, suggesting better epithelial barrier
• N-acetylglucosamine, a precursor for epithelial glycosaminoglycan synthesis, increased biomarkers of epithelial regeneration, and circulating growth factors

Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial

Chandwe K, Bwakura-Dangarembizi M, Amadi B, Tawodzera G, Ngosa D, Dzikiti A, Chulu N, Makuyana R, Zyambo K, Mutasa K, Mulenha C, Besa E, Sturgeon JP, Mudzingwa S, Simunyola B, Kazhila L, Zyambo M, Sonkwe H, Mutasa B, Chipunza M, Suramba V, Langhaug L, Mudenda V, Murch SH, Hill S, Playford RJ, VanBuskitk K, Prendergast AJ, Kelly P.
Nature Communcations 2024

This is an interventinal trial examining novel interventions in children with severe acute malnutrition (SAM)

• n=125 children recruited from Zimbabwe and Zambia
• Teduglutide, a GLP2 analogue reduces a composite score for gut inflammation
• All interventions were safe

Inflammation and epithelial repair predict mortality, hospital readmission, and growth recovery in complicated severe acute malnutrition

Sturgeon JP, Tome J, Dumbura C, Majo FD, Ngosa D, Mutasa K, Zyambo K, Besa E, Chandwe K, Kapoma C, Mwapenya B, Nathoo KJ, Bourke CD, Ntozini R, Chasekwa B, Smuk M, Bwakura-Dangarembizi M, Amadi B, Kelly P, Prendergast AJ
Science Translational Medicine 2024 [Free access via here]   

This paper examines the inflammatory changes in children following admission to hospital with severe acute malnutrition (SAM)

• Inflammatory biomarkers remain abnormal for at least 48 weeks following discharge, compared with community controls
• This incudes inflammation across different body compartments, including acute inflammatory processes, and vascular inflammation.
• There is an interplay between this inflammation, and the levels of growth factors seen.
• The levels of the growth factors, in the face of this higher levels of inflammation, is correlated with better outcomes over that 48 weeks

Risk factors for inpatient mortality among children with severe acute malnutrition in Zimbabwe and Zambia

Sturgeon JP, Mufukari W, Tome J, Dumbura C, Majo FD, Ngosa D, Chandwe K, Kapoma C, Mutasa K, Nathoo KJ, Bourke CD, Ntozini R, Bwakura-Dangarembizi M, Amadi B, Kelly P, Prendergast AJ & the HOPE-SAM study team
European Journal of Clinical Nutrition 2023   

Risk factors for inpatient mortality in children admitted to hospital with severe acute malnutrition (SAM) in the HOPE-SAM study

• presence of oedema, shock, sepsis, persistent diarrhoea, lack of a toilet at home, and recruitment at one Harare site were all independently associated with inpatient mortality.
• This incudes inflammation across different body compartments, including acute inflammatory processes, and vascular inflammation.
• Oedematous children had a significantly higher birthweight than those without oedema

Severe acute malnutrition promotes bacterial binding over proinflammatory cytokine secretion by circulating innate immune cells

Phiri TN, Mutasa K, Rukobo S, Govha M, Mushayanembwa P, Mwakamui S, Haider T, Zyambo K, Dumbura C, Tome J, Runodamoto T, Chidamba L, Majo FD, Ngosa D, Chandwe K, Kapoma C, Mwapenya B, Mufukari W, Sturgeon JP, Robertson RC, Smuk M, Ntozini R, Nathoo K, Amadi B, Kelly P, Bwakura-Dangarembizi M, Prendergast AJ, Bourke CD
Science Advances 2023  

This paper reveals that children with severe acute malnutrition (SAM) show altered immune cell function, with enhanced bacterial binding but reduced inflammatory response, potentially contributing to their high post-discharge morbidity and mortality.

Fat and lean mass predict time to hospital readmission or mortality in children treated for complicated severe acute malnutrition in Zimbabwe and Zambia

Bwakura-Dangarembizi M, Dumbura C, Ngosa D, Majo FD, Piper JD, Sturgeon JP, Nathoo KJ, Amadi B, Norris S, Chasekwa B, Ntozini R, Wells JC, Kelly P, Prendergast AJ, and the HOPE-SAM Study Team
British Journal of Nutrition 2022  

This paper looks at how body composition (fat and lean mass) measured by skinfold thicknesses and impedance analysis, predicts mortality and readmission in children with SAM. It finds that low discharge lean and peripheral fat mass significantly increase risk, and suggests risk stratification and interventions to improve post-discharge care.

  Recovery of children following hospitalisation for complicated severe acute malnutrition

M Bwakura-Dangarembizi, C Dumbara, B Amadi, B Chasekwa, D Ngosa, F D Majo, J P Sturgeon, K Chandwe, C Kapoma, C D Bourke, R C Robertson, K J Nathoo, R Ntozini, S A Norris, P Kelly, A J Prendergast
Maternal & Child Nutrition 2021  

This paper examines the nutritional recovery of children hospitalised with complicated severe acute malnutrition (SAM) in the year after discharge.

• One-in-six children were readmitted into hospital over the year after discharge and one-in-eight remained undernourished.
• Nonoedematous SAM, ongoing SAM at the time of dis- charge and underlying cerebral palsy were independent risk factors for poor outcome.
• Low HAZ was a risk factor for hospital readmission and poor nutritional recovery.

  Children With Noncritical Infections Have Increased Intestinal Permeability, Endotoxemia and Altered Innate Immune Responses

J P Sturgeon, C D Bourke, A J Prendergast
The Pediatric Infectious Disease Journal 2019  

This paper explores the immune changes seen in children admitted to hospital with non-critical infections. The same monocyte HLA-DR reductions are seen as in more critically ill children, such changes being associated with future functional immunosuppression. These chages were also associated with increased gut permeability, and circulating endotoxin, suggesting a cause for the changes.

C-Reactive Protein (CRP) levels in neonatal meningitis in England: an analysis of national variations in CRP cut-offs for lumbar puncture

J P Sturgeon, B Zanetti, D Lindo
BMC Pediatrics 2018
This paper looks at the CRP levels that NHS trusts in England considering doing lumbar punctures in neonates with suspected sepsis, and how they differ from the NICE guidance. Many trusts do not follow the NICE guidance of CRP >10mg/mL for lumbar punctures, and this is reflected in the poor sensitivity and specificity seen in neonates with meningitis from across the country.

Platelet-leucocyte aggregation is augmented in cirrhosis andfurther increased by platelet transfusion

S Stoy, V C Patel, J P Sturgeon, G K Manakkat Vijay, T Lisman, W Bernal, D L Shawcross
Alimentary Pharmacology and Therapeutics 2018  
Building on my previous work below, this paper looks at the effect platelets (or their secreted components) have on leukocyte function, and that in patients with cirrhosis the transfusion of platelets affects other leukocyte functions in vitro. Given the balanced immune dysfunction in cirrhosis, this suggests there needs to be more consideration of the true effects of transfusing these patients.

  Could Abnormal Neutrophil-Platelet Interactions and Complex Formation Contribute to OxidativeStress and Organ Failure in Cirrhosis?

J P Sturgeon, G K Manakkat Vijay, J Ryan, W Bernal, D L Shawcross
Hepatology 2015  
This short report looks at the effect that platelets from patients with cirrhosis have on neutrophils, and shows they are less good at inhiiting oxidative burst than healthy control platelets. This could suggest that there might be some effect from any transfusion of healthy platelets in such patients.

The Variable Rate Intravenous Insulin Infusion Protocol

B Collard, J P Sturgeon, N Patel, S Asharia
BMJ Open Quality 2013   
This paper looks at the service improvement of a trialled new insulin infusion protocol in partients needing a sliding scale.

Inflammation: the driver of poor outcomes among children with severe acute malnutrition?

Sturgeon JP, Njunge JM, Bourke CD, Gonzales GB, Robertson RC, Bwakura-Dangarembizi M, Berkley JA, Kelly P, Prendergast AJ
Nutrition Reviews 2023
Narrarive review examining the role of inflammation in the pathogenesis of the changes seen in children with SAM. Suggestions for future treatments, and therapeutic targets, and comparisons to other diseases that seem to be driven by inflammation.

Postdischarge interventions for children hospitalized with severe acute malnutrition: a systematic review and meta-analysis

CCA Noble, JP Sturgeon, M Bwakura-Dangarembizi, MP Kelly, B Amadi, AJ Prendergast
American Journal of Clinical Nutrition 2021
A systematic review paper examining independent risk factors for interventions for post-discharge mortality in children hospitalised with severe acute malnutrition. Several biological and psychosocial interventions including pre/pro biotics, and psychological interventions show promise in improving outcomes in children following hospitalization for SAM, and should be further explored with larger, powered, randomized controlled trials.

Predictors of inpatient mortality among children hospitalized for severe acute malnutrition: a systematic review and meta-analysis

R Karunaratne*, J P Sturgeon*, R Patel, A J Prendergast
American Journal of Clinical Nutrition 2020
A review paper examining independent risk factors for in-patient mortality in severe acute malnutrition (SAM). Examining studies published since 2000, we have shown that there are seven independent predictors for in-patient mortality in children under 60 months admitted with SAM: HIV, Weight-for-height z-score, diarrhoea, pneumonia, presence of shock, and lack of appetite.
This article has an accompanying editorial.

Recent insights into thepathogenesis of hepaticencephalopathy and treatments

J P Sturgeon, D L Shawcross
Expert Reviews in Gastroenterology and Hepatology 2015
A review paper examining the relationship between inflammation, ammonia, and hepatic encephalopathy, as well as new treatments for the disease incliding non-absorbable antiiotics such as rifaximin-a.

Going Out on a Limb: Do Not Delay Diagnosis of Necrotizing Fasciitis in Varicella Infection

J P Sturgeon, L Segal, A Verma
Pediatric Emergency Care 2015  

An unusual case of abdominal distension: pneumoperitoneumsecondary to pneumomediastinum in a patient with chronicobstructive pulmonary disease

J P Sturgeon, B R B Collard, A K K Patel, L Devoto
BMJ Case Reports 2012

Commentary: Mechanisms of kwashiorkor-associated immune suppression: Insights from human, mouse, and pig studies

GB Gonzales, CD Bourke, J P Sturgeon, JM Njunge, RC Robertson, MP Kelly, JA Berkley
Frontiers in Immunology 2022

Should funders driving for universal open access in research be obliged to ensure freedom of publication for all?

J P Sturgeon
BMJ 2019

Antibiotic prescribing in the paediatric emergency department and the impact of education

D Gkentzi, R Ramachandran, E Day, L Anguvaa, M Borg, N Siva, J Sturgeon, T Jaiganesh, M Sharland, K Doerholt
Journal of paediatrics and child health 2014

Intravenous Access in Children in the Emergency Department

J P Sturgeon, R Lifford, F Cantle
Pediatric emergency care 2014