Urinary tract imaging in infants with spina bifida: a selective approach to a baseline DMSA.

INTRODUCTION: There is no general agreement among paediatric urologists on how infants with spina bifida (SB) should be investigated after birth. Recently the EUA/ESPU guidelines have been published recommending a baseline DMSA scan in the first year of life and a Voiding Cystourethrogram (VCUG) or Videourodynamic (VUD) between the second and third month of life. OBJECTIVE: The aim of this study was to evaluate the outcome of renal investigations in the first year of life in infants with SB to verify if an early DMSA scan is indicated in the management of this group of patients. METHODS: All renal imaging, Renal and Bladder Ultrasound (RBUS), VCUGs, VUDs and DMSA were reviewed by two independent assessors to evaluate outcome. RESULTS: Seventy patients with spina bifida (40 girls) were enrolled between June 2015 and February 2020. An early VUD detected vesico-ureteral reflux (VUR) in 8/49 (16%) of patients. An early VUD also gave additional information on detrusor under or over activity, bladder trabeculation, end filling detrusor pressure (EFDP) and sphincteric incompetence. DMSA scan detected renal scarring in 4/68 (6%) patients. Three of these 4 patients had significant history of febrile UTIs while the fourth patient had grade 2 left sided VUR. CONCLUSIONS: The initial assessment of a newborn with myelodysplasia includes a Renal and Bladder Ultrasound during birth hospitalization. This study confirms the recently published EUA/ESPU guidelines on the management of neurogenic bladder in children and adolescents, which recommend a VUD or VCUG & Cystomanometry with Electromyogram (CMG) (if VUD not available) in the first 6-12 weeks of life. A selective approach to DMSA scan only in infants with SB who either had a febrile UTI or vesico-ureteric reflux would not have missed any scarring or dysplasia and would have saved 58 unnecessary nuclear scans.

Osteoarthritis-associated basic calcium phosphate crystals alter immune cell metabolism and promote M1 macrophage polarization.

OBJECTIVE: A number of studies have demonstrated that molecules called 'alarmins' or danger-associated molecular patterns (DAMPs), contribute to inflammatory processes in the OA joint. Metabolic reprogramming of immune cells, including macrophages, is emerging as a prominent player in determining immune cell phenotype and function. The aim of this study was to investigate if basic calcium phosphate (BCP) crystals which are OA-associated DAMPs, impact on macrophage phenotype and metabolism. METHODS: Human monocyte derived macrophages were treated with BCP crystals and expression of M1 (CXCL9, CXCL10) and M2 (MRC1, CCL13)-associated markers was assessed by real-time PCR while surface maturation marker (CD40, CD80 & CD86) expression was assessed by flow cytometry. BCP induced metabolic changes were assessed by Seahorse analysis and glycolytic marker expression (hexokinase 2(HK2), Glut1 and HIF1α) was examined using real-time PCR and immunoblotting. RESULTS: Treatment with BCP crystals upregulated mRNA levels of CXCL9 and CXCL10 while concomitantly downregulating expression of CCL13 and MRC1. Furthermore, BCP-treated macrophages enhanced surface expression of the maturation makers, CD40, CD80 and CD86. BCP-treated cells also exhibited a shift towards glycolysis as evidenced by an increased ECAR/OCR ratio and enhanced expression of the glycolytic markers, HK2, Glut1 and HIF1α. Finally, BCP-induced macrophage activation and alarmin expression was reduced in the presence of the glycolytic inhibitor, 2-DG. CONCLUSIONS: This study not only provides further insight into how OA-associated DAMPs impact on immune cell function, but also highlights metabolic reprogramming as a potential therapeutic target for calcium crystal-related arthropathies.

Growth plate extracellular matrix-derived scaffolds for large bone defect healing.

Limitations associated with demineralised bone matrix and other grafting materials have motivated the development of alternative strategies to enhance the repair of large bone defects. The growth plate (GP) of developing limbs contain a plethora of growth factors and matrix cues which contribute to long bone growth, suggesting that biomaterials derived from its extracellular matrix (ECM) may be uniquely suited to promoting bone regeneration. The goal of this study was to generate porous scaffolds from decellularised GP ECM and to evaluate their ability to enhance host mediated bone regeneration following their implantation into critically-sized rat cranial defects. The scaffolds were first assessed by culturing with primary human macrophages, which demonstrated that decellularisation resulted in reduced IL-1ß and IL-8 production. In vitro, GP derived scaffolds were found capable of supporting osteogenesis of mesenchymal stem cells via either an intramembranous or an endochondral pathway, demonstrating the intrinsic osteoinductivity of the biomaterial. Furthermore, upon implantation into cranial defects, GP derived scaffolds were observed to accelerate vessel in-growth, mineralisation and de novo bone formation. These results support the use of decellularised GP ECM as a scaffold for large bone defect regeneration.

In-hospital stroke: characteristics and outcomes.

In-hospital stroke (IS) made up 6.5% of strokes recorded in the Irish National Stroke Register in 2012. International research has demonstrated poorer outcomes post IS compared to out of hospital stroke (OS). We aimed to profile all IS and OS over a 22 month period and compare the two groups by gathering data from the HIPE portal stroke register. The study site is a primary stroke centre. IS represented 11% (50/458) of total strokes with over half (27/50, 54%) admitted initially with medical complaints. IS patients had a significantly longer length of stay (79.2 +/- 87.4 days vs. 21.9 +/- 45.9 days, p < 0.01) and higher mortality (13/50 vs. 39/408, p < 0.01). Patients in the IS group were also less likely to receive stroke unit care (1/50 vs. 136/408, p < 0.01). This study demonstrates the significant morbidity and mortality associated with IS and highlights the need for efforts to be made to optimize identification and management of acute stroke in this cohort.