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Systemic Salmonella infection commonly induces prolonged splenomegaly in murine or human hosts. Although this increase in splenic cellularity is often assumed to be due to the recruitment and expansion of leukocytes, the actual cause of splenomegaly remains unclear. We monitored spleen cell populations during Salmonella infection and found that the most prominent increase is found in the erythroid compartment. At the peak of infection, the majority of spleen cells are immature CD71−Ter119+ reticulocytes, indicating that massive erythropoiesis occurs in response to Salmonella infection. Indeed, this increase in RBC precursors corresponded with marked elevation of serum erythropoietin (EPO). Furthermore, the increase in RBC precursors and EPO production required innate immune signaling mediated by Myd88/TRIF. Neutralization of EPO substantially reduced the immature RBC population in the spleen and allowed a modest increase in host control of infection. These data indicate that early innate immunity to Salmonella initiates marked splenic erythropoiesis and may hinder bacterial clearance.

Acknowledgements: These studies were supported by funding from the British Heart

Early experience with the GORE Acuseal is encouraging. Patency and bacteremia rates are at least comparable to standard polytetrafluoroethylene grafts. ecAVGs have permitted cannulation within 24 hours of insertion and line avoidance in the majority of patients. Nearly three-quarters of patients achieved a definitive "personal vascular access solution" from their ecAVG.

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Patients with bilateral central vein stenosis often require more than one vascular access modality to achieve a "personal access solution." Native long saphenous vein loops provided the best long-term patency. Expedited renal transplantation with priority local allocation of DCD organs to patients with precarious vascular access provides a potential solution to this difficult problem.

BackgroundGuidance varies regarding the optimal timing of arteriovenous fistula (AVF) creation. The aim of this study was to evaluate the association between uraemia, haemodialysis and early AVF failure.MethodsImmunoblotting and cell proliferation assays were performed on vascular smooth muscle cells (VSM) cells isolated from long saphenous vein samples to evaluate the cells’ ability to proliferate when stimulated with uraemic (post-dialysis) and hyperuraemic (pre-dialysis) serum. Clinical data was collected prospectively for 569 consecutive radiocephalic (RCF) and brachiocephalic (BCF) fistulae. The primary outcome was AVF failure at 6 weeks. Dialysis status (haemodialysis (HD); pre-dialysis (Pre-D)), eGFR and serum urea were evaluated to determine if they affected early AVF failure.ResultsHuman VSM cells demonstrated increased capacity to proliferate when stimulated with hyperuraemic serum. There was no significant difference in early failure rate of either RCF or BCF depending on dialysis status (pre-D RCF 31.4% (n = 188); pre-D BCF 22.4% (n = 165); HD RCF 29.3% (n = 99); HD BCF 25.9% (n = 116); p = 0.34). There was no difference in mean eGFR between those patients with early AVF failure and those without (11.2+/-0.2 ml/min/1.73 m2 vs. 11.6+/-0.4 ml/min/1.73 m2; p = 0.47). Uraemia was associated with early AVF failure (serum urea: 35.0+/-0.7 mg/dl vs. 26.6+/-0.3 mg/dl (p < 0.001)).ConclusionsWe present the first in vivo evidence of an association between adverse early AVF outcomes and uraemia. This is supported mechanistically by in vitro work demonstrating a pro-mitogenic effect of hyperuraemic serum. We hypothesise that uraemia-driven upregulation of VSM cell proliferation at the site of surgical insult in contributes to higher early AVF failure rates.

T hrough-knee amputation accounts for just 2.8% of annual amputations in England. Traditionally it is viewed as an operation with poor outcomes, and its use limited. We present a case series and review of articles published on through knee amputation.The literature review covers the 17 papers identified on through-knee amputation in peripheral vascular disease. The results are summarised and discussed, with favourable outcomes in terms of perioperative mortality and primary healing demonstrated in the majority of papers.In the case series, 14 patients who underwent through knee amputation were retrospectively reviewed. Perioperative mortality was 7%. Primary healing was achieved in 79% of cases. Functional outcomes were excellent, with predicted functional activity achieved in 81% of survivors, with 34% ambulating regularly.In conclusion, through-knee amputation should be considered as an alternative to transfemoral amputation, as perioperative mortality, healing rates and functional outcomes appear excellent, both in this series and the majority of others published. Br J Diabetes Vasc Dis 2012;12:26-32