Patient survival after simultaneous ALPPS and colorectal resection

BACKGROUND: Liver resection combined with colorectal surgery (CRS) is the only curative option in many patients presenting with synchronous colorectal cancer and liver metastases (CRLM). Simultaneous resection has been shown to offer benefits in patients with low hepatic tumor load; however, in the setting of in situ colorectal tumor with extensive CRLM and a small predicted future liver remnant (FLR), the use of simultaneous ALPPS and CRS is controversial, lacking outcome data. METHODS: Thirty-one cases of simultaneous ALPPS and CRS prospectively entered into the International ALPPS Registry were examined. Univariate analysis was used to identify factors associated with 90-day mortality after stage-2. RESULTS: Thirty patients (97%) completed both stages. CRS was performed during stage-1 in 22 patients (73%). Seven patients (23%) had severe complications (Clavien-Dindo ≥ IIIb) following stage-2 ALPPS. The 90-day mortality rate was 15%. Patients who had a severe complication after stage-1 were significantly more likely to have 90-day mortality following stage-2 (p = 0.002). MELD score > 10 on postoperative day-5 after stage-1 was also significantly associated with 90-day mortality (p = 0.011). Disease-free survival and overall survival were 36% and 76% at 1 year, respectively. CONCLUSIONS: In light of the high mortality and poor long-term survival identified in this series, the adoption of ALPPS with CRS cannot be recommended without further data. Patients who suffer severe complications or have an elevated MELD score after stage-1 are at higher risk of mortality following stage-2

Staphylococcus aureus Transporters Hts, Sir, and Sst Capture Iron Liberated from Human Transferrin by Staphyloferrin A, Staphyloferrin B, and Catecholamine Stress Hormones, Respectively, and Contribute to Virulence ▿

Staphylococcus aureus is a frequent cause of bloodstream, respiratory tract, and skin and soft tissue infections. In the bloodstream, the iron-binding glycoprotein transferrin circulates to provide iron to cells throughout the body, but its iron-binding properties make it an important component of innate immunity. It is well established that siderophores, with their high affinity for iron, in many instances can remove iron from transferrin as a means to promote proliferation of bacterial pathogens. It is also established that catecholamine hormones can interfere with the iron-binding properties of transferrin, thus allowing infectious bacteria access to this iron pool. The present study demonstrates that S. aureus can use either of two carboxylate-type siderophores, staphyloferrin A and staphyloferrin B, via the transporters Hts and Sir, respectively, to access the transferrin iron pool. Growth of staphyloferrin-producing S. aureus in serum or in the presence of holotransferrin was not enhanced in the presence of catecholamines. However, catecholamines significantly enhanced the growth of staphyloferrin-deficient S. aureus in human serum or in the presence of human holotransferrin. It was further demonstrated that the Sst transporter was essential for this activity as well as for the utilization of bacterial catechol siderophores. The substrate binding protein SstD was shown to interact with ferrated catecholamines and catechol siderophores, with low to submicromolar affinities. Experiments involving mice challenged intravenously with wild-type S. aureus and isogenic mutants demonstrated that the combination of Hts, Sir, and Sst transport systems was required for full virulence of S. aureus