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Objective: To test the hypothesis that the addition of an aminoglycoside to a ß-lactam antibiotic could provide better outcomes than ß-lactam monotherapy for the initial empirical treatment of hematological neutropenic patients with subsequently documented Gram-negative bacilli (GNB) bloodstream infection (BSI). Methods: Multinational, retrospective, cohort study of GNB BSI episodes in hematological neutropenic patients in six centers (2010–2017). Combination therapy (ß-lactam plus aminoglycoside) was compared to ß-lactam monotherapy. The primary endpoint was the case-fatality rate assessed at 7 and 30-days from BSI onset. Secondary endpoints were nephrotoxicity and persistent BSI. Propensity score (PS) matching was performed. Results: Among 542 GNB BSI episodes, 304 (56%) were initially treated with combination therapy, with cefepime plus amikacin being most common (158/304, 52%). Overall, Escherichia coli (273/304, 50.4%) was the main etiological agent, followed by Pseudomonas aeruginosa, which predominated in the combination group [76/304 (25%) vs. 28/238 (11.8%); p<0.001]. Multidrug resistance rates were similar between groups [83/294 (28.2%) vs. 63/233 (27%); p=0.95]. In the multivariate analysis combination therapy was associated with lower 7-day case-fatality rate (OR 0.37, 95%CI 0.14-0.91;p=0.035) with a tendency towards lower mortality at 30 days (OR 0.56, 95%CI 0.29–1.08;p=0.084). After PS-matching, these differences remained for the 7-day case-fatality rate (OR 0.33, 95%CI 0.13–0.82;p=0.017). In addition, aminoglycoside use was not significantly associated with renal function impairment (OR 1.12, 95%CI 0.26–4.87;p=0.9). Conclusions: The addition of an aminoglycoside to the initial empirical therapy regimen for febrile neutropenic hematological patients should be considered.

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Titanium (Ti) and Ti alloys have been used for decades for bone prostheses due to its mechanical reliability and good biocompatibility. However, the high stiffness of Ti implants and the lack of bioactivity are pending issues that should be improved to minimize implant failure. The stress shielding effect, a result of the stiffness mismatch between titanium and bone, can be reduced by introducing a tailored structural porosity in the implant. In this work, porous titanium structures were produced by direct ink writing (DIW), using a new Ti ink formulation containing a thermosensitive hydrogel. A thermal treatment was optimized to ensure the complete elimination of the binder before the sintering process, in order to avoid contamination of the titanium structures. The samples were sintered in argon atmosphere at 1200 °C, 1300 °C or 1400 °C, resulting in total porosities ranging between 72.3% and 77.7%. A correlation was found between the total porosity and the elastic modulus of the scaffolds. The stiffness and yield strength were similar to those of cancellous bone. The functionalization of the scaffold surface with a cell adhesion fibronectin recombinant fragment resulted in enhanced adhesion and spreading of osteoblastic-like cells, together with increased alkaline phosphatase expression and mineralization.