Susceptibility of Dental Enamel of Different Ages to Caries-Like Lesion Development.

This study investigated the impact of estimated age, anatomical location, and the presence of wear facets on the susceptibility of enamel to develop caries-like lesions. Extracted human premolars (n = 261) had their age estimated between 10 and 93 years old, using established forensic methods. Specimens of enamel (4 × 4 mm) were prepared from the middle of the buccal surfaces, preserving the outer surface layer. The central area of the block (4 × 1 mm) was protected with nail polish and used as an internal control. The specimens were demineralized for 8 days (with 0.1 M acetic acid, 1.28 mM Ca, 0.74 mM Pi, and 0.03 µg F/mL, pH 5.0), to simulate caries-like lesion development. They were then scanned individually using microtomography, and digital 2D images were used to calculate the outcomes of integrated mineral concentration loss (ΔZ in µm/g/cm3) and lesion depth (LD in µm) at 3 locations, i.e., the cervical, middle, and occlusal thirds. The presence of natural surface wear facets was considered in the analysis. Data were evaluated using a linear mixed-effects models (α = 0.05). ΔZ increased significantly as a function of estimated tooth age at all 3 locations, and this increase was greater after the age of 30 years (p < 0.001), when a higher ΔZ was found in the occlusal third than in the middle and cervical thirds (p < 0.001). LD increased only in the occlusal third before the age of 30 years (p = 0.039) and this increase was significantly greater after 30 years at all 3 locations (p < 0.01), with no differences among them (p > 0.15). The presence of wear facets significantly increased ΔZ and LD (p < 0.001 for both). Overall, we concluded that the susceptibility of enamel to developing caries-like lesions increased with estimated dental age. This effect was more pronounced after the estimated age of 30 years and in the presence of natural tooth wear facets.

Severe Infusion-Related Adverse Events and Renal Failure in Patients Receiving High-Dose Intravenous Polymyxin B.

The use of very high doses of polymyxin B (PMB) against carbapenem-resistant Gram-negative bacilli has been addressed in in vitro experiments as a strategy to improve bacterial killing and suppress resistance emergence. However, the toxicities of very high doses in patients are unknown. We conducted a retrospective cohort study assessing patients receiving PMB at >3 mg/kg of body weight/day or a total dose of ≥250 mg/day. The main outcomes were severe infusion-related adverse events according to the Common Terminology Criteria for Adverse Events and the renal failure category of RIFLE criteria for acute kidney injury (AKI) during treatment. A total of 222 patients were included for analysis of infusion-related events. The mean PMB dose was 3.61 ± 0.97 mg/kg/day (median total dose/day = 268 mg). Severe infusion-related adverse events occurred in two patients, resulting in an incidence of 0.9% (95% confidence interval, 0.2 to 3.2%); one was classified as a life-threatening adverse event, and one was classified as a severe adverse event. Renal failure was analyzed in 115 patients, and 25 (21.7%) patients presented renal failure (54 [47.0%] developed any degree of AKI, categorized as risk [27.8%], injury [25.9%], and failure [46.3%]). Treatment with a vasoactive drug, concomitant treatment with nephrotoxic drugs, and baseline creatinine clearance were independent risk factors for renal failure. Neither the PMB daily dose scaled by body weight nor the total daily dose was associated with renal failure. The in-hospital mortality rate was 60% (134 patients): 26% of deaths (57 patients) occurred during treatment, and none occurred during infusion. Our data suggest that high-dose schemes have an acceptable safety profile and could be further tested in clinical trials assessing strategies to improve patient outcomes and minimize the emergence of PMB resistance.