Cefazolin Monotherapy Versus Cefazolin Plus Aminoglycosides for Antimicrobial Prophylaxis of Type III Open Fractures.

BACKGROUND: There are conflicting recommendations between organizations regarding aminoglycoside use for the prophylaxis of type III open fractures. STUDY QUESTION: To compare cefazolin monotherapy versus cefazolin plus aminoglycoside therapy for prophylaxis of type III open fractures in trauma patients. STUDY DESIGN: This was a multicenter, retrospective, cohort study conducted in 3 academic medical centers in the United States. Consecutive adult trauma patients with type III open fractures between January 2014 and September 2016 were included. Patients were divided into 2 groups: (1) cefazolin monotherapy versus (2) cefazolin plus aminoglycoside. MEASURES AND OUTCOMES: The primary outcome measure was the occurrence of infection at the open fracture site. The secondary outcome measure was the occurrence of acute kidney injury. RESULTS: There were 134 patients included in the study cohort. Of these, 39 received cefazolin monotherapy and 95 received cefazolin plus aminoglycoside. Overall, the mean age was 39 ± 15 years, 105 (78%) were male, and the most common fracture location was tibia/fibula (n = 74, 56%). Infection at the open fracture site occurred in 6 of 39 patients (15%) in the cefazolin monotherapy group and 15 of 95 patients (16%) in the cefazolin plus aminoglycoside group (P = 1.000). Acute kidney injury occurred in 0 of 39 (0%) in the cefazolin monotherapy group and 1 of 95 (1%) in the cefazolin plus aminoglycoside group (P = 1.000). CONCLUSIONS: Cefazolin monotherapy may be appropriate for antimicrobial prophylaxis of type III open fractures in trauma patients.

FoxO1 is a critical regulator of M2-like macrophage activation in allergic asthma.

BACKGROUND: The pathogenesis of asthma and airway obstruction is the result of an abnormal response to different environmental exposures. The scientific premise of our study was based on the finding that FoxO1 expression is increased in lung macrophages of mice after allergen exposure and human asthmatic patients. Macrophages are capable of switching from one functional phenotype to another, and it is important to understand the mechanisms involved in the transformation of macrophages and how their cellular function affects the peribronchial stromal microenvironment. METHODS: We employed a murine asthma model, in which mice were treated by intranasal insufflation with allergens for 2-8 weeks. We used both a pharmacologic approach using a highly specific FoxO1 inhibitor and genetic approaches using FoxO1 knockout mice (FoxO1fl/fl LysMcre). Cytokine level in biological fluids was measured by ELISA and the expression of encoding molecules by NanoString assay and qRT-PCR. RESULTS: We show that the levels of FoxO1 gene are significantly elevated in the airway macrophages of patients with mild asthma in response to subsegmental bronchial allergen challenge. Transcription factor FoxO1 regulates a pro-asthmatic phenotype of lung macrophages that is involved in the development and progression of chronic allergic airway disease. We have shown that inhibition of FoxO1 induced phenotypic conversion of lung macrophages and downregulates pro-asthmatic and pro-fibrotic gene expression by macrophages, which contribute to airway inflammation and airway remodeling in allergic asthma. CONCLUSION: Targeting FoxO1 with its downstream regulator IRF4 is a novel therapeutic target for controlling allergic inflammation and potentially reversing fibrotic airway remodeling.

Higher insulin infusion rate but not 24-h insulin consumption is associated with hypoglycemia in critically ill patients.

AIMS: To assess the association between insulin infusion rates, and 24-h insulin consumption on hypoglycemia in the intensive care unit (ICU). METHODS: This was a retrospective case-control study, conducted at an academic institution in the United States. Adult patients admitted to the ICU receiving intravenous insulin infusions for blood glucose control were included. Hypoglycemic (blood glucose <70 mg/dL) patients were matched 1:1 with non-hypoglycemic controls based on age, gender, and body mass index. Multivariable conditional logistic regression analyses were conducted to determine the effect of: (1) weight-adjusted insulin infusion rate (units/kg/h), (2) non-weight-adjusted insulin infusion rate (units/h), or (3) 24-h insulin consumption (units/day) on hypoglycemia. RESULTS: A total of 122 patients were included in the study (61 cases, 61 controls). Compared to those patients who received <0.05 units/kg/h, the odds of hypoglycemia was higher in those who received was ≥0.1 units/kg/h (OR 4.57, 95% CI 1.45-14.41, p=0.010). Compared to those patients who received <4 units/h, the odds of hypoglycemia was higher in those who received was ≥8 units/h (4.17, 95% CI 1.18-14.75, p=0.027). The risk of hypoglycemia did not increase with higher 24-h insulin consumption. CONCLUSIONS: Higher insulin infusion rates rather than 24-h insulin consumption may be associated with hypoglycemia in critically ill patients in the ICU.

Predicting the toxicity of substituted phenols to aquatic species and its changes in the stream and effluent waters.

The changes in the acute toxicity of 16 phenols toward Selenastrum capricornutum and Daphnia magna were examined as a function of their physical/chemical properties. The results demonstrated that phenols with a higher octanol-water partition coefficient (K(ow)) had a higher toxicity toward aquatic organisms. The toxicity of phenols was closely related to the log K(ow) values, with correlation coefficients of 0.93 (except for the nitrophenols) and 0.89 for S. capricornutum and D. magna, respectively. The changes in the phenols toxicities in the site waters (i.e., stream and effluent waters) were investigated by calculating the water effect ratios (WER) from the results of the toxicity tests in the site waters using D. magna. The results showed that the degree of ionization for each phenolic compound was altered by the differences in the dissociation constant (pK(a)), and the change in the toxicity could be predicted. Therefore, the WER should be considered when the toxicity of phenolic compounds is estimated in site waters. The quantitative structure-activity relationships (QSAR) study showed that the toxicity of the phenols to D. magna could be predicted by the hydrophobicity (log K(ow)) alone and by combining the log K(ow) with pK(a), while the toxicity to S. capricornutum was predicted by a combination of hydrophobicity (log K(ow)) and E(LUMO) (or pK(a)).