Bloodstream infections due to Carbapenem-Resistant Enterobacteriaceae in hematological patients: assessment of risk factors for mortality and treatment options.

PURPOSE: Bloodstream infection (BSI) caused by Carbapenem-Resistant Enterobacteriaceae (CRE) are associated with poor outcomes in hematological patients. The aim of this study was to identify risk factors for mortality and evaluate the value of epidemiological feature of carbapenemases in guiding antimicrobial treatment options. METHODS: Hematological patients with monomicrobial CRE BSI between January 2012 and April 2021 were included. The primary outcome was all-cause mortality 30 days after BSI onset. RESULTS: A total of 94 patients were documented in the study period. Escherichia coli was the most common Enterobacteriaceae, followed by Klebsiella pneumoniae. 66 CRE strains were tested for carbapenemase genes, and 81.8% (54/66) were positive, including NDM (36/54), KPC (16/54), IMP (1/54). Besides, one E. coli isolate was found to express both NDM and OXA-48-like genes. Overall, 28 patients received an antimicrobial treatment containing ceftazidime-avibactam (CAZ-AVI), of which 21 cases were combined with aztreonam. The remaining 66 patients were treated with other active antibiotics (OAAs). The 30-day mortality rate was 28.7% (27/94) for all patients, and was only 7.1% ((2/28) for patients treated with CAZ-AVI. In multivariate analysis, the presence of septic shock at BSI onset (OR 10.526, 95% CI 1.376-76.923) and pulmonary infection (OR 6.289, 95% CI 1.351-29.412) were independently risk factors for 30-day mortality. Comparing different antimicrobial regimens, CAZ-AVI showed a significant survive benefit than OAAs (OR 0.068, 95% CI 0.007-0.651). CONCLUSION: CAZ-AVI-containing regimen is superior to OAAs for CRE BSI. As the predominance of blaNDM in our center, we recommend the combination with aztreonam when choose CAZ-AVI.

Geniposide ameliorated dexamethasone-induced endoplasmic reticulum stress and mitochondrial apoptosis in osteoblasts.

ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliver has been traditionally used for treatment of various diseases, including osteoporosis, knee pain, and paralysis. The extract of Eucommia ulmoides has been reported to stimulate the bone formation and suppress the bone resorption, leading to protection against osteoporosis (OP). Geniposide (GEN) has been considered as one of the effective compounds responsible for the therapeutic efficacy of Eucommia ulmoides against OP. AIM OF THE STUDY: To explore whether GEN protected against dexamethasone (DEX)-induced osteoporosis (OP) by activating NRF2 expression and inhibiting endoplasmic reticulum (ER) stress. MATERIALS AND METHODS: The DEX-induced rat OP models were duplicated. The pathological changes were examined by histological/immunohistochemical evaluation and micro-computed tomography (micro-CT) assessment. Apoptosis was detected by a flow cytometer. Mitochondrial Ca2+ concentrations and mitochondrial membrane potential were detected. Western blot assays were used to detect the protein expression. RESULTS: GEN effectively reversed DEX-induced pathological changes of trabecular bone in rats. In addition, the DEX-increased expression of ATF4/CHOP was also ameliorated. In MC3T3-E1 cells, DEX promoted endoplasmic reticulum (ER) stress and mitochondrial apoptosis. Inhibition of ER stress abolished the induction of apoptosis by DEX. Similarly, GEN significantly ameliorated DEX-induced mitochondrial apoptosis. The possible underlying mechanism might be associated with the pharmacological effects of GEN on activating the expression of NRF2 and alleviating ER stress in DEX-treated MC3T3-E1 cells. CONCLUSION: GEN ameliorated DEX-induced ER stress and mitochondrial apoptosis in osteoblasts.

Fucoidan Extracted from Undaria pinnatifida: Source for Nutraceuticals/Functional Foods.

The importance of fucoidan as a functional ingredient in food, health products, and pharmaceutics is well-recognized due to its beneficial biological effects. Fucoidan is usually extracted from brown seaweeds, including Undaria pinnatifida. Fucoidan exhibits beneficial bio-activity and has antioxidant, anticancer, and anticoagulant properties. This review focuses on the biological activity of U. pinnatifida-derived fucoidan and investigates its structure⁻activity or fraction⁻activity relationship. It also describes several fucoidan extracts, along with their claimed anticancer effects. It aims to provide information and thoughts for future research such as the development of fucoidan into functional foods or nutraceuticals.

Decreased expression of vitamin D receptor may contribute to the hyperimmune status of patients with acquired aplastic anemia.

Acquired aplastic anemia (AA) is an immune-mediated bone marrow failure syndrome. 1α,25-Dihydroxyvitamin D3 [1,25(OH)2 D3 ], the biologically active metabolite of vitamin D, is a critical modulator of immune response via binding with vitamin D receptor (VDR). Previous studies have established that 1,25(OH)2 D3 and VDR were involved in the pathogenesis of some autoimmune diseases. In this study, we evaluated the involvement of 1,25(OH)2 D3 and VDR on T-cell responses in AA. Plasma 25(OH)D3 levels were comparable between patients with AA and healthy controls. Surprisingly, VDR mRNA was significantly lower in untreated patients with AA than in healthy controls. Subsequent in vitro experiments revealed that 1,25(OH)2 D3 treatment suppressed the proliferation of lymphocytes and inhibited the secretion of interferon-γ, tumor necrosis factor-α, and interleukin-17A, meanwhile promoting the production of transforming growth factor-ß1 in patients with AA. Moreover, 1,25(OH)2 D3 inhibited the differentiation of type 1 and Th17 cells but induced the differentiation of type 2 and regulatory T cells. Interestingly, VDR mRNA was elevated in healthy controls after 1,25(OH)2 D3 treatment, but not in patients with AA. In conclusion, decreased expression of VDR might contribute to the hyperimmune status of AA and appropriate vitamin D supplementation could partly correct the immune dysfunction by strengthening signal transduction through VDR in patients with AA.