BackgroundCommensal microbiota deteriorate in critically ill patients. The preventive effects of probiotic/synbiotic therapy on microbiota and septic complications have not been thoroughly clarified in patients with sepsis. The objective of this study was to evaluate whether synbiotics have effects on gut microbiota and reduce complications in mechanically ventilated patients with sepsis.MethodsSepsis patients who were mechanically ventilated in the intensive care unit (ICU) were included in this randomized controlled study. Patients receiving daily synbiotics (Bifidobacterium breve strain Yakult, Lactobacillus casei strain Shirota, and galactooligosaccharides) initiated within 3 days after admission (the Synbiotics group) were compared with patients who did not receive synbiotics (the No-Synbiotics group). The primary outcome was infectious complications including enteritis, ventilator-associated pneumonia (VAP), and bacteremia within 4 weeks from admission. The secondary outcomes included mortality within 4 weeks, fecal bacterial counts, and organic acid concentration. Enteritis was defined as the acute onset of continuous liquid stools for more than 12 h.ResultsSeventy-two patients completed this trial; 35 patients received synbiotics and 37 patients did not receive synbiotics. The incidence of enteritis was significantly lower in the Synbiotics than the No-Synbiotics group (6.3% vs. 27.0%; p < 0.05). The incidence of VAP was also significantly lower in the Synbiotics than the No-Synbiotics group (14.3% vs. 48.6%; p < 0.05). The incidence of bacteremia and mortality did not differ significantly between the two groups. In the analysis of fecal bacteria, the number of Bifidobacterium and Lactobacillus in the Synbiotics group was significantly higher than that in the No-Synbiotics group. In the analysis of fecal organic acids, total organic acid concentration, especially the amounts of acetate, were significantly greater in the Synbiotics group than in the No-Synbiotics group at the first week (p < 0.05).ConclusionsProphylactic synbiotics could modulate the gut microbiota and environment and may have preventive effects on the incidence of enteritis and VAP in patients with sepsis.Trial registrationUMIN, R000007633. Registered on 29 September 2011.

Epidermal keratinocytes in psoriatic lesions are characterized by activated Stat3, and increased levels of cytokines and growth factors that promote Stat3 activation have been found within psoriatic lesions. K5.Stat3C transgenic mice, in which keratinocytes express a constitutively active Stat3, develop psoriasis-like skin lesions. In this study, we examined whether STA-21, a small Stat3 inhibitor, could be useful in ameliorating the skin lesions not only in the model mouse but also in human psoriasis. Treatment with STA-21 markedly inhibited the cytokine-dependent nuclear translocation of Stat3 in normal human keratinocytes in vitro. Keratinocyte proliferation was inhibited by STA-21 in a dose-dependent manner through downregulation of c-Myc and cyclin D1, whereas involucrin, transglutaminase 1, and keratin 10 levels were upregulated. Topical application of STA-21 abolished the generation of skin lesions in K5.Stat3C mice. Finally, we treated psoriasis patients with STA-21-containing ointment in a nonrandomized study. Psoriatic lesions in six of the eight patients showed improvement after topical STA-21 treatment for 2 weeks. Therefore, we conclude that targeting Stat3 may lead to a therapy for psoriasis.

Sepsis remains a major cause of death. Cytokines interact closely with each other and play a crucial role in the progression of sepsis. We focussed on the associations of a cytokine network with prognosis and disease severities in sepsis. This retrospective study included 31 patients with sepsis and 13 healthy controls. Blood samples were collected from patients on days 1, 2, 4, 6, 8, 11 and 15 and from healthy controls. Levels of PAI-1, IFN-α, IFN-γ, IL-1β, IL-6, IL-8, IL-12/IL-23p40, IL-17A, TNF-α, MCP-1, IL-4 and IL-10 were measured. SOFA, JAAM DIC and ISTH DIC scores were evaluated at the same times blood samples were taken. Network analysis revealed a network formed by PAI-1, IL-6, IL-8, MCP-1 and IL-10 on days 1, 2 and 4 throughout the acute phase of sepsis. There were positive correlations of each cytokine and the combined score (IL-6 + IL-8 + IL-10 + MCP-1) with the SOFA, JAAM DIC and ISTH DIC scores throughout the acute phase. A Cox proportional hazards model focussed on the acute phase showed that the above combined score was significantly related with patient prognosis, suggesting that the cytokine network of IL-6, IL-8, MCP-1 and IL-10 could play a pivotal role in the acute phase of sepsis.

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Background Malaria is one of the most severe public health issues that result in massive morbidity and mortality in most countries of the sub-Saharan Africa (SSA). This study aimed to determine the scope of household, accessibility to malaria care and factors associated with household malaria in the Democratic Republic of Congo (DRC). Methods This was a community-based cross-sectional study conducted in an urban and a rural sites in which 152 households participated, including 82 urban and 70 rural households (1029 members in total). The ‘malaria indicator questionnaire’ (MIQ) was anonymously answered by household heads (respondents), reporting on malaria status of household members in the last 12 months. Results There were 67.8% of households using insecticide-treated bed nets (ITN) only, 14.0% used indoor residual spraying (IRS) only, 7.3% used ordinary bed nets (without insecticide treatment), 1.4% used mosquito repelling cream, 2.2% combined ITN and IRS, whereas 7.3% of households did not employ any preventive measure; p < 0.01). In addition, 96.7% of households were affected by malaria (at least one malaria case), and malaria frequency per household was relatively high (mean: 4.5 ± 3.1 cases reported) in the last 12 months. The mean individual malaria care expenditure was relatively high (101.6 ± 10.6 USD) in the previous 12 months; however, the majority of households (74.5%) earned less than 50 USD monthly. In addition, of the responders who suffered from malaria, 24.1% did not have access to malaria care at a health setting. Furthermore, a multivariate analysis with adjustment for age, education level and occupation showed that household size (OR = 1.43 ± 0.13; 95% CI 1.18–1.73; p < 0.001), inappropriate water source (OR = 2.41 ± 0.18; 95% CI 1.17–2.96; p < 0.05) absence of periodic water, sanitation and hygiene (WASH) intervention in residential area (OR = 1.63 ± 1.15; 95% CI 1.10–2.54; p < 0.05), and rural residence (OR = 4.52 ± 2.47; 95% CI 1.54–13.21; p < 0.01) were associated with household malaria. Conclusion This study showed that household size, income, WASH status and rural site were malaria-associated factors. Scaling up malaria prevention through improving WASH status in the residential environment may contribute to reducing the disease burden.

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