BackgroundBloodstream infections are associated with high morbidity and mortality, both of which contribute substantially to healthcare costs. The effects of early administration of appropriate antimicrobials on the prognosis and timing of defervescence of bacteremic patients remain under debate.MethodsIn a 6-year retrospective, multicenter cohort, adults with community-onset bacteremia at the emergency departments (EDs) were analyzed. The period from ED arrival to appropriate antimicrobial administration and that from appropriate antimicrobial administration to defervescence was regarded as the time-to-appropriate antibiotic (TtAa) and time-to-defervescence (TtD), respectively. The primary study outcome was 30-day mortality after ED arrival. The effects of TtAa on 30-day mortality and delayed defervescence were examined after adjustment for independent predictors of mortality, which were recognized by a multivariate regression analysis.ResultsOf the total 3194 patients, a TtAa-related trend in the 30-day crude (γ = 0.919, P = 0.01) and sepsis-related (γ = 0.909, P = 0.01) mortality rate was evidenced. Each hour of TtAa delay was associated with an average increase in the 30-day crude mortality rate of 0.3% (adjusted odds ratio [AOR], 1.003; P < 0.001) in the entire cohort and 0.4% (AOR, 1.004; P < 0.001) in critically ill patients, respectively, after adjustment of independent predictors of 30-day crude mortality. Of 2469 febrile patients, a TtAa-related trend in the TtD (γ = 0.965, P = 0.002) was exhibited. Each hour of TtAa delay was associated with an average 0.7% increase (AOR, 1.007; P < 0.001) in delayed defervescence (TtD of ≥ 7 days) after adjustment of independent determinants of delayed defervescence. Notably, the adverse impact of the inappropriateness of empirical antimicrobial therapy (TtAa > 24 h) on the TtD was noted, regardless of bacteremia severity, bacteremia sources, or causative microorganisms.ConclusionsThe delay in the TtAa was associated with an increasing risk of delayed defervescence and 30-day mortality for adults with community-onset bacteremia, especially for critically ill patients. Thus, for severe bacteremia episodes, early administration of appropriate empirical antimicrobials should be recommended.

While melatonin is known to have protective effects in mitochondria-related diseases, aging, and neurodegenerative disorders, there is poor understanding of the effects of melatonin treatment on mitophagy in Alzheimer's disease (AD).We used proteomic analysis to investigate the effects and underlying molecular mechanisms of oral melatonin treatment on mitophagy in the hippocampus of 4-month-old wild-type mice versus age-matched 5 × FAD mice, an animal model of AD. 5 × FAD mice showed disordered mitophagy and mitochondrial dysfunction as revealed by increased mtDNA, mitochondrial marker proteins and MDA production, decreased electron transport chain proteins and ATP levels, and colocalization of Lamp1 and Tomm20. Melatonin treatment reversed the abnormal expression of proteins in the signaling pathway of lysosomes, pathologic phagocytosis of microglia, and mitochondrial energy metabolism. Moreover, melatonin restored mitophagy by improving mitophagosome-lysosome fusion via Mcoln1,

High-sensitivity cTnT and NT-proBNP were independently associated with incident PAD, particularly its severe form, CLI. Although future studies are warranted to investigate pathophysiological mechanisms behind these associations, our study suggests the usefulness of cardiac markers to identify individuals at high risk of CLI.

BackgroundWe conducted an analysis of data from the ARIC (Atherosclerosis Risk in Communities) study to assess the independent association of obesity with peripheral artery disease (PAD) and critical limb ischemia (CLI).Methods and ResultsAll black and white ARIC participants without prevalent PAD at baseline (1987–1989) were included. We used Cox proportional hazards models adjusting for potential confounders and then potential mediators to quantify the association between body mass index (BMI) and incident hospitalizations related to PAD without CLI and with CLI through 2013. Our analysis included 13 988 men and women followed for a median of 24 years. Incident PAD without CLI and PAD with CLI occurred in 373 and 201 participants, respectively. After adjusting for potential confounders, higher BMI at baseline was associated with increased risk of PAD without CLI when BMI was modeled continuously (hazard ratio per 1‐SD increment in BMI: 1.23; 95% confidence interval, 1.11–1.37) and with PAD with CLI regardless of whether BMI was modeled categorically (P<0.05) or continuously (hazard ratio per 1‐SD increment in BMI: 1.51; 95% confidence interval, 1.34–1.69). The associations of BMI with PAD without CLI and with CLI were attenuated after further accounting for potential mediators but remained significant for PAD with CLI when BMI was linearly modeled (hazard ratio per 1‐SD increment in BMI: 1.19; 95% confidence interval, 1.04–1.36). The positive association between BMI and PAD with CLI was stronger than the association between BMI and PAD without CLI for all models (P<0.001).ConclusionsIn the general population, BMI is positively associated with incident hospitalized PAD after adjusting for potential confounders, particularly its most severe form of CLI. Maintaining an optimal weight, in addition to controlling other cardiovascular risk factors, may play a role in reducing risk of PAD with CLI.

The association between normal thyroid function and diabetic kidney disease (DKD) has gained increasing attention. The present study evaluated the relationship between normal thyroid hormone levels and DKD in type 2 diabetes mellitus (T2DM) patients. A total of 862 type 2 diabetes patients were enrolled in this cross-sectional study in Xi’an, Shaanxi Province, China. The subjects were evaluated for anthropometric measurements, thyroid function and DKD. Of 862 patients, 246 (28.5%) suffered from DKD, and the prevalence of DKD did not differ between men and women. The prevalence of DKD showed a significantly decreasing trend across the quartiles based on free triiodothyronine (FT3) levels (41.1%, 30.6%, 23.8%, and 18.9%, P < 0.001). In comparison with all participants categorized in the first FT3 quartile group (FT3-Q1) (<4.380), the adjusted odds ratio of DKD in the second FT3 quartile group (FT3-Q2), the third FT3 quartile group (FT3-Q3), and the fourth FT3 quartile group (FT3-Q4) were 0.655(95%CI: 0.406–1.057), 0.493(95%CI: 0.299–0.813), 0.406(0.237–0.697) (P < 0.05). Also, similar results were observed in men. Conversely, none of the FT3 groups was associated with DKD in women. The present study showed that FT3 within normal range was negatively correlated with DKD in T2DM patients.

Glucose transporter 1 (GLUT1) plays an important role in the transport and metabolism of glucose in cancer cells. An increasing number of studies have explored the connection between GLUT1 expression and prognosis in non-small cell lung cancer (NSCLC), but the results have been controversial. Therefore, we conducted a meta-analysis to obtain a comprehensive evaluation of the prognostic value of GLUT1 in NSCLC. Relevant studies from PubMed, Embase, and Web of Science were searched. Hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were used as the effective measures. A total of 10 studies involving 1,665 patients were included in this meta-analysis. The results showed that GLUT1 overexpression was associated with poor overall survival (HR = 2.21; 95% CI, 1.42–3.42; p < 0.001) and disease-free survival (HR = 1.73; 95% CI, 1.35–2.23; p < 0.001). Furthermore, elevated GLUT1 expression correlated with sex (OR = 2.29; 95% CI, 1.17–4.49; p = 0.015), advanced tumor stage (OR = 2.46; 95% CI, 1.79–3.38; p < 0.001), histology (OR = 6.99; 95% CI, 4.71–10.38; p < 0.001), and large tumor size (OR = 2.77; 95% CI, 1.73–4.44; p < 0.001). This meta-analysis revealed overexpression of GLUT1 to be a biomarker of worse prognosis in NSCLC.

Stroke is the most common cerebrovascular disease, the second leading cause of death behind heart disease and is a major cause of long-term disability worldwide. Currently, systemic immunomodulatory therapy based on intravenous cells is attracting attention. The immune response to acute stroke is a major factor in cerebral ischaemia (CI) pathobiology and outcomes. Over the past decade, the significant contribution of the spleen to ischaemic stroke has gained considerable attention in stroke research. The changes in the spleen after stroke are mainly reflected in morphology, immune cells and cytokines, and these changes are closely related to the stroke outcomes. Autonomic nervous system (ANS) activation, release of central nervous system (CNS) antigens and chemokine/chemokine receptor interactions have been documented to be essential for efficient brain-spleen cross-talk after stroke. In various experimental models, human umbilical cord blood cells (hUCBs), haematopoietic stem cells (HSCs), bone marrow stem cells (BMSCs), human amnion epithelial cells (hAECs), neural stem cells (NSCs) and multipotent adult progenitor cells (MAPCs) have been shown to reduce the neurological damage caused by stroke. The different effects of these cell types on the interleukin (IL)-10, interferon (IFN), and cholinergic anti-inflammatory pathways in the spleen after stroke may promote the development of new cell therapy targets and strategies. The spleen will become a potential target of various stem cell therapies for stroke represented by MAPC treatment.

The relationship between normal thyroid function and type 2 diabetes mellitus (T2DM) has been a particular focus for concern. The present study determined the relationship between thyroid hormone levels and the prevalence of diabetic retinopathy (DR) in T2DM patients. A cross-sectional study (n = 633) was performed in Xi’an, Shaanxi Province, China. Subjects were evaluated for anthropometric measurements, thyroid function, and diabetic retinopathy. Logistic regression models were used to assess the relationships between thyroid hormones and DR. Of 633 patients, 243 (38.4%) patients suffered from DR. The prevalence of DR showed a significantly decreasing trend across the quartiles based on free triiodothyronine (FT3) (FT3 quartile 1 group [FT3-Q1] <4.35 pmol/L, FT3 quartile 2 group [FT3-Q2] 4.35–4.70 pmol/L, FT3 quartile 3 group [FT3-Q3] 4.70–5.08 pmol/L, and FT3 quartile 4 group [FT3-Q4] ≥5.08 pmol/L) (56.7%, 42.5%, 33.1%, 23.8%, P<0.001). In comparison with all participants categorized in FT3-Q1, the multivariable adjusted odds ratios (95% confidence interval) of DR in FT3-Q2, FT3-Q3, and FT3-Q4 were 0.587 (0.340–1.012), 0.458 (0.258–0.813), and 0.368 (0.201–0.673), (P=0.055, P=0.008, P=0.001), respectively. FT3 levels within the normal range are negatively associated with DR in euthyroid patients with type 2 diabetes. Further studies should be aimed at clarifying the relationship between thyroid hormones and T2DM.