Charcot Pathogenesis: A Study of In Vivo Gene Expression

Charcot neuroarthropathy is a rare but often difficult to manage disease in the neuropathic patient. Early signs such as unremarkable edema, marginal trauma, or minor infection can activate a cascade of bony destruction and lead to gross prominence or deformity, with dire consequences. The exact molecular mechanism is poorly understood. Current theory states that an inflammatory reaction leads to the activation of osteoclasts mediated by specific cytokines. Our study sought to test the genetic expression of certain biomarkers in diabetic patients with and without Charcot neuroarthropathy compared with patients with and without diabetes or neuropathy. A total of 30 patients participated in the study, 17 (57%) males and 13 (43%) females. Peripheral blood samples were drawn, and gene expression was measured using real-time polymerase chain reaction. The expression levels of receptor activator of nuclear factor kappa-B ligand and osteoprotegerin showed no significant increase in the Charcot neuroarthropathy group compared with the healthy control group. We determined that the levels of receptor activator of nuclear factor kappa-B ligand and osteoprotegerin were not significantly increased in Charcot neuroarthropathy patients compared with healthy control patients. These results demonstrate a need for further investigation into alternative molecular pathways to determine the exact mechanism of the disease process.     

DNR directives are established early in mechanically ventilated intensive care unit patients

Purpose

Setting treatment goals in the intensive care unit (ICU) often involves resuscitation decisions. Our objective was to study the rate of establishing do-not-resuscitate (DNR) directives, determinants, and outcomes of those directives for mechanically ventilated patients.

Methods

In a multicentre observational study, we included consecutive adults with no DNR directives within 24 hr of ICU admission who were mechanically ventilated for at least 48 hr. We identified the rate with which DNR directives were established, and factors associated with these directives.

Results

Among 765 patients, DNR directives were established for 231 (30.2%) patients; 143 (62.1%) of these were established within the first week. Factors independently associated with a DNR directive were: patient age [> 75 yr (hazard ratio [HR] 2.3, 95% confidence interval 1.5–3.4], 65 to 74yr(HR 1.8, 1.2–2.7), 50 to 64 yr (HR 1.4, 1.0–2.2) relative to < 50 yr); medical rather than surgical diagnosis (HR 1.8, 1.3–2.5); multiple organ dysfunction score (HR 1.7 for each five-point increment, 1.4–2.0); physician prediction of ICU survival [< 10% (HR 15.0, 6.7–33.6)], 10 to 40% [(HR 5.0, 2.3–11.2), 41 to 60% (HR 4.0, 1.8–9.0) relative to > 90%]; and physician perception of patient preference to limit life support (no advanced life support [(HR 5.8, 3.6–9.4) or partial advanced life support (HR 3.2, 2.2–4.6) compared to full measures].

Conclusion

One third of mechanically ventilated patients had DNR directives established early during their ICU stay after the first 24 hr of admission. The strongest predictors of DNR directives were physician prediction of low probability of survival, physician perception of patient preference to limit life support, organ dysfunction, medical diagnosis and age.     

Effect of probiotics and synbiotics on blood glucose: a systematic review and meta-analysis of controlled trials

Purpose

High fasting blood glucose (FBG) can lead to chronic diseases such as diabetes mellitus, cardiovascular and kidney diseases. Consuming probiotics or synbiotics may improve FBG. A systematic review and meta-analysis of controlled trials was conducted to clarify the effect of probiotic and synbiotic consumption on FBG levels.

Methods

PubMed, Scopus, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature databases were searched for relevant studies based on eligibility criteria. Randomized or non-randomized controlled trials which investigated the efficacy of probiotics or synbiotics on the FBG of adults were included. Studies were excluded if they were review articles and study protocols, or if the supplement dosage was not clearly mentioned.

Results

A total of fourteen studies (eighteen trials) were included in the analysis. Random-effects meta-analyses were conducted for the mean difference in FBG. Overall reduction in FBG observed from consumption of probiotics and synbiotics was borderline statistically significant (?0.18 mmol/L 95 % CI ?0.37, 0.00; p = 0.05). Neither probiotic nor synbiotic subgroup analysis revealed a significant reduction in FBG. The result of subgroup analysis for baseline FBG level ≥7 mmol/L showed a reduction in FBG of 0.68 mmol/L (?1.07, ?0.29; ρ < 0.01), while trials with multiple species of probiotics showed a more pronounced reduction of 0.31 mmol/L (?0.58, ?0.03; ρ = 0.03) compared to single species trials.

Conclusion

This meta-analysis suggests that probiotic and synbiotic supplementation may be beneficial in lowering FBG in adults with high baseline FBG (≥7 mmol/L) and that multispecies probiotics may have more impact on FBG than single species.