The effect of ephedrine on intraoperative hypothermia

BACKGROUND: Prevention of intraoperative hypothermia has become a standard of operative care. Since ephedrine has a thermogenic effect and it is frequently used to treat hypotension during anesthesia, this study was designed to determine the effect of ephedrine on intraoperative hypothermia of patients who are undergoing spine surgery. METHODS: Twenty-four patients were randomly divided to receive an ephedrine (the ephedrine group, n = 12) or normal saline (the control group, n = 12) infusion for 2 h. The esophageal temperature (the core temperature), the index finger temperature (the peripheral temperature) and the hemodynamic variables such as the mean blood pressure and heart rate were measured every 15 minutes after the intubation. RESULTS: At the end of the study period, the esophageal temperature and hemodynamic variables were significantly decreased in the control group, whereas those in the ephedrine group were stably maintained. The index finger temperature was significantly lower in the ephedrine group compared to that in the control group, suggesting the prevention of core-to-peripheral redistribution of the heat as the cause of temperature maintenance. CONCLUSIONS: An intraoperative infusion of ephedrine minimized the decrease of the core temperature and it stably maintained the hemodynamic variables during spine surgery with the patient under general anesthesia.ope

Liquid Heparin Anticoagulant Produces More Negative Bias in the Determination of Ionized Magnesium than Ionized Calcium

The ionized calcium level in blood is known to be falsely decreased when self-prepared liquid heparin anticoagulant is used, due to dilution and binding effects. The effect of liquid heparin on the determination of ionized magnesium is not as well understood. We compared the effect of liquid sodium heparin on the determination of ionized calcium and magnesium in 44 clinical samples using two types of user-prepared heparin syringes which differed in the amount of residual heparin from the BD Preset™ reference syringe. With the type 1 syringe, the liquid heparin was expelled once or twice such that some heparin could be left in the dead space at the syringe hub, while the liquid sodium heparin was thoroughly expelled from the type 2 syringe. The ionized magnesium levels obtained with the type 1 syringe were significantly lower than the reference value (by 0.068 mmol/L) (p < 0.0001), while the value obtained with the type 2 syringe differed less from the reference, by only 0.014 mmol/L (p < 0.0001). The heparin binding effect resulted in more negative bias in ionized magnesium (- 0.026 ± 0.032 mmol/L) than in ionized calcium (- 0.009 ± 0.042 mmol/L, p < 0.0001). In conclusion, we recommend using lyophilized, calcium-balanced, heparinized syringes for the determination of ionized magnesium and ionized calcium due to the increased negative bias in ionized magnesium determinations. When user-prepared syringes are used, the thorough evacuation of heparin solution should be strictly prescribed

Prognostic value of neutrophil/lymphocyte ratio and mean platelet volume/platelet ratio for 1-year mortality in critically ill patients

Several studies have reported that the neutrophil to lymphocyte ratio (NLR) and mean platelet volume (MPV) are associated with poor prognosis. This study investigated whether NLR and/or the MPV/platelet ratio could function as predictive markers of mortality in critically ill patients. We retrospectively reviewed 1,154 patients admitted to the intensive care unit (ICU) between January 2017 and December 2017. Patients were divided into 2 groups according to 1-year mortality. We compared the NLR and MPV/platelet ratio on each day of ICU admission. Patients were classified into tertiles based on their NLR and MPV/platelet ratios, and the incidence of 1-year mortality was compared. Kaplan-Meier survival curves were plotted to evaluate their potential as prognostic factors for 1-year mortality. The NLR and MPV/platelet ratio were higher in the non-survivor group than in the survivor group. The incidence of 1-year mortality was the highest in the third tertile for both the NLR and MPV/platelet ratio. The MPV/platelet ratio was an independent predictor for 1-year mortality based on the Kaplan-Meier survival analysis. Our data showed that the MPV/platelet ratio is a predictive factor for 1-year mortality in critically ill patients.11Nsciescopu

Prealbumin is Not Sensitive Indicator of Nutrition and Prognosis in Critical Ill Patients

It was reported that 30-50% of inpatients are in a malnutrition status. Measuring the prealbumin level is a sensitive and cost-effective method for assessing the severity of illness in critically or chronically ill patients. However it is uncertain whether or not the prealbumin level correlates with the level of nutrition support and outcomes in critically ill patients. The aim of this study was to evaluate serum prealbumin level as an indicator of the effectiveness of nutrition support and the prognosis in critically ill patients. Forty-four patients who received total parenteral nutrition for more than 7 days at an intensive care unit (ICU) were studied. The serum prealbumin was measured at the initial time of nutrition support and at the almost seventh day since the first measurement. The patients were allocated into two groups. In Group 1 (n=31) and 2 (n=13), the prealbumin level increased and decreased, respectively. Age, APACHE II score, nutrition status, nutritional requirement and amount of supply, mortality, hospital day and ICU day in the two groups were compared. The serum prealbumin level increased in 31 out of the 44 patients. The average calorie intake was 1334 Kcal/day (83% of energy requirement) in Group 1 and 1170 kcal/day (76% of energy requirement) in Group 2 (p=0.131). The mortality was 42% in Group 1 and 54% in Group 2 (p=0.673). The average hospital day/ ICU day in Groups 1 and 2 were 80 days/38 days and 60 days/31 days respectively. In conclusion, in critically ill patients, the serum prealbumin level did not respond sensitively to nutritional support. In addition an increase in the prealbumin level dose not indicate a better prognosis for critically ill patients

House Dust Mite Induces Expression of Intercellular Adhesion Molecule-1 in EoL-1 Human Eosinophilic Leukemic Cells

The house dust mite (HDM) is considered to be the most common indoor allergen associated with bronchial asthma. In this study, we investigated whether crude extract of the HDM Dermatophagoides farinae could activate human eosinophilic leukemic cells (EoL-1) to induce upregulation of cell-surface adhesion molecules. When EoL-1 cells were incubated with D. farinae extract, expression of intercellular adhesion molecule-1 (ICAM-1) significantly increased on the cell surfaces compared to cells incubated with medium alone. In contrast, surface expression of CD11b and CD49d in EoL-1 cells was not affected by D. farinae extract. In addition, pretreatment of cells with NF-κB inhibitor (MG-132) or JNK inhibitor (SP600125) significantly inhibited ICAM-1 expression promoted by HDM extract. However, neither p38 MAP kinase inhibitor nor MEK inhibitor prevented HDM-induced ICAM-1 expression in EoL-1 cells. These results suggest that crude extract of D. farinae induces ICAM-1 expression in EoL-1 cells through signaling pathways involving both NF-κB and JNK

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field