A prospective randomized controlled study of combined spinal-general anesthesia vs. general anesthesia for laparoscopic gynecological surgery: Opioid sparing properties

Study objectiveWe aimed to determine the magnitude of peri-operative opioid sparing effect when general anesthesia is combined with spinal analgesia for laparoscopic gynecological surgery.DesignA prospective randomized controlled study; a three-group trial with two comparisons (each intervention group to control).SettingOperating room and postoperative recovery area.PatientsPatients aged between 18 and 65 years with American Society of Anesthesiologists physical status 1 or 2 who were scheduled for inpatient elective laparoscopic gynecological surgery with expected pneumoperitoneum duration of at least 20 min. Of 102 randomized patients, 99 completed the study.InterventionsPatients were randomized to general anesthesia alone (control group) or combined with very-low-dose (levobupivacaine 3.75 mg; sufentanil 2.5 μg) or low-dose (levobupivacaine 7.5 mg; sufentanil 2.5 μg) spinal analgesia.MeasurementsPrimary endpoints were perioperative opioid consumption and pain scores (11-point numeric rating scale) at 30 min, 1 h, 2 h, 4 h and 24 h post-surgery. Secondary endpoints were patient satisfaction with anesthetic care and participation in research, sevoflurane consumption and adverse effects.Main resultsIntra-operative sufentanil (median [95% CI]) consumption was 16.1 (10.5–22.6) μg/h in the control group versus 4.7 (3.2–9.2) μg/h in the very-low-dose and versus 2.9 (0.0–4.0) μg/h in the low-dose spinal analgesia groups (p < 0.001, for both comparisons). Median (95% CI) piritramide consumption at 24 h post-surgery was 7.5 (3–8) mg in the control group versus 5 (0–7.5) mg in the very-low dose spinal analgesia group (p = 0.182) and versus 2 (0–2.5) mg in the low-dose spinal analgesia group (p = 0.001). Postoperative pain scores were consistently <3 only in the low dose spinal analgesia group. Patient satisfaction with anesthetic care and participation in research was very high in all groups.ConclusionsLow-dose spinal analgesia in combination with general anesthesia reduces peri-operative opioid consumption in laparoscopic gynecological surgery in immediate postoperative period.     

Trans-anethole attenuates diet-induced nonalcoholic steatohepatitis through suppressing TGF-β-mediated fibrosis

BackgroundNonalcoholic Steatohepatitis (NASH) is the most severe type of non-alcoholic fatty liver disease (NAFLD) and one of the most common chronic liver diseases, leading to the increased risk of liver failure, cirrhosis and hepatocellular carcinoma. Trans-anethole was reported to have anti-inflammatory, anti-obesity and anti-diabetic activities. However, its role in NASH remains unknown. Therefore, we aimed to explore the effect of Trans-anethole on NASH.MethodsEight-week-old C57BL/6 mice were fed on a methionine- and choline-deficient (MCD) diet for 8 weeks to induce NASH in mice, and on the meanwhile, mice were also orally administrated with or without 100 mg/kg Trans-anethole daily to evaluate the effect of Trans-anethole on NASH.ResultsTrans-anethole dose-dependently ameliorated liver injury in MCD diet-fed mice, then the most effective dose of Trans-anethole 100 mg/kg was chosen. Trans-anethole significantly attenuated hepatic steatosis, inflammation and hepatic fibrosis in MCD diet-induced NASH mice. Moreover, Trans-anethole reduced hepatic fibrosis by inhibiting transforming growth factor-beta signaling pathway both in vivo and in vitro.ConclusionTrans-anethole effectively ameliorated NASH in MCD diet-fed mice, which suggested that Trans-anethole might serve as a therapeutic strategy for NASH.     

Targeting AGEs-RAGE pathway inhibits inflammation and presents neuroprotective effect against hepatic ischemia-reperfusion induced hippocampus damage

BackgroundThe present study aimed to investigate the role of AGEs-RAGE signaling and its potential as a treatment target in hepatic ischemia-reperfusion (HIR)-induced hippocampus damage.MethodsHIR operation was conducted in mice, followed by collection of hippocampus tissue at 1 day, 3 days and 7 days. Additionally, low dose, moderate dose and high dose FPS-ZM1 (RAGE inhibitor) was intraperitoneally injected into HIR mice. Besides, sham operation was conduced in mice which served as control.ResultsHIR increased the hippocampal damage and enhanced its neuron apoptosis within 3 days, which recovered to some extent from day 3 to day 7 post operation. Meanwhile, the expressions of AGEs, RAGE, the downstream proteins in AGEs-RAGE signaling pathway (including PI3K, pAKT, pNKκB p65 and pERK1/2), and the inflammatory cytokines (including IL-1β, IL-6, TNF-α) were increased within 3 days, but were reduced from day 3 to day 7 post operation by HIR. Notably, moderate and high dose of FPS-ZM1 attenuated hippocampal damage, inhibited its neuron apoptosis, inactivated AGEs-RAGE signaling, and suppressed the expressions of inflammatory cytokines (including IL-1β, IL-6, TNF-α); but lose dose of FPS-ZM1 failed to achieve these effects.ConclusionsTargeting AGEs-RAGE pathway inhibits inflammation and presents neuroprotective effect against HIR-induced hippocampus damage.     

Prognostic value of lactate in prehospital care as a predictor of early mortality

BackgroundPrehospital Emergency Medical Services must attend to patients with complex physiopathological situations with little data and in the shortest possible time. The objective of this work was to study lactic acid values and their usefulness in the prehospital setting to help in clinical decision-making.Study designWe conducted a longitudinal prospective, observational study on patients over 18 years of age who, after being evaluated by the Advanced Life Support Unit, were taken to the hospital between April and June 2018. We analyzed demographic variables, prehospital lactic acid values and early mortality (<30 days). The area under the curve of the receiver operating characteristic was calculated for the prehospital value of lactic acid.ResultsA total of 279 patients were included in our study. The median age was 68 years (interquartile range: 54–80 years). Overall 30-day mortality was 9% (25 patients). The area under the curve for lactic acid to predict overall mortality at 30 days of care was 0.82 (95% CI: 0.76–0.89). The lactate value with the best sensitivity and specificity overall was 4.25 mmol/L with a sensitivity of 84% (95% CI: 65.3–93.6) and specificity of 70% (95% CI: 65.0–76.1).ConclusionsThe level of lactic acid can be a complementary tool in the field of prehospital emergencies that will guide us early in the detection of critical patients.     

Emergency department mortality: Fair and square

ObjectiveThis study explored the therapeutic approaches used for end-of-life (EOL) patients admitted to the emergency department (ED) and examined whether the decision to perform life-extending treatment (LET) or to allow natural death (AND) depends on patient characteristics, medical staff variables, and ED setting.MethodsA retrospective archive study was conducted from January 2015 to December 2017 in the ED of a tertiary hospital. The study sample were 674 EOL patients who had died in the ED. For each patient, data were collected and measured for dying process (LET vs. AND), patient characteristics, ED-setting variables, and medical-staff characteristics.ResultsThe proportion of EOL patients undergoing LET increased from 18.1% in 2015 to 25.9% in 2016 and to 30.3% in 2017 (p = .010), and a quarter of them were treated by emergency medical services. Males tended to receive LET more than females (p < .001). An association was found between Jewish physicians and nurses and AND (p = .001). Heavier workload in the ED and greater severity of the triage classification predicted more LET (OR-1.67, CI = 1.05–1.76, p = .003 and OR = 1.42, CI-0.60-0.81, p < .001, respectively). Receiver operating characteristic analysis showed that patient characteristics contributed most crucially to the therapeutic approaches (C statistic 0.624–0.675, CI-0.62-0.71).ConclusionsThe therapeutic approach used for EOL patients in the ED depends on variables in all three treatment layers: patient, medical staff, and ED setting. Applicable national programs should be developed to ensure that no external factors influence the dying-process decision.     

Effect of breastfeeding on immunogenicity of oral live-attenuated human rotavirus vaccine: a randomized trial in HIV-uninfected infants in Soweto,South Africa

Objective

To investigate the effect of abstention from breastfeeding, for an hour before and after each vaccination, on the immune responses of infants to two doses of rotavirus vaccine.

Methods

In Soweto, South Africa, mother–infant pairs who were uninfected with human immunodeficiency virus (HIV) were enrolled as they presented for the “6-week” immunizations of the infants. Each infant was randomly assigned to Group 1 – in which breastfeeding was deferred for at least 1 h before and after each dose of rotavirus vaccine – or Group 2 – in which unrestricted breastfeeding was encouraged. Enzyme-linked immunosorbent assays were used to evaluate the titres of rotavirus-specific IgA in samples of serum collected from each infant immediately before each vaccine dose and 1 month after the second dose. Among the infants, a fourfold or greater increase in titres of rotavirus-specific IgA following vaccination was considered indicative of seroconversion.

Findings

The evaluable infants in Group 1 (n = 98) were similar to those in Group 2 (n = 106) in their baseline demographic characteristics and their pre-vaccination titres of anti-rotavirus IgA. After the second vaccine doses, geometric mean titres of anti-rotavirus IgA in the sera of Group-1 infants were similar to those in the sera of Group-2 infants (P = 0.685) and the frequency of seroconversion in the Group-1 infants was similar to that in the Group-2 infants (P = 0.485).

Conclusion

Among HIV-uninfected South African infants, abstention from breastfeeding for at least 1 h before and after each vaccination dose had no significant effect on the infants’ immune response to a rotavirus vaccine.     

A Variational Bayes Discrete Mixture Test for Rare Variant Association

Recently, many statistical methods have been proposed to test for associations between rare genetic variants and complex traits. Most of these methods test for association by aggregating genetic variations within a predefined region, such as a gene. Although there is evidence that “aggregate” tests are more powerful than the single marker test, these tests generally ignore neutral variants and therefore are unable to identify specific variants driving the association with phenotype. We propose a novel aggregate rare‐variant test that explicitly models a fraction of variants as neutral, tests associations at the gene‐level, and infers the rare‐variants driving the association. Simulations show that in the practical scenario where there are many variants within a given region of the genome with only a fraction causal our approach has greater power compared to other popular tests such as the Sequence Kernel Association Test (SKAT), the Weighted Sum Statistic (WSS), and the collapsing method of Morris and Zeggini (MZ). Our algorithm leverages a fast variational Bayes approximate inference methodology to scale to exome‐wide analyses, a significant computational advantage over exact inference model selection methodologies. To demonstrate the efficacy of our methodology we test for associations between von Willebrand Factor (VWF) levels and VWF missense rare‐variants imputed from the National Heart, Lung, and Blood Institute's Exome Sequencing project into 2,487 African Americans within the VWF gene. Our method suggests that a relatively small fraction (～10%) of the imputed rare missense variants within VWF are strongly associated with lower VWF levels in African Americans.