Supplemental peri-operative intravenous crystalloids for postoperative nausea and vomiting: an abridged Cochrane systematic review

We conducted a Cochrane systematic review on the effectiveness of supplemental intravenous crystalloid administration in preventing postoperative nausea and vomiting. We included randomised controlled trials of patients undergoing surgery under general anaesthesia and given supplemental peri-operative intravenous crystalloid. Our primary outcomes were the risk of postoperative nausea and the risk of postoperative vomiting. We assessed the risk of bias for each included study and applied the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework for the certainty of evidence. We included 41 studies. We found that the intervention probably reduces the overall risk of postoperative nausea, the risk ratio (95%CI) being 0.62 (0.51–0.75) (I² = 57%, p < 0.00001, 18 studies; 1766 participants; moderate-certainty evidence). It also probably reduces the risk of postoperative nausea within 6 h of surgery, with a risk ratio (95%CI) of 0.67 (0.58 to 0.78) (I² = 9%, p < 0.00001, 20 studies; 2310 participants; moderate-certainty evidence) and by around 24 h, the risk ratio (95%CI) being 0.47 (0.32–0.69) (I² = 38%, p = 0.0001, 17 studies; 1682 participants; moderate-certainty evidence). Supplemental intravenous crystalloid probably also reduces the overall risk of postoperative vomiting, with a risk ratio (95%CI) of 0.50 (0.40–0.63) (I² = 31%, p < 0.00001, 20 studies; 1970 participants; moderate-certainty evidence). The beneficial effect on vomiting was seen both within 6 h and by around 24 h postoperatively.     

Improved accuracy of anticoagulant dose prediction using a pharmacogenetic and artificial neural network-based method

Background

The unpredictability of acenocoumarol dose needed to achieve target blood thinning level remains a challenge. We aimed to apply and compare a pharmacogenetic least-squares model (LSM) and artificial neural network (ANN) models for predictions of acenocoumarol dosing.

Methods

LSM and ANN models were used to analyze previously collected data on 174 participants (mean age: 67.45 SD 13.49 years) on acenocoumarol maintenance therapy. The models were based on demographics, lifestyle habits, concomitant diseases, medication intake, target INR, and genotyping results for CYP2C9 and VKORC1. LSM versus ANN performance comparisons were done by two methods: by randomly splitting the data as 50 % derivation and 50 % validation cohort followed by a bootstrap of 200 iterations, and by a 10-fold leave-one-out cross-validation technique.

Results

The ANN-based pharmacogenetic model provided higher accuracy and larger R value than all other LSM-based models. The accuracy percentage improvement ranged between 5 % and 24 % for the derivation cohort and between 12 % and 25 % for the validation cohort. The increase in R value ranged between 6 % and 31 % for the derivation cohort and between 2 % and 31 % for the validation cohort. ANN increased the percentage of accurately dosed subjects (mean absolute error ≤1 mg/week) by 14.1 %, reduced the percentage of mis-dosed subjects (mean absolute error 2-3 mg/week) by 7.04 %, and reduced the percentage of grossly mis-dosed subjects (mean absolute error ≥4 mg/week) by 24 %.

Conclusions

ANN-based pharmacogenetic guidance of acenocoumarol dosing reduces the error in dosing to achieve target INR. These results need to be ascertained in a prospective study.     

Evaluation of Alum-Naltrexone Adjuvant Activity,on Efficacy of Anti-Leishmania Immunization with Autoclaved Leishmania major (MRHO/IR/75/ER) Antigens in BALB/C Mice

Background

Naltrexone, an opioid receptor antagonist shifts the immune response toward a Th1 profile. In the current study, we evaluated the efficacy of the mixture of NTX and alum, as a new adjuvant, to enhance immune response and induce protection against Leishmania major in a mouse model.

Methods

BALB/c mice were immunized three times either autoclaved L. major promastigotes’ antigens alone or in combination with the adjuvant alum, naltrexone or the alum–naltrexone mixture. Both humoral and cellular immune responses were assessed two weeks after the last immunization and compared with control mice.

Results

The administration of alum- NTX in combination with the parasite antigen, significantly increased production of IFN-γ IFN-γ /IL-5 ratio, lymphocyte proliferation and improved DTH response against L. major. There was no significant difference in survival following challenge among groups.

Conclusion

Immunization with the alum– naltrexone mixture as an adjuvant, in combination with the autoclaved L. major promastigotes antigens, can enhance cellular immunity and shift the immune responses to a Th1 pattern.     

Retraction Note: Screening and identification of bioactive compounds from citrus against non-structural protein 3 protease of hepatitis C virus genotype 3a by fluorescence resonance energy transfer assay and mass spectrometry

Retraction note: Khan M, Rauf W, Habib F, Rahman M, Iqbal M. Screening and identification of bioactive compounds from citrus against non-structural protein 3 protease of hepatitis C virus genotype 3a by fluorescence resonance energy transfer assay and mass spectrometry. World J Hepatol 2020; 12(11): 976-992 PMID: 33312423 DOI: 10.4254/wjh.v12.i11.976. The online version of the original article can be found at https://www.wjgnet.com/1948-5182/full/v12/i11/976.htm.     

Hepatitis C virus infection in a community in the Nile Delta: risk factors for seropositivity

The purpose of this study was to identify risk factors for hepatitis C virus (HCV) infection in a rural village in the Nile Delta with a high prevalence of antibodies to HCV (anti-HCV). One half of the village households were systematically selected, tested for anti-HCV, and interviewed: 973 of 3,999 (24.3%) subjects were anti-HCV-positive (reflecting prior HCV infection but not necessarily current liver disease), with nearly equal prevalence among males and females. Anti-HCV prevalence increased sharply with age among both males and females, from 9.3% in those 20 years of age and younger to >50% in those older than 35, suggesting a cohort effect with reduced transmission in recent years. Multivariate regression was used to estimate independent effects of risk factors on seropositivity. Among those over 20 years of age, the following risk factors were significantly associated with seropositivity: age (P <.001); male gender (odds ratio [OR] = 2.5, 95% CI = 1.3-4.7); marriage (OR = 4.1, 2.4-6.9); anti-schistosomiasis injection treatment (OR = 2.0, 1.3-2.9); blood transfusion (OR = 1.8, 1.1-2.9), invasive medical procedure (surgery, catheterization, endoscopy, and/or dialysis) (OR = 1.5, 1.1-1.9); receipt of injections from "informal" health care provider (OR = 1.3, 1.0-1.6); and cesarean section or abortion (OR = 1.4, 1.0-1.9). Exposures not significantly related to anti-HCV positivity in adults included: history of, or active infection with, Schistosoma mansoni, sutures or abscess drainage, goza smoking in a group, and shaving by community barbers. Among those 20 years old or younger, no risk factors were clearly associated with anti-HCV positivity; however, circumcision for boys by informal health care providers was marginally associated with anti-HCV (OR = 1.7, 1.0-3.0). Prevention programs focused primarily on culturally influenced risks in rural Egyptian communities are being implemented and evaluated.     

Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases

CARD15 is a major susceptibility gene for a frequent multifactorial chronic inflammatory bowel disorder, Crohn disease (CD). By using NF-kappaB activation assays, the cytosolic CARD15 was shown to efficiently detect bacterial peptidoglycan (PGN), reminiscent of the PGN recognition protein surveillance mechanism in Drosophila. The 3 CD-associated variants and 13 additional variants carried by CD patients demonstrated impaired PGN-dependent response revealing null, hypomorphic, or dominant-negative properties. Quantitative parametrization of this response, computed from the patients' CARD15 genotypes, was predictive of several variable CD manifestations. In contrast, CARD15 alleles associated with Blau's syndrome promoted PGN-independent NF-kappaB activation, an observation that accounts for the minimal microbial input in the etiology of this dominant, monogenic inflammatory disorder affecting solely aseptic sites.     

Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice.

gamma-Glutamyl transpeptidase (GGT) is an ectoenzyme that catalyzes the first step in the cleavage of glutathione (GSH) and plays an essential role in the metabolism of GSH and GSH conjugates of carcinogens, toxins, and eicosanoids. To learn more about the role of GGT in metabolism in vivo, we used embryonic stem cell technology to generate GGT-deficient (GGTm1/GGTm1) mice. GGT-deficient mice appear normal at birth but grow slowly and by 6 weeks are about half the weight of wild-type mice. They are sexually immature, develop cataracts, and have coats with a gray cast. Most die between 10 and 18 weeks. Plasma and urine GSH levels in the GGTm1/GGTm1 mice are elevated 6-fold and 2500-fold, respectively, compared with wild-type mice. Tissue GSH levels are markedly reduced in eye, liver, and pancreas. Plasma cyst(e)ine levels in GGTm1/GGTm1 mice are reduced to approximately 20% of wild-type mice. Oral administration of N-acetylcysteine to GGTm1/GGTm1 mice results in normal growth rates and partially restores the normal agouti coat color. These findings demonstrate the importance of GGT and the gamma-glutamyl cycle in cysteine and GSH homeostasis.