Surgical Pharmacy for Optimizing Medication Therapy Management Services within Enhanced Recovery after Surgery (ERAS®) Programs.

Drug-related problems (DRPs) are common among surgical patients, especially older patients with polypharmacy and underlying diseases. DRPs can potentially lead to morbidity, mortality, and increased treatment costs. The enhanced recovery after surgery (ERAS) system has shown great advantages in managing surgical patients. Medication therapy management for surgical patients (established as "surgical pharmacy" by Guangdong Province Pharmaceutical Association (GDPA)) is an important part of the ERAS system. Improper medication therapy management can lead to serious consequences and even death. In order to reduce DRPs further, and promote the rapid recovery of surgical patients, the need for pharmacists in the ERAS program is even more pressing. However, the medication therapy management services of surgical pharmacy and how surgical pharmacists should participate in ERAS programs are still unclear worldwide. Therefore, this article reviews the main perioperative medical management strategies and precautions from several aspects, including antimicrobial agents, antithrombotic agents, pain medication, nutritional therapy, blood glucose monitoring, blood pressure treatment, fluid management, treatment of nausea and vomiting, and management of postoperative delirium. Additionally, the way surgical pharmacists participate in perioperative medication management, and the relevant medication pathways are explored for optimizing medication therapy management services within the ERAS programs. This study will greatly assist surgical pharmacists' work, contributing to surgeons accepting that pharmacists have an important role in the multidisciplinary team, benefitting medical workers in treating, counseling, and advocating for their patients, and further improving the effectiveness, safety and economy of medication therapy for patients and promoting patient recovery.

Nongenetic and genetic predictors of haemodynamic instability induced by propofol and opioids: A retrospective clinical study.

AIM: Propofol and opioids are commonly used in anaesthesia, but are highly susceptible to haemodynamic instability, thereby threatening the patient's surgical safety and prognosis. The purpose of this study was to investigate the predictors of haemodynamic instability and establish its predictive model. METHODS: A total of 150 Chinese patients undergoing thyroid or breast surgery participated in the study, with target-controlled infusion concentrations of propofol, opioids dosage, heart rate (HR), mean arterial pressure (MAP) and Narcotrend Index recorded at key points throughout the procedure. The Agena MassARRAY system was used to genotype candidate single nucleotide polymorphisms related to pharmacodynamics and pharmacokinetics of propofol and opioids. RESULTS: Among nongenetic factors, baseline HR (R = -.579, P < .001) and baseline MAP (R = -.725, P < .001) had a significant effect on the haemodynamic instability. Among genetic factors, the CT/CC genotype of GABRB1 rs4694846 (95% confidence interval [CI]: -11.309 to -3.155), AA/AG of OPRM1 rs1799971 (95%CI: 0.773 to 10.290), AA of CES2 rs8192925 (95%CI: 1.842 to 9.090) were associated with higher HR instability; the AA/GG genotype of NR1I2 rs6438550 (95%CI: 0.351 to 7.761), AA of BDNF rs2049046 (95%CI: -9.039 to -0.640) and GG of GABBR2 rs1167768 (95%CI: -10.146 to -1.740) were associated with higher MAP instability. The predictive models of HR and MAP fluctuations were developed, accounting for 45.0 and 59.2% of variations, respectively. CONCLUSION: We found that cardiovascular fundamentals and genetic variants of GABRB1, GABBR2, OPRM1, BDNF, CES2 and NR1I2 are associated with cardiovascular susceptibility, which can provide a reference for haemodynamic management in clinical anaesthesia.

Mechanisms of Compound Sophora flavescens (Kushen) Decoction for the Treatment of Ulcerative Colitis based on Network Pharmacology and Molecular Docking Technology.

BACKGROUND: The compound Sophora flavescenes (Kushen) decoction was found to reduce the inflammatory symptom of Ulcerative Colitis (UC). However, there exists a very limited understanding of the molecular pharmacological mechanisms. OBJECTIVE: This study aimed to explore the mechanism of compound Sophora flavescens (Kushen) decoction in treating ulcerative colitis from the perspective of network pharmacology. METHODS: Active components and potential targets of compound Sophora flavescens (Kushen) decoction were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. GeneCards and other databases were used to predict and screen ulcerative colitis-related genes. Cytoscape software was applied to construct the "drugactive component-disease-target" network. GO function and KEGG pathway enrichment analyses revealed the potential pathway of the compound Sophora flavescenes (Kushen) decoction for UC. RESULTS: After the screening, a total of 124 active ingredients and 163 potential therapeutic targets for UC were obtained from the compound Sophora flavescens (Kushen) decoction. Protein interaction network analysis showed that 15 key targets could be identified for the possible treatment of UC. GO and KEGG analyses showed that the active ingredients in the compound Sophora flavescens (Kushen) decoction were mainly enriched in 2556 biological processes and 172 signaling pathways. CONCLUSION: The study showed that the compound Sophora flavescens (Kushen) decoction has therapeutic effects on UC through multi-component, multi-target, and multi-pathway.

A single nucleotide polymorphism-based formula to predict the risk of propofol TCI concentration being over 4 µg mL-1 at the time of loss of consciousness.

We aim to develop a formula based on single nucleotide polymorphisms (SNPs) to predict whether the propofol target-controlled infusion (TCI) concentration would be over 4 µg mL-1 at the time of loss of consciousness (LOC). We recruited 184 patients undergoing thyroid or breast surgeries with propofol anaesthesia. A total of 48 SNPs of CYP2B6, CYP2C9, UGT1A9, HNF4A, ABCB1, ABCC4, ABCG2, GABRA2, GABRA4, GABRB1, GABRB3, GABRG2, GABBR2, GAD1, SLC1A3, BDNF, and NRXN1, previously associated with propofol metabolic and pharmacology pathway, were genotyped. The formula was developed in the training cohort using the least absolute shrinkage and selection operator logistic regression model, and then validated in the testing cohort. The SNPs, GABBR2 rs1167768, GABBR2 rs1571927, NRXN1 rs601010, BDNF rs2049046, GABRA4 rs1512135, UGT1A9 rs11692021, GABBR2 rs2808536, HNF4A rs1884613, GABRB3 rs2017247, and CYP2B6 rs3181842 were selected to construct the SNP-based formula, which was used to calculate the risk score for over 4 µg mL-1 TCI concentration of propofol at the time of LOC. Patients in the high-risk group were more likely to require a propofol concentration higher than 4 µg mL-1 and presented a longer LOC latency. The SNP-based formula may significantly improve the safety and effectiveness of propofol-induced anaesthesia.

The Effects of Gene Variations of GABRA2, GABRB1, GABRG2, GAD1 and SLC1A3 on Patients with Propofol During Anesthesia Induction.

PURPOSE: Propofol is one of the most commonly used intravenous sedatives in general anesthesia, while the individual variations of propofol are apparent. The objective of this study was to investigate the influence of genetic variations in GABAergic neurons and glutamatergic neurons on time to loss of consciousness (LOC) and the incidence of hypotension during anesthesia induction. PATIENTS AND METHODS: A total of 140 Chinese patients undergoing thyroid surgery or breast surgery were recruited. Genotyping of candidate genes was carried out using the Agena Bioscience MassARRAY system. Anesthesia induction was initiated with a propofol target plasma concentration (Cp) of 4.0 µg mL-1. The LOC latency, systolic blood pressure, diastolic blood pressure, mean arterial pressure were documented. RESULTS: We found that GABRA2 rs35496835, GABRB1 rs1372496, GABRG2 rs11135176, GABRG2 rs209358, GAD1 rs3791878, SLC1A3 rs1049522 and gender were significant determinants of the patient's LOC latency following propofol administration. GABRA2 rs11503014 was highly correlated with blood pressure reduction during anesthesia induction. Multiple linear regression analysis revealed that GABRB1 rs1372496, GABRG2 rs11135176, and SLC1A3 rs1049522 accounted for 35.3% variations in LOC latency following propofol administration. CONCLUSION: Our findings indicate that genetic variants of GABRA2, GABRB1, GABRG2, GAD1 and SLC1A3 may have influence on propofol susceptibility, which would be an important guidance towards building clinical models that can precisely predict the efficacy of propofol with various populations before surgery.

Comprehensive analysis of the prognostic value of the chemokine-like factor-like MARVEL transmembrane domain-containing family in gastric cancer.

BACKGROUND: The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family refers to a family of transcriptional repressor genes. CMTMs are closely associated with the epigenetic regulatory mechanisms and development of multiple malignancies, including gastric cancer. However, their specific biological functions and prognostic values in gastric cancer have yet to be elucidated. METHODS: Tumor sample datasets were retrieved and analyzed using databases including Oncomine, STRING, GEPIA2, cBioportal, and Kaplan-Meier plotter. To investigate the prognostic role of CMTMs in gastric cancer, we applied unsupervised hierarchical clustering analysis of CMTM gene expression patterns. RESULTS: While the mRNA levels of CMTM1/3/6/7/8 were upregulated in gastric cancer, CMTM2/4/5 showed no statistically significant difference at the mRNA level in patients with gastric cancer. Moreover, the mRNA expressions of different CMTMs exhibited strong correlations with various clinical parameters of patients with gastric cancer, including tumor stage, metastatic lymph node status, H. pylori status, and tumor grade. Also, the results suggested that elevated levels of CMTM3/5 mRNA had a significant association (P<0.05) with poor overall survival, progression-free survival, and post-progression survival. Conversely, elevated expression of CMTM2/4/6 mRNA had a significant association with better overall survival, progression-free survival, and post-progression survival. Unsupervised hierarchical clustering analysis successfully identified 2 major clusters of patients as follows: signature #1: CMTM4/6/8 and signature #2: CMTM1/2/3/5/7. Signature #2 was closely correlated with poorer overall survival, which indicated that the expression pattern of the CMTM family could be a novel prognostic factor for patients with gastric cancer. CONCLUSIONS: These results suggest that the expression levels of CMTM genes possibly have prognostic value as a biomarker of gastric cancer.

Identification of candidate biomarkers and therapeutic drugs of colorectal cancer by integrated bioinformatics analysis.

Most colorectal cancer (CRC) patients are diagnosed with advanced stages and low prognosis. We aimed to identify potential diagnostic and prognostic biomarkers, as well as active small molecules of CRC. Microarray data (GSE9348, GSE35279, and GSE106582) were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by the GEO2R platform. Common DEGs were selected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Cytoscape software was used to construct protein-protein interaction networks and identify hub genes. Hub genes were evaluated by Kaplan-Meier survival analysis in the GEPIA database and validated in two independent microarray data (GSE74602 and GSE83889). Common DEGs were used to select active small molecules by the connectivity map database. A total of 166 DEGs were identified as common DEGs. GO analysis demonstrated that common DEGs were significantly enriched in the apoptotic process, cell proliferation, and cell adhesion. KEGG analysis indicated that the most enriched pathways were the PI3K-Akt signaling pathway and extracellular matrix-receptor interaction. COL1A2, THBS2, TIMP1, and CXCL8 significantly upregulated in colorectal tumor. High expressions of COL1A2, THBS2, and TIMP1 were associated with poor survival, while high expressions of CXCL8 were associated with better survival. We selected 11 small molecules for CRC therapy. In conclusion, we found key dysregulated genes associated with CRC and potential small molecules to reverse them. COL1A2, THBS2, TIMP1, and CXCL8 may act as diagnostic and prognostic biomarkers of CRC.

Determination of dexmedetomidine by UHPLC-MS/MS and its application to evaluate the effect of dexmedetomidine concentration on the target-controlled infusion concentration of propofol.

The combination of dexmedetomidine (DEX) and propofol (PPF) is extensively used in the field of anaesthesiology. This study aimed to develop and validate a rapid, simple and sensitive ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of DEX in human plasma. The method was applied to evaluate the effect of DEX concentration on the target-controlled infusion (TCI) concentration of PPF. Analytes were separated on a Waters XTERRA® MS C18 column with a mobile phase of acetonitrile-methanol-water containing 0.1% formic acid and 5 mM ammonium acetate (70:10:20, v/v/v) at a flow-rate of 0.3 mL/min. Mass spectrometry was performed in the positive selection reaction monitoring mode. The 201.12 → 95.12 and 515.29 → 275.68 mass transitions of DEX and IS (telmisartan), respectively, were monitored. The calibration curve of DEX was linear over the concentrations of 0.1-10 ng/mL. The intra-batch and inter-batch precisions of quality control samples were less than 10.05% and had accuracies of less than 6.25%. The newly developed method was successfully applied to quantify the DEX concentrations of plasma samples from 34 patients who were co-medicated with DEX prior to receiving anaesthesia by PPF. Results showed that comedication with DEX could reduce the requirements of PPF. Specifically, it was firstly found that the concentration of DEX is negatively correlated with the TCI concentration of PPF at the time of loss of consciousness.