Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) remain common and distressing complications following surgery. The routine use of opioid analgesics for perioperative pain management is a major contributing factor to both PONV and PDNV after surgery. PONV and PDNV can delay discharge from the hospital or surgicenter, delay the return to normal activities of daily living after discharge home, and increase medical costs. The high incidence of PONV and PDNV has persisted despite the introduction of many new antiemetic drugs (and more aggressive use of antiemetic prophylaxis) over the last two decades as a result of growth in minimally invasive ambulatory surgery and the increased emphasis on earlier mobilization and discharge after both minor and major surgical procedures (e.g. enhanced recovery protocols). Pharmacologic management of PONV should be tailored to the patient’s risk level using the validated PONV and PDNV risk-scoring systems to encourage cost-effective practices and minimize the potential for adverse side effects due to drug interactions in the perioperative period. A combination of prophylactic antiemetic drugs with different mechanisms of action should be administered to patients with moderate to high risk of developing PONV. In addition to utilizing prophylactic antiemetic drugs, the management of perioperative pain using opioid-sparing multimodal analgesic techniques is critically important for achieving an enhanced recovery after surgery. In conclusion, the utilization of strategies to reduce the baseline risk of PONV (e.g. adequate hydration and the use of nonpharmacologic antiemetic and opioid-sparing analgesic techniques) and implementing multimodal antiemetic and analgesic regimens will reduce the likelihood of patients developing PONV and PDNV after surgery.

Management strategies for the treatment and prevention of postoperative/postdischarge nausea and vomiting: an updated review

Simple Summary MicroRNAs (miRNAs) are a class of highly conserved small, non-protein coding RNAs with often-deregulated expression in cancer. miR-21 is a well-studied cancer-associated microRNA which is able to regulate proliferation, apoptosis, and invasion. The aim of this study was to investigate the molecular pathways which govern miR-21 expression in gastric cancer (GC), and to assess the therapeutic benefit of targeting miR-21 function with a small, synthetic miR-21 antagomir. We confirmed that miR-21 expression in a preclinical model of early gastric cancer is dependent on Stat3 downstream of the IL-6 family cytokine-mediated activation of gp130 receptor signaling. Antagomir therapy curbed gastric tumor growth, and restricted epithelial-to-mesenchymal transition and matrix remodeling. Our study established miR-21 as a promising anti-cancer target in GC. Abstract MicroRNA-21 (miR-21) is a small, non-coding RNA overexpressed in gastric cancer and many other solid malignancies, where it exhibits both pro-and anti-tumourigenic properties. However, the pathways regulating miR-21 and the consequences of its inhibition in gastric cancer remain incompletely understood. By exploiting the spontaneous Stat3-dependent formation of inflammation-associated gastric tumors in Gp130F/F mice, we functionally established miR-21 as a Stat3-controlled driver of tumor growth and progression. We reconciled our discoveries by identifying several conserved Stat3 binding motifs upstream of the miR-21 gene promoter, and showed that the systemic administration of a miR-21-specific antisense oligonucleotide antagomir reduced the established gastric tumor burden in Gp130F/F mice. We molecularly delineated the therapeutic benefits of miR-21 inhibition with the functional restoration of PTEN in vitro and in vivo, alongside an attenuated epithelial-to-mesenchymal transition and the extracellular matrix remodeling phenotype of tumors. We corroborated our preclinical findings by correlating high STAT3 and miR-21 expression with the reduced survival probability of gastric cancer patients. Collectively, our results provide a molecular framework by which miR-21 mediates inflammation-associated gastric cancer progression, and establish miR-21 as a robust therapeutic target for solid malignancies characterized by excessive Stat3 activity.

/pdf/onco-mir-21-promotes-stat3-dependent-gastric-cancer-c7tq7opo.pdf

Onco-miR-21 Promotes Stat3-Dependent Gastric Cancer Progression

Objectives Pregabalin is a drug for neuropathic pain. Antipronociceptive properties of pregabalin have led to its recent use as an adjuvant to the multimodal postoperative pain regimen. This meta-analysis was conducted to evaluate the efficacy of perioperative pregabalin on acute and chronic postsurgical pain (CPSP) after breast cancer surgery. Methods A meta-analysis including 8 randomized controlled trials searched from MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted. Subgroup analysis was performed according to doses and timecourse of pregabalin administration. Review Manager 5.3 was selected to conduct the meta-analysis. Results Preoperative pregabalin in breast cancer surgery alleviated acute postoperative pain at rest 24 hours after surgery by 0.31 points on an 0 to 10 Numerical Rating Scale (95% confidence interval [CI] -0.57 to -0.05). Morphine consumption showed a decrease in postoperative use by 1.09 mg (95% CI: -1.61 to -0.57). The incidence of CPSP 3 months after surgery was reduced to 46% (95% CI: 0.25-0.85). Postoperative nausea and vomiting, dizziness, and sedation showed no overall significant reductions. However, a decrease in the incidence of postoperative nausea and vomiting and an increase in the incidence of dizziness were noted when patients received 300 mg of pregabalin before surgery. Discussion This study demonstrated that pregabalin showed more efficacy on chronic pain than acute pain after a breast cancer surgery. Further study based on doses and treatment course of pregabalin should be conducted to establish stronger evidence of treatment effects.

Perioperative Pregabalin for Preventive Analgesia in Breast Cancer Surgery: A Meta-analysis of Randomized Controlled Trials.

Novel mouse GABA uptake inhibitors with enhanced inhibitory activity toward mGAT3/4 and their effect on pain threshold in mice.

Already used for the treatment of some allergic and inflammatory diseases, such as asthma or atopic dermatitis, dupilumab has also been approved as add-on therapy for patients with CRSwNP, and it could represent the keystone to reducing the remission time as well as to improve healing and quality of life. On the other hand, the role of miRNAs as potential biomarkers of immune modulation is emerging. We analyzed the effects of a short-time treatment with dupilumab in patients with CRSwNP, analyzing the immune response modification as well as miRNAs modulations. First, in this early observation stage, all patients experienced remarkable improvement and were clinically stable. Indeed, we observed a significant decrease in CD4+ T cells and a significant reduction in total IgE (p < 0.05) and serum IL-8 levels (p < 0.01), indicating a reduction in the general inflammatory condition. In addition, we analyzed a panel of about 200 circulating miRNAs. After treatment, we noted a significant downregulation of hsa-mir-25-3p (p-value = 0.02415) and hsa-mir-185-5p (p-value = 0.04547), two miRNAs involved in the proliferation, inflammation, and dug-resistance, in accordance with the clinical status of patients. All these preliminary data aimed to identify new biomarkers of prognosis, identifiable with non-invasive procedures for patients. Further, these patients are still under observation, and others with different levels of responsiveness to treatment need to be enrolled to increase the statistical data.

/pdf/spotlight-on-a-short-time-treatment-with-the-il-4-il-13-1o583npb.pdf

Spotlight on a Short-Time Treatment with the IL-4/IL-13 Receptor Blocker in Patients with CRSwNP: microRNAs Modulations and Preliminary Clinical Evidence

Background Identification of more promising microRNAs (miRNAs) are being extensively studied with respect to colorectal cancer (CRC), since CRC is the leading cause of cancer deaths and most common malignant tumors worldwide. A series of colon cancer (CCa) samples from The Cancer Genome Atlas (TCGA) were analyzed to provide a new perspective into this field. Methods The expression of miRNAs, mRNAs and the clinical data of 437 CRC patients were downloaded from the TCGA database. The survival-related differentially expressed miRNAs (sDMIRs) and mRNAs were detected by COX regression analysis. The high-risk group and low-risk group were separated by the median risk score of the risk score model. The potential clinical characteristics of these sDMIRs were analyzed by R software. The potential molecular mechanisms of these sDMIRs were explored by computational biology. The expression levels of three sDMIRs were explored by qPCR in CRC samples. Results Three DMIRs (hsa-miR-21-3p, hsa-miR-194-3p and hsa-miR-891a-5p) correlated with the most remarkable prognostic values of CRC patients were selected to establish the risk score model (RSM) by univariate and multivariate COX regression analysis and the survival probability of the low-risk group was longer than that in the high-risk group. We detected the target genes of three sDMIRs and the potential molecular mechanisms of these sDMIRs. We further verified the high expression levels of hsa-miR-21-3p and hsa-miR-194-3p were associated with the early T-stages, while hsa-miR-891a-5p illustrated the reversed result. Conclusion Our study demonstrated three sDMIRs with significantly clinical values illustrated the potential predicting values in the prognosis of CRC patients. Our results may provide a new perspective for the diagnostic methods and treatment strategies in CRC patients.

Establishing a three-miRNA signature as a prognostic model for colorectal cancer through bioinformatics analysis.

Pregabalin can decrease acute pain and postoperative nausea and vomiting in hysterectomy: A meta-analysis

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Establishing a three-miRNA signature as a prognostic model for colorectal cancer through bioinformatics analysis.

Pregabalin can decrease acute pain and postoperative nausea and vomiting in hysterectomy: A meta-analysis