Evaluating the efficacy and safety of perianal injection of liposomal ropivacaine HR18034 for postoperative analgesia following hemorrhoidectomy: A multicenter, randomized, double-blind, controlled phase II clinical trial.

STUDY OBJECTIVE: HR18034, composed of the ropivacaine encapsulated in multi-lamellar, concentric circular structure liposomes as the major component and a small amount of free ropivacaine, has performed well in animal experiments and phase I clinical trials. This trial was to investigate the efficacy, safety, pharmacokinetic profile and the minimum effective dose of HR18034 for postoperative analgesia after hemorrhoidectomy compared with ropivacaine. DESIGN: A multicenter, randomized, double-blind trial. SETTING: 19 medical centers in China. PATIENTS: 85 patients undergoing hemorrhoidectomy between October 2022 to November 2022. INTERVENTIONS: Patients were randomly divided into HR 18034 190 mg group, 285 mg group, 380 mg group and ropivacaine 75 mg group, receiving single local anesthetic perianal injection for postoperative analgesia. MEASUREMENTS: The primary outcome was the area under the resting state NRS score -time curve within 72 h after injection. The second outcomes included the proportion of patients without pain, the proportion of patients not requiring rescue analgesia, cumulative morphine consumption for rescue analgesia, etc. Safety was evaluated by adverse events incidence and plasma ropivacaine concentrations were measured to explore the pharmacokinetic characteristics of HR18034. MAIN RESULTS: The areas under the NRS score (at rest and moving states)-time curve were significantly lower in HR 18034 380 mg group than ropivacaine 75 mg at 24 h, 48 h, and 72 h after administration. However, this superiority was not observed in HR18034 190 mg group and 285 mg group. There was no difference in cumulative morphine consumption for rescue analgesia between HR 18034 groups and ropivacaine group. CONCLUSIONS: HR 18034 380 mg showed superior analgesic efficacy and equivalent safety compared to ropivacaine 75 mg after hemorrhoidectomy, thus preliminarily determined as minimum effective dose.

Severe Hypertensive Response to Atropine Therapy for Bradycardia Associated with Dexmedetomidine: Case Report and Literature Review.

Dexmedetomidine is a selective and potent α2-adrenoceptor agonist used for sedation, analgesia, and anxiolysis, with minimal respiratory depression; therefore, it is widely used in clinical practice. Transient hypertension has been reported to be an indication for the use of dexmedetomidine. The authors report three female patients who experienced hypertensive crisis when used atropine to treat bradycardia caused by dexmedetomidine. The transient hypertension is a relatively common side effect of dexmedetomidine, hypertensive crisis seen with coadministration of atropine is much less frequently reported. This is the first report to describe the use of atropine to treat bradycardia induced by dexmedetomidine, which may cause severe hypertension in female patients. They discuss the reason for and treatment of hypertension caused by administration of atropine and dexmedetomidine together and review the relevant literature.

Postoperative Adverse Cardiovascular Events Associated with Leptin and Adverse Age After Elective Major Non-Cardiac Surgery: An Asian Single-Center Study.

BACKGROUND The postoperative adverse cardiovascular events (PACE) after surgery can result in prolonged length of stay and poorer prognosis. The purpose of this Asian single-center study was to investigate the potential predicative role of leptin for PACE in elderly patients undergoing major non-cardiac surgery. MATERIAL AND METHODS The patients in the study were prospectively recruited from a series of elderly patients (≥60 years) undergoing elective major non-cardiac surgery (≥2 hours) in our hospital from June 2013 to June, 2016. The demographic and clinical data and the preoperative serum biomarkers of each participant were recorded in details. Suspected PACE were assessed by the same experienced expert based on clinical, blood, and other accessory tests. The univariate and multiple logistic regression analyses were plotted to evaluate the potential independent predictive factors for PACE. RESULTS A total of 270 elderly patients (145 males and 125 females), undergoing major elective non-cardiac surgery, were finally enrolled in this study. Older age, higher revised cardiac risk index score, higher levels of systolic blood pressure, B-type natriuretic peptide and leptin, the preoperative medication of beta blocker and lipid-lowering agents were positive predictors of PACE by univariate analyses (p<0.05). Our results indicated that preoperative leptin level (OR 1.84, 95% CI 1.08-3.42; p=0.015) and advanced age (OR 0.24, 95% CI 0.09-0.94; p=0.041) were significantly associated with the occurrence of PACE by multiple logistic regression analyses. CONCLUSIONS Preoperative serum leptin level and advanced age were two independent risk factors for PACE among elderly patients undergoing elective major non-cardiac surgery.

High TUG1 expression is associated with chemotherapy resistance and poor prognosis in esophageal squamous cell carcinoma.

PURPOSE: Long noncoding RNAs (lncRNAs) play critical roles in diverse biological processes such as tumorigenesis and metastasis. Taurine upregulated gene 1 (TUG1) is a cancer-related lncRNA that is associated with chromatin-modifying complexes and plays an important role in gene regulation. In this study, we determined the expression patterns of TUG1 in esophageal squamous cell carcinoma (ESCC) and evaluated its clinical significance. METHODS: The expression level of TUG1 was examined in 218 pairs of ESCC and adjacent non-cancerous tissues by using quantitative real-time polymerase chain reaction. The relationship between TUG1 expression and clinical features and prognosis was statistically analyzed. RESULTS: The expression level of TUG1 was significantly upregulated in ESCC tissues compared with paired adjacent normal tissues. High TUG1 expression was significantly correlated with chemotherapy resistance. Survival analysis showed that patients with high TUG1 expression had poor prognosis, especially for cases with well and moderate differentiation, ulcerative type, smaller size, and chemotherapy-sensitive tumors. CONCLUSIONS: Our findings suggest that elevated TUG1 expression is related to chemotherapy resistance and may help predict a poor prognostic outcome of ESCC. TUG1 may provide a potential therapeutic target for ESCC.

The impact of pri-miR-218 rs11134527 on the risk and prognosis of patients with esophageal squamous cell carcinoma.

MicroRNA-218 (miR-218) acts as a tumor suppressor in numerous types of cancer by regulation of the expression of target genes. The aim of this study was to investigate whether polymorphisms in miR-218 LAMB3 pathway were associated with the risk and prognosis of esophageal squamous cell carcinoma (ESCC). Pri-mir-218 rs11134527 and LAMB3 rs2566 were genotyped in ESCC patients and 745 controls to assess their associations with cancer risk and overall survival. Pri-mir-218 rs11134527 was significantly associated with a decreased risk of ESCC under codominant, recessive and additive models. Although there was a significant association between rs11134527 and better survival of ESCC patients under codominant, recessive and additive models, the association disappeared after adjustment for TNM and LNM. However, further stratified analysis revealed that the association remained significant in patients with TNM stages I and II or non-LNM. Our data suggest that pri-miR-218 rs11134527 may contribute to the genetic susceptibility and prognosis for ESCC in Chinese Han population.

Decreased circulating miR-375: a potential biomarker for patients with non-small-cell lung cancer.

MicroRNAs (miRNAs) are directly involved in cancer initiation, progression and metastasis. Alterations of miRNAs expression in cancer tissue may be reflected in circulation.We attempted to investigate the expression and clinical significance of plasma miR-20a, miR-31 and miR-375 in patients with non-small cell lung cancer (NSCLC). The plasma levels of miR-20a, miR-31 and miR-375 in 164 NSCLC patients and 164 healthy controls (discovery cohort)were evaluated and compared among various clinicopathological characteristics. The relationship between miRNA expression and clinical outcome of NSCLC patients was examined in an independent cohort (53 cases and 53 controls). The expression level of miR-375 in tissue was also examined. Plasma miR-375 levels in NSCLC patients were significantly decreased in both patient cohorts (P b 0.05). In addition, patients with metastatic NSCLC had lower plasma miR-375 expression than those with non-metastatic NSCLC (P b 0.05). Survival analysis showed that patients with low miR-375 expression had worse overall survival rates than those with high miR-375 expression (hazard ratios (HR)=1.537 (1.046­2.258), P=0.029). This association was independently validated in a separate cohort of 53 NSCLC patients (HR=2.406, 95% CI 1.170­4.945, P=0.017). The expression level of miR-375 was also found to be significantly down-regulated in NSCLC tissues compared with paracancerous tissues (P b 0.001). These findings indicate that miR-375 has an important role in NSCLC initiation and progression, and may be an independent poor prognostic factor in NSCLC patients.