Effects of opioids administered via intravenous or epidural patient-controlled analgesia after caesarean section: A network meta-analysis of randomised controlled trials.

Background: Post-caesarean section analgesia is important physiologically and psychologically for both mothers and infants. Patient-controlled analgesia is a well-established method of administering opioids for postoperative pain. However, to date, no study has systematically investigated the effects of opioids administered through intravenous patient-controlled analgesia (IVPCA) or patient-controlled epidural analgesia (PCEA) in parturients who have undergone caesarean section. Methods: This systematic review and network meta-analysis aimed to evaluate the analgesic and adverse effects of opioids administered via IVPCA or PCEA in parturients who have undergone a caesarean section. PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched from inception through 02 10, 2022 for relevant records. Randomised controlled trials (RCTs) that compared opioids administered via IVPCA or PCEA and reported outcomes of interest were included. Studies were excluded if the solution for patient-controlled analgesia contained antiemetics and/or other analgesics in addition to opioids. The methodological quality of RCTs was assessed using the revised Cochrane Risk of Bias Tool. Summary data were extracted from each eligible study. The primary outcome was pain intensity, and the secondary outcomes were opioid-related adverse effects. Frequentist network meta-analyses were performed using a contrast-based random-effects model. This study is registered with PROSPERO, CRD42021254040. Findings: Twenty-three studies with 2589 parturients were included. Compared with IVPCA morphine as a reference treatment, PCEA fentanyl had better analgesic effects at 4 h (mean difference [MD] in the visual analogue scale score, -0.75; 95% confidence interval [CI] [-1.16, -0.34]) and 8 h (MD, -0.93; 95% CI [-1.57, -0.28]) and yielded lower odds of developing nausea/vomiting (odds ratio [OR], 0.27; 95% CI [0.09, 0.80]) and sedation/drowsiness (OR, 0.22; 95% CI [0.11, 0.45]). However, PCEA fentanyl may be more likely to cause pruritus than IVPCA treatments. Interpretation: Considering the analgesic efficacy; opioid-induced nausea, vomiting, and sedation; and the well-being of breastfed infants, PCEA fentanyl may be the treatment of choice for post-caesarean section analgesia. Funding: The Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (TCRD-TPE-111-27).

Effects of Short-Acting Opioids on Intraocular Pressure during General Anesthesia: Systematic Review and Network Meta-Analysis.

Intraocular pressure (IOP) is crucial to the well-being of eyes. During anesthesia, the administration of succinylcholine and endotracheal intubation are associated with an increase in IOP, which may be attenuated by short-acting opioids. However, the drug of choice among the commonly used short-acting opioids is unclear. This study aimed to evaluate the effects of fentanyl, sufentanil, alfentanil, and remifentanil on IOP measured after the administration of succinylcholine and after endotracheal intubation in patients undergoing general anesthesia. Five databases were searched. Randomized controlled trials (RCTs) that compared short-acting opioids and reported at least one of the clinical outcomes of interest were included. Nine RCTs with 357 patients were included. Remifentanil (1 µg kg-1) more effectively alleviated the increase in IOP than the placebo after the administration of succinylcholine [mean difference (MD) of IOP, -3.64; confidence interval (CI), -5.47 to -1.81 and after endotracheal intubation (MD, -9.71; CI, -11.91 to -7.51). Remifentanil (1 µg kg-1) ranked the best in terms of both attenuating the increase in IOP after the administration of succinylcholine [surface under the cumulative ranking curve (SUCRA), 0.91; normalized entropy (NE), 0.47; and after endotracheal intubation (SUCRA, 0.89; NE, 0.54) among all of the treatments. Remifentanil (1 µg kg-1) should be considered the drug of choice in the circumstances where increased IOP is a great concern.

Concise synthesis and biological activity evaluation of novel pyrazinyl-aryl urea derivatives against several cancer cell lines, which can especially induce T24 apoptotic and necroptotic cell death.

Based on the structural modification of regorafenib, 28 pyrazinyl-aryl urea derivatives were synthesized and their in vitro antiproliferative activities were evaluated. Six compounds (5-16, 5-17, 5-18, 5-19, 5-22, and 5-23) exhibited favorable inhibitory activity against the human bladder cancer T24 cell line, and 5-23 demonstrated the strongest inhibitory activity (IC50 = 4.58 ± 0.24 µM) with high selectivity. Compound 5-23 induced apoptosis in the low concentration range (≤7.5 µM) combined with shorter incubation time (≤10 h) via the activation of caspases, while high concentrations and prolonged incubation times led to necroptotic cell death by activating the RIPK1/RIPK3/MLKL signaling pathway. Induced apoptosis and necroptosis were closely associated with intracellular reactive oxygen species generation and decreased mitochondrial membrane potential. Compared with regorafenib, 5-23 displayed improved pharmacokinetic profiles in an in vivo rat model. Molecular docking and structure-activity relationship analyses were in agreement with the biological data. Compound 5-23 may be a potent anti-bladder cancer agent and this small molecule can be considered as a promising structure for further optimization.

Correction: Concise synthesis and biological activity evaluation of novel pyrazinyl-aryl urea derivatives against several cancer cell lines, which can especially induce T24 apoptotic and necroptotic cell death.

[This corrects the article DOI: 10.1039/D1MD00306B.].

A Meta-Analysis of Comparing Intermittent Epidural Boluses and Continuous Epidural Infusion for Labor Analgesia.

With the development of medical equipment and techniques in labor anesthesia, it is a major issue to investigate the risks and treatment effects among techniques such as continuous epidural infusion (CEI) and intermittent epidural bolus (IEB). However, there is a controversial result regarding two techniques. This study was conducted through meta-analysis of randomized controlled trials (RCTs) for labor analgesia between the CEI and IEB techniques. The pooled results were presented as weighted mean differences (WMDs) together with 95% confidence intervals (CIs) and odds ratios (ORs) together with 95% CIs, respectively. Eleven RCTs were included in this meta-analysis. Four hundred sixty-five parturients accepted CEI, whereas 473 parturients accepted IEB labor analgesia. Elven identified low- risk bias studies were recruited for meta-analysis. The results presented no statistical difference in cesarean delivery rate between IEB and CEI (OR, 0.96; 95% CI, 0.67-1.37) and duration of second stage of labor (WMD, -3.82 min; 95% CI, -8.28 to 0.64). IEB had statistically significant lessened risk of instrumental delivery (OR, 0.59; 95% CI, 0.39-0.90) and for the use in local anesthetic (WMD, -1.71 mg bupivacaine equivalents per hour; 95% CI, -1.88 and -1.55). Accepted IEB had a higher score of maternal satisfaction (WMD, -6.95 mm; 95% CI, -7.77 to -6.13). Based on evidence, IEB showed a greater benefit for slightly reducing the use in local anesthetic, reduced risk of instrumental delivery, and improved maternal satisfaction for the requirement of labor epidural analgesia for healthy women. In the future, more studies need to be conducted to practice the IEB regimen and explore its influence on labor analgesia.

Synthesis and in vitro anti-bladder cancer activity evaluation of quinazolinyl-arylurea derivatives.

Based on the structural modification of molecular-targeted agent sorafenib, a series of quinazolinyl-arylurea derivatives were synthesized and evaluated for their anti-proliferative activities against six human cancer cell lines. Compared with other cell lines tested, T24 was more sensitive to most compounds. Compound 7j exhibited the best profile with lower IC50 value and favorable selectivity. In this study, we focused on 7j-induced death forms of T24 cells and tried to elucidate the reason for its potent proliferative inhibitory activity. Compound 7j treatment could trigger three different cell death forms including apoptosis, ferroptosis, and autophagy; which form would occur depended on the concentrations and incubation time of 7j: (1) Lower concentrations within the initial 8 h of 7j treatment led to apoptosis-dependent death. (2) Ferroptosis and autophagy occurred in the case of higher concentrations combining with extended incubation time through effectively regulating the Sxc-/GPx4/ROS and PI3K/Akt/mTOR/ULK1 pathways, respectively. (3) The above death forms were closely associated with intracellular ROS generation and decreased mitochondrial membrane potential induced by 7j. In molecular docking and structure-activity relationship analyses, 7j could bind well to the active site of the corresponding receptor glutathione peroxidase 4 (GPx4). Compound 7j could be a promising lead for molecular-targeted anti-bladder cancer agents' discovery.

Optimal measuring timing of cystatin C for early detection of contrast-induced acute kidney injury: A systematic review and meta-analysis.

OBJECTIVE: The optimal measuring timing of serum/plasma Cystatin C (CysC) for early detection of contrast-induced acute kidney injury (CIAKI) remains un-studied. We elucidated further on this issue. METHODS: We searched PubMed, MEDLINE, and Embase from inception until March 2018 for studies evaluating diagnostic accuracy of CysC for detecting CIAKI in patients exposed to contrast agents during diagnostic examinations or cardiac/peripheral catheterizations. RESULTS: A total of 10 relevant studies, comprising 2554 patients, were included and divided into the <24 -h and 24 -h groups based on CysC measuring timing (i.e., hours after contrast agent exposure). Compared with creatinine, pooled diagnostic odds ratio of CysC for detecting CIAKI of the <24 -h and 24 -h groups was 7.59 (95 % confidence interval [CI]: 1.31-44.08) and 53.81 (95 % CI: 13.57-213.26). Pooled sensitivity of the <24 -h and 24 -h groups was 0.81 and 0.88. Pooled specificity of the <24 -h and 24 -h groups was 0.64 and 0.88, respectively. Area under the hierarchical summary receiver operating characteristic curve of the <24 -h and 24 -h groups was 0.75 and 0.93. CONCLUSIONS: Measuring CysC at 24 h after contrast agent exposure shows higher diagnostic accuracy for early detection of CIAKI than measuring CysC at <24 h after contrast agent exposure.

Red man syndrome following the use of vancomycin-loaded bone cement in the primary total knee replacement: A case report.

RATIONALE: Red man syndrome (RMS) is the most common allergic reaction to vancomycin. It generally occurs during rapid infusion of vancomycin; only few cases have been reported as results of local vancomycin administration. We hereby report a rare case where RMS developed after insertion of vancomycin-loaded bone cement in a primary total knee replacement (TKR). PATIENT CONCERNS: A 74-year-old woman was admitted for a left TKR due to severe osteoarthritis. Erythematous changes over face, trunk, and extremities developed after the use of vancomycin-loaded bone cement. DIAGNOSES: According to the clinical manifestations, the patient was diagnosed with vancomycin-induced RMS. INTERVENTIONS: She was treated with fluid challenge and intravenous ephedrine, followed by intravenous diphenhydramine and hydrocortisone. OUTCOMES: The patient's symptoms and signs relieved within 1 h after treatment. LESSONS: Vancomycin-induced RMS may occur after the routine use of vancomycin-loaded bone cement in the primary TKR replacement.