An epidermal growth factor receptor-targeting immunotoxin based on IgG shows potent antitumor activity against head and neck cancer.

The epidermal growth factor receptor (EGFR) is an important target for cancer therapies. Many head and neck cancer (HNC) cells have been reported to overexpress EGFR; therefore, anti-EGFR therapies have been attempted in patients with HNC. However, its clinical efficacy is limited owing to the development of drug resistance. In this study, we developed an EGFR-targeting immunotoxin consisting of a clinically proven anti-EGFR IgG (cetuximab; CTX) and a toxin fragment (LR-LO10) derived from Pseudomonas exotoxin A (PE) using a novel site-specific conjugation technology (peptide-directed photo-crosslinking reaction), as an alternative option. The immunotoxin (CTX-LR-LO10) showed specific binding to EGFR and properties of a typical IgG, such as stability, interactions with receptors of immune cells, and pharmacokinetics, and inhibited protein synthesis via modification of elongation factor-2. Treatment of EGFR-positive HNC cells with the immunotoxin resulted in apoptotic cell death and the inhibition of cell migration and invasion. The efficacy of CTX-LR-LO10 was evaluated in xenograft mouse models, and the immunotoxin exhibited much stronger tumor suppression than CTX or LR-LO10. Transcriptome analyses revealed that the immunotoxins elicited immune responses and altered the expression of genes related to its mechanisms of action. These results support the notion that CTX-LR-LO10 may serve as a new therapeutic agent targeting EGFR-positive cancers.

mu-Opioid Receptor Polymorphisms and Breast Cancer Recurrence in Adult Korean Women Undergoing Breast Cancer Surgery: A Retrospective Study.

Background: Genetic variations of mu-opioid receptors are well known to contribute to growth and progression of tumors. The most common single-nucleotide polymorphism (SNP) in the mu-opioid receptor 1 gene (OPRM1) is the A118G mutation. We examined the association between the recurrent breast cancer and genotypes of OPRM1 A118G SNP (AA vs. AG vs. GG) in Korean women population. Methods: We analysed medical records and genetic data of 200 patients aged more than 20 who underwent primary breast cancer surgery from June 2012 to June 2014 and diagnosed recurrent breast cancer from June 2012 to September 2019. Results: The incidence of recurrent breast cancer was 6.1%, 8.2%, and 4.8% in genotype AA, AG and GG, respectively (p=0.780). The incidence of recurrent breast cancer in volatile anaesthesia group was 7.0% and 7.1% in total intravenous anaesthesia (TIVA) group (RR = 0.984, 95% CI = 0.328 - 2.951; p = 0.978). Conclusion: OPRM1 A118G SNP had no influence on breast cancer recurrence in Korean women. Anaesthesia technique did not show significant effect on the incidence of recurrent breast cancer.

Postoperative residual neuromuscular blockade after reversal based on a qualitative peripheral nerve stimulator response: A randomised controlled trial.

BACKGROUND: Incomplete recovery of neuromuscular blockade is a common postoperative adverse event in the postanaesthesia care unit. OBJECTIVE: We examined and compared the incidence of residual neuromuscular blockade when the recommended dose of neostigmine or sugammadex was administered according to a qualitative nerve stimulator response. DESIGN: A randomised controlled trial. SETTING: A tertiary care hospital in South Korea from September 2017 to November 2017. PATIENTS: Eighty patients aged between 18 and 69 years were included in this study. All were patients scheduled to undergo elective laparoscopic cholecystectomy and who had an American Society of Anaesthesiologists physical status of one or two were eligible. INTERVENTIONS: Patients were allocated randomly to receive neostigmine or sugammadex at the end of surgery. The doses of the reversal agents were based on the response to peripheral nerve stimulation, which was discontinued after administration of the reversal agent. MAIN OUTCOME MEASURES: The primary outcome was the incidence of postoperative residual neuromuscular blockade. The secondary outcomes were the incidences of symptoms or signs of residual neuromuscular blockade such as hypoxaemia, inability to maintain head-lift for 5 s and diplopia. RESULTS: The incidence of residual neuromuscular blockade on arrival in the recovery room was 44.4% in the neostigmine group and 0% in the sugammadex group (P < 0.0001, relative risk = 1.80, 95% confidence interval 1.36 to 2.41). The incidences of adverse events in the recovery room were low and comparable between the groups. CONCLUSION: The incidence of residual neuromuscular blockade on arrival in the recovery room was significantly higher in the neostigmine group than that in the sugammadex group. However, the incidence of adverse events was similar in the neostigmine and sugammadex groups. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03292965.

Korean clinical practice guidelines for diagnostic and procedural sedation.

Safe and effective sedation depends on various factors, such as the choice of sedatives, sedation techniques used, experience of the sedation provider, degree of sedation-related education and training, equipment and healthcare worker availability, the patient's underlying diseases, and the procedure being performed. The purpose of these evidence-based multidisciplinary clinical practice guidelines is to ensure the safety and efficacy of sedation, thereby contributing to patient safety and ultimately improving public health. These clinical practice guidelines comprise 15 key questions covering various topics related to the following: the sedation providers; medications and equipment available; appropriate patient selection; anesthesiologist referrals for high-risk patients; pre-sedation fasting; comparison of representative drugs used in adult and pediatric patients; respiratory system, cardiovascular system, and sedation depth monitoring during sedation; management of respiratory complications during pediatric sedation; and discharge criteria. The recommendations in these clinical practice guidelines were systematically developed to assist providers and patients in sedation-related decision making for diagnostic and therapeutic examinations or procedures. Depending on the characteristics of primary, secondary, and tertiary care institutions as well as the clinical needs and limitations, sedation providers at each medical institution may choose to apply the recommendations as they are, modify them appropriately, or reject them completely.

Assessment of the effects of sugammadex on coagulation profiles using thromboelastographic parameters.

This study evaluated the effects of sugammadex at conventional doses of 2 and 4 mg/kg on the coagulation profile by analyzing thromboelastographic parameters and performing a traditional laboratory coagulation analysis. A total of 100 patients undergoing arthroscopic shoulder surgery were enrolled. The patients were randomly divided into the 2 mg and 4 mg groups. The laboratory coagulation test and thromboelastographic analysis were performed before and 15 min after administering sugammadex. Prothrombin time (PT) was significantly prolonged after sugammadex administration than before it in intragroup comparisons of the 2 mg group (12.8 ± 0.6 s vs. 13.6 ± 0.7 s, p < 0.001) and the 4 mg group (13.0 ± 0.5 s vs. 13.7 ± 0.5 s, p < 0.001). R time, derived from thromboelastography, was also significantly prolonged after sugammadex administration (4.7 ± 1.8 min vs. 5.8 ± 2.1 min, p = 0.005). In conclusion, the conventional doses of 2 or 4 mg/kg sugammadex prolonged PT. Sugammadex 4 mg/kg also prolonged R time, although the value was within the normal range. Therefore, physicians should be cautious with the higher sugammadex dose, particularly in patients with a high risk of bleeding because the higher dose was associated with less coagulation.Trial registration: KCT0002133 (https://cris.nih.go.kr).

Author Correction: Assessment of the effects of sugammadex on coagulation profiles using thromboelastographic parameters.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Effect of Intraoperative Magnesium Sulphate Infusion on Emergence Agitation after Ambulatory Ophthalmic Surgery in Children.

This study investigated whether intraoperative infusion of magnesium sulphate reduces the incidence of emergence agitation (EA) in paediatric patients who undergo ambulatory ophthalmic surgery using the Paediatric Anaesthesia Emergence Delirium (PAED) scale. Ninety-two paediatric patients who were scheduled for elective ophthalmic surgery were randomly allocated to two groups: control or magnesium. In the magnesium group, patients received an initial intravenous loading dose of 30 mg/kg of 10% solution of magnesium sulphate over 10 min and then a continuous infusion of 10 mg/kg×h during the surgery. In the control group, an equal volume of 0.9% isotonic saline was administered in the same way as in the magnesium group. The PAED scale was assessed at 15-min intervals until the PAED score reached below 10 at the postanaesthetic care unit. EA was defined as a PAED score of 10 or higher. Of the 86 patients recruited, 44 and 42 were allocated to the control and magnesium groups, respectively. The incidence of EA was 77.3% in the control group and 57.1% in the magnesium group (odds ratio, 0.392; 95% confidence interval, 0.154 to 0.997; p = 0.046). The intraoperative infusion of magnesium sulphate significantly reduced the incidence of EA.

Effects of deep neuromuscular blockade on the stress response during laparoscopic gastrectomy Randomized controlled trials.

Maintaining deep neuromuscular block during surgery improves surgical space conditions. However, its effects on patient outcomes have not been well documented. We examined whether maintaining deep neuromuscular blockade during surgery could decrease the stress response compared to moderate neuromuscular blockade. Patients undergoing laparoscopic gastrectomy were randomly allocated to either the moderate (train-of-four counts of 1-2) or deep (post-tetanic counts of 1-2) neuromuscular blockade group. The primary outcome variable was the postoperative blood level of interleukin-6, and the secondary outcome variables were intraoperative or postoperative blood levels of tumor necrosis factor-α, interleukin-1ß, interleukin-8, and C-reactive protein. A total of 96 patients were recruited and 88 (44 in each group) were included in the analyses. The levels of tumor necrosis factor-α and interleukin-1ß measured at the end of surgery, interleukin-6 and interleukin-8 measured at 2 h postoperatively, and C-reactive protein measured at 48 h postoperatively were all significantly increased compared to the preoperative values, but there were no differences between the moderate and deep neuromuscular block groups. We found no differences in surgical stress response measured using determining levels of interleukin-6 and other mediators released between the moderate and deep neuromuscular blockade groups in patients undergoing laparoscopic gastrectomy.

Anticancer Activity of an Oplopanax elatus Stem Extract and Biologically Active Isolated Compounds.

BACKGROUND AND METHODS: Oplopanax elatus (Nakai) Nakai is used in folk medicine in China. In this study, the antiproliferative activity of an O. elatus fraction extracted by ethyl acetate (EF) was tested on human breast cancer MCF-7 cells, human colon cancer HCT-116 cells, and human stomach cancer AGS cells. The potential mechanism of antiproliferation was also investigated using an apoptosis assay. RESULTS: The results showed that the EF remarkably suppressed proliferation of human breast, stomach, and colon cancer cells. Further apoptosis tests by flow cytometry and immunoblot analyses showed the EF inhibited HCT-116 cell proliferation by inducing apoptosis. The bioassay-monitored fractionation of the EF resulted in the isolation of two polyacetylenes, falcarindiol (compound 1) and oplopandiol (compound 2), with falcarindiol possessing the strongest antiproliferative activity in colon cancer cells. CONCLUSION: Together, this study evaluated the anticancer activity of an O. elatus extract against human cancer cells, and provided the basis for further development of this herbal extract for the treatment of cancer.

Usefulness of intraoperative real-time three-dimensional transesophageal echocardiography in preprocedural evaluation of cortriatriatum -a case report-.

Cortriatriatum is a rare congenital cardiac disorder with fibromuscular band (diaphragm) dividing the left atrium (LA) into the proximal and distal parts. Surgical correction of cortriatriatum requires full preoperative evaluation of the structural anomalies including the LA diaphragm and their pathophysiology. In the present case, a 44 year-old lady diagnosed as cortriatriatum underwent surgical correction. Intraoperative three-dimensional transesophageal echocardiography provided detailed information regarding the shape and extent of the LA diaphragm, which had been partially evaluated by preoperative two-dimensional transthoracic and transesophageal echocardiography, and facilitated the intraoperative patient management and surgical decision making.