Background: Intraoperative hemoglobin (Hb) monitoring is critical for ensuring patient safety during bimaxillary orthognathic surgery. Intraoperative Hb monitoring performed using portable devices with arterial blood samples is invasive, is time-consuming, and lacks the ability to provide real-time information. This retrospective study investigated the correlation between continuous and real-time total Hb (SpHb) using a Masimo Radical 7 device and Hb levels derived by portable devices during bimaxillary orthognathic surgery. Methods: Patients who underwent elective bimaxillary orthognathic surgery were enrolled. The correlation between SpHb and laboratory Hb (Lab-Hb) was evaluated immediately after the induction of anesthesia (T1) and at surgical closure (T2) and compared with postoperative Hb. Results: Eighty-eight patients were included. The correlation coefficients between SpHb and Lab-Hb were 0.795 and 0.859 at T1 and T2, respectively. The correlation coefficient between Lab-Hb at T2 and postoperative Hb was 0.918. A Bland-Altman analysis of the Lab-Hb at T2 and postoperative Hb showed a mean bias of 0.49. Conclusion In conclusion, here we demonstrated acceptable accuracy of the SpHb measured by the Masimo Radical 7 device during bimaxillary orthognathic surgery. However, SpHb is valuable as an adjunct value to Lab-Hb and a substitute for Hb monitoring due to its wide limits of agreement. These findings suggest that SpHb can help guide the timing of invasive blood sampling for Hb measurements, which may facilitate earlier intervention and treatment.

Background: Intraoperative hemoglobin (Hb) monitoring is critical for ensuring patient safety during bimaxillary orthognathic surgery. Intraoperative Hb monitoring performed using portable devices with arterial blood samples is invasive, is time-consuming, and lacks the ability to provide real-time information. This retrospective study investigated the correlation between continuous and real-time total Hb (SpHb) using a Masimo Radical 7 device and Hb levels derived by portable devices during bimaxillary orthognathic surgery. Methods: Patients who underwent elective bimaxillary orthognathic surgery were enrolled. The correlation between SpHb and laboratory Hb (Lab-Hb) was evaluated immediately after the induction of anesthesia (T1) and at surgical closure (T2) and compared with postoperative Hb. Results: Eighty-eight patients were included. The correlation coefficients between SpHb and Lab-Hb were 0.795 and 0.859 at T1 and T2, respectively. The correlation coefficient between Lab-Hb at T2 and postoperative Hb was 0.918. A Bland-Altman analysis of the Lab-Hb at T2 and postoperative Hb showed a mean bias of 0.49. Conclusion In conclusion, here we demonstrated acceptable accuracy of the SpHb measured by the Masimo Radical 7 device during bimaxillary orthognathic surgery. However, SpHb is valuable as an adjunct value to Lab-Hb and a substitute for Hb monitoring due to its wide limits of agreement. These findings suggest that SpHb can help guide the timing of invasive blood sampling for Hb measurements, which may facilitate earlier intervention and treatment.

Background: Intraoperative hemoglobin (Hb) monitoring is critical for ensuring patient safety during bimaxillary orthognathic surgery. Intraoperative Hb monitoring performed using portable devices with arterial blood samples is invasive, is time-consuming, and lacks the ability to provide real-time information. This retrospective study investigated the correlation between continuous and real-time total Hb (SpHb) using a Masimo Radical 7 device and Hb levels derived by portable devices during bimaxillary orthognathic surgery. Methods: Patients who underwent elective bimaxillary orthognathic surgery were enrolled. The correlation between SpHb and laboratory Hb (Lab-Hb) was evaluated immediately after the induction of anesthesia (T1) and at surgical closure (T2) and compared with postoperative Hb. Results: Eighty-eight patients were included. The correlation coefficients between SpHb and Lab-Hb were 0.795 and 0.859 at T1 and T2, respectively. The correlation coefficient between Lab-Hb at T2 and postoperative Hb was 0.918. A Bland-Altman analysis of the Lab-Hb at T2 and postoperative Hb showed a mean bias of 0.49. Conclusion In conclusion, here we demonstrated acceptable accuracy of the SpHb measured by the Masimo Radical 7 device during bimaxillary orthognathic surgery. However, SpHb is valuable as an adjunct value to Lab-Hb and a substitute for Hb monitoring due to its wide limits of agreement. These findings suggest that SpHb can help guide the timing of invasive blood sampling for Hb measurements, which may facilitate earlier intervention and treatment.

Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

Sedation methods for dental treatment are increasingly explored. Recently, ketofol, which is a combination of ketamine and propofol, has been increasingly used because the advantages and disadvantages of propofol and ketamine complement each other and increase their effectiveness. In this review, we discuss the pharmacology of ketamine and propofol, use of ketofol in various clinical situations, and differences in efficacy between ketofol and other sedatives.

Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3, and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III–IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of severe toxicity such as intense diarrhea or neutropenia.

Background: Nonobstetric surgery is sometimes required during pregnancy, and neck abscess or facial bone fracture surgery cannot be postponed in pregnant women. However, dental surgery can be stressful and can cause inflammation, and the inflammatory response is a well-known major cause of preterm labor. Propofol is an intravenous anesthetic commonly used for general anesthesia and sedation. Studies investigating the effect of propofol on human amnion are rare. The current study investigated the effects of propofol on lipopolysaccharide (LPS)-induced inflammatory responses in human amnion-derived WISH cells. Methods: WISH cells were exposed to LPS for 24 h and co-treated with various concentrations of propofol (0.01–1 μg/ml). Cell viability was measured using the MTT assay. Nitric oxide (NO) production was analyzed using a microassay based on the Griess reaction. The protein expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE 2), p38, and phospho-p38 was analyzed using western blotting. Results: Propofol did not affect the viability and NO production of WISH cells. Co-treatment with LPS and propofol reduced COX-2 and PGE 2 protein expression and inhibited p38 phosphorylation in WISH cells. Conclusion Propofol does not affect the viability of WISH cells and inhibits LPS-induced expression of inflammatory factors. The inhibitory effect of propofol on inflammatory factor expression is likely mediated by the inhibition of p38 activation.

Background: Inflammatory dental diseases that occur during pregnancy can cause preterm labor and/or intrauterine growth restriction. Therefore, proactive treatment of dental diseases is necessary during pregnancy. Dexmedetomidine (DEX) is a widely used sedative in the dental field, but research on the effect of DEX on pregnancy is currently insufficient. In this study, we investigated the effects of co-treatment with DEX and lipopolysaccharide (LPS) on inflammatory responses in human amnion-derived WISH cells. Methods: Human amnion-derived WISH cells were treated with 0.001, 0.01, 0.1, and 1 μg/mL DEX with 1 μg/mL LPS for 24 h. Cytotoxicity of WISH cells was evaluated by 3-(4,5-)-2,5-diphenyltetrazolium bromide (MTT) assay. The protein expression of cyclooxygenase-2 (COX-2), prostaglandin E 2 (PGE 2 ), p38, and nuclear factor kappa B (NF-κB) was examined by western blot analysis. The mRNA expression of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α was analyzed by real-time quantitative polymerase chain reaction. Results: Co-treatment with DEX and LPS showed no cytotoxicity in the WISH cells. The mRNA expression of IL-1β and TNF-α decreased after co-treatment with DEX and LPS. DEX and LPS co-treatment decreased the protein expression of COX-2, PGE 2 , phospho-p38, and phospho-NF-κB in WISH cells. Conclusion Co-treatment with DEX and LPS suppressed the expression of COX-2 and PGE 2 , as well as pro-inflammatory cytokines such as IL-1β and TNF-α in WISH cells. In addition, the anti-inflammatory effect of DEX and LPS co-treatment was mediated by the inhibition of p38/NF-κB activation.

Background/Aims: Patients with pancreatic cancer (PC) generally have poor clinical outcomes. Early determination of their prognosis is crucial for developing a therapeutic strategy. Recently, various inflammatory markers have been validated as prognostic indicators for many cancers, including PC. However, few studies have evaluated these markers together. Thus, the purpose of this study was to comprehensively evaluate the value of inflammatory markers as prognostic indicators in patients with advanced PC treated with gemcitabine-based chemotherapy as the first line regimen. Methods: This was a single-center retrospective study evaluating 302 patients with advanced PC who began first line treatment between November 2004 and August 2016. These patients were monitored until June 2017. Survival rates were assessed with univariate and multivariate analyses. Continuous variables were separated using the normal range or ideal cut-off levels determined by receiver operating curve analyses. Results: Among inflammatory markers evaluated, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and C-reactive protein (CRP) to albumin ratio (CRP-albumin ratio) were independent predictors of overall survival (hazard ratio, 1.712, 1.345, and 1.454, respectively). Difference in survival rates was significant (p < 0.001) among three groups divided by the number of marker-related risks. Conclusions Baseline inflammatory markers including NLR, PLR, and CRP-albumin ratio are useful in predicting survival rates in patients with PC. Combining these three markers is proven to be valuable.

Transient receptor potential canonical 4 (TRPC4) channel is a nonselective calcium-permeable cation channels. In intestinal smooth muscle cells, TRPC4 currents contribute more than 80% to muscarinic cationic current (mIcat). With its inward-rectifying current-voltage relationship and high calcium permeability, TRPC4 channels permit calcium influx once the channel is opened by muscarinic receptor stimulation. Polyamines are known to inhibit nonselective cation channels that mediate the generation of mIcat. Moreover, it is reported that TRPC4 channels are blocked by the intracellular spermine through electrostatic interaction with glutamate residues (E728, E729). Here, we investigated the correlation between the magnitude of channel inactivation by spermine and the magnitude of channel conductance. We also found additional spermine binding sites in TRPC4. We evaluated channel activity with electrophysiological recordings and revalidated structural significance based on Cryo-EM structure, which was resolved recently. We found that there is no correlation between magnitude of inhibitory action of spermine and magnitude of maximum current of the channel. In intracellular region, TRPC4 attracts spermine at channel periphery by reducing access resistance, and acidic residues contribute to blocking action of intracellular spermine; channel periphery, E649; cytosolic space, D629, D649, and E687.
Amino Acids ; Binding Sites ; Calcium ; Cytosol ; Glutamic Acid ; Myocytes, Smooth Muscle ; Permeability ; Polyamines ; Receptors, Muscarinic ; Spermine ; Transient Receptor Potential Channels