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Background In a star-shaped network, pairwise comparisons link treatments with a reference treatment (often placebo or standard care), but not with each other. Thus, comparisons between non-reference treatments rely on indirect evidence, and are based on the unidentifiable consistency assumption, limiting the reliability of the results. We suggest a method of performing a sensitivity analysis through data imputation to assess the robustness of results with an unknown degree of inconsistency. Methods The method involves imputation of data for randomized controlled trials comparing non-reference treatments, to produce a complete network. The imputed data simulate a situation that would allow mixed treatment comparison, with a statistically acceptable extent of inconsistency. By comparing the agreement between the results obtained from the original star-shaped network meta-analysis and the results after incorporating the imputed data, the robustness of the results of the original star-shaped network meta-analysis can be quantified and assessed. To illustrate this method, we applied it to two real datasets and some simulated datasets. Results Applying the method to the star-shaped network formed by discarding all comparisons between non-reference treatments from a real complete network, 33% of the results from the analysis incorporating imputed data under acceptable inconsistency indicated that the treatment ranking would be different from the ranking obtained from the star-shaped network. Through a simulation study, we demonstrated the sensitivity of the results after data imputation for a star-shaped network with different levels of within- and between-study variability. An extended usability of the method was also demonstrated by another example where some head-to-head comparisons were incorporated. Conclusions Our method will serve as a practical technique to assess the reliability of results from a star-shaped network meta-analysis under the unverifiable consistency assumption.

Objectives To quantify the heterogeneity of fibrosis boundaries in idiopathic pulmonary fibrosis (IPF) using the Gaussian curvature analysis for evaluating disease severity and predicting survival. Methods We retrospectively included 104 IPF patients and 52 controls who underwent baseline chest CT scans. Normal lungs below − 500 HU were segmented, and the boundary was three-dimensionally reconstructed using in-house software. Gaussian curvature analysis provided histogram features on the heterogeneity of the fibrosis boundary. We analyzed the correlations between histogram features and the gender-age-physiology (GAP) and CT fibrosis scores. We built a regression model to predict diffusing capacity of carbon monoxide (DLCO) using the histogram features and calculated the modified GAP (mGAP) score by replacing DLCO with the predicted DLCO. The performances of the GAP, CT-GAP, and mGAP scores were compared using 100 repeated random-split sets. Results Patients with moderate-to-severe IPF had more numerous Gaussian curvatures at the fibrosis boundary, lower uniformity, and lower 10th to 30th percentiles of Gaussian curvature than controls or patients with mild IPF (all p < 0.0033). The 20th percentile was most significantly correlated with the GAP score (r = − 0.357; p < 0.001) and the CT fibrosis score (r = − 0.343; p = 0.001). More numerous Gaussian curvatures, higher entropy, lower uniformity, and 10th to 30th percentiles (p < 0.001–0.041) were associated with mortality. The mGAP score was comparable to the GAP and CT-GAP scores for survival prediction (mean C-indices, 0.76 vs. 0.79 vs. 0.77, respectively). Conclusions Gaussian curvatures of fibrosis boundaries became more heterogeneous as the disease progressed, and heterogeneity was negatively associated with survival in IPF. Key Points • Gaussian curvature of the fibrotic lung boundary was more heterogeneous in patients with moderate-to-severe IPF than those with mild IPF or normal controls. • The 20th percentile of the Gaussian curvature of the fibrosis boundary was linearly correlated with the GAP score and the CT fibrosis score. • A modified GAP score that replaced the diffusing capacity of carbon monoxide with a composite measure using histogram features of the Gaussian curvature of the fibrosis boundary showed a comparable ability to predict survival to both the GAP and the CT-GAP score. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-020-07594-y.

Intravenous dexamethasone and dexmedetomidine, in conjunction with peripheral nerve blockade, have each been reported to prolong the duration of analgesia. This study tested whether combined use further prolongs analgesia duration after supraclavicular brachial plexus block (BPB) in patients undergoing orthopedic upper extremity surgery. One hundred twenty patients were randomized 1:1:1:1 to Control (saline bolus and midazolam infusion [0.05 mg/kg loading, 20 µg/kg/h thereafter]); DMED (saline bolus and dexmedetomidine infusion [1 μg/kg loading, 0.4 μg/kg/h thereafter]); DEXA (dexamethasone [10 mg] bolus and midazolam infusion); and DMED-DEXA (dexmedetomidine infusion and dexamethasone bolus) groups. The primary outcome was the duration of postoperative analgesia, defined as the time from the end of the BPB to the first dose of analgesia via a patient-controlled device. Median (interquartile range) times to first dose of analgesia in the Control, DMED, DEXA, and DMED-DEXA groups were 8.1 (6.2–11.6), 9.0 (8.1–11.3), 10.7 (8.1–20.5), and 13.2 (11.5–19.1) hours, respectively (p < 0.001). Pairwise comparisons showed significant prolongation of analgesia in the DEXA included groups compared with the non-DEXA included groups (DEXA vs. control, p = 0.045; DEXA vs. DMED, p = 0.045; DMED-DEXA vs. control, p < 0.001; DMED-DEXA vs. DMED, p < 0.001). A mixed effect model showed that dexamethasone was the only significant factor for the prolongation of analgesia (p < 0.001). Intravenous dexamethasone prolonged the analgesia duration of supraclavicular BPB after orthopedic upper extremity surgery. The concurrent use of mild to moderate sedation dose of intravenous dexmedetomidine in addition to intravenous dexamethasone showed no additional benefit to the prolongation of analgesia.

Preclinical studies suggest that repeated exposure to anesthetics during a critical period of neurodevelopment induces long-term changes in synaptic transmission, plasticity, and behavior. Such changes are of great concern, as similar changes have also been identified in animal models of neurodevelopmental disorders (NDDs) such as autism. Because of overlapping synaptic changes, it is also possible that anesthetic exposures have a more significant effect in individuals diagnosed with NDDs. Thus, we evaluated the effects of early, multiple anesthetic exposures in BTBR mice, an inbred strain that displays autistic behavior. We discovered that three cycles of sevoflurane anesthesia (2.5%, 1 h) with 2-h intervals between each exposure in late postnatal BTBR mice did not aggravate, but instead improved pathophysiological mechanisms involved with autistic behavior. Sevoflurane exposures restored E/I balance (by increasing inhibitory synaptic transmission), and increased mitochondrial respiration and BDNF signaling in BTBR mice. Most importantly, such changes were associated with reduced autistic behavior in BTBR mice, as sociability was increased in the three-chamber test and repetitive behavior was reduced in the self-grooming test. Our results suggest that anesthetic exposures during neurodevelopment may affect individuals diagnosed with NDDs differently.

Purpose This study aimed to evaluate vitamin D status at birth in very-low-birth-weight infants (VLBWIs

The overactivity of cannabinoid 1 receptor (CB1R) is associated with obesity and type 2 diabetes. First-generation CB1R antagonists, such as rimonabant, offered therapeutic advantages for the control of obesity and related metabolic abnormalities, but their therapeutic potential was limited by undesirable neuropsychiatric side effects. Here, we evaluated AJ5012 as a novel potent peripheral CB1R antagonist and, using this antagonist, investigated the role of peripheral CB1R on adipose tissue inflammation in obese mouse models. AJ5012 had a high degree of CB1R and cannabinoid 2 receptor selectivity but a low brain:plasma concentration ratio without eliciting centrally mediated neurobehavioral effects. In diet-induced obese (DIO) mice, AJ5012 did not reduce food intake but did induce a significant weight loss, likely owing to an increased energy expenditure. It was as effective as rimonabant for the improvement of hormonal or metabolic abnormalities, glycemic control, and insulin sensitivity. The treatment of DIO and leptin receptor-deficient mice with AJ5012 also exhibited effects comparable to rimonabant for the prevention of macrophage infiltration, activation of the nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome, and production of proinflammatory cytokines, which resulted in the suppression of adipose tissue inflammation. In addition to macrophage, activation of CB1R in 3T3-L1 adipocytes induced the expression of proinflammatory genes, which was fully inhibited by AJ5012. Our findings identified AJ5012 as a novel peripheral CB1R antagonist and suggest that peripheral CB1R blockade might break the links between insulin resistance and adipose tissue inflammation.-Han, J. H., Shin, H., Park, J.-Y., Rho, J. G., Son, D. H., Kim, K. W., Seong, J. K., Yoon, S.-H., Kim, W. A novel peripheral cannabinoid 1 receptor antagonist, AJ5012, improves metabolic outcomes and suppresses adipose tissue inflammation in obese mice.

Opioid-sparing effects of nefopam during patient-controlled analgesia (PCA) are well demonstrated. We hypothesized that postoperative pain control with an opioid-equivalent dose of nefopam as a single analgesic agent for PCA would not be inferior to fentanyl in laparoscopic gynecologic surgery. In total, 135 patients were randomly assigned to the N (nefopam 200 mg), NF (fentanyl 500 mcg + nefopam 100 mg), and F (fentanyl 1000 mcg) groups (n = 45 patients per group). The primary outcome was the numerical rating scale (NRS) score at rest at 6 h postoperatively, and the non-inferiority limit was set to 1. Secondary outcomes were pain severity and incidence of nausea and vomiting for 48 h postoperatively. Mean differences (MD) in primary outcome between the N and F groups were 0.4 (95% confidence interval (CI) −0.5 to 1.3). The upper limit of 95% CI exceeded the non-inferiority limit. The N group showed higher pain scores than the NF group (MD, 1.1, 95% CI, 0.3–1.9) in pairwise comparisons. No significant intergroup differences were observed in the cumulative dose of PCA usage and incidence of postoperative nausea and vomiting (PONV). In laparoscopic gynecological surgery, nefopam alone showed limited efficacy for postoperative pain control.

Introduction and purposes: Communities need to pay attention to the maintenance of public access defibrillators (PADs) installed in their jurisdictions to ensure that the PADs are always available. The purpose of this study is to assess the maintenance status of the PAD and to investigate the effect of periodic inspections on the maintenance status of the PAD. Methods: From 2013 to 2018, PADs installed in Seoul Metropolitan area were eligible. After an 8-hour PAD inspection training, an inspector visited the PAD site once a year to check the defibrillator. The inspector checked the maintenance status of the PAD using the checklist and conducted a questionnaire on PAD management from the PAD manager. At the end of inspection, the inspector gave an instruction on PAD maintenance and usage to the person in charge. Results: A total of 18,011 PADs including 3,134 in 2013, 3402 in 2014, 5622 in 2015, 5909 in 2016, 5552 in 2017, and 3615 in 2018 were inspected. During study period, there was a tendency to improve accessibility to PAD including obstacles around the defibrillator (from 9.3% in 2013 to 0.8% in 2018, p trend=0.006) and installation of PAD signs (from 34.3% in 2013 to 99.9% in 2018, p trend=0.007). Maintenance status of PAD was improved in terms of normal operation (from 94.0% in 2013 to 99.7% in 2018, p trend=0.010), normal battery charge status (from 95.6% in 2013 to 99.7% in 2018, p trend=0.037), and availability of valid electrodes (from 97.1% in 2013 to 99.8% in 2018, p trend=0.035). There was no difference in the frequency of actual use to the victims (from 0.7% in 2013 to 1.1% in 2018, p trend=0.803). Conclusions: Periodic inspections improve maintenance status of the PAD and its availability.

Preclinical animal studies have continuously reported the possibility of long-lasting neurotoxic effects after general anesthesia in young animals. Such studies also show that the neurological changes induced by anesthesia in young animals differ by their neurodevelopmental stage. Exposure to anesthetic agents increase dendritic spines and induce sex-dependent changes of excitatory/inhibitory synaptic transmission in late postnatal mice, a critical synaptogenic period. However, the mechanisms underlying these changes remain unclear. Abnormal activation of the mammalian target of rapamycin (mTOR) signaling pathway, an important regulator of neurodevelopment, has also been shown to induce similar changes during neurodevelopment. Interestingly, previous studies show that exposure to general anesthetics during neurodevelopment can activate the mTOR signaling pathway. This study, therefore, evaluated the role of mTOR signaling after exposing postnatal day (PND) 16/17 mice to sevoflurane, a widely used inhalation agent in pediatric patients. We first confirmed that a 2-h exposure of 2.5% sevoflurane could induce widespread mTOR phosphorylation in both male and female mice. Pretreatment with the mTOR inhibitor rapamycin not only prevented anesthesia-induced mTOR phosphorylation, but also the increase in mitochondrial respiration and male-dependent enhancement of excitatory synaptic transmission. However, the changes in inhibitory synaptic transmission that appear after anesthesia in female mice were not affected by rapamycin pretreatment. Our results suggest that mTOR inhibitors may act as potential therapeutic agents for anesthesia-induced changes in the developing brain.

Sugammadex can rapidly reverse neuromuscular blockade and has several advantages over cholinesterase inhibitors. It is unclear, however, whether administration of sugammadex in the absence of intraoperative deep neuromuscular blockade has direct clinical benefits. The present study retrospectively assessed the ability of sugammadex to prevent post-operative respiratory adverse events in patients undergoing laparoscopic colorectal surgery in the absence of routine deep neuromuscular blockade. The medical records of patients who underwent laparoscopic colorectal surgery from 2014 to 2018 in a tertiary care hospital were reviewed. Patients who underwent reversal of neuromuscular blockade with sugammadex or pyridostigmine were subjected to propensity score matching. To assess their relative effects on post-operative adverse respiratory events (defined as a composite of SpO2 < 94% in the post-anesthesia care unit, additional oxygen supplementation during ward transfer or stay, and emergency use of sugammadex in the post-anesthesia care unit), the incidence of these effects was compared in propensity score matched groups of patients treated with sugammadex or pyridostigmine. Of the 602 patients, 210 remained in each group after propensity score matching. The incidence of post-operative respiratory adverse events did not differ significantly in the two groups. These findings suggest that the unrestricted administration of sugammadex not preceded by intra-operative deep neuromuscular blockade does not have clinical benefits, when compared with pyridostigmine, in preventing post-operative respiratory adverse events.

In this paper, we have developed the intellectual Kegel trainer with the bio-feedback. The one is smart health care system that can treat an evacuation impediment and urination polyuria with the low frequency stimulation module. Then this detects the shrinkage power of the pelvis muscles and correlates an smart phone entertainment application program for the users. In order to recover the function of pelvic muscles, we use the intellectual smart health care trainer with several biofeedback function. Such a trainer makes to strength the weakness pelvic muscles by biofeedback training and get exercise the pelvic muscles in physical suppress. The biofeedback training against the physical suppress can have strengthen the pelvic muscles and can display the operation graph of strengthen movement in monitor. Finally, It can be ensured the safety through EMI and performance test.

This study aimed to evaluate inspiratory lung expansion in patients with interstitial lung disease (ILD) using histogram analyses based on advanced image registration between inspiratory and expiratory CT scans. We included 16 female ILD patients and eight age- and sex-matched normal controls who underwent full-inspiratory and expiratory CT scans. The CT scans were sequentially aligned based on the surface, landmarks, and attenuation of the lung parenchyma. Histogram analyses were performed on the degree of lung expansion (DLE) of each pixel between the aligned images in x-, y-, z-axes, and 3-dimensionally (3D). The overall mean registration error was 1.9 mm between the CT scans. The DLE

We aimed to evaluate the comparative efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 inhibitors (SGLT2i), or thiazolidinedione (TZD) as an adjunctive treatment in patients with poorly controlled type 2 diabetes mellitus (T2DM) on insulin therapy. We searched Medline, Embase, the Cochrane Library, and ClinicalTrials.gov through April 2016. Bayesian network meta-analyses were performed with covariate adjustment. The primary outcome was the change in glycated hemoglobin A1c (HbA1c) from baseline. Fifty randomized controlled trials covering 15,494 patients were included. GLP-1RA showed the greatest HbA1c-lowering effect compared to the control (−0.84%; 95% credible interval, −1.00% to −0.69%), followed by TZD (−0.73%; −0.93 to −0.52%), SGLT2i (−0.66%; −0.84% to −0.48%), and DPP4i (−0.54%; −0.68% to −0.39%). SGLT2i showed the greatest fasting plasma glucose reduction. GLP-1RA and SGLT2i showed greater body weight reduction, whereas TZD increased body weight. TZD was ranked the highest in terms of insulin dose reduction. The risk of hypoglycemia was increased with TZD or GLP-1RA. The study provides the best available evidence on the comparative efficacy and safety of non-insulin anti-diabetic agents on top of pre-existing insulin therapy for inadequately controlled T2DM patients.

Sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have complementary mode of action. For the meta-analysis comparing the efficacy and safety between SGLT2 inhibitor plus DPP4 inhibitor (SGLT2i/DPP4i) and placebo plus DPP4 inhibitor (PCB/DPP4i) in patients with type 2 diabetes mellitus (T2DM), we selected randomized controlled trials from electronic databases by predefined criteria. The primary outcome of interest was the change in glycated hemoglobin A1c (HbA1c) from baseline. Of 605 potentially relevant studies, 7 eligible RCTs comprising 2,082 patients were included.SGLT2i/DPP4i showed a greater reduction in HbA1c (weighted mean difference −0.6%, 95% CI −0.7 to −0.5%), fasting plasma glucose, 2 h postprandial plasma glucose, and body weight compared to PCB/DPP4i. The risk of hypoglycemia increased in SGLT2i/DPP4i compared to that in PCB/DPP4i only when insulin or sulfonylureas were included as a background therapy. The risk of urinary tract infection was not increased in SGLT2i/DPP4i; however, the risk of genital infection increased upon adding SGLT2 inhibitors to pre-existing DPP4 inhibitors. In conclusion, compared to PCB/DPP4i, SGLT2i/DPP4i achieved better glycemic control and greater weight reduction without increasing the risk of hypoglycemia and urinary tract infection in patients with inadequately controlled T2DM.

Aims/Introduction The combination of dipeptidyl peptidase-4 (DPP4) inhibitors and α-glucosidase inhibitors (AGIs) might provide an additive or synergistic glucose-lowering effect, as they have a complementary mode of action. In the present study, we examined the efficacy and safety of the addition of a DPP4 inhibitor to patients with type 2 diabetes inadequately controlled with an AGI. Materials and Methods We carried out an electronic search of MEDLINE, EMBASE, the Cochrane Library and Clinicaltrials.gov through October 2016. Randomized controlled trials written in English that compared DPP4 inhibitors plus AGI (DPP4i/AGI) and placebo plus AGI (PCB/AGI) in patients with type 2 diabetes were selected. Data on the study characteristics, efficacy and safety outcomes were extracted, and the risk of potential biases was assessed. The efficacy and safety of DPP4i/AGI and PCB/AGI were compared. Results Of 756 potentially relevant published articles and 40 registered trials, five studies including 845 patients randomized to DPP4i/AGI and 832 patients randomized to PCB/AGI were included for meta-analysis. Compared with PCB/AGI, DPP4i/AGI showed a greater reduction in glycated hemoglobin (weighted mean difference −1.2%, 95% confidence interval −1.6 to −0.8), fasting plasma glucose and 2-h postprandial plasma glucose levels, with no increase in bodyweight. The risks of hypoglycemia and gastrointestinal adverse events were similar between DPP4i/AGI and PCB/AGI. Conclusions The addition of a DPP4 inhibitor to patients with type 2 diabetes inadequately controlled with an AGI achieved better glycemic control without further increasing the risk of weight gain and hypoglycemia.

Background Intraoperative hypothermia is common in patients undergoing general anesthesia during arthroscopic hip surgery. In the present study, we assessed the effect of heating and humidifying the airway with a heated wire humidification circuit (HHC) to attenuate the decrease of core temperature and prevent hypothermia in patients undergoing arthroscopic hip surgery under general anesthesia. Methods Fifty-six patients scheduled for arthroscopic hip surgery were randomly assigned to either a control group using a breathing circuit connected with a heat and moisture exchanger (HME) (n = 28) or an HHC group using a heated wire humidification circuit (n = 28). The decrease in core temperature was measured from anesthetic induction and every 15 minutes thereafter using an esophageal stethoscope. Results Decrease in core temperature from anesthetic induction to 120 minutes after induction was lower in the HHC group (-0.60 ± 0.27℃) compared to the control group (-0.86 ± 0.29℃) (P = 0.001). However, there was no statistically significant difference in the incidence of intraoperative hypothermia or the incidence of shivering in the postanesthetic care unit. Conclusions The use of HHC may be considered as a method to attenuate intraoperative decrease in core temperature during arthroscopic hip surgery performed under general anesthesia and exceeding 2 hours in duration.

SummaryBackground The second trimester is a period of neurogenesis and neuronal migration, which can be affected by exposure to anesthetics. Studies also suggest that multiple exposures may have a greater impact on neurodevelopment. Aim We investigated whether in utero single or multiple exposures to anesthetics caused long-term behavior changes. Methods Pregnant mice were randomly divided into four groups on gestational day 14 (GD 14). Mice in the Control × 1 group were exposed to 100% oxygen for 150 min. Mice in the Sevo × 1 group were also exposed to 100% oxygen for 150 min, except that 2.5% sevoflurane was added during the first 120 min. Mice in the Control × 3 and Sevo × 3 group were identically treated as Control × 1 and Sevo × 1 group for three consecutive days, respectively (GD 14–16). Behavioral tests were performed only with the male offspring at the age of 2–4 months. Synaptic plasticity was also compared by inducing long-term potentiation in acute hippocampal slices. Results Single or multiple sevoflurane exposures in pregnant mice during the second trimester did not cause long-lasting behavioral consequences or changes in long-term synaptic plasticity of their offspring. Conclusion Our study suggests that neither single nor multiple exposures of mice to sevoflurane during the fetal developmental period induces long-term behavioral dysfunctions or affects long-term synaptic plasticity. Additional studies focusing on early stages of neurodevelopment are necessary to confirm the effects of sevoflurane exposure during pregnancy.

In order to deal with the nonstationary signatures of phasor measurement units (PMU) signals, this paper presents a wavelet-based detection algorithm. Moreover, for an application to PMU for event detection purpose, it is necessary for us to classify detected events into unexpected real power related accidents, such as generator trip or automated control, such as reactive power injection. The proposed normalized wavelet energy function calculates the root mean square (RMS) of detail coefficients from time-synchronized voltage and frequency that reflect nonstationary occurrence of significant changes in signals. For a robust detection, wavelet-based detection parameter is designed with consideration of nonstationary characteristics of events. Also, there are distinct transients in voltage and frequency caused by different event types, and distinct results are key-idea of event classification. Besides the determination of event occurrences, one can obtain the information of event characteristics that include event types and zonal information of event from the proposed method. Moreover, successful results of detection and classification in real-world cases are presented in this paper.

The Jackson table has minimal effects on cardiac function because it does not elevate abdominal and thoracic pressures. In addition, it decreases venous congestion and increases exposure of the surgical field. However, the hips and knees are flexed with inappropriate padding, and venostasis is promoted and increased. Pulmonary thromboembolism (PTE) is fatal; thus immediate diagnosis and treatment are essential. However, clinical signs of intraoperative PTE are difficult to discern. Thrombolytic therapy can be considered as first-line therapy, but bleeding limits its use. The authors report a case of PTE resulting from patient positional change after spine surgery, and the use of immediate postoperative recombinant tissue-type plasminogen activator.

Regional anesthesia for non-obstetric surgery in parturients is a method to decrease patient and fetal risk during general anesthesia. Thoracic interfascial nerve block can be used as an analgesic technique for surgical procedures of the thorax. The Pecs II block is an interfascial block that targets not only the medial and lateral pectoral nerves, but also the lateral cutaneous branch of the intercostal nerve. Pecto-intercostal fascial block (PIFB) targets the anterior cutaneous branch of the intercostal nerve. The authors successfully performed a modified Pecs II block and PIFB without complications in a parturient who refused general anesthesia for breast surgery.

Background Intravenous anesthesia has been reported to have a favorable effect on the prognosis of cancer patients. This study was performed to analyze data regarding the relation between anesthetics and the prognosis of cancer patients in our hospital. Methods The medical records of patients who underwent surgical resection for gastric, lung, liver, colon, and breast cancer between January 2006 and December 2009 were reviewed. Depending on the type of anesthetic, it was divided into total intravenous anesthesia (TIVA) or volatile inhaled anesthesia (VIA) group. The 5-year overall survival outcomes were analyzed by log-rank test. Cox proportional hazards modeling was used for sensitivity. Results The number of patients finally included in the comparison after propensity matching came to 729 in each group. The number of surviving patients at 5 years came to 660 (90.5%) in the TIVA and 673 (92.3%) in the VIA. The type of anesthetic did not affect the 5-year survival rate according to the log-rank test (P = 0.21). Variables associated with a significant increase in the hazard of death after multivariable analysis were male sex and metastasis at surgery. Conclusions There were no differences in 5-year overall survival between two groups in the cancer surgery. Trial registration Trial registration: CRIS KCT0004101. Retrospectively registered 28 June 2019.

ObjectiveAlthough opioids may induce nausea and vomiting, they possess sedative effects and can reduce intraoperative nausea and vomiting (IONV). This study assessed the effect of adding fentanyl to midazolam on sedation levels and IONV during cesarean section under spinal anesthesia.MethodsEighty parturients scheduled for elective cesarean section were enrolled in the study. Following fetal delivery, patients were administered 0.05 mg/kg of midazolam plus 0.03 mL/kg of normal saline (M group) or 0.05 mg/kg of midazolam plus 1.5 μg/kg of fentanyl (MF group). The primary outcome was the incidence of IONV. The secondary outcomes were incidence of postoperative nausea and vomiting (PONV), intraoperative sedation level, and five-point patient satisfaction score (PSS).ResultsThe IONV incidence was significantly lower in the MF group compared with the M group (5% [2/40] vs. 25% [10/40]). The PONV incidence did not differ significantly between the groups. The intraoperative sedation level tended to be deeper in the MF group. The 5-point PSS was significantly higher in the MF group. There was a strong correlation between the sedation level and IONV incidence.ConclusionsAdding fentanyl to midazolam is effective for sedation and to prevent IONV in women who are undergoing cesarean section under spinal anesthesia.

Currently, sevoflurane and remifentanil are utilized frequently for the inhalation induction of anesthesia. However, there is currently an insufficient amount of clinical data regarding the inhalation induction of sevoflurane after the administration of remifentanil.80 patients undergoing elective surgery were allocated randomly to four groups. Group A inhaled only sevoflurane at 8 vol%. Other groups were administered 3 ng/ml of remifentanil and inhaled sevoflurane at 8 vol% (group B) or 6 vol% (group C) or 4 vol% (group D). All groups also received 0.6 mg/kg of rocuronium. The blood pressure and heart rate were measured at pre-induction, and before and after tracheal intubation. After operation, the patients??levels of satisfaction with the inhalation induction were evaluated.The time to loss of consciousness was substantially longer in group D than in the other groups, but no significant differences were noted among the groups in terms of satisfaction scores. The HR in groups B, C and D increased significantly after pre-intubation as compared to baseline in group A. The HR decreased significantly during induction as compared to group A. The MAP in groups B, C and D decreased significantly at 1 and 2 minutes after tracheal intubation as compared to group A. In group D only, we noted no significant differences in the MAP as compared to baseline at 1, 2 minutes after tracheal intubation.4 vol% sevoflurane was a more appropriate concentration for the inhalation induction of anesthesia when coupled with 3 ng/ml of remifentanil.

This study aimed to evaluate inspiratory lung expansion in patients with interstitial lung disease (ILD) using histogram analyses based on advanced image registration between inspiratory and expiratory CT scans. We included 16 female ILD patients and eight age- and sex-matched normal controls who underwent full-inspiratory and expiratory CT scans. The CT scans were sequentially aligned based on the surface, landmarks, and attenuation of the lung parenchyma. Histogram analyses were performed on the degree of lung expansion (DLE) of each pixel between the aligned images in x-, y-, z-axes, and 3-dimensionally (3D). The overall mean registration error was 1.9 mm between the CT scans. The DLE3D in ILD patients was smaller than in the controls (mean, 17.6 mm vs. 26.9 mm; p = 0.023), and less heterogeneous in terms of standard deviation, entropy, and uniformity (p Z of the lower lungs. A forced vital capacity tended to be weakly correlated with mean (r2 = 0.210; p = 0.074), and histogram parameters (r2 = 0.194–0.251; p = 0.048–0.100) of the DLE3D in the lower lung in ILD patients. Our findings indicate that reduced and less heterogeneous inspiratory lung expansion in ILD patients can be identified by using advanced accurate image registration.

Obesity-induced adipose tissue inflammation, in which the NLRP3 inflammasome is a pivotal mediator, is implicated in the development of insulin resistance. Cannabinoid 1 receptor (CB1R) antagonists have been shown to improve insulin resistance and the associated metabolic abnormalities, but their therapeutic development was discontinued due to neuropsychiatric side effects. Although growing evidence suggests the role of CB1Rs in proinflammatory signaling, their direct effects on adipose tissue inflammation have not yet been evaluated. Here we report that the peripherally restricted CB1R antagonist AJ5012, which exhibits beneficial metabolic effects comparable with its brain-penetrant parent compound rimonabant, suppresses macrophage infiltration into white adipose tissue, activation of the NLRP3 inflammasome, and production of proinflammatory cytokines in diet-induced obese mice. Moreover, we identified the downstream signaling pathways by which CB1R regulates proinflammatory gene expression. These results suggest that peripheral CB1R blockade improves obesity-induced insulin resistance by suppressing adipose tissue inflammation via the NLRP3 inflammasome. Disclosure J. Kim: None. J. Yoon: None. E. Kim: None. S. Yoon: None. W. Kim: None.

The selective loss of dopaminergic neurons in Parkinson's disease (PD) is associated with microglial activation. Therefore, the importance of early therapeutic intervention to inhibit microglial activation would be an effective strategy to alleviate the progression of PD. α-Asarone, an active compound found in Araceae and Annonaceae plant species has been used to improve various disease conditions including central nervous system disorders. In the present study the in vitro and in vivo therapeutic effects of α-asarone isolated from the rhizome of Acorus gramineus Solander was evaluated on microglia-mediated neuroinflammation and neuroprotection. Lipopolysaccharide (LPS)-stimulated BV-2 microglial cells were used to evaluate in vitro effects. 1-methyl-4 phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced mouse model of PD was developed to study the neuroprotective effects of α-asarone in vivo. The results indicated that α-asarone significantly attenuated the LPS-stimulated increase in neuroinflammatory responses and suppressed pro-inflammatory cytokine production in BV-2 cells. Mechanistic study revealed that α-asarone inhibited the LPS-stimulated activation via regulation of nuclear factor kappa-B by blocking degradation of inhibitor kappa B-alpha signaling in BV-2 microglial cells. In in vivo studies, MPTP intoxication to mice resulted in brain microglial activation and significant behavioral deficits. Prophylactic treatment with α-asarone suppressed microglial activation and attenuated PD-like behavioral impairments as assessed by the Y-maze and pole tests. Taken together, these data demonstrate that α-asarone is a promising neuroprotective agent that should be further evaluated and developed for future prevention and treatment of microglia-mediated neuroinflammatory conditions including PD.

This study is about estimation methods for the population pharmacokinetic and pharmacodymic model. This is a nonlinear mixed effect model, and it is difficult to find estimates of parameters because of nonlinearity. In this study, we examined theoretical background of various estimation methods provided by NONMEM, which is the most widely used software in the pharmacometrics area. We focused on estimation methods using a stochastic sampling approach - IMP, IMPMAP, SAEM and BAYES. The SAEM method showed the best performance among methods, and IMPMAP and BAYES methods showed slightly less performance than SAEM. The major obstacle to a stochastic sampling approach is the running time to find solution. We propose new approach to find more precise initial values using an ITS method to shorten the running time.

Proper selection of magnetic material is very important to maximize the power transfer efficiency (PTE) in case of the conductor in the receiving coil. The effects of the relative permeability and loss tangent of the magnetic material are investigated. A relatively low complex permeability ensures a high efficiency in wireless power transfer system (WPT) at 6.78 MHz. To maximize the PTE, the properties of the selected ferrite sheet should include a relative permeability higher than 200, a thickness of 600 um, and a loss tangent less than 0.01. Although 2-layer ferrite sheets show lower PTE than those of complex of complex of ferrite sheets, they have relatively high permeabilities and low core losses, which are beneficial in e real environments.

The high Q-factor coil with negative impedance converter (NIC) is investigated. The NIC leads to the enhanced transmission efficiency at a long distance for wireless power transfer (WPT) with magnetic resonance coupling method. The negative resistance generated by the NIC reduces the resistance of the coil. The coils were considered for the practical application such as effects of the ferrite and conductor. The transmitter (TX coil) is presented 250 mm by 250 mm with thickness of 0.9 mm, and has the impedance of 20+j1480 Ohm and the Q-factor of 76. The Q-factor of the TX coil was enhanced from 76 to 1640 due to the negative resistance of 15 Ohm, which was about 21 times higher than that of the conventional one. The power transmission efficiency (PTE) was measured with respect to the transmission distance between the TX and RX coils. The PTE of the system was 29% at a distance of 300 mm. This result shows that the PTE was greatly improved at a long distance when the NIC was applied.

BACKGROUND: There has been little data reporting the usefulness of intensivist-performed bedside drainage of pleural effusion via ultrasound (US)-guided pigtail catheter. The objective of this study is to clarify the usefulness and safety of these methods in comparison with radiologist-performed procedures. METHODS: Data of patients with pleural effusion treated with US-guided pigtail catheter drainage were analyzed. All procedures were performed from September 2012 to September. 2013 by a well-trained intensivist or radiologist. RESULTS: Pleural effusion was drained in 25 patients in 33 sessions. A radiologist performed 21 sessions, and an intensivist performed 12 sessions. Procedures during mechanical ventilation were performed in 15 (71.4%) patients by a radiologist and in 10 (83.3%) by an intensivist (p = 0.678). The success rate was not significantly different in radiologist- and intensivist-performed procedures, 95.2% (20/21) and 83.3% (10/12), respectively (p = 0.538). The average duration for procedures (including in-hospital transfer) was longer in radiologist-performed cases (p = 0.001). Although the results are limited because of the small population size, aggravation of oxygenation, CO2 retention, and decrease of mean arterial blood pressure were not statistically different in the groups. Pigtail-associated complications including hemothorax, pneumothorax, hepatic perforation, empyema, kink in the catheter, and subcutaneous hematoma were not found. CONCLUSIONS: Intensivist-performed bedside drainage of pleural effusion via ultrasound (US)-guided pigtail catheter is useful and safe and may be recommended in some patients in an intensive care unit.

This paper demonstrates that the vehicle sideslip can be estimated through the kinematic relationship of velocity measurements from two low-cost GPS receivers. To compensate for the low update rate of low-cost GPS receivers, acceleration/angular rate measurements from an inertial measurement unit (IMU) are merged with the GPS measurements using an extended Kalman filter (EKF). Two technical challenges were addressed: 1) unsynchronized updates of the two GPS receivers and 2) significant delays in GPS velocity measurement. A stochastic observability analysis reveals that the proposed method guarantees the observability when a vehicle has nonzero yaw rates. Experimental verification shows that the vehicle sideslip is estimated regardless of surface friction levels under several maneuvers.

This paper presents a novel method that estimates the vehicle sideslip angle for a wide range of surface frictions and road bank angles by combining measurements of a magnetometer, Global Positioning System (GPS), and inertial measurement unit (IMU). To reject disturbances in the magnetometer, a new stochastic filter is designed and integrated on the Kalman filter framework. The significant latency in a low-cost GPS velocity measurement is addressed by “measurement shifting,” and biases in the IMU measurements are estimated through state augmentation. Dual Kalman filters are employed in the sensor fusing framework. A comprehensive simulation study was conducted to prove the feasibility of the method. Finally, the performance and accuracy are verified through extensive experiments.

Traumatic sternoclavicular joint dislocation is an uncommon injury, and posterior sternoclavicular dislocation occurs less frequently compared to anterior sternoclavicular dislocation. However, this type of dislocation has the potential for serious complications due to compression or laceration of the mediastinal structures. The diagnosis can be difficult using plain radiographs alone due to radiographic-anatomic superimposition. Therefore, posterior sternoclavicular dislocation is easily missed at the initial clinical evaluation. Contrast-enhanced computed tomography is required for a definite diagnosis and to assess associated mediastinal injuries.

Through the study of Bohenggyuljangbuyongyakbubyo(輔行訣臟腑用藥法要) focusing on the newly illuminated subject `The study of Donhuang(敦煌學)` of China, the author analyzed and researched Donhuangzhongyiyakjunseo Bohenggyuljangbuyongyakbubyo(敦煌中醫藥全書 輔行訣臟腑用 藥法要) in order to study and report the origin of prescriptions from Sanghanjabbyungron(傷寒雜病論), which was written by Zhangzhongjing(張仲景). Among around 50 prescriptions included in Bohenggyul, 18 prescriptions similar to Sanghanjabbyungron could be classified in five different manners as follows. 1) There are nine examples whose prescription composition and chief virtue are same but names different. 2) There are five examples whose prescription composition is same but chief virtue and names different. 3) There are two examples whose names are same but prescription composition and chief virtue different. 4) There is one example of prescription as a combination of two or more prescriptions. 5) There is one example whose prescription composition and possible variations of prescription are same but chief virtue different.

Purpose: To investigate a correlation between vertical fixation disparity and stereopsis by analyzing distribution of types of vertical fixation disparity. Methods: In this study, RANDOT(R) stereotest partly using random dot was used in stereopsis tests. The vertical fixation disparity in close proximity categorized fixation disparity slope into six types on the basis of the result of measurement in when two thin lines, one for one eye looks, become overlapped as a line by adding into prism with Wesson fixation disparity card while maintaining a distance of 25 cm from patients. Results: In the types of near vertical fixation disparity curve, targeting 43 people, the first type 55.82% was the most distributed, the second type is the least 23.25%, the third type of 4.65%, the fourth type of 4.65%, the fifth type of 6.98%, the sixths types of 4.65% were distributed. The result of a correlation analysis, which shows the degree of linear correlation between two variables, represented that stereopsis is not correlated with Y-intercept (r = -0.07) which show vertical fixation disparity, associated phoria (r = -0.03) and dissociated phoria (r = -0.00), but it was not statistically significant (p>0.05). Fixation disparity slope of vertical fixation disparity (r = 0.36) was shown to have a positive correlation with stereopsis. It has a low positive correlation and a meaningful statistics (p0.05), while it had a high correlation as well as a statistically significant with associated phoria (r = 0.89). There was a negative correlation between Y-intercept and fixation disparity slope of vertical fixation disparity (r = -0.33). It showed a low relationship but statistically valuable (p>0.05). As a result of regression analysis, the stereopsis was changed as 7.631" if vertical fixation disparity changes 1' and the vertical fixation disparity changed as 0.017' if stereopsis changes 1', and the change was statistically significant (p

Beraprost sodium, sodium (±)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H-cyclopenta[b]benzofuran-5-butyrate), an orally absorbable prostacyclin derivative (PGI2), has marked ischemic symptom treatments like ulcer and pain with chronic arterial occlusion. The purpose of the present study was to evaluate the bioequivalence of two beraprost sodium tablets, Samchundang Berastolin tablet (Samchundang Pharm. Co., Ltd.) and Jeil Berasil tablet (Jeil Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of beraprost from the two beraprost sodium formulations was tested using KP IX Apparatus II method with various dissolution media. Thirty-two healthy Korean male volunteers, 23.44 ± 1.48 years in age and 65.95 ± 8.94 kg in body weight, were divided into two groups and a randomized 2 × 2 crossover study was employed. After single administration, three tablets containing 20 μg as beraprost sodium, blood samples were taken at predetermined time intervals and the concentrations of beraprost in serum were determined using a LC/MS/MS method with multiple reaction-monitoring. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as AUCt, Cmax and Tmax were calculated, and computer programs (Equiv Test and K-BE Test 2002) were utilized for the statistical analysis of the parameters using logarithmically transformed AUCt, Cmax and un-transformed Tmax. The results showed that the differences between two formulations based on the reference drug, Jeil Berasil tablet, were 2.12, 0.15 and 4 % for AUCt, Cmax, and Tmax, respectively. There were no sequence effects between two formulations in these parameters. The 90 % confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8–log 1.25 (e.g., log 0.9114–log 1.0912 and log 0.8471–log 1.1253 for AUCt and Cmax, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Samchundang Berastolin tablet was bioequivalent to Jeil Berasil tablet.

The purpose of the present study was to evaluate the bioequivalence of two torasemide tablets, Torem (Roche Korea Co., Ltd., Korea, reference drug) and Torad (Samchundang Pharmaceutical Co., Ltd., Korea, test drug) tablet, according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-eight healthy male Korean volunteers, 23.68 ± 1.79 years in age and 67.59 ± 9.87 kg in body weight, were divided into two groups and received each medicine at the torasemide dose of 10 mg in a randomized 2 × 2 crossover study. After a single administration, blood samples were taken at predetermined time intervals and the serum concentrations of torasemide were monitored by an HPLC–UV. The in vitro dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as AUCt (the area under the serum concentration–time curve from time zero to 12 h), Cmax (maximum serum drug concentration), and Tmax (time to reach Cmax) were calculated, and computer programs (equiv test and K-BE test 2002) were utilized for the statistical analysis of the parameters using logarithmically transformed AUCt and Cmax. The results showed that the differences between two formulation based on the reference drug, −2.84, −1.22 and 15.91 % for AUCt, Cmax, and Tmax, respectively. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90 % confidence intervals using logarithmically transformed data were within the acceptance range of log0.80 to log1.25 (e.g., log0.9305−log1.0043 and log0.9422−log1.0903 for AUCt and Cmax, respectively). Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Torad tablet and Torem tablet are bioequivalent.

This study investigated the effects of genetic polymorphisms in organic cation transporter (OCT) genes, such as OCT1-3, OCTN1, MATE1, and MATE2-K, on metformin pharmacokinetics. Of particular interest was the influence of genetic polymorphisms as covariates on the variability in the population pharmacokinetics (PPK) of metformin using nonlinear mixed effects modeling (NONMEM). In a retrospective data analysis, data on subjects from five independent metformin bioequivalence studies that used the same protocol were assembled and compared with 96 healthy control subjects who were administered a single oral 500 mg dose of metformin. Genetic polymorphisms of OCT2-808 G > T and OCTN1-917C > T had a significant (P T and OCTN1-917C > T variants on the CL/F were significant (P T, along with OCT2-808 G > T genetic polymorphisms, could be useful in titrating the optimal metformin dose.

Background/Aims: Baseline serum lactate dehydrogenase (LDH) level is a well-known prognostic factor in patients with non-Hodgkin's lymphoma; however, its role beyond initial diagnosis has not yet been defined. Methods: This study was conducted as a retrospective analysis of patients with diffuse large B cell lymphoma (DLBCL) treated with R-CHOP21, who had undergone regular checks for LDH during immunochemotherapy (n = 119) and during the posttreatment follow-up period after complete remission (CR; n = 100). The 119 patients were classified into 4 groups according to their baseline and change in LDH level during treatment, and an analysis of tumor response and survival was performed. The value of LDH as a predictor for relapse was evaluated among the patients with regular follow-up visits after achieving CR. Results: An increased LDH level during immunochemotherapy had no impact on tumor response or survival, and only the LDH status ‘before' treatment was a prognostic marker. The sensitivity, specificity, positive predictive value and negative predictive value of serum LDH for detecting relapse after CR were 47.4, 86.5, 9.3 and 98.3%, respectively. Conclusion: The measurement of LDH level beyond initial diagnosis has no clear benefit in predicting disease progression or relapse in patients with DLBCL treated with R-CHOP21.

Purpose To evaluate histogram and texture parameters on pretreatment dynamic contrast material-enhanced (DCE) magnetic resonance (MR) images in lung cancer in terms of temporal change, optimal time for analysis, and prognostic potential. Materials and Methods This retrospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. Thirty-eight patients with pathologically proved lung cancer undergoing standard pretreatment DCE MR imaging were included. A fat-suppressed, T1-weighted, volume-interpolated breath-hold MR sequence was performed every 30 seconds for 300 and 480 seconds after contrast material administration. A region of interest was manually drawn in the largest cross-sectional area of the tumor on DCE MR images to extract semiquantitative perfusion, histogram, and texture parameters. Predictability of 2-year progression-free survival (PFS) was analyzed by using the Kaplan-Meier method and Cox regression analysis. Results MR histogram and texture parameters increased rapidly 30-60 seconds after contrast material administration. Standard deviation and entropy then plateaued, whereas skewness and kurtosis rapidly decreased. Univariate Cox regression analysis revealed that standard deviation and entropy were significant predictors of survival; their statistical significance was preserved from 60 to 300 seconds, with the smallest P values (P ≤ .001) occurring from 120 to 180 seconds. At multivariate Cox regression analysis, entropy was the sole significant predictor of 2-year PFS (hazard ratio at 180 seconds, 10.098 [95% confidence interval: 1.579, 64.577], P = .015; hazard ratio at 120 seconds: 11.202 [95% confidence interval: 1.761, 71.260], P = .010). Conclusion Histogram and texture parameter changes varied after contrast material injection. The 120-180-second window after contrast material injection was optimal for MR imaging-derived texture parameter and entropy at DCE MR imaging. (©) RSNA, 2016 Online supplemental material is available for this article.

Purpose: Hepatobiliary surgery has changed dramatically in recent decades with the advent of laparoscopic techniques. The aim of this retrospective study was to compare survival rates according to stages, adjusting for important prognostic factors. Methods: A retrospective study of a 17-year period from January 1994 to April 2011 was carried out. The cases studied were divided into two time period cohorts, those treated in the first 9-years (n = 109) and those treated in the last 7-years (n = 109). Results: An operation with curative intent was performed on 218 patients. The 5-year survival rates according to the depth of invasion were 86% (T1), 56% (T2), 45% (T3), and 5% (T4). The number of cases of incidental gallbladder cancer found during 3,919 laparoscopic cholecystectomies was 96 (2.4%). Incidental gallbladder cancer revealed a better survival rate (P = 0.003). Iatrogenic bile spillage was found in 20 perforations of the gallbladder during laparoscopic cholecystectomies, 16 preoperative percutaneous transhepatic gallbladder drainages and 16 percutaneous transhepatic biliary drainages; only percutaneous transhepatic biliary drainage patients showed a significantly lower survival rate than patients without iatrogenic bile spillage (P ＜ 0.034). Chemoradiation appeared to improve overall survival (P ＜ 0.001). Multivariate analysis also revealed that time period, type of surgery, surgical margin, lymphovascular invasion, lymph node involvement, and chemoradiation therapy had significant effects. Conclusion: This study found that the prognosis of gallbladder cancer is still determined by the stage at presentation due to the aggressive biology of this tumor. Early diagnosis, radical resection and appropriate adjuvant therapy can increase overall survival.