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Abstract Trastuzumab emtansine (T-DM1) is widely utilized as a second-line and subsequent treatment for metastatic HER2+ breast cancer and has shown promise in early breast cancer treatment, particularly in adjuvant settings for residual disease after neoadjuvant chemotherapy. However, concerns have arisen regarding long-term hepatic adverse drug reactions (ADRs) not identified in clinical trials. We investigated potential safety signals of T-DM1 in hepatobiliary disorders and the time-to-onset of ADRs using the FDA Adverse Event Reporting System (FAERS) database. Suspected ADRs were extracted and divided into two groups: T-DM1 (N = 3387) and other drugs (N = 11,833,701). Potential signal for T-DM1 in hepatobiliary disorder were identified (reporting odds ratio [ROR] = 5.66, 95% confidence interval [CI] = 5.11–6.27; information component [IC] = 2.35, 95% Credibility Interval [Crl] = 2.18–2.51). A breast cancer indicated subgroup analysis (2519 T-DM1; 172,329 other drugs) also identified a potential safety signal (ROR = 3.28, 95% CI = 2.92–3.68; IC = 1.53, 95%CrI = 1.35–1.71). The median time-to-onset for T-DM1-associated hepatobiliary disorders was 41 days. For prolonged and chronic hepatobiliary disorders, median times were 322.5 and 301.5 days, respectively. These findings highlight the need for further research to inform clinical decisions on optimal T-DM1 treatment duration, balancing benefits with potential adverse reactions.

This study aims to develop high-capacity hard carbon anode materials for alkali-ion batteries by controlling the microstructures of non-graphitic hard carbon through an annealing protocol and investigating the effects on the alkali-ion storage mechanisms using physical, chemical, and electrochemical analytical techniques. The hard carbon materials were synthesized at temperatures ranging from 900 °C to 1600 °C. Those synthesized at 1100 °C with high surface area and abundant defects exhibited the highest reversible capacity in Li- and K-ion systems, with the storage dominated by surface-adsorption mechanisms. In contrast, the hard carbon compounds prepared at 1400 °C with numerous curve-featured pores delivered the highest reversible capacity in the Na-ion system, indicating that these pores are the preferred Na-ion storage sites, particularly in low-voltage plateau regions. This study provides a comprehensive understanding of the relationship between microstructures and alkali-ion storage mechanisms in non-graphitic hard carbon and highlights the importance of tailoring the microstructures of hard carbon to achieve high specific capacity for the desired alkali-ion species.

Abstract Background To evaluate the correlation between single- and multi-slice cross-sectional thoracolumbar and whole-body compositions. Methods We retrospectively included patients who underwent whole-body PET–CT scans from January 2016 to December 2019 at multiple institutions. A priori-developed, deep learning-based commercially available 3D U-Net segmentation provided whole-body 3D reference volumes and 2D areas of muscle, visceral fat, and subcutaneous fat at the upper, middle, and lower endplate of the individual T1–L5 vertebrae. In the derivation set, we analyzed the Pearson correlation coefficients of single-slice and multi-slice averaged 2D areas (waist and T12–L1) with the reference values. We then built prediction models using the top three correlated levels and tested the models in the validation set. Results The derivation and validation datasets included 203 (mean age 58.2 years; 101 men) and 239 patients (mean age 57.8 years; 80 men). The coefficients were distributed bimodally, with the first peak at T4 (coefficient, 0.78) and the second peak at L2-3 (coefficient 0.90). The top three correlations in the abdominal scan range were found for multi-slice waist averaging (0.92) and single-slice L3 and L2 (0.90, each), while those in the chest scan range were multi-slice T12–L1 averaging (0.89), single-slice L1 (0.89), and T12 (0.86). The model performance at the top three levels for estimating whole-body composition was similar in the derivation and validation datasets. Conclusions Single-slice L2–3 (abdominal CT range) and L1 (chest CT range) analysis best correlated with whole-body composition around 0.90 (coefficient). Multi-slice waist averaging provided a slightly higher correlation of 0.92.

Abstract Desflurane is known to have a larger vasodilatory effect than that of sevoflurane. However, its generalizability and effect size in actual clinical practice are yet to be proven. Patients aged ≥ 18 years who underwent noncardiac surgery under general anesthesia using inhalation anesthetics (desflurane or sevoflurane) were matched 1:1 by propensity score. The mean intraoperative perfusion index (PI) of each patient were compared between the two groups. Propensity score matching of 1680 patients in the study cohort identified 230 pairs of patients. PI was significantly higher in the desflurane group (median of paired difference, 0.45; 95% CI 0.16 to 0.74, p = 0.002). PI durations below 1.0 and 1.5 were significantly longer in the sevoflurane group. Mean arterial pressure (MAP) and durations of low MAP did not differ significantly between the two groups. Generalized linear mixed models revealed that the use of sevoflurane, mean MAP, mean heart rate, age, and duration of anesthesia had significant negative effects (lower PI), whereas mean age-adjusted minimum alveolar concentration of inhalation agent had a positive effect on PI (higher value). Intraoperative PI was significantly higher in patients administered desflurane than sevoflurane. However, the impact of the choice between desflurane and sevoflurane on intraoperative PI in this clinical setting was minimal.

Abstract Background Dental care in cancer patients tends to be less prioritized. However, limited research has focused on major dental treatment events in cancer patients after the diagnosis. This study aimed to examine dental treatment delays in cancer patients compared to the general population using a national claims database in South Korea. Method The Korea National Health Insurance Service-National Sample Cohort version 2.0, collected from 2002 to 2015, was analyzed. Treatment events were considered for stomatitis, tooth loss, dental caries/pulp disease, and gingivitis/periodontal disease. For each considered event, time-dependent hazard ratios and associated 95% confidence intervals were calculated by applying a subdistribution hazard model with time-varying covariates. Mortality was treated as a competing event. Subgroup analyses were conducted by type of cancer. Results The time-dependent subdistribution hazard ratios (SHRs) of stomatitis treatment were greater than 1 in cancer patients in all time intervals, 2.04 within 30 days after cancer diagnosis, and gradually decreased to 1.15 after 5 years. The SHR for tooth loss was less than 0.70 within 3 months after cancer diagnosis and increased to 1 after 5 years. The trends in SHRs of treatment events for other dental diseases were similar to those observed for tooth loss. Subgroup analyses by cancer type suggested that probability of all dental treatment event occurrence was higher in head and neck cancer patients, particularly in the early phase after cancer diagnosis. Conclusion Apart from treatments that are associated with cancer therapy, dental treatments in cancer patients are generally delayed and cancer patients tend to refrain from dental treatments. Consideration should be given to seeking more active and effective means for oral health promotion in cancer patients.

Abstract Background Blood pressure measurement is an essential element during intraoperative patient management. However, errors caused by changes in transducer levels can occur during surgery. Methods This single center, prospective, observational study enrolled 25 consecutive patients scheduled for elective cardiac surgery with invasive arterial and central venous pressure (CVP) monitoring. Hydrostatic pressures caused by level differences (leveling pressure) between a reference point (on the center of the left biceps brachii muscle) and the transducers (fixed on the right side of the operating table) for arterial and central lines were continuously measured using a leveling transducer. Adjusted pressures were calculated as measured pressure – leveling pressure. Hypotension (mean arterial pressure 20 mmHg) levels were determined using unadjusted and adjusted pressures. Results Twenty-two patients were included in the analysis. Leveling pressure ≥ 3 mmHg and ≥ 5 mmHg observed at 46.0 and 18.7% of pooled data points, respectively. Determinations of hypotension using unadjusted and adjusted pressures showed disagreements ranging from 3.3 to 9.4% depending on the cutoffs. Disagreements in defined levels of CVP and PAP were observed at 23.0 and 17.2% of the data points, respectively. Conclusions The errors in pressure measurement due to changes in transducer level were not trivial and caused variable disagreements in the determination of MAP, CVP, and PAP levels. To prevent distortions in intraoperative hemodynamic management, strategies should be sought to minimize or adjust for these errors in clinical practice. Trial registration cris.nih.go.kr (KCT0006510).

The micrometer-scale reticulated structure of highly sulfur-philic nitrogen-doped graphene oxide (NrGO) that is achieved by chemically controlling the nitrogen-doping degree improves the chemical and electrochemical stability of the active sulfur while providing sufficient sulfur/electrolyte interface for a facile electrochemical process so that a high specific energy of 325 W h kg-1 can be achieved.

To date, Li2S has drawn significant attention as a positive electrode active material for rechargeable lithium cells due to its high theoretical specific capacity and capability of pairing with a lithium-free anode which can obviate any safety concern of the lithium metal anode when using sulfur. In recent years, various approaches have been employed to develop Li/Li2S rechargeable cells for commercialization that meet the performance goals for high energy/power applications. It is expected that high lithium sulfide-loading cells with long cycle life, an excellent capacity delivery and low electrolyte:sulfur weight ratio (E/S ratio) can be achieved. Here, we report a Li2S electrode comprised of a novel Li2S/KB@Cf nanocomposite which delivers an areal capacity of 7.56 mAh cm-2 and good cycling stability with a mass loading of 11.29 mg cm-2 and a robust 3-dimensional (3D) aluminum foam current collector with a high open area. The high conductivity and scalability of the active material, the availability of 3D current collection for the active material and the control of the electrolyte/sulfur ratio offer the potential of realization of practical Li/S cells.

Abstract To investigate the associations of weekend catch-up sleep (WCS) and high-sensitivity C-reactive protein (hs-CRP) levels according to bedtime inconsistency in the Korean population. In this cross-sectional study using the Korea National Health and Nutrition Examination Survey (2016–2018) with 17,665 participants, four groups were defined: no-WCS (WCS within ± 1 h of weekday sleep time), moderate WCS (1 ≤ , 2 h difference between weekend and weekday bedtimes. Outcomes were divided into quartiles based on the hs-CRP level: Lowest (

Rational design of sulfur electrodes is exceptionally important in enabling a high-performance lithium/sulfur cell. Constructing a continuous pore structure of the sulfur electrode that enables facile lithium ion transport into the electrode and mitigates the reconstruction of sulfur is a key factor for enhancing the electrochemical performance. Here, we report a three-dimensionally (3D) aligned sulfur electrode cast onto conventional aluminum foil by directional freeze tape casting. The 3D aligned sulfur-graphene oxide (S-GO) electrode consisting of few micron thick S-GO layers with 10-20 μm interlayer spacings demonstrates significant improvement in the performance of the Li/S cell. Moreover, the freeze tape cast graphene oxide electrode exhibits homogeneous reconfiguration behavior in the polysulfide catholyte cell tests and demonstrated extended cycling capability with only 4% decay of the specific capacity over 200 cycles. This work emphasizes the critical importance of proper structural design for sulfur-carbonaceous composite electrodes.

Abstract This study aimed to assess the trend of the maintenance status and usability of public automated external defibrillators (AEDs). Public AEDs installed in Seoul from 2013 to 2017 were included. An inspector checked the maintenance status and usability of the AEDs annually using a checklist. During the study period, 23,619 AEDs were inspected. Access to the AEDs was improved, including the absence of obstacles near the AEDs (from 90.2% in 2013 to 99.1% in 2017, p

Objectives Because climatic and air-pollution factors are known to influence the occurrence of respiratory diseases, we used these factors to develop machine learning models for predicting the occurrence of respiratory diseases. Methods We obtained the daily number of respiratory disease patients in Seoul. We used climatic and air-pollution factors to predict the daily number of patients treated for respiratory diseases per 10,000 inhabitants. We applied the relief-based feature selection algorithm to evaluate the importance of feature selection. We used the gradient boosting and Gaussian process regression (GPR) methods, respectively, to develop two different prediction models. We also employed the holdout cross-validation method, in which 75% of the data was used to train the model, and the remaining 25% was used to test the trained model. We determined the estimated number of respiratory disease patients by applying the developed prediction models to the test set. To evaluate the performance of each model, we calculated the coefficient of determination (R2) and the root mean square error (RMSE) between the original and estimated numbers of respiratory disease patients. We used the Shapley Additive exPlanations (SHAP) approach to interpret the estimated output of each machine learning model. Results Features with negative weights in the relief-based algorithm were excluded. When applying gradient boosting to unseen test data, R2 and RMSE were 0.68 and 13.8, respectively. For GPR, the R2 and RMSE were 0.67 and 13.9, respectively. SHAP analysis showed that reductions in average temperature, daylight duration, average humidity, sulfur dioxide (SO2), total solar insolation amount, and temperature difference increased the number of respiratory disease patients, whereas increases in atmospheric pressure, carbon monoxide (CO), and particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5) increased the number of respiratory disease patients. Conclusion We successfully developed models for predicting the occurrence of respiratory diseases using climatic and air-pollution factors. These models could evolve into public warning systems.

A novel ionic liquid-containing electrolyte has been demonstrated to improve charging efficiency, lifetime and safety of Li/S cells. However, the high viscosity of the ionic liquid can reduce the kinetics of the electrochemical process and degrade the wettability the S electrode by the electrolyte, which limits electrochemical utilization of the active S. To realize the advantages of the ionic liquid in the electrolyte, while maintaining good cell performances, we have investigated the critical properties of polymeric binders such as polyvinylidene fluoride (PVDF), styrene-butadiene rubber (SBR), carboxymethyl cellulose (CMC), polyacrylic acid (PAA) and lithium polyacrylate (LiPAA) for the S electrode operated in ionic liquid-containing electrolytes. The PAA binder electrode showed the most promising cell performance which is attributed to its good physical stability and wettability. Moreover, the cell performance of the PAA binder electrode was further improved by combining the PAA binder with the PVDF binder, which enhances the specific capacity up to 1.3 times higher than that of the PAA binder electrode.

Lithium/Sulfur (Li/S) cells are a promising chemistry with potential to deliver a step-change in energy density compared to state-of-the-art Li-ion batteries. To minimize the environmental impact of the Li/S cell manufacturing and to compete with Li-ion cells in both performance and cost, electrodes cast using an aqueous process are highly desirable. Here we describe the discovery and application of a lithiated redox-mediating supramolecular binder based on the well-known n-type semiconductor, perylene bisimide, that forms high-fidelity sulfur electrodes from water-processed slurries. A 1.4-fold improvement in sulfur utilization at 3.0 C and 58% increase in capacity retention after 250 cycles at 1.5 C are reported for the prelithiated, supramolecular binder compared to control samples. These improvements are attributed to the self-assembly of lithiated perylene bisimide binders in water to yield nanowire web morphologies that increase interfacial area between electrode components and exhibit enhanced electrode-current collector adhesion.

The ambient-temperature rechargeable lithium/sulfur (Li/S) cell is a strong candidate for the beyond lithium ion cell since significant progress on developing advanced sulfur electrodes with high sulfur loading has been made. Here we report on a new sulfur electrode active material consisting of a cetyltrimethylammonium bromide-modified sulfur-graphene oxide-carbon nanotube (S-GO-CTA-CNT) nanocomposite prepared by freeze-drying. We show the real-time formation of nanocrystalline lithium sulfide (Li2S) at the interface between the S-GO-CTA-CNT nanocomposite and the liquid electrolyte by in situ TEM observation of the reaction. The combination of GO and CNT helps to maintain the structural integrity of the S-GO-CTA-CNT nanocomposite during lithiation/delithiation. A high S loading (11.1 mgS/cm2, 75% S) S-GO-CTA-CNT electrode was successfully prepared using a three-dimensional structured Al foam as a substrate and showed good S utilization (1128 mAh/g S corresponding to 12.5 mAh/cm2), even with a very low electrolyte to sulfur weight ratio of 4. Moreover, it was demonstrated that the ionic liquid in the electrolyte improves the Coulombic efficiency and stabilizes the morphology of the Li metal anode.

Abstract 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.

π-Stacked perylene bisimide (PBI) molecules are implemented here as highly networked, redox-active supramolecular polymer binders in sulfur cathodes for lightweight and energy-dense Li-S batteries. We show that the in operando reduction and lithiation of these PBI binders sustainably reduces Li-S cell impedance relative to nonredox active conventional polymer binders. This lower impedance enables high-rate cycling in Li-S cells with excellent durability, a critical step toward unlocking the full potential of Li-S batteries for electric vehicles and aviation.

Cognitive decline and memory impairment induced by oxidative brain damage are the critical pathological hallmarks of Alzheimer’s disease (AD). Based on the potential neuroprotective effects of AD−1 small molecule, we here explored the possible underlying mechanisms of the protective effect of AD-1 small molecule against scopolamine-induced oxidative stress, neuroinflammation, and neuronal apoptosis. According to our findings, scopolamine administration resulted in increased AChE activity, MDA levels, and decreased antioxidant enzymes, as well as the downregulation of the antioxidant response proteins of Nrf2 and HO-1 expression; however, treatment with AD−1 small molecule mitigated the generation of oxidant factors while restoring the antioxidant enzymes status, in addition to improving antioxidant protein levels. Similarly, AD−1 small molecule significantly increased the protein expression of neuroprotective markers such as BDNF and CREB and promoted memory processes in scopolamine-induced mice. Western blot analysis showed that AD−1 small molecule reduced activated microglia and astrocytes via the attenuation of iba-1 and GFAP protein expression. We also found that scopolamine enhanced the phosphorylation of NF-κB/MAPK signaling and, conversely, that AD−1 small molecule significantly inhibited the phosphorylation of NF-κB/MAPK signaling in the brain regions of hippocampus and cortex. We further found that scopolamine promoted neuronal loss by inducing Bax and caspase-3 and reducing the levels of the antiapoptotic protein Bcl-2. In contrast, AD−1 small molecule significantly decreased the levels of apoptotic markers and increased neuronal survival. Furthermore, AD−1 small molecule ameliorated scopolamine-induced impairments in spatial learning behavior and memory formation. These findings revealed that AD−1 small molecule attenuated scopolamine-induced cognitive and memory dysfunction by ameliorating AChE activity, oxidative brain damage, neuroinflammation, and neuronal apoptosis.

Fully lithiated lithium sulfide (Li2S) has become a promising cathode material for Li/S cells due to its high theoretic capacity (1166 mA h g-1) and specific energy (2600 W h kg-1). However, low utilization of sulfur and poor rate capability still hinder the practical application of Li/S cells. In this paper, a carbon coated Li2S/graphene composite (Li2S/G@C) was developed by incorporating Li2S nano spheres with single-layered graphene and further forming a durable protective carbon layer on the surface of the Li2S particles using a facile CVD method. The high rate capability and remarkable cycle life of the Li2S/G@C cathode were demonstrated, which was mainly attributed to the unique structure of the Li2S/G@C that can significantly improve not only the electrical conductivity, but also the mechanical stability of the sulfur cathode.

Abstract 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.

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.

(1) Background: Previous studies reported limited performance of arterial pressure waveform-based cardiac output (CO) estimation (FloTrac/Vigileo system; CO-FloTrac) compared with the intermittent thermodilution technique (COint). However, errors due to bolus maneuver and intermittent measurements of COint could limit its use as a reference. The continuous thermodilution technique (COcont) may relieve such limitations. (2) Methods: The performance of CO-FloTrac was retrospectively assessed using continuous recordings of intraoperative physiological data acquired from patients who underwent off-pump coronary artery bypass graft (OPCAB) surgery with CO monitoring using both CO-FloTrac and COcont. Optimal time adjustments between the two measurements were determined based on R-squared values. (3) Results: A total of 134.2 h of data from 30 patients was included in the final analysis. The mean bias was –0.94 (95% CI, −1.35 to −0.52) L/min and the limits of agreements were −3.64 (95% CI, −4.44 to −3.08) L/min and 1.77 (95% CI, 1.21 to 2.57) L/min. The percentage error was 66.1% (95% CI, 52.4 to 85.8%). Depending on the time scale and the size of the exclusion zone, concordance rates ranged from 61.0% to 75.0%. (4) Conclusion: Despite the time adjustments, CO-FloTrac showed non-negligible overestimation, clinically unacceptable precision, and poor trending ability during OPCAB surgery.

In recent years, lithium/sulfur (Li/S) cells have attracted great attention as a candidate for the next generation of rechargeable batteries due to their high theoretical specific energy of 2600 W·h kg(-1), which is much higher than that of Li ion cells (400-600 W·h kg(-1)). However, problems of the S cathode such as highly soluble intermediate species (polysulfides Li2Sn, n = 4-8) and the insulating nature of S cause poor cycle life and low utilization of S, which prevents the practical use of Li/S cells. Here, a high-rate and long-life Li/S cell is proposed, which has a cathode material with a core-shell nanostructure comprising Li2S nanospheres with an embedded graphene oxide (GO) sheet as a core material and a conformal carbon layer as a shell. The conformal carbon coating is easily obtained by a unique CVD coating process using a lab-designed rotating furnace without any repetitive steps. The Li2S/GO@C cathode exhibits a high initial discharge capacity of 650 mA·h g(-1) of Li2S (corresponding to the 942 mA·h g(-1) of S) and very low capacity decay rate of only 0.046% per cycle with a high Coulombic efficiency of up to 99.7% for 1500 cycles when cycled at the 2 C discharge rate.

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

Abstract Background Radiologic assessments of baseline and post-treatment tumor burden are subject to measurement variability, but the impact of this variability on the objective response rate (ORR) and progression rate in specific trials has been unpredictable on a practical level. In this study, we aimed to develop an algorithm for evaluating the quantitative impact of measurement variability on the ORR and progression rate. Methods First, we devised a hierarchical model for estimating the distribution of measurement variability using a clinical trial dataset of computed tomography scans. Next, a simulation method was used to calculate the probability representing the effect of measurement errors on categorical diagnoses in various scenarios using the estimated distribution. Based on the probabilities derived from the simulation, we developed an algorithm to evaluate the reliability of an ORR (or progression rate) (i.e., the variation in the assessed rate) by generating a 95% central range of ORR (or progression rate) results if a reassessment was performed. Finally, we performed validation using an external dataset. In the validation of the estimated distribution of measurement variability, the coverage level was calculated as the proportion of the 95% central ranges of hypothetical second readings that covered the actual burden sizes. In the validation of the evaluation algorithm, for 100 resampled datasets, the coverage level was calculated as the proportion of the 95% central ranges of ORR results that covered the ORR from a real second assessment. Results We built a web tool for implementing the algorithm (publicly available at http://studyanalysis2017.pythonanywhere.com/). In the validation of the estimated distribution and the algorithm, the coverage levels were 93 and 100%, respectively. Conclusions The validation exercise using an external dataset demonstrated the adequacy of the statistical model and the utility of the developed algorithm. Quantification of variation in the ORR and progression rate due to potential measurement variability is essential and will help inform decisions made on the basis of trial data.

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.

This study aimed to search the α-glucosidase inhibitors from the barks part of Artocarpus elasticus. The responsible compounds for α-glucosidase inhibition were found out as dihydrobenzoxanthones (1–4) and alkylated flavones (5–6). All compounds showed a significant enzyme inhibition toward α-glucosidase with IC50s of 7.6–25.4 μM. Dihydrobenzoxanthones (1–4) exhibited a competitive inhibition to α-glucosidase. This competitive behaviour was fully characterised by double reciprocal plots, Yang’s method, and time-dependent experiments. The compound 1 manifested as the competitive and reversible simple slow-binding, with kinetic parameters k3 = 0.0437 µM−1 min−1, k4 = 0.0166 min−1, and = 0.3795 µM. Alkylated flavones (5–6) were mixed type I (KI < KIS) inhibitors. The binding affinities (KSV) represented by all inhibitors were correlated to their concentrations and inhibitory potencies (IC50). Moreover, compounds 1 and 5 were identified as new ones named as artoindonesianin W and artoflavone B, respectively. Molecular modelling study proposed the putative binding conformation of competitive inhibitors (1–4) to α-glucosidase at the atomic level.

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.

Objective Although 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. Methods Eighty 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). Results The 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. Conclusions Adding fentanyl to midazolam is effective for sedation and to prevent IONV in women who are undergoing cesarean section under spinal anesthesia.

BackgroundIntraoperative 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.MethodsFifty-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.ResultsDecrease 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.ConclusionsThe 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.

Triclosan has been widely used as an antimicrobial agent. However, triclosan was found to cause toxicity, including muscle contraction disturbances, carcinogenesis, and endocrine disorders. In addition, it was found to affect central nervous system function adversely and even have ototoxic effects. Conventional methods for detecting such triclosan can be performed easily. However, the conventional detection methods are inadequate in precisely reflecting the impact of toxic substances on stressed organisms. Therefore, a test model for the toxic environment at the molecular level through the organism is needed. From that point of view, Daphnia magna is being used as a ubiquitous model. D. magna has the advantages of easy cultivation, a short lifespan and high reproductive capacity, and high sensitivity to chemicals. Therefore, the protein expression pattern of D. magna that appear in response to chemicals can be utilized as biomarkers for detecting specific chemicals. In this study, we characterized the proteomic response of D. magna following triclosan exposure via two‐dimensional (2D) gel electrophoresis. As a result, we confirmed that triclosan exposure completely suppressed D. magna 2‐domain hemoglobin protein and evaluated this protein as a biomarker for triclosan detection. We constructed the HeLa cells in which the GFP gene was controlled by D. magna 2‐domain hemoglobin promoter, which under normal conditions, expressed GFP, but upon triclosan exposure, suppressed GFP expression. Consequently, we consider that the HeLa cells containing the pBABE‐HBF3‐GFP plasmid developed in this study can be used as novel biomarkers for triclosan detection. [ABSTRACT FROM AUTHOR]

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.

BackgroundThe beach chair position (BCP) can cause significant hypotension. Epinephrine is used to prolong the duration of local anesthetics; it is also absorbed into blood and can exert systemic effects. This study determined the effects of epinephrine mixed with ropivacaine for an interscalene block (ISB) on hemodynamic changes related to BCP.MethodsPatient data collected from March 2013 to August 2014 were used retrospectively. We divided the patients into three groups: 1) ISB only, 2) I+G (general anesthesia after ISB without epinephrine), and 3) I+E+G (general anesthesia after ISB with epinephrine). Mean blood pressure (MBP) and heart rate (HR) were measured for 30 minutes at 5-minute intervals.ResultsThe study analyzed data from 431 patients. MBP tended to decrease gradually in the groups I+G and I+E+G. There were significant differences in MBP between the groups I+G and I, and between the groups I+G and I+E+G. Group I+E+G showed a significant increase in HR compared with the other two groups.ConclusionsISB with an epinephrine mixture did not prevent hypotension caused by the BCP after general anesthesia. HR increased only in response to the epinephrine mixture. A well-planned prospective study is required to compare hemodynamic changes in that context.