Efficacy of intraoperative blood salvage and autotransfusion in living-donor liver transplantation: a retrospective propensity matched case-control study.

Background: Liver transplantation (LT) may be associated with massive blood loss and the need for allogeneic blood transfusion. Intraoperative blood salvage autotransfusion (IBSA) can reduce the need for allogeneic blood transfusion. This study aimed to investigate the effectiveness of blood salvage in LT. Methods: Among 355 adult patients who underwent elective living-donor LT between January 1, 2019, and December 31, 2022, 59 recipients without advanced hepatocellular carcinoma received IBSA using Cell Saver (CS group). Based on sex, age, model for end-stage liver disease (MELD) score, preoperative laboratory results, and other factors, 118 of the 296 recipients who did not undergo IBSA were matched using propensity score (non-CS group). The primary outcome was the amount of intraoperative allogenic red blood cell (RBC) transfusion. Comparisons were made between the two groups regarding the amount of other blood components transfused and postoperative laboratory findings. Results: The transfused allogeneic RBC for the CS group was significantly lower than that of the non-CS group (1,506.0 ml vs. 1,957.5 ml, P = 0.026). No significant differences in the transfused total fresh frozen plasma (FFP), platelets, cryoprecipitate, and estimated blood loss were observed between the two groups. The postoperative allogeneic RBC transfusion was significantly lower in the CS group than in the non-CS group (1,500.0 ml vs. 2,100.0 ml, P = 0.039). No significant differences in postoperative laboratory findings were observed at postoperative day 1 (POD1) and discharge. Conclusions: Using IBSA during LT can effectively reduce the need for perioperative allogeneic blood transfusions without causing subsequent coagulopathy.

Preoperative mild cognitive impairment as a risk factor of postoperative cognitive dysfunction in elderly patients undergoing spine surgery.

Introduction: Any persistent degree of cognitive impairment in older adults is a concern as it can progress to dementia. This study aimed to determine the incidence and risk factors for early postoperative cognitive dysfunction (POCD) in elderly patients undergoing spine surgery. Methods: Patients were enrolled from a previous prospective observational study after screening for normal cognitive function using the Mini Mental State Examination (MMSE). Cognitive function was evaluated before surgery and at 1 week, month, and year post-surgery using MMSE and Montreal Cognitive Assessment scores (MoCA). Mild cognitive impairment (MCI) was determined using the MoCA scores adjusted for age. POCD was defined as a drop of three or more points on the MMSE 1 week post-surgery. Multivariate logistic analysis was performed to identify POCD risk factors. Results: A total of 427 patients were included. Eighty-five (20%) had pre-existing MCI. The MCI group showed lower MoCA scores at each time point (baseline, 1 week after surgery, 1 month after surgery, 1 year after surgery) compared to the non-MCI group. Those in the MCI group had a higher rate of admission to intensive care unit after surgery, postoperative delirium, and POCD 1 week post-surgery, than those in the non-MCI group (16.5% vs. 6.7%, p = 0.008; 27.1% vs. 15.8%, p = 0.024; and 18.8% vs. 8.2%, p < 0.001, respectively). Among them, 10.3% were assessed for POCD on postoperative day 7 and self-reported poor social roles and physical functioning 1 week postoperatively. Conclusion: Preoperative MCI was seen in ~20% of surgical patients aged >70 years. POCD was seen in ~20% of patients with pre-existing MCI, and ~ 10% of those without. Benzodiazepine use, significant comorbidities, pre-existing MCI, and depressive tendencies were risk factors for POCD.

Differential effects of sevoflurane and desflurane on frontal intraoperative electroencephalogram dynamics associated with postoperative delirium.

STUDY OBJECTIVE: Intraoperative electroencephalogram (EEG) patterns associated with postoperative delirium (POD) development have been studied, but the differences in EEG recordings between sevoflurane- and desflurane-induced anesthesia have not been clarified. We aimed to distinguish the EEG characteristics of sevoflurane and desflurane in relation to POD development. DESIGN AND PATIENTS: We collected frontal four-channel EEG data during the maintenance of anesthesia from 148 elderly patients who received sevoflurane (n = 77) or desflurane (n = 71); 30 patients were diagnosed with delirium postoperatively. The patients were divided into four subgroups based on anesthetics and delirium status: sevoflurane delirium (n = 17), sevoflurane non-delirium (n = 60), desflurane delirium (n = 13), and desflurane non-delirium (n = 58). We compared spectral power, coherence, and pairwise phase consistency (PPC) between sevoflurane and desflurane, and between non-delirium and delirium groups for each anesthetic. MAIN RESULTS: In patients without POD, the sevoflurane non-delirium group exhibited higher EEG spectral power across 8.5-35 Hz (99.5% CI bootstrap analysis) and higher PPC from alpha to gamma bands (p < 0.005) compared to the desflurane non-delirium group. Conversely, in patients with POD, no significant EEG differences were observed between the sevoflurane and desflurane delirium groups. For the sevoflurane-induced patients, the sevoflurane delirium group had significantly lower power within 7.5-31.5 Hz (99.5% CI bootstrap analysis), reduced coherence over 8.9-23.8 Hz (99.5% CI bootstrap analysis), and lower PPC values in the alpha band (p < 0.005) compared with the sevoflurane non-delirium group. For the desflurane-induced patients, there were no significant differences in the EEG patterns between delirium and non-delirium groups. CONCLUSIONS: In normal patients without POD, sevoflurane demonstrates a higher power spectrum and prefrontal connectivity than desflurane. Furthermore, reduced frontal alpha power, coherence, and connectivity of intraoperative EEG could be associated with an increased risk of POD. These intraoperative EEG characteristics associated with POD are more noticeable in sevoflurane-induced anesthesia than in desflurane-induced anesthesia.

Indoor air quality and its determinants in underground shopping malls in Korea.

Underground shopping malls (USMs) are often open or semi-open environments with interconnected passageways, resulting in the sharing of indoor air. However, indoor air quality (IAQ) within these spaces can vary due to many diverse emission sources. We investigated the relationships between IAQ and geographical areas, as well as IAQ and store types, within USMs, in Korea. In 2020, we studied 10 different USMs, with a total of 128 outlets. We conducted comprehensive IAQ assessments (including measurements of fine particles (PM2.5), aldehydes, and volatile organic compounds (VOCs)) in stores, passages, and outdoor areas. The stores were categorized into three types: clothing, fashion accessories, and food services. Additionally, we measured environmental factors such as CO2 levels and presence of storefront walls. PM2.5 levels were higher outdoors, whereas aldehyde and VOC levels exhibited elevations within passages and the interior of stores than in the outdoor environment. The store-to-passage ratios for PM2.5, individual aldehydes, and VOC concentrations ranged from 1.06 to 4.93. Formaldehyde and total VOC (TVOC) concentrations were found to be elevated in clothing and fashion accessory stores, whereas PM2.5 concentrations were more prominent in food service establishments. Specific individual compounds, including propionaldehyde, hexaldehyde, benzene, n-heptane, toluene, n-octane, xylene, d-limonene, n-undecane, n-dodecane, and ethylbenzene concentrations exhibited associations with store types. Multivariate regression models demonstrated positive associations between most aldehydes and VOCs with CO2 concentrations and presence of storefront walls. This study underscored variations within USMs based on area and store type. Aldehyde and VOC concentrations were notably higher in clothing and fashion accessory stores than in food service outlets; these elevations were closely linked to CO2 levels and presence of storefront walls. These findings suggest that monitoring CO2 levels within USM stores, optimizing air-conditioning systems, and designing future stores without storefront walls can collectively contribute to an overall improvement of IAQ within USMs.

Prognostic role of body composition in peritoneal carcinomatosis patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Bioelectric impedance analysis (BIA)-measured body composition and nutritional status have been used as prognostic indicators in various cancer cohorts. This study investigated whether BIA could provide information on prognosis in peritoneal carcinomatosis patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We retrospectively analyzed the data of 99 patients with preoperative BIA data among those who underwent CRS and HIPEC. The association between BIA-derived parameters and intraoperative peritoneal cancer index (PCI) score was assessed. Predictive analysis for the occurrence of postoperative morbidities including major complications (Clavien-Dindo classification 3-4) and re-admission within 30 days after surgery as well as 1 year mortality was also performed. RESULTS: BIA-derived mineral (r = 0.224, p = 0.027), fat (r = - 0.202, p = 0.048), and total body water (TBW)/fat-free mass (FFM) (r = - 0.280, p = 0.005) showed significant associations with intraoperative PCI score. Lower TBW/FFM was an independent predictor of major postoperative complications (OR 0.047, 95% CI 0.003-0.749, p = 0.031) and re-admission (OR 0.094, 95% CI 0.014-0.657, p = 0.017) within 30 days after surgery. Higher fat mass was also independently associated with a higher risk of major postoperative complications (OR 1.120, 95% CI 1.006-1.248, p = 0.039) and re-admission (OR 1.123, 95% CI 1.024-1.230, p = 0.013). Intraoperative PCI score > 20 (OR 4.489, 95% CI 1.191-16.917, p = 0.027) and re-admission within 30 days after surgery (OR 5.269, 95% CI 1.288-21.547, p = 0.021) independently predicted postoperative 1-year mortality. CONCLUSIONS: We demonstrate that preoperative BIA-derived TBW/FFM and fat mass were significantly correlated with metastatic extent, assessed by PCI score, in patients with peritoneal carcinomatosis. In addition, BIA-derived TBW/FFM and fat mass showed independent predictability for postoperative 30-day major complications and re-admission in patients undergoing CRS and HIPEC. Our findings suggest that assessment of BIA may improve discrete risk stratification in patients who are planned to receive CRS and HIPEC.

Investigation of Hole-Transfer Dynamics through Simple EL De-Convolution in Non-Fullerene Organic Solar Cells.

In conventional fullerene-based organic photovoltaics (OPVs), in which the excited electrons from the donor are transferred to the acceptor, the electron charge transfer state (eECT) that electrons pass through has a great influence on the device's performance. In a bulk-heterojunction (BHJ) system based on a low bandgap non-fullerene acceptor (NFA), however, a hole charge transfer state (hECT) from the acceptor to the donor has a greater influence on the device's performance. The accurate determination of hECT is essential for achieving further enhancement in the performance of non-fullerene organic solar cells. However, the discovery of a method to determine the exact hECT remains an open challenge. Here, we suggest a simple method to determine the exact hECT level via deconvolution of the EL spectrum of the BHJ blend (ELB). To generalize, we have applied our ELB deconvolution method to nine different BHJ systems consisting of the combination of three donor polymers (PM6, PBDTTPD-HT, PTB7-Th) and three NFAs (Y6, IDIC, IEICO-4F). Under the conditions that (i) absorption of the donor and acceptor are separated sufficiently, and (ii) the onset part of the external quantum efficiency (EQE) is formed solely by the contribution of the acceptor only, ELB can be deconvoluted into the contribution of the singlet recombination of the acceptor and the radiative recombination via hECT. Through the deconvolution of ELB, we have clearly decided which part of the broad ELB spectrum should be used to apply the Marcus theory. Accurate determination of hECT is expected to be of great help in fine-tuning the energy level of donor polymers and NFAs by understanding the charge transfer mechanism clearly.

Re-Emergence of HMPV in Gwangju, South Korea, after the COVID-19 Pandemic.

The non-pharmaceutical interventions implemented to prevent the spread of COVID-19 have affected the epidemiology of other respiratory viruses. In South Korea, Human metapneumovirus (HMPV) typically occurs from winter to the following spring; however, it was not detected for two years during the COVID-19 pandemic and re-emerged in the fall of 2022, which is a non-epidemic season. To examine the molecular genetic characteristics of HMPV before and after the COVID-19 pandemic, we analyzed 427 HMPV-positive samples collected in the Gwangju area from 2018 to 2022. Among these, 24 samples were subjected to whole-genome sequencing. Compared to the period before the COVID-19 pandemic, the incidence rate of HMPV in 2022 increased by 2.5-fold. Especially in the age group of 6-10 years, the incidence rate increased by more than 4.5-fold. In the phylogenetic analysis results, before the COVID-19 pandemic, the A2.2.2 lineage was predominant, while in 2022, the A2.2.1 and B2 lineage were observed. The non-pharmaceutical interventions implemented after COVID-19, such as social distancing, have reduced opportunities for exposure to HMPV, subsequently leading to decreased acquisition of immunity. As a result, HMPV occurred during non-epidemic seasons, influencing the age distribution of its occurrences.

Resting-state prefrontal EEG biomarker in correlation with postoperative delirium in elderly patients.

Postoperative delirium (POD) is associated with adverse outcomes in elderly patients after surgery. Electroencephalography (EEG) can be used to develop a potential biomarker for degenerative cerebral dysfunctions, including mild cognitive impairment and dementia. This study aimed to explore the relationship between preoperative EEG and POD. We included 257 patients aged >70 years who underwent spinal surgery. We measured the median dominant frequency (MDF), which is a resting-state EEG biomarker involving intrinsic alpha oscillations that reflect an idle cortical state, from the prefrontal regions. Additionally, the mini-mental state examination and Montreal cognitive assessment (MoCA) were performed before surgery as well as 5 days after surgery. For long-term cognitive function follow up, the telephone interview for cognitive status™ (TICS) was performed 1 month and 1 year after surgery. Fifty-two (20.2%) patients were diagnosed with POD. A multivariable logistic regression analysis that included age, MoCA score, Charlson comorbidity index score, Mini Nutritional Assessment, and the MDF as variables revealed that the MDF had a significant odds ratio of 0.48 (95% confidence interval 0.27-0.85). Among the patients with POD, the postoperative neurocognitive disorders could last up to 1 year. Low MDF on preoperative EEG was associated with POD in elderly patients undergoing surgery. EEG could be a novel potential tool for identifying patients at a high risk of POD.

Anti-Inflammatory Effects of Spirodela polyrhiza (L.) SCHLEID. Extract on Contact Dermatitis in Mice-Its Active Compounds and Molecular Targets.

Spirodela polyrhiza (L.) SCHLEID. has been used to treat epidemic fever, dysuria, and various skin ailments, such as measles eruptions, eczema, and pruritus, in China, Japan, and Korea. In this study, the active compounds in S. polyrhiza and their target genes were identified by network-based analysis. Moreover, the study evaluated the effects of a 70% ethanolic extract of S. polyrhiza (EESP) on skin lesions, histopathological changes, inflammatory cytokines, and chemokines in mice with contact dermatitis (CD) induced by 1-fluoro-2,4-dinitrobenzene (DNFB), and examined the inhibitory effects of EESP on mitogen-activated protein kinase (MAPK) signalling pathways. In our results, 14 active compounds and 29 CD-related target genes were identified. Among them, tumour necrosis factor (TNF) and interleukin 6 (IL-6) were identified as hub genes, and luteolin and apigenin showed a strong binding affinity with TNF (<-8 kcal/mol) and IL-6 (<-6 kcal/mol). Our in vivo studies showed that topical EESP ameliorated DNFB-induced skin lesions and histopathological abnormalities, and reduced the levels of TNF-α, interferon (IFN)-É£, IL-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues. In conclusion, our findings suggest the potential for dermatological applications of S. polyrhiza and suggest that its anti-dermatitis action is related to the inhibition of TNF and IL-6 by luteolin and luteolin glycosides.

Effect of an aluminum chloride hemostatic agent on the dentin shear bond strength of a universal adhesive.

Objectives: This study investigated the effect of an aluminum chloride hemostatic agent on the shear bond strength (SBS) of a universal adhesive to dentin. Materials and Methods: Eighty extracted human molars were trimmed at the occlusal dentin surfaces and divided mesiodistally. According to hemostatic agent application, specimens were randomly allocated into control (C) and hemostatic agent (Traxodent; H) groups. Each group was divided into 4 subgroups according to the adhesive system (n = 20): Scotchbond Multi-Purpose (SBER), Clearfil SE Bond (CLSE), All-Bond Universal etch-and-rinse mode (ALER), and All-Bond Universal self-etch mode (ALSE). SBS was measured for half of the specimens at 24 hours, and the other half were thermocycled in water baths (group T). Fracture surfaces were examined to determine the failure mode. The SBS was measured, and data were analyzed using 1-way analysis of variance, the Student's t-test, and the Tukey honestly significant difference test (p = 0.05). Results: No significant differences in SBS were found between groups C and H for any adhesive system at 24 hours. After thermocycling, a statistically significant difference was observed between CT+ALSE and HT+ALSE (p < 0.05). When All-Bond Universal was applied to hemostatic agent-contaminated dentin, the SBS of H+ALSE was significantly lower than that of H+ALER (p < 0.05). The SBER subgroups showed no significant differences in SBS regardless of treatment and thermocycling. Conclusions: When exposed dentin was contaminated by an aluminum chloride hemostatic agent before dentin adhesive treatment, application of All-Bond Universal in etch-and-rinse mode was superior to self-etch mode.

Pressure changes in the endotracheal tube cuff in otorhinolaryngologic surgery: a prospective observational study.

Objective: Inflation of the endotracheal tube cuff is needed for providing ventilation. Cuff pressure should be maintained inside the appropriate range to prevent critical airway complications. The purpose of this study is to evaluate the pressure changes in the endotracheal tube cuff during otorhinolaryngologic surgery. Design and method: This single-center observational study was conducted at Severance Hospital in Korea between April 2020 and November 2020. Patients aged >20 years scheduled to undergo otorhinolaryngological surgical procedures were enrolled. Patients undergoing planned tracheostomy and those who were slated for uncuffed endotracheal tube use were excluded. Intubation was performed after the induction of general anesthesia. A pressure transducer was connected to the pilot balloon of the endotracheal tube, and cuff pressure was continuously monitored until extubation. If the cuff pressure was not appropriate for more than 5 min, it was adjusted to the appropriate range by injecting or removing air. The percentage of time for which the cuff pressure remained within the appropriate range was calculated and defined as the time in the therapeutic range (TTR). The presumed cause for the rise or fall in cuff pressure was identified. Results: In total 199 patients, alterations in cuff pressure outside the appropriate range occurred in 191 patients (96.0%). The mean TTR was 79.7% (SD 25.0%), and head and neck surgery had the lowest mean TTR of 69.0% compared to ear and nose surgeries (94.2 and 82.1%, respectively). Sixty-eight patients (34.2%) demonstrated inadequate endotracheal tube cuff pressure for more than 20% of the total anesthesia time. Twenty-six patients (13.1%) demonstrated optimal endotracheal tube cuff pressure for less than 50% of the total anesthesia time. The causative factors inducing inappropriate cuff pressure were found to vary, including positional changes, surgical procedure, anatomical manipulation, and anesthetic procedure. Conclusion: In otorhinolaryngologic surgery, cuff pressure increased or decreased outside the appropriate range due to various factors. Therefore, we suggest close continuous monitoring of cuff pressure during anesthesia for otorhinolaryngologic surgery. Clinical trial registration: clinicaltrials.gov, identifier NCT03938493.

Comparison of preoxygenation efficiency measured by the oxygen reserve index between high-flow nasal oxygenation and facemask ventilation: a randomised controlled trial.

BACKGROUND: High-flow nasal oxygenation and the oxygen reserve index (ORI), which is a non-invasive and innovative modality that reflects the arterial oxygen content, are used in general anaesthesia. This study compares the preoxygenation efficiency (measured by the ORI) of high-flow nasal oxygenation and facemask ventilation during the induction process. METHODS: This single-centre, two-group, randomised controlled trial included 197 patients aged ≥ 20 years who underwent orotracheal intubation for general anaesthesia for elective surgery. The patients were randomly allocated to receive preoxygenation via facemask ventilation or high-flow nasal oxygenation. The ORI was measured and compared between both groups. RESULTS: The ORI increased during preoxygenation in all patients. At 1 min of preoxygenation, the ORI was significantly higher in the high-flow nasal oxygenation group (0.34 ± 0.33) than in the facemask ventilation group (0.21 ± 0.28; P = 0.003). The highest ORI was not significantly different between the two groups (0.68 ± 0.25 in the high-flow nasal oxygenation group vs. 0.70 ± 0.28 in the facemask ventilation group; P = 0.505). CONCLUSIONS: High-flow nasal oxygenation results in an oxygenation status similar to that provided by facemask ventilation during the induction process of general anaesthesia; therefore, high-flow nasal oxygenation is a feasible preoxygenation method. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04291339).

Efficacy of high-flow nasal oxygen during drug-induced sleep endoscopy in patients with obstructive sleep apnea.

PURPOSE: High-flow nasal oxygenation (HFNO) can provide a low level of continuous positive airway pressure and alveolar recruitment. We aimed to compare the efficacy of pre-oxygenation with HFNO and low-flow nasal oxygenation (LFNO) during drug-induced sleep endoscopy (DISE). METHODS: In the LFNO group, preoxygenation was performed for 10 min at 3 L·min-1. In the HFNO group, preoxygenation was performed for 10 min at 30 L·min-1 at a fraction of inspired oxygen of 100% using the Optiflow device. From the start of sedative administration to the end of DISE, vital signs were monitored continuously. The primary outcome was the lowest oxygen saturation (SpO2) during DISE. RESULTS: Of 24 patients enrolled, 12 were randomly assigned to the LFNO and 12 to the HFNO groups. The prevalence of hypoxia events was 75% in the LFNO group and 58% in the HFNO group. The difference in lowest oxygen saturation between the two groups was not significant between the two groups (P=0.665). The lowest SpO2 during all procedures was comparable between the two groups (86.8 ± 6.5% in the LFNO group and 87.2 ± 8.0% in the HFNO group; P=0.912). CONCLUSIONS: The findings suggest that HFNO may not be superior to LFNO as a preoxygenation tool to prevent hypoxia during DISE.

Evaluation of Fitness and Accuracy of Milled and Three-Dimensionally Printed Inlays.

OBJECTIVE: This article compares and evaluates the marginal and internal fitness and three-dimensional (3D) accuracy of class II inlays fabricated using Tescera (TS) resin, milling of hybrid and zirconia blocks, and 3D printing with NextDent C&B. MATERIALS AND METHODS: Fifty-two mesio-occlusal inlays were fabricated using conventional method with TS, milling of Lava Ultimate (LU), milling of Zolid Fx multilayer (ZR), and 3D printing (n = 13 each). The marginal and internal fitness were evaluated at six points in the mesio-distal section of a replica under a digital microscope (160× magnification), and the accuracy was evaluated using 3D software. Analyses were conducted using t-test, one-way analysis of variance (ANOVA) and two-way ANOVA, while Duncan's multiple range test was used for post hoc analyses (α = 0.05). RESULTS: The marginal and internal fitness of the 3D and ZR were significantly superior to that of the TS and LU. For LU, ZR, and 3D, a significant discrepancy between the marginal gap and internal gap was observed (p < 0.05). On evaluating accuracy, trueness was significantly higher in ZR than in TS and LU; precision was significantly higher in 3D and ZR than in TS and LU (p < 0.05). CONCLUSION: The marginal and internal fitness and the accuracy of TS, ZR, and 3D were within the clinically acceptable range. The marginal and internal fitness and accuracy of 3D were better than those of TS and LU, which are commonly used in dentistry. There is immense potential for using 3D-printed inlays in routine clinical practice.

Efficient and Moisture-Stable Inverted Perovskite Solar Cells via n-Type Small-Molecule-Assisted Surface Treatment.

Defect states at the surface and grain boundaries of perovskite films have been known to be major determinants impairing the optoelectrical properties of perovskite films and the stability of perovskite solar cells (PeSCs). Herein, an n-type conjugated small-molecule additive based on fused-unit dithienothiophen[3,2-b]-pyrrolobenzothiadiazole-core (JY16) is developed for efficient and stable PeSCs, where JY16 possesses the same backbone as the widely used Y6 but with long-linear n-hexadecyl side chains rather than branched side chains. Upon introducing JY16 into the perovskite films, the electron-donating functional groups of JY16 passivate defect states in perovskite films and increase the grain size of perovskite films through Lewis acid-base interactions. Compared to Y6, JY16 exhibits superior charge mobility owing to its molecular packing ability and prevents decomposition of perovskite films under moisture conditions owing to their hydrophobic characteristics, improving the charge extraction ability and moisture stability of PeSCs. Consequently, the PeSC with JY16 shows a high power conversion efficiency of 21.35%, which is higher than those of the PeSC with Y6 (20.12%) and without any additive (18.12%), and outstanding moisture stability under 25% relative humidity, without encapsulation. The proposed organic semiconducting additive will prove to be crucial for achieving highly efficient and moisture stable PeSCs.

A Double-Blind, Randomized, Placebo-Controlled, Phase II Clinical Study To Evaluate the Efficacy and Safety of Camostat Mesylate (DWJ1248) in Adult Patients with Mild to Moderate COVID-19.

Although several antiviral agents have become available for coronavirus disease 2019 (COVID-19) treatment, oral drugs are still limited. Camostat mesylate, an orally bioavailable serine protease inhibitor, has been used to treat chronic pancreatitis in South Korea, and it has an in vitro inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical trial in mild to moderate COVID-19 patients. We randomly assigned patients to receive either camostat mesylate (DWJ1248) or placebo orally for 14 days. The primary endpoint was time to clinical improvement of subject symptoms within 14 days, measured using a subjective 4-point Likert scale. Three hundred forty-two patients were randomized. The primary endpoint was nonsignificant, where the median times to clinical improvement were 7 and 8 days in the camostat mesylate group and the placebo group, respectively (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.84 to 1.43; P = 0.50). A post hoc analysis showed that the difference was greatest at day 7, without reaching significance. In the high-risk group, the proportions of patients with clinical improvement up to 7 days were 45.8% (50/109) in the camostat group and 38.4% (40/104) in the placebo group (odds ratio [OR] = 1.33; 95% CI, 0.77 to 2.31; P = 0.31); the ordinal scale score at day 7 improved in 20.0% (18/90) of the camostat group and 13.3% (12/90) of the placebo group (OR = 1.68; 95% CI, 0.75 to 3.78; P = 0.21). Adverse events were similar in the two groups. Camostat mesylate was safe in the treatment of COVID-19. Although this study did not show clinical benefit in patients with mild to moderate COVID-19, further clinical studies for high-risk patients are needed. (This trial was registered with ClinicalTrials.gov under registration no. NCT04521296).

MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer.

BACKGROUND: The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. METHODS: We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. RESULTS: MHY4571 inhibited PKA activity (> 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. CONCLUSIONS: Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment.

Neuroprotective Effect of Dexmedetomidine against Postoperative Cognitive Decline via NLRP3 Inflammasome Signaling Pathway.

Dexmedetomidine (Dex), widely used as a sedative in surgical procedures and intensive care units, induces sympatholytic, anxiolytic, analgesic, and sedative effects. Postoperative cognitive dysfunction (POCD) is routinely observed in postoperative care following surgery and general anesthesia. The NLRP3 inflammasome complex plays a critical role in innate immune response by detecting pathogenic microorganisms and activating pro-inflammatory cytokines. Although there are numerous protective effects of Dex among the neurological diseases, specific mechanisms including NLRP3 inflammasome-mediated neuroinflammation via oxidative stress response in a POCD model are not fully understood. Here, we investigated whether Dex exhibits neurocognitive effects through the NLRP3 inflammasome signaling in a POCD mouse model using a neurobehavioral test and ELISA analysis. We also confirmed the level of oxidative stress-related response in the in vitro system in the POCD model. Furthermore, we evaluated the NLRP3 inflammasome complex by immunoprecipitation analysis. In summary, the results of the present study indicated that Dex showed a neuroprotective effect in the POCD model by reducing oxidative stress response through NLRP3 inflammasome-mediated neuroinflammation.

Development of Machine Learning Models Predicting Estimated Blood Loss during Liver Transplant Surgery.

The incidence of major hemorrhage and transfusion during liver transplantation has decreased significantly over the past decade, but major bleeding remains a common expectation. Massive intraoperative hemorrhage during liver transplantation can lead to mortality or reoperation. This study aimed to develop machine learning models for the prediction of massive hemorrhage and a scoring system which is applicable to new patients. Data were retrospectively collected from patients aged >18 years who had undergone liver transplantation. These data included emergency information, donor information, demographic data, preoperative laboratory data, the etiology of hepatic failure, the Model for End-stage Liver Disease (MELD) score, surgical history, antiplatelet therapy, continuous renal replacement therapy (CRRT), the preoperative dose of vasopressor, and the estimated blood loss (EBL) during surgery. The logistic regression model was one of the best-performing machine learning models. The most important factors for the prediction of massive hemorrhage were the disease etiology, activated partial thromboplastin time (aPTT), operation duration, body temperature, MELD score, mean arterial pressure, serum creatinine, and pulse pressure. The risk-scoring system was developed using the odds ratios of these factors from the logistic model. The risk-scoring system showed good prediction performance and calibration (AUROC: 0.775, AUPR: 0.753).