A Phase II Study About Efficacy and Safety of the Continuous IntraVenous Infusion of Ketamine as Adjuvant to Opioids in Terminally Ill Cancer Patients With Refractory Cancer Pain (CIVIK Trial).

BACKGROUND: Ketamine has been used to control refractory cancer pain as an adjuvant to opioids. We conducted a prospective phase II study to investigate the efficacy and safety of 5-day continuous intravenous infusion (CIVI) of Ketamine in terminally ill cancer patients with refractory cancer pain. METHODS: Hospitalized terminally ill cancer patients with refractory cancer pain were enrolled. Refractory cancer pain was indicated by requirements for 4 or more rescue opioids or pain intensity using numerical rating scale > personalized pain goal (PPG) despite of intravenous morphine equivalent daily dose (IV MEDD) ≥ 120 mg/day. The CIVI of ketamine was increased from .05 mg/kg/hour to .5 mg/kg/hour by .05 every 8 hours if pain intensity exceeded PPG or if number of rescue opioids ≥2 during prior 8 hours was required. The primary end-point was overall pain response rate, which indicates complete response (both rescue opioid ≤3/day and pain intensity ≤ PPG) plus partial response (rescue opioid ≤3/day), without unacceptable toxicities. RESULTS: Among 21 eligible patients enrolled between September 2019 and January 2023, 20 were analyzed. Most pain mechanisms were mixed type (n = 15, 75%), with neuropathic component (n = 17, 85%). The baseline background opioids were IV MEDD 186 mg/24hour (range, 124-592), number of rescue opioids was 6 (IQR, 5-9), and median PPG was 4 (IQR, 3-4). The overall pain response rate was 50% (n = 10) including 40% (n = 8) for complete pain response and 10% (n = 2) for partial pain response. CONCLUSION: This study showed efficacy of gradually increasing CIVI of ketamine for terminally ill cancer patients with refractory cancer pain. CIVI of ketamine could be a useful tool in these patients considering the limited treatment options. (NCT03362073, Initial Release: November 15, 2017).

Validation of MELD 3.0 in patients with alcoholic liver cirrhosis using prospective KACLiF cohort.

BACKGROUND AND AIM: The Model for End-Stage Liver Disease (MELD) is a reliable prognostic tool for short-term outcome prediction in patients with end-stage liver disease. MELD 3.0 was introduced to enhance the predictive accuracy. This study assessed the performance of MELD 3.0, in comparison to MELD and MELD-Na, in patients with alcoholic liver cirrhosis. METHODS: This multicenter prospective cohort study comprised patients with alcoholic cirrhosis admitted for acute deterioration of liver function in the Republic of Korea between 2015 and 2019. This study compared the predictive abilities of MELD, MELD-Na, and MELD 3.0, for 30-day and 90-day outcomes, specifically death or liver transplantation, and explored the factors influencing these outcomes. RESULTS: A total of 1096 patients were included in the study, with a mean age of 53.3 ± 10.4 years, and 82.0% were male. The mean scores for MELD, MELD-Na, and MELD 3.0 at the time of admission were 18.7 ± 7.2, 20.6 ± 7.7, and 21.0 ± 7.8, respectively. At 30 and 90 days, 7.2% and 14.1% of patients experienced mortality or liver transplantation. The areas under the receiver operating characteristic curves for MELD, MELD-Na, and MELD 3.0 at 30 days were 0.823, 0.820, and 0.828; and at 90 days were 0.765, 0.772, and 0.776, respectively. Factors associated with the 90-day outcome included concomitant chronic viral hepatitis, prolonged prothrombin time, elevated levels of aspartate transaminase, bilirubin, and creatinine, and low albumin levels. CONCLUSION: MELD 3.0 demonstrated improved performance compared to previous models, although the differences were not statistically significant.

Dynamic Assessment of Modified Quick Sequential Organ Failure Assessment in Acutely Deteriorated Patients with Chronic Liver Disease.

Background/Aims: Quick sequential organ failure assessment (qSOFA) has been suggested to identify those who have poor outcomes in patients with suspected infection. We aimed to evaluate the ability of the modified qSOFA (m-qSOFA) to identify high-risk patients in acutely deteriorated patients with chronic liver disease (CLD), especially acute-on-chronic liver failure (ACLF). Methods: We used the data of both Korean Acute-on-Chronic Liver Failure (KACLiF) and Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and m-qSOFA≥2 was considered high. Results: Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than patients with low m-qSOFA (Ps<0.05). Subgroup analysis by ACLF showed that patients with high m-qSOFA had lower TFS than patients with low m-qSOFA. m-qSOFA was an independent prognostic factor (hazard ratios (HR)=2.604, 95% confidence interval (CI) 1.353-5.013, P=0.004 in KACLiF and HR=1.904, 95% CI 1.484-2.442, P<0.001 in AARC). The patients with low m-qSOFA at baseline but high m-qSOFA on the 7th day had a significantly lower 1-month TFS than the patients with high m-qSOFA at baseline but low m-qSOFA on the 7th day (52.6% vs. 89.4%, P<0.001 in KACLiF and 26.9% vs. 61.5%, P<0.001 in AARC). Conclusion: Baseline and dynamic changes in m-qSOFA were useful to identify patients with a high risk of organ failure development and short-term mortality among CLD patients with acute deterioration.

Sex reporting of cells used in cancer research: A systematic review.

Sex and gender disparities in biomedical research have been emphasized to improve scientific knowledge applied for the health of both men and women. Despite sex differences in cancer incidence, prognosis, and responses to therapeutic agents, mechanistic explanations at molecular levels are far from enough. Recent studies suggested that cell sex is an important biological variable due to differences in sex chromosome gene expression and differences in events associated with developmental biology. The objective of this study was to analyze the reporting of sex of cells used in cancer research using articles published in Cancer Cell, Molecular Cancer, Journal of Hematology & Oncology, Journal for ImmunoTherapy of Cancer, and Cancer Research in 2020, and to examine whether there exists any sex bias. We found that the percentage of cells with sex notation in the article was 36.5%. Primary cells exhibited higher sex notation compared to cell lines. A higher percentage of female cells were used in cell cultures with sex notation. Also, sex-common cells omitted sex description more often compared to sex-specific cells. None of the cells isolated from embryo and esophagus reported the cell sex in the article. Our results indicate cell sex report in cancer research is limited to a small proportion of cells used in the study. These results call for acknowledging the sex of cells to increase the applicability of biomedical research discoveries.

Development and Evaluation of Nursing Clinical Practice Education Using M-Learning.

This study aims to develop and evaluate the effectiveness of nursing practice education using mobile learning or m-learning for nursing students. A nonequivalent control group post-test design was used. Overall, 42 nursing students participated in the study. A three-week nursing practice education program was developed using the Analysis, Design, Development, Implementation, and Evaluation (ADDIE) model. The course was implemented on the basis of Gagne's nine instructional situations. The findings demonstrated improvements in clinical competency (t = 7.44, p < 0.001) and problem solving (t = 2.29, p = 0.028). Accordingly, the study recommends introducing m-learning in nursing practice education using tablet PCs, as part of a newer nursing practicum training strategy that takes into account the factors identified in this study. It is also suggested that a continuous m-learning approach and development plan for nursing students be prepared to achieve technically advanced nursing practice education.

The novel linkage between Fuz and Gpr161 genes regulates sonic hedgehog signaling during mouse embryonic development.

Sonic hedgehog (Shh) signaling regulates embryonic morphogenesis utilizing primary cilia, the cell antenna acting as a signaling hub. Fuz, an effector of planar cell polarity (PCP) signaling, involves Shh signaling via cilia formation, while the G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling. The range of phenotypic malformations observed in mice bearing mutations in either of these two genes is similar; however, their functional relations have not been previously explored. This study identified the genetic and biochemical link between Fuz and Gpr161 in mouse embryonic development. Fuz was genetically epistatic to Gpr161 via Shh signaling during mouse embryonic development. The FUZ biochemically interacted with GPR161, and Fuz regulated Gpr161 ciliary trafficking via ß-arrestin2. Our study suggested the novel Gpr161-Fuz axis that regulates Shh signaling during mouse embryonic development.

Machine learning methods for developing a predictive model of the incidence of delirium in cardiac intensive care units.

INTRODUCTION AND OBJECTIVES: Delirium, recognized as a crucial prognostic factor in the cardiac intensive care unit (CICU), has evolved in response to the changing demographics among critically ill cardiac patients. This study aimed to create a predictive model for delirium for patients in the CICU. METHODS: This study included consecutive patients admitted to the CICU of the Samsung Medical Center. To assess the candidate variables for the model: we applied the following machine learning methods: random forest, extreme gradient boosting, partial least squares, and Plmnet-elastic.net. After selecting relevant variables, we performed a logistic regression analysis to derive the model formula. Internal validation was conducted using 100-repeated hold-out validation. RESULTS: We analyzed 2774 patients, 677 (24.4%) of whom developed delirium in the CICU. Machine learning-based models showed good predictive performance. Clinically significant and frequently important predictors were selected to construct a delirium prediction scoring model for CICU patients. The model included albumin level, international normalized ratio, blood urea nitrogen, white blood cell count, C-reactive protein level, age, heart rate, and mechanical ventilation. The model had an area under the receiver operating characteristics curve (AUROC) of 0.861 (95%CI, 0.843-0.879). Similar results were obtained in internal validation with 100-repeated cross-validation (AUROC, 0.854; 95%CI, 0.826-0.883). CONCLUSIONS: Using variables frequently ranked as highly important in four machine learning methods, we created a novel delirium prediction model. This model could serve as a useful and simple tool for risk stratification for the occurrence of delirium at the patient's bedside in the CICU.

Advances in Biocarbon and Soft Material Assembly for Enthalpy Storage: Fundamentals, Mechanisms, and Multimodal Applications.

High-value-added biomass materials like biocarbon are being actively pursued integrating them with soft materials in a broad range of advanced renewable energy technologies owing to their advantages, such as lightweight, relatively low-cost, diverse structural engineering applications, and high energy storage potential. Consequently, the hybrid integration of soft and biomass-derived materials shall store energy to mitigate intermittency issues, primarily through enthalpy storage during phase change. This paper introduces the recent advances in the development of natural biomaterial-derived carbon materials in soft material assembly and its applications in multidirectional renewable energy storage. Various emerging biocarbon materials (biochar, carbon fiber, graphene, nanoporous carbon nanosheets (2D), and carbon aerogel) with intrinsic structures and engineered designs for enhanced enthalpy storage and multimodal applications are discussed. The fundamental design approaches, working mechanisms, and feature applications, such as including thermal management and electromagnetic interference shielding, sensors, flexible electronics and transparent nanopaper, and environmental applications of biocarbon-based soft material composites are highlighted. Furthermore, the challenges and potential opportunities of biocarbon-based composites are identified, and prospects in biomaterial-based soft materials composites are presented.

New prognostic model for hospitalized patients with alcoholic cirrhosis and Maddrey's discriminant function <32.

BACKGROUND & AIMS: Few studies have investigated the prognosis of patients with non-severe alcoholic hepatitis (Non-SAH). The study aimed to develop a new prognostic model for patients with especially Non-SAH. METHODS: We extracted 316 hospitalized patients with alcoholic cirrhosis without severe alcoholic hepatitis, defined as Maddrey's discriminant function score lower than 32, from the retrospective Korean Acute-on-Chronic Liver Failure (KACLiF) cohort to develop a new prognostic model (training set), and validated it in 419 patients from the prospective KACLiF cohort (validation set). Prognostic factors for death and liver transplantation were analyzed to construct a prognostic model. RESULTS: Twenty-one and 24 patients died within 6 months in both sets, respectively. In the training set, the highest area under the curve (AUC) of conventional prognostic models was 0.765, 0.732, and 0.684 for 1-, 3-, and 6-month mortality, respectively. Refractory ascites, vasopressor use, and hyponatremia were independently associated with mortality of cirrhotic patients with Non-SAH. The new model consisted of four variables: past deterioration, neutrophil proportion > 70%, Na < 128 mmol/L, and vasopressor use. It showed the highest accuracy for short-term mortality in the training and validation sets (0.803 and 0.786; 0.797 and 0.776; and 0.789 and 0.721 for 1-, 3-, and 6-month mortality, respectively). CONCLUSION: There is a group of patients with high risk among those classified as Non-SAH. The new model will help stratifying cirrhotic patients with Non-SAH more accurately in terms of prognosis. The patients with high Non-SAH score need to monitor closely and might be considered for preemptive liver transplantation. TRIAL REGESTRATION: ClinicalTrials.gov identifier: NCT02650011.

The effects of dietary self-monitoring intervention on anthropometric and metabolic changes via a mobile application or paper-based diary: a randomized trial.

BACKGROUND/OBJECTIVES: Weight loss via a mobile application (App) or a paper-based diary (Paper) may confer favorable metabolic and anthropometric changes. SUBJECTS/METHODS: A randomized parallel trial was conducted among 57 adults whose body mass indices (BMIs) were 25 kg/m2 or greater. Participants randomly assigned to either the App group (n = 30) or the Paper group (n = 27) were advised to record their foods and supplements through App or Paper during the 12-week intervention period. Relative changes of anthropometries and biomarker levels were compared between the 2 intervention groups. Untargeted metabolic profiling was identified to discriminate metabolic profiles. RESULTS: Out of the 57 participants, 54 participants completed the trial. Changes in body weight and BMI were not significantly different between the 2 groups (P = 0.11). However, body fat and low-density lipoprotein (LDL)-cholesterol levels increased in the App group but decreased in the Paper group, and the difference was statistically significant (P = 0.03 for body fat and 0.02 for LDL-cholesterol). In the metabolomics analysis, decreases in methylglyoxal and (S)-malate in pyruvate metabolism and phosphatidylcholine (lecithin) in linoleic acid metabolism from pre- to post-intervention were observed in the Paper group. CONCLUSIONS: In the 12-week randomized parallel trial of weight loss through a App or a Paper, we found no significant difference in change in BMI or weight between the App and Paper groups, but improvement in body fatness and LDL-cholesterol levels only in the Paper group under the circumstances with minimal contact by dietitians or health care providers. Trial Registration: Clinical Research Information Service Identifier: KCT0004226.

Pax3 lineage-specific deletion of Gpr161 is associated with spinal neural tube and craniofacial malformations during embryonic development.

Sonic hedgehog (Shh) signaling is the morphogen signaling that regulates embryonic craniofacial and neural tube development. G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling, and its inactivation in mice results in embryo lethality associated with craniofacial defects and neural tube defects. However, the structural defects of later embryonic stages and cell lineages underlying abnormalities have not been well characterized due to the limited lifespan of Gpr161 null mice. We found that embryos with Pax3 lineage-specific deletion of Gpr161 presented with tectal hypertrophy (anterior dorsal neuroepithelium), cranial vault and facial bone hypoplasia (cranial neural crest), vertebral abnormalities (somite) and the closed form of spina bifida (posterior dorsal neuroepithelium). In particular, the closed form of spina bifida was partly due to reduced Pax3 and Cdx4 gene expression in the posterior dorsal neural tubes of Gpr161 mutant embryos with decreased Wnt signaling, whereas Shh signaling was increased. We describe a previously unreported role for Gpr161 in the development of posterior neural tubes and confirm its role in cranial neural crest- and somite-derived skeletogenesis and midbrain morphogenesis in mice.

Coagulation Factor Expression and Composition of Arterial Thrombi in Cancer-Associated Stroke.

BACKGROUND: Cancer is associated with an increased risk of stroke. Tumor cells activate platelets, induce a coagulation cascade, and generate thrombin. The composition of thrombi may reflect the mechanism of thrombosis, aiding the determination of the treatment strategy. Here, we investigated the composition and expression of coagulation factors in the thrombi of patients with cancer-associated stroke. METHODS: Patients with stroke who underwent endovascular thrombectomy between September 2014 and June 2020 and whose cerebral thrombi were obtained were divided into those with cancer-associated stroke (cancer group) and propensity score-matched patients without cancer (control group), using 1:1 matching based on age and sex. Immunohistochemistry was performed of the thrombi, and the composition and expression of coagulation factors were compared between groups. RESULTS: Among the 320 patients who underwent endovascular thrombectomy and who had thrombi obtained, this study included 23 patients with cancer and 23 matched controls. In both groups, the median age was 65 years, and 12 patients (52.2%) were men. Platelet composition was significantly higher in the cancer group than in the control group (median [interquartile range], 51.3% [28.0%-61.4%] versus 9.5% [4.8%-14.0%]; P<0.001). Among coagulation factors, thrombin (26.2% [16.2%-52.7%] versus 4.5% [1.3%-7.2%]; P<0.001) and tissue factors (0.60% [0.34%-2.06%] versus 0.37% [0.22%-0.60%]; P=0.024) were higher and factor X was lower (1.25% [0.39%-3.60%] versus 2.33% [1.67%-4.48%]; P=0.034) in the cancer group. There was a positive correlation between thrombin and platelets in the cancer group (r=0.666; P=0.001) but not in the control group (r=-0.167; P=0.627). CONCLUSIONS: Cerebral thrombi in patients with cancer-associated stroke showed higher proportions of platelets, thrombin, and tissue factors, suggesting their key roles in arterial thrombosis in cancer and providing a therapeutic perspective for preventing stroke in patients with cancer-associated stroke.

Clinical Usefulness of Immune Profiling for Differential Diagnosis between Crohn's Disease, Intestinal Tuberculosis, and Behcet's Disease.

It is important to make a differential diagnosis between inflammatory diseases of the bowel with similar clinical and endoscopic features. The profiling of immune cells could be helpful for accurately diagnosing inflammatory bowel diseases. We compared immune marker expression between Crohn's disease (CD), intestinal Behcet's disease (BD), and intestinal tuberculosis (TB) and evaluated the usefulness of immune profiling in differentiating between these diseases. Biopsy specimens were acquired around ulcerations on the terminal ileum or cecum from five patients with each disease. Panel 1 included multiplex immunohistochemistry staining for CD8, CD4, Foxp3, CD20, programmed death-1, and granzyme B. CD56, CD68, CD163, CD11c, and HLA-DR were analyzed in panel 2. The differences in cytotoxic T cells (CD8+CD4-Fopx3-CD20-), helper T cells (CD8-CD4+Fopx3-CD20-), and regulatory T cells (CD8-CD4+Fopx3+CD20-) were also not significant. However, M1 macrophage (CD68+CD163-HLA-DR-) cell densities were significantly higher in intestinal BD than in other diseases. The expression level of dendritic cells (CD56-CD68-CD163-CD11c+HLA-DR+) was highest in intestinal TB and lowest in intestinal BD. The expression of immune cells, including M1 macrophages and dendritic cells, was different between CD, intestinal BD, and intestinal TB. Immune profiling can be helpful for establishing differential diagnoses of inflammatory bowel diseases.

Prognosis of Patients with Chronic Hepatitis C Genotype 1b Infection Treated Using Daclatasvir/Asunaprevir after Sustained Virologic Response: A 6-Year Multicenter Prospective Observational Study.

Aim and Objectives: Direct-acting antiviral (DAA) therapy can cure chronic hepatitis C (CHC), and daclatasvir (DCV)/asunaprevir (ASV) was the first interferon-free DAA therapy introduced in Korea. Patients who achieve sustained virologic response (SVR) after DAA treatment are expected to have good prognoses. Therefore, in this study, we aimed to investigate the prognosis of these patients. Materials and Methods: This multicenter prospective observational study included patients with CHC who achieved SVR after DCV/ASV treatment. The primary endpoint was hepatocellular carcinoma (HCC) occurrence, which was reviewed annually. Results: We included 302 patients (median follow-up duration: 38 [16.5-60.0] months; median age: 58 [49-67] years) in the study. Cirrhosis was observed in 103 patients (34.1%), and the median Child-Pugh score was 5.0. HCC occurred in 16 patients (5.3%) within six years post-SVR; these patients were older and had higher cirrhosis prevalence, alpha-fetoprotein levels, and fibrosis-4 index scores than did those without HCC development. Cox proportional hazards analysis revealed that age > 71 years (p = 0.005) and cirrhosis (p = 0.035) were significant risk factors for HCC occurrence. Conclusions: Although the prognoses of patients who achieved SVR with DCV/ASV therapy were generally good, the risk for HCC was present, especially in older patients and in those with cirrhosis. Hence, early treatment at younger ages and regular follow-up surveillance after achieving SVR are warranted.

Pax3 lineage-specific deletion of Gpr161 is associated with spinal neural tube and craniofacial malformations during embryonic development.

Shh signaling is the morphogen signaling that regulates embryonic craniofacial and neural tube development. G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling, and its inactivation in mice results in embryo lethality with craniofacial and neural tube defects (NTDs). However, the structural defects of later embryonic stages in Gpr161 null mice and cell lineages underlying abnormalities were not well characterized due to their limited lifespan. We found the Pax3 lineage-specific deletion of Gpr161 in mice presented with tectal hypertrophy (anterior dorsal neuroepithelium), cranial vault and facial bone hypoplasia (cranial neural crest (CNC)), vertebral abnormalities (somite), and the closed form of spina bifida (posterior dorsal neuroepithelium). In particular, the closed form of spina bifida is partly due to the reduced Pax3 and Cdx4 gene expression of the posterior dorsal neural tubes of Gpr161 mutant embryos involving decreased Wnt signaling whereas Shh signaling was increased. This study provides the novel role of Gpr161 in the posterior neural tube development and confirms its role on CNC- and somite-derived skeletogenesis and midbrain morphogenesis in mice.

Cancer Prediction With Machine Learning of Thrombi From Thrombectomy in Stroke: Multicenter Development and Validation.

BACKGROUND: We aimed to develop and validate machine learning models to diagnose patients with ischemic stroke with cancer through the analysis of histopathologic images of thrombi obtained during endovascular thrombectomy. METHODS: This was a retrospective study using a prospective multicenter registry which enrolled consecutive patients with acute ischemic stroke from South Korea who underwent endovascular thrombectomy. This study included patients admitted between July 1, 2017 and December 31, 2021 from 6 academic university hospitals. Whole-slide scanning was performed for immunohistochemically stained thrombi. Machine learning models were developed using transfer learning with image slices as input to classify patients into 2 groups: cancer group or other determined cause group. The models were developed and internally validated using thrombi from patients of the primary center, and external validation was conducted in 5 centers. The model was also applied to patients with hidden cancer who were diagnosed with cancer within 1 month of their index stroke. RESULTS: The study included 70 561 images from 182 patients in both internal and external datasets (119 patients in internal and 63 in external). Machine learning models were developed for each immunohistochemical staining using antibodies against platelets, fibrin, and erythrocytes. The platelet model demonstrated consistently high accuracy in classifying patients with cancer, with area under the receiver operating characteristic curve of 0.986 (95% CI, 0.983-0.989) during training, 0.954 (95% CI, 0.937-0.972) during internal validation, and 0.949 (95% CI, 0.891-1.000) during external validation. When applied to patients with occult cancer, the model accurately predicted the presence of cancer with high probabilities ranging from 88.5% to 99.2%. CONCLUSIONS: Machine learning models may be used for prediction of cancer as the underlying cause or detection of occult cancer, using platelet-stained immunohistochemical slide images of thrombi obtained during endovascular thrombectomy.

Anatomic Variations of the Lateral Branch of the Supraorbital Nerve Observed in Endoscopic Forehead Surgery.

Surgeons dissect carefully in the medial third of the supraorbital rim to preserve the supraorbital nerve (SON) during surgical forehead rejuvenation. However, the anatomic variations of SON exit from the frontal bone have been researched in cadaver or imaging studies. In this study, we report a variation in the lateral branch of SON observed in an endoscopic view during forehead lifts. A retrospective review of 462 patients who underwent endoscopy-assisted forehead lifts between January 2013 and April 2020 was performed. Data, including the location, number, and form of the exit point and thickness of SON and its lateral branch variant, were recorded and reviewed intraoperatively, utilizing high-definition endoscopic assistance. Thirty-nine patients and 51 sides were included, and all patients were female, with a mean age of 44.53 (18-75) years. This nerve exited a foramen in the frontal bone ~8.82 ± 2.79 mm lateral to SON and ~1.89 ± 1.34 mm from the supraorbital margin vertically. Observed thickness variations of the lateral branch of SON included 20 small, 25 medium, and 6 large nerves. This study revealed various positional and morphologic variations of the lateral branch of SON in an endoscopic view. Thus, surgeons can be alerted of the anatomic variations of SON and establish careful dissection during procedures. In addition, the findings of this study will be useful in planning nerve blocks, filler injections, and migraine treatments in the supraorbital region.

Comparison between Two-Dimensional and Point Shear Wave Elastography Techniques in Evaluating Liver Fibrosis Using Histological Staging as the Reference Standard: A Prospective Pilot Study.

Evaluation of hepatic fibrosis is essential to prevent liver-related morbidity and mortality. Although various types of ultrasound shear wave elastography (SWE) have been used and validated, there are limited studies on the relatively newer technique, two-dimensional SWE (2D-SWE). Therefore, this study aimed to compare the diagnostic performances of 2D-SWE and point SWE (p-SWE) for evaluating liver fibrosis using histology as the reference standard. To measure liver stiffness (LS) values, 87 patients underwent 2D-SWE and p-SWE using the same machine. Technical failures and unreliable measurements were also evaluated. The diagnostic performances of 2D-SWE and p-SWE were compared using area under the receiver operating characteristic (AUROC) curve analysis. No technical failures were observed in either method; however, unreliable measurements were less frequent in 2D-SWE (1/87 [1.1%]) than in p-SWE (8/87 [9.2%]) (p < 0.001). The AUROC of the LS values of 2D-SWE were significantly higher than those of p-SWE for diagnosing significant fibrosis (0.965 vs. 0.872, p = 0.022) and cirrhosis (0.994 vs. 0.886, p = 0.042). In conclusion, 2D-SWE is more reliable and accurate than p-SWE for diagnosing hepatic fibrosis.

Size-reduced fexuprazan 20 mg demonstrated the optimal bioavailability and bioequivalence with the reference formulation.

Fexuprazan (DWP14012), a potassium-competitive acid blocker, is a medical formulation prescribed to inhibit the secretion of gastric acid. The present study encompasses a comparative evaluation of pharmacokinetic (PK) analysis between the previous (reference) and size-reduced (test) formulation of fexuprazan 20 mg in healthy subjects. The study employed a randomized, open-label, single-dose, 2-sequence, 2-period, crossover design with a 7-day wash-out between periods. A total of 24 subjects were enrolled in this randomized study. During each period, the 21 subjects received either the test or reference formulation. Blood samples were collected at multiple time point ranging from 0 (pre-dose) to 48 hours post-dosing for PK analysis. The calculated PK parameters were considered bioequivalent when the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) were within the bioequivalence limit of 0.8-1.25. Safety and tolerability were included in the evaluation. A total of 20 subjects completed the study. Point estimates (90% CIs) of the GMRs were 1.1014 (0.9892-1.2265) for the maximum plasma concentration and 1.0530 (0.9611-1.1536) for the area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration, between the test and reference formulations. The reference and size-reduced test formulations of fexuprazan were well tolerated with no reports of serious adverse events. In conclusion, size-reduced and previous formulations of fexuprazan 20 mg were bioequivalent with regard to PKs, safety and tolerability.

Loss of F-Box and Leucine Rich Repeat Protein 5 (FBXL5) Expression Is Associated With Poor Survival in Patients With Hepatocellular Carcinoma After Curative Resection: A Two-institute Study.

BACKGROUND/AIM: Alteration of F-box and leucine-rich repeat protein 5 (FBXL5), an iron-sensing ubiquitin ligase, might be related with carcinogenesis of hepatocellular carcinoma (HCC), by disturbing cellular iron homeostasis. However, the clinical implications of FBXL5 expression using patient samples need to be elucidated. PATIENTS AND METHODS: We collected HCC tissue samples from two institutes: Samsung Medical Center (n=259) and Hallym University Sacred Heart Hospital (n=115) and evaluated FBXL5 expression using immunohistochemistry. Using cut-off values determined by X-tile software, association between FBXL5 expression and several clinicopathological parameters was investigated. For external validation, the Cancer Genome Atlas (TCGA) cohort was used. RESULTS: The best cutoff value for FBXL5 IHC expression associated with recurrence-free survival (RFS) was 5%. Low FBXL5 expression was found in 18.7% of the total 374 HCCs and was associated with non-viral etiology (p=0.019). Low FBXL5 expression was related with inferior disease-specific survival (DSS, p=0.002) and RFS (p=0.001) and also was an independent prognostic factor for DSS and RFS. In addition, cases with low FBLX5 mRNA levels showed inferior DSS and RFS (p<0.001 and p=0.002, respectively) compared to high FBLX5 mRNA levels in the TCGA cohort. CONCLUSION: Down-regulation of FBXL5 expression in HCCs might be associated with poor prognosis. FBXL5 might be a prognostic biomarker of HCCs and a potential therapeutic target in conjunction with iron homeostasis.