Prognostic Value of Erythroblastic Leukemia Viral Oncogene Homolog 2 and Neuregulin 4 in Hepatocellular Carcinoma.

Although the roles of erythroblastic leukemia viral oncogene homolog 2 (ERBB2), neuregulin 4 (NRG4), and mitogen-inducible gene 6 (MIG6) in epidermal growth factor receptor signaling in hepatocellular carcinoma (HCC) and other malignancies have been previously investigated, the prognostic value of their serum levels in HCC remains undetermined. In the present study, correlations between serum levels and tumor characteristics, overall survival, and tumor recurrence were analyzed. Furthermore, the prognostic potential of the serum levels of these biomarkers was evaluated relative to that of alpha-fetoprotein. Both ERBB2 and NRG4 correlated with the Barcelona Clinic Liver Cancer stage, ERBB2 correlated with the tumor-maximal diameter, and NRG4 correlated with a tumor number. Cox proportional hazards regression analysis revealed that ERBB2 (hazard ratio [HR], 2.719; p = 0.007) was an independent prognostic factor for overall survival. Furthermore, ERBB2 (HR, 2.338; p = 0.002) and NRG4 (HR, 431.763; p = 0.001) were independent prognostic factors for tumor recurrence. The products of ERBB2 and NRG4 had a better area under the curve than alpha-fetoprotein for predicting 6-month, 1-year, 3-year, and 5-year mortality. Therefore, these factors could be used to evaluate prognosis and monitor treatment response in patients with HCC.

CT-based Hounsfield unit values reflect the degree of steatohepatitis in patients with low-grade fatty liver disease.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Ultrasound, the most used tool for diagnosing NAFLD, is operator-dependent and shows suboptimal performance in patients with mild steatosis. However, few studies have been conducted on whether alternative noninvasive methods are useful for diagnosing mild hepatic steatosis. Also, little is known about whether noninvasive tests are useful for grading the severity of hepatic steatosis or the degree of intrahepatic inflammation. Therefore, we aimed to evaluate whether the HSI, the FLI and HU values in CT could be used to discriminate mild hepatic steatosis and to evaluate the severity of hepatic steatosis or the degree of intrahepatic inflammation in patients with low-grade fatty liver disease using liver biopsy as a reference standard. METHODS: Demographic, laboratory, CT imaging, and histological data of patients who underwent liver resection or biopsy were analyzed. The performance of the HSI, HU values and the FLI for diagnosing mild hepatic steatosis was evaluated by calculating the area under the receiver operating characteristic curve. Whether the degree of hepatic steatosis and intrahepatic inflammation could be predicted using the HSI, HU values or the FLI was also analyzed. Moreover, we validate the results using magnetic resonance imaging proton density fat fraction as an another reference standard. RESULTS: The AUROC for diagnosing mild hepatic steatosis was 0.810 (p < 0.001) for the HSI, 0.732 (p < 0.001) for liver HU value, 0.802 (p < 0.001) for the difference between liver and spleen HU value (L-S HU value) and 0.813 (p < 0.001) for the FLI. Liver HU and L-S HU values were negatively correlated with the percentage of hepatic steatosis and NAFLD activity score (NAS) and significantly different between steatosis grades and between NAS grades. The L-S HU value was demonstrated the good performance for grading the severity of hepatic steatosis and the degree of intrahepatic inflammation. CONCLUSIONS: The HU values on CT are feasible for stratifying hepatic fat content and evaluating the degree of intrahepatic inflammation, and the HSI and the FLI demonstrated good performance with high sensitivity and specificity in diagnosing mild hepatic steatosis.

Outcomes of laparoscopic radiofrequency ablation versus percutaneous radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND: Few studies have compared the therapeutic outcomes in patients with HCC who underwent laparoscopic radiofrequency ablation (LRFA) versus percutaneous radiofrequency ablation (PRFA) for hepatocellular carcinoma (HCC). Therefore, this study compared the recurrence and survival outcomes of the two RFA methods in patients with HCC. METHODS: Recurrence and overall survival outcomes were evaluated in 307 patients who underwent LRFA (n = 151) or PRFA (n = 156) as a treatment method for de novo HCC. Inverse probability of treatment weighting (IPTW) analysis was performed to reduce the impact of treatment selection bias. RESULTS: There were no significant differences in major baseline characteristics between the LRFA and PRFA groups. However, the proportion of cirrhotic patients was higher in the LRFA group, whereas the LRFA group had more tumors and a more advanced tumor-node-metastasis stage. Moreover, the mean tumor size was significantly larger in the LRFA group than in the PRFA group. In a multivariate analysis, serum albumin level, more than three tumors, and the RFA method were identified as significant predictors of recurrence-free survival. Moreover, for the overall survival of HCC patients, serum albumin levels, days of hospital stay during RFA, and the RFA method were independent predictors. In the IPTW-adjusted analysis, the LRFA group showed significantly higher recurrence-free survival and overall survival. CONCLUSIONS: Our study revealed that compared with PRFA, LRFA was associated with longer recurrence-free survival and favorable overall survival in patients with HCC. Therefore, LRFA should be considered the primary therapy in patients with HCC eligible for RFA.

Status of Using Complementary and Alternative Medicine among Patients with Cancer in Korea: an Online Survey of Online Cancer Support Groups (KCSG PC21-20).

PURPOSE: An increasing number of patients with cancers are interested in complementary and alternative medicine (CAM), which lacks scientific evidence. This study aimed to determine how CAM was used and how media affected patients in online cancer support groups (OCSG). Materials and Methods: Between August 18 and September 12, 2021, an online survey was conducted among the members of OCSG. The survey consisted of five parts: baseline characteristics, attitudes toward and experience with CAM, source of information and reliabilities, experience with anthelmintics, and online health information literacy and usage. RESULTS: Among the 644 responders, a total of 221 patients with cancer completed the survey, and 78.2% (173/221) used CAM. The users' median age was 52 years; 46.8% were males, and 43.9% had metastatic disease. Fifty-three CAM users (30.6%) discussed their physicians about CAM. In addition, 16.2% (28/173) of CAM users had the experience of anthelmintics. The use of anthelmintics in patients with cancers was associated with younger age (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.84 to 0.95), metastatic disease (OR, 10.88; 95% CI, 3.39 to 34.86), previous exposure to CAM information (OR, 5.57; 95% CI, 1.01 to 30.72), experience with more types of CAM (OR, 1.98; 95% CI, 1.29 to 3.05), and side effects (OR, 5.10; 95% CI 1.46 to 17.75). CONCLUSION: Use of anthelmintics, a CAM of which information is widespread online, is affected by several factors. This study will provide essential information for developing a CAM management strategy in this digital age.

Validation and Comparison of the Japanese Score and Other Scores in Patients with Nonvariceal Upper Gastrointestinal Bleeding: A Retrospective Study.

BACKGROUND: Various scoring systems have been developed to predict endoscopic intervention, mortality, and rebleeding in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB); however, they have not been sufficiently validated in Korea. Therefore, this study aimed to evaluate the usefulness of several scoring systems in Korea by validating and comparing the Japanese score and other scores in Korean people with NVUGIB. METHODS: The medical records of 1,368 patients with NVUGIB were reviewed to collect statistical, clinical, laboratory, and endoscopic data. The Japanese score, ABC score, Glasgow-Blatchford Bleeding Score (GBS), and MAP score were calculated retrospectively at a single research institution. These scores for predicting the need for endoscopic intervention, mortality, and rebleeding were calculated and evaluated using the area under the receiver operating characteristic curve. RESULTS: Of 1,368 patients, 88.5% required endoscopic intervention, 4.1% died within 30 days, and 12.6% experienced rebleeding. The Japanese score was effective for predicting endoscopic intervention, and the ABC score was best for predicting 30-day mortality. Sex, age, hematemesis, blood urea nitrogen, and American Society of Anesthesiologists score were found to be predictors of the need for endoscopic intervention. CONCLUSION: The Japanese score did not prove useful in Koreans with upper gastrointestinal bleeding. Additional research is needed due to the limitations of a retrospective study conducted in a single research institute.

The Tri-iodothyronine (T3) Level Is a Prognostic Factor for Patients With Advanced NSCLC: Receiving Immune Checkpoint Inhibitors and Is Associated With Liver Metastasis.

Background: Endocrine hormones influence tumor progression and the response to treatment. Despite the importance of immune checkpoint inhibitors (ICIs) as treatments for advanced non-small cell lung cancer (NSCLC), few studies have explored the effects of hormone levels in NSCLC patients on the effectiveness of ICI therapies. We thus investigated the effects of baseline blood markers in patients with advanced NSCLC on ICI treatments. Methods: Patients with advanced NSCLC who received programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors at Chungnam National University Hospital between December 2016 and November 2020 and who lacked any history of thyroid gland-related diseases were analyzed retrospectively. We collected clinical information and baseline laboratory data, including the levels of endocrine hormones, cytokines, complete blood counts (CBCs), and peripheral blood chemistry panels. We explored the relationships of hormone levels with clinical outcomes (overall survival [OS], progression-free survival [PFS], and best response), liver metastasis, and blood markers using the Kaplan-Meier method, Cox's proportional hazards regression, and logistic regression. Results: A total of 113 patients were enrolled. A shorter PFS was independently associated with liver metastasis, higher cortisol levels, and lower hemoglobin (Hb) levels; a shorter OS was associated with liver metastasis, lower tri-iodothyronine (T3) levels, higher lactate dehydrogenase (LDH) levels, and lower albumin levels. Patients with low T3 levels exhibited a shorter PFS and OS, and a poorer best response. Patients with low T3 levels tended to have higher disease progression rates, lower levels of adrenocorticotropic hormone (ACTH), C-peptide, albumin, Hb, and neutrophil-to-lymphocyte ratio, and higher levels of interleukin (IL)-6, white blood cells, platelets, compared with those with normal T3 levels. We found a significant association between a low T3 level and liver metastasis. Conclusions: We found the baseline T3 level was associated with both prognosis and the response to ICIs in patients with advanced NSCLC, probably reflecting impaired liver function and systemic inflammation induced by the interaction of T3 with other biomarkers, such as IL-6, ACTH, cortisol, C-peptide, Hb, LDH, and albumin.

Early Supported Discharge and Transitional Care Management After Stroke: A Systematic Review and Meta-Analysis.

Objective: To investigate the available evidence on early supported discharge (ESD) and transitional care (TC) delivery service in patients with cerebrovascular disease. Methods: A systematic literature search was conducted to collect all available evidence on the use of ESD and TC services. We included cluster-randomized pragmatic trials or randomized controlled trials (RCTs) that recruited patients with stroke or transient ischemic attack to receive either conventional care or any care service intervention that included rehabilitation or support provided by professional medical personnel with the aim of accelerating and supporting home discharge. Relevant data were electronically searched through international databases (Cochrane Library, EMBASE, and PubMed) and incorporated into a summary grid to investigate research outcomes and provide a narrative synthesis. Furthermore, we compared the outcomes in terms of length of hospital stay, patient and caregiver outcomes, and mortality through meta-analysis. Results: We identified and included a total of 20 publications of various original randomized studies. There were 18 studies conducted in western countries and 2 in eastern countries. The meta-analysis revealed a tendency that ESD or TC could decrease the length of hospital stay more than the usual care [standardized mean difference (SMD) -0.13; 95% confidence interval (CI) -0.31 to 0.04 days; P = 0.14]. Moreover, there was a tendency that ESD resulted in better activities of daily living (ADL) than usual care (SMD 0.29; 95% CI -0.04 to 0.61; P = 0.08). Patient outcome based on modified Rankin scale (mRS) score (SMD -0.11; 95% CI -0.38 to 0.17; P = 0.45] and mortality (odds ratio 0.80; 95% CI 0.56-1.17; P = 0.25) did not reveal any significant difference. The Caregiver Strain Index revealed no difference. Conclusion: We did not find a large effect size for the use of TC and ESD. When implementing the TC and ESD model from western to Asian countries, services should be prepared and implemented in accordance with national medical rehabilitation pathways for cerebrovascular disease.

Comparative Pharmacokinetics Between a Fixed-Dose Combination of Pitavastatin/Valsartan 4/160 mg and the Corresponding Individual Components Through a Partial Replicated Crossover Design in Healthy Male Subjects.

Hypertension and hyperlipidemia are often comorbid, requiring combination therapies of antihypertensive drugs and antihyperlipidemia drugs. Taking 1 fixed-dose combination (FDC) may increase patient compliance rather than taking each of the drugs separately. This study aimed to evaluate the pharmacokinetic bioequivalence between an FDC of pitavastatin/valsartan 4/160 mg and the corresponding individual components. Considering that valsartan is a highly variable drug for maximum plasma concentration (Cmax ), an open-label, randomized, partial replicated crossover study was conducted in 54 healthy subjects. The subjects received a single oral dose of the FDC of pitavastatin/valsartan 4/160 mg in 1 period or the corresponding individual components in the other 2 periods. The geometric mean ratios and their 90%CIs of the FDC to the corresponding individual components for Cmax and area under the concentration-time curve from time 0 to the last measurable time point were 1.05 (90%CI, 0.96-1.15) and 0.10 (90%CI, 0.95-1.04) for pitavastatin and 1.15 (90%CI, 1.06-1.25) and 1.06 (0.99-1.14) for valsartan, respectively. The geometric mean ratios (90%CIs) for area under the concentration-time curve from time 0 to the last measurable time point and Cmax of both drugs were included in the bioequivalence criteria. In conclusion, the FDC of pitavastatin/valsartan 4/160 mg showed pharmacokinetic equivalence with the corresponding individual components.

Validation and modification of existing mortality prediction models for lower gastrointestinal bleeding: a retrospective study.

BACKGROUND: Lower gastrointestinal bleeding (LGIB) often subsides without medical intervention; however, in some cases, the bleeding does not stop and the patient's condition worsens. Therefore, predicting severe LGIB in advance can aid treatment. This study aimed to evaluate variables related to mortality from LGIB and propose a scoring system. METHODS: In this retrospective study, we reviewed the medical records of patients who visited the emergency room with hematochezia between January 2016 and December 2020. Through regression analysis of comorbidities, medications, vital signs, laboratory investigations, and duration of hospital stay, variables related to LGIB-related mortality were evaluated. A scoring system was developed and the appropriateness with an area under the receiver operating characteristics curve (AUROC) was evaluated and compared with other existing models. RESULTS: A total of 932 patients were hospitalized for LGIB. Variables associated with LGIB-related mortality were the presence of cancer, heart rate > 100 beats/min, blood urea nitrogen level ≥ 30 mg/dL, an international normalized ratio > 1.50, and albumin level ≤ 3.0 g/dL. The AUROCs of the models CNUH-4 and CNUH-5 were 0.890 (p < 0.001; cutoff, 2.5; 95% confidence interval, 0.0851-0.929) and 0.901 (p < 0.001; cutoff, 3.5; 95% confidence interval, 0.869-0.933), respectively. CONCLUSIONS: The model developed for predicting the risk of LGIB-related mortality is simple and easy to apply clinically. The AUROC of the model was better than that of the existing models.

Bioequivalence for a Fixed-Dose Combination Formulation of Bazedoxifene and Cholecalciferol Compared With the Corresponding Single Entities Given Together.

A fixed-dose combination (FDC) formulation of bazedoxifene 20 mg and cholecalciferol 8 mg was developed to increase medication compliance and convenience for osteoporosis patients. This study was conducted to demonstrate bioequivalence by comparing the pharmacokinetic (PK) profiles and tolerability of an FDC tablet and the individual component tablets. A randomized, open-label, single-dosing, 2-treatment, 2-period, 2-sequence crossover study was conducted in 52 healthy subjects. All subjects were randomly assigned to 2 sequences, and they received FDC tablets of bazedoxifene and cholecalciferol and individual component tablets. Serial blood samples for PK evaluation were collected up to 24 hours predose and 120 hours postdose, and the PK parameters were estimated by noncompartmental methods. Throughout the study, tolerability was assessed based on adverse events, vital signs, and clinical laboratory tests. Of the enrolled 52 subjects, 47 subjects completed the study. The results, the geometric mean ratios (GMRs) and 90% confidence intervals (90%CIs), of bazedoxifene Cmax and AUC0-t for FDC to single entities given together were 0.98 (0.91-1.05) and 1.02 (0.97-1.07), respectively. The GMRs (90%CIs) of cholecalciferol Cmax and AUC0-t for FDC to single entities given together were 0.96 (0.91-1.00) and 0.94 (0.90-0.99), respectively. Overall, the GMRs (90%CIs) of the PK parameter of bazedoxifene and cholecalciferol fell within the conventional bioequivalence range of 0.8-1.25. There were no clinically significant differences in the safety profile between the 2 treatments. In conclusion, this study confirmed the development of a new FDC drug by demonstrating that the FDC formulation of bazedoxifene and cholecalciferol is biologically equivalent to the coadministered individual formulations.

Predictor of Subungual Melanoma against Benign Longitudinal Melanonychia: A Retrospective Cohort Study from Korea.

BACKGROUND: Longitudinal melanonychia (LM) is a common clinical finding. Most cases of LM are benign, and a wait-and-see approach is preferred in the management of this condition. Nevertheless, it is important for clinicians to distinguish subungual melanoma (SUM) from other benign LMs. OBJECTIVE: To evaluate the demographic and clinicopathologic characteristics of LM in the Korean population and to identify the predictor of SUM against other benign conditions. METHODS: This was a single-center retrospective cohort study including patients who underwent nail biopsy for LM from January 2000 to May 2019. To identify the predictor of SUM, receiver operating characteristic (ROC) analyses was performed. RESULTS: A total of 68 cases of biopsy-proven LM were included in the analysis. Among the 68 cases, 8 were SUM. In univariable analysis, patients diagnosed with SUM were older (p=0.035) and had a longer disease duration (p=0.004). They also showed multicolor pigmentation of LM (p=0.022), a larger width of LM (p<0.001), and associated nail plate dystrophy (p=0.010) than patients diagnosed with benign conditions. In multivariable logistic regression, width of LM showed statistical significance (odds ratio, 1.083; 95% confidence interval, 1.018~1.153). ROC analysis suggested that an LM width >28% of the whole nail was the predictor of SUM (area under the curve=0.883; p<0.001). CONCLUSION: SUM has distinct demographic and clinical features. The width of LM can predict SUM against other benign LMs.

Which scoring system should be used for non-variceal upper gastrointestinal bleeding? Old or new?

BACKGROUND AND AIM: Several scoring systems for predicting outcomes in patients with non-variceal upper gastrointestinal bleeding (NVUGIB) have recently been devised, but not sufficiently validated. We compared the predictive accuracy of several scoring systems and assessed the usefulness of new scoring systems. METHODS: The medical records of 1048 patients with NVUGIB were reviewed to collect demographic, clinical, laboratory, and endoscopic data. The areas under the receiver operating characteristic curve (AUROCs) were calculated for the ABC, new Japanese scoring system, Progetto Nazionale Emorrhagia Digestiva (PNED), and other scores to compare their predictive accuracy for 30-day mortality, therapeutic intervention, rebleeding, and prolonged hospital stay (≥ 10 days). Outcome predictors were identified by multivariate analysis. RESULTS: The ABC, new Japanese scoring system, and PNED scores best predicted 30-day mortality (AUROC 0.907), need for therapeutic intervention (AUROC 0.707), and rebleeding (AUROC 0.874), respectively (all P < 0.001). The ABC and PNED scores were similarly better at predicting prolonged hospital stay (ABC AUROC: 0.765; PNED AUROC: 0.790; both P < 0.001). Thirty-day mortality was related to sex, systolic blood pressure (SBP), syncope, estimated glomerular filtration rate (eGFR), albumin, heart failure, disseminated malignancy, chronic obstructive pulmonary disease (COPD), and liver cirrhosis. Sex, age, SBP, hematemesis, blood urea nitrogen, and eGFR independently predicted the need for therapeutic intervention. Sex, SBP, pulse, albumin level, heart failure, disseminated malignancy, and COPD predicted rebleeding. CONCLUSION: The outcomes of patients with NVUGIB were better predicted by newly developed than by old scoring systems.

Comparison of pharmacokinetics and safety characteristics between two olopatadine hydrochloride 5 mg tablet formulations in healthy Korean subjects.

Histamine acts by binding to four histamine receptors (H1 to H4), of which the H1 is known to participate in dilate blood vessels, bronchoconstriction, and pruritus. Olopatadine hydrochloride blocks the release of histamine from mast cells and it inhibits H1 receptor activation. Olopatadine hydrochloride is anti-allergic agent that is effectively used. The object of this study had conducted to compare the pharmacokinetics (PKs) and safety characteristics between olopatadine hydrochloride 5 mg (test formulation) and olopatadine hydrochloride 5 mg (reference formulation; Alerac ®) in Korean subjects. This study had conducted an open-label, randomized, fasting condition, single-dose, 2-treatment, 2-period, 2-way crossover. Subjects received single-dosing of reference formulation or test formulation in each period and blood samples were collected over 24 hours after administration for PK analysis. A wash-out period of 7 days was placed between the doses. Plasma concentration of olopatadine were determined using liquid chromatography-tandem spectrometry mass (LC-MS/MS). A total of 32 subjects were enrolled and 28 subjects completed. There were not clinical significantly different in the safety between two treatment groups for 32 subjects who administered the study drug more than once. The geometric mean ratio of test formulation to reference formulation and its 90% confidence intervals for The peak plasma concentration (Cmax) and the areas under the plasma concentration-time curve from 0 to the last concentration (AUClast) were 1.0845 (1.0107-1.1637) and 1.0220 (1.0005-1.0439), respectively. Therefore, the test formulation was bioequivalent in PK characteristics and was equally safe as the reference formulation. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0005943.

Hospital-level variation in follow-up strategies after percutaneous coronary intervention, revealed in health claims data of Korea.

This study sought to determine hospital variation in the use of follow-up stress testing (FUST) and invasive coronary angiography (FUCAG) after percutaneous coronary intervention (PCI). The claims records of 150,580 Korean patients who received PCI in 128 hospitals between 2008 and 2015 were analyzed. Patient were considered to have undergone FUST and FUCAG, when these testings were performed within two years after discharge from the index hospitalization. Hierarchical generalized linear and frailty models were used to evaluate binary and time-to-event outcomes. Hospital-level risk-standardized FUCAG and FUST rates were highly variable across the hospitals (median, 0.41; interquartile range [IQR], 0.27-0.59; median, 0.22; IQR, 0.08-0.39, respectively). The performances of various models predicting the likelihood of FUCAG and FUST were compared, and the best performance was observed with the models adjusted for patient case mix and individual hospital effects as random effects (receiver operating characteristic curves, 0.72 for FUCAG; 0.82 for FUST). The intraclass correlation coefficients of the models (0.41 and 0.68, respectively) indicated that a considerable proportion of the observed variation was related to individual institutional effects. Higher hospital-level FUCAG and FUST rates were not preventive of death or myocardial infarction. Increased repeat revascularizations were observed in hospitals with higher FUCAG rates.

Pharmacokinetic equivalence of CT-P17 to high-concentration (100 mg/ml) reference adalimumab: A randomized phase I study in healthy subjects.

This study aimed to demonstrate pharmacokinetic (PK) equivalence of a single dose of the proposed adalimumab biosimilar CT-P17 to United States-licensed adalimumab (US-adalimumab) and European Union-approved adalimumab (EU-adalimumab). This double-blind, parallel-group, phase I trial (clinicaltrials.gov NCT03970824) was conducted at 10 hospitals (Republic of Korea), in which healthy subjects (1:1:1) were randomized to receive a single 40 mg (100 mg/ml) subcutaneous injection of CT-P17, US-adalimumab, or EU-adalimumab. Primary end points were PK equivalence in terms of: area under the concentration-time curve from time zero to infinity (AUC0-inf ); AUC from time zero to the last quantifiable concentration (AUC0-last ); and maximum serum concentration (Cmax ). PK equivalence was concluded if 90% confidence intervals (CIs) for percent ratios of geometric least squares means (GLSMs) for pairwise comparisons were within the equivalence margin of 80-125%. Additional PK end points, safety, and immunogenicity were evaluated. Of the 312 subjects who were randomized (103 CT-P17; 103 US-adalimumab; 106 EU-adalimumab), 308 subjects received study drug. AUC0-inf , AUC0-last , and Cmax were equivalent among CT-P17, US-adalimumab, and EU-adalimumab, because 90% CIs for the ratios of GLSMs were within the 80-125% equivalence margin for each pairwise comparison. Secondary PK end points, safety, and immunogenicity were similar between treatment groups. In conclusion, PK equivalence for single-dose administration of CT-P17, EU-adalimumab, and US-adalimumab was demonstrated in healthy adults. Safety and immunogenicity profiles were comparable between treatment groups and consistent with previous reports for adalimumab biosimilars.

Development and Validation of a Risk Scoring Model for Early Prediction of Severe Colon Ischemia.

BACKGROUND: Colon ischemia (CI) is injury to the intestines secondary to insufficient blood flow. Its clinical severity can range from mild to life-threatening. AIMS: To investigate predictive risk factors for CI and propose a scoring model for severe outcomes. METHODS: We retrospectively analyzed the medical records of patients admitted to Chungnam National University Hospital from January 2010 to December 2018. CI was defined as severe when patients required surgery immediately or after initial conservative management, death occurred after hospitalization, or symptoms persisted after 2 weeks. By controlling for possible confounders from the logistic regression analysis, we obtained a new risk scoring model for the early prediction of severe CI. Furthermore, using the area under the receiver operating characteristics curve (AUROC), we assessed the accuracy of the model. RESULTS: A total of 274 patients endoscopically diagnosed with CI were included, of whom 181 had severe CI. In the multivariate analysis, tachycardia, elevated C-reactive protein, Favier endoscopic classification stage ≥ 2, and history of hypertension were independently and significantly associated with severe CI. The AUROC of the model was 0.749. CONCLUSIONS: This risk scoring model based on the presence of tachycardia, elevated C-reactive protein level, unfavorable endoscopic findings by Favier's classification, and the history of hypertension could be used to predict severe CI outcomes at an early stage.

Comparison of conventional and modified endoscopic mucosal resection methods for the treatment of rectal neuroendocrine tumors.

BACKGROUND/AIM: Small rectal neuroendocrine tumors (NETs) confined to the submucosa are endoscopically resectable. Because most rectal NETs are submucosal tumors, conventional endoscopic mucosal resection (cEMR) may not result in a complete resection. This study investigated whether modified EMRs, namely endoscopic submucosal resection with ligation (ESMR-L), EMR with precutting (EMR-P), and strip biopsy are superior to cEMR for achieving histologically complete resection (HCR) of rectal NETs. METHODS: Medical records of 215 patients who were treated with endoscopic resections for rectal NETs between January 2011 and July 2019 were retrospectively enrolled. Of the patients, 110, 33, 29, and 43 underwent cEMR, ESMR-L, EMR-P, and strip biopsy, respectively. For each method, HCR and en bloc resection rates, procedure times, and complication rates were measured. RESULTS: HCR was achieved with cEMR, EMR-P, ESMR-L, and strip biopsies for 74.5%, 90.9%, 93.1%, and 90.7% of cases, respectively. The HCR rate for cEMR was inferior to those of the modified EMRs (p = 0.045 for cEMR vs. EMR-P; p = 0.031 for cEMR vs. ESMR-L; p = 0.027 for cEMR vs. strip biopsy). Among the three modified EMRs, there was no significant difference in achieving HCR (p = 1.000). En bloc resection (p = 0.096) and complication rates (p = 0.071) were not significantly different among the four EMR methods, although EMR-P required the longest procedure time (p = 0.000). CONCLUSIONS: All three modified EMRs are superior to cEMR and are equally effective for achieving HCR of rectal NETs.

Changes in poor self-rated health status among elderly Koreans over 10 years: Community Health Survey 2008-2017.

AIM: This study investigated the change in self-rated health (SRH) status among elderly Koreans and sought influential factors affecting SRH by reference to data collected during the Korean Community Health Survey 2008-2017. METHODS: We obtained raw data from the Korea Community Health Survey for 10 years (2008-2017), which included sociodemographic and health information on Koreans aged ≥65 years (242 552 men and 349 586 women). SRH was measured using the SRH scale and divided into not-poor and poor. Logistic regression analyses of poor SRH were performed using a weighted sampling method and interaction models (year × variables) to represent the entire Korean elderly population and estimate the changes in poor SRH over time. RESULTS: The proportion of elderly subjects in the population increased over 10 years. After adjusting for all confounding variables, the weighted adjusted odds ratios for poor SRH decreased consistently between 2008 and 2017 (men: 0.64, 95% confidence interval 0.50-0.81; women: 0.62, 0.46-0.83). The odds ratios for poor SRH were markedly higher in subjects who reported being stressed (men: 7.02, 5.89-8.38; women 6.14, 5.33-7.08) and those who lacked formal education (men: 2.42, 2.18-2.69; women 3.12, 2.59-3.75) over times. CONCLUSIONS: Despite the increase in the proportion of the elderly, poor SRH among elderly Koreans decreased over the past 10 years. Poor SRH was associated with high-level perceived stress and a lower educational level in both elderly men and women. Geriatr Gerontol Int 2020; 20: 1190-1195.

Self-expandable metal stent of esophagogastric junction versus pyloric area obstruction in advanced gastric cancer patients: Retrospective, comparative, single-center study.

Upper gastrointestinal stenting is a palliative treatment for relieving symptoms such as nausea, vomiting, and dietary intake in patients with obstruction due to inoperable advanced stomach cancer. Self-expandable metal stent (SEMS) implantation for malignant obstruction has recently become more effective, safer, and less expensive than operative modality. It also has better short-term outcomes, particularly a shorter hospital stay and a more rapid return to oral intake, than surgical treatment. However, there is no comparative analysis regarding the efficacy, side effects, and survival rate of stenting between the esophagogastric junction (EGJ) and pyloric obstructions.To compare the prognoses and complications after SEMS implantation between EGJ and pyloric obstructions in advanced gastric cancer.Among advanced gastric cancer patients with gastrointestinal obstruction diagnosed from January 2008 to December 2017 at the Gastroenterology Department of Chungnam National University Hospital, 42 and 76 patients presented with EGJ (EGJ obstruction group) and gastric pyloric obstructions (pyloric obstruction group), respectively. We retrospectively reviewed the survival period, changes in food intake, and complications of these patients before and after SEMS placement.The prevalences of aspiration pneumonia were 11.9% (5/42) and 2.6% (2/76) in the EGJ and pyloric obstruction groups, respectively, before SEMS placement (P value: .041). Other symptoms associated with gastric malignant obstruction were not statistically different between the groups. Success rate and adverse events did not significantly differ between the EGJ and pyloric obstruction groups. There was no difference in frequency of stent reinsertion procedures performed owing to reobstruction, but the reprocedure average period was statistically significantly longer in the EGJ obstruction group [EGJ obstruction: 158.3 days (±42.4); pyloric obstruction: 86.0 days (±29.1)] (P value: .022). As an index of improved dietary status, the Gastric Outlet Obstruction Scoring System score was not significantly different between the groups before and after SEMS placement.The EGJ and pyloric obstruction groups did not significantly differ in prognosis or complication rates. However, EGJ stent was more stable than pyloric stent when reobstruction was considered.

A randomized, open-label, crossover study to compare the safety and pharmacokinetics of two tablet formulations of tenofovir (tenofovir disoproxil and tenofovir disoproxil fumarate) in healthy subjects.

PURPOSE: This study was performed to compare the pharmacokinetic properties and assess bioequivalence for the test formulation (HUG116 tablet; tenofovir disoproxil) and reference formulation (Viread tablet; tenofovir disoproxil fumarate). MATERIALS AND METHODS: A randomized, open-label, single-dosing, two-treatment, two-period, two-sequence cross-over study was conducted in 50 healthy subjects. All subjects were randomly assigned to one of the two sequences, and they received a single dose of test or reference formulation in the first period and the alternative formulation during the next period under fasting conditions. Serial blood samples for pharmacokinetic evaluation were collected up to 72 hours post dose, and the pharmacokinetic parameters were estimated by noncompartmental methods. Throughout the study, tolerability was assessed based on adverse events, vital signs, and clinical laboratory tests. RESULTS: The test formulation showed similar pharmacokinetic profiles to those of the reference formulation. The geometric mean ratio and 90% confidence interval (CI) of the test formulation to the reference formulation for maximum plasma concentration (Cmax) was 0.93 (0.87 - 0.99), and the corresponding value for the area under the concentration-time curve from time zero to time of last quantifiable concentration (AUCt) was 0.94 (0.89 - 0.99). Both CIs were within the conventional bioequivalence range of 0.8 - 1.25. The tolerability profile was not significantly different between the test and reference formulations. CONCLUSION: This study found that the PKs of the test formulation (HUG116 tablet; tenofovir disoproxil) and reference formulation (Viread tablet; tenofovir disoproxil fumarate) were similar, and the test formulation met the regulatory criteria for assuming bioequivalence with the reference formulation.