Background/Aims: Quick sequential organ failure assessment (qSOFA) is believed to identify patients at risk of poor outcomes in those with suspected infection. We aimed to evaluate the ability of modified qSOFA (m-qSOFA) to identify high-risk patients among those with acutely deteriorated chronic liver disease (CLD), especially those with acute-onchronic liver failure (ACLF). Methods: We used data from both the Korean Acute-on-Chronic Liver Failure (KACLiF) and the 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 an 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 those with low m-qSOFA (Ps<0.05). Subgroup analysis by ACLF showed that patients with high m-qSOFA had lower TFS than those 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 day 7 had a significantly lower 1-month TFS than those with high m-qSOFA at baseline but low m-qSOFA on day 7 (52.6% vs. 89.4%, P<0.001 in KACLiF and 26.9% vs. 61.5%, P<0.001 in AARC). Conclusions Baseline and dynamic changes in m-qSOFA may identify patients with a high risk of developing organ failure and short-term mortality among CLD patients with acute deterioration.

Methyl salicylate is widely used in various topical products, including sports creams, ointments, patches, and oral hygiene products. These products are mainly used for localized treatment of musculoskeletal pain. Given their intended topical application, their ingestion can result in salicylic acid poisoning due to their high concentrations of methyl salicylate. Symptoms of salicylic acid poisoning may include dizziness, vomiting, hallucinations, seizures, and, in severe cases, unconsciousness, respiratory failure, and circulatory disorders. We report a case of a 71-year-old male who ingested Mensolatum Lotion to commit suicide and died.

The aim of this study was to elucidate the diatomological investigation and the forensic role of spleen tissue in cases of drowning or non-drowning. Specimens of spleen tissue and other organ tissue from 136 drowning cases, as well as 21 cases where death resulted from causes other than drowning (acting as controls), were examined for the presence of diatoms. The diatom test was performed on all cases using the acid digestion method, involving fumed nitric acid on a hot sand bath. The presence of diatoms in spleen tissue was observed in drowning cases but not in non-drowning cases. Diatoms in spleen tissue showed a positive association with drowning (P=0.011). Among the 136 drowning cases, diatoms were most frequently found in lung tissue (n=134, 99%), followed by spleen (n=33, 24%), kidney (n=28, 21%), liver (n=27, 20%), and heart (n=22, 16%) tissues. Moreover, in 95 cases where putrefaction did not progress, diatoms were detected in spleen tissues in 14 cases, indicating that the highest detection rate among other enclosed organ tissues, excluding lung tissues. Furthermore, a significant correlation was observed between the presence of diatoms in spleen tissue and those in enclosed organs, including the liver, kidney, and heart, but not in lung tissues. Our results revealed a significant correlation between the presence of diatoms in spleen tissue and drowning. Thus, the present study provides evidence that the presence of diatoms in spleen tissue may be a reliable indicator of death by drowning.

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Activation of the NLRP3 inflammasome is critical for host defense as well as the progression of inflammatory diseases through the production of the proinflammatory cytokine IL-1β, which is cleaved by active caspase-1. It has been reported that overactivation of the NLRP3 inflammasome contributes to the development and pathology of acne vulgaris. Therefore, inhibiting activation of the NLRP3 inflammasome may provide a new therapeutic strategy for acne vulgaris. In this study, we investigated whether auranofin, an anti-rheumatoid arthritis agent, inhibited NLRP3 inflammasome activation, thereby effectively treating acne vulgaris.Auranofin suppressed NLRP3 inflammasome activation induced by Propionibacterium acnes, reducing the production of IL-1β in primary mouse macrophages and human sebocytes. In a P. acnes-induced acne mouse model, injection of P. acnes into the ears of mice induced acne symptoms such as redness, swelling, and neutrophil infiltration. Topical application of auranofin (0.5 or 1%) to mouse ears significantly reduced the inflammatory symptoms of acne vulgaris induced by P. acnes injection. Topical application of auranofin led to the downregulation of the NLRP3 inflammasome activated by P. acnes in mouse ear skin. These results show that auranofin inhibits the NLRP3 inflammasome, the activation of which is associated with acne symptoms. The results further suggest that topical application of auranofin could be a new therapeutic strategy for treating acne vulgaris by targeting the NLRP3 inflammasome.

Background/Aims: This study examined the risk factors associated with mortality in cirrhotic patients hospitalized with variceal bleeding, and evaluated the effects of acute-on-chronic liver failure (ACLF) on the prognosis of these patients. Methods: This study was retrospectively conducted on patients registered in the Korean acute-on-chronic liver failure study cohort, and on 474 consecutive cirrhotic patients hospitalized with variceal bleeding from January 2013 to December 2013 at 21 university hospitals. ACLF was defined as described by the European Association for the Study of Liver-Chronic Liver Failure Consortium. Results: Among a total of 474 patients, 61 patients were diagnosed with ACLF. The cumulative overall survival (OS) rate was lower in the patients with ACLF than in those without (P<0.001), and patients with higher ACLF grades had a lower OS rate (P<0.001). The chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score was identified as a significant prognostic factor in patients hospitalized with variceal bleeding (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.30–1.50; P<0.001), even in ACLF patients with variceal bleeding (HR, 1.32; 95% CI, 1.19–1.46, P<0.001). Concerning the prediction of the mortality risk at 28- and 90-day using CLIF-SOFA scores, c-statistics were 0.895 (95% CI, 0.829–0.962) and 0.897 (95% CI, 0.842–0.951), respectively, and the optimal cut-off values were 6.5 and 6.5, respectively. Conclusions In cirrhotic patients hospitalized with variceal bleeding, the prognosis was poor when accompanied by ACLF, especially depending upon CLIF-SOFA score. CLIF-SOFA model well predicted the 28-day or 90-day mortality for cirrhotic patients who experienced variceal bleeding.

BACKGROUND/AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and brushing cytology are used worldwide to diagnose pancreatic and biliary malignant tumors. Liquid-based cytology (LBC) has been developed and it is currently used to overcome the limitations of conventional smears (CS). In this study, the authors aimed to compare the diagnostic value of the CellPrepPlus (CP; Biodyne) LBC method with CS in samples obtained using EUS-FNA and brushing cytology. METHODS: This study prospectively enrolled 75 patients with pancreatic or biliary lesions from June 2012 to October 2013. For cytological analyses, including inadequate specimens, benign and atypical were further classified into benign, and suspicious and malignant were subcategorized as malignant. Sensitivity, specificity, accuracy, and positive predictive values (PPV) and negative predictive values (NPV) were evaluated. RESULTS: In the EUS-FNA based cytological analysis of pancreatic specimens, CP had a sensitivity of 60.7%; specificity, 100%; accuracy, 77.1%; PPV, 100%; and NPV, 64.5%. CS had a sensitivity of 85.7%; specificity, 100%; accuracy, 91.7%; PPV, 100%; and NPV, 83.3%. In the brushing cytology based analysis of biliary specimens, CP had sensitivity of 53.1%; specificity, 100%; accuracy, 54.5%; PPV, 100%; and NPV, 6.3%. CS had a sensitivity of 78.1%; specificity, 100%; accuracy, 78.8%; PPV, 100%; and NPV, 12.5%. CONCLUSIONS: Our study found that CP had a lower sensitivity because of low cellularity compared with CS. Therefore, CP (LBC) has a lower diagnostic accuracy for pancreatic EUS-FNA based and biliary brush cytology based analyses compared with CS.
Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Humans ; Methods ; Prospective Studies ; Sensitivity and Specificity

OBJECTIVE: Clinical Assessment Interview for Negative Symptoms (CAINS) has recently been developed to improve measurement of negative symptoms in schizophrenia. We performed a multi-center study to validate the Korean version of the CAINS (CAINS-K) and explore potential cultural variation. METHODS: One hundred eighty schizophrenia patients diverse in demographic and illness profile were recruited from four centers in Korea. Along with the CAINS-K, the Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Calgary Depression Scale for Schizophrenia (CDSS), a self-report measure of behavioral inhibition and activation (BIS/BAS) and neurocognitive tasks were administered to verify external validities. RESULTS: The CAINS-K showed high internal-consistency (0.92) and inter-rater reliability (0.77). Exploratory Factor Analysis replicated a two-factor structure of the original scale including motivation/pleasure and expression deficits dimensions. Korean patients tended to report lower pleasure compared to American patients in the prior study. The CAINS-K showed an adequate convergent validity with the SANS, negative symptoms of the BPRS, and BAS. A divergent validity was supported as the CAINS-K showed zero or only weak correlations with other symptoms of the BPRS, depression from the CDSS, and neurocognitive tasks. CONCLUSION: The CAINS-K demonstrated high internal consistency and adequate external validities, and is expected to promote studies on negative symptoms in Korean patients with schizophrenia.
Brief Psychiatric Rating Scale ; Depression ; Humans ; Korea ; Pleasure ; Schizophrenia

BACKGROUND/AIMS: Metronomic chemotherapy (MET) is frequently administered in comparatively low doses as a continuous chemotherapeutic agent. The aim of this study was to evaluate the feasibility and overall survival (OS) of MET compared to sorafenib for advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). METHODS: A total of 54 patients with advanced HCC and PVTT who had undergone MET were analyzed between 2005 and 2013. A total of 53 patients who had undergone sorafenib therapy were analyzed as the control group. The primary endpoint of this study was OS. RESULTS: The median number of MET cycles was two (1-15). The OS values for the MET group and sorafenib group were 158 days (132-184) and 117 days (92-142), respectively (P=0.029). The Cox proportional-hazard model showed that a higher risk of death was correlated with higher serum alpha fetoprotein level (≥400 mg/dL, hazard ratio [HR]=1.680, P=0.014) and Child-Pugh class B (HR=1.856, P=0.008). CONCLUSIONS: MET was associated with more favorable outcomes in terms of overall survival than was sorafenib in patients with advanced HCC with PVTT, especially in patients with poor liver function. Therefore, MET can be considered as a treatment option in patients with advanced HCC with PVTT and poor liver function.
Administration, Metronomic ; alpha-Fetoproteins ; Carcinoma, Hepatocellular* ; Drug Therapy* ; Humans ; Liver* ; Portal Vein ; Thrombosis