OBJECTIVES: To investigate the therapeutic mechanism of Thesium chinense Turcz. (TCT) for antibiotic-associated diarrhea (AAD). METHODS: Network pharmacology, KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD, the key signaling pathways and the binding between the active components in TCT and the core protein targets. In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride, the effects of daily gavage of 1% carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg (n=10) on body weight and diarrhea were observed. HE staining, ELISA, 16S rRNA sequencing, and Western blotting were used to examine pathologies, expression levels of IL-6 and TNF-α, changes in gut microbiota, and protein expressions of EGFR, p-EGFR, PI3K, p-PI3K, Akt, and p-Akt in the colon tissues of the mice. RESULTS: We identified a total of 66 active components of TCT and 68 core targets including EGFR, STAT3 and PIK3CA. KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway. Molecular docking showed that EGFR had the highest binding affinity with coniferin, and the EGFR-coniferin complex maintained a stable conformation at 10 ns, whose stability was also confirmed by Gibbs free energy analysis. In the mouse models of AAD, treatment with TCT significantly improved colonic tissue morphology, decreased colonic levels of TNF-α and IL-6, increased gut microbiota diversity, and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides. TCT treatment also markedly reduced protein expressions of p-EGFR, p-PI3K and p-Akt in the colon tissues of the mice. CONCLUSIONS TCT can alleviate AAD in mice by modulating gut microbiota composition, regulating the EGFR/PI3K/Akt signaling pathway, and reducing TNF‑α and IL-6 expressions.
Animals ; Gastrointestinal Microbiome/drug effects* ; Signal Transduction/drug effects* ; Mice ; ErbB Receptors/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Diarrhea/drug therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Anti-Bacterial Agents/adverse effects* ; Drugs, Chinese Herbal/therapeutic use* ; Molecular Docking Simulation

BACKGROUND/AIMS: Hepatic damage during transarterial chemoembolization (TACE) is a critical complication in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE. METHODS: This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC. RESULTS: Of the 108 patients, 30 (27.8%) patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1%) patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008). In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013), hypoalbuminemia (HR=3.990, P=0.015), and absence of antiviral therapy (HR=7.597, P=0.006) were significantly associated with treatment-related hepatic decompensation. CONCLUSIONS: Our findings suggest that preemptive antiviral therapy significantly reduces the risk of acute hepatic deterioration. Preventing hepatic deterioration during TACE by applying such a preemptive approach may facilitate the continuation of anticancer therapy and thus improve long-term outcomes.
Aged ; Antiviral Agents/*therapeutic use ; Bilirubin/blood ; Carcinoma, Hepatocellular/*therapy ; Chemoembolization, Therapeutic/*adverse effects ; Female ; Gastrointestinal Hemorrhage/etiology ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B/complications/*drug therapy ; Humans ; Hypoalbuminemia/etiology ; Incidence ; Liver/physiopathology ; Liver Diseases/epidemiology/*etiology ; Liver Neoplasms/*therapy ; Male ; Middle Aged ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Treatment Outcome

OBJECTIVE: We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. MATERIALS AND METHODS: In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. RESULTS: The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. CONCLUSION: Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*adverse effects/therapeutic use ; Ascites/pathology/radiography ; Benzamides/*adverse effects/therapeutic use ; Echocardiography/methods ; Edema/pathology/radiography ; Female ; Gastrointestinal Stromal Tumors/drug therapy/pathology/*radiography ; Gastrointestinal Tract/pathology/*radiography ; Heart Failure/radiography ; Humans ; Male ; Middle Aged ; Molecular Targeted Therapy/*adverse effects ; Pericardial Effusion/pathology/radiography ; Peritoneal Neoplasms/diagnosis/radiography/secondary ; Piperazines/*adverse effects/therapeutic use ; Pleural Effusion/pathology/radiography ; Pyrimidines/*adverse effects/therapeutic use ; Radiology ; Retrospective Studies ; Tomography, X-Ray Computed

Helicobacter pylori can cause variety of upper gastrointestinal disorders such as peptic ulcer, mucosa associated lymphoid tissue (MALT)-lymphoma, and gastric cancer. The prevalence of H. pylori infection has significantly decreased in Korea since 1998 owing to active eradication of H. pylori. Along with its decrease, the prevalence of peptic ulcer has also decreased. However, the mean age of gastric ulcer increased and this is considered to be due to increase in NSAID prescription. Gastric cancer is one of the leading causes of cancer deaths in Korea and Japan, and IARC/WHO has classified H. pylori as class one carcinogen of gastric cancer. Despite the decreasing prevalence of H. pylori infection, the total number of gastric cancer in Korea has continuously increased from 2006 to 2011. Nevertheless, the 5 year survival rate of gastric cancer patients significantly increased from 42.8% in 1993 to 67% in 2010. This increase in survival rate seems to be mainly due to early detection of gastric cancer and endoscopic mucosal dissection treatment. Based on these findings, the prevalence of peptic ulcer is expected to decrease even more with H. pylori eradication therapy and NSAID will become the main cause of peptic ulcer. Although the prevalence of gastric cancer has not changed along with decreased the prevalence of H. pylori, gastric cancer is expected to decrease in the long run with the help of eradication therapy and endoscopic treatment of precancerous lesions.
Anti-Bacterial Agents/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Gastrointestinal Diseases/complications/*epidemiology ; Helicobacter Infections/complications/drug therapy/epidemiology ; Humans ; Lymphoma, B-Cell, Marginal Zone/epidemiology ; Peptic Ulcer/epidemiology/etiology ; Prevalence ; Stomach Neoplasms/etiology/mortality/pathology

No abstract available.
Adult ; Antineoplastic Agents/*adverse effects ; Antitubercular Agents/therapeutic use ; Biopsy ; Female ; Gastrointestinal Stromal Tumors/*drug therapy/pathology/surgery ; Humans ; Imatinib Mesylate/*adverse effects ; Lung Diseases, Interstitial/*chemically induced/diagnosis ; Mycobacterium tuberculosis/*isolation & purification ; Protein Kinase Inhibitors/*adverse effects ; Rectal Neoplasms/*drug therapy/pathology/surgery ; Tomography, X-Ray Computed ; Tuberculosis, Pulmonary/diagnosis/drug therapy/*microbiology

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Imatinib mesylate is recommended as adjuvant therapy for GIST after surgical resection. However, drug-related adverse events are common. A 74-year-old female with metastatic GIST who was managed with imatinib experienced severe adverse events, including skin rashes, tremor, and alopecia, etc. The imatinib dose was reduced and the size of the metastatic GIST continued to decrease and adverse events showed significant improvement.
Aged ; Antineoplastic Agents/adverse effects/*therapeutic use ; Exanthema/etiology ; Female ; Gastrointestinal Neoplasms/diagnosis/*drug therapy/pathology ; Gastrointestinal Stromal Tumors/diagnosis/*drug therapy/pathology ; Humans ; Imatinib Mesylate/adverse effects/*therapeutic use ; Immunohistochemistry ; Proto-Oncogene Proteins c-kit/metabolism ; Tomography, X-Ray Computed

BACKGROUND/AIMS: The dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT). METHODS: Two sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT. RESULTS: In the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively. CONCLUSIONS: A reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.
Adult ; Aged ; Area Under Curve ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Gastrointestinal Diseases/etiology ; Graft Rejection/prevention & control ; Humans ; Immunosuppressive Agents/blood/*pharmacokinetics ; Leukopenia/etiology ; Liver/pathology ; Liver Failure/*therapy ; *Liver Transplantation ; Male ; Middle Aged ; Mycophenolic Acid/adverse effects/*analogs & derivatives/blood/pharmacokinetics ; ROC Curve ; Retrospective Studies ; Tacrolimus/therapeutic use ; Tissue Donors

BACKGROUND/AIMS: This study assessed the antiviral efficacy and safety of tenofovir disoproxil fumarate (TDF) for up to 12 months in Korean treatment-naive chronic hepatitis B (CHB) patients. METHODS: A total of 411 treatment-naive CHB patients who had been treated with TDF for at least 3 months (median 5.6) were consecutively enrolled. Clinical, biochemical, virological parameters and treatment adherence were routinely assessed every 3 months. RESULTS: The median age was 51.3 years, 63.0% of the patients were male, 49.6% were HBeAg (+), and 210 patients had liver cirrhosis. The median baseline HBV DNA was 5.98 (SD 1.68) log10 IU/mL. Among the patients completing week 48, 83.3% had a complete virologic response (CVR, <12 IU/mL by HBV PCR assay), and 88.2% had normalized levels of alanine aminotransferase (ALT). The cumulative probabilities of CVR at 3, 6, 9 and 12 months were 22.8%, 53.1%, 69.3% and 85.0%. During the follow-up period, 9.8% patients achieved HBeAg loss and 7.8% patients achieved HBeAg seroconversion. There was no virological breakthrough after initiating TDF. The most common TDF-related adverse event was gastrointestinal upset, and three patients discontinued TDF therapy. However, no serious life-threatening side effect was noted. CONCLUSIONS: In a clinical practice setting, TDF was safe and highly effective when administered for 12 months to Korean treatment-naive CHB patients.
Adenine/adverse effects/*analogs & derivatives/therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Alanine Transaminase/blood ; Antiviral Agents/adverse effects/*therapeutic use ; Cohort Studies ; DNA, Viral/blood ; Female ; Gastrointestinal Diseases/epidemiology/etiology ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*drug therapy/virology ; Humans ; Liver Cirrhosis/etiology ; Male ; Middle Aged ; Organophosphonates/adverse effects/*therapeutic use ; Republic of Korea ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the efficacy of dietary therapy of qi-yin-reinforcing porridge for the alleviation of clinical symptoms during FOLFOX chemotherapy.

METHODSA single-case randomized controlled study was carried out. Fourteen patients with gastrointestinal tumors accepting FOLFOX chemotherapy were enrolled using self-crossover control design. On days 1-7 of chemotherapy, the dietary therapy experimental group and the placebo control group were given dietary therapy of qi-yin-reinforcing porridge and dextrin-prepared porridge which had the same appearance, smell, color and taste as the qi-yin-reinforcing porridge, respectively. Fourteen clinical symptoms, including debility, vomiting and nausea, etc. were observed.

RESULTSTen patients completed the study and were estimable. The qi-yin-reinforcing porridge demonstrated certain efficacy in alleviating clinical symptoms of patients with gastrointestinal tumors during the period of chemotherapy. Better effect of alleviating debility was found in the dietary therapy experimental group than in the placebo control group, and the difference was statistically significant (Z=2.27, P=0.02). No statistically significant difference was found between the experimental group and the control group with respect to the effect of alleviating the other 13 clinical symptoms including anorexia, nausea, vomiting, dry stool, loose stool, etc. and body weight (P>0.05).

CONCLUSIONDietary therapy of qi-yin-reinforcing porridge shows an additional benefit in alleviating debility of patients during chemotherapy and deserves clinical use and popularization.

Aged ; Antineoplastic Agents ; adverse effects ; pharmacology ; therapeutic use ; Body Weight ; drug effects ; Coix ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gastrointestinal Neoplasms ; diet therapy ; drug therapy ; Humans ; Male ; Middle Aged ; Oryza

BACKGROUND/AIMS: Our aim was to assess the long-term data regarding efficacy and safety of infliximab (IFX) treatment for refractory Crohn's disease (CD) patients in our tertiary teaching hospital. METHODS: We have retrospectively analyzed the medical records of 89 CD patients who underwent IFX treatment between March 2003 and February 2011 at Kyung Hee University Hospital (Seoul, Korea). The primary outcome measurements were the rates of initial clinical response (CR) at 10 weeks after the 1st IFX infusion and sustained CR at the end of the follow-up. Overall adverse events related to IFX treatment were also evaluated. RESULTS: The mean (SD) follow-up period of eligible 80 patients was 33.7 (21.9) months. A total of 77 patients (96%) showed initial clinical response, but 8 patients showed loss of response to IFX during the follow-up. Finally, 59 patients (59/77, 76.6%) showed sustained CR at the end of the study. Logistic regression analyses showed that an initial CR at 10 weeks was the independent predictor associated with sustained CR (OR 22.286, 95% CI 2.742-132.717, p=0.001). Overall adverse events reported in 18 patients (18/80, 23.3%), including 3 serious infection (pulmonary tuberculosis and herpes zoster). CONCLUSIONS: Treatment with IFX was efficacious and relatively safe for refractory CD patients in Korea. An initial CR at 10 weeks was significantly associated with sustained CR.
Adult ; Antibodies, Monoclonal/adverse effects/*therapeutic use ; Crohn Disease/*drug therapy ; Female ; Follow-Up Studies ; Gastrointestinal Agents/adverse effects/*therapeutic use ; Herpes Zoster/etiology ; Humans ; Logistic Models ; Male ; Odds Ratio ; Retrospective Studies ; Treatment Outcome ; Tuberculosis, Pulmonary/etiology ; Young Adult