Background/Aims: This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods: The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results: Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.

Activated phosphoinositide 3-kinase δ syndrome (APDS)1 is caused by gain-of-function mutations in PIK3CD, which encodes the catalytic p110δ subunit of phosphoinositide 3 kinase. We describe three patients with APDS1, the first thereof in Korea. Therein, we investigated clinical manifestations of APDS1 and collected data on the efficacy and safety profile of sirolimus, a mammalian target of rapamycin inhibitor and pathway-specific targeted medicine. The same heterozygous PIK3CD mutation was detected in all three patients (E1021K). After genetic diagnosis, all patients received sirolimus and experienced an excellent response, including amelioration of lymphoproliferation and improvement of nodular mucosal lymphoid hyperplasia in the gastrointestinal tract. The median trough level of sirolimus was 5.5 ng/mL (range, 2.8–7.5) at a dose of 2.6–3.6 mg/m2. Two patients who needed highdose, short-interval, immunoglobulin-replacement treatment (IGRT) had a reduced requirement for IGRT after initiating sirolimus, and the dosing interval was extended from 2 and 3 weeks to 4 weeks. The IgG trough level after sirolimus treatment (median, 594 mg/dL; range, 332–799 mg/dL) was significantly higher than that before sirolimus treatment (median, 290 mg/dL; range, 163–346 mg/dL) (p<0.001). One episode of elevated serum creatinine with a surge of sirolimus (Patient 2) and episodes of neutropenia and oral stomatitis (Patient 1) were observed. We diagnosed the first three patients with APDS1 in Korea. Low-dose sirolimus may alleviate clinical manifestations thereof, including hypogammaglobulinemia.

BACKGROUND/AIMS: We evaluated the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) in patients with chronic hepatitis C virus (HCV) infection on hemodialysis. METHODS: We performed a single-arm, multicenter prospective study. Twenty-one chronic hemodialysis patients with HCV infection were prospectively enrolled from February 2016 to April 2017. We evaluated the virological responses at weeks 4, 12, and 24 (end of treatment [EOT]) and the sustained virological response at 12 weeks after the EOT (SVR12). The tolerability and safety of the drugs were also assessed. RESULTS: None of the 20 patients had the NS5A resistance-associated variant (NS5A RAV), and one patient was indeterminate for the NS5A RAV. Seventeen patients (80%) completed the 24 weeks of treatment with DCV and ASV. Four patients discontinued the study prior to week 12. In an intention-to-treat analysis, the SVR12 was 76.1%. In a per-protocol analysis, patients who completed DCV and ASV treatment achieved an SVR12 of 100%. DCV and ASV were well tolerated by the majority of patients. Three patients discontinued treatment due to adverse events (AEs) including dizziness, dyspnea, and neutropenia. The patient with indeterminate NS5A RAV showed viral breakthrough and discontinued treatment. CONCLUSIONS: DCV and ASV combination therapy in chronic hemodialysis patients with HCV infection achieved a high SVR12 rate with few AEs. To maximize the SVR12 rate, it is important to identify candidates by baseline RAV testing. Close monitoring of the safety and tolerability of DCV and ASV may be necessary in HCV-infected patients on hemodialysis. (ClinicalTrials.gov ID NCT02580474)
Dizziness ; Dyspnea ; Hepacivirus ; Hepatitis C ; Hepatitis C, Chronic ; Hepatitis ; Humans ; Neutropenia ; Prospective Studies ; Renal Dialysis

BACKGROUND/AIMS: Sofosbuvir plus ribavirin is a standard treatment for patients infected with chronic hepatitis C virus (HCV) genotype 2 in Korea. The purpose of this study was to examine the efficacy and safety of this treatment in Korean patients with chronic HCV genotype 2 infection. METHODS: We retrospectively analyzed clinical data of patients treated with sofosbuvir plus ribavirin for chronic HCV genotype 2 from May 2016 to December 2017 at eight hospitals located in the Daejeon-Chungcheong area. RESULTS: A total of 172 patients were treated with sofosbuvir plus ribavirin. Of them, 163 patients completed the treatment, and 162 patients were tested for sustained virologic response 12 weeks after treatment discontinuation (SVR12). Mean age was 59.6±12.3 years (27–96), and 105 (64.4%) patients were female. Of the total patients, 49 (30.1%) were diagnosed with cirrhosis, and 31 of them were treated for 16 weeks. Sofosbuvir plus ribavirin was the first-line treatment for 144 (88.3%) patients. Eleven (6.7%) patients were intolerant to previous interferon-based treatment. Eight (5.0%) patients relapsed after interferon-based treatment. HCV RNA non-detection rate at 4, 8, and 12 weeks was 97.5%, 99.1%, and 99.3%, respectively, and SVR12 was 98.8% (161/163). During treatment, 18 (11.0%) patients had to reduce their administrated dose of ribavirin because of anemia. One patient stopped the treatment because of severe anemia. Other adverse events, including dizziness, indigestion, and headache, were found in 26 (16.0%) patients. CONCLUSIONS: A 12-16 week treatment with sofosbuvir plus ribavirin is remarkably effective and well tolerated in Korean patients with chronic HCV genotype 2 infection.
Anemia ; Dizziness ; Dyspepsia ; Female ; Fibrosis ; Genotype ; Headache ; Hepacivirus* ; Hepatitis C* ; Hepatitis C, Chronic ; Hepatitis* ; Humans ; Korea ; Retrospective Studies* ; Ribavirin* ; RNA ; Sofosbuvir*

BACKGROUND: The basophil activation test (BAT) is a promising tool for monitoring allergen-specific immunotherapy responses. OBJECTIVE: We aimed to investigate the changes in basophil activation in response to the inhalant allergens of house dust mite (HDM) and mugwort pollen during immunotherapy in patients with allergic rhinitis. METHODS: We enrolled patients with allergic rhinitis who were to receive subcutaneous immunotherapy for the inhalant allergens HDM or mugwort. A BAT was performed to assess CD63 upregulation in response to allergen stimulation using peripheral blood collected from the patients prior to immunotherapy and at 3, 6, 12, and 24 months after beginning immunotherapy. Rhinitis symptoms were evaluated using the rhinitis quality of life questionnaire (RQLQ) at 1-year intervals. RESULTS: Seventeen patients (10 with HDM sensitivity, 3 with mugwort sensitivity, and 4 with sensitivity to both HDM and mugwort) were enrolled in the study. Basophil reactivity to HDM did not change significantly during 24 months of immunotherapy. However, a significant reduction in basophil reactivity to mugwort was observed at 24-month follow-up. There was no significant association between the change in clinical symptoms by RQLQ and the change in basophil reactivity to either allergen. The change in allergen-specific basophil reactivity to HDM was well correlated with the change in nonspecific basophil activation induced by anti-FcεRI antibody, although basophil reactivity to anti-FcεRI antibody was not significantly reduced during immunotherapy. CONCLUSION: Suppression of CD63 upregulation in the BAT was only observed with mugwort at 2-year follow-up. However, the basophil response did not reflect the clinical response to immunotherapy.
Allergens ; Artemisia ; Basophils ; Desensitization, Immunologic ; Dust ; Follow-Up Studies ; Humans ; Immunotherapy ; Pollen ; Pyroglyphidae ; Quality of Life ; Rhinitis ; Rhinitis, Allergic ; Up-Regulation

Gastric outlet obstruction (GOO) is a disease that causes pyloric canal or duodenal atresia by various etiologies. It is mainly caused by malignancy or peptic ulcer and rarely caused by corrosive injury, gastric polyp, pyloric stenosis, bezoar, or biliary stone. We report a rare case of GOO due to unreported etiology. A 74-year-old male patient with medical history of hypertension, diabetes mellitus, and stroke came to the emergency medical center with a chief complaint of acute stomachache. On abdominal computed tomography, it was diagnosed as GOO due to gall bladder distension from acute cholecystitis. During conservative treatment and antibiotics administration, gastrofibroscopy and magnetic resonance cholangiopancreatography was performed to determine other etiologies; however, the final diagnosis was made as acute cholecystitis. After laparoscopic cholecystectomy, he was discharged without specific complications. On a pathology examination postoperation, there was no specific diagnosis, except for acute cholecystitis. Gastric outlet obstruction is caused by various etiologies, with the course of treatment being dependent on the specific etiology. We report a rare case of GOO caused by gall bladder distension due to acute cholecystitis. Various etiologies should be considered carefully to include even the rare etiologies for choosing the correct treatment.
Abdominal Pain ; Aged ; Anti-Bacterial Agents ; Bezoars ; Cholangiopancreatography, Magnetic Resonance ; Cholecystectomy, Laparoscopic ; Cholecystitis ; Cholecystitis, Acute* ; Diabetes Mellitus ; Diagnosis ; Emergencies ; Gastric Outlet Obstruction* ; Humans ; Hypertension ; Male ; Pathology ; Peptic Ulcer ; Polyps ; Pyloric Stenosis ; Stroke ; Urinary Bladder*

PURPOSE: KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo. MATERIALS AND METHODS: The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects. RESULTS: KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho-Src and proliferative-signaling molecules were down-regulated in KX-01-sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01-induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01-sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model. CONCLUSION: KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.
Aneuploidy ; Animals ; Breast Neoplasms ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line ; Fluorescent Antibody Technique ; Heterografts ; In Vitro Techniques ; Mice ; Microtubules ; Mitosis* ; src-Family Kinases* ; Triple Negative Breast Neoplasms ; Tubulin ; Wound Healing

BACKGROUND/AIMS: To determine the incidence and clinical characteristics of tuberculosis (TB) medication-associated Clostridium difficile infection. METHODS: This multicenter study included patients from eight tertiary hospitals enrolled from 2008 to 2013. A retrospective analysis was conducted to identify the clinical features of C. difficile infection in patients who received TB medication. RESULTS: C. difficile infection developed in 54 of the 19,080 patients prescribed TB medication, representing a total incidence of infection of 2.83 cases per 1,000 adults. Fifty-one of the 54 patients (94.4%) were treated with rifampin. The patients were usually treated with oral metronidazole, which produced improvement in 47 of the 54 patients (87%). Twenty-three patients clinically improved with continuous rifampin therapy for C. difficile infection. There were no significant differences in improvement between patients treated continuously (n=21) and patients in whom treatment was discontinued (n=26). CONCLUSIONS: The incidence of C. difficile infection after TB medication was not low considering the relatively low TB medication dosage compared to other antibiotics. It may not be always necessary to discontinue TB medication. Instead, decisions concerning discontinuation of TB medication should be based on TB status.
Adult ; Aged ; Aged, 80 and over ; Anti-Infective Agents/therapeutic use ; Antibiotics, Antitubercular/*adverse effects ; *Clostridium difficile ; Enterocolitis, Pseudomembranous/chemically induced/drug therapy/*epidemiology ; Female ; Humans ; Incidence ; Male ; Metronidazole/therapeutic use ; Middle Aged ; Retrospective Studies ; Rifampin/*adverse effects ; Treatment Outcome ; Tuberculosis/*drug therapy

Pulmonary Langerhans cell histiocytosis is an uncommon diffuse cystic lung disease in adults. In rare cases, it can involve extrapulmonary organs and lead to endocrine abnormalities such as central diabetes insipidus. A 42-year-old man presented with polyphagia and polydipsia, as well as a dry cough and dyspnea on exertion. Magnetic resonance imaging of the hypothalamic-pituitary system failed to show the posterior pituitary, which is a typical finding in patients with central diabetes insipidus. This condition was confirmed by a water deprivation test, and the patient was also found to have type 2 diabetes mellitus. Computed tomographic scanning of the lungs revealed multiple, irregularly shaped cystic lesions and small nodules bilaterally, with sparing of the costophrenic angles. Lung biopsy through video-assisted thoracoscopic surgery revealed pulmonary Langerhans cell histiocytosis. On a follow-up visit, only 1 year after the patient had quit smoking, clinical and radiological improvement was significant. Here, we report an uncommon case of pulmonary Langerhans cell histiocytosis that simultaneously presented with diabetes insipidus and diabetes mellitus.
Adult* ; Biopsy ; Cough ; Diabetes Insipidus ; Diabetes Insipidus, Neurogenic* ; Diabetes Mellitus* ; Diabetes Mellitus, Type 2 ; Dyspnea ; Follow-Up Studies ; Histiocytosis, Langerhans-Cell* ; Humans ; Lung ; Lung Diseases ; Magnetic Resonance Imaging ; Male* ; Polydipsia ; Smoke ; Smoking ; Smoking Cessation ; Thoracic Surgery, Video-Assisted ; Water Deprivation

BACKGROUND: Although nutritional problems associated with dialysis are well described, nutritional problems after renal transplantation have received little attention. Nutrition interventions play an important role in prevention and management of common health problems associated with renal transplantation such as obesity, hypertension, diabetes, and cardiovascular disease. METHODS: Sixty-four kidney transplant recipients who received post-transplant management at our hospital replied to the questionnaire. The questionnaire included 102 questions on the amount and types of Korean foods that they consumed last week. Nutritional elements of diet in renal transplant patients who consume Korean food were analyzed on the basis of the survey. RESULTS: The mean energy and protein of daily intake were 2,088+/-1,016 kcal and 75.5+/-38.2 g. Patients' diets were generally sufficient, but characterized by deficiencies in vitamin B2, vitamin D, niacin, calcium, and magnesium intake. CONCLUSIONS: Dietary advice is required with regard to intake of some nutritional elements for kidney transplant recipients who consume Korean foods. Their main nutritional problem is obesity after transplantation. Attention should be paid to prevention of nutritional imbalance.
Calcium ; Cardiovascular Diseases ; Dialysis ; Diet ; Humans ; Hypertension ; Kidney Transplantation ; Kidney* ; Magnesium ; Niacin ; Obesity ; Surveys and Questionnaires ; Riboflavin ; Transplantation ; Vitamin D