Purpose: This study aimed to provide compelling evidence of anti-staphylococcal beta-lactam use for methicillin-susceptible Staphylococcus aureus bloodstream infection (MSSA BSI). Materials and Methods: We retrospectively collected data on patients with MSSA BSI who were admitted to two academic tertiary-care hospitals from 2010 to 2018. Only patients who received nafcillin, cefazolin, vancomycin, or teicoplanin as definitive therapy were included. The primary outcome was 28-day mortality. To perform unbiased comparisons between both treatments, we used inverse probability of treatment weighting (IPTW) analysis. Results: A total of 359 patients were divided into two groups based on the definitive therapy used: beta-lactams (n=203), including nafcillin or cefazolin; and glycopeptides (n=156), including vancomycin or teicoplanin. In the IPTW analysis, glycopeptides were associated with significantly increased odds of 28-day mortality (adjusted odds ratio, 3.37; 95% confidence interval, 1.71– 6.61; p<0.001). The rate of primary outcome in prespecified subgroups was largely consistent with the main analysis. Conclusion Definitive therapy with beta-lactams in patients with MSSA BSI was associated with lower 28-day mortality compared to definitive therapy with glycopeptides.

Background and Objectives: Recent studies have described direct reprogramming of mouse and human somatic cells into induced neural stem cells (iNSCs) using various combinations of transcription factors. Although iNSC technology holds a great potential for clinical applications, the low conversion efficiency and limited reproducibility of iNSC generation hinder its further translation into the clinic, strongly suggesting the necessity of highly reproducible method for human iNSCs (hiNSCs). Thus, in orderto develop a highly efficient and reproducible protocol for hiNSC generation, we revisited the reprogramming potentials of previously reported hiNSC reprogramming cocktails by comparing the reprogramming efficiency of distinct factor combinations including ours. Methods: We introduced distinct factor combinations, OSKM (OCT4+SOX2+KLF4+C-MYC), OCT4 alone, SOX2 alone, SOX2+HMGA2, BRN4+SKM+SV40LT (BSKMLT), SKLT, SMLT, and SKMLT and performed comparative analysis of reprogramming potentials of distinct factor combinations in hiNSC generation. Results: Here we show that ectopic expression of five reprogramming factors, BSKMLT leads the robust hiNSC generation (>80 folds enhanced efficiency) from human somatic cells compared with previously described factor combinations. With our combination, we were able to observe hiNSC conversion within 7 days of transduction. Throughout further optimization steps, we found that both BRN4 and KLF4 are not essential for hiNSC conversion. Conclusions Our factor combination could robustly and reproducibly generate hiNSCs from human somatic cells with distinct origins. Therefore, our novel reprogramming strategy might serve as a useful tool for hiNSC-based clinical application.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. METHODS: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. RESULTS: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. CONCLUSIONS: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.
Acetaminophen ; Acetates ; Acetic Acid ; Anti-Inflammatory Agents, Non-Steroidal ; Cicatrix ; Classification ; Cyclooxygenase 2 Inhibitors ; Diethylpropion ; Drug Hypersensitivity ; Drug Hypersensitivity Syndrome ; Hospitals, University ; Incidence ; Korea ; Phenotype ; Propionates ; Prospective Studies ; Retrospective Studies ; Salicylates ; Salicylic Acid ; Stevens-Johnson Syndrome

PURPOSE: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) to antiepileptic drug (AED), are rare, but result in significant morbidity and mortality. We investigated the major culprit drugs, clinical characteristics, and clinical course and outcomes of AED-induced SCARs using a nationwide registry in Korea. METHODS: A total of 161 patients with AED-induced SCARs from 28 referral hospitals were analyzed. The causative AEDs, clinical characteristics, organ involvements, details of treatment, and outcomes were evaluated. We compared the clinical and laboratory parameters between SJS/TEN and DRESS according to the leading causative drugs. We further determined risk factors for prolonged hospitalization in AED-induced SCARs. RESULTS: Carbamazepine and lamotrigine were the most common culprit drugs causing SCARs. Valproic acid and levetiracetam also emerged as the major causative agents. The disease duration and hospital stay in carbamazepine-induced SJS/TEN were shorter than those in other AEDs (P< 0.05, respectively). In younger patients, lamotrigine caused higher incidences of DRESS than other drugs (P= 0.045). Carbamazepine, the most common culprit drug for SCARs, was associated with a favorable outcome related with prolonged hospitalization in SJS (odds ratio, 0.12; 95% confidence interval, 0.02-0.63, P= 0.12), and thrombocytopenia was found to be a risk factor for prolonged hospitalization in DRESS. CONCLUSION: This was the first large-scale epidemiological study of AED-induced SCARs in Korea. Valproic acid and levetiracetam were the significant emerging AEDs causing SCARs in addition to the well-known offending AEDs such as carbamazepine and lamotrigine. Carbamazepine was associated with reduced hospitalization, but thrombocytopenia was a risk factor for prolonged hospitalization. Our results suggest that the clinical characteristics and clinical courses of AED-induced SCARs might vary according to the individual AEDs.
Anticonvulsants ; Carbamazepine ; Cicatrix ; Drug Hypersensitivity Syndrome ; Epidemiologic Studies ; Hospitalization ; Humans ; Incidence ; Korea ; Length of Stay ; Mortality ; Referral and Consultation ; Risk Factors ; Stevens-Johnson Syndrome ; Thrombocytopenia ; Valproic Acid

Enteropathy-type T-cell lymphoma (ETL) or enteropathy-associated T-cell lymphoma is a very rare malignant intestinal tumor. ETL is usually diagnosed by surgery. Endoscopic findings of ETL are not well known, and there are few reports of findings from endoscopy that has been performed only using white light. Additionally, there are no definite treatment guidelines for ETL. Therefore, we report a case of ETL diagnosed by enteroscopy with imaging-enhanced endoscopy and also review recently developed treatment options.
Endoscopy ; Enteropathy-Associated T-Cell Lymphoma ; Humans ; Light ; Lymphoma, T-Cell ; T-Lymphocytes

The interleukin-33 (IL-33)/ST2 pathway has emerged as an intercellular signaling system that participates in antigen-allergen response, autoimmunity and fibrosis. It has been suggested that IL-33/ST2 signaling has been involved in the pathogenesis of rheumatoid arthritis (RA), because IL-33 and its receptor have been specifically mapped to RA synovium. The aim of this study was to determine the levels of IL-33 and sST2 in sera and synovial fluids in patients with RA. The serum level of IL-33 was significantly higher in patients with RA (294.9 +/- 464.0 pg/mL) than in healthy controls (96.0 +/- 236.9 pg/mL, P = 0.002). The synovial fluid level of IL-33 was significantly higher in RA patients than in osteoarthritis patients. The level of serum sST2 was higher in RA patients than in healthy controls (P = 0.042). A significant relationship was found between the levels of IL-33 and IL-1beta (r = 0.311, P = 0.005), and IL-33 and IL-6 (r = 0.264, P = 0.017) in 81 RA patients. The levels of IL-33, sST2 and C-reactive protein decreased after conventional disease-modifying antirheumatic drugs treatment in 10 patients with treatment-naive RA. Conclusively, IL-33 is involved in the pathogenesis of RA and may reflect the degree of inflammation in patients with RA.
Adult ; Aged ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/blood/drug therapy/*pathology ; C-Reactive Protein/analysis ; Female ; Humans ; Interleukin-1beta/analysis/blood ; Interleukin-6/analysis/blood ; Interleukins/*analysis/blood ; Male ; Middle Aged ; Osteoarthritis/blood/pathology ; Receptors, Cell Surface/*analysis/blood ; Synovial Fluid/metabolism

BACKGROUND/AIMS: This study compared the clinical benefits of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) with pemetrexed to identify the clinical parameters that correlated with response. METHODS: A retrospective chart review examined patients who were 1) treated with EGFR TKI or pemetrexed, 2) diagnosed with advanced non-squamous non-small-cell lung cancer, and 3) previously treated with platinum-based chemotherapy in Soonchunhyang Bucheon Hospital. RESULTS: Sixty-one patients (18 erlotinib, 18 gefitinib, 25 pemetrexed) were investigated from February 2002 to August 2009. The median follow-up period was 37 months (7~97 months). Overall, their median age was 63 years, 41 patients were non-smokers, 57 patients had adenocarcinoma, and 55 patients were at stage IV. Twenty-one patients received the study drugs as second-line chemotherapy, and others as third-line or more. No significant differences in the overall response rate (erlotinib 33.3% vs. gefitinib 38.9% vs. pemetrexed 20.0%) and progression-free survival (erlotinib 1.9 months vs. gefitinib 3.0 months vs. pemetrexed 2.9 months) were found among the three groups. Female gender was related to a good response to EGFR TKIs (p=0.047). Skin rash in the erlotinib group (p=0.037) and adenocarcinoma in the pemetrexed group (p=0.02) were related to improved progression-free survival. Few side effects were reported. CONCLUSIONS: Both EGFR TKIs and pemetrexed therapy for non-squamous non-small-cell lung cancer were efficient and tolerable after the failure of first-line platinum-based chemotherapy. Further prospective studies are needed to validate the predictive role of the suggested clinical parameters in this study.
Adenocarcinoma ; Disease-Free Survival ; Exanthema ; Female ; Follow-Up Studies ; Glutamates ; Guanine ; Humans ; Lung ; Lung Neoplasms ; Protein-Tyrosine Kinases ; Quinazolines ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Erlotinib Hydrochloride ; Pemetrexed

Standard antituberculous therapy, including isoniazid (INH), rifampin, ethambutol, and pyrazinamide (PZA), is widely used to treat active tuberculosis. The most important side effect is hepatotoxicity. In a standard four-drug regimen, PZA was the most common cause of drug-induced hepatitis and was dose-related. The incidence of drug-induced hepatitis is high at doses of 40~70 mg/kg per day but has fallen significantly since the recommended dose was reduced. Liver toxicity induced by PZA is rare at doses of 25 mg/kg per day or less. PZA-induced fulminant hepatic failure is also rare but fatal. We report a case of fulminant hepatic failure caused by a re-challenge of PZA.
Drug-Induced Liver Injury ; Ethambutol ; Incidence ; Isoniazid ; Liver ; Liver Failure, Acute* ; Pyrazinamide* ; Rifampin ; Tuberculosis

PURPOSE: We wanted to determine the clinical characteristics and prognosis according to the VEGF expression in stage II cervical carcinoma patients treated with definitive radiotherapy. MATERIALS AND METHODS: We enrolled 31 patients who were diagnosed with cervical cancer from 1995 to 2003 at Samsung Medical Center and their paraffin block tissue samples were available for study. The median age of the patients was 65 years. The mean tumor size was 4.1 cm (range: 1.2~8.2 cm). Seven patients (22.6%) were suspected of having pelvic lymph node metastasis. An external beam irradiation dose of 45-56.4 Gy was administered to the whole pelvis with a 15 MV linear accelerator, and an additional 24 Gy was given to point A by HDR intracavitary brachytherapy. VEGF staining was defined as positive when more than 10% of the tumor cells were stained. The median follow-up duration was 58 months. RESULTS: A positive VEGF expression was observed in 21 patients (67.7%). There was no significant correlation between the VEGF expression and pelvic lymph node metastasis, tumor size and the response of radiotherapy. During follow-up, 7 patients had recurrence. The complete response rate was not significant between the VEGF (-) and VEGF (+) tumors. However, the VEGF (+) tumors showed a significantly higher recurrence rate in comparison with the VEGF (-) tumors (p=0.040). The three year disease-free survival rates were 100% and 66.7%, respectively, for patients with VEGF (-) or VEGF (+) tumor (p=0.047). CONCLUSION: The VEGF expression was a significant factor for recurrence and disease-free survival. However, the significance of the VEGF expression is still controversial because of the various definitions of VEGF expression and the mismatches of the clinical data in the previous studies.
Brachytherapy ; Cervix Uteri* ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Paraffin ; Particle Accelerators ; Pelvis ; Prognosis ; Radiotherapy* ; Recurrence ; Uterine Cervical Neoplasms ; Vascular Endothelial Growth Factor A*

Mucosal bridge, endoscopically observed, is a cord-like mucosal connection across the lumen. The bridge is very elastic and stretches easily, unlike granulation tissue. Mucosal bridges of the esophagus have been occasionally described in various circumstances, particularly in congenital or acquired origin as the inflammatory diseases. The occurrence of mucosal bridges due to inflammatory process may arise anywhere from the esophagus to the colon. It has been more frequently reported in the colon than in the esophagus, stomach, and duodenum. We experienced four cases of esophageal mucosal bridges and three of them were accompanied by esophageal diverticulum. We report these cases with a review of relevant literatures.
Colon ; Diverticulum ; Diverticulum, Esophageal ; Duodenum ; Esophagus* ; Granulation Tissue ; Stomach