Objective: To compare the clinical and radiological features of various etiologies of chronic diffuse lacrimal gland enlargement. Materials and Methods: We retrospectively reviewed 91 consecutive patients who underwent surgical biopsy for chronic diffuse lacrimal gland enlargement and were diagnosed with non-specific dacryoadenitis (DA) (n = 42), immunoglobulin G4-related dacryoadenitis (IgG4-RD) (n = 33), and lymphoma (n = 16). Data on patient demographics, clinical presentation, and CT imaging findings (n = 73) and MRI (n = 43) were collected. The following radiologic features of lacrimal gland enlargement were evaluated: size, unilaterality, wedge sign, angle with the orbital wall, heterogeneity, signal intensity, degree of enhancement, patterns of dynamic contrast-enhanced, and apparent diffusion coefficient value. Radiological features outside the lacrimal glands, such as extra-lacrimal orbital involvement and extra-orbital head and neck involvement, were also evaluated. The clinical and radiological findings were compared among the three diseases. Results: Compared to the DA and IgG4-RD groups, the lymphoma group was significantly older (mean 59.9 vs. 46.0 and 49.4 years, respectively; p = 0.001) and had a higher frequency of unilateral involvement (62.5% vs. 31.0% and 15.2%, respectively;p = 0.004). Compared to the IgG4-RD and lymphoma groups, the DA group had significantly smaller lacrimal glands (2.3 vs. 2.8 and 3.3 cm, respectively; p < 0.001) and a lower proportion of cases with a wedge sign (54.8% vs. 84.8% and 87.5%, respectively; p = 0.005). The IgG4-RD group showed more frequent involvement of the extra-orbital head and neck structures, including the infraorbital nerve (36.4%), paranasal sinus (72.7%), and salivary gland (58.6%) compared to the DA and lymphoma groups (4.8%–28.6%) (all p < 0.005). Conclusion Patient age, unilaterality, lacrimal gland size, wedge sign, and extra-orbital head and neck involvement differed significantly different between lymphoma, DA, and IgG4-RD. Our results will be useful for the differential diagnosis and proper management of chronic lacrimal gland enlargement.

The purpose of this extension study was to assess the long-term efficacy and safety of gemigliptin 50 mg in patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who had completed the initial 24-week study comparing gemigliptin monotherapy with placebo were eligible to enrol. In the open-label, 28-week extension study, all enrolled patients received gemigliptin, regardless of the treatment received during the initial 24-week study period. The mean reduction±standard deviation (SD) in glycosylated hemoglobin (HbA1c) observed after 24 weeks of treatment (–0.6%±1.1%) was further decreased for the gemi-gemi group and the mean change in HbA1c at week 52 from baseline was –0.9%±1.2% (P<0.0001). For the pbo-gemi group, HbA1c decreased after they were switched to gemigliptin, and the mean change in HbA1c at week 52 from baseline was –0.7%±1.2% (P<0.0001). Furthermore, the overall incidence of adverse events demonstrated that gemigliptin was safe and well tolerated up to 52 weeks.

The purpose of this extension study was to assess the long-term efficacy and safety of gemigliptin 50 mg in patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who had completed the initial 24-week study comparing gemigliptin monotherapy with placebo were eligible to enrol. In the open-label, 28-week extension study, all enrolled patients received gemigliptin, regardless of the treatment received during the initial 24-week study period. The mean reduction±standard deviation (SD) in glycosylated hemoglobin (HbA1c) observed after 24 weeks of treatment (–0.6%±1.1%) was further decreased for the gemi-gemi group and the mean change in HbA1c at week 52 from baseline was –0.9%±1.2% (P<0.0001). For the pbo-gemi group, HbA1c decreased after they were switched to gemigliptin, and the mean change in HbA1c at week 52 from baseline was –0.7%±1.2% (P<0.0001). Furthermore, the overall incidence of adverse events demonstrated that gemigliptin was safe and well tolerated up to 52 weeks.

Anti-Bacterial Agents ; Cefazolin ; Drug Hypersensitivity ; Electronic Health Records ; Humans ; Hypersensitivity ; Hypersensitivity, Immediate ; Intradermal Tests ; Mass Screening ; Medical Records ; Prospective Studies ; Seoul ; Skin Tests ; Skin ; Specialization

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

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: To investigate the effect of oncostatin M (OSM) on protein expression levels and enzymatic activities of matrix metalloprotainase (MMP)-2 and MMP-9 in primary trophoblasts and the invasiveness thereof under normoxia and hypoxia conditions. MATERIALS AND METHODS: Protein expression levels and enzymatic activities of MMP-2 and MMP-9 in primary trophoblasts under normoxia and hypoxia conditions were examined by Western blot and zymography, respectively. Effects of exogenous OSM on the in vitro invasion activity of trophoblasts according to oxygen concentration were also determined. Signal transducer and activator of transcription 3 (STAT3) siRNA was used to determine whether STAT3 activation in primary trophoblasts was involved in the effect of OSM. RESULTS: OSM enhanced protein expression levels and enzymatic activities of MMP-2 and MMP-9 in term trophoblasts under hypoxia condition, compared to normoxia control (p < 0.05). OSM-induced MMP-2 and MMP-9 enzymatic activities were significantly suppressed by STAT3 siRNA silencing under normoxia and hypoxia conditions (p < 0.05). Hypoxia alone or OSM alone did not significantly increase the invasiveness of term trophoblasts. However, the invasion activity of term trophoblasts was significantly increased by OSM under hypoxia, compared to that without OSM treatment under normoxia. CONCLUSION: OSM might be involved in the invasiveness of extravillous trophoblasts under hypoxia conditions via increasing MMP-2 and MMP-9 enzymatic activities through STAT3 signaling. Increased MMP-9 activity by OSM seems to be more important in primary trophoblasts.
Anoxia* ; Blotting, Western ; In Vitro Techniques ; Oncostatin M* ; Oxygen ; RNA, Small Interfering ; STAT3 Transcription Factor ; Trophoblasts*

BACKGROUND: The purpose of this study was to compare the fetal/infant mortality risk associated with each additional week of expectant management to that associated with immediate delivery in women with multiple gestations. METHODS: This was a retrospective national cohort study of 94,170 multiple deliveries, 92,619 (98.4%) twin and 1,352 (1.44%) triplet pregnancies, between 32 0/7 and 42 6/7 weeks of gestation recorded in the Korean vital statistics database. We investigated the risks of stillbirth and infant death after birth in Korea according to the week of gestation in twin and triplet pregnancies. RESULTS: The risk of stillbirth significantly increased between 34 and 35 weeks of gestation and between 37 and 38 weeks of gestation in twin pregnancies and between 34 and 37 weeks of gestation in triplet pregnancies. The risk of infant death following delivery gradually decreased as pregnancies approached full term. Week-by-week differences were statistically significant between 33 and 34 weeks, with decreasing risks of infant death at advancing gestational ages in twin pregnancies. At 37 weeks of gestation, the relative risk of mortality was significantly higher with expectant management compared with immediate delivery (relative risk, 3.00; 95% confidence interval, 1.41–6.38). CONCLUSION: In twin pregnancies, delivery at 37 weeks of gestation can minimize the risks of stillbirth and infant death in uncomplicated cases, although individual maternal and fetal characteristics must be considered when determining the optimal timing of delivery. In multiple pregnancies, close fetal surveillance is needed after 34 weeks of gestation.
Cohort Studies* ; Delivery, Obstetric ; Female ; Gestational Age ; Humans ; Infant Death* ; Infant* ; Korea ; Mortality ; Parturition ; Pregnancy ; Pregnancy, Multiple* ; Pregnancy, Triplet ; Pregnancy, Twin ; Retrospective Studies ; Stillbirth* ; Twins ; Vital Statistics

OBJECTIVE: To assess intra- and inter-observer reproducibility of a new point shear wave elastography technique (pSWE, S-Shearwave, Samsung Medison) and compare its accuracy in assessing liver stiffness (LS) with an established pSWE technique (Virtual Touch Quantification, VTQ). MATERIALS AND METHODS: Thirty-three patients were enrolled in this Institutional Review Board-approved prospective study. LS values were measured by VTQ on an Acuson S2000 system (Siemens Healthineer) and S-Shearwave on an RS-80A (Samsung Medison) in the same session, followed by two further S-Shearwave sessions for inter- and intra-observer variation at 8-hour intervals. The technical success rate (SR) and reliability of the measurements of both pSWE techniques were compared. The intra- and inter-observer reproducibility of S-Shearwave was determined by intraclass correlation coefficients (ICCs). LS values were measured by both methods of pSWE. The diagnostic performance in severe fibrosis (F ≥ 3) and cirrhosis (F = 4) was evaluated using the receiver operating characteristics curve analysis and the Obuchowski measure with the LS values of transient elastography as the referenced standard. RESULTS: The VTQ (100%, 33/33) and S-Shearwave (96.9%, 32/33) techniques did not display a significant difference in technical SR (p = 0.63) or reliability of LS measurements (96.9%, 32/33; 93.9%, 30/32, respectively, p = 0.61). The inter- and intra-observer agreement for LS measurements using the S-Shearwave technique was excellent (ICC = 0.98 and 0.99, respectively). The mean LS values of both pSWE techniques were not significantly different and exhibited a good correlation (r = 0.78). To detect F ≥ 3 and F = 4, VTQ and S-Shearwave showed comparable diagnostic accuracy as indicated by the following outcomes: areas under receiver operating characteristics curve (AUROC) = 0.87 (95% confidence intervals [CI] 0.70–0.96), 0.89 for VTQ (95% CI 0.74–0.97), respectively; and AUROC = 0.84 (95% CI 0.67–0.94), 0.94 (95% CI 0.80–0.99) for S-Shearwave (p > 0.48), respectively. The Obuchowski measures were similarly high for S-Shearwave and VTQ (0.94 vs. 0.95). CONCLUSION: S-Shearwave shows excellent inter- and intra-observer agreement and diagnostic effectiveness comparable to VTQ in detecting LS.
Elasticity Imaging Techniques ; Fibrosis ; Humans ; Liver Cirrhosis ; Liver Diseases* ; Liver* ; Observer Variation ; Prospective Studies* ; ROC Curve

OBJECTIVE: To evaluate the prevalence and associated factors involved in cellulitis with lymphangitis among a group of Korean patients who were being treated for lymphedema. We present our epidemiologic research and we also report a systematic review of these types of cases. METHODS: This was a retrospective medical record study among 1,246 patients diagnosed with lymphedema. The study was carried out between January 2006 and December 2012 at the Kosin University Gospel Hospital and Seoul National University Bundang Hospital. Cases were examined for onset time, affected site, seasonal trend, and recurrence pattern of lymphedema, lymphangitis, and cellulitis. We also evaluated the history of blood-cell culture and antibiotic use. RESULTS: Ninety-nine lymphedema patients experienced complications such as cellulitis with accompanying lymphangitis. Forty-nine patients had more than two recurrences of cellulitis with lymphangitis. The incidence and recurrence of cellulitis with lymphangitis were significantly higher in the patients with lower-extremity lymphedema. There was a significant trend toward higher cellulitis prevalence in the lower-extremity lymphedema group according to the time of lymphedema onset. Among the cellulitis with lymphangitis cases, 62 cases were diagnosed through blood-cell culture; 8 of these 62 cultures were positive for β-hemolytic streptococci. CONCLUSION: The prevalence rate of cellulitis with lymphangitis in patients with lymphedema was 7.95%, and the prevalence of recurrent episodes was 3.93%. Especially, there was high risk of cellulitis with lymphangitis after occurrence of lower-extremity lymphedema with passage of time. Lymphedema patients should be fully briefed about the associated risks of cellulitis before treatment, and physicians should be prepared to provide appropriate preventive education.
Cellulitis* ; Education ; Humans ; Incidence ; Lymphangitis ; Lymphedema* ; Medical Records ; Prevalence* ; Recurrence ; Retrospective Studies ; Seasons ; Seoul