Background/Aims: The eCura system, a scoring model for stratifying the lymph node metastasis risk after noncurative endoscopic resection for early gastric cancer (EGC), has been internally validated, primarily for differentiated-type EGC. We aimed to externally validate this model for undifferentiated-type EGC. Methods: This multicenter, retrospective cohort study included 634 patients who underwent additional surgery (radical surgery group, n=270) or were followed up without additional treatment (no additional treatment group, n=364) after noncurative endoscopic resection for undifferentiated-type EGC between 2005 and 2015. The lymph node metastasis and survival rates were compared according to the risk categories. Results: For the radical surgery group, the lymph node metastasis rates were 2.6%, 10.9%, and 14.8% for the low-, intermediate-, and high-risk eCura categories, respectively (p for trend=0.003). For the low-, intermediate-, and high-risk categories in the no additional treatment group, the overall survival (92.7%, 68.9%, and 80.0% at 5 years, respectively, p<0.001) and cancer-specific survival rates (99.7%, 94.7%, and 80.0% at 5 years, respectively, p<0.001) differed significantly. In the multivariate analysis, the hazard ratios (95% confidence interval) in the no additional treatment group relative to the radical surgery group were 3.18 (1.41 to 7.17; p=0.005) for overall mortality and 2.60 (0.46 to 14.66; p=0.280) for cancer-specific mortality in the intermediate-tohigh risk category. No such differences were noted in the low-risk category. Conclusions The eCura system can be applied to undifferentiated-type EGC. Close follow-up without additional treatment might be considered for low-risk patients, while additional surgery is recommended for intermediate- and high-risk patients.

Pleomorphic adenoma is the most common benign neoplasm of the salivary glands. Its three malignant variants include carcinoma ex pleomorphic adenoma, carcinosarcoma, and metastasizing pleomorphic adenoma. Among the subtypes of carcinoma ex pleomorphic adenoma, high-grade mucoepidermoid carcinoma has rarely been reported. Additionally, metastasizing pleomorphic adenoma is rare.We report the imaging findings of a high-grade mucoepidermoid carcinoma ex metastasizing pleomorphic adenoma of the parotid gland and parapharyngeal space in a 42-year-old man.

Pleomorphic adenoma is the most common benign neoplasm of the salivary glands. Its three malignant variants include carcinoma ex pleomorphic adenoma, carcinosarcoma, and metastasizing pleomorphic adenoma. Among the subtypes of carcinoma ex pleomorphic adenoma, high-grade mucoepidermoid carcinoma has rarely been reported. Additionally, metastasizing pleomorphic adenoma is rare.We report the imaging findings of a high-grade mucoepidermoid carcinoma ex metastasizing pleomorphic adenoma of the parotid gland and parapharyngeal space in a 42-year-old man.

Background/Aims: To prevent the perinatal transmission of hepatitis B virus (HBV) from mother to child, administration of an antiviral agent during pregnancy has been attempted in women who are either hepatitis B e antigen positive or have a high viral load. In this systematic review and meta-analysis with randomized controlled trials, we analyzed the efficacy and safety of tenofovir disoproxil fumarate (TDF) in preventing the perinatal transmission of HBV in pregnant women who have high HBV DNA titers. Methods: Multiple comprehensive databases (PubMed, EMBASE, and Cochrane databases) were searched for studies evaluating the efficacy of TDF for the prevention of perinatal transmission of HBV. Results: Two studies (one open label study and one double blind study) were included and analyzed. Intention-to-treat analysis (527 pregnancies) showed that the preventive effect of TDF was not significant (odds ratio [OR], 0.53; 95% confidence interval[CI], 0.13 to 2.17; p = 0.38, I2 = 81%). However, the per-protocol analysis showed that TDF significantly reduced perinatal transmission (OR, 0.10; 95% CI, 0.01 to 0.77; p = 0.03, I2 = 0%). There was no significant difference between the TDF group and the control group with respect to maternal and fetal safety outcomes. Conclusions In pregnant women who have high HBV DNA titers, TDF can reduce the perinatal transmission from mother to child without significant adverse events.

Graft-versus-host disease (GVHD), a life-threatening complication after bone marrow transplantation (BMT), is induced by activation of alloreactive donor T cells. Our previous study demonstrated that transplantation of myeloid differentiation factor 88 (MyD88)-deficient knockout (KO) bone marrow (BM) resulted in aggravation of GVHD. Here, to understand the cellular mechanism, we performed longitudinal in vivo imaging and flow cytometric analyses followed by transcriptome and functional examination of donor MyD88-KO BM progenies in GVHD hosts, using a major histocompatibility complex-matched but minor histocompatibility antigen-mismatched C57BL/6→BALB.B model. In GVHD hosts with MyD88-KO BMT, donor BM-derived CD11b+Gr-1+ cells were found to undergo cell death, a fate significantly different from the explosive expansion shown by the wild type (WT) counterparts, and also from the moderate expansion of the WT or MyD88-KO BM-derived cells in non-GVHD hosts. It was also revealed that MyD88-KO CD11b+Gr-1+ cells preferred differentiation into CD11c+ dendritic cells (DCs) to expansion as myeloid-derived suppressor cells in GVHD hosts or in high inflammatory in vitro conditions. These CD11c+ DCs comprised the majority of MyD88-KO CD11b+Gr-1+ apoptotic cells in GVHD hosts. Their ability to cross-present alloantigens of host origin contributed to the enhancement of T cell alloreactivity, causing GVHD aggravation and eventually death through the killing function of activated T cells. These results provide insights into the roles of MyD88 in myelopoiesis of donor BM and the protective effects in GVHD hosts, helpful information for development of a strategy to control GVHD.
Bone Marrow Cells* ; Bone Marrow Transplantation ; Bone Marrow* ; Cell Death ; Dendritic Cells* ; Graft vs Host Disease ; Histocompatibility ; Homicide ; Humans ; In Vitro Techniques ; Isoantigens ; Myeloid Differentiation Factor 88 ; Myelopoiesis ; T-Lymphocytes ; Tissue Donors* ; Transcriptome

The molecular mechanism underlying the initiation of somatic cell reprogramming into induced pluripotent stem cells (iPSCs) has not been well described. Thus, we generated single-cell-derived clones by using a combination of drug-inducible vectors encoding transcription factors (Oct4, Sox2, Klf4 and Myc) and a single-cell expansion strategy. This system achieved a high reprogramming efficiency after metabolic and epigenetic remodeling. Functional analyses of the cloned cells revealed that extracellular signal-regulated kinase (ERK) signaling was downregulated at an early stage of reprogramming and that its inhibition was a driving force for iPSC formation. Among the reprogramming factors, Myc predominantly induced ERK suppression. ERK inhibition upregulated the conversion of somatic cells into iPSCs through concomitant suppression of serum response factor (SRF). Conversely, SRF activation suppressed the reprogramming induced by ERK inhibition and negatively regulated embryonic pluripotency by inducing differentiation via upregulation of immediate early genes, such as c-Jun, c-Fos and EGR1. These data reveal that suppression of the ERK-SRF axis is an initial molecular event that facilitates iPSC formation and may be a useful surrogate marker for cellular reprogramming.

Meningitis is a common central nervous system (CNS) complication of the mumps, a viral infection, but encephalitis and meningoencephalitis are less common in mumps. We describe magnetic resonance imaging findings of acute mumps meningoencephalitis in a 32-year-old male who showed bilateral hippocampal lesions without preceding parotitis. Although it is rare, hippocampal involvement should be considered a CNS complication of mumps infection.
Adult ; Brain ; Central Nervous System ; Encephalitis ; Hippocampus ; Humans ; Magnetic Resonance Imaging* ; Male ; Meningitis ; Meningoencephalitis* ; Mumps* ; Parotitis*

BACKGROUND: Although intraoperative opioids provide more comfortable anesthesia and reduce the use of postoperative analgesics, it may cause opioid induced hyperalgesia (OIH). OIH is an increased pain response to opioids and it may be associated with N-methyl-D-aspartate (NMDA) receptor. This study aimed to determine whether intraoperative nefopam or ketamine, known being related on NMDA receptor, affects postoperative pain and OIH after continuous infusion of intraoperative remifentanil. METHODS: Fifty-four patients undergoing laparoscopic cholecystectomy were randomized into three groups. In the nefopam group (N group), patients received nefopam 0.3 mg/kg at the induction of anesthesia followed by a continuous infusion of 0.065 mg/kg/h. In the ketamine group (K group), patients received ketamine 0.3 mg/kg at the induction of anesthesia followed by a continuous infusion of 3 µg/kg/min. The control group did not received any other agents except for the standard anesthetic regimen. Postoperative pain score, first time and number of demanding rescue analgesia, OIH and degrees of drowsiness/sedation scale were examined. RESULTS: Co-administrated nefopam or ketamine significantly reduced the total amount of intraoperative remifentanil and postoperative supplemental morphine. Nefopam group showed superior property over control and ketamine group in the postoperative VAS score and recovery index (alertness and respiratory drive), respectively. Nefopam group showed lower morphine consumption than ketamine group, but not significant. CONCLUSIONS: Both nefopam and ketamine infusion may be useful in managing in postoperative pain control under concomitant infusion of remifentanil. However, nefopam may be preferred to ketamine in terms of sedation.
Analgesia ; Analgesics ; Analgesics, Opioid ; Anesthesia ; Cholecystectomy, Laparoscopic* ; Humans ; Hyperalgesia ; Ketamine* ; Morphine ; N-Methylaspartate ; Nefopam* ; Pain, Postoperative*

PURPOSE: Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) binds to low-density lipoprotein. The levels of Lp-PLA2 reflect the plaque burden, and are upregulated in acute coronary syndrome (ACS). We investigated the diagnostic value of Lp-PLA2 levels and found that it might be a potential biomarker for ACS. MATERIALS AND METHODS: We classified 226 study participants into three groups: patients without significant stenosis (control group), patients with significant stenosis with stable angina (SA group), and patients with ACS (ACS group). RESULTS: Lp-PLA2 and high-sensitivity C-reactive protein (hs-CRP) levels were significantly greater in the ACS group than in the SA group (p=0.044 and p=0.029, respectively). Multivariate logistic regression analysis revealed that Lp-PLA2 levels are significantly associated with ACS (odds ratio=1.047, p=0.013). The addition of Lp-PLA2 to the ACS model significantly increased the global chi2 value over traditional risk factors (28.14 to 35.602, p=0.006). The area under the receiver operating characteristic curve for Lp-PLA2 was 0.624 (p=0.004). The addition of Lp-PLA2 level to serum hs-CRP concentration yielded an integrated discrimination improvement of 0.0368 (p=0.0093, standard error: 0.0142) and improved the ability to diagnose ACS. CONCLUSION: Lp-PLA2 levels are related to plaque stability and might be a diagnostic biomarker for ACS.
1-Alkyl-2-acetylglycerophosphocholine Esterase/*blood ; Acute Coronary Syndrome/*blood/physiopathology ; Aged ; Aged, 80 and over ; Angina Pectoris ; Biological Markers/blood ; C-Reactive Protein/*metabolism ; Coronary Angiography ; Female ; Humans ; Lipoproteins, LDL/*blood ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Plaque, Atherosclerotic/blood ; ROC Curve ; Risk Factors