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Background Both human and mouse allergic contact dermatitis (ACD) frequently demonstrates a combined type 1 and type 2 immune response. However, the relative importance of type 2 immunity in this setting has been incompletely understood yet. Objective To explore an effector function of type 2 immunity in ACD with mixed type 1/type 2 immune response. Methods Gene expression characteristics of contact hypersensitivity (CHS) model was examined by quantitative polymerase chain reaction. Cytokine profile of T cells was analyzed by flow cytometry. The involvement of type 2 immunity was assessed by antibody-mediated cytokine neutralization and cell depletion. The role of specific subset of cutaneous dendritic cells was evaluated using diphtheria toxin-induced cell-depleting mouse strains. Results Oxazolone-induced CHS revealed a combination of type 1/type 2 gene expression. The severity of oxazolone-induced CHS was ameliorated by neutralization of IL-4 but not of IFN-γ, indicating that type 2 immunity plays a dominant effector function in this mixed type 1/type 2 model. Mechanistically, type 2 effector immunity was mounted by CD301b+Langeirn− dermal dendritic cells in part through thymic stromal lymphopoietin-interleukin 7 receptor alpha signaling-dependent manner. Conclusion Our findings suggest the clinical rationale for targeting type 2 immunity as a relevant therapeutic strategy for the mixed immune phenotype of ACD.

Introduction: The aim of this study was to evaluate the prognostic value of the number of lymph nodes removed in breast cancer patients who undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC). Methods: We included patients who were diagnosed with invasive breast cancer and cytology with proven involved axillary node metastasis at diagnosis and treated with NAC followed by curative surgery at Samsung Medical Center between January 2007 and December 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Results: Among 772 patients with NAC and ALND, there were 285 ypN0, 258 ypN1, 135 ypN2, and 94 ypN3 cases. The median follow-up duration was 69.0 months. The group with less than 10 lymph nodes number (

Antibody mediated rejection (AMR) after adult ABO-incompatible living donor liver transplantation (ABO-I LDLT) induced hepatic necrosis or diffuse intrahepatic biliary complications, which were related with poor graft and patient survival. Various desensitization protocols have been used to overcome these problems. Since using rituximab, the outcomes of ABO-I LDLT show a similar survival rate to those of ABO-compatible living donor liver transplantation. However, diffuse bile duct complications still occur after ABO-I LDLT. We have reviewed the past and current immune strategies for desensitization and to provide outcomes and ABO incompatibility-related complications in ABO-I LDLT.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder with an incidence of approximately 1 in 5,000 to 10,000 live births. TSC has various clinical manifestations such as multiple hamartomas in systemic organs, including the skin. Angiofibromas are the most common skin lesions in patients with TSC. Although benign, angiofibromas develop in childhood and puberty, and can be psychosocially disfiguring for patients. Skin lesions in TSC, specifically angiofibromas, have no significant risk of malignant transformation after puberty; thus, they require no treatment if not prominent. However, the presentation of TSC is important owing to its impact on patient cosmesis. Surgical treatment and laser therapy are the mainstream treatments for angiofibromas. Although the evidence is limited, topical mammalian target of rapamycin inhibitors such as sirolimus (rapamycin) are effective in facial angiofibroma treatment. We describe an adult patient with an angiofibroma who had an excellent response to treatment with topical rapamycin after a single session of carbon dioxide (CO2) laser ablation. The patient showed no sign of relapse or recurring lesions for a year. CO2 laser ablation may serve as a new paradigm of treatment for angiofibromas in TSC. Since the selection of laser devices can be limited for some institutions, we suggest a rather basic but highly effective approach for angiofibroma treatment that can be generally applied with the classic CO2 device.

Background and purpose Neurological involvement in Behcet's disease [neuro-Behcet's disease (NBD)] is uncommon, but it is worth investigating since it can cause substantial disability. However, difficulties exist in understanding the clinical features of NBD due to regional variations and the lack of studies utilizing well-established diagnostic criteria. We therefore analyzed the clinical features of patients with NBD based on the recent international consensus recommendation. Methods We retrospectively searched electronic databases for patients with Behcet's disease (BD) between 2000 and 2017, and reviewed their medical records. Based on the recent international consensus recommendation, patients with definite or probable NBD were included. Results Of 9,817 patients with the diagnosis code for BD, 1,682 (17.1%) visited the neurology clinic and 110 (1.1%) were classified as NBD. Ninety-eight patients exhibited parenchymal NBD and 12 exhibited nonparenchymal NBD. Their age at the onset of NBD was 37.6±10.6 years and the male-to-female ratio was 1.24:1. Brainstem syndrome (43.9%) was the most common condition in the 98 patients with parenchymal NBD, followed by multifocal (32.7%) and spinal cord (12.2%) syndromes. 72.4% exhibited acute NBD and 27.6% exhibited a progressive disease course. Frequent manifestations included pyramidal signs (52.0%), headache (45.9%), dysarthria (42.9%), and fever (31.6%). A frequent pattern in brain MRI was an upper brainstem lesion extending to the thalamus and basal ganglia. Conclusions Approximately 1% of the patients with suspected BD exhibited NBD. Neurologists must understand the clinical characteristics of NBD in order to perform the differential diagnosis and management of these patients.

BackgroundCirculating tumour cells (CTCs) have emerged as liquid biopsy biomarker providing non-invasive assessment of cancer progression and biology. We investigated whether longitudinal analysis of CTCs could monitor disease progression, response to chemotherapy, and survival in patients with unresectable pancreatic ductal adenocarcinoma (PDAC).MethodsCTCs were isolated using a centrifugal microfluidic disc from serially collected peripheral blood with clinical assessments. CTCs were enumerated with immunostaining against Epithelial cell adhesion molecule, Cytokeratin, Plectin-1 and CD45.ResultsCTCs were detected in 91.7% of 52 patients with unresectable PDAC at the time of diagnosis. CTC numbers were not statistically different across tumour sizes, stages and metastatic sites. The absolute CTC counts after chemotherapy was inversely related to survival, and the decreased number of CTCs after the first cycle of chemotherapy was significantly associated with longer survival.ConclusionsIdentifying CTCs and monitoring CTC changes after chemotherapy could be a useful prognostic marker for survivals in patients with unresectable PDACs.FundingThis work was supported by a grant from SK Chemical Research Fund of the Korean Society of Gastroenterology (Grant No.800-20130378) and a grant from Korean Gastroenterology Fund for Future Development. This study was granted by the Korean Health Technology R&D Project, Ministry of Health & Welfare funded by the Korean Government (Grant No. HI12C1845), and work by Y.K.Cho was partially supported by IBS-R020-D1 funded by the Korean Government. This research was supported by Collaborative Genome Program for Fostering New Post-Genome industry through the National Research Foundation (NRF) funded by the Korean government (MSIT) (Grant No. NRF-2017M3C9A5031002), and also supported by National Research Foundation (NRF) grant funded by the Korean government (MSIT) (Grant No. 2019R1C1C1008646).Clinical Trial NumberClinicalTrials.gov Identifier No. NCT02934984

The use of kidneys from donation after brain death (DBD) donors with acute kidney injury (AKI) is a strategy to expand the donor pool. The aim of this study was to evaluate how kidney transplantation (KT) from a donor with AKI affects long-term graft survival in various situations. All patients who underwent KT from DBD donors between June 2003 and April 2016 were retrospectively reviewed. The KDIGO (Kidney Disease: Improving Global Outcomes) criteria were used to classify donor AKI. The cohort included 376 donors (no AKI group, n = 117 [31.1%]; AKI group n = 259 [68.9%]). Death-censored graft survival was similar according to the presence of AKI, AKI severity, and the AKI trend (p = 0.929, p = 0.077, and p = 0.658, respectively). Patients whose donors had AKI who received using low dose (1.5 mg/kg for three days) rabbit anti-thymocyte globulin (r-ATG) as the induction agent had significantly superior death-censored graft survival compared with patients in that group who received basiliximab (p = 0.039). AKI in DBD donors did not affect long-term death-censored graft survival. Low-dose r-ATG may be considered as an induction immunosuppression in recipients receiving kidneys with AKI because it showed better graft survival than basiliximab.

The use of kidneys from donation-after-brain-death (DBD) donors with acute kidney injury (AKI) is a strategy to expand the donor pool. The aim of this study was to evaluate how kidney transplantation (KT) from a donor with AKI affects long-term graft survival in various situations. All patients who underwent KT from DBD donors between June 2003 and April 2016 were retrospectively reviewed. The KDIGO (Kidney Disease: Improving Global Outcomes) criteria were used to classify donor AKI. The cohort included 376 donors (no AKI group, n = 117 [31.1%]; AKI group n = 259 [68.9%]). Death-censored graft survival was similar according to the presence of AKI, AKI severity, and the AKI trend (p = 0.929, p = 0.077, and p = 0.658, respectively). Patients whose donors had AKI who received using low dose (1.5 mg/kg for three days) rabbit anti-thymocyte globulin (r-ATG) as the induction agent had significantly superior death-censored graft survival compared with patients in that group who received basiliximab (p = 0.039). AKI in DBD donors did not affect long-term death-censored graft survival. Low-dose r-ATG may be considered as an induction immunosuppression in recipients receiving kidneys with AKI because it showed better graft survival than basiliximab.

The association between psoriasis and risk of psychiatric diseases has not been thoroughly evaluated in a large longitudinal cohort of the Asian population. We conducted a nationwide cohort study encompassing more than 1.6 million Koreans with a 12-year follow-up period. Patients were considered to be in the psoriasis cohort if they had an incident diagnostic code for psoriasis and included patients were followed up until they developed any psychiatric disease. In adjusted models, psoriasis patients (n = 10 868) were at an 18% increased risk for depression (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.09-1.26), 16% for anxiety disorders (HR, 1.16; 95% CI, 1.08-1.26), and 21% for somatoform disorders (HR, 1.21; 95% CI, 1.08-1.34) compared with the referent cohort (n = 1 620 055). Patients with moderate-to-severe psoriasis had a higher risk of developing depression and somatoform disorders than patient with mild disease (depression, HR, 1.28; 95% CI, 1.07-1.54 vs HR, 1.17; 95% CI, 1.07-1.27; somatoform disorders, HR, 1.60; 95% CI, 1.26-2.03 vs HR, 1.13; 95% CI, 1.00-1.28). Our results highlight the burden of psychiatric diseases in patients with psoriasis in Korea and suggest that appropriate medical support for possible mental illness is warranted in Asian psoriatic patients.

Recurrent aphthous stomatitis (RAS) is a common disorder characterized by episodic ulcerations in the oral mucosa. Although colchicine has been a common systemic treatment for RAS, there is still considerable uncertainty regarding its efficacy and drug survival in this setting.We aimed to study drug survival, efficacy, and safety of colchicine for the treatment of RAS, especially in the real clinical setting.Between 2012 and 2016, 150 patients given colchicine for RAS were selected for a single-centre retrospective study of real-world efficacy and drug survival.Among the 114 patients who qualified, 81.6% showed moderate or substantial responses (25% improvement). Gastrointestinal complications (16.7%), neutropenia (3.5%), and liver enzyme elevation (4.4%) were reported within 2 weeks after initiating treatment. Delayed adverse manifestations were rare. One year after onset, colchicine use was sustained in roughly one-half (49.5%) of patients, whereas many (30.3%) had discontinued the drug, primarily due to lack of efficacy or adverse events. In Cox proportional hazard analysis, minor ulcers were identified as potential determinants of longer drug survival owing to less probability of non-efficacy. However, major ulcers had emerged as predictors of early discontinuation due to lack of efficacy.In patients with RAS, colchicine may be an effective and safe treatment amenable to long-term maintenance. Monitoring of adverse events within 2 weeks after initiating treatment is advisable to ensure safe administration.

The association between psoriasis and risk of atherosclerotic cardiovascular disease has not been thoroughly evaluated in a large longitudinal cohort of an Asian population. We conducted a nationwide population-based retrospective cohort study encompassing more than 1.7 million Koreans with a 15-year follow-up period. The period prevalence of psoriasis was 0.33% among the baseline participants (1997-2000). In Cox proportional hazard analyses, the individuals with psoriasis had a higher adjusted hazard ratio (HR) for incidence of overall atherosclerotic cardiovascular disease (HR, 1.18; 95% confidence interval [CI], 1.09-1.27) compared with controls. Subgroup analyses revealed that the risk for myocardial infarction was commonly increased in both sexes with moderate to severe psoriasis (male: HR, 2.09; 95% CI, 1.35-3.24; female: HR, 3.23; 95% CI, 1.34-7.76), whereas the risk for ischemic stroke was specifically increased in female individuals with moderate to severe psoriasis (HR, 2.02; 95% CI, 1.24-3.30). Our data suggest that appropriate medical screening for possible cardiovascular comorbidities is warranted in Asian psoriatic patients according to disease severity and sex.

Background The association between psoriasis and risk of malignancy has not been thoroughly evaluated in a large longitudinal cohort of Asian population. Objective To determine the long-term risk of malignancy in Korean adult patients with psoriasis. Methods We conducted a nationwide population-based prospective cohort study with a 15-year observational period. During the baseline period (1997-2000), total 1 773 786 Korean subjects who received health insurance from the National Health Insurance System were enrolled and 5788 subjects were defined as a psoriasis group. The number of new-onset malignancy was collected during the observational period (2001-2015). Results Patients with psoriasis had a higher adjusted hazard ratio (aHR) for development of overall malignancy [aHR 1.08, 95% confidence interval (CI) 1.00-1.18] and gastric cancer (aHR 1.31, 95% CI 1.08-1.58) compared to controls. The risks of non-Hodgkin lymphoma and non-melanoma skin cancer were significantly increased only in patients with psoriasis who received systemic treatments (aHR 2.86, 95% CI 1.07-7.61 and aHR 3.93, 95% CI 1.47-10.47, respectively). Conclusion Psoriasis is associated with long-term risk for overall malignancy in Koreans, which was primarily driven by the increased risk of gastric cancer.

Donor safety and graft results of pure laparoscopic living donor right hepatectomy (LLDRH) have previously been compared with those of open living donor right hepatectomy (OLDRH). However, the clinical outcomes of recipients at 1-year follow-up have never been accurately compared. We aimed to compare 1-year outcomes of recipients of living donor right liver transplantation (LRLT) using pure LLDRH and OLDRH. From May 2013 to May 2017, 197 consecutive recipients underwent LRLT. Donor hepatectomies were performed either by OLDRH (n = 127) or pure LLDRH (n = 70). After propensity score matching, 53 recipients were included in each group for analysis. The clinical outcomes at 1-year follow-up were compared between the 2 groups. The primary outcome was recipient death or graft failure during the 1-year follow-up period. In the propensity-matched analysis, the incidence of death or graft failure during the 1-year follow-up period was not different between the 2 groups (3.8% versus 5.7%; odds ratio [OR], 1.45; 95% confidence interval [CI], 0.24-8.95; P = 0.69). However, the composite of Clavien-Dindo 3b-5 complications was more frequent in the pure LLDRH group (OR, 2.62; 95% CI, 1.15-5.96; P = 0.02). In conclusion, although pure LLDRH affords a comparable incidence of fatal complications in recipients, operative complications may increase at the beginning of the program. The safety of the recipients should be confirmed to accept pure LLDRH as a feasible option.

Purpose Herpes zoster (HZ) is caused by reactivation of the varicella zoster virus, which occurs frequently in liver transplant recipients with impaired cellular immunity. The purpose of this study was to evaluate the incidence and risk factors for HZ after adult liver transplantation (LT). Methods In our institution, 993 patients underwent adult LT from January 1997 to December 2013. We retrospectively analyzed the incidence rate of HZ and risk factors for HZ after LT. Results Of 993 LT recipients, 101 (10.2%) were diagnosed with HZ. The incidence of HZ at 1, 3, 5, and 10 years was 6.6%, 9.1%, 10.0%, and 11.9%, respectively. Therefore, we observed that the incidence of HZ after LT was 16.3 per 1,000 person-years. Older age (≥50 years) at LT and mycophenolate mofetil (MMF) exposure were independent risk factors of HZ infection after adult LT. Conclusion Patients older than 50 years or with MMF exposure are considered to be at high risk for HZ. Therefore, adult liver recipients with such factors should not be given strong immunosuppression treatments.

The RNA-dependent RNA polymerase (RdRp) of hepatitis C virus (HCV) is the essential catalytic enzyme for viral genome replication. It initiates minus-strand RNA synthesis from a highly conserved 98-nt sequence, called the X-RNA, at the 3'-end of the plus-strand viral genome. In this study, we evaluated the antiviral effects of peptide nucleic acids (PNAs) targeting the X-RNA. Our in vitro RdRp assay results showed that PNAs targeting the three major stem-loop (SL) domains of X-RNA can inhibit RNA synthesis initiation. Delivery of X-RNA-targeted PNAs by fusing the PNAs to cell-penetrating peptides (CPPs) into HCV-replicating cells effectively suppressed HCV replication. Electrophoretic mobility shift assays revealed that the PNA targeting the SL3 region at the 5'-end of X-RNA dissociated the viral RdRp from the X-RNA. Furthermore, delivery of the SL3-targeted PNA into HCV-infected cells resulted in the suppression of HCV RNA replication without activation of interferon β expression. Collectively, our results indicate that the HCV X-RNA can be effectively targeted by CPP-fused PNAs to block RNA-protein and/or RNA-RNA interactions essential for viral RNA replication and identify X-RNA SL3 as an RdRp binding site crucial for HCV replication. In addition, the ability to inhibit RNA synthesis initiation by targeting HCV X-RNA using antisense PNAs suggests their promising therapeutic potential against HCV infection.

Hepatitis C virus (HCV) infection is a serious threat to human health worldwide. In spite of the continued search for specific and effective anti-HCV therapies, the rapid emergence of drug-resistance variants has been hampering the development of anti-HCV drugs designed to target viral enzymes. Targeting host factors has therefore emerged as an alternative strategy offering the potential to circumvent the ever-present complication of drug resistance. We previously identified protein kinase C-related kinase 2 (PRK2) as a cellular kinase that phosphorylates the HCV RNA-dependent RNA polymerase (RdRp). Here, we report the anti-HCV activity of HA1077, also known as fasudil, and Y27632, which blocks HCV RdRp phosphorylation by suppressing PRK2 activation. Treatment of a Huh7 cell line, stably expressing a genotype 1b HCV subgenomic replicon RNA, with 20 microm each of HA1077 and Y27632 reduced the HCV RNA level by 55% and 30%, respectively. A combination of the inhibitors with 100 IU/mL interferon alpha (IFN-alpha) significantly potentiated the anti-HCV drug activities resulting in approximately a 2-log(10) viral RNA reduction. We also found that IFN-alpha does not activate PRK2 as well as its upstream kinase PDK1 in HCV-replicating cells. Furthermore, treatment of HCV-infected cells with 20 microm each of HA1077 and Y27632 reduced the levels of intracellular viral RNA by 70% and 92%, respectively. Taken together, the results identify PRK2 inhibitors as potential antiviral drugs that act by suppressing HCV replication via inhibition of viral RNA polymerase phosphorylation.