Purpose: Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL). Materials and Methods: After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes. Results: Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE. Conclusion Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.

Purpose: Analysis of circulating tumor DNA (ctDNA) in blood could allow noninvasive genetic analysis of primary tumors. Although there have been unmet needs for noninvasive methods in patients with primary central nervous system lymphoma (PCNSL), it is still not determined whether plasma ctDNA analysis could be useful for patients with PCNSL. Materials and Methods: Targeted deep sequencing of 54 genes was performed in cell-free DNA isolated from plasma samples collected pretreatment, during treatment, and at the end of treatment in 42 consecutively diagnosed PCNSL patients between January 2017 and December 2018. Results: Targeted sequencing of plasma cell-free DNA detected somatic mutations representing ctDNA in 11 cases (11/41, 27%). The detection of ctDNA was not related to the concentration of cell-free DNA or tumor volume. The mutation profiles of these 11 cases varied between patients. The most frequently mutated gene was PIM1 (4/11, 36.4%), whereas KMT2D, PIK3CA, and MYD88 were each observed in three patients (3/11, 27%). The mutations of 13 genes were concordantly found in primary tumor tissue and plasma ctDNA, giving a detection sensitivity of 45%. During the serial tracking of seven patients with complete response, the disappearance of ctDNA mutations was found in four patients, whereas three patients had detected ctDNA mutation at the end of treatment. Conclusion The plasma ctDNA mutation analysis still has limited value for surveillance and predicting treatment outcomes of PCNSL because the detection efficiency was lower than other systemic lymphomas. Thus, analytical platforms should be improved to overcome anatomical hurdles associated with PCNSL.

Exenatide extended-release was recently developed as an antidiabetic drug; it acts as a glucagon-like peptide-1 receptor agonist. A 54-year-old male visited our clinic complaining of a subcutaneous tender nodule on his left thigh that had developed over the course of 1 week. The patient had received exenatide extended-release injections for 5 months to treat diabetes. A histopathologic examination showed septal and lobular panniculitis with lymphohistiocyte and eosinophil infiltration. The patient was diagnosed with eosinophilic panniculitis (EP) due to exenatide extended- release injection. EP is a rare type of panniculitis characterized by a prominent infiltrate of eosinophils in the subcutaneous fat layer. It is a histologic reaction pattern that is associated with various clinical conditions. Among the injection- site reactions reported in exenatide extended-release users, injection-site nodules occur infrequently. Clinicians who treat diabetics who use exenatide extended-release should be aware of the possible occurrence of injection-site nodules.

BACKGROUND: Alopecia areata (AA), a chronic, relapsing hair-loss disorder, is considered to be a T-cell-mediated autoimmune disease. Cold-inducible RNA-binding protein (CIRP) belongs to a family of cold-shock proteins that respond to cold stress, and has been identified as a damage-associated molecular pattern (DAMP) molecule that triggers the inflammatory response. Recent studies have shown that high-mobility group box 1, another DAMP molecule, is elevated in serum and scalp tissue of AA patients, suggesting a relationship between DAMP molecules and the pathogenesis of AA. OBJECTIVE: To investigate the clinical significance of serum CIRP levels in AA. METHODS: The serum levels of CIRP were compared between 68 patients with AA and 20 healthy controls. Additionally, the correlation between CIRP level and various clinical parameters was evaluated. RESULTS: The serum CIRP levels were significantly higher in AA patients compared to healthy subjects. Moreover, there was an association between the serum CIRP level and clinical characteristics, such as disease duration and disease activity. However, there was no significant difference in the serum CIRP level among the clinical types of AA (AA multiplex, alopecia totalis, and alopecia universalis). CONCLUSION: These results suggest that CIRP may play a significant role in the pathogenesis of AA and could be a potential biologic marker for monitoring the disease activity of AA.
Alopecia Areata ; Alopecia ; Autoimmune Diseases ; Biomarkers ; Healthy Volunteers ; Humans ; Inflammation ; RNA-Binding Proteins ; Scalp

PURPOSE: The purpose of this study was to evaluate the clinical features and the long-term outcomes of primary conjunctival marginal zone B-cell lymphoma (MZBCL) patients who were treated with radiation therapy (RT). MATERIALS AND METHODS: Retrospective data of 79 patients with 121 primary conjunctival MZBCL lesions were collected from January 1, 2001 till June 30, 2014. All lesions were treated by local RT (26 Gy) with patient-specific customized lens-shielding device. RESULTS: The current Korean patients' cohort showed younger median age at diagnosis (38 years), great female preponderance (78.5%) and more frequent bilateral involvement (53.2%) than the previous studies. Following 26 Gy's RT, excellent clinical outcomes were achieved: 5-year rates of overall survival, local relapse-free survival, and contralateral relapse-free survival were 100%, 98.1%, and 91.5%, respectively. Two patients (2.5%) developed local relapse and five (6.3%) developed relapse at initially uninvolved contralateral conjunctiva with median interval of 52.9 months, and late adverse events of grade 2 and 3 occurred in seven (8.8%) and two (2.5%) patients, respectively. CONCLUSION: 26 Gy's RT was highly effective and safe, with the use of lens-shielding device, in treating patients with primary conjunctival MZBCL.
Cohort Studies ; Conjunctiva ; Diagnosis ; Female ; Humans ; Lymphoma, B-Cell, Marginal Zone* ; Radiotherapy ; Recurrence ; Retrospective Studies

BACKGROUND: Risk factors for bone avascular necrosis (AVN), a common late complication after kidney transplantation (KT), are not well known. METHODS: Patients that underwent living-donor KT at Asan Medical Center between January 2009 and July 2016 were included in this retrospective study to determine the incidence and risk factors for AVN after KT. RESULTS: Among 1,570 patients that underwent living-donor KT, 33 (2.1%) developed AVN during a mean follow-up of 49.8±25.0months. Additionally, AVN was diagnosed at a mean of 13.9±6.6 months after KT. The mean cumulative corticosteroid dose during the last follow-up in patients without AVN (9,108±3,400 mg) was higher than that that in patients with AVN (4,483±1,114 mg) until AVN development (P < 0.01). More patients among those with AVN (n=4, 12.1%) underwent steroid pulse treatment because of biopsy-proven rejections during the first 6 months after KT than patients without AVN (n=68, 4.4%; P=0.04). Female (hazard ratio [HR], 2.29; P=0.04) and steroid pulse treatment during the first 6 months (HR, 2.31; P=0.02) were significant AVN risk factors as revealed by the Cox proportional multivariate analysis. However, no significant differences in rejection-free graft survival rates were observed between the two groups (P=0.67). CONCLUSIONS: Steroid pulse treatment within 6 months of KT and being female were independent risk factors for AVN development.
Chungcheongnam-do ; Female ; Follow-Up Studies ; Graft Survival ; Humans ; Immunosuppression ; Incidence ; Kidney Transplantation* ; Kidney* ; Multivariate Analysis ; Necrosis* ; Osteonecrosis ; Retrospective Studies ; Risk Factors

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) may be one of the important causes of cryptogenic hepatocellular carcinoma (HCC). The aim of this study was to evaluate whether patients with cryptogenic HCC share clinical features similar to that of NAFLD. METHODS: Cryptogenic HCC was defined as HCC that occurs in patients with the following conditions: HBsAg(-), anti-HCV(-), and alcohol ingestion of less than 20 g/day. All patients diagnosed with cryptogenic HCC from 2005 to 2012 (cryptogenic HCC group), and all patients diagnosed with HBV associated HCC between 2008 and 2012 (HBV-HCC group) were enrolled in the present study. Clinical features, BMI, lipid profiles, presence of diabetes mellitus, hypertension, and metabolic syndrome were compared between the two groups. RESULTS: Cryptogenic HCC group was composed of 35 patients (19 males and 16 females) with a mean age of 70+/-11 years. HBV-HCC group was composed of 406 patients (318 males and 88 females) with a mean age of 56+/-7 years. Patients in the cryptogenic HCC group were older (p=0.001) and female dominant (p=0.042) than those in the HBV-HCC group. There were no differences in the laboratory test results including lipid profiles and Child-Turcotte-Pugh class between the two groups. Patients in the cryptogenic HCC group had higher prevalence of diabetes (37% vs. 17%, p=0.015), hypertension (49% vs. 27%, p=0.051), metabolic syndrome (37% vs. 16%, p=0.001), and higher BMI (25.3 kg/m2 vs. 24.1 kg/m2, p=0.042) than those in the HBV-HCC group. The tumor stage was more advanced (stage III and IV) at diagnosis in the cryptogenic HCC group than in the HBV-HCC group (60% vs. 37%, p=0.007). CONCLUSIONS: Cryptogenic HCC has clinical features similar to that of NAFLD and is diagnosed at a more advanced tumor stage.
Age Factors ; Aged ; Body Mass Index ; Carcinoma, Hepatocellular/*diagnosis/etiology/pathology ; Diabetes Complications ; Diabetes Mellitus/pathology ; Female ; Hepatitis B/complications ; Humans ; Hypertension/complications ; Lipids/blood ; Liver Neoplasms/*diagnosis/etiology/pathology ; Male ; Metabolic Syndrome X/complications ; Middle Aged ; Neoplasm Staging ; Non-alcoholic Fatty Liver Disease/*diagnosis/pathology ; Risk Factors ; Severity of Illness Index ; Sex Factors

No abstract available.
Anesthesia ; Cardiopulmonary Bypass ; Humans ; Lung ; Pneumothorax

OBJECTIVE: Preimplantation genetic diagnosis (PGD) is an assisted reproductive technique for couples carrying genetic risks. Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuropathy, with a prevalence rate of 1/2,500. In this study, we report on our experience with PGD cycles performed for CMT types 1A and 2F. METHODS: Before clinical PGD, we assessed the amplification rate and allele drop-out (ADO) rate of multiplex fluorescent polymerase chain reaction (PCR) followed by fragment analysis or sequencing using single lymphocytes. We performed six cycles of PGD for CMT1A and one cycle for CMT2F. RESULTS: Two duplex and two triplex protocols were developed according to the available markers for each CMT1A couple. Depending on the PCR protocols, the amplification rates and ADO rates ranged from 90.0% to 98.3% and 0.0% to 11.1%, respectively. For CMT2F, the amplification rates and ADO rates were 93.3% and 4.8%, respectively. In case of CMT1A, 60 out of 63 embryos (95.2%) were diagnosed and 13 out of 21 unaffected embryos were transferred in five cycles. Two pregnancies were achieved and three babies were delivered without any complications. In the case of CMT2F, a total of eight embryos were analyzed and diagnosed. Seven embryos were diagnosed as unaffected and four embryos were transferred, resulting in a twin pregnancy. Two healthy babies were delivered. CONCLUSION: This is the first report of successful pregnancy and delivery after specific PGD for CMT disease in Korea. Our PGD procedure could provide healthy babies to couples with a high risk of transmitting genetic diseases.
Alleles ; Charcot-Marie-Tooth Disease* ; Embryonic Structures ; Family Characteristics ; Korea ; Lymphocytes ; Polymerase Chain Reaction ; Pregnancy ; Pregnancy, Twin ; Preimplantation Diagnosis* ; Prevalence ; Prostaglandins D ; Reproductive Techniques, Assisted

PURPOSE: Total knee replacement is one of the most painful orthopedic procedures, and effective pain relief is essential for early mobility and discharge from hospital. The aim of this study was to evaluate whether addition of single-injection femoral nerve block to epidural analgesia would provide better postoperative pain control, compared to epidural analgesia alone, after total knee replacement. MATERIALS AND METHODS: Thirty-eight patients received a single-injection femoral nerve block with 0.25% levobupivacaine (30 mL) combined with epidural analgesia (femoral nerve block group) and 40 patients received epidural analgesia alone (control group). Pain intensity and volume of patient-controlled epidural analgesia medication and rescue analgesic requirements were measured in the first 48 hours after surgery at three time periods; 0-6 hours, 6-24 hours, and 24-48 hours. Also, side effects such as nausea, vomiting, and pruritus were evaluated. RESULTS: Median visual analog scale at rest and movement was significantly lower until 48 hours in the femoral nerve block group. Patient-controlled epidural analgesia volume was significantly lower throughout the study period, however, rescue analgesia requirements were significantly lower only up to 6 hours in the femoral nerve block group. The incidences of nausea and vomiting and rescue antiemetic requirement were significantly lower in the femoral nerve block group up to 6 hours. CONCLUSION: The combination of femoral nerve block with epidural analgesia is an effective pain management regimen in patients undergoing unilateral total knee replacement.
Aged ; Analgesia, Epidural/*methods ; Analgesia, Patient-Controlled/*methods ; Anesthetics, Local/administration & dosage/therapeutic use ; Arthroplasty, Replacement, Knee/*methods ; Bupivacaine/administration & dosage/analogs & derivatives/therapeutic use ; Female ; Femoral Nerve/*drug effects ; Humans ; Injections ; Male ; Middle Aged ; Nerve Block/*methods