No abstract available.
Ductus Arteriosus, Patent* ; Endarteritis*

PURPOSE: Rheumatoid arthritis (RA) is a common, chronic inflammatory arthritis that develops most often in women. Gonadal hormones may account for the sexual dimorphism in the immune response and for the greater incidence of autoimmune disease in females. Gonadotrophin-releasing hormone (GnRH), one of the gonadal hormones, plays an important role in immune system modulation. This study examined the effects of single nucleotide polymorphisms (SNP) in GnRH on gender differences in the pathophysiology of RA. MATERIALS AND METHODS: The presence of SNPs rs2659590, rs2321248, rs6186, rs6185, and rs2321049 in the human GnRH1 gene was confirmed in Korean RA patients by Taqman(R) SNP genotyping assays. A total of 153 unrelated female, Korean RA patients and 96 female Korean controls participated. RESULTS: There were no significant associations between GnRH1 polymorphisms and RA. However, we found that the rs2659590, rs6185 and rs2321248 polymorphism might be associated with a susceptibility to aberrantly high erythrocyte sedimentation rates in female RA patients. CONCLUSION: Additional studies, with a larger number of patients and in different populations will be required to assess whether GnRH1 polymorphisms and these haplotypes could be used as susceptibility or resistance markers in RA. To our knowledge, this study is the first to analyze associations between SNPs of GnRH1 and RA.
Arthritis ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Blood Sedimentation ; Female ; Gonadal Hormones ; Gonadotropin-Releasing Hormone ; Haplotypes ; Humans ; Immune System ; Incidence ; Polymorphism, Single Nucleotide

BACKGROUND: Both human leukocyte antigen (HLA) class I and programmed death-ligand 1 (PD-L1) molecules are known to play important roles in cancer immunity. In this study, we evaluated HLA class I expression in resected adenocarcinoma of the lung, and investigated its prognostic impact in correlation with PD-L1 expression. METHODS: HLA class I and PD-L1 expression was evaluated by immunohistochemistry in a total of 403 resected lung adenocarcinomas using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed. RESULTS: HLA class I expression was reduced in 91.6% of adenocarcinoma, and more frequently reduced in patients with younger age, absence of vascular invasion, and low pathologic stage (p = .033, p = .007, and p = .012, respectively). Positive PD-L1 expression in tumor cells was 16.1% (1% cut-off), and associated with poor differentiation, presence of vascular invasion and nodal metastasis (p < .001, p = .002, and p = .032, respectively). On survival analysis, HLA class I or PD-L1 expression alone did not show any statistical significance. On the integrated analysis, HLA class I (+)/PD-L1 (+) subgroup showed a significantly shorter overall survival than other groups (p = .001). Multivariate analysis revealed that coexpression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p < .001; hazard ratio, 6.106; 95% confidence interval, 2.260 to 16.501). CONCLUSIONS: Lung adenocarcinoma with coexpression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite HLA expression.
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung ; Humans ; Immunohistochemistry ; Leukocytes ; Lung ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis

Viral infections can be causative in many glomerular disease, and human immunodeficiency virus (HIV) infection is closely related to a collapsing focal segmental glomerulosclerosis (FSGS). This is known as HIV associated nephropathy (HIVAN) and is characterized clinically by proteinuria, often of sudden onset, with rapidly progressive renal dysfunction resulting in end stage renal disease (ESRD) over several months. Increasingly, other primary renal diseases are being described in HIV infected patients, including IgA nephropathy, an immune complex lupus-like neprhopathy, and tubulonephritis. We observed rare HIVAN case presenting membranous glomerulonephritis with nephrotic syndrome in a woman who was positive for HIV without hepatitis B viral infection. She was treated with Methylprednisolone 60 mg/day, zidovudine 600 mg/day, efavirenz 60 mg/day, and lamivudine 300 mg/day for 5 months. After treatment, proteinuria decreased from 4,092 mg/day to 419 mg/day and CD4 T cell count rose from 594/mL to 1,176/mL. The effectiveness and safety of corticosteroids in the treatment of HIVAN remained controversial but this case showed good response for steroid with triple antiviral therapy about HIVAN especially membranous glomerulonephritis.
Adrenal Cortex Hormones ; AIDS-Associated Nephropathy ; Antigen-Antibody Complex ; Cell Count ; Female ; Glomerulonephritis, IGA ; Glomerulonephritis, Membranous* ; Glomerulosclerosis, Focal Segmental ; Hepatitis B ; HIV Infections* ; HIV* ; Humans ; Kidney Failure, Chronic ; Lamivudine ; Methylprednisolone ; Nephrotic Syndrome ; Proteinuria ; Zidovudine

Background: Activating mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) are predictive biomarkers for response to EGFR–tyrosine kinase inhibitor (TKI) therapy in lung adenocarcinoma (LUAD). Here, we characterized the clinicopathologic features associated with EGFR mutations via peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper) and evaluated the feasibility of targeted deep sequencing for detecting the mutations. Methods: We examined EGFR mutations in exons 18 through 21 for 2,088 LUADs from July 2017 to April 2020 using PANAMutyper. Of these, we performed targeted deep sequencing in 73 patients and evaluated EGFR-mutation status and TKI clinical response. Results: EGFR mutation was identified in 55.7% of LUADs by PANAMutyper, with mutation rates higher in females (69.3%) and never smokers (67.1%) and highest in the age range of 50 to 59 years (64.9%). For the 73 patients evaluated using both methods, next-generation sequencing (NGS) identified EGFR mutation–positive results in 14 of 61 patients (23.0%) who were EGFR-negative according to PANAMutyper testing. Of the 10 patients reportedly harboring a sensitizing mutation according to NGS, seven received TKI treatment, with all showing partial response or stable disease. In the 12 PANAMutyper-positive cases, NGS identified two additional mutations in exon 18, whereas a discordant negative result was observed in two cases. Conclusions Although PANAMutyper identified high frequencies of EGFR mutations, targeted deep sequencing revealed additional uncommon EGFR mutations. These findings suggested that appropriate use of NGS may benefit LUAD patients with otherwise negative screening test results.

Purpose: Pulmonary sarcomatoid carcinoma (PSC) is a rare aggressive subtype of non–small cell lung cancer (NSCLC) with limited therapeutic strategies. We attempted to elucidate the evolutionary trajectories of PSC using multiregional and longitudinal tumor samples. Materials and Methods: A total of 31 patients were enrolled in this study and 11 longitudinal samples were available from them. Using whole exome sequencing data, we analyzed the mutational signatures in both carcinomatous and sarcomatous areas in primary tumors of the 31 patients and longitudinal samples obtained from 11 patients. Furthermore, digital droplet polymerase chain reaction (ddPCR), and programmed death-ligand 1 (PD-L1) immunohistochemistry using the Ventana SP263 assay were performed. Results: TP53 was identified as the most frequently altered gene in the primary (74%) and metastatic (73%) samples. MET exon 14 skipping mutations, confirmed by ddPCR, and TP53 mutations were mutually exclusive; whereas, MET exon 14 skipping mutations frequently co-occurred with MDM2 amplification. Metastatic tumors showed dissimilar genetic profiles from either primary component. During metastasis, the signatures of APOBEC decreased in metastatic lesions compared with that in primary lesions. PSC showed higher MET and KEAP1 mutations and stronger PD-L1 protein expression compared with that recorded in other NSCLCs. Conclusion Decreased APOBEC signatures and subclonal diversity were detected during malignant progression in PSC. Frequent MET mutations and strong PD-L1 expression distinguished PSC from other NSCLCs. The aggressiveness and therapeutic difficulties of PSC were possibly attributable to profound intratumoral and intertumoral genetic diversity. Next-generation sequencing could suggest the appropriate treatment strategy for PSC.

Hemorrhagic fever with renal syndrome is an acute disease characterized by fever, headache, bleeding tendency, and anuria. We recently treated a case of hemorrhagic fever in a renal allograft patient with renal syndrome. A 43-year-old woman presented with high fever, headache, and myalgia for 4 days. In February 1998, she had undergone allograft kidney transplantation following treatment with cyclosporine and steroids. Allograft function was stable. Hantaan virus infection was demonstrated by serology during the first hospital week. Her clinical course progressed through febrile, hypotensive, oliguria, polyuria, and recovery phases. The patient was successfully treated with continuous renal replacement therapy and supportive management with maintenance doses of immunosuppressive agents.
Acute Disease ; Adult ; Anuria ; Cyclosporine ; Female ; Fever ; Hantaan virus ; Headache ; Hemorrhage ; Hemorrhagic Fever with Renal Syndrome ; Humans ; Kidney Transplantation ; Oliguria ; Polyuria ; Renal Replacement Therapy ; Steroids ; Transplantation, Homologous

PURPOSE: During hemodialysis (HD) in patients with end-stage renal disease (ESRD) and preexisting liver cirrhosis (LC), there is a risk of inadequate ultrafiltration due to either intradialytic hypotension or a coagulopathy causing complications from alteration of clotting factors and platelets. Peritoneal dialysis has several benefits over HD for cirrhotic patients including proper hemodynamic stability, avoidance of anticoagulants and direct removal of ascitic fluid. We compared the factors associated with the survival rates in patients with ESRD and LC undergoing dialysis. METHODS: We analyzed 41 ESRD patients with LC (HD 23 patients, PD 18 patients). Their characteristics and laboratory findings at the beginning of dialysis, and survival rates were retrospectively analyzed. RESULTS: There was no significant difference in survival time with the treatment modality. The patients with severe ascites at the beginning of dialysis, low albumin (serum albumin <3.0 g/dL), high modified Child-Pugh score (MCP score > or =7) and low hemoglobin (Hb) level (Hb <10 g/dL) had poor survival. The multivariate analysis showed that age, the amount of ascites, the initial Hb level and the modified Child-Pugh score were risk factors for death. CONCLUSION: PD was an effective renal replacement therapy for patients with ESRD and LC. Patients with a modified Child-Pugh classification of A and B were not significantly different with regard to survival rates. Therefore, PD may be a safe and effective option for patients with ESRD and LC.
Anticoagulants ; Ascites ; Ascitic Fluid ; Classification ; Dialysis ; Hemodynamics ; Humans ; Hypotension ; Kidney Failure, Chronic* ; Liver Cirrhosis* ; Liver* ; Multivariate Analysis ; Peritoneal Dialysis* ; Renal Dialysis* ; Renal Replacement Therapy ; Retrospective Studies ; Risk Factors ; Survival Rate ; Ultrafiltration

BACKGROUND/AIMS: Coagulopathy is a common complication of snakebite, but there is little information on the clinical importance of coagulopathy. We analyzed the characteristics of coagulopathy after envenomation. METHODS: Ninety-eight patients who experienced snakebite were enrolled in this study. We divided all the patients into three groups by the ISTH DIC scoring system: the normal, simple coagulopathy and DIC groups. The coagulopathy group included both the simple coagulopathy and DIC groups. We then conducted a case-control study. RESULTS: There was a significant decrease in the Hct, protein, albumin, ALP and cholesterol levels in the coagulopathy group, and only the cholesterol level was deceased in the DIC group (p<0.05). Leukocytosis and rhabdomyolysis were significantly associated with coagulopathy, and hemolysis and rhabdomyolysis were associated with DIC (p<0.05). The presence of rhabdomyolysis was considered a risk factor for coagulopathy (p<0.05). These conditions continued for up to six to seven days after the snakebite. CONCLUSIONS: Evaluation of coagulopathy with using these characteristics is helpful to properly manage the patients who experience snakebite.
Animals ; Blood Coagulation Disorders/*etiology ; Case-Control Studies ; Female ; Hemolysis/drug effects ; Humans ; Incidence ; Leukocytosis/etiology ; Male ; Retrospective Studies ; Rhabdomyolysis/etiology ; Risk Factors ; Snake Bites/*complications