Lung Disease Diagnostic Model Through IgG Sensitization to Microbial Extracellular Vesicles

Purpose@#Recently, there has been a rise in the interest to understand the composition of indoor dust due to its association with lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Furthermore, it has been found that bacterial extracellular vesicles (EVs) within indoor dust particles can induce pulmonary inflammation, suggesting that these might play a role in lung disease. @*Methods@#We performed microbiome analysis of indoor dust EVs isolated from mattresses in apartments and hospitals. We developed diagnostic models based on the bacterial EVs antibodies detected in serum samples via enzyme-linked immunosorbent assay (ELISA) in this analysis. @*Results@#Proteobacteria was the most abundant bacterial EV taxa observed at the phylum level while Pseudomonas, Enterobacteriaceae (f) and Acinetobacter were the most prominent organisms at the genus level, followed by Staphylococcus. Based on the microbiome analysis, serum anti-bacterial EV immunoglobulin G (IgG), IgG1 and IgG4 were analyzed using ELISA with EV antibodies that targeted Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae and Pseudomonas aeruginosa. The levels of anti-bacterial EV antibodies were found to be significantly higher in patients with asthma, COPD and lung cancer compared to the healthy control group. We then developed a diagnostic model through logistic regression of antibodies that showed significant differences between groups with smoking history as a covariate. Four different variable selection methods were compared to construct an optimal diagnostic model with area under the curves ranging from 0.72 to 0.81. @*Conclusions@#The results of this study suggest that ELISA-based analysis of anti-bacterial EV antibodies titers can be used as a diagnostic tool for lung disease. The present findings provide insights into the pathogenesis of lung disease as well as a foundation for developing a novel diagnostic methodology that synergizes microbial EV metagenomics and immune assays.

Lung Disease Diagnostic Model Through IgG Sensitization to Microbial Extracellular Vesicles

Purpose@#Recently, there has been a rise in the interest to understand the composition of indoor dust due to its association with lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Furthermore, it has been found that bacterial extracellular vesicles (EVs) within indoor dust particles can induce pulmonary inflammation, suggesting that these might play a role in lung disease. @*Methods@#We performed microbiome analysis of indoor dust EVs isolated from mattresses in apartments and hospitals. We developed diagnostic models based on the bacterial EVs antibodies detected in serum samples via enzyme-linked immunosorbent assay (ELISA) in this analysis. @*Results@#Proteobacteria was the most abundant bacterial EV taxa observed at the phylum level while Pseudomonas, Enterobacteriaceae (f) and Acinetobacter were the most prominent organisms at the genus level, followed by Staphylococcus. Based on the microbiome analysis, serum anti-bacterial EV immunoglobulin G (IgG), IgG1 and IgG4 were analyzed using ELISA with EV antibodies that targeted Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae and Pseudomonas aeruginosa. The levels of anti-bacterial EV antibodies were found to be significantly higher in patients with asthma, COPD and lung cancer compared to the healthy control group. We then developed a diagnostic model through logistic regression of antibodies that showed significant differences between groups with smoking history as a covariate. Four different variable selection methods were compared to construct an optimal diagnostic model with area under the curves ranging from 0.72 to 0.81. @*Conclusions@#The results of this study suggest that ELISA-based analysis of anti-bacterial EV antibodies titers can be used as a diagnostic tool for lung disease. The present findings provide insights into the pathogenesis of lung disease as well as a foundation for developing a novel diagnostic methodology that synergizes microbial EV metagenomics and immune assays.

Erratum: Plasmacytoid Dendritic Cells Contribute to the Protective Immunity Induced by Intranasal Treatment with Fc-fused Interleukin-7 against Lethal Influenza Virus Infection

In the publication by Kang et al., typographical error has been detected in acknowledgements.

The Effect of Naïve Tenofovir Dipivoxil Fumarate Monotherapy in Patients with Chronic Hepatitis B: 2-Year Results of a Real-world Single-center Study / 대한내과학회지

BACKGROUND/AIMS: An incomplete virological response has been observed to tenofovir dipivoxil fumarate (TDF) in nucleos(t)ide analogue (NA)-experienced chronic hepatitis B (CHB) patients. This study investigated the efficacy of TDF in NA-naïve CHB patients 96 weeks after treatment. METHODS: CHB patients treated with TDF were enrolled retrospectively between November 2012 and January 2016. We assessed virological and biochemical parameters. RESULTS: The study enrolled 179 NA-naïve patients with a median follow-up duration of 59.6 weeks. The serum hepatitis B virus (HBV) DNA level decreased significantly during treatment. The complete virological response (CVR) rate was 83.21% at week 96. In univariate analyses, the predictors of a CVR at 96 weeks were the baseline HBV DNA level (CVR vs. no-CVR, HBV DNA log10 mean value 7.34 vs. 7.86, 95% confidential interval [CI]: -7.89 to -7.37; p < 0.001) and male sex (CVR vs. no-CVR, 49.1% vs. 81.3%, odds ratio [OR] 0.22, 95% CI: 0.06 to 0.87; p = 0.025). In the multivariate analysis, male sex predicted a CVR at week 96. The CVR was significantly lower in males than in females (OR 0.12, 95% CI: 0.02 to 0.96; p = 0.046). CONCLUSIONS: TDF was effective for treating CHB for more than 2 years in NA-naïve patients.

Plasmacytoid Dendritic Cells Contribute to the Protective Immunity Induced by Intranasal Treatment with Fc-fused Interleukin-7 against Lethal Influenza Virus Infection

Developing a novel vaccine that can be applied against multiple strains of influenza virus is of utmost importance to human health. Previously, we demonstrated that the intranasal introduction of Fc-fused IL-7 (IL-7-mFc), a long-acting cytokine fusion protein, confers long-lasting prophylaxis against multiple strains of influenza A virus (IAV) by inducing the development of lung-resident memory-like T cells, called T(RM)-like cells. Here, we further investigated the mechanisms of IL-7-mFc-mediated protective immunity to IAVs. First, we found that IL-7-mFc treatment augments the accumulation of pulmonary T cells in 2 ways: recruiting blood circulating T cells into the lung and expanding T cells at the lung parenchyma. Second, the blockade of T cell migration from the lymph nodes (LNs) with FTY720 treatment was not required for mounting the protective immunity to IAV with IL-7-mFc, suggesting a more important role of IL-7 in T cells in the lungs. Third, IL-7-mFc treatment also recruited various innate immune cells into the lungs. Among these cells, plasmacytoid dendritic cells (pDCs) play an important role in IL-7-mFc-mediated protective immunity through reducing the immunopathology and increasing IAV-specific cytotoxic T lymphocyte (CTL) responses. In summary, our results show that intranasal treatment with IL-7-mFc modulates pulmonary immune responses to IAV, affecting both innate and adaptive immune cells.

Septic Shock in Pyogenic Liver Abscess: Clinical Considerations / 대한소화기학회지

BACKGROUND/AIMS: Pyogenic liver abscess (PLA) is a life-threatening condition, despite advances in diagnostic technology and strategies for treatment. A strong predictor of mortality in this condition is septic shock. This study describes clinical, biochemical, and radiologic features in patients with PLA with or without septic shock, with the intent of describing risk factors for septic shock. METHODS: Of 358 patients with PLA enrolled, 30 suffered septic shock and the remaining 328 did not. We reviewed the medical records including etiologies, underlying diseases, laboratory, radiologic and microbiologic findings, methods of treatment and treatment outcomes. RESULTS: The case fatality rate was 6.1%. In univariate analysis, the presence of general weakness, mental change, low platelet level, prolonged PT, high BUN level, high creatinine level, low albumin level, high AST level, high CRP level, abscess size >6 cm, the presence of gas-forming abscess, APACHE II score ≥20, and the presence of Klebsiella pneumoniae infection were significantly associated with septic shock. Multivariate analysis showed the presence of mental change (p=0.004), gas-forming abscess (p=0.012), and K. pneumoniae infection (p=0.027) were independent predictors for septic shock. CONCLUSIONS: The presence of mental change, gas-forming abscess, and K. pneumoniae infection were independent predictors for septic shock in patients with PLA.

Pyogenic Liver Abscess: Changes in Clinical Features over the Last 10 Years / 대한내과학회지

BACKGROUND/AIMS: A pyogenic liver abscess is an acute bacterial infection that can potentially lead to life-threatening sepsis. This study examined the clinical features and changing trends of pyogenic liver abscess over the last 10 years. METHODS: We investigated patient characteristics, laboratory findings, blood and abscess culture results, location and characteristics of the abscess, and treatment modality in the medical records of 146 patients. We divided them into three groups by period: period 1, 23 patients in 2002-2003; period 2, 46 patients in 2007-2008; and period 3, 77 patients in 2012-2013. RESULTS: The mean patient age was 64.3 +/- 15.1 years and 87 of the 146 patients were male (59.6%). Period 2 had a higher prevalence of chronic alcoholics (30.4% vs. 10.4%) and lower prevalence of fever and chills (73.9% vs. 92.2%) compared with period 3. Klebsiella pneumoniae was the most commonly cultured bacteria and the microbiological findings did not differ among the three periods. Pyogenic liver abscesses were more common in the right liver. The lengths of hospital stay and treatment modalities were similar in all three periods. CONCLUSIONS: Although there were slight differences in symptoms among the periods, there were no changes in the liver abscess characteristics, i.e., location, size, and culture results. As there were no changes, the treatment strategy also did not change. We should continue to investigate the clinical features of liver abscess.

Is Chemoprevention of Pancreatic Cancer Possible by Aspirin Consumption? / 대한소화기학회지

No abstract available.

Differential Expression of E-Cadherin, beta-Catenin, and S100A4 in Intestinal Type and Nonintestinal Type Ampulla of Vater Cancers

BACKGROUND/AIMS: Epithelial-mesenchymal transition (EMT)-related proteins may exhibit differential expression in intestinal type or pancreatobiliary type ampulla of Vater carcinomas (AVCs). We evaluated the expression of E-cadherin, beta-catenin, and S100A4 in intestinal and nonintestinal type AVCs and analyzed their relationships with clinicopathological variables and survival. METHODS: A clinicopathological review of 105 patients with AVCs and immunohistochemical staining for E-cadherin, beta-catenin, and S100A4 were performed. The association between clinicopathological parameters, histological type, and expression of EMT proteins and their effects on survival were analyzed. RESULTS: Sixty-five intestinal type, 35 pancreatobiliary type, and five other types of AVCs were identified. The severity of EMT changes differed between the AVC types; membranous loss of E-cadherin and beta-catenin was observed in nonintestinal type tumors, whereas aberrant nonmembranous beta-catenin expression was observed in intestinal type tumors. EMT-related changes were more pronounced in the invasive tumor margin than in the tumor center, and these EMT-related changes were related to tumor aggressiveness. Among the clinicopathological parameters, a desmoplastic reaction was related to overall survival, and the reaction was more severe in nonintestinal type than in intestinal type AVCs. CONCLUSIONS: Dysregulation of E-cadherin, beta-cadherin, and S100A4 expression may play a role in the carcinogenesis and tumor progression of AVCs.

Comparison of Malnutrition Risk between Patients with Liver Cirrhosis and Viral Hepatitis Carrier: A Single Center Study / 대한소화기학회지

BACKGROUND/AIMS: It is well-known that patients with chronic liver disease commonly have nutritional deficiency. In the present study, we investigated the differences in malnutrition risk between patients with liver cirrhosis and viral hepatitis carrier. METHODS: Patients with chronic liver disease who have been hospitalized at Konyang University Hospital from May 2012 to April 2013 were analyzed retrospectively. The malnutrition risk was divided into three categories (low, intermediate, and high) according to Konyang University Hospital Malnutrition Screening, which include BMI, serum albumin, total lymphocyte count (TLC), hemoglobin, weight change, appetite, and dysphagia, within 24 hours of hospitalization. RESULTS: Among a total of 460 patients, 313 had liver cirrhosis (LC), and 147 were viral hepatitis carriers. Age (p<0.001), serum albumin level (p<0.001), TLC (p=0.011), hemoglobin (p<0.001) and serum cholesterol level (p=0.005) were significant different between the two groups. However, there were no difference in height, weight, and BMI. The malnutrition risk of the patients with viral hepatitis carrier was significantly lower than that of the patients with LC (p<0.001). In addition, among 313 patients with LC, malnutrition risk of the patients with Child-Pugh class A (n=150) was significantly lower than that of the patients with class B (n=90) or C (n=73) (p<0.001). CONCLUSIONS: Viral hepatitis carrier group had significantly lower malnutrition risk than LC group. The risk of malnutrition in Child-Pugh class A group was significantly lower than that in class B or C group.

Cryptococcal meningitis in a patient with chronic hepatitis C treated with pegylated-interferon and ribavirin

Various adverse events have been reported during combination therapy with pegylated (PEG)-interferon-alpha and ribavirin, although opportunistic infections, especially cryptococcal meningitis, are very rare. A 61-year-old woman complained of headaches and a fever during treatment of a chronic hepatitis C virus (HCV) infection. She had been treated for 7 months. Her headaches were refractory to analgesics, and she developed subtle nuchal rigidity. The cerebral spinal fluid (CSF) revealed a white blood cell count of 205/mm3, 51 mg/dL protein, 35 mg/dL glucose, and negative Cryptococcus antigen. The CSF culture resulted in no growth. Five days later, the CSF was positive for Cryptococcus antigen. We administered amphotericin B and flucytosine, followed by fluconazole. Approximately 2 months later, she was discharged. For the first time, we report a case of cryptococcal meningitis during the treatment of chronic HCV with PEG-interferon-alpha and ribavirin.

Is There a Difference in the Prevalence of Gastroesophageal Reflux Disease between Peritoneal Dialysis and Hemodialysis Patients? / 대한소화기학회지

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disorder in patients with chronic kidney disease (CKD). However, little is known about the prevalence of GERD in dialysis patients. The aim of the present study was to investigate the difference in the prevalence of GERD in peritoneal dialysis and hemodialysis patients. METHODS: From July 2010 to August 2011, peritoneal dialysis patients (n=30) and hemodialysis patients (n=38) were enrolled. The prevalences of GERD were assessed at a single center with endoscopic findings and interviews using a questionnaire. Also, risk factors of GERD were evaluated. RESULTS: The prevalences of GERD in peritoneal dialysis and hemodialysis patients were 33.3% and 39.5% (p=0.748), respectively. The prevalences of erosive reflux esophagitis (ERD) in peritoneal dialysis and hemodialysis patients were 16.7% and 23.7% (p=0.477), respectively. The prevalences of nonerosive reflux disease (NERD) in peritoneal dialysis and hemodialysis patients were 16.7% and 13.2% (p=0.685), respectively. The prevalences of GERD, ERD and NERD were higher than those of the general population. The risk factor for GERD was age in hemodialysis patients. CONCLUSIONS: The prevalence of GERD in dialysis patients was higher than that in the general population. However, there was no significant difference between peritoneal dialysis and hemodialysis patients.

A Case of Splenic Pseudocyst Complicated by Acute Pancreatitis / 대한소화기학회지

Splenic pseudocyst is a rare disease associated with chronic and acute pancreatitis splenic pseudocyst is treated by distal pancreatectomy and splenectomy. A 47-year old woman with a 10-year history of alcohol abuse presented with epigastric and left upper quadrant pain of 3 days duration. Abdominal CT showed a 4.0x4.5 cm sized cystic lesion in the tail of the pancreas. Analgesics was administrated for the relief of abdominal pain. On the 4th hospital day, the patient complained more of left upper quadrant pain, so we took follow up CT scans. On follow up CT, one large splenic pseudocyst with size of 9.5x4.5x10.0 cm was noted. The patient was treated conservatively by percutaneous catheter drainage and discharged on the 13th hospital day. This case is the first case report of splenic pseudocyst treated conservatively, not by surgery in Korea.

Cecal Fecaloma Due to Intestinal Tuberculosis: Endoscopic Treatment

Colorectal fecaloma is a mass of accumulated feces that is much harder in consistency than a fecal impactation. The rectosigmoid area is the common site for fecalomas and the cecum is the most unusual site. Diagnosis is usually made by distinctive radiographic findings of a mobile intraluminal mass with a smooth outline and no mucosal attachment. Most of the fecalomas are successfully treated by conservative methods such as laxatives, enemas and rectal evacuation. When conservative treatments have failed, endoscopic procedures or a surgical intervention may be needed. We report here that a cecal fecaloma caused by intestinal tuberculosis scar was successfully removed by endoscopic procedures.

An Intraluminal Gallbladder and Bile Duct Hematoma after a Percutaneous Biopsy of Hepatic Adenoma / 대한내과학회지

Hepatocellular adenoma is a rare, but benign, tumor mostly found in women taking oral contraceptives. Hepatocellular adenoma must be treated when bleeding of the tumor, intraperitoneal hemorrhage, or malignant transformation occurs. A percutaneous liver biopsy is relatively safe and effective, but carries the risk of mild complications, such as pain, temporary hypotension, and bleeding, and severe complications, such as intraperitoneal bleeding, peritonitis, pneumothorax, hemothorax, other organ injury, and sepsis. We treated a 33-year-old woman with hemobilia and gallbladder hematoma following a sono-guided percutaneous liver biopsy. Complete quadrantectomy with anterior lobe resection was done after angiography and embolization of the hepatic artery.

Endoscopic Findings and Clinical Significance of Portal Hypertensive Colopathy / 대한소화기학회지

BACKGROUND/AIMS: The endoscopic findings and clinical relevance of portal hypertensive colopathy are not well described in Korea. We aimed to do a retrospective study of mucosal changes in the colon of patients with liver cirrhosis and to find their association with clinical characteristics. METHODS: We reviewed the clinical data and endoscopic findings of 48 patients with liver cirrhosis and 48 patients, matched for age and sex, with irritable bowel disease (IBS) who underwent colonoscopy over a 5 year span. RESULTS: Patients with liver cirrhosis were more likely to have colitis-like lesions and vascular abnormalities than IBS patients. Low platelet count (p=0.005) and severe esophageal varices (p=0.011) were associated with portal hypertensive colopathy, whereas the etiologies and severity of cirrhosis were not associated with these findings. CONCLUSIONS: Portal hypertensive colopathy can be defined with colitis-like lesions or vascular lesions. These lesions are more frequently present in patients with more severe esophageal varices and thrombocytopenia.

Clinical Aspects of Intraabdominal Cystic Lymphangioma in Korea / 대한소화기학회지

BACKGROUND/AIMS: Cystic lymphangioma is an uncommon disease, and rarely develops in the intraabdomen. The aim of this article was to discuss about clinical characteristics of intraabdominal cystic lymphangioma developed in Korea. METHODS: Age, sex, symptoms, locations and size of the lesions, diagnostic methods, treatments, complications and recurrence were analyzed in 13 pathologically confirmed cases of intraabdominal cystic lymphangioma and 18 cases of literature consideration reported in Korea. RESULTS: Intraabdominal cystic lymphangioma commonly developed in adults compared to the other lymphangioma, and frequently located in the mesentery. Abdominal pain was the most common symptom, but it was a non-specific finding. Tenderness and abdominal mass were not significantly associated. The size of mass was diverse. Abdominal ultrasonography and abdominal CT were diagnostic tools most commonly used, but preoperative diagnosis was possible only in 22.6%. All patients were discharged without any complications, and no recurrence was reported. CONCLUSIONS: Preoperative diagnosis of intraabdominal cystic lymphangioma is difficult and symptoms and signs are not specific. Intra-abdominal cystic lymphangioma should be suspected in patients with non specific abdominal pain and intraabdominal mass and active diagnostic evaluation is mandatory.

Clinical Features of Pyogenic Liver Abscess according to Age Group / 대한소화기학회지

BACKGROUND/AIMS: Pyogenic liver abscess remains a major diagnostic and therapeutic challenge, despite advances in diagnostic technology and new strategies for treatment. This study was conducted to compare the differences in clinical features and outcomes of pyogenic liver abscess according to age. METHODS: In total, 166 patients were enrolled and included 63 (75 years old, group III) patients in each group. We reviewed the medical records retrospectively including etiology, underlying diseases, characteristics of the liver abscess, laboratory and microbiologic findings, treatment, and outcome of the patients. RESULTS: Group I had higher prevalence rates of male patients and chronic alcoholics, but lower prevalence rates of biliary disease, hypertension, and malignancy. In laboratory findings, group II had higher incidence of thrombocytopenia, elevated blood urea nitrogen and creatinine. There were no differences in symptoms and microbiologic findings in blood and pus among the three groups. Liver abscesses were more common in right liver in Group I. The lengths of stay and the treatment modalities were similar in three groups. CONCLUSIONS: Although there were differences in sex ratio, etiology, underlying disease among the different age groups, they did not cause difference in treatment and clinical outcome of pyogenic liver abscess. Thus, we recommend active treatments in patients of all age.

An Ectopic Opening of the Common Bile Duct into the Duodenal Bulb: The Clinical Features and Endoscopic Treatment / 대한소화기내시경학회지

BACKGROUND/AIMS: An ectopic opening of the common bile duct (CBD) into the duodenal bulb is known to cause biliary tract diseases or peptic ulcer. Yet such a case is extremely rare and the clinical significance of this malformation has not yet been clarified. METHODS: Ten patients with an ectopic opening in the duodenal bulb and who were treated at 4 hospitals in the Chungcheong province area were enrolled. Their clinical and radiographic features and the treatment for their combined biliary diseases were retrospectively analysed. RESULTS: The mean age of the ten patients was 73 years (range: 38~84 years, 8 men, 2 women) Eight of 10 patients had clinical signs and symptoms (RUQ abdominal pain: 5, epigastric pain: 3, fever: 3, Melena: 1). The two patients without symptoms were incidentally found to have an ectopic orifice during the evaluation for bile duct dilatation and a regular health check-up, respectively. Nine had duodenal ulcer scars or bulb deformities. Four had active duodenal ulcers and one of them had bleeding from the active duodenal ulcer, which was treated by endoscopic sclerotheraphy. Six of the 10 patients (60%) had biliary tract diseases (CBD stones: 4, cholangitis without CBD stone: 1, IHD stone: 1). Cholangiography was used for evaluation in 9 patients, and it showed dilatation of the CBD or IHD in 7 (78%), a tapered common bile duct at the distal CBD in 7 (78%) and a hook-shaped distal CBD in 8 (89%). Six patients' biliary tract diseases were treated endoscopically (ERCP: 4, PTCS: 2). Duodenal perforation occurred in 1 (10%), who was successfully managed by medical treatment. CONCLUSIONS: An ectopic opening of the CBD in the duodenal bulb is frequently associated with recurrent duodenal ulcer and biliary tract disease. Combined biliary tract disease can be successfully treated endoscopically.

A case of idiopathic eosinophilic cholecystitis / 대한내과학회지

Eosinophilic cholecystitis is a rare form of cholecystitis that is clinically indistinguishable from the predominant form of calculous cholecystitis. Histologically, it is characterized by a dense, transmural leukocyte infiltrate composed of more than 90% eosinophils. A 60-year-old woman complained of right upper quadrant pain. She had no allergic or medicine history. An abdominal CT scan revealed thickened gallbladder wall but no cholelithiasis, and a cholecystectomy was performed. Histologic examination showed transmural eosinophilic infiltration of the gallbladder wall.