Endoscopic closure of iatrogenic colon perforation using dual-channel endoscope with an endoloop and clips: methods and feasibility data (with videos).

BACKGROUND: Colon perforation is the most serious complication associated with colonoscopic procedures. We performed a novel purse-string suture technique to close the iatrogenic colonic perforation using dual-channel endoscope with an endoloop and clips. METHODS: Iatrogenic colon perforations developed during diagnostic colonoscopy referred to a tertiary hospital over 10 years were considered for this endoscopic closure. An endoloop was inserted through the left channel of the endoscope and placed around the defect. The first clip was placed at the proximal site of the defect through the other channel of the endoscope, and the endoloop was anchored on the mucosa around the defect. Then, subsequent clips were placed next to previous clips and the endoloop was fixed. After the defect was encircled by the endoloop and clips, the rim of the opening was approximated by fastening the endoloop with a purse-string technique. RESULTS: A total of 8 patients were admitted to our hospital because of iatrogenic colon perforations during diagnostic colonoscopy. Of these, 2 underwent laparoscopic surgery and 6 underwent endoscopic closure by this novel purse-string suture technique. The estimated diameters of the perforations were 20 mm. All cases were successfully treated in the endoscopy unit without sedation or general anesthesia, and recovered without any complication or subsequent operation. Abdominal pain had nearly resolved within 3 days after the procedure in all patients, and only mild peritonitis was observed. CONCLUSIONS: Iatrogenic colon perforation can be treated with a purse-string suture technique using dual-channel endoscope with an endoloop and clips. This technique can be useful for relatively large colon perforations associated with diagnostic colonoscopy.

Diagnostic yield of stool culture and predictive factors for positive culture in patients with diarrheal illness.

We aimed to investigate the diagnostic yield of stool cultures and identify predictive factors for positive cultures in patients with diarrheal illness.A total of 13,327 patients who underwent stool cultures due to diarrheal illness were reviewed. Stool cultures were performed for enteric pathogens, including Salmonella, Shigella, Vibrio, Klebsiella oxytoca, and Yersinia. The culture-positive group was compared with the culture-negative group who were randomly selected from culture negative patients.A total of 196 patients (1.47%) were diagnosed with positive stool culture. In 196 culture positive patients, Salmonella spp. (75.0%) was detected most commonly, followed by Vibrio (19.4%). Univariate analyses showed fever (>37.8°C), vomiting, duration and frequency of diarrhea, and high C-reactive protein (CRP) were significantly associated with positive stool culture. Multivariate analysis showed fever (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.25-4.35; P = .008), ≥5/day of diarrhea (OR, 3.52; 95% CI, 1.93-6.44; P < .001) and >50 mg/L of CRP (OR, 2.27; 95% CI, 1.18-4.36; P = .014) were independent predictors for positive stool culture. OR in patients with all 3 factors was 6.55 (95% CI, 2.56-16.75; P < .001). Vomiting (OR, 0.32; 95% CI, 0.17-0.57; P < .001) was a negative predictive factor.Diagnostic yield of stool culture in patients with diarrheal illness is very low. Fever, frequency of diarrhea, and high CRP are predictors for positive stool cultures. These findings may lead to more discerning and cost-effective utilization of stool culture by clinicians.

Odisolane, a Novel Oxolane Derivative, and Antiangiogenic Constituents from the Fruits of Mulberry (Morus alba L.).

Mulberry, the fruit of Morus alba L., is known as an edible fruit and commonly used in Chinese medicines as a warming agent and as a sedative, tonic, laxative, odontalgic, expectorant, anthelmintic, and emetic. Systemic investigation of the chemical constituents of M. alba fruits led to the identification of a novel oxolane derivative, (R*)-2-((2S*,3R*)-tetrahydro-2-hydroxy-2-methylfuran-3-yl)propanoic acid (1), namely, odisolane, along with five known heterocyclic compounds (2-6). The structure of the new compound was elucidated on the basis of HR-MS, 1D and 2D NMR ((1)H-(1)H COSY, HSQC, HMBC, and NOESY) data analysis. Compound 1 has a novel skeleton that consists of 8 carbon units with an oxolane ring, which until now has never been identified in natural products. The isolated compounds were subjected to several activity tests to verify their biological function. Among them, compounds 1, 3, and 5 significantly inhibited cord formation in HUVECs. The action mechanism of compound 3, which had the strongest antiangiogenic activity, was mediated by decreasing VEGF, p-Akt, and p-ERK protein expression. These results suggest that compounds isolated from M. alba fruits might be beneficial in antiangiogenesis therapy for cancer treatment.

The synergistic impact of nonalcoholic fatty liver disease and metabolic syndrome on subclinical atherosclerosis.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a well-known contributor for the development of cardiovascular disease (CVD). We examined the influence of NAFLD and metabolic syndrome (MetS) on markers of subclinical atherosclerosis, including carotid intima-media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV) and ankle-brachial pressure index (ABI), after adjusting for cardiometabolic risk factors. DESIGN: A cross-sectional study. PATIENTS AND MEASUREMENTS: The association between NAFLD, MetS and markers of subclinical atherosclerosis was assessed in 955 participants without CVD using multiple logistic regression analysis after adjusting for multiple cardiometabolic risk variables. RESULTS: After adjusting for age and sex, CIMT and baPWV were found to be significantly correlated with multiple cardiometabolic risk variables, whereas ABI was only associated with obesity parameters. The prevalence of NAFLD differed significantly according to the presence of subclinical atherosclerosis as defined by both CIMT and baPWV (P = 0·004 and P = 0·007, respectively). After adjusting for potential confounding factors, NAFLD or MetS was not associated with subclinical atherosclerosis as defined by CIMT and baPWV. However, individuals with both NAFLD and MetS had a significantly higher risk of subclinical atherosclerosis as defined by CIMT (OR = 2·06, 95% CI = 1·13-3·74) or baPWV (OR = 2·64, 95% CI = 1·46-4·76) compared to normal subjects, even after adjusting for potential confounders. CONCLUSIONS: The results show that NAFLD and MetS have a synergistic impact on the subclinical atherosclerosis, which suggests that individuals with both NAFLD and MetS should be strongly advised to engage in CVD prevention strategies.

Implications of Pericardial, Visceral and Subcutaneous Adipose Tissue on Vascular Inflammation Measured Using 18FDG-PET/CT.

OBJECTIVE: Pericardial adipose tissue (PAT) is associated with adverse cardiometabolic risk factors and cardiovascular disease (CVD). However, the relative implications of PAT, abdominal visceral and subcutaneous adipose tissue on vascular inflammation have not been explored. METHOD AND RESULTS: We compared the association of PAT, abdominal visceral fat area (VFA), and subcutaneous fat area (SFA) with vascular inflammation, represented as the target-to-background ratio (TBR), the blood-normalized standardized uptake value measured using 18F-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET) in 93 men and women without diabetes or CVD. Age- and sex-adjusted correlation analysis showed that PAT, VFA, and SFA were positively associated with most cardiometabolic risk factors, including systolic blood pressure, LDL-cholesterol, triglycerides, glucose, insulin resistance and high sensitive C-reactive proteins (hsCRP), whereas they were negatively associated with HDL-cholesterol. In particular, the maximum TBR (maxTBR) values were positively correlated with PAT and VFA (r = 0.48 and r = 0.45, respectively; both P <0.001), whereas SFA showed a relatively weak positive relationship with maxTBR level (r = 0.31, P = 0.003). CONCLUSION: This study demonstrated that both PAT and VFA are significantly and similarly associated with vascular inflammation and various cardiometabolic risk profiles.

The dipeptidyl peptidase-IV inhibitor inhibits the expression of vascular adhesion molecules and inflammatory cytokines in HUVECs via Akt- and AMPK-dependent mechanisms.

Recently, dipeptidyl peptidase-IV (DPP-IV) inhibitor, a major anti-hyperglycemic agent, has received substantial attention as a possible therapeutic target for inflammatory diseases such as atherosclerosis. However, the direct molecular mechanisms through which DPP-IV inhibitor mediates anti-inflammatory effects in vascular endothelial cells have not been clarified. The effects of the DPP-IV inhibitor, gemigliptin, were analyzed in human umbilical vein endothelial cells (HUVECs) and THP-1 cells. Using Western blotting, we demonstrated that gemigliptin efficiently increased the level of AMP-activated protein kinase (AMPK) and Akt phosphorylation in a dose-dependent manner. The levels of lipopolysaccharide (LPS)-mediated phosphorylated nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) were significantly decreased after gemigliptin treatment. Furthermore, gemigliptin reduced LPS-induced expression of adhesion molecules and inflammatory cytokines such as vascular cell adhesion molecule-1 (VCAM-1), E-selectin, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-1ß (IL-1ß), and IL-6 in HUVECs. In macrophage-like THP-1 cells, gemigliptin effectively inhibited LPS- and low-density lipoprotein (LDL)-induced foam cell formation. However, these anti-inflammatory and anti-atherosclerotic effects of gemigliptin in HUVECs and THP-1 cells were significantly reduced after treatment with an AMPK or an Akt inhibitor. Our results suggest that gemigliptin efficiently inhibited LPS-induced pro-inflammatory effects in vascular endothelial cells by attenuating NF-κB and JNK signaling via Akt/AMPK-dependent mechanisms. Therefore, the DPP-IV inhibitor, gemigliptin, may directly protect the vascular endothelium against inflammatory diseases such as atherosclerosis.

Association between body size phenotype and sleep duration: Korean National Health and Nutrition Examination Survey V (KNHANES V).

OBJECTIVE: Recent studies reported the presence of unique subsets of body size phenotypes that are more susceptible or more resistant to the development of obesity-associated metabolic disorders, although the underlying mechanism is not yet fully elucidated. We investigated the association between body size phenotypes and sleep duration after adjusting potential confounding factors. MATERIALS AND METHODS: We analyzed data from the Korean National Health and Nutrition Examination Survey V (KNHANES V), a nation-wide, population-based health survey including 9077 Korean adults. The average amount of sleep per night was categorized as: ≤6, 7, 8, and ≥9 h. Body size phenotypes were classified based on body mass index (BMI) and presence of metabolic syndrome; metabolically healthy and normal weight (MHNW), metabolically abnormal but normal weight (MANW), metabolically healthy but obese (MHO), and metabolically abnormal obese (MAO). RESULTS: According to sleep duration, there were significant differences in age, gender, BMI, waist circumference, and blood pressure (all P <0.05). Multivariate analysis showed that obese groups (MHO and MAO) had significantly shorter sleep durations than non-obese groups (MHNW and MANW) (6.78±0.04 vs. 6.93±0.03, P <0.001). Sleep duration was significantly different according to body size phenotype, irrespective of confounding factors, such as age, gender, smoking status, alcohol consumption, physical activity, income, and education (MHO; 6.73±0.05, MAO; 6.82±0.05, MHNW; 6.94±0.04, and MANW; 6.91±0.05; P <0.001). CONCLUSION: Sleep duration is independently associated with body size phenotype after adjusting for confounding factors in the Korean population.

Waist-to-hip ratio is better at predicting subclinical atherosclerosis than body mass index and waist circumference in postmenopausal women.

OBJECTIVE: Body fat distribution becomes more central after menopause. Although some studies have identified the superiority of various anthropometric indices to assess general health outcomes, very limited studies have compared the efficacy of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) to predict subclinical atherosclerosis according to menopausal status. METHODS: In total, 442 participants (209 premenopausal women and 233 postmenopausal women) were prospectively enrolled from the Health Promotion Center of Korea University Guro Hospital. We examined subclinical atherosclerosis using carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (baPWV). RESULTS: In premenopausal women, all anthropometric parameters such as BMI, WC and WHR were positively correlated with baPWV and CIMT values, whereas in postmenopausal women, only WHR was positively correlated with baPWV values (0.27, P<0.01), and WC and WHR were positively correlated with CIMT (0.15, P<0.05 and 0.21, P<0.01, respectively). By receiver operating characteristic (ROC) curve analyses, WHR was superior to the other anthropometric indices to predict carotid atherosclerosis in postmenopausal women. Furthermore, the normal weight (BMI<23kg/m(2)) with higher WHR group had a significantly thicker CIMT when compared to the normal weight with lower WHR group (0.76mm vs. 0.68mm, P<0.01) and even the overweight subjects with BMI≥23kg/m(2) (0.76mm vs. 0.70mm, P<0.01) in postmenopausal women. CONCLUSIONS: The present study shows that WHR has the best potential for predicting subclinical atherosclerosis compared to BMI and WC in postmenopausal women. CLINICAL TRIALS NUMBER: NCT01594710.

Impact of visceral fat on skeletal muscle mass and vice versa in a prospective cohort study: the Korean Sarcopenic Obesity Study (KSOS).

OBJECTIVES: Sarcopenia and visceral obesity have been suggested to aggravate each other, resulting in a vicious cycle. However, evidence based on prospective study is very limited. Our purpose was to investigate whether visceral fat promotes a decrease in skeletal muscle mass and vice versa. METHODS: We observed changes in anthropometric and body composition data during a follow-up period of 27.6 ± 2.8 months in 379 Korean men and women (mean age 51.9 ± 14.6 years) from the Korean Sarcopenic Obesity Study (KSOS). Appendicular lean soft tissue (ALST) mass was calculated using dual-energy X-ray absorptiometry, and visceral fat area (VFA) was measured using computed tomography at baseline and follow-up examination. RESULTS: ALST mass significantly decreased, whereas trunk and total fat mass increased in both men and women despite no significant change in weight and body mass index. In particular, women with visceral obesity at baseline had a greater decrease in ALST mass than those without visceral obesity (P = 0.001). In multiple linear regression analysis, baseline VFA was an independent negative predictor of the changes in ALST after adjusting for confounding factors including age, gender, life style and body composition parameters, insulin resistance, high sensitivity C-reactive protein and vitamin D levels (P = 0.001), whereas the association between baseline ALST mass and changes in VFA was not statistically significant (P = 0.555). CONCLUSIONS: This longitudinal study showed that visceral obesity was associated with future loss of skeletal muscle mass in Korean adults. These results may provide novel insight into sarcopenic obesity in an aging society.

Adipose gene expression profiles related to metabolic syndrome using microarray analyses in two different models.

BACKGROUND: Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist has a wide-ranging influence on multiple components of metabolic syndrome. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a useful animal model of metabolic syndrome. To determine genes related to metabolic syndrome, we examined overlapping genes that are simultaneously decreased by PPAR-γ agonists and increased in OLETF rats using microarrays in two different models. METHODS: In the first microarray analysis, PPAR-γ agonist-treated db/db mice were compared to standard diet-fed db/db mice. In the second microarray analysis, OLETF rats were compared to Long-Evans Tokushima Otsuka (LETO) rats (control of OLETF rats). RESULTS: Among the overlapping genes, in the present study, we validated that lipocalin-2 expression was significantly decreased in the visceral adipose tissue of PPAR-γ agonist-treated db/db mice compared to standard diet-fed db/db mice and increased in OLETF rats compared to LETO rats using real time reverse transcription polymerase chain reaction. Furthermore, we showed for the first time that lipocalin-2 expression was significantly increased in the visceral adipose tissues of obese humans compared with nonobese humans. In addition, the expression level of lipocalin-2 in human visceral adipose tissue had a significant positive correlation with body mass index, serum interleukin-6, adipocyte fatty acid binding protein levels, and white blood cell count. CONCLUSION: Lipocalin-2 was confirmed to be a significant adipokine affected by PPAR-γ agonist and obesity in the present study. Also, for the first time in human visceral adipose tissue, it was determined that the expression of lipocalin-2 from obese humans was significantly increased and correlated with circulating inflammatory markers.

Dipeptidyl petidase-IV inhibitor (gemigliptin) inhibits tunicamycin-induced endoplasmic reticulum stress, apoptosis and inflammation in H9c2 cardiomyocytes.

The direct effects of dipeptidyl peptidase-IV (DPP-IV) inhibitors on endoplasmic reticulum (ER) stress-induced apoptosis and inflammation in cardiomyocytes have not been elucidated. H9c2 cell viability, which was reduced by tunicamycin, was increased after DPP-IV inhibitor gemigliptin treatment. Gemigliptin significantly decreased the tunicamycin-mediated increase in glucose regulated protein 78 (GRP78) expression and ER stress-mediated signaling molecules such as protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C-EBP homologous protein (CHOP) and inositol-requiring enzyme 1α (IRE1α)/c-Jun N-terminal kinase (JNK)-p38. Furthermore, gemigliptin effectively induced Akt phosphorylation in a dose-dependent manner. Using flow cytometry and Hoechst staining, we showed that treatment with Akt inhibitor significantly blocked the anti-apoptotic effects mediated by gemigliptin. The reduction in tunicamycin-induced GRP78 level and PERK/CHOP pathway activity by gemigliptin was reversed after treatment with Akt inhibitor. In conclusion, gemigliptin effectively inhibited ER stress-induced apoptosis and inflammation in cardiomyocytes via Akt/PERK/CHOP and IRE1α/JNK-p38 pathways, suggesting its direct protective role in cardiovascular diseases.

Acute pyelonephritis with anaplastic thyroid carcinoma producing granulocyte colony-stimulating factor.

Paraneoplastic leukocytosis was defined as elevated white blood cell (WBC) levels caused by cytokines, likely produced by the tumor itself, without evidence of infection or myeloproliferative disease. We report a case of anaplastic thyroid carcinoma with leukocytosis caused by elevated production of granulocyte colony-stimulating factor (G-CSF) by the carcinoma. Initially, acute pyelonephritis (APN) was diagnosed and treatment for APN was ongoing, but the WBC count steadily increased to 68.8×10(9)/L. She was diagnosed with anaplastic thyroid carcinoma on her neck mass, and the serum concentration of G-CSF was found to be markedly increased at 1,010 pg/mL. In spite of supportive care, the patient's condition rapidly deteriorated and the patient died on day 23 of hospital stay. Leukocytosis without definite evidence of infection could be a paraneoplastic manifestation in patients with malignant tumors, and paraneoplastic leukocytosis may be related to poor prognosis.

Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome.

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.

A case of paraneoplastic limbic encephalitis associated with small cell lung cancer.

Paraneoplastic limbic encephalitis (PLE) is a rare syndrome characterized by memory impairment, affective and behavioral disturbances and seizures. Among many different neoplasms known to cause PLE, small cell lung cancer (SCLC) is the most frequently reported. The pathogenesis is not fully understood but is believed to be autoimmune-related. We experienced a patient with typical clinical features of PLE. A 67-year-old man presented with seizure and disorientation. Brain magnetic resonance imaging demonstrated high signal intensity in the bilateral amygdala and hippocampus in flair and T2-weighted images suggestive of limbic encephalitis. Cerebrospinal fluid tapping revealed no evidence of malignant cells or infection. Positron emission tomography/computed tomography showed a lung mass with pleural effusion and a consequent biopsy confirmed the diagnosis of PLE associated with SCLC. The patient was subsequently treated with chemotherapy and neurologic symptoms gradually improved.