Sepsis is one of the significant causes of morbidity and mortality. The burden caused by sepsis has continued to increase in recent years in the Korea, highlighting the urgent need for the implementation of strategies to improve sepsis treatment outcomes. We therefore designed a web-based sepsis registry system (“Korean Registry for Improving Sepsis Survival” [KISS]) protocol to be used in hospitals in the Korea for evaluation of the epidemiology and clinical characteristics of patients with sepsis, via an analysis of outcome predictors. The inclusion criteria of this registry are as follows: adult patients ≥18 years admitted to the participating hospitals who are diagnosed with sepsis or septic shock. Demographic and clinical information data of the patients will be collected from hospital medical records and will be recorded in a case report form, which will be entered into a web-based data management system. The analysis of the collected data will be performed as follows: (1) epidemiological and clinical characteristics of sepsis and septic shock, (2) application of sepsis bundles and antibiotic stewardship, and (3) audit and feedback. In conclusion, we aim to build the comprehensive web-based sepsis registry in the Korea through a nation-wide network of participating hospitals. Information collected and analyzed through the KISS can be used for further improvements in the clinical management of sepsis. Furthermore, the KISS will facilitate research leading to the formulation of public health policies regarding sepsis bundle and antibiotic stewardship strategies in the Korea.

Purpose: Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. Materials and Methods: To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. Results: Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. Conclusion We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

BACKGROUND/AIMS: Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). METHODS: Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. RESULTS: Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. CONCLUSIONS: Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.
Colon ; Colonic Neoplasms ; Colorectal Neoplasms* ; Humans ; Liver ; Lung ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Rectal Neoplasms ; Rectum ; Republic of Korea

Infective endocarditis (IE) is not a common cause of stroke. Considering the high mortality rates, however, IE should always be considered as a possible cause of stroke even when the chances are low. Atrioesophageal fistula is a life-threatening condition that can cause IE and subsequent stroke, but the diagnosis is often delayed due to its rarity. We report a case of multiple embolic infarcts caused by infective endocarditis associated with atrioesophageal fistula after radiofrequency catheter ablation for atrial fibrillation.
Atrial Fibrillation ; Catheter Ablation ; Diagnosis ; Endocarditis ; Esophageal Fistula ; Fistula ; Mortality ; Stroke

Nephronophthisis-related ciliopathy (NPHP-RC) is a common genetic cause of end-stage renal failure during childhood and adolescence and exhibits an autosomal recessive pattern of inheritance. Genetic diagnosis is quite limited owing to genetic heterogeneity in NPHP-RC. We designed a novel approach involving the step-wise screening of Sanger sequencing and targeted exome sequencing for the genetic diagnosis of 55 patients with NPHP-RC. First, five NPHP-RC genes were analyzed by Sanger sequencing in phenotypically classified patients. Known pathogenic mutations were identified in 12 patients (21.8%); homozygous deletions of NPHP1 in 4 juvenile nephronophthisis patients, IQCB1/NPHP5 mutations in 3 Senior–Løken syndrome patients, a CEP290/NPHP6 mutation in 1 Joubert syndrome patient, and TMEM67/MKS3 mutations in 4 Joubert syndrome patients with liver involvement. In the remaining undiagnosed patients, we applied targeted exome sequencing of 34 ciliopathy-related genes to detect known pathogenic mutations in 7 (16.3%) of 43 patients. Another 18 likely damaging heterozygous variants were identified in 13 NPHP-RC genes in 18 patients. In this study, we report a variety of pathogenic and candidate mutations identified in 55 patients with NPHP-RC in Korea using a step-wise application of two genetic tests. These results support the clinical utility of targeted exome sequencing to resolve the issue of allelic and genetic heterogeneity in NPHP-RC.
Adolescent ; Diagnosis* ; Exome* ; Genetic Heterogeneity* ; Humans ; Kidney Failure, Chronic ; Korea ; Liver ; Mass Screening ; Wills

PURPOSE: The aim of this study was to examine the expression of E-cadherin, beta-catenin, Cdx2, MMP7 in gastric cancer and to evaluate the clinical significance of these molecules in tumor recurrence within 2 years of pT2 and N1/N2 gastric cancer. METHODS: In 122 patients who underwent radical resection of gastric cancer, we investigated the association between the expression of these molecules and clinicopathologic factors by immunohistochemistry. The included criteria were pT2 and N1 or N2 (6th AJCC TNM). RESULTS: The expression of MMP7 was significantly associated with N stage (N1 vs. N2) (P=0.011). The negative expression of beta-catenin was strongly correlated with tumor recurrence within a 2-year period. However, the expression of these molecules was not related with recurrent sites. Multivariate analysis demonstrated that negative expression of beta-catenin was an independent predictor for tumor recurrence within 2 years (OR 2.366; 95% CI 1.056~5.297; P=0.036). CONCLUSION: Negative expression of beta-catenin may serve as a significant indicator for predicting tumor recurrence within a 2-year period in pT2 and N1/N2 gastric cancer.
beta Catenin ; Cadherins ; Humans ; Immunohistochemistry ; Multivariate Analysis ; Recurrence ; Stomach Neoplasms

PURPOSE: Generally, a mucinous carcinoma (Muc) of the colon show higher rates of microsatellite instability (MSI) than a non-mucinous carcinoma (non-Muc). Mutated methylenetetrahydrofolate reductase (MTHFR) brings about low enzyme activity, which may reduce genomic DNA methylation. These processes may be critical for the oncogenic transformation of human cells. We compared the relationship of MSI and MTHFR polymorphism in Muc to that in non-Muc. METHODS: From March 2003 to August 2007, genomic DNA was isolated from whole blood and tissue specimens of 285 colorectal cancer patients (Muc: 31 cases, non-Muc: 254 cases) and 448 normal control patients. These were subjected to MSI analysis and MTHFR genotyping by using PCR-based restriction fragment length polymorphism analyses. RESULTS: MSI was significantly more frequent in the Muc group (40.7%) than in the non- Muc group (14.8%). The frequencies of polymorphism of MTHFR 677C>T were CC (31.5%), CT (57%), and TT (11.5%) in the patient group and 32.4%, 53.1%, and 14.5% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 677C>T were CC (36%), CT (56%), TT (8%), and in the non-Muc group, they were 31.1%, 57%, and 11.9%. The frequencies of polymorphism of MTHFR 1298A>C were AA (73%), AC (21.3%), and CC (5.7%) in the patient group and 69.6%, 28.6%, and 1.8% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 1298A>C were AA (50%), AC (30%), and CC (20%), and in the non-Muc group, they were 76%, 20.3%, and 3.7%. The Muc group showed higher frequencies of the CC variant than the non-Muc group (P-value=0.018). No relation between MSI and MTHFR polymorphisms were seen in any comparison of the Muc and the non-Muc groups. CONCLUSIONS: The Muc group showed higher rates of MSI than the non-Muc group, but no definite difference between the Muc and the non-Muc groups was noted in the case of polymorphism of MTHFR 677C>T. However, the TT-type variant showed slightly lower frequencies in the Muc group than in the non-Muc group. On the contrary, the Muc group showed a higher rate of the CC variant in polymorphism of MTHFR 1298A>C. These inconsistent results seem to be due to the small size of the Muc group, so further study is needed.
Adenocarcinoma, Mucinous ; Colon ; Colorectal Neoplasms ; DNA ; DNA Methylation ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; Microsatellite Instability ; Microsatellite Repeats ; Mucins ; Oxidoreductases ; Polymorphism, Restriction Fragment Length ; Succinimides ; Tetrahydrofolates

Reversible posterior leukoencephalopathy syndrome (RPLS) is characterized clinically by headache, seizure, altered mental status and visual impairment. Neuroimaging shows reversible white matter edema predominantly in the parietal and occipital lobes. RPLS has been associated with a variety of conditions, including hypertensive encephalopathy, renal failure, immunosupressive therapy, and autoimmune diseases such as systemic lupus erythematosus (SLE). We report a young woman of SLE presented with headache, generalized tonic-clonic seizure and altered mental status, after taking azathioprine and cyclosporine. The brain magnetic resonance images showed bilateral hyperintensitiy in the posterior parietal, occipital, temporal lobes and cerebellum on T2-weighted images and fluid attenuated inversion recovery images, whereas diffusion-weighted images showed isointensity in the same distribution. The patient was improved clinically and radiologically one week after the control of hypertension and discontinuation of cyclosporine.
Autoimmune Diseases ; Azathioprine ; Brain ; Cerebellum ; Cyclosporine* ; Edema ; Female ; Headache ; Humans ; Hypertension ; Hypertensive Encephalopathy ; Lupus Erythematosus, Systemic ; Neuroimaging ; Occipital Lobe ; Posterior Leukoencephalopathy Syndrome* ; Rabeprazole ; Renal Insufficiency ; Seizures ; Temporal Lobe ; Vision Disorders

BACKGROUND: It is important to maintain adequate intravascular volume during off-pump coronary artery bypass surgery (OPCAB) to prevent hypotension. The aim of this study was to assess the effect of acute volume loading with new colloid solution, 6% hydroxyethyl starch (HES) 130/0.4 on hemodynamics and coagulation in patients undergoing OPCAB. METHODS: With the IRB approval, forty patients undergoing OPCAB were allocated to two groups receiving 10 ml/kg of Plasma solution A (Control group, n = 21) or HES 130/0.4 (HES group, n = 19) for 30 min before pericardiotomy. We measured hemodynamic variables and coagulation parameters at 10 min after anesthesia induction (T1), 10 min after fluid loading (T2), 10 min after Y-graft formation (T3), and after sternum closure. Amount of infused fluid, blood loss, tranfusion and urine output were recorded intraoperatively and for 16 hr after surgery. Thromboelastography and electrolytes were also measured. RESULTS: Both groups were similar in demographic data and fluid/blood volume during and after surgery. Cardiac index and right ventricular ejection fraction were maintained throughout the surgery in HES group but were decreased in Control group. The ratio of arterial oxygen partial pressure to inhaled oxygen fraction was increased in HES group after surgery. Thromboelastography and other parameters didn't demonstrate significant differences between the groups. CONCLUSIONS: Acute HES loading before pericardiotomy could prevent the decrease of cardiac index and right ventricular ejection fraction in OPCAB patients. Additionally, it showed desirable effects on oxygenation without adverse effects on coagulation.
Anesthesia ; Colloids ; Coronary Artery Bypass, Off-Pump* ; Electrolytes ; Ethics Committees, Research ; Hemodynamics ; Hemostasis ; Humans ; Hypotension ; Oxygen ; Partial Pressure ; Pericardiectomy ; Plasma ; Starch* ; Sternum ; Stroke Volume ; Thrombelastography ; Transplants*

Cushing's syndrome results from prolonged exposure to high levels of glucocorticoid hormones. ACTH-dependent Cushing's syndrome accounts for about 85% of endogenous causes. Autonomous pituitary ACTH secretion, called Cushing's disease, is responsible for 80% of these causes, whereas ectopic ACTH secretion is responsible for 20% of them. Appropriate therapy of patients with Cushing's syndrome depends on accurate diagnosis and classification of the disorder. In addition to the history and clinical evaluation, the laboratory evaluation of a patient with Cushingoid appearance is necessary to establish the diagnosis and determine the cause of hypercortisolism. A major problem in the differential diagnosis of ACTH-dependent Cushing's syndrome is distinguishing Cushing's disease from the ectopic ACTH syndrome. Both entities can have similar clinical and laboratory features. In addition, both pituitary microadenoma and ectopic ACTH-secreting tumors may be radiologically occult. Bilateral inferior petrosal sinus and peripheral vein catheterization with simultaneous collection of samples for measurement of ACTH is one of the most specific tests available to localize the source of ACTH production. We report two cases of Cushing's syndrome diagnosed by inferior petrosal sinus sampling associated with normal or low ACTH levels on routine basal hormone assay.
ACTH Syndrome, Ectopic ; Adrenocorticotropic Hormone* ; Catheterization ; Catheters ; Classification ; Cushing Syndrome* ; Diagnosis ; Diagnosis, Differential ; Humans ; Petrosal Sinus Sampling ; Plasma* ; Veins