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1.  Scoring Systems for Predicting Mortality after Liver Transplantation 
PLoS ONE  2014;9(9):e107138.
Liver transplantation can prolong survival in patients with end-stage liver disease. We have proposed that the Sequential Organ Failure Assessment (SOFA) score calculated on post-transplant day 7 has a great discriminative power for predicting 1-year mortality after liver transplantation. The Chronic Liver Failure - Sequential Organ Failure Assessment (CLIF-SOFA) score, a modified SOFA score, is a newly developed scoring system exclusively for patients with end-stage liver disease. This study was designed to compare the CLIF-SOFA score with other main scoring systems in outcome prediction for liver transplant patients.
We retrospectively reviewed medical records of 323 patients who had received liver transplants in a tertiary care university hospital from October 2002 to December 2010. Demographic parameters and clinical characteristic variables were recorded on the first day of admission before transplantation and on post-transplantation days 1, 3, 7, and 14.
The overall 1-year survival rate was 78.3% (253/323). Liver diseases were mostly attributed to hepatitis B virus infection (34%). The CLIF-SOFA score had better discriminatory power than the Child-Pugh points, Model for End-Stage Liver Disease (MELD) score, RIFLE (risk of renal dysfunction, injury to the kidney, failure of the kidney, loss of kidney function, and end-stage kidney disease) criteria, and SOFA score. The AUROC curves were highest for CLIF-SOFA score on post-liver transplant day 7 for predicting 1-year mortality. The cumulative survival rates differed significantly for patients with a CLIF-SOFA score ≤8 and those with a CLIF-SOFA score >8 on post-liver transplant day 7.
The CLIF-SOFA score can increase the prediction accuracy of prognosis after transplantation. Moreover, the CLIF-SOFA score on post-transplantation day 7 had the best discriminative power for predicting 1-year mortality after liver transplantation.
PMCID: PMC4162558  PMID: 25216239
2.  Adrenal Dysfunction in Portal Hypertensive Rats with Acute Hemorrhage 
PLoS ONE  2014;9(3):e92093.
Nitric oxide (NO) participates in shock and poorer portal hypotensive effect to vasoconstrictors in portal hypertension with hemorrhage, the so-called splanchnic hyposensitivity. Relative adrenal insufficiency accompanies hemorrhagic shock and is found in liver disease, the ‘hepatoadrenal syndrome’, but the relevant interactions remain unsettled. Portal hypertensive rats were induced by partial portal vein ligation (PVL). Experiments were performed on the 14th day post PVL: (I) ACTH stimulation test for rats without or with hemorrhage; (II) Glypressin response (mean arterial pressure, MAP; portal pressure, PP) in rats (a) without hemorrhage or with hemorrhage, injected with (b) distilled water (DW), (c) dexamethasone 3 mg/kg; (III) To survey the dose-dependent effects of glucocorticoid without being confounded by endogenous adrenal hormone, glypressin response was surveyed in PVL rats with adrenalectomy: (a) without hemorrhage or with hemorrhage, injected with (b) DW; (c) dexamethasone 3 mg/kg; (d) dexamethasone 5 mg/kg. Plasma tumor necrosis factor-α (TNF-α) concentrations and abdominal aorta (AA), superior mesenteric artery (SMA) NO synthases (NOS) mRNA expressions were determined. The results showed that ACTH induced corticosterone release similarly in PVL rats with or without hemorrhage. In bleeding PVL rats, dexamethasone (1) down-regulated AA NOS and enhanced glypressin-induced MAP elevation; (2) did not influence glypressin-induced PP reduction; (3) reduced TNF-α. In bleeding PVL and adrenalectomized rats, high-dose dexamethasone (1) down-regulated AA/SMA NOS; (2) enhanced glypressin-induced MAP elevation and PP reduction; (3) reduced TNF-α. In conclusion, bleeding portal hypertensive rats failed to enhance corticosterone release, suggesting a relative adrenal insufficiency. High-dose dexamethasone reversed systemic hypotension and splanchnic hyporesponsiveness to glypressin in adrenalectomized PVL rats accompanied by TNF-α and NOS down-regulation, suggesting the importance of adequate adrenocorticoid supplement in portal hypertension with hemorrhage and adrenal dysfunction.
PMCID: PMC3954870  PMID: 24633079
3.  Steatocystoma multiplex as initial impression of non-small cell lung cancer with complete response to gefitinib 
Cutaneous metastases are rare and seldom present at the time of first diagnosis of cancer. Data from various studies show that 1-12% of lung cancer patients experience tumor spread to the skin. The scalp, chest, and abdomen are favored sites of skin metastases from lung cancers, but metastases to multiple skin sites in a single patient are rarely reported. We describe a 56-year-old lung adenocarcinoma patient, initially diagnosed with steatocystoma multiplex who responded well to gefitinib treatment. The efficacy of conventional chemotherapy for cutaneous metastases has been limited because of the relatively poor blood supply to the skin. It has been demonstrated that tyrosine kinase inhibitor (TKI), gefitinib, has significant clinical benefit in lung cancer patients with epidermal growth factor receptor (EGFR) mutation even in metastases to the brain. However, the therapeutic response to gefitinib in patients with skin metastases is seldom mentioned in the literature. We report one case of lung adenocarcinoma with multiple skin metastases that were successfully treated with gefitinib.
PMCID: PMC3937749  PMID: 24653640
Steatocystoma multiplex; lung cancer; adenocarcinoma; gefitinib
4.  Risk Models and Scoring Systems for Predicting the Prognosis in Critically Ill Cirrhotic Patients with Acute Kidney Injury: A Prospective Validation Study 
PLoS ONE  2012;7(12):e51094.
Cirrhotic patients with acute kidney injury (AKI) admitted to intensive care units (ICUs) show extremely high mortality rates. We have proposed the MBRS scoring system, which can be used for assessing patients on the day of admission to the ICU; this new system involves determination of mean arterial pressure (MAP) and bilirubin level and assessment of respiratory failure and sepsis. We had used this scoring system to analyze the prognosis of ICU cirrhotic patients with AKI in 2008, and the current study was an external validation of this scoring system.
A total of 190 cirrhotic patients with AKI were admitted to the ICU between March 2008 and February 2011. We prospectively analyzed and recorded the data for 31 demographic parameters and some clinical characteristic variables on day 1 of admission to the ICU; these variables were considered as predictors of mortality.
The overall in-hospital mortality rate was 73.2% (139/190), and the 6-month mortality rate was 83.2% (158/190). Hepatitis B viral infection (43%) was observed to be the cause of liver disease in most of the patients. Multiple logistic regression analysis indicated that the MBRS and Acute Physiology and Chronic Health Evaluation III (ACPACHE III) scores determined on the first day of admission to the ICU were independent predictors of in-hospital mortality in patients. In the analysis of the area under the receiver operating characteristic (AUROC) curves, the MBRS scores showed good discrimination (AUROC: 0.863±0.032, p<0.001) in predicting in-hospital mortality.
On the basis of the results of this external validation, we conclude that the MBRS scoring system is a reproducible, simple, easy-to-apply evaluation tool that can increase the prediction accuracy of short-term prognosis in critically ill cirrhotic patients with AKI.
PMCID: PMC3517580  PMID: 23236437
5.  Modified endoscopic submucosal dissection with enucleation for treatment of gastric subepithelial tumors originating from the muscularis propria layer 
BMC Gastroenterology  2012;12:124.
Gastric subepithelial tumors are usually asymptomatic and observed incidentally during endoscopic examination. Although most of these tumors are considered benign, some have a potential for malignant transformation, particularly those originating from the muscularis propria layer. For this type of tumor, surgical resection is the standard treatment of choice. With recent advent of endoscopic resection techniques and devices, endoscopic submucosal dissection (ESD) has been considered as an alternative way of treatment. The aim of this study is to demonstrate the feasibility of a modified ESD technique with enucleation for removal of gastric subepithelial tumors originating from the muscularis propria layer, and to evaluate its efficacy and safety.
From November 2009 to May 2011, a total of 16 patients received a modified ESD with enucleation for their subepithelial tumors. All tumors were smaller than 5 cm and originated from the muscularis propria layer of the stomach, as shown by endoscopic ultrasonography (EUS). The procedure was conducted with an insulated-tip knife 2. Patient’s demographics, tumor size and pathological diagnosis, procedure time, procedure-related complication, and treatment outcome were reviewed.
Fifteen of the sixteen tumors were successful complete resection. The mean tumor size measured by EUS was 26.1 mm (range: 20–42 mm). The mean procedure time was 52 minutes (range: 30–120 minutes). Endoscopic features of the 4 tumors were pedunculated and 12 were sessile. Their immunohistochemical diagnosis was c-kit (+) stromal tumor in 14 patients and leiomyoma in 2 patients. There was no procedure-related perforation or overt bleeding. During a mean follow up duration of 14.8 months (range: 6–22 months), there was no tumor recurrence or metastasis.
Using a modified ESD with enucleation for treatment of gastric subepithelial tumors originating from the muscularis propria layer and larger than 2 cm, complete resection can be successfully performed without serious complication. It is a safe and effective alternative to surgical therapy for these tumors of 2 to 5 cm in size.
PMCID: PMC3508821  PMID: 22978826
Endoscopic submucosal dissection; Gastrointestinal stromal tumors; Endoscopic ultrasonography
6.  The Role of Age in Predicting the Outcome of Caustic Ingestion in Adults: A Retrospective Analysis 
BMC Gastroenterology  2011;11:72.
Although the outcomes of caustic ingestion differ between children and adults, it is unclear whether such outcomes differ among adults as a function of their age. This retrospective study was performed to ascertain whether the clinical outcomes of caustic ingestion differ significantly between elderly and non-elderly adults.
Medical records of patients hospitalized for caustic ingestion between June 1999 and July 2009 were reviewed retrospectively. Three hundred eighty nine patients between the ages of 17 and 107 years were divided into two groups: non-elderly (< 65 years) and elderly (≥ 65 years). Mucosal damage was graded using esophagogastroduodenoscopy (EGD). Parameters examined in this study included gender, intent of ingestion, substance ingested, systemic and gastrointestinal complications, psychological and systemic comorbidities, severity of mucosal injury, and time to expiration.
The incidence of psychological comorbidities was higher for the non-elderly group. By contrast, the incidence of systemic comorbidities, the grade of severity of mucosal damage, and the incidence of systemic complications were higher for the elderly group. The percentages of ICU admissions and deaths in the ICU were higher and the cumulative survival rate was lower for the elderly group. Elderly subjects, those with systemic complications had the greatest mortality risk due to caustic ingestion.
Caustic ingestion by subjects ≥65 years of age is associated with poorer clinical outcomes as compared to subjects < 65 years of age; elderly subjects with systemic complications have the poorest clinical outcomes. The severity of gastrointestinal tract injury appears to have no impact on the survival of elderly subjects.
PMCID: PMC3141751  PMID: 21672200
7.  Secretome-Based Identification of ULBP2 as a Novel Serum Marker for Pancreatic Cancer Detection 
PLoS ONE  2011;6(5):e20029.
To discover novel markers for improving the efficacy of pancreatic cancer (PC) diagnosis, the secretome of two PC cell lines (BxPC-3 and MIA PaCa-2) was profiled. UL16 binding protein 2 (ULBP2), one of the proteins identified in the PC cell secretome, was selected for evaluation as a biomarker for PC detection because its mRNA level was also found to be significantly elevated in PC tissues.
ULBP2 expression in PC tissues from 67 patients was studied by immunohistochemistry. ULBP2 serum levels in 154 PC patients and 142 healthy controls were measured by bead-based immunoassay, and the efficacy of serum ULBP2 for PC detection was compared with the widely used serological PC marker carbohydrate antigen 19-9 (CA 19-9).
Immunohistochemical analyses revealed an elevated expression of ULPB2 in PC tissues compared with adjacent non-cancerous tissues. Meanwhile, the serum levels of ULBP2 among all PC patients (n = 154) and in early-stage cancer patients were significantly higher than those in healthy controls (p<0.0001). The combination of ULBP2 and CA 19-9 outperformed each marker alone in distinguishing PC patients from healthy individuals. Importantly, an analysis of the area under receiver operating characteristic curves showed that ULBP2 was superior to CA 19-9 in discriminating patients with early-stage PC from healthy controls.
Collectively, our results indicate that ULBP2 may represent a novel and useful serum biomarker for pancreatic cancer primary screening.
PMCID: PMC3098863  PMID: 21625447
8.  Identification of MYO18A as a Novel Interacting Partner of the PAK2/βPIX/GIT1 Complex and Its Potential Function in Modulating Epithelial Cell Migration 
Molecular Biology of the Cell  2010;21(2):287-301.
MYO18A is found as a novel PAK2 binding partner via βPIX/GIT1. MYO18A-depleted cells showed dramatic changes in shape, actin stress fiber and membrane ruffle formation, and displayed increases in the number and size of focal adhesions and a decrease in cell migration, suggesting an important role of MYO18A in regulating epithelial cell migration.
The p21-activated kinase (PAK) 2 is known to be involved in numerous biological functions, including the regulation of actin reorganization and cell motility. To better understand the mechanisms underlying this regulation, we herein used a proteomic approach to identify PAK2-interacting proteins in human epidermoid carcinoma A431 cells. We found that MYO18A, an emerging member of the myosin superfamily, is a novel PAK2 binding partner. Using a siRNA knockdown strategy and in vitro binding assay, we discovered that MYO18A binds to PAK2 through the βPIX/GIT1 complex. Under normal conditions, MYO18A and PAK2 colocalized in lamellipodia and membrane ruffles. Interestingly, knockdown of MYO18A in cells did not prevent formation of the PAK2/βPIX/GIT1 complex, but rather apparently changed its localization to focal adhesions. Moreover, MYO18A-depleted cells showed dramatic changes in morphology and actin stress fiber and membrane ruffle formation and displayed increases in the number and size of focal adhesions. Migration assays revealed that MYO18A-depleted cells had decreased cell motility, and reexpression of MYO18A restored their migration ability. Collectively, our findings indicate that MYO18A is a novel binding partner of the PAK2/βPIX/GIT1 complex and suggest that MYO18A may play an important role in regulating epithelial cell migration via affecting multiple cell machineries.
PMCID: PMC2808764  PMID: 19923322
9.  Critical illness-related corticosteroid insufficiency in patients with severe acute biliary pancreatitis: a prospective cohort study 
Critical Care  2009;13(4):R123.
Gallstones are the most common cause of acute pancreatitis worldwide. Patients with severe acute biliary pancreatitis (SABP) constitute a subgroup of severe acute pancreatitis (SAP) patients in whom systemic inflammation may be triggered and perpetuated by different mechanisms. The aim of this prospective investigation was to examine the adrenal response to corticotropin and the relationship between adrenal function and outcome in patients with SABP.
Thirty-two patients with SABP were enrolled in this study. A short corticotropin (250 μg) stimulation test (SST) was performed within the first 24 hours of admission to the ICU. Critical illness related corticosteroid insufficiency (CIRCI) was defined as follows: baseline value less than 10 μg/dL, or cortisol response less than 9 μg/dL.
CIRCI occurred in 34.4% of patients. The patients with CIRCI were more severely ill as evidenced by higher APACHE II and SOFA scores and numbers of organ system dysfunction on the day of SST. The in-hospital mortality for the entire group was 21.9%. The CIRCI group had a higher hospital mortality rate compared to those with normal adrenal function (45.5% vs. 9.5%, P = 0.032). The hospital survivors had a higher cortisol response to corticotropin (17.4 (8.3–27.1) vs. 7.2 (1.7–12) μg/dL, P = 0.019). The cortisol response to corticotropin inversely correlated with SOFA score and the number of organ dysfunction on the day of SST. The rates of pancreatic necrosis and bacteremia were significantly higher in the CIRCI group (100% vs 42.9%, P = 0.002; 81.8% vs 23.8%, P = 0.003, respectively).
CIRCI is common in patients with SABP. It is associated with bacteremia, multiple organ dysfunction and increased mortality.
PMCID: PMC2750175  PMID: 19630953

Results 1-9 (9)