Huang-Yang Chen

Clinical correlates of antifungal macrodilution susceptibility test results for non-AIDS patients with severe Candida infections treated with fluconazole.

ABSTRACT Although the clinical correlates of the reference antifungal susceptibility test results in hematogenous and deep-seatedCandida infection are still controversial, we evaluated the clinical correlates of this test in deep-seatedCandida infections in non-AIDS patients. Thirty-two non-AIDS patients with hematogenous or deep-seated Candidainfections were treated with intravenous fluconazole (400 mg a day), and the clinical outcomes were evaluated. Coexisting bacterial infections were treated with appropriate antibiotics, superinfection or reinfection was excluded, inadequate fluconazole therapy was avoided, and essential surgical intervention was performed. The MICs of fluconazole for these 32 Candida isolates were determined according to the M27-A procedure approved by the National Committee on Clinical Laboratory Standards. MICs were interpreted as susceptible (≤8 μg/ml), dose-dependent susceptible (16 to 32 μg/ml), and resistant (≥64 μg/ml) according to the criteria of the M27-A standard. The success rates were 79% (19 of 24; 95% confidence interval [CI], 59 to 93%) in the susceptible category, 66% (4 of 6; 95% CI, 19 to 95%) in the dose-dependent susceptible category, and 0% (0 of 2; 95% CI, 0 to 84%) in the resistant category. We conclude that the clinical correlation of the reference antifungal susceptibility test results is high in hematogenous and deep-seatedCandida infections.

Effect of Parenteral Selenium Supplementation in Critically Ill Patients: A Systematic Review and Meta-Analysis

Background It is currently unclear whether parenteral selenium supplementation should be recommended in the management of critically ill patients. Here we conducted a systematic review and meta-analysis to assess the efficacy of parenteral selenium supplementation on clinical outcomes. Methods/Principal Findings Randomized trials investigating parenteral selenium supplementation administered in addition to standard of care to critically ill patients were included. CENTRAL, Medline, EMBASE, the Science Citation Index, and CINAHL were searched with complementary manual searches. The primary outcome was all-cause mortality. Trials published in any language were included. Two authors independently extracted data and assessed trial quality. A third author was consulted to resolve disagreements and for quality assurance. Twelve trials were included and meta-analysis was performed on nine trials that recruited critically ill septic patients. These comprised 965 participants in total. Of these, 148 patients (30.7%) in the treatment groups, and 180 patients (37.3%) in control groups died. Parenteral selenium treatment significantly reduced all-cause mortality in critically ill patients with sepsis (relative risk [RR] 0.83, 95% CI 0.70–0.99, p = 0.04, I2 = 0%). Subgroup analyses demonstrated that the administration schedule employing longer duration (RR 0.77, 95% CI 0.63–0.94, p = 0.01, I2 = 0%), loading boluses (RR 0.73, 95% CI 0.58–0.94, p = 0.01, I2 = 0%) or high-dose selenium treatment (RR 0.77, 95% CI 0.61–0.99, p = 0.04, I2 = 0%) might be associated with a lower mortality risk. There was no evidence of adverse events. Conclusions/Significance Parenteral selenium supplementation reduces risk of mortality among critically ill patients with sepsis. Owing to the varied methodological quality of the studies, future high-quality randomized trials that directly focus on the effect of adequate-duration of parenteral selenium supplementation for severe septic patients are needed to confirm our results. Clinicians should consider these findings when treating this high-risk population. Systematic Review Registration PROSPERO 2011; CRD42011001768

Prospective Randomized Study for Comparison of Open Surgery with Laparoscopic-Assisted Placement of Tenckhoff Peritoneal Dialysis Catheter—A Single Center Experience and Literature Review

BACKGROUND The ideal method for catheter placement in patients undergoing peritoneal dialysis remains debatable. This prospective study intends to clarify whether laparoscopic assisted percutaneous puncture is superior to open surgery. MATERIALS AND METHODS From 2002 to 2006, 77 patients receiving first catheter placement were enrolled and randomized to either an open group of 40 patients or a laparoscopic group of 37 patients. Patient characteristics, operation-related data, procedural complications, and clinical outcome were compared by using the statistical software SPSS ver. 11.5 (SPSS, Chicago, IL). RESULTS Laparoscopy had a longer operative time (68.32+/-31.90 versus 46.68+/-15.99 min; P<0.001), shorter wound length (1.69+/-0.46 versus 2.34+/-0.84 cm; P<0.001), and higher costs (P<0.001) compared with open surgery. Laparoscopy tended to have a higher incidence of pericannular bleeding (21.6% versus 7.5%) and a lower rate of early catheter migration (2.7% versus 15.0%), but its early/late/overall complication rate did not statistically differ. No surgical mortality occurred. Rate and cause of overall mortality or catheter dropout did not statistically differ. Catheter longevity was equivalent in both groups. CONCLUSIONS Laparoscopic assisted percutaneous puncture exhibited no superiority to open surgery. As a matter of fact, open surgerys shorter operative time and reduced equipment requirement can increase cost-effectiveness. Therefore, conventional open surgery is recommended for most patients with primary catheter placement.

Candida peritonitis due to peptic ulcer perforation: incidence rate, risk factors, prognosis and susceptibility to fluconazole and amphotericin B

Sixty-two cases of peritonitis due to peptic ulcer perforation were diagnosed between January 2000 and December 2000. Of these 62 cases, 23 isolates of Candida in 23 cases (CP) were cultured from peritoneal fluid. Cultures of peritoneal fluid of 10 (BP) of the remaining 39 cases was positive for bacteria only. Cultures of peritoneal fluid of the remaining 29 cases was negative. Comparison of CP, BP and culture-negative cases did not reveal any significant risk factor. Of the 23 Candida isolates, the Candida species and 48-h MICs of fluconazole and amphotericin B (mean, range ug/ml) were C. albicans 18 (0.688, 0.125-1.0; 0.297, 0.031-0.5), C. glabrata 3 (0.542, 0.125-1.0; 0.25, 0.125-0.5), C. tropicalis 1 (0.25; 0.5), C. intermedia 1 (1.0; 0.125) respectively. Mortality rates of CP, BP and culture-negative peritonitis due to infection were 5/23(21.7%), 0/10 and 1/29(3.4%) respectively. Without effective antifungal therapy, the mortality rate of CP was not low.

Evaluation of the potential therapeutic role of a new generation of vitamin D analog, MART-10, in human pancreatic cancer cells in vitro and in vivo.

Pancreatic cancer is a lethal disease with no known effective chemotherapy and radiotherapy, and most patients are diagnosed in the late stage, making them unsuitable for surgery. Therefore, new therapeutic strategies are urgently needed. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is known to possess antitumor actions in many cancer cells in vitro and in vivo models. However, its clinical use is hampered by hypercalcemia. In this study, we investigated the effectiveness and safety of a new generation, less calcemic analog of 1α,25(OH)2D3, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), in BxPC-3 human pancreatic carcinoma cells in vitro and in vivo. We demonstrate that MART-10 is at least 100-fold more potent than 1α,25(OH)2D3 in inhibiting BxPC-3 cell proliferation in a time- and dose-dependent manner, accompanied by a greater upregulation of cyclin-dependent kinase inhibitors p21 and p27 and a greater downregulation of cyclin D3 and cyclin-dependent kinases 4 and 5, leading to a greater increase in the fraction of cells in G0/G1 phase. No induction of apoptosis and no effect on Cdc25 phosphatases A and C were observed in the presence of either MART-10 or 1α,25(OH)2D3. In a xenograft mouse model, treatment with 0.3 µg/kg body weight of MART-10 twice/week for 3 weeks caused a greater suppression of BxPC-3 tumor growth than the same dose of 1α,25(OH)2D3 without inducing hypercalcemia and weight loss. In conclusion, MART-10 is a promising agent against pancreatic cancer growth. Further clinical trial is warranted.

19-Nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10) is a potent cell growth regulator with enhanced chemotherapeutic potency in liver cancer cells

The discovery that the active form of vitamin D, 1α,25-dihydroxyvitamin D [1α,25(OH)(2)D] can modulate cellular proliferation and differentiation of cancer cells has led to its potential application as a chemotherapeutic agent to treat a variety of cancers. However, the use of 1α,25(OH)(2)D is limited due to its lethal side effect of hypercalcemia upon systemic administration. To overcome this drawback, numerous analogs have been synthesized. In this report, we examined the anti-proliferative activity of a new analog, 19-nor-2α-(3-hydroxypropyl)-1α,25(OH)(2)D(3) (MART-10), in HepG2 liver cancer cells, and studied the potential mechanisms mediating this action. We found that MART-10 exhibited approximately 100-fold greater activity than 1α,25(OH)(2)D(3) in inhibiting HepG2 cell proliferation as determined by cell number counting method. MART-10 was also approximately 100-fold more potent than 1α,25(OH)(2)D(3) in the upregulation of p21 and p27, that in turn arrested HepG2 cells at the G(0)/G(1) phase to a greater extent. Given that no active caspase 3 was detected and treatment with 1α,25(OH)(2)D(3) or MART-10 did not further increase the fractions of apoptotic and necrosis cells over the controls, the growth-inhibitory effect of 1α,25(OH)(2)D(3) and MART-10 on HepG2 cells may not involve apoptosis. Overall, our findings suggest that MART-10 is a good candidate as a novel therapeutic regimen against liver cancer. Further pre-clinical studies using animal models and the subsequent human clinical trials are warranted.

Liver angiosarcoma, a rare liver malignancy, presented with intraabdominal bleeding due to rupture--a case report.

Liver angiosarcoma is a rare disease, however it still ranks as the third of most common primary liver maligancies. The prognosis of liver angiosarcoma is very poor with almost all patients with this kind of disease die within 2 years after diagnosis. No specific symptoms and signs are closely associated with this disease. Here, we report a case presenting shock status at first due to rupture of liver angiosarcoma- induced internal bleeding. After emergent transarterial embolization (TAE), she received partial hepatectomy two weeks later. 4 months after operation, she is still with a good performance status without obvious recurrence or metastasis identified.

Diagnostic performance of alpha-fetoprotein, lens culinaris agglutinin-reactive alpha-fetoprotein, des-gamma carboxyprothrombin, and glypican-3 for the detection of hepatocellular carcinoma: a systematic review and meta-analysis protocol

BackgroundDiagnosis of early-stage hepatocellular carcinoma (HCC) followed by curative resection or liver transplantation offers the best chance for long-term patient survival. Clinically, ultrasonography has suboptimal sensitivity for detecting early-stage HCC. Several serological tests including alpha-fetoprotein (AFP), the ratio of lens culinaris agglutinin-reactive alpha-fetoprotein to total AFP (AFP-L3/AFP), des-gamma carboxyprothrombin (DCP), and glypican-3 (GPC-3) have been widely investigated as diagnostic biomarkers for early-stage HCC in at-risk populations. However, these tests are not recommended for routine HCC screening. Our objective is to determine the diagnostic performance of AFP, AFP-L3/AFP, DCP, and GPC-3 for the detection of HCC, particularly early-stage tumors meeting the Milan criteria.Methods/designWe will include cross-sectional studies that consecutively or randomly recruit target populations. We will search the Cochrane Library, Medline, Embase, Science Citation Index, and the Chinese National Knowledge Infrastructure. We will also search the MEDION and ARIF databases to identify diagnostic systematic reviews that include primary studies. Reference lists of relevant reviews will be searched for additional trials. Language restrictions will not be applied. Two reviewers will independently screen study eligibility and extract data. Methodological quality will be assessed according to the revised tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Two authors will apply the QUADAS-2 assessment to all the included studies, and any discrepancies will be resolved by the third author. The following test characteristics will be extracted into 2 × 2 tables for all included studies: true positives, false positives, true negatives, and false negatives. Study-specific estimates of sensitivity and specificity with 95% confidence intervals will be displayed in forest plots. When possible, we will use the bivariate random-effects model or the Rutter and Gatsonis hierarchical summary receiver operating characteristic model for statistical analysis. To investigate heterogeneity, we will include study designs, population characteristics, test characteristics, and types of reference standard as the study-level variables.DiscussionOur systematic review will allow patients, clinicians, and researchers to determine the diagnostic performance of AFP, AFP-L3/AFP, DCP, and GPC-3 for the detection of early-stage HCC and the potential roles of these diagnostic biomarkers in the existing diagnostic pathways.Systematic Review Registration: PROSPERO 2013; CRD42013003879

A systematic review and meta‐analysis of adjuvant interferon therapy after curative treatment for patients with viral hepatitis‐related hepatocellular carcinoma

The efficacy of adjuvant interferon treatment for the management of patients with viral hepatitis‐related hepatocellular carcinoma (HCC) following curative treatment is controversial. We have conducted a systematic review with meta‐analysis to assess the effects of adjuvant interferon therapy on survival outcomes. Randomized and nonrandomized studies (NRSs) comparing adjuvant interferon treatment with the standard of care for viral hepatitis‐related HCC after curative treatment were included. CENTRAL, Medline, EMBASE and the Science Citation Index were searched with complementary manual searches. The primary outcomes were recurrence‐free survival (RFS) and overall survival (OS). Nine randomized trials and 13 NRSs were included in the meta‐analysis. These nine randomized trials included 942 participants, of whom, 490 were randomized to the adjuvant interferon treatment group and 452 to the control group. The results of meta‐analysis showed unexplained heterogeneity for both RFS and OS. The 13 NRSs included 2214 participants, of whom, 493 were assigned to the adjuvant interferon treatment group and 1721 to the control group. The results of meta‐analysis showed that, compared with controls, adjuvant interferon treatment significantly improved the RFS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.52–0.84, I2 = 29%] and OS (HR 0.43, 95% CI 0.34–0.56, I2 = 0%) of patients with hepatitis C virus‐related HCC following curative treatment. There was little evidence for beneficial effects on patients with hepatitis B virus‐related HCC. Future research should be aimed at clarifying whether the effects of adjuvant interferon therapy are more prominent in hepatitis C patients with sustained virological responses.

Pancreaticoduodenectomy Versus Frey's Procedure for Chronic Pancreatitis: Preliminary Data on Outcome and Pancreatic Function

PurposeSeveral surgical treatments have been proposed for treating chronic pancreatitis (CP), including standard pancreaticoduodenectomy (PD), pylorus-preserving PD, Begers procedure, and Freys procedure; however, few studies have compared pre- and postoperative pancreatic function in patients undergoing surgery for CP.MethodsBetween 1996 and 2003, 42 patients with CP underwent pancreatic head resection; as PD in 17 and as Freys procedure in 25. Freys procedure was chosen if the pancreatic duct was dilated more than 5 mm. We conducted this prospective, nonrandomized study to compare the pre- and postoperative status after PD or Freys procedure by evaluating pancreatic function and symptom relief.ResultsThe demographic features, surgical morbidity, and mortality were similar in the two groups. Pancreatic exocrine function improved, pain subsided, and complications of the adjacent organs resolved after surgery in both groups. Similar postoperative endocrine and exocrine functional results were observed in both groups. Freys procedure was associated with a significantly shorter hospital stay than PD (10.6 versus 15.4 days, respectively; (P < 0.0001)).ConclusionThere were no significant difference in operative time, surgical morbidity, or mortality rates between PD and Freys procedure. Both procedures were equally effective in terms of pain relief, improvement of pancreatic exocrine function, and control of complications affecting the adjacent organs; however, Freys procedure was associated with a significantly shorter hospital stay.