Non-nosocomial healthcare-associated infective endocarditis in Taiwan: an underrecognized disease with poor outcome

<p>Abstract</p> <p>Background</p> <p>Non-nosocomial healthcare-associated infective endocarditis (NNHCA-IE) is a new category of IE of increasing importance. This study described the clinical and microbiological characteristics and outcome of NNHCA-IE in Taiwan.</p> <p>Methods</p> <p>A retrospective study was conducted of all patients with IE admitted to the Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan over a five-year period from July 2004 to July 2009. The clinical and microbiological features of NNHCA-IE were compared to those of community-acquired and nosocomial IE. Predictors for in-hospital death were determined.</p> <p>Results</p> <p>Two-hundred episodes of confirmed IE occurred during the study period. These included 148 (74%) community-acquired, 30 (15%) non-nosocomial healthcare-associated, and 22 (11%) nosocomial healthcare-associated IE. <it>Staphylococcus aureus </it>was the most frequent pathogen. Patients with NNHCA-IE compared to community-acquired IE, were older (median age, 67 vs. 44, years, <it>p </it>< 0.001), had more MRSA (43.3% vs. 9.5%, <it>p </it>< 0.001), more comorbidity conditions (median Charlson comorbidity index [interquartile range], 4[2-6] vs. 0[0-1], <it>p </it>< 0.001), a higher in-hospital mortality (50.0% vs. 17.6%, <it>p </it>< 0.001) and were less frequently recognized by clinicians on admission (16.7% vs. 47.7%, <it>p </it>= 0.002). The overall in-hospital mortality rate for all patients with IE was 25%. Shock was the strongest risk factor for in-hospital death (odds ratio 7.8, 95% confidence interval 2.4-25.2, <it>p </it>< 0.001).</p> <p>Conclusions</p> <p>NNHCA-IE is underrecognized and carries a high mortality rate. Early recognition is crucial to provide optimal management and improve outcome.</p

Shape-Controlled Synthesis of ZnS Nanostructures: A Simple and Rapid Method for One-Dimensional Materials by Plasma

In this paper, ZnS one-dimensional (1D) nanostructures including tetrapods, nanorods, nanobelts, and nanoslices were selectively synthesized by using RF thermal plasma in a wall-free way. The feeding rate and the cooling flow rate were the critical experimental parameters for defining the morphology of the final products. The detailed structures of synthesized ZnS nanostructures were studied through transmission electron microscope, X-ray diffraction, and high-resolution transmission electron microscope. A collision-controlled growth mechanism was proposed to explain the growth process that occurred exclusively in the gas current by a flowing way, and the whole process was completed in several seconds. In conclusion, the present synthetic route provides a facile way to synthesize ZnS and other hexagonal-structured 1D nanostructures in a rapid and scalable way

Neuroprotection of Tanshinone IIA against Cerebral Ischemia/Reperfusion Injury through Inhibition of Macrophage Migration Inhibitory Factor in Rats

. Recent studies have demonstrated that TSA has protective effects against focal cerebral I/R injury. However, little is known about the underlying mechanisms. Here we put forward the hypothesis that TSA acts through inhibition of MIF expression during focal cerebral I/R injury in rats.Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 hours. This was followed by reperfusion. We measured neurological deficits, brain water content, and infarct volume, and found that neurological dysfunction, brain edema, and brain infarction were significantly attenuated by TSA 6 hours after reperfusion. We also measured myeloperoxidase (MPO) activity at 6 and 24 hours, and found that neutrophil infiltration was significantly higher in the vehicle+I/R group than in the TSA+I/R group. ELISA demonstrated that TSA could inhibit MIF expression and the release of TNF-α and IL-6 induced by I/R injury. Western blot analysis and immunofluorescence staining showed that MIF expression was significantly lower in the TSA+I/R group than in the vehicle+I/R group. MIF was found almost all located in neurons and hardly any located in astrocytes in the cerebral cortex. Western blot analysis and EMSA demonstrated that NF-κB expression and activity were significantly increased in the vehicle+I/R group. However, these changes were attenuated by TSA.Our results suggest that TSA helps alleviate the proinflammatory responses associated with I/R-induced injury and that this neuroprotective effect may occur through down-regulation of MIF expression in neurons

Large Fragment Pre-S Deletion and High Viral Load Independently Predict Hepatitis B Relapse after Liver Transplantation

Hepatitis B virus (HBV) associated end-stage liver diseases are the leading causes of liver transplantation (LT) in Taiwan. Relapse of hepatitis B occurs after LT, raising the risk of graft failure and reducing patient survival. Although several oral antiviral agents have been approved for anti-HBV treatment, lamivudine (LAM) remained to be the most widely used preventive regimen in Taiwan. While several clinical predictors have been identified for hepatitis B relapse, the predictive roles of the histopathological characteristics in liver explants as well as the genotypic features of the viruses in pre-LT serum samples have not been assessed. Between September 2002 and August 2009, 150 consecutive hepatitis B surface antigen (HBsAg) positive patients undergoing LT were included for outcome analysis following assessment of the clinicopathological and virological factors prior to LT. Kaplan-Meier analyses discovered that pre-operative LAM treatment ≤3 months; membranous distribution and higher expression of tissue HBsAg in liver explants; preoperative viral load ≧106 copies/ml; and presence of large fragment (>100 base pairs) pre-S deletion (LFpreSDel) correlated significantly with hepatitis B relapse. Multivariate Cox regression analysis showed that the presence of LFpreSDel (P = 0.001) and viral load ≧106 copies/mL (P = 0.023) were independent predictors for hepatitis B relapse. In conclusion, besides high viral load, LFpreSDel mutation is an important independent predictor for hepatitis B relapse after LT. More aggressive preventive strategies should be applied for patients carrying these risk factors

The role of PET/CT in detection of gastric cancer recurrence

<p>Abstract</p> <p>Background</p> <p>In the course of surveillance of gastric cancer recurrence after curative resection, contrast CT scan is used in general. However, new findings from CT scan are not always confirmatory for the recurrence. In this case, we usually use short-term follow up strategy or therapeutic intervention with clinical decision. Recently, the use of fusion Positron Emission Tomography/Computed Tomography (PET/CT) is increasing. The purpose of this study is to evaluate the efficacy and usefulness of PET/CT for detecting recurrence of gastric cancer after curative resection.</p> <p>Methods</p> <p>Fifty two patients who received curative resection of gastric cancer and had undergone PET/CT and contrast CT for surveillance of recurrence until Dec 2006 in Seoul National University Hospital were analyzed retrospectively. Recurrence of gastric cancer was validated by histologic confirmation (n = 17) or serial contrast CT follow up with at least 5 month interval (n = 35). McNemar's test and Fisher's exact test were used to evaluate sensitivity and specificity of PET/CT and contrast CT.</p> <p>Results</p> <p>Of 52 patients, 38 patients were confirmed as recurrence. The sensitivity was 68.4% (26/38) for PET/CT and 89.4% (34/38) for contrast CT (p = 0.057). The specificity was 71.4% (10/14) and 64.2% (9/14), respectively (p = 1.0). In terms of the recurred sites, the sensitivity and specificity of PET/CT were similar to those of contrast CT in all sites except peritoneum. Contrast CT was more sensitive than PET/CT (p = 0.039) for detecting peritoneal seeding. Additional PET/CT on contrast CT showed no further increase of positive predictive value regardless of sites. Among 13 patients whose image findings between two methods were discordant and tissue confirmation was difficult, the treatment decision was made in 7 patients based on PET/CT, showing the final diagnostic accuracy of 42.8% (3/7).</p> <p>Conclusion</p> <p>PET/CT was as sensitive and specific as contrast CT in detection of recurred gastric cancer except peritoneal seeding. However, additional PET/CT on contrast CT did not increase diagnostic accuracy in detection of recurred gastric cancer. Further studies are warranted to validate the role of PET/CT in detection of gastric cancer recurrence.</p

A systematic molecular and pharmacologic evaluation of AKT inhibitors reveals new insight into their biological activity.

Background AKT, a critical effector of the phosphoinositide 3-kinase (PI3K) signalling cascade, is an intensely pursued therapeutic target in oncology. Two distinct classes of AKT inhibitors have been in clinical development, ATP-competitive and allosteric. Class-specific differences in drug activity are likely the result of differential structural and conformational requirements governing efficient target binding, which ultimately determine isoform-specific potency, selectivity profiles and activity against clinically relevant AKT mutant variants.Methods We have carried out a systematic evaluation of clinical AKT inhibitors using in vitro pharmacology, molecular profiling and biochemical assays together with structural modelling to better understand the context of drug-specific and drug-class-specific cell-killing activity.Results Our data demonstrate clear differences between ATP-competitive and allosteric AKT inhibitors, including differential effects on non-catalytic activity as measured by a novel functional readout. Surprisingly, we found that some mutations can cause drug resistance in an isoform-selective manner despite high structural conservation across AKT isoforms. Finally, we have derived drug-class-specific phosphoproteomic signatures and used them to identify effective drug combinations.Conclusions These findings illustrate the utility of individual AKT inhibitors, both as drugs and as chemical probes, and the benefit of AKT inhibitor pharmacological diversity in providing a repertoire of context-specific therapeutic options

Heterogeneous Pattern of Retinal Nerve Fiber Layer in Multiple Sclerosis. High Resolution Optical Coherence Tomography: Potential and Limitations

BACKGROUND: Recently the reduction of the retinal nerve fibre layer (RNFL) was suggested to be associated with diffuse axonal damage in the whole CNS of multiple sclerosis (MS) patients. However, several points are still under discussion. (1) Is high resolution optical coherence tomography (OCT) required to detect the partly very subtle RNFL changes seen in MS patients? (2) Can a reduction of RNFL be detected in all MS patients, even in early disease courses and in all MS subtypes? (3) Does an optic neuritis (ON) or focal lesions along the visual pathways, which are both very common in MS, limit the predication of diffuse axonal degeneration in the whole CNS? The purpose of our study was to determine the baseline characteristics of clinical definite relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients with high resolution OCT technique. METHODOLOGY: Forty-two RRMS and 17 SPMS patients with and without history of uni- or bilateral ON, and 59 age- and sex-matched healthy controls were analysed prospectively with the high resolution spectral-domain OCT device (SD-OCT) using the Spectralis 3.5mm circle scan protocol with locked reference images and eye tracking mode. Furthermore we performed tests for visual and contrast acuity and sensitivity (ETDRS, Sloan and Pelli-Robson-charts), for color vision (Lanthony D-15), the Humphrey visual field and visual evoked potential testing (VEP). PRINCIPAL FINDINGS: All 4 groups (RRMS and SPMS with or without ON) showed significantly reduced RNFL globally, or at least in one of the peripapillary sectors compared to age-/sex-matched healthy controls. In patients with previous ON additional RNFL reduction was found. However, in many RRMS patients the RNFL was found within normal range. We found no correlation between RNFL reduction and disease duration (range 9-540 months). CONCLUSIONS: RNFL baseline characteristics of RRMS and SPMS are heterogeneous (range from normal to markedly reduced levels)