Impact of de-escalation therapy on clinical outcomes for intensive care unit-acquired pneumonia

Introduction

De-escalation therapy is a strategy currently used for the management of nosocomial pneumonia. In this study, we evaluated clinical outcomes and risk factors related to de-escalation therapy in patients with intensive care unit (ICU)-acquired pneumonia.

Methods

This was a retrospective observational cohort study of ICU patients who developed pneumonia more than 48 hours after admission to the ICU at Samsung Medical Center from September 2004 to December 2007.

Results

The 137 patients comprised 44 (32.1%) who received de-escalation therapy and 93 in the non-de-escalation group. The de-escalation group showed a lower pneumonia-related mortality rate than the non-de-escalation group by day 14 (2.3% vs. 10.8%, respectively; P = 0.08) and by day 30 (2.3% vs. 14%, respectively; P = 0.03) after the diagnosis of pneumonia. The variables independently associated with ICU-acquired pneumonia-related mortality included the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the modified Clinical Pulmonary Infection Score (CPIS) after 5 days with pneumonia. The non-de-escalation group had significantly higher APACHE II score and modified CPIS after 5 days with ICU-acquired pneumonia compared to the de-escalation group. Among all patients, 20.4% (28 of 137) had negative cultures for pathogens, and 42.9% (12 of 28) received de-escalation therapy. The latter 12 patients received de-escalation therapy and survived 30 days after the diagnosis of pneumonia.

Conclusions

Patients in the de-escalation group showed a significantly lower mortality rate compared to patients in the non-de-escalation group. De-escalation therapy can be safely provided to patients with ICU-acquired pneumonia if they are clinically stable by day 5, even in those whose respiratory specimen cultures yield no specific pathogens.     

Close correlation of p53 mutation to microvascular invasion in hepatocellular carcinoma

Mutation of p53 is a poor prognostic indicator of hepatocellular carcinoma (HCC). Although poor histologic differentiation of HCC has been associated with p53 mutations, the exact reasons for unfavorable clinical outcomes in patients with HCC remain to be clarified. In this study, we evaluate the association between p53 mutation and histopathologic features of HCCs, as well as tumor recurrences and survival. We examined 20 HCCs and surrounding liver tissues from patients who underwent surgical resection, and we performed direct sequencing of p53 gene. p53 mutations were found in 9 of 20 HCCs; none were found in the surrounding liver tissue. p53 mutations were frequent in large, multinodular, and poorly differentiated HCCs. Five of 9 with p53 mutation (in contrast, none of 11 with wild-type mutation) showed microvascular invasions. Hepatocellular carcinoma recurred in 6 of 9 with p53 mutation, in contrast to only 2 of 11 with wild-type mutation. The 1-year survival rate with p53 mutation was significantly lower than that with wild-type. In conclusion, it is suggested that p53 mutations tend to be commonly associated with microvascular invasions, which may result in micrometastasis, followed by frequent recurrences.     

Pharmacological unmasking microarray approach-based discovery of novel DNA methylation markers for hepatocellular carcinoma

DNA methylation is one of the main epigenetic mechanisms and hypermethylation of CpG islands at tumor suppressor genes switches off these genes. To find novel DNA methylation markers in hepatocellular carcinoma (HCC), we performed pharmacological unmasking (treatment with 5-aza-2'-deoxycytidine or trichostatin A) followed by microarray analysis in HCC cell lines. Of the 239 promoter CpG island loci hypermethylated in HCC cell lines (as revealed by methylation-specific PCR), 221 loci were found to be hypermethylated in HCC or nonneoplastic liver tissues. Thirty-three loci showed a 20% higher methylation frequency in tumors than in adjacent nonneoplastic tissues. Correlation of individual cancer-related methylation markers with clinicopathological features of HCC patients (n = 95) revealed that the number of hypermethylated genes in HCC tumors was higher in older than in younger patients. Univariate and multivariate survival analysis revealed that the HIST1H2AE methylation status is closely correlated with the patient's overall survival (P = 0.022 and P = 0.010, respectively). In conclusion, we identified 221 novel DNA methylation markers for HCC. One promising prognostic marker, HIST1H2AE, should be further validated in the prognostication of HCC patients.     

Effects of a 2-, 3- and 4-electrode stimulator design on current dispersion on the surface and into the limb during electrical stimulation in controls and patients with wounds

Electrical stimulation is a widely used modality in the field of physical therapy and exercise physiology. The most common method for the application of electrical stimulation is a two-electrode system where one electrode is the source and the other is a reference. However, recent studies report that a more effective delivery system can be achieved if more than two electrodes are used. In the present investigation, the circuitry to deliver electrical stimulation through a 2-, 3- or 4-electrode delivery system was designed. The system was evaluated by its ability to deliver current on the surface of the skin as well as deep into the quadriceps muscle in six control subjects and in and around wounds in six other subjects. The results of the experiments showed that much better depth of penetration was achieved in a 4-electrode system (one electrode was on the opposite side of the limb and three electrodes were on top of the limb) than in either a 2- or a 3-electrode delivery system. In non-wounded skin, given the same current from the stimulator, the current in the quadriceps muscle was found to be double with a 4-electrode versus a 2-electrode system. In wounds, this same finding was seen. Here, blood flow, an indicator of the effectiveness of electrical stimulation in wounds, was three times higher if a multi-channel stimulator was used versus a 2-channel stimulator. Thus a multi-channel electrical stimulation system is more effective than a 2-electrode system.     

Current management of hepatocellular carcinoma:An Eastern perspective

Hepatocellular carcinoma(HCC) is one of the leading causes of cancer death, especially in Eastern areas. With advancements in diagnosis and treatment modalities for HCC, the survival and prognosis of HCC patients are improving. However, treatment patterns are not uniform between areas despite efforts to promote a common protocol. Although many hepatologists in Asian countries may adopt the principles of the Barcelona Clinic Liver Cancer staging system, they are also independently making an effort to expand the indications of each treatment and to combine therapies for better outcomes. Several expanded criteria for liver transplantation in HCC have been developed in Asian countries. Living donor liver transplantation is much more commonly performed in these countries than deceased donor liver transplantation, and it may be preceded by other treatments such as the down-staging of tumors. Local ablation therapies are often combined with transarterial chemoembolization( TACE) and the outcome is comparable to that of surgical resection. The indications of TACE are expanding, and there are new types of transarterial therapies. Although data on drug-eluting beads, TACE, and radioembolization in Asian countries are still relatively sparse compared with Western countries, these methods are gradually gaining popularity because of better tolerability and the possibility of improved response rates. Hepatic arterial infusion chemotherapy and radiotherapy are not included in Western guidelines, but are currently being used actively in several Asian countries. For more advanced HCCs, appropriate combinations of TACE, radiotherapy, and sorafenib can be considered, and emerging data indicate improved outcomes of combination therapies compared with single therapies. To include these paradigm shifts into newer treatment guidelines, more studies may be needed, but they are certainly in progress.     

Comparison of the skin biophysical parameters of Southeast Asia females: forehead–cheek and ethnic groups

Background Regional and ethnic (racial) differences in skin properties are well known. However, regional and racial studies are limited and have studied skin properties using an insufficient number of subjects and limited ethnic groups, except in the case of some recent studies. Objective The aim of this study was (1) to compare the skin biophysical parameter among the large scale of Southeast Asia females group and (2) to compare skin properties of the forehead and cheek. Methods We measured and compared seven skin biophysical parameters, such as skin hydration, sebum, skin pH, melanin index, erythema index, skin elasticity and transepidermal water loss (TEWL), of the forehead and cheek of a large population of Indonesian (n = 200), Vietnamese (n = 100) and Singaporean females (n = 97). Results At the point of site difference, there were significant differences in five biophysical parameters (skin hydration, skin pH, melanin index, erythema index and skin elasticity) in Indonesian females. In Vietnamese and Singaporean women, they were significant differences in five biophysical parameters (skin hydration, skin pH, melanin index, erythema index and TEWL). At the point of ethnic difference, the Indonesian women had the highest skin pH and melanin index between the different ethnic groups. Vietnamese women had the highest skin hydration and TEWL in the forehead, whereas Singaporean women had the highest skin elasticity. Conclusion The skin biophysical parameters are different between the forehead and cheek among Southeast Asian females. It also reveals that the biophysical parameters are different in same racial group.     

Pilot study on combination of azacitidine and low-dose cytarabine for patients with refractory anemia with excess blast

This study analyzed the outcomes of the combination of azacitidine and low-dose cytarabine in patients newly diagnosed with refractory anemia with excess blast (RAEB). Patients were treated with azacitidine 75 mg/m² for 7 days subcutaneously and cytarabine 20 mg/m² intravenously for 7 days every 28 days. The assigned regimen was repeated for two cycles, then the patients treated with azacytidine alone until progression or allogeneic stem cell transplantation (allo-SCT). Eighteen patients with 5 RAEB-1 and 13 RAEB-2 were enrolled in the current study. After two cycles of the combination therapy, responses were achieved in nine patients (50.0%): four complete response (CR) (22.2%), one partial response (5.6%), two marrow-CR (11.1%), and two hematologic improvement (11.1%). Four patients (22.2%) progressed to acute leukemia during two cycles of the combination therapy. The 1-year overall survival (OS) was 87.5% for the early response group (responses at two cycles) and 0% for the late response group (responses at four cycles, p = 0.042). Plus, the median survival time was 476 days (range, 37–718 days) for the early response group and 221 days (range, 193–249 days) for the late response group. The 1-year OS was 100% for the patients who underwent allo-SCT and 73.4% for those without allo-SCT. In summary, the combination therapy showed promising response rate when compared to treatment with azacitidine alone. However, it was limited in terms of preventing leukemic transformation. Allo-SCT would seem to be the only available treatment that can alter disease progression.     

Risk factors and effects on long-term outcomes of cardiac troponin I elevation after drug-eluting stent implantation in patients with stable coronary artery disease

This study evaluated the risk factors of postprocedure cardiac troponin I (cTnI) increase and its effects on repeat revascularization and on overall clinical outcomes in patients with angina and normal preprocedural cTnI levels who underwent successful drug-eluting stent implantation. Postprocedure cTnI increase (≥0.5 ng/ml) was observed in 207 of 802 patients (25.8%). Patients with cTnI increase had more extensive coronary disease than patients without cTnI increase, which necessitated for the cTnI group more multilesion interventions and a longer total stent length. In multivariate analysis, total stent length (odds ratio 1.02, 1.01 to 1.03, p = 0.001) and use of glycoprotein IIb/IIIa inhibitors (3.07, 1.54 to 6.11, p <0.001) were identified as independent predictors of cTnI increase. During a median follow-up of 42 months, however, there were no significant between-group differences in Kaplan-Meier estimates of any repeat revascularization (24.8% vs 18.4%, hazard ratio 1.085, 0.723 to 1.627, p = 0.694) and major adverse cardiovascular events (27.0% vs 22.4%, 1.022, 0.703 to 1.485, p = 0.911). In conclusion, patients with postprocedure cTnI increase had more severe baseline coronary disease and received more complex interventional procedures. However, cTnI increase after successful drug-eluting stent implantation was not associated with an increased risk of repeat revascularization or of other adverse events.