Preferred use of polyhexanide in orthopedic surgery

In orthopedic and trauma surgery, the most frequently used antiseptic is polyhexanide. Its favored application is based on prepossessing tissue compatibility in contrast to various antiseptics and a high antimicrobiological effect. Recent studies showed toxic effects of this antiseptic on human chondrocytes. The aim of this study was to further analyze the toxic and apoptotic effects of polyhexanide on primary human chondrocytes. The hypothesis of this study was that polyhexanide induces apoptosis on human chondrocytes. Primary human chondrocytes were isolated and cultured from human donors with osteoarthritis of the knee who underwent total arthroplasty and had no indication of infection. Polyhexanide at a standard concentration of 0.04% was added to the monolayer cultures. Early and late apoptotic cells were analyzed by flow cytometric detection of annexin V, active caspases, and 7AAD, and by fluorescence microscopy using annexin V and propidium iodide staining. Flow cytometric analysis demonstrated an increase of annexin V and active caspases expression of human chondrocytes after incubation with polyhexanide. Fluorescence microscopy demonstrated a high number of annexin V positive and propidium iodide negative early apoptotic cells. The data show that polyhexanide promotes apoptosis on primary human chondrocytes in vitro, which may indicate the use of polyhexanide in septic joint surgery.     

Genetic variation in IL28B and treatment-induced clearance of hepatitis C virus in HIV-positive patients with acute and chronic hepatitis C

Recently, a IL28B (rs 12979860) gene polymorphism was identified as a predictor for response to hepatitis C virus-specific treatment in human immunodeficiency virus (HIV)-uninfected and -infected patients with chronic hepatitis C. In an analysis of HIV-infected patients with acute hepatitis C, we found that the IL28B genotype was associated with serum levels of hepatitis C virus RNA, g-GT, and CD4 cell count. In contrast to HIV-infected patients with chronic hepatitis C, the IL28B genotype was not significantly associated with treatment response rates in patients with acute hepatitis C. Thus, effects of the IL28B single-nucleotide polymorphism may differ in HIV-infected patients with chronic and acute hepatitis C.     

Aggressive End-of-Life Care Significantly Influenced Propensity for Hospice Enrollment Within the Last Three Days of Life for Taiwanese Cancer Decedents

ContextLate hospice enrollment exacts a substantial toll from patients, families, hospices, and society. The relationship between the propensity for late hospice enrollment and aggressive health services received at the end of life (EOL) has been underinvestigated.ObjectivesTo identify determinants of hospice enrollment within the last three days of life.MethodsRetrospective population-based cohort study using administrative data for 31,529 Taiwanese cancer decedents who used hospice care in their last year of life.ResultsRates of hospice enrollment within the last three days of life (16.80%–18.73%) remained constant over 2001–2006. After adjustment for patient demographics and disease characteristics, physician specialty, availability of health care resources at the hospital and regional levels, and historical trends, late hospice enrollment was more likely if Taiwanese cancer patients received chemotherapy, had multiple emergency room visits or hospital admissions, and used the intensive care unit in their last month of life (adjusted odds ratio [95% confidence interval] (AOR [95% CI]): 1.61 [1.44–1.80], 1.40 [1.29–1.52], 1.78 [1.51–2.09], and 1.45 [1.19–1.76], respectively). Late hospice enrollment was less likely for patients with hospital stays >14 days or who received cardiopulmonary resuscitation in their last month of life (AOR [95% CI]: 0.51 [0.45–0.58] and 0.41 [0.25–0.65], respectively).ConclusionAggressive EOL care played a more significant role than patient, physician, or hospital characteristics in determining the propensity of Taiwanese cancer patients to be enrolled in hospice care within their last three days of life. Clinical and health policies should aim to avoid aggressive care when it will not benefit patients but may preclude timely hospice enrollment.     

Extrapolation in the analysis of lung aeration by computed tomography: a validation study

Introduction

Computed tomography (CT) is considered the gold standard for quantification of global or regional lung aeration and lung mass. Quantitative CT, however, involves the exposure to ionizing radiation and requires manual image processing. We recently evaluated an extrapolation method which calculates quantitative CT parameters characterizing the entire lung from only 10 reference CT-slices thereby reducing radiation exposure and analysis time. We hypothesized that this extrapolation method could be further validated using CT-data from pigs and sheep, which have a different thoracic anatomy.

Methods

We quantified volume and mass of the total lung and differently aerated lung compartments in 168 ovine and 55 porcine whole-lung CTs covering lung conditions from normal to gross deaeration. Extrapolated volume and mass parameters were compared to the respective values obtained by whole-lung analysis. We also tested the accuracy of extrapolation for all possible numbers of CT slices between 15 and 5. Bias and limits of agreement (LOA) were analyzed by the Bland-Altman method.

Results

For extrapolation from 10 reference slices, bias (LOA) for the total lung volume and mass of sheep were 18.4 (-57.2 to 94.0) ml and 4.2 (-21.8 to 30.2) grams, respectively. The corresponding bias (LOA) values for pigs were 5.1 (-55.2 to 65.3) ml and 1.6 (-32.9 to 36.2) grams, respectively. All bias values for differently aerated lung compartments were below 1% of the total lung volume or mass and the LOA never exceeded ± 2.5%. Bias values diverged from zero and the LOA became considerably wider when less than 10 reference slices were used.

Conclusions

The extrapolation method appears robust against variations in thoracic anatomy, which further supports its accuracy and potential usefulness for clinical and experimental application of quantitative CT.     

Computed tomographic assessment of lung weights in trauma patients with early posttraumatic lung dysfunction

Introduction

Quantitative computed tomography (qCT)-based assessment of total lung weight (M_lung) has the potential to differentiate atelectasis from consolidation and could thus provide valuable information for managing trauma patients fulfilling commonly used criteria for acute lung injury (ALI). We hypothesized that qCT would identify atelectasis as a frequent mimic of early posttraumatic ALI.

Methods

In this prospective observational study, M_lung was calculated by qCT in 78 mechanically ventilated trauma patients fulfilling the ALI criteria at admission. A reference interval for M_lung was derived from 74 trauma patients with morphologically and functionally normal lungs (reference). Results are given as medians with interquartile ranges.

Results

The ratio of arterial partial pressure of oxygen to the fraction of inspired oxygen was 560 (506 to 616) mmHg in reference patients and 169 (95 to 240) mmHg in ALI patients. The median reference M_lung value was 885 (771 to 973) g, and the reference interval for M_lung was 584 to 1164 g, which matched that of previous reports. Despite the significantly greater median M_lung value (1088 (862 to 1,342) g) in the ALI group, 46 (59%) ALI patients had M_lung values within the reference interval and thus most likely had atelectasis. In only 17 patients (22%), M_lung was increased to the range previously reported for ALI patients and compatible with lung consolidation. Statistically significant differences between atelectasis and consolidation patients were found for age, Lung Injury Score, Glasgow Coma Scale score, total lung volume, mass of the nonaerated lung compartment, ventilator-free days and intensive care unit-free days.

Conclusions

Atelectasis is a frequent cause of early posttraumatic lung dysfunction. Differentiation between atelectasis and consolidation from other causes of lung damage by using qCT may help to identify patients who could benefit from management strategies such as damage control surgery and lung-protective mechanical ventilation that focus on the prevention of pulmonary complications.     

Dickkopf-1 as a mediator and novel target in malignant bone disease

Bone metastases are a common problem of many malignancies, including myeloma, breast and prostate cancer. The Wnt inhibitor Dickkopf-1 has been shown to be involved in the process of bone lesions by impairing osteoblast activity. This review will focus on the role of Dickkopf-1 as a mediator of malignant bone disease and discuss its potential as a novel therapeutic target.