Post-operative critical care management of patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC)

<p>Abstract</p> <p>Background</p> <p>Cytoreductive surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC) results in a number of physiological changes with effects on the cardiovascular system, oxygen consumption and coagulation. The Critical Care interventions required by this cohort of patients have not yet been quantified.</p> <p>Methods</p> <p>This retrospective audit examines the experience of a Specialist Tertiary Centre in England over an 18 month period (January 2009-June 2010) during which 69 patients underwent CRS and HIPEC. All patients were extubated in the operating theatre and transferred to the Critical Care Unit (CCU) for initial post-operative management.</p> <p>Results</p> <p>Patients needed to remain on the CCU for 2.4 days (0.8-7.8). There were no 30 day mortalities. The majority of patients (70.1%) did not require post-operative organ support. 2 patients who developed pneumonia post-operatively required respiratory support. 18 (26.1%) patients required vasopressor support with norepinephrine with a mean duration of 13.94 hours (5-51 hours) and mean dose of 0.04 mcg/kg/min. Post-operative coagulopathy peaked at 24 hours. A significant drop in serum albumin was observed.</p> <p>Conclusion</p> <p>The degree of organ support required post-operatively is minimal. Early extubation is efficacious with the aid of epidural analgesia. Critical Care monitoring for 48 hours is desirable in view of the post-operative challenges.</p

Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms. Methodology/Principal Findings: We have generated fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as confirmed by immunocytochemical analysis of cell specific markers. The three YG8R mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat stability, together with reduced expression of frataxin and reduced aconitase activity compared to control Y47R cells. Furthermore, YG8R cells also show increased sensitivity to oxidative stress and downregulation of Pgc-1α and antioxidant gene expression levels, especially Sod2. We also analysed various DNA mismatch repair (MMR) gene expression levels and found that YG8R cells displayed significant reduction in expression of several MMR genes, which may contribute to the GAA repeat stability. Conclusions/Significance: We describe the first fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be differentiated into neurons and glia. These novel FRDA mouse cell models, which exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources to further study FRDA molecular pathogenesis. They will also provide very useful tools for preclinical testing of frataxin-increasing compounds for FRDA drug therapy, for gene therapy, and as a source of cells for cell therapy testing in FRDA mice. © 2014 Sandi et al

Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer

There is increasing evidence suggesting that short telomeres and subsequent genomic instability contribute to malignant transformation. Telomere shortening has been described as a mechanism to explain genetic anticipation in dyskeratosis congenita and Li-Fraumeni syndrome. Since genetic anticipation has been observed in familial breast cancer, we aimed to study telomere length in familial breast cancer patients and hypothesized that genetic defects causing this disease would affect telomere maintenance resulting in shortened telomeres. Here, we first investigated age anticipation in mother-daughter pairs with breast cancer in 623 breast cancer families, classified as BRCA1, BRCA2, and BRCAX. Moreover, we analyzed telomere length in DNA from peripheral blood leukocytes by quantitative PCR in a set of 198 hereditary breast cancer patients, and compared them with 267 control samples and 71 sporadic breast cancer patients. Changes in telomere length in mother-daughter pairs from breast cancer families and controls were also evaluated to address differences through generations. We demonstrated that short telomeres characterize hereditary but not sporadic breast cancer. We have defined a group of BRCAX families with short telomeres, suggesting that telomere maintenance genes might be susceptibility genes for breast cancer. Significantly, we described that progressive telomere shortening is associated with earlier onset of breast cancer in successive generations of affected families. Our results provide evidence that telomere shortening is associated with earlier age of cancer onset in successive generations, suggesting that it might be a mechanism of genetic anticipation in hereditary breast cancer

The diagnostic suitability of a xerostomia questionnaire and the association between xerostomia, hyposalivation and medication use in a group of nursing home residents

The study objective was to explore the diagnostic suitability of the Xerostomia Inventory and the association between xerostomia, hyposalivation and medication use in a group of nursing home residents. A cross-sectional study was carried out in 50 physically impaired nursing home residents (20 men) with a mean age of 78.1 years (range, 53–98) in The Netherlands. The Xerostomia Inventory-Dutch version was completed for all residents and the data were subjected to exploratory factor analysis to determine the diagnostic suitability. Residents’ data on xerostomia, whole saliva secretion rates and hyposalivation-related medications used were collected and statistically analyzed. The diagnostic suitability of the Xerostomia Inventory-Dutch version appeared restricted. The prevalence of xerostomia was 52%, without gender and age difference. The prevalence of hyposalivation was 24% for resting, 60% for chewing-stimulated and 18% for acid-stimulated whole saliva. All whole saliva secretion rates were significantly lower in women than in men and in older than in younger residents. Forty-four percent of all medications used were hyposalivation-related and women used significantly more medications than men. Xerostomia was significantly negatively correlated with the resting whole saliva secretion rate. The number of hyposalivation-related medications used was not significantly correlated with the various whole saliva secretion rates. In nursing home residents, xerostomia, hyposalivation and using hyposalivation-related medications seem common and partially associated features

More Evidence that Depressive Symptoms Predict Mortality in COPD Patients: Is Type D Personality an Alternative Explanation?

The present study attempted to replicate our previous finding that depressive symptoms are a risk factor for mortality in stable chronic obstructive pulmonary disease (COPD), but in a different population with a different measure of depressive symptoms. We further investigated whether type D personality is associated with mortality in patients with COPD and whether it explains any relationship observed between depressive symptoms and mortality. In 122 COPD patients, mean age 60.8 +/- 10.3 years, 52% female, and mean forced expiratory volume in 1 s (FEV(1)) 41.1 +/- 17.6%pred, we assessed body mass index, post bronchodilator FEV(1), exercise capacity, depressive symptoms with the Hospital Anxiety and Depression Scale, and type D with the Type D Scale. In the 7 years follow-up, 48 (39%) deaths occurred. The median survival time was 5.3 years. Depressive symptoms (hazard ratio = 1.07, 95% confidence intervals = 1.00-1.14) were an independent risk factor for mortality. Type D was not associated with mortality. We can rule out type D as an explanation for the relationship between depressive symptoms and mortality observed in this sample. However, ambiguity remains as to the interpretation of the value of depressive symptoms in predicting death