Vascular complications in steroid treated patients undergoing transfemoral aortic valve implantation

• Steroids if taken chronically or periprocedurally contribute to delayed wound healing and decreased vascular patency
• Access site complications after diagnostic interventional procedures carry significant morbidity, increased cost, and prolonged hospital stay
• TAVI offers high risk surgical candidates with severe aortic stenosis a significant survival advantage

     

Proteins associated with poly(A)+RNA of cockerel liver: effects of estradiol stimulation.

The protein population of poly(A)-containing messenger ribonucleoprotein (mRNP) from cockerel liver was analyzed before and after estradiol induction. Polysomal and free mRNP were isolated by thermal elution from oligo(dT)-cellulose. The proteins were separated by two-dimensional electrophoresis (of which the first dimension was a nonequilibrium pH gradient) and were visualized by silver staining. In order to determine similarities and differences between proteins of various mRNP fractions, trace amounts of 125I-labeled protein from one fraction were coelectrophoresed with stainable amounts of protein from another fraction on the same gel. Of 27 proteins analyzed, 15 were common to polysomal and free mRNP, 7 were specific to polysomal mRNP, and 5 were specific to free mRNP. Moreover, estradiol strongly influenced 11 proteins. Six proteins changed either in relative intensity or in distribution between polysomal and free mRNP fractions. Three major proteins appeared in both fractions, and two additional proteins disappeared from the free mRNP fraction after estradiol treatment. The results suggest that the protein population in polysomal mRNP is quite complex and that the profound influence of estradiol on protein synthesis in cockerel liver may be connected to changes in the protein composition of mRNP.     

Induction of oral tolerance in splenocyte recipients toward pretransplant antigens ameliorates chronic graft versus host disease in a murine model

Chronic graft versus host disease (cGVHD) is a major complication that can develop after bone marrow transplantation. It involves an immune-mediated attack by transplanted donor lymphocytes, and often results in inflammatory damage of host target organs. Immune hyporesponsiveness induced by oral antigen administration has been recently shown to prevent the development of cGVHD in a murine model. The aim of this study was to evaluate whether tolerance induction in bone marrow transplant (BMT) recipients after transplantation, toward their pretransplant antigens, can alleviate preexisting cGVHD in a mouse model. cGVHD was generated by infusing 2.5 x 10(7) splenocytes from B10.D2 donor mice, to sublethally irradiated (6 Gy) BALB/c recipient mice, which differ by minor histocompatibility antigens. Transplantation resulted in cGVHD, with characteristic scleroderma-like cutaneous fibrosis, increased skin collagen content, decreased body weight, and hepatic and small bowel inflammation. Oral tolerance was induced by feeding recipient BALB/c mice with proteins extracted from BALB/c splenocytes for 11 days after B10.D2 splenocyte transplantation. Tolerance induction was evidenced by a significant reduction in mixed lymphocyte response of effector splenocytes from tolerant BALB/c mice transplanted with B10.D2 splenocytes against BALB/c target splenocytes. Oral tolerance decreased skin collagen deposits. Reduction of collagen alpha1(I) gene expression and skin collagen were shown by in situ hybridization and histochemistry, respectively. Liver and bowel biopsy specimens revealed less inflammation. Serum IL-10 levels were higher in tolerant mice than in controls, whereas IFNgamma was significantly reduced. Oral tolerance of BMT recipients toward their pretransplant antigens after splenocyte transplantation down-regulated the immune attack by transplanted cells, thus ameliorating cGVHD.     

Pneumococcal vaccine targeting strategy for older adults: Customized risk profiling

Background

Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting.

Methods

Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008–2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting.

Results

In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia.

Conclusions

We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international guidelines. Health care managers and policy-makers may consider the strategic potential of utilizing clinical and administrative databases for creating population-specific risk prediction models to inform vaccination campaigns.     

Detection of Cerebral Hyperperfusion Syndrome after Carotid Endarterectomy with CT Perfusion

We present the case of a 60‐year‐old female patient, who developed symptomatic internal carotid artery stenosis and subsequently underwent carotid endarterectomy. Four days after an uneventful surgery the patient developed confusion, seizures, and was admitted to the ICU. CT perfusion revealed reduced ispilateral time‐to‐peak and mean‐transient‐time and increased cerebral blood volume and cerebral blood flow, confirming the diagnosis of cerebral hyperperfusion syndrome. We thus propose CT perfusion as a diagnostic means for cerebral hyperperfusion syndrome, a syndrome that remains underdiagnosed.     

Quantitative Peripheral Blood Perturbations of γδ T Cells in Human Disease and Their Clinical Implications

Human γδ T cells, which play innate and adaptive, protective as well as destructive, roles in the immune response, were discovered in 1986, but the clinical significance of alterations of the levels of these cells in the peripheral blood in human diseases has not been comprehensively reviewed. Here, we review patterns of easily measurable changes of this subset of T cells in peripheral blood from relevant publications in PubMed and their correlations with specific disease categories, specific diagnoses within disease categories, and prognostic outcomes. These collective data suggest that enumeration of γδ T cells and their subsets in the peripheral blood of patients could be a useful tool to evaluate diagnosis and prognosis in the clinical setting.