Cascade plasma filtration during the first year after CABG in patients with hyperlipidemia refractory to statins

ObjectiveTo evaluate the effect of a 12-month course of weekly lipid apheresis on vein graft patency after coronary artery bypass grafting (CABG) in patients with hyperlipidemia refractory to statins.MethodsIn a 12-month prospective controlled clinical trial we enrolled 34 male patients (mean age 57 ± 8 years) who passed through successful CABG and low-density lipoprotein cholesterol (LDL-C) level >2.6 mmol/L prior to the operation despite statin treatment. Patients were allocated into 2 groups: active (n = 17, weekly apheresis by cascade plasma filtration (CPF) plus atorvastatin), and control (n = 17, atorvastatin alone). Graft patency was evaluated by multislice computed tomography at 3 months and by angiography at 12 months after an operation.ResultsBoth groups were comparable in clinical and biochemical characteristics. During each CPF procedure, LDL-C level decreased by 64 ± 9%, apoB – by 65 ± 8%, Lp(a) – by 52 ± 15%,; these changes were significant compared to baseline and the control group. Mean net difference in LDL-C level between apheresis and control groups was 1.1 ± 0.3 mmol/L. Vein graft patency at study end was 88.2% (45 of 51) in the apheresis group versus 72.7% (40 of 55) in the control group (p = 0.05). Use of apheresis was associated with decreased vein graft occlusions by 46%: relative risk 0.54; 95% confidence interval 0.27 to 1.02; p = 0.05.ConclusionOur data suggest that the use of lipoprotein apheresis with CPF results in a better vein graft patency during the first year after CABG in patients with hyperlipidemia refractory to statins.     

Evaluation of noninvasive markers for the diagnosis of cystic fibrosis liver disease

Abstract

Objectives: In cystic fibrosis (CF), liver disease (LD) is the third leading cause of mortality. As liver biopsy was considered inconsistent in CFLD diagnosis, a combination of modalities were utilized in the conventional Debray criteria (DC). More recently, noninvasive liver fibrosis biomarkers were applied by Koh et al (New criteria-NC). In the current study, we aimed to evaluate noninvasive biomarkers for the CFLD diagnosis.

Methods: Longitudinal data were collected from a cohort of genetically confirmed CF patients. CFLD was diagnosed by both DC and NC. Apart from transient elastography (TE)?>?6.8?kPa, biomarkers incorporated in the NC included AST/ALT-ratio (AAR)?≥?1, FIB-4 index ≥3.25 and APRI >0.50.

Results: 62 patients with CF, [56.5% male, age at enrollment 25 (22–31) years], were prospectively followed-up for 33 (28–36) months. Sixteen (25.8%) and 27 (43.5%) patients met DC and NC, respectively. Twenty-four fulfilling NC had at least one positive biomarker (6 TE, 7 AAR, 6 both TE and AAR, 2 both APRI and AAR and 3 both APRI and TE). Thirteen (48.1%) had diffuse LD/cirrhosis by the NC and all had at least one additional parameter classifying them as CFLD. From the 14 (51.8%) with no-diffuse-LD, 64.3%, 14.3% and 21.4% had 2, 3 and 4 of the necessary modalities incorporated in NC, respectively, confirming their classification as CFLD. TE was 100% specific to rule in CFLD but had a moderate sensitivity.

Conclusions: NC were able to identify 17.7% more CFLD patients compared to DC. The multiple biomarkers incorporated in NC may enhance the ability to detect CFLD.     

Electromechanical Relationship in Hypertrophic Cardiomyopathy

We examined whether there is a relationship between repolarization abnormalities on electrocardiography (EKG) and deformation abnormalities by echocardiography. Analysis of baseline EKGs and mechanical (echo-based deformation) changes was performed in 128 patients with a clinical diagnosis of hypertrophic cardiomyopathy (HCM). Patients with left ventricular hypertrophy (LVH) or repolarization abnormalities had higher septal thickness when compared to patients with normal EKG. Patients with EKG evidence of LVH or QT_c prolongation had lower systolic velocity, systolic strain, systolic strain rate, late diastolic velocity, and late diastolic strain rate than patients with a normal EKG. Patients with strain pattern or ST depression/T-wave inversion had lower systolic velocity, systolic strain, systolic strain rate, early diastolic velocity, and late diastolic velocity when compared to patients with normal EKGs. LVH and repolarization abnormalities on surface EKG are markers of impaired systolic and diastolic mechanics in HCM.     

Combined virus-like particle-based polyepitope DNA/protein HIV-1 vaccine design, immunogenicity and toxicity studies

We have previously described designing of polyepitope immunogens TBI and TCI, to stimulate the humoral and cellular immune responses to HIV-1. Here, immunogens TBI and TCI were used to create new vaccine construct named CombiHIVvac (Combined HIV-1 vaccine). CombiHIVvac is a virus-like particles (VLP) containing the DNA vaccine pcDNA-TCI as a core encapsulated within a spermidine-polyglucin-TBI conjugate. The immunogenic and toxic properties of the candidate vaccine CombiHIVvac have been studied. CombiHIVvac induces a strong humoral and CTL responses in mice; the antibodies are highly specific and are able to neutralize HIV-1 in vitro. Preclinical study demonstrated that CombiHIVvac does not cause long-term changes in physiological, biochemical and morphological parameters in immunized animals and thus can be recommended for clinical trials.     

Influence of the restorative procedure factors on stress values in premolar with MOD cavity: a finite element study

In order to investigate the influence of cusp reduction, cavity isthmus width, and restorative material on stress values in premolar with mesio-occlusal-distal (MOD) cavity, numerical simulations were done on three-dimensional (3D) models of a maxillary second premolar designed using computerized tomography (CT) scan images. The use of four restorative materials (direct resin composite, direct resin composite with resin-modified glass-ionomer cement as the base, indirect resin composite, ceramic), three cavity preparation designs (without cusp coverage, 2-mm palatal cusp coverage, 2-mm palatal and buccal cusp coverage), and two cavity isthmus widths (1/2 and 2/3 intercuspal width) were simulated. After applying a static load of 200 N on the occlusal surface of the tooth, von Mises stresses in the enamel, dentin, and restoration were calculated using finite element analysis (FEA). Stress values in the enamel were primarily influenced by cavity preparation design, while restorative material showed higher contribution in dentin. The lowest stress values were obtained in models with cusp coverage and indirect restorations. Cavity isthmus width had minimal influence on stress values in tooth structures. None of the investigated factors determined stress values in the restoration. In conclusion, the use of ceramic restoration covering both palatal and buccal cusp provided the most favourable stress distribution of premolars with MOD cavity.

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Detection of misfolded prion protein in blood with conformationally sensitive peptides

BACKGROUND: The long-standing goal of a preclinical diagnostic test for transmissible spongiform encephalopathy (TSE) has recently become urgent because of the discovery that humans with variant Creutzfeldt-Jakob disease can transmit disease via blood transfusions. STUDY DESIGN AND METHODS: The misfolded protein diagnostic (MPD) assay employs a pyrene-labeled palindromic sequence of prion peptides that undergoes a cascade of coil to beta-sheet conversion in the presence of the misfolded prion protein (PrP(TSE)). The ability of the assay to detect PrP(TSE) in brain, serum, and plasma was tested. The basic protocol involved a several-hour incubation of 200-microL sample volumes with the peptide reagent in 96-well plates, after which fluorescence was monitored by a fluorescence plate reader with an excitation wavelength of 350 nm and emission scanning wavelength range of 365 to 600 nm. RESULTS: Target specificity for PrP(TSE) was documented by correlation of assay signal with Western blot signals in brain tissue from TSE-infected, normal, and knockout mice and negative assay signals by use of reagents with different peptide sequences. When applied to plasma or serum, the assay discriminated between samples from a variety of experimental and natural TSE infections compared to uninfected controls, with a sensitivity threshold of approximately 1 infectious dose per mL in pooled plasma from TSE-infected mice. CONCLUSIONS: The MPD assay is a sensitive and specific test for the detection of PrP(TSE) that may be useful in both preclinical and clinical diagnosis of TSE diseases of animals and humans.     

Romidepsin in peripheral and cutaneous T‐cell lymphoma: mechanistic implications from clinical and correlative data

Romidepsin is an epigenetic agent approved for the treatment of patients with cutaneous or peripheral T‐cell lymphoma (CTCL and PTCL). Here we report data in all patients treated on the National Cancer Institute 1312 trial, demonstrating long‐term disease control and the ability to retreat patients relapsing off‐therapy. In all, 84 patients with CTCL and 47 with PTCL were enrolled. Responses occurred early, were clinically meaningful and of very long duration in some cases. Notably, patients with PTCL receiving romidepsin as third‐line therapy or later had a comparable response rate (32%) of similar duration as the total population (38%). Eight patients had treatment breaks of 3·5 months to 10 years; in four of six patients, re‐initiation of treatment led to clear benefit. Safety data show slightly greater haematological and constitutional toxicity in PTCL. cDNA microarray studies show unique individual gene expression profiles, minimal overlap between patients, and both induction and repression of gene expression that reversed within 24 h. These data argue against cell death occurring as a result of an epigenetics‐mediated gene induction programme. Together this work supports the safety and activity of romidepsin in T‐cell lymphoma, but suggests a complex mechanism of action.     

Clinical and virologic outcomes in patients with oseltamivir-resistant seasonal influenza A (H1N1) infections: results from a clinical trial

Nineteen patients with oseltamivir-resistant seasonal influenza A (H1N1) infections were randomized to receive oseltamivir or placebo. Nasopharyngeal swabs were obtained, and clinical and virologic outcomes were compared, stratified by early or late treatment. Neuraminidase inhibition assay and pyrosequencing for H275Y confirmed resistance. Twelve (63%) patients received oseltamivir; 8 (67%) received late treatment. Seven (37%) patients received placebo; 6 (86%) presented >48 hours after onset. Time to 50% decrease in symptom severity, complete symptom resolution, and first negative culture were shortest among the early treatment group. While sample size prohibits a strong conclusion, future studies should evaluate for similar trends.     

Assessing the Awareness of and Willingness to Participate in Cancer Clinical Trials Among Immigrant Latinos

Clinical trials are considered the gold standard of evidence about the efficacy of cancer prevention, early detection, and treatment interventions. A paucity of data exists on determinants of clinical trial participation in the growing US Latino population despite poor cancer outcomes in this group. This study seeks to describe correlates of awareness of and willingness to participate in clinical trials among largely Central, North, and South American Latinos using safety-net clinics. Between June 2007 and November 2008, we conducted an interviewer-administered, Spanish-language cross-sectional survey (n = 944). Logistic regression was used to assess effects of health information sources and psychosocial variables on awareness of and intention to participate in clinical trials. Analyses were completed in spring 2010. While only 48% knew what a clinical trial was, when explained, 65% indicated a willingness to participate. Providers were the most common source of health information. Use of Internet for health information, trust in health information, and higher education each independently increased the odds of clinical trial awareness, but obtaining information from providers did not. Contacting the Cancer Information Service and psychosocial factors were each independently associated with intent to join a clinical trial, while demographic factors were not. Information channels such as the Internet may be effective in conveying clinical trial information to Latinos. Providers being cited as the most common source of health information but not being associated with knowledge about or intent to participate in trials suggests a missed opportunity for communication to this population.