Cytosorb® haemoadsorption: a potential game changer for patients needing myocardial surgical revascularisation

Cytosorb, an extracorporeal blood purification system, utilises the principles of haemoadsorption to remove low molecular weight substances from the blood, including multiple cytokines such as interleukin (IL)-1b, IL-6, IL-8, and tumour necrosis factor-α, and anti-platelet drugs aiming to improve clinical outcomes. Given the prominent role of pro-inflammatory cytokines in various inflammatory states, Cytosorb has seen growing application as a therapeutic immunomodulator including surgery. This review focuses on the effects of the use of Cytosorb in patients undergoing coronary artery bypass grafting (CABG) and the indications of removal of cytokines and anti-platelet agents such as ticagrelor. The evidence supports the feasibility and safety profile of Cytosorb, with no device-related adverse events reported in all studies. Initial studies suggest significant potential for Cytosorb in urgent or emergency CABG surgery to remove anti-platelet medication with promising benefits on clinical outcomes including fewer blood product transfusions, decreased length of intensive care unit stay, and lower re-sternotomy rates. Furthermore, a cost saving analysis indicated that intraoperative removal of ticagrelor with Cytosorb would be cost effective in the setting of emergency cardiac surgery. However, the evidence remains inconclusive when Cytosorb is used in elective CABG surgery for cytokine removal. Definite high quality clinical trials for both indications for Cytosorb in CABG surgery are needed to clarify if there is a clinically significant benefit in clinical outcomes. There is substantial trial activity for the application of Cytosorb in higher risk cardiac surgery to establish the place of Cytosorb in future treatment pathways in cardiac surgery

Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome

Background and objective The long-QT syndrome (LQTS) is associated with premature sudden cardiac deaths affecting whole families and is caused by mutations in genes encoding for cardiac proteins. When the same mutation is found in different families (recurrent mutations), this may imply either a common ancestor (founder) or multiple de novo mutations. We aimed to review recurrent mutations in patients with LQTS. Methods By use of our databases, we investigated the number of mutations that were found recurrently (at least three times) in LQT type 1-3 patients in the Netherlands. We studied familial links in the apparently unrelated probands, and we visualised the geographical distribution of these probands. Our results were compared with published literature of founder effects in LQTS outside the Netherlands. Results We counted 14 recurrent LQT mutations in the Netherlands. There are 326 identified carriers of one of these mutations. For three of these mutations, familial links were found between apparently unrelated probands. Conclusion Whereas true LQT founder mutations are described elsewhere in the world, we cannot yet demonstrate a real founder effect of these recurrent mutations in the Netherlands. Further studies on the prevalence of these mutations are indicated, and haplotype-sharing of the mutation carriers is pertinent to provide more evidence for founder mutation-based LQTS pathology in our countr

Effects of evidence-based strategies to reduce the socioeconomic gradient of uptake in the English NHS Bowel Cancer Screening Programme (ASCEND): four cluster-randomised controlled trials

This study is funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research Programme ( RP-PG-0609-10106 ) and partly supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North Thames (MCT and RR

Meta-analysis of breast cancer mortality benefit and overdiagnosis adjusted for adherence: improving information on the effects of attending screening mammography

Background: Women require information about the impact of regularly attending screening mammography on breast cancer mortality and overdiagnosis to make informed decisions. To provide this information we aimed to meta-analyse randomised controlled trials adjusted for adherence to the trial protocol. Methods: Nine screening mammography trials used in the Independent UK Breast Screening Report were selected. Extending an existing approach to adjust intention-to-treat (ITT) estimates for less than 100% adherence rates, we conducted a random-effects meta-analysis. This produced a combined deattenuated prevented fraction and a combined deattenuated percentage risk of overdiagnosis. Results: In women aged 39–75 years invited to screen, the prevented fraction of breast cancer mortality at 13-year follow-up was 0.22 (95% CI 0.15–0.28) and it increased to 0.30 (95% CI 0.18–0.42) with deattenuation. In women aged 40–69 years invited to screen, the ITT percentage risk of overdiagnosis during the screening period was 19.0% (95% CI 15.2–22.7%), deattenuation increased this to 29.7% (95% CI 17.8–41.5%). Conclusions: Adjustment for nonadherence increased the size of the mortality benefit and risk of overdiagnosis by up to 50%. These estimates are more appropriate when developing quantitative information to support individual decisions about attending screening mammography

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

QTc and psychopharmacs: are there any differences between monotherapy and polytherapy

<p>Abstract</p> <p>Background</p> <p>Some psychotropic drugs are connected with prolongation of QT interval, increased risk of cardiac arrhythmias and greater incidence of sudden death, especially when used in combination. Concomitant use of antipsychotics and antidepressants is not rare in our clinical practice. The study compares the length of QT interval in patients on monotherapy with an antipsychotic or an antidepressant and patients taking polytherapy (an antipsychotic agent combined with an antidepressant).</p> <p>Methods</p> <p>Sixty-one hospitalized women who met the ICD-10 criteria for schizophrenia, schizoaffective psychosis, delusional disorder and mood disorder were included in the study. The monotherapy group was consisted of thirty-two women treated with an antipsychotic or an antidepressant while the polytherapy group was composed of twenty-nine women treated with an antipsychotic agent plus an antidepressant. Two electrocardiograms (ECGs) were obtained for each patient: the first was carried out before the treatment and the second after two weeks of treatment.</p> <p>Statistical analysis was carried out by SPSS program and included unpaired and paired t test and Fisher's exact test.</p> <p>Results</p> <p>Mean baseline QTc values did not differ between the groups (439 ± 22 ms was the same value found in the both groups; unpaired t test, p > 0.5). Mean QTc intervals after two weeks of treatment were also similar (439 ± 24 ms in the monotherapy group and 440 ± 20 ms in the polytherapy group; unpaired t test, p > 0.5). Fisher's exact test did not reveal significant difference in the number of patients with borderline (451–470 ms) or prolonged (> 470 ms) QTc between groups, neither before treatment nor after two weeks of treatment. Twenty two women of the total of sixty one patients (36%) had QTc > 450 ms before applying therapy.</p> <p>Conclusion</p> <p>We did not find significant QT prolongation in our patients after two weeks of treatment with antipsychotics and/or antidepressants. The QTc interval length did not differ significantly in the monotherapy and the polytherapy group. More than one third of included women exceeded the threshold value of borderline QTc interval (450 ms) before starting treatment. This finding calls for caution when prescribing drugs to female psychiatric patients, especially if they have other health problems.</p

Genome Sequence of Erythromelalgia-Related Poxvirus Identifies it as an Ectromelia Virus Strain

Erythromelagia is a condition characterized by attacks of burning pain and inflammation in the extremeties. An epidemic form of this syndrome occurs in secondary students in rural China and a virus referred to as erythromelalgia-associated poxvirus (ERPV) was reported to have been recovered from throat swabs in 1987. Studies performed at the time suggested that ERPV belongs to the orthopoxvirus genus and has similarities with ectromelia virus, the causative agent of mousepox. We have determined the complete genome sequence of ERPV and demonstrated that it has 99.8% identity to the Naval strain of ectromelia virus and a slighly lower identity to the Moscow strain. Small DNA deletions in the Naval genome that are absent from ERPV may suggest that the sequenced strain of Naval was not the immediate progenitor of ERPV

In Situ Distribution of HIV-Binding CCR5 and C-Type Lectin Receptors in the Human Endocervical Mucosa

The endocervical mucosa is believed to be a primary site of HIV transmission. However, to date there is little known about the distribution of the HIV co-receptor CCR5 and the HIV-binding C-type lectin receptors, including Langerin, dendritic cell (DC)-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN) and mannose receptor (MR) at this site. We therefore characterized the expression of these molecules in the endocervix of HIV seronegative women by computerized image analysis. Endocervical tissue biopsies were collected from women (n = 6) undergoing hysterectomy. All study individuals were diagnosed with benign and non-inflammatory diseases. CCR5+ CD4+ CD3+ T cells were found within or adjacent to the endocervical epithelium. The C-type lectin Langerin was expressed by intraepithelial CD1a+ CD4+ and CD11c+ CD4+ Langerhans cells, whereas DC-SIGN+ MR+ CD11c myeloid dendritic cells and MR+ CD68+ macrophages were localized in the submucosa of the endocervix. The previously defined immune effector cells including CD8+, CD56+, CD19+ and IgD+ cells were also found in the submucosa as well as occasional CD123+ BDCA-2+ plasmacytoid dendritic cells. Understanding the spatial distribution of potential HIV target cells and immune effector cells in relation to the endocervical canal forms a basis for deciphering the routes of HIV transmission events in humans as well as designing HIV-inhibiting compounds

The effect of a supplementary ('Gist-based') information leaflet on colorectal cancer knowledge and screening intention: a randomized controlled trial.

Guided by Fuzzy Trace Theory, this study examined the impact of a 'Gist-based' leaflet on colorectal cancer screening knowledge and intentions; and tested the interaction with participants' numerical ability. Adults aged 45-59 years from four UK general practices were randomly assigned to receive standard information ('The Facts', n = 2,216) versus standard information plus 'The Gist' leaflet (Gist + Facts, n = 2,236). Questionnaires were returned by 964/4,452 individuals (22 %). 82 % of respondents reported having read the information, but those with poor numeracy were less likely (74 vs. 88 %, p < .001). The 'Gist + Facts' group were more likely to reach the criterion for adequate knowledge (95 vs. 91 %; p < .01), but this was not moderated by numeracy. Most respondents (98 %) intended to participate in screening, with no group differences and no interaction with numeracy. The improved levels of knowledge and self-reported reading suggest 'The Gist' leaflet may increase engagement with colorectal cancer screening, but ceiling effects reduced the likelihood that screening intentions would be affected

PET imaging of the autonomic myocardial function: methods and interpretation.

Cardiac positron emission tomography (PET) is mainly applied in myocardial perfusion and viability detection. Noninvasive imaging of myocardial innervation using PET is a valuable additional methodology in cardiac imaging. Novel methods and different PET ligands have been developed to measure presynaptic and postsynaptic function of the cardiac neuronal system. Obtained PET data can be analysed quantitatively or interpreted qualitatively. Thus far, PET is not a widely used clinical application in autonomic heart imaging; however, due to its technical advantages, the excellent properties of the imaging agents, and the availability of tools for quantification, it deserves a better position in the clinic. From a historical point of view, the focus of PET software packages for image analysis was mainly oncology and neurology driven. Actually, commercially available software for cardiac PET image analysis is still only available for the quantification of myocardial blood flow. Thus far, no commercial software package is available for the interpretation and quantification of PET innervation scans. However, image data quantification and analysis of kinetic data can be performed using adjusted generic tools. This paper gives an overview of different neuronal PET ligands, interpretation and quantification of acquired PET data