Enabling heterogeneous data integration and biomedical event prediction through ICT: The test case of cancer reoccurrence

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Intradermal Indocyanine Green for In Vivo Fluorescence Laser Scanning Microscopy of Human Skin: A Pilot Study

BACKGROUND: In clinical diagnostics, as well as in routine dermatology, the increased need for non-invasive diagnosis is currently satisfied by reflectance laser scanning microscopy. However, this technique has some limitations as it relies solely on differences in the reflection properties of epidermal and dermal structures. To date, the superior method of fluorescence laser scanning microscopy is not generally applied in dermatology and predominantly restricted to fluorescein as fluorescent tracer, which has a number of limitations. Therefore, we searched for an alternative fluorophore matching a novel skin imaging device to advance this promising diagnostic approach. METHODOLOGY/PRINCIPAL FINDINGS: Using a Vivascope®-1500 Multilaser microscope, we found that the fluorophore Indocyanine-Green (ICG) is well suited as a fluorescent marker for skin imaging in vivo after intradermal injection. ICG is one of few fluorescent dyes approved for use in humans. Its fluorescence properties are compatible with the application of a near-infrared laser, which penetrates deeper into the tissue than the standard 488 nm laser for fluorescein. ICG-fluorescence turned out to be much more stable than fluorescein in vivo, persisting for more than 48 hours without significant photobleaching whereas fluorescein fades within 2 hours. The well-defined intercellular staining pattern of ICG allows automated cell-recognition algorithms, which we accomplished with the free software CellProfiler, providing the possibility of quantitative high-content imaging. Furthermore, we demonstrate the superiority of ICG-based fluorescence microscopy for selected skin pathologies, including dermal nevi, irritant contact dermatitis and necrotic skin. CONCLUSIONS/SIGNIFICANCE: Our results introduce a novel in vivo skin imaging technique using ICG, which delivers a stable intercellular fluorescence signal ideal for morphological assessment down to sub-cellular detail. The application of ICG in combination with the near infrared laser opens new ways for minimal-invasive diagnosis and monitoring of skin disorders

Control of hyperglycaemia in paediatric intensive care (CHiP): study protocol.

BACKGROUND: There is increasing evidence that tight blood glucose (BG) control improves outcomes in critically ill adults. Children show similar hyperglycaemic responses to surgery or critical illness. However it is not known whether tight control will benefit children given maturational differences and different disease spectrum. METHODS/DESIGN: The study is an randomised open trial with two parallel groups to assess whether, for children undergoing intensive care in the UK aged <or= 16 years who are ventilated, have an arterial line in-situ and are receiving vasoactive support following injury, major surgery or in association with critical illness in whom it is anticipated such treatment will be required to continue for at least 12 hours, tight control will increase the numbers of days alive and free of mechanical ventilation at 30 days, and lead to improvement in a range of complications associated with intensive care treatment and be cost effective. Children in the tight control group will receive insulin by intravenous infusion titrated to maintain BG between 4 and 7.0 mmol/l. Children in the control group will be treated according to a standard current approach to BG management. Children will be followed up to determine vital status and healthcare resources usage between discharge and 12 months post-randomisation. Information regarding overall health status, global neurological outcome, attention and behavioural status will be sought from a subgroup with traumatic brain injury (TBI). A difference of 2 days in the number of ventilator-free days within the first 30 days post-randomisation is considered clinically important. Conservatively assuming a standard deviation of a week across both trial arms, a type I error of 1% (2-sided test), and allowing for non-compliance, a total sample size of 1000 patients would have 90% power to detect this difference. To detect effect differences between cardiac and non-cardiac patients, a target sample size of 1500 is required. An economic evaluation will assess whether the costs of achieving tight BG control are justified by subsequent reductions in hospitalisation costs. DISCUSSION: The relevance of tight glycaemic control in this population needs to be assessed formally before being accepted into standard practice

Age and gender influence on HIDRAdisk outcomes in adalimumab-treated hidradenitis suppurativa patients

Background Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease characterized by a significant impairment of patients' quality of life (QoL). It has been recently found that clinical severity of HS does not correlate well with QoL. Therefore, it is important to enhance the evaluation of severity considering the disease burden on QoL. Recently, a new graphical tool able to better describe HS burden, the so-called HIDRAdisk, has been introduced. Objective To investigate the utility of HIDRAdisk in clinical practice before and after treatment and to analyse whether specific factors such as age and gender may influence the outcomes in patients with moderate-to-severe HS. Methods A single-centre retrospective study on 24 patients (13F/11M, mean age 38 +/- 15 years) with moderate-to-severe HS was performed. Clinical data (disease severity and quality of life) were collected at baseline and after 12 weeks of adalimumab. Results HIDRAdisk showed significantly better improvements in males (69.8 +/- 6.2-49.6 +/- 10.8) compared to females (80.7 +/- 6.0-72.3 +/- 6.7), P &lt;0.001. A significant correlation was found in the total population between HS severity values measured through the modified Sartorius score (mSS) and QoL measured through HIDRAdisk. As regards the relationship between disease outcomes and age, a trend for better HIDRAdisk outcomes in younger patients (&lt;40 years) compared to older ones was observed. Conclusions HIDRAdisk appears as a complete and informative tool which can easily measure the global burden of HS, guiding treatment choice and evaluating its efficacy

Plasma Chemokine Levels Are Associated with the Presence and Extent of Angiographic Coronary Collaterals in Chronic Ischemic Heart Disease

In patients with chronic ischemic heart disease (IHD), the presence and extent of spontaneously visible coronary collaterals are powerful determinants of clinical outcome. There is marked heterogeneity in the recruitment of coronary collaterals amongst patients with similar degrees of coronary artery stenoses, but the biological basis of this heterogeneity is not known. Chemokines are potent mediators of vascular remodeling in diverse biological settings. Their role in coronary collateralization has not been investigated. We sought to determine whether plasma levels of angiogenic and angiostatic chemokines are associated with of the presence and extent of coronary collaterals in patients with chronic IHD.We measured plasma concentrations of angiogenic and angiostatic chemokine ligands in 156 consecutive subjects undergoing coronary angiography with at least one ≥90% coronary stenosis and determined the presence and extent of spontaneously visible coronary collaterals using the Rentrop scoring system. Eighty-eight subjects (56%) had evidence of coronary collaterals. In a multivariable regression model, the concentration of the angiogenic ligands CXCL5, CXCL8 and CXCL12, hyperlipidemia, and an occluded artery were associated with the presence of collaterals; conversely, the concentration of the angiostatic ligand CXCL11, interferon-γ, hypertension and diabetes were associated with the absence of collaterals (ROC area 0.91). When analyzed according to extent of collateralization, higher Rentrop scores were significantly associated with increased concentration of the angiogenic ligand CXCL1 (p<0.0001), and decreased concentrations of angiostatic ligands CXCL9 (p<0.0001), CXCL10 (p = 0.002), and CXCL11 (p = 0.0002), and interferon-γ (p = 0.0004).Plasma chemokine concentrations are associated with the presence and extent of spontaneously visible coronary artery collaterals and may be mechanistically involved in their recruitment

Impact of pre-oxidation on the reactivity and conductivity in H2–H2O atmosphere of a ferritic stainless steel for high temperature water vapour electrolysis

International audienceThe as-rolled K41X (AISI 441) ferritic stainless steel presents unusual behaviour when exposed in H2-H2O atmosphere at 800°C, with growth of non-protective iron oxides at its surface. The impact of pre-oxidation in air is investigated in this paper. The pre-oxidation induces the formation of a thin chromia layer at the steel surface. The results obtained after subsequent oxidation for 100 hours in H2-H2O atmosphere evidence a change in the surface reactivity behaviour of the as-rolled alloy: iron oxides formation is avoided and high temperature behaviour (reactivity and conductivity) is improved. Air pre-oxidation seems a promising solution for large scale use of K41X as-rolled steel in H2-H2O atmosphere at high temperature