Association of multiple biomarkers and classical risk factors with early carotid atherosclerosis: results from the Gutenberg Health Study

Background

In the Gutenberg Health Study, a random sample of the population was scanned with vascular ultrasound for early atherosclerosis. A continuous classical risk marker model (waist circumference, HbA1c, LDL/HDL ratio, pack years and pulse pressure) was compared to a model of modern biomarkers (C-reactive protein, troponin I, N-terminal pro B-type natriuretic peptide, copeptin, mid-regional pro-adrenomedullin, and asymmetric dimethylarginine) with regard to the ability of ruling out abnormal intima-media thickness (IMT), respectively, carotid plaques.

Methods

Data of the first consecutive 5,000 participants (aged 35–74 years; 2,540 men, 2,460 women) were analyzed. IMT was measured at both common carotid arteries using an edge detection system. Plaques were defined as protrusion of ≥1.5 mm in common, internal and external carotid artery.

Results

For classical risk factors, in comparison to a model of six modern biomarkers, regarding the variable (a) IMT>0.85 mm negative and positive predictive value (NPV and PPV) were 0.98 and 0.16 for both the classical risk factor model and the biomarker model. The second variable (b) presence of plaque could be ruled out with an NPV of 0.84 and identified with a PPV of 0.61 for classical risk factors, and 0.84 and 0.58 for biomarkers, respectively. Values were calculated using logistic regression analysis.

Conclusion

Classical risk factors allow ruling out pathologic IMT and presence of carotid plaques in a population of primary prevention in a reliable way. Modern biomarkers performed almost equally well but did not provide further information.     

Chronic sclerosing sialadenitis as one of the immunoglobulin G4-related diseases: a clinicopathological study of six cases from Central Europe

Laco J, Ryska A, Celakovsky P, Dolezalova H, Mottl R & Tucek L (2011) Histopathology 58 , 1157–1163 Chronic sclerosing sialadenitis as one of the immunoglobulin G4‐related diseases: a clinicopathological study of six cases from Central Europe Aims: Chronic sclerosing sialadenitis (CSS) has been proposed recently to be a member of the group of IgG4‐related diseases in Japanese and American series. The aim of our study was to validate these results in a cohort of European patients. Methods and results: Our CSS series included four females and two males, aged 32–76 years, all presenting with unilateral swelling of submandibular gland. Microscopically, all CSS‐cases showed similar morphology with preservation of lobular architecture accentuated by cellular fibrous bands, dense lymphoplasmacytic inflammation and varied acinar atrophy. Ductal lymphocytes were detected in three cases. In five cases, the presence of intraductal secretory material accompanied by parenchymal neutrophils was observed. Obliterative phlebitis was seen in three cases. The inflammatory infiltrate was composed of T and B lymphocytes and polyclonal plasma cells. The median number of IgG‐positive plasma cells per high‐power field (HPF) was 157; median number of IgG4‐positive plasma cells per HPF was 133. Median value of the IgG4:IgG ratio was 0.84. Conclusions: This is the first European series to demonstrate that CSS belongs to the family of IgG4‐related disease. Unlike previous studies, in CSS we found rarely described ductal lymphocytes and parenchymal neutrophils. CSS displays consistent morphology with increased numbers of IgG4‐positive plasma cells, and should be regarded as a member of the IgG4‐related disease group.     

Angiographic score assessment improves cardiovascular risk prediction: the clinical value of SYNTAX and Gensini application

Background

Severity of coronary artery disease (CAD) is related to cardiovascular outcome. We aimed to assess the long-term follow-up depending on Synergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) and Gensini score for prognosis. Both scores increase with complexity and thus reflect risk of cardiovascular events.

Methods and results

We determined complexity and extent of CAD by the SYNTAX and Gensini score in the AtheroGene cohort (N = 1,974, with 22.6 % women). The endpoint was non-fatal myocardial infarction (N = 132) and cardiovascular death (N = 159) over a median follow-up of 5.4 (Q1: 5.23/Q3: 5.57) years up to 8 years maximum (follow-up rate 99.4 %). For SYNTAX score, the following distribution was used: low (≤22, N = 1,404), medium (23–32, N = 314), high score (>32, N = 256). Gensini score was split into thirds. Cox regression analysis showed a hazard ratio (HR) of 1.5 (95 % confidence interval 1.16–1.95; p = 0.0024) for the log transformed SYNTAX score in a fully adjusted model and a HR of 1.41 (95 % CI 1.13–1.77; p = 0.0025) for the Gensini score. The SYNTAX score alone had a C-index of 0.62, whereas adding clinical variables increased the C-index to 0.67. Similar results were obtained for the Gensini score. Regarding the SYNTAX score using net reclassification index, discrimination of events and non-events was enhanced by 37.2 % in a model of clinical variables and biomarkers and by 31.8 % for the Gensini score.

Conclusion

The SYNTAX and Gensini score in combination with clinical variables could be used to predict the cardiovascular prognosis during a long-term follow-up of up to 8 years in CAD patients.     

Quantification and rationalization of the higher affinity of sodium over potassium to protein surfaces

For a series of different proteins, including a structural protein, enzyme, inhibitor, protein marker, and a charge-transfer system, we have quantified the higher affinity of Na+ over K+ to the protein surface by means of molecular dynamics simulations and conductivity measurements. Both approaches show that sodium binds at least twice as strongly to the protein surface than potassium does with this effect being present in all proteins under study. Different parts of the protein exterior are responsible to a varying degree for the higher surface affinity of sodium, with the charged carboxylic groups of aspartate and glutamate playing the most important role. Therefore, local ion pairing is the key to the surface preference of sodium over potassium, which is further demonstrated and quantified by simulations of glutamate and aspartate in the form of isolated amino acids as well as short oligopeptides. As a matter of fact, the effect is already present at the level of preferential pairing of the smallest carboxylate anions, formate or acetate, with Na+ versus K+, as shown by molecular dynamics and ab initio quantum chemical calculations. By quantifying and rationalizing the higher preference of sodium over potassium to protein surfaces, the present study opens a way to molecular understanding of many ion-specific (Hofmeister) phenomena involving protein interactions in salt solutions.     

In vivo magnetic resonance imaging of dendritic cell migration into the draining lymph nodes of mice

Dendritic cell (DC) migration into the draining lymph nodes is critical for T cell priming. Here, we show that magnetic resonance imaging (MRI) can be used to visualize DC migration in vivo. We combined clinically approved small particles of iron oxide (SPIO) with protamine sulfate to achieve efficient uptake by murine bone marrow-derived DC. SPIO-DC were largely unaltered and after injection into the footpads of mice, they migrated into the T cell areas of the draining lymph nodes, which could be visualized by MRI. Distinct MRI signal reduction patterns correlated with the detection of SPIO-DC mainly within Thy-1.2+ B220- T cell areas, as confirmed by iron staining and immunohistology. Clear signal reduction patterns could still be observed with 1x10(6) injected SPIO-DC at high resolution, resulting in the detection of about 2000 DC. Control injections of homing-incompetent SPIO-DC derived from CCR7-/- mice or SPIO alone did not reach the T cell areas. Taken together, the results demonstrate that clinically approved contrast agents allow the non-invasive visualization of DC migration into the draining lymph node by MRI in vivo at high resolution. This protocol therefore also allows dynamic imaging of immune responses and MRI-based tracking of human DC in patients.     

A case report of the treatment of diabetic foot ulcers using a sodium hyaluronate and iodine complex

Diabetic foot ulcers are difficult to heal due to defects in local microvasculature and persistent, concomitant infection. Despite the best medical care, amputation is often a management option for this problem. The authors have developed a new and unique system for wound treatment, which is based on a combination of high molecular weight sodium hyaluronate with an iodine complex-Hyiodine (Contipro C, Dolní Dobrouc, Czech Republic). In this case report, the authors present an observational study on a series of patients with diabetic foot disease with nonhealing wounds treated with Hyiodine. The effect of the HA-iodine complex was studied on 18 patients suffering from complicated foot diabetic wounds. The HA-iodine complex was either spread directly over the wound, or more frequently, gauze was immersed in the HA-iodine complex and then put on/into the wound. Then several layers of dry gauze covered the wound. This dressing was changed every 24 hours. Wound healing was monitored daily, and wound pictures were taken each second week. Clinical improvement was observed in the majority. This suggests that the HA-iodine complex dressing has potential that needs to be developed from controlled studies.