Aims/hypothesis: Type 2 diabetes has been demonstrated to predispose to aortic valve calcification. We investigated whether type 2 diabetes concomitant to aortic stenosis (AS) enhances valvular inflammation and coagulation activation via upregulated expression of NF-κB, with subsequent increased expression of bone morphogenetic protein 2 (BMP-2). Methods: In this case–control study, 50 individuals with severe isolated AS and concomitant type 2 diabetes were compared with a control group of 100 individuals without diabetes. The median (IQR) duration of diabetes since diagnosis was 11 (7–18) years, and 36 (72%) individuals had HbA_1c ≥48 mmol/mol (≥6.5%). Stenotic aortic valves obtained during valve replacement surgery served for in loco NF-κB, BMP-2, prothrombin (FII) and active factor X (FXa) immunostaining. In vitro cultures of valve interstitial cells (VICs), isolated from obtained valves were used for mechanistic experiments and PCR investigations. Results: Diabetic compared with non-diabetic individuals displayed enhanced valvular expression of NF-κB, BMP-2, FII and FXa (all p ≤ 0.001). Moreover, the expression of NF-κB and BMP-2 positively correlated with amounts of valvular FII and FXa. Only in diabetic participants, valvular NF-κB expression was strongly associated with serum levels of HbA_1c, and moderately with fructosamine. Of importance, in diabetic participants, valvular expression of NF-κB correlated with aortic valve area (AVA) and maximal transvalvular pressure gradient. In vitro experiments conducted using VIC cultures revealed that glucose (11 mmol/l) upregulated expression of both NF-κB and BMP-2 (p < 0.001). In VIC cultures treated with glucose in combination with reactive oxygen species (ROS) inhibitor (N-acetyl-l-cysteine), the expression of NF-κB and BMP-2 was significantly suppressed. A comparable effect was observed for VICs cultured with glucose in combination with NF-κB inhibitor (BAY 11–7082), suggesting that high doses of glucose activate oxidative stress leading to proinflammatory actions in VICs. Analysis of mRNA expression in VICs confirmed these findings; glucose caused a 6.9-fold increase in expression of RELA (NF-κB p65 subunit), with the ROS and NF-κB inhibitor reducing the raised expression of RELA by 1.8- and 3.2-fold, respectively. Conclusions/interpretation: Type 2 diabetes enhances in loco inflammation and coagulation activation within stenotic valve leaflets. Increased valvular expression of NF-κB in diabetic individuals is associated not only with serum HbA_1c and fructosamine levels but also with AVA and transvalvular gradient, indicating that strict long-term glycaemic control is needed in AS patients with concomitant type 2 diabetes. This study suggests that maintaining these variables within the normal range may slow the rate of AS progression. Graphical

Objectives: Atmospheric pressure is the most objective weather factor because regardless of if outdoors or indoors it affects all objects in the same way. The majority of previous studies have used the average daily values of atmospheric pressure in a bioclimatic analysis and have found no...

The incidence of accidental hypothermia (core temperature ≤35 °C) is difficult to estimate, as the affected population is heterogeneous. Both temperature and clinical presentation should be considered while determining severity, which is difficult in a prehospital setting. Extracorporeal rewarming is advocated for all Swiss Staging System class IV (hypothermic cardiac arrest) and class III (hypothermic cardiac instability) patients. Veno-arterial extracorporeal membrane oxygenation (ECMO) is the method of choice, as it not only allows a gradual, controlled increase of core body temperature, but also provides respiratory and hemodynamic support during the unstable period of rewarming and reperfusion. This poses difficulties with the coordination of patient management, as usually only cardiac referral centers can deliver such advanced treatment. Further special considerations apply to subgroups of patients, including drowning or avalanche victims. The principle of ECMO implantation in severely hypothermic patients is no different from any other indication, although establishing vascular access in a timely manner during ongoing resuscitation and maintaining adequate flow may require modification of the operating technique, as well as aggressive fluid resuscitation. Further studies are needed in order to determine the optimal rewarming rate and flow that would favor brain and lung protection. Recent analysis shows an overall survival rate of 40.3%, while additional prognostic factors are being sought for determining those patients in whom the treatment is futile. New cannulas, along with ready-to-use ECMO sets, are being developed that would enable easy, safe and efficient out-reach ECMO implantation, thus shortening resuscitation times. Moreover, national guidelines for the management of accidental hypothermia are needed in order that all patients that would benefit from extracorporeal rewarming would be provided with such treatment. In this perspective article, we discuss burning problems in ECMO therapy in hypothermic patients, outlining the important research goals to improve the outcomes.

Elevated asymmetric dimethylarginine (ADMA) is associated with an increased risk of coronary artery disease. A prognostic value of ADMA following coronary artery bypass grafting (CABG) is unknown. The aim of the current study was to assess the effect of CABG on ADMA and oxidative stress and determine their associations with postoperative complications. In 158 consecutive patients (35 women, 123 men, aged 65.2 ± standard deviation 8.2 years) undergoing isolated, elective CABG procedure, we measured plasma ADMA and 8-iso-prostaglandin F_2α (8-iso-PGF_2α) preoperatively and twice postoperatively: 18–36 h and 5–7 days after surgery. The primary end points were postoperative myocardial infarction (PMI) and in-hospital cardiovascular death. ADMA increased from 0.56 ± 0.06 μmol/l at baseline by 68% to 0.94 ± 0.11 μmol/l at 18–36 h after CABG, and then decreased by 20% to 0.75 ± 0.12 μmol/l on 5–7 days postoperatively (P = 0.0001 for all comparisons). A similar pattern of changes was observed for 8-iso-PGF_2α. Thirteen (8.2%) patients developed PMI, and 6 patients (3.8%) died during the early postoperative period because of extensive PMI. PMI and early perioperative mortality were positively associated with ADMA and 8-iso-PGF_2α. A marked increase of ADMA and oxidative stress is observed within the first days following CABG, and is associated with unfavourable early post-CABG outcomes, including PMI and in-hospital cardiovascular death.