Tumor-associated macrophages are involved in tumor progression in papillary renal cell carcinoma

Tumor-associated macrophages (TAMs) play a key role in cancer development. Especially, the immunosuppressive M2 phenotype is associated with increased tumor growth, invasiveness and metastasis. The differentiation of macrophages to the alternative phenotype M2 is mediated, inter alia, by macrophage colony-stimulating factor (M-CSF). Papillary renal cell carcinoma (RCC) represents a rare tumor type which, based upon histological criteria, can be subdivided into two subtypes (I and II), of which type II is associated with poor prognosis. In both subtypes, typically, a dense infiltrate of macrophages is found. In the present study, the expression of CD68, CD163, M-CSF, Ki-67, and CD31 was examined in 30 type I and 30 type II papillary RCCs (n?=?60). Both types of papillary RCCs contained an equally dense infiltrate of CD68-positive macrophages. Nearly all macrophages in papillary RCC type II expressed CD163, a characteristic for M2 macrophages. In type I papillary RCC, less than 30 % of macrophages expressed CD163. Furthermore, tumor cells in type II papillary RCC expressed significantly more M-CSF and showed increased (Ki-67 expression defined) proliferative activity in comparison with type I papillary RCC. In addition, the (CD31 defined) capillary density was higher in type II than in type I papillary RCC. A dense infiltrate of M2 phenotype TAM and high M-CSF expression in tumor cells are key features of type II papillary RCC. These findings might explain why the prognosis of papillary RCC type II is worse than that of type I.     

Treatment Optimization of Aortocoronary Dissection as a Complication After Heart Catheterization Using Coronary Computerized Tomographic Angiography

We present the case of a 71-year-old patient with a chronic total occlusion of the right coronary artery (RCA) resulting in a retrograde aortic dissection as a complication of coronary intervention. Acute therapy consisted of coronary stent implantation into the proximal RCA to cover the dissection's entry. One day after, computed tomography-guided angiography revealed a progression of the intramural aortic hematoma with a residual dissection at the RCA ostium. Recurrent coronary angiography was performed to implant another stent covering the entry. Imaging at follow-up demonstrated complete coverage of the Dunning dissection and regression of the intramural aortic hematoma.     

Chronic kidney disease impairs prognosis in electrical storm

Journal of Interventional Cardiac Electrophysiology - The study sought to assess the prognostic impact of chronic kidney disease (CKD) in patients with electrical storm (ES). ES represents a...     

Long-term prognostic value of mid-regional pro-adrenomedullin and C-terminal pro-endothelin-1 in patients with acute myocardial infarction.

BACKGROUND: Mid-regional pro-adrenomedullin (MR-proADM) and endothelin-1 have been shown to predict mortality of patients with acute myocardial infarction. However, the prognostic value of both biomarkers in predicting long-term clinical events after acute myocardial infarction remains unclear. METHODS: In a prospective study, 30 patients suffering from acute ST elevation myocardial infarction or non-ST elevation myocardial infarction were enrolled. Measurements of MR-proADM and CT-pro-endothelin-1 (CT-proET-1) were performed at initial presentation, 2 or 3 days and 4 months after acute myocardial infarction. Long-term clinical events (e.g., recurrent myocardial infarction, percutaneous transluminal coronary angioplasty, aorto-coronary venous bypass or cardiogenic shock) were documented over a period from the 4th until the 10th month. RESULTS: Both MR-proADM and CT-proET-1 were able to differentiate patients with subsequent long-term clinical events (n=11) from those without (n=19). At the time of acute myocardial infarction, median MR-proADM level of the event group was 0.69 nmol/L as compared to 0.59 nmol/L of the no-event group (p=0.036). A difference was still observed after 3 days (event group median 0.66 nmol/L; no-event group median 0.57 nmol/L; p=0.022). Accordingly, median CT-proET-1 level was 72.9 pmol/L in the event group as compared to a median of 54.4 pmol/L in patients in the no-event group (p=0.009) 3 days after acute myocardial infarction. Within the acute phase, patients with MR-proADM levels > or =0.67 nmol/L were 3 times more likely (relative risk 2.8; 95% confidence interval 1.2-6.9; p=0.042) to suffer from a future clinical event. The area under the curve (AUC) was 0.71 (95% confidence interval 0.51-0.86; p=0.046). After 3 days, patients with CT-proET-1 levels > or =57 pmol/L were 6 times more likely (relative risk 5.9; 95% confidence interval 0.9-40.4; p=0.036) to suffer from a future clinical event. The AUC was 0.76 (95% confidence interval 0.55-0.90; p=0.015). CONCLUSIONS: Elevated levels of MR-proADM and CT-proET-1 during the acute phase of myocardial infarction may predict an adverse long-term clinical outcome.     

TIMP-1 gene polymorphism: are genetics able to predict outcome of septic patients?

The multicenter study conducted by Lorente and coworkers - published in the previous issue of Critical Care - suggests that levels of tissue inhibitor of metalloproteinase (TIMP)-1 in association with the 372 T/C genetic polymorphism of TIMP-1 are promising markers to predict the clinical outcome of septic patients. TIMPs bind to active matrix metalloproteinases and, amongst other effects, inhibit their proteolytic activity of the extracellular matrix. Previous clinical studies showed increased plasma levels of TIMP-1 in nonsurvivors of sepsis, and showed associations between the 372 T/C genetic polymorphism of TIMP-1 and increased risk of developing certain diseases. In recent years, there has been great interest in understanding whether genetic determinants of the host response to systemic infections are associated with poor outcome. Furthermore, the pharmacogenomics of sepsis may allow us to target immune-modulating therapies. Measurement of TIMP-1 protein levels and TIMP-1 polymorphism 372 T/C in the intensive care setting could therefore be an attractive noninvasive tool to determine the outcome of septic patients, and might help to select patients potentially benefitting from a target-specific immune-modulatory therapy directed to matrix metalloproteinase/TIMP homeostasis.     

Levels of oxidized low-density lipoproteins are increased in patients with severe sepsis

Background

It was hypothesized that the inflammatory response of patients with severe sepsis may result in changes of plasma levels of oxidized low-density lipoproteins (ox-LDLs) and that drotrecogin α (activated) (DAA) (Xigris, Eli Lilly and Company [Indiana 46285, USA]) may influence ox-LDL levels.

Materials and Methods

The ox-LDL levels were measured in severe septic patients on day 1, 4, and 7 of severe sepsis. Patients were treated either with or without DAA.

Results

The ox-LDL levels increased significantly (P < .05) from day 1 to day 7 (day 1, mean ± SEM, 25.4 ± 1.8 U/L; day 4, mean ± SEM, 34.3 ± 2.1 U/L; day 7, mean ± SEM, 38.3 ± 2.1 U/L) in all patients (n = 68). The ox-LDL levels increased significantly from day 1 to day 7 both in patients treated with (n = 31) and without DAA (n = 37) (P < .001) (DAA-group: day 1, mean ± SEM, 24.4 ± 2.8 U/L; day 4, mean ± SEM, 35.5 ± 2.9 U/L; day 7, mean ± SEM, 40.7 ± 3.2 U/L) (control group: day 1, mean ± SEM, 26.3 ± 2.8 U/L; day 4, mean ± SEM, 33.2 ± 2.9 U/L; day 7, mean ± SEM, 36.4 ± 2.9 U/L). No significant differences of ox-LDL levels were observed between both groups at any point of time (P > .05).

Conclusions

The ox-LDL concentrations increase significantly during the first week of severe sepsis and are not affected by administration of drotrecogin α (activated) (Xigris).     

Koronare Herzerkrankung

Herz - Die koronare Herzkrankheit (KHK) stellt eine häufige strukturelle Ursache für einen Herzstillstand im höheren Alter dar, während hierfür beim jungen Erwachsenen eher...