WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Venous thromboembolism is a frequent complication in critically ill patients that has a negative impact on patient outcomes. • Critically ill patients have significantly lower plasma anti‐factor‐Xa activity levels compared with control patients after administration of subcutaneous heparin. • The clinical relevance of the different anti‐factor‐Xa levels after prophylactic doses of low molecular weight heparin (LMWH) in critically ill patients is not completely understood. WHAT THIS STUDY ADDS • The standard dose of 40 mg enoxaparin led to a significant increase in anti‐FXa levels in this selected cohort of ICU patients with normal renal function. • This study found only subtle pharmacokinetic differences, but a comparable pharmacodynamic action, after enoxaparin administration in critically ill and normal medical ward patients. • Thrombin generation with TGA RC‐low and TGA RC‐high reagents was significantly reduced in ICU and normal ward patients after receiving LMWH. Both readouts appear equally useful for estimating the pharmacodynamics of enoxaparin. • The ex vivo model of thrombosis was used for the first time in patients to evaluate the anti‐thrombotic activity of LMWH. This method did not show any difference in thrombus formation after administration of enoxaparin in the individual group of patients. Aim In critically ill patients, reduced anti‐FXa plasma activity following subcutaneous administration of enoxaparin or nadroparin has been described. In this study, we aimed to investigate the bioactivity of enoxaparin in critically ill patients and controls. Methods A prospective, controlled, open label study was performed on a medical intensive care unit (ICU) and a general medical ward. Fifteen ICU patients (male = 12, median age 52 years [IQR 40−65], with a median Simplified Acute Physiology Score of 30 [IQR 18−52]) and sex‐ and age‐matched medical ward patients were included. The anti‐FXa plasma activity was measured after a single subcutaneous dose of 40 mg enoxaparin. The thrombus size of a clot formed in an ex vivo perfusion chamber and endogenous thrombin potential (ETP) were measured. Results The anti‐FXa plasma activity increased significantly after enoxaparin administration, with peak levels at 3 h after treatment, but was comparable between the ICU and medical ward groups (median 0.16 IU ml−1[IQR 0−0.22 IU ml−1]vs. 0.2 IU ml−1[IQR 0.15−0.27 IU ml−1], respectively, P= 0.13). The area under the anti‐FXa activity curve from 0–12 h was similar between the groups (median 0.97 IU ml−1 h [IQR 0.59−2.1] and 1.48 IU ml−1 h1[IQR 0.83−1.62], P= 0.42 for the ICU group compared with the control group, respectively). The ETP was lower in the ICU group (P < 0.05) at baseline, but it was comparable at 3 h between the groups. Thrombus size decreased at 3 h compared with predose (P= 0.029) and was not different between the groups. Conclusion Similar bioactivity was achieved with a standard dose of subcutaneous enoxaparin in this selected cohort of ICU and general ward patie...

Malignant melanoma is a life-threatening skin cancer increasingly diagnosed in the western world. In advanced disease the prognosis is grave. Growth and metastasis formation in melanomas are regulated by a network of cytokines, cytokine-receptors, and adhesion molecules. However, little is known about surface antigens and target expression profiles in human melanomas. We examined the cell surface antigen profile of human skin melanoma cells by multicolor flow cytometry, and compared their phenotype with 4 melanoma cell lines (A375, 607B, Mel-Juso, SK-Mel28). Melanoma cells were defined as CD45−/CD31− cells co-expressing one or more melanoma-related antigens (CD63, CD146, CD166). In most patients, melanoma cells exhibited ErbB3/Her3, CD44/Pgp-1, ICAM-1/CD54 and IGF-1-R/CD221, but did not express CD20, ErbB2/Her2, KIT/CD117, AC133/CD133 or MDR-1/CD243. Melanoma cell lines were found to display a similar phenotype. In most patients, a distinct subpopulation of melanoma cells (4–40%) expressed the erythropoietin receptor (EPO-R) and ErbB4 together with PD-1 and NGF-R/CD271. Both the EPO-R+ and EPO-R− subpopulations produced melanoma lesions in NOD/SCID IL-2Rgammanull (NSG) mice in first and secondary recipients. Normal skin melanocytes did not express ErbB4 or EPO-R, but expressed a functional KIT receptor (CD117) as well as NGF-R, ErbB3/Her3, IGF-1-R and CD44. In conclusion, melanoma cells display a unique composition of surface target antigens and cytokine receptors. Malignant transformation of melanomas is accompanied by loss of KIT and acquisition of EPO-R and ErbB4, both of which are co-expressed with NGF-R and PD-1 in distinct subfractions of melanoma cells. However, expression of EPO-R/ErbB4/PD-1 is not indicative of a selective melanoma-initiating potential.

Although total plasma concentrations of ertapenem were lower in diabetics than reported for healthy subjects, free interstitial tissue concentrations in diabetics were similar to those known from healthy volunteers. Penetration of ertapenem into the interstitium of inflamed tissue of diabetic feet was not impaired in spite of angiopathy. Daily doses of >1 g of ertapenem might be considered to optimize bactericidal effects in diabetic foot infections caused by moderately susceptible strains.

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Squamous cell carcinoma (SCC) is the second most common type of skin cancer after basal cell carcinoma (BCC). The overall prevalence of BCC is 3 times higher than that of SCC, but this can vary when looking at specific locations such as the hand, where SCC is much more common than BCC. Carcinoma (or epithelioma) cuniculatum is a rare variant of SCC. It was originally described as a verrucous carcinoma of the soles. Exceptionally, it can arise in other parts of the skin. We report a rare case of carcinoma cuniculatum of the right thenar region with bone and lymph node involvement.