In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2 Gy/fraction/day). Irradiated macrophages remained viable and metabolically active, despite DNA damage. NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity. A significant increase of pro-inflammatory macrophage markers CD80, CD86 and HLA-DR, but not CCR7, TNF and IL1B was observed after 10 Gy cumulative doses, while anti-inflammatory markers CD163, MRC1, VCAN and IL-10 expression decreased, suggesting the modulation towards a more pro-inflammatory phenotype. Moreover, ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate, without affecting matrix metalloproteases (MMP)2 and MMP9 activity. Importantly, irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis. Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy.

This article describes cases of anti-tumor necrosis factor (TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis (AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics.

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IntroductionObesity-related comorbidities are present in young obese children, providing a platform for early adult cardiovascular disorders.ObjectivesTo compare and correlate markers of adiposity to metabolic disturbances, vascular and cardiac morphology in a European pediatric obese cohort.MethodsWe carried out an observational and transversal analysis in a cohort consisting of 121 obese children of both sexes, between the ages of 6 and 17 years. The control group consisted of 40 children with normal body mass index within the same age range. Markers of adiposity, plasma lipids and lipoproteins, homeostasis model assessment-insulin resistance, common carotid artery intima-media thickness and left ventricular diameters were analyzed.ResultsThere were statistically significant differences between the control and obese groups for the variables analyzed, all higher in the obese group, except for age, high-density lipoprotein cholesterol and adiponectin, higher in the control group. In the obese group, body mass index was directly correlated to left ventricular mass (r=0.542; p=0.001), the homeostasis model assessment-insulin resistance (r=0.378; p=<0.001) and mean common carotid artery intima-media thickness (r=0.378; p=<0.001). In that same group, insulin resistance was present in 38.1%, 12.5% had a combined dyslipidemic pattern, and eccentric hypertrophy was the most common left ventricular geometric pattern.ConclusionsThese results suggest that these markers may be used in clinical practice to stratify cardiovascular risk, as well as to assess the impact of weight control programs.

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