Groin Pain Syndrome Italian Consensus Conference on terminology, clinical evaluation and imaging assessment in groin pain in athlete.

The nomenclature and the lack of consensus of clinical evaluation and imaging assessment in groin pain generate significant confusion in this field. The Groin Pain Syndrome Italian Consensus Conference has been organised in order to prepare a consensus document regarding taxonomy, clinical evaluation and imaging assessment for groin pain. A 1-day Consensus Conference was organised on 5 February 2016, in Milan (Italy). 41 Italian experts with different backgrounds participated in the discussion. A consensus document previously drafted was discussed, eventually modified, and finally approved by all members of the Consensus Conference. Unanimous consensus was reached concerning: (1) taxonomy (2) clinical evaluation and (3) imaging assessment. The synthesis of these 3 points is included in this paper. The Groin Pain Syndrome Italian Consensus Conference reached a consensus on three main points concerning the groin pain syndrome assessment, in an attempt to clarify this challenging medical problem.

HIV-infected long-term nonprogressors display a unique correlative pattern between the interleukin-7/interleukin-7 receptor circuit and T-cell homeostasis.

BACKGROUND: We hypothesized that there may be a correlation between the interleukin-7 (IL-7)/IL-7 receptor (IL-7R) regulatory system and parameters of T-cell homeostasis in HIV-infected long-term nonprogressors (LTNPs) as compared with patients with disease progression. METHODS: The possibility of a correlation between T-cell homeostatic parameters and IL-7/IL-7R was investigated in 22 LTNPs (CD4 count > or =500 cells/microL for >10 years) vs. HIV-positive patients at different disease stages [12 early: CD4 count > or =400 cells/microL ; 15 late (AIDS-presenters): CD4 count < or =150 cells/microL ]. RESULTS: Compared with early-stage HIV-positive patients, LTNPs displayed a higher circulating IL-7 concentration (P=0.05), which was positively associated with higher IL-7Ralpha expression and a higher T-cell receptor excision circle (TREC) content specifically within CD4 cells (P<0.05). Compared with late-stage disease patients, early-stage disease patients displayed a lower IL-7 concentration (P<0.01) and higher percentages of IL-7Ralpha+ CD4 and CD8 cells (P=0.05). IL-7 was positively correlated with the percentage of TREC+ CD4 cells (P<0.01), which translated into a higher percentage of naïve CD4 cells in early-stage disease patients than in late-stage disease patients; however, the CD4 cells in early-stage disease patients were less enriched in recent thymic emigrants (RTEs) compared with LTNPs (P<0.05). In late-stage AIDS-developing patients, substantially increased IL-7 was correlated with a decreased percentage of IL-7Ralpha+ CD4 cells (P=0.01), which resulted in these patients having a significantly lower percentage of naïve T cells (P<0.01) and a significantly lower content of TREC (P<0.01) than the other patients. CONCLUSIONS: The maintenance of high CD4 cell counts in LTNPs was associated with a specific IL-7/IL-7R pattern characterized by increased IL-7 and highest IL-7Ralpha-expressing CD4 cells relative to other patients. Compared with patients with late-stage disease, LTNPs displayed a phenotypically naïve, less activated CD4 cell pool highly enriched in RTEs, suggesting the existence of a compensatory IL-7-mediated pathway specifically sustaining peripheral CD4 counts.

Normal human lung fibroblasts differently modulate interleukin-10 and interleukin-12 production by monocytes: implications for an altered immune response in pulmonary chronic inflammation.

The ability of lung fibroblasts to modulate the immune response has been evaluated by analyzing the synthesis and release of interleukin (IL)-10 and IL-12 by lipopolysaccharide (LPS)-stimulated peripheral blood monocytes exposed to pulmonary fibroblast conditioned medium (FCM). IL-10 and IL-12 contents and gene expression were markedly modified by treatment with FCM as measured by ELISA (+97.5 +/- 12.8% and -68 +/- 7.3% for IL-10 and IL-12, respectively), immunocytochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR). These effects appeared to be mediated by prostaglandin E(2) (PGE(2)) as the modified release of both cytokines was reduced by treatment with indomethacin and mimicked by addition of exogenous PGE(2.) As a result of the enhanced production of IL-10, exposure of LPS/interferon (IFN)-gamma-activated monocytes to FCM was also able to reduce the expression of the class II major histocompatibility complex (MHC) molecule, human leukocyte-associated antigen-DR (HLA-DR) (-51.8 +/- 8.7%) and of the costimulatory molecule, CD40 (-53.9 +/- 11.7%). The expression of both molecules was completely restored when monocytes were pretreated with a neutralizing anti-IL-10 monoclonal antibody. The FCM obtained from fibrotic lung fibroblasts was instead less efficacious in potentiating LPS-stimulated IL-10 release and, consequently, in reducing HLA-DR and CD40 expression, suggesting that an impairment of the immune regulation operated by fibroblasts may be involved in the maintenance of chronic pulmonary inflammation.

Different expression of TNF-alpha receptors and prostaglandin E(2 )Production in normal and fibrotic lung fibroblasts: potential implications for the evolution of the inflammatory process.

Normal human lung fibroblasts downregulate the production of tumor necrosis factor (TNF)-alpha by activated monocytes through the production of prostaglandin E(2) (PGE(2)), contributing to the local control of the inflammatory process. In this study, we provide evidence that fibroblasts derived from diseased tissue, such as fibrotic lung fibroblasts, exhibit different functional features compared with normal cells, with particular regard to their modulatory role. Indeed, fibrotic fibroblasts (FF) spontaneously produced less PGE(2) (3,300 +/- 410 pg/ml) compared with normal fibroblasts (NF) (7,500 +/- 270 pg/ml) and, as a consequence, they showed a reduced ability to downregulate the production of TNF-alpha by lipopolysaccharide (LPS)- activated monocytes. The percentage of inhibition induced by normal cells on the production of TNF-alpha by LPS-activated monocytes was 61 +/- 5.9%, whereas the inhibitory effect exerted by fibrotic cells was reduced to 32 +/- 4% (P < 0.01). We have also observed that the ability of TNF-alpha to induce PGE(2) was impaired in FF and was related to a reduced expression of cyclooxygenase 2. This was possibly due to the reduction of the expression of TNF receptors (TNFRs) in fibrotic cell lines compared with normal cell lines. Flow cytometry revealed that the mean fluorescence intensity (MFI) of both isoforms of TNFR was significantly lower in FF compared with NF. The MFI of TNFR1 was 3. 55 +/- 0.12 for NF and 1.78 +/- 0.35 for FF (P < 0.001). The MFI of TNFR2 was 1.95 +/- 0.27 for NF and 0.99 +/- 0.16 for FF (P < 0.01). The analysis of the effect of TNF-alpha on some functions associated with collagen metabolism in NF and FF showed an increase of the expression of the receptor for collagen type I (alpha(2)beta(1) integrin) in NF (42 +/- 10%) and an even larger increase in FF (102 +/- 23%) (P < 0.05). Interestingly, unlike NF, TNF-alpha failed to increase matrix metalloproteinase 1 levels in FF and did not cause any growth inhibition in these cells. The reduced capability of fibrotic cells to produce PGE(2) either spontaneously or after TNF-alpha treatment may lead to an unrestrained release of TNF-alpha from activated monocytes and, as a result of the reduced expression of TNFRs, to a different response of these cells to TNF-alpha. These changes may be important in the evolution of the inflammatory process, potentially contributing to its transformation into a chronic and self-perpetuating process.