The connective tissue disorders (CTDs), also called collagen vascular diseases (CVDs), represent a heterogeneous group of immunologically mediated inflammatory disorders with a large variety of affected organs. Individuals with a CTD (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, polymyositis/dermatomyositis and mixed connective tissue disease) are susceptible to respiratory involvement. When the lungs are affected, an increasing mortality and morbidity in CVDs occurs. Interstitial lung disease (ILD) is established as a clinical corollary across the spectrum of CTDs, with an overall incidence estimated at 15%.Therefore, pivotal clinical dilemmas remain in the evaluation and management of ILD involvement in CVDs. Critical questions are the presence of fibrosis and whether the disease is clinically significant. Moreover, the clinician has to decide if treatment is warranted and which is the best therapeutic approach. The use of additional tests, such as pulmonary function tests, high-resolution computed tomography scan, bronchoalveolar lavage fluid and surgical lung biopsy, deserves better discussion. The present review focuses on establishing the diagnosis of ILD in CTD, and on evaluating disease activity and prognosis. This will provide the basis for therapeutic decisions that will be discussed, including an overview of recent advances.

The metabolic support of the critically ill patient is a relatively new target of active research and little is as yet known about the effects of critical illness on metabolism. The nonthyroidal illness syndrome, also known as the low T3 syndrome or euthyroid sick syndrome, describes a condition characterized by abnormal thyroid function tests encountered in patients with acute or chronic systemic illnesses. The laboratory parameters of this syndrome include low serum levels of triiodothyronine (T3) and high levels of reverse T3, with normal or low levels of thyroxine (t4) and normal or low levels of thyroid-stimulating hormone (TSH). This condition may affect 60 to 70% of critically ill patients. The changes in serum thyroid hormone levels in the critically ill patient seem to result from alterations in the peripheral metabolism of the thyroid hormones, in TSH regulation, in the binding of thyroid hormone to transport-protein and in receptor binding and intracellular uptake. Medications also have a very important role in these alterations. Hormonal changes can be seen within the first hours of critical illness and, interestingly, these changes correlate with final outcome. Data on the beneficial effect of thyroid hormone treatment on outcome in critically ill patients are so far controversial. Thyroid function generally returns to normal as the acute illness resolves.

Idiopathic pulmonary fibrosis (IPF) is associated with aberrant repair, persistence of collagen deposition, and the development of vascular remodeling. However, the role of angiogenesis in the pathogenesis of IPF is still undetermined. The aim of this study was to evaluate the combined mRNA expression of vascular endothelial growth factor A (VEGFA), fibroblast growth factor 2 (FGF2), insulin-like growth factor 1 (IGF1) epidermal growth factor (EGF), and its receptor (EGFR) in lung tissue obtained from IPF patients. We have also investigated the expression of chemokine CXCL12/stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, to identify alterations that maybe implicated in the pathogenesis of IPF. The subjects studied consisted of two distinct groups: patients with IPF (n = 25) and subjects (control) undergoing thoracic surgery for reasons other than interstitial lung disease (n = 10). Expression analysis of the aforementioned growth factors and biological axis CXCL12/CXR4 analysis were performed using real-time RT-PCR. IGF-1, EGF, and FGF2 mRNA levels are significantly decreased in the patients compared to the controls (p = 0.028, p = 0.023 and p = 0.009, respectively). SDF1-TR1 and SDF1-TR2 transcript levels were significantly lower in patients compared to controls (p = 0.017 and p = 0.001). Significant coexpression of VEGF mRNA with IGF mRNA was observed in the group of the patients (p = 0.017). An additional coexpression of VEGF mRNA with SDF1-TR1 mRNA was demonstrated(p = 0.030). Our results show a downregulation in angiogenetic mechanisms in IPF. However, our results should be further verified by measuring other angiogenetic pathways in more samples.

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Abstract. increased permeability of the pleural microvasculature is generally attributed to the substances that are released in inflammatory and malignant pleural effusions, although the exact pathogenetic mechanisms of malignant pleural effusions are unclear. current therapies used to prevent the re-accumulation of pleural fluid and relieve symptoms are of variable efficacy and may cause serious adverse effects. Understanding the mechanisms of fluid accumulation would hopefully permit the development of more specific, effective and safer treatment modalities. angiogenesis, pleural vascular increased permeability and inflammation are considered central to the pathogenesis of malignant pleural effusions. Vascular endothelial growth factor (VEGF) is a member of the VEGF/platelet-derived factor gene family and consists of at least six isoforms. Since it was shown that VEGF contributes to the formation of malignant pleural effusions, there have been some attempts to implicate, therapeutically, this finding using different molecules (ZD6474, PTK 787 and bevacizumab). However, the role of the biological axis of VEGF and angiopoietins needs further investigation in both the pathogenesis and the treatment of malignant pleural effusion. in both non-small-cell lung carcinoma and breast cancer, it has been shown that the ligand for CXCR4, CXCL12 or SDF-1α, exhibited peak levels of expression in organs that were the preferred destination for their respective metastases. Recent findings imply that new therapeutic strategies aimed at blocking the SDF-1-CXCR4 axis may have significant applications for patients by modulating the trafficking of hemato/lymphopoietic cells and inhibiting the metastatic behavior of tumor cells as well. The purpose of this report is to review novel pathogenetic and therapeutic implications regarding the angiogenetic pathways in malignant pleural effusions.

Background: The role of angiogenesis in the pathogenesis of pleural effusion (PE) has not been determined. The expression of angiogenic factors may represent useful markers for the diagnosis and prediction of disease outcome. To measure the pleural fluid (PF) and serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and Tie receptor tyrosine kinase (Tie-2) in order to investigate their role in the pathogenesis of PEs. Methods: Sixty-seven, 17 with transudative PEs due to heart failure and 50 with exudative PEs (malignant, 22; inflammatory, 15; undiagnosed, 13) were included in the study. PF and serum levels of the growth factors (VEGF, bFGF and Tie-2) were measured using enzymelinked immunosorbent assays. Results: PF and serum VEGF levels but not bFGF and Tie-2 levels were higher (po0.005) in exudates than in transudates. PF VEGF levels were significantly higher in malignant than inflammatory and undiagnosed PEs (p ¼ 0.03). In addition, PF Tie-2 levels were not found different in malignant or in parapneumonic PEs. Conclusion: Our results showed that VEGF is one of the main mediators in exudative PEs, but this effect is not mediated through the angiogenetic pathway Ang-1/Tie-2. However, the role of angiogenesis and its pathways in the pathogenesis of exudative PEs needs further exploration.

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Background. Skin and soft tissue infections (SSTIs) in cancer patients represent a diagnostic challenge, as etiologic diagnosis is often missing, and clinical assessment of severity is difficult. Few studies have described (SSTIs) in patients with solid tumours (STs). Patients and Methods. Records of patients with ST and SSTI, cared for at the University Hospital of Heraklion, from 2002 to 2006 were retrospectively studied. Results. A total of 81 episodes of SSTIs, occurring in 71 patients with ST, have been evaluated. Their median age was 65 years (34–82). The most common underlying malignancy was breast cancer in 17 patients (24%). Most episodes (89%) occurred in nonneutropenics. Cellulitis/erysipelas was the most common clinical presentation (56; 69%). Bacterial cultures were possible in 29 (36%) patients. All patients received antimicrobial therapy, while in 17 episodes (21%) an incision and drainage was required. Treatment failure occurred in 20 episodes (25%). Five patients (7%) died due to sepsis. None was neutropenic. Severe sepsis on admission (P = 0.002) and prior blood transfusion (P = 0.043) were independent predictors of treatment failure. Conclusion. SSTIs can be life threatening among patients with ST. Early diagnosis and appropriate treatment are of the utmost importance, since sepsis was proven a significant factor of unfavourable outcome.