Scleroderma (SSc) is a rare and heterogeneous immune-mediated disease involving the connective tissue and microvasculature whose pathogenesis remains unclear. Data concerning T and natural killer (NK) cell abnormalities and cytokine levels in the peripheral blood (PB) from patients with SSc are scarce, and the results are contradictory. The present study aimed to analyze the changes of T lymphocytes, NK cells, and T helper (Th)-related cytokines in the PB of patients with SSc in comparison to healthy individuals and its relation to disease subtype and stage, organ involvement, and nailfold capillaroscopic changes. A non-random convenience sample of 57 scleroderma patients was utilized. Fifty-five out of the 57 patients studied were women (97 %); 10 patients presented pre-scleroderma (pre-SSc) and 47 SSc: 34 limited cutaneous SSc (lcSSc) and 13 diffuse cutaneous SSc (dcSSc). Patients with SSc were classified in early (n = 7), intermediate (n = 10), and late (n = 30) disease. Blood samples were analyzed by flow cytometry for total T cells, CD4+ and CD8+ T cell subsets, total NK cells, and CD56+low and CD56+high NK cell subsets. T cells were further analyzed for the expression of the CD56 adhesion molecule and activation-related markers (HLA-DR, CD45RO). In addition, the serum levels of Th1-, Th2-, and Th17-related cytokines were measured by flow cytometry. Twenty-five healthy individuals recruited from the blood bank were used as controls. Patients had lower numbers of total lymphocytes and T cells comparing to healthy controls. Both CD4+ and CD8+ T cells were decreased, but differences were statistically significant only for CD8+ and CD8+ CD45RO+ T cells. These alterations were seen in patients with SSc but not in patients with pre-SSc, and, in general, they were more pronounced in patients with dcSSc than in patients with lcSSc, in patients with vascular involvement than in those without, as well as in patients having active and late nailfold capillaroscopic patterns. CD56+ T cells were also decreased in SSc patients, especially in those with active/late capillaroscopic patterns or with severe lung disease. Diminished numbers of circulating NK cells were also observed in patients with lcSSc and in those with early disease. No statistically significant changes were found in serum cytokine levels, as compared with controls. Patients with SSc had major alterations in circulating CD8+ and CD56+ T cells, as well as in NK cells, suggesting that these cells may play a relevant role in SSc pathogenesis, probably operating at different phases and/or at different organs. In addition, the serum levels of Th1, Th2, and Th17 cytokines did not provide useful information for evaluating T cell polarization in SSc.
Abstract:The authors describe a case of a 48--year--old man who presented with four weeks of fever,
<b><i>Introduction:</i></b> End-stage liver disease (ESLD) is the advanced phase of most liver diseases. The cure is liver transplantation (LT), only available for a minority of patients. This review summarizes the evidence regarding palliative care (PC) in ESLD patients awaiting LT. <b><i>Methods:</i></b> Review of the literature available in Medline, Scopus and Web of Knowledge, with keywords ESLD and PC. <b><i>Results:</i></b> Fifteen of the 230 articles reviewed met the inclusion criteria. Ten main themes were addressed: symptom burden; perspectives of life-sustaining treatment and comfort for patients, families and health professionals; goals of care discussions; patient and family needs; quality of life; PC and survival; referral to PC, barriers and opportunities; integration of PC; outpatient care and cost-effectiveness analysis. The referral of patients to PC was only evaluated in a few studies, all of which reported low referral rates. Better knowledge of how PC professionals can support other professionals was considered important, and also better ways to integrate PC were considered essential. <b><i>Conclusion:</i></b> ESLD patients awaiting LT have a significant need for PC and, despite the insufficient response, were reported to benefit from this type of care. Future research is essential to determine the means to overcome barriers and better integrate PC for ESLD patients awaiting LT.
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