Corticosteroid-treated Patients Research Articles

Severe pneumonia in mycophenolate mofetil combined with low-dose corticosteroids-treated patients with immunoglobulin A nephropathy

The tolerance of mycophenolate mofetil (MMF; Shanghai Roche, China) in Lee Classes III, IV, and V immunoglobulin A nephropathy (IgAN) remains unclear. This article reports nine cases of severe pneumonia (SP), including pneumocystis pneumonia (PCP) and cytomegalovirus (CMV) pneumonia, and its risk factors in MMF plus low-dose corticosteroid-treated patients with Lee Classes III, IV, and V IgAN. Fifty-three patients with IgAN were included in this single-center study. The treatment regimen was MMF (1–1.5 g/d) plus low-dose corticosteroids (0.5 mg/kg/d). SP was defined as diffuse bilateral lung infiltrate with respiratory failure. PCP was diagnosed by detecting the organisms in the sputum and bronchoalveolar lavage. CMV infection was diagnosed through serum screening for CMV-IgG and IgM antibodies and CMV-DNA testing by a real-time polymerase chain reaction assay. The risk factors of SP were analyzed. Nine cases (16.9%) of SP occurred in this study. All SP developed at approximately the 10th–14th week after the initiation of the regimen: PCP was diagnosed in four cases and CMV infection in two cases. Renal function impairing was more serious in patients with SP than in those without SP, as evidenced by estimated glomerular filtration rate (p = 0.019) and serum creatinine level (p = 0.016). Six of the nine SPs occurred in MMP plus low-dose methylprednisolone group, which was statistically higher than that in the MMF plus low-dose prednisone group (p = 0.000). The incidence of SP in this study was 16.9%. Chronically impaired renal function and the use of methylprednisolone may be the risk factors for SP.

Contraception in patients with systemic lupus erythematosus and antiphospholipid syndrome.

Contraceptive choice in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) is challenging but important. Long-acting forms of contraception such as the progesterone intrauterine device (IUD) or subdermal implant are preferable for most patients. Estrogen-containing hormonal contraceptives may be used in stable, inactive SLE patients but are contraindicated in patients with positive antiphospholipid antibodies (aPL). The levonorgestrel IUD is a good alternative for many APS patients and often decreases menstrual blood loss. It is prudent to avoid depot medroxyprogesterone acetate (DMPA) in corticosteroid-treated or other patients at risk for osteoporosis because of the inhibition of ovulation. Effective and safe contraception in patients with SLE and APS permits planning for pregnancy during inactive disease and while on pregnancy-compatible medications, preventing a poorly timed pregnancy that may jeopardize maternal and/or fetal health.

Novel approach for analysis of bronchoalveolar lavage fluid (BALF) using HPLC-QTOF-MS-based lipidomics: lipid levels in asthmatics and corticosteroid-treated asthmatic patients.

To better understand the respiratory lipid phenotypes of asthma, we developed a novel method for lipid profiling of bronchoalveolar lavage fluid (BALF) using HPLC-QTOF-MS with an internal spectral library and high-throughput lipid-identifying software. The method was applied to BALF from 38 asthmatic patients (18 patients with nonsteroid treated bronchial asthma [NSBA] and 20 patients with steroid treated bronchial asthma [SBA]) and 13 healthy subjects (NC). We identified 69 lipids, which were categorized into one of six lipid classes: lysophosphatidylcholine (LPC), phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylserine (PS), sphingomyelin (SM) and triglyceride (TG). Compared with the NC group, the individual quantity levels of the six classes of lipids were significantly higher in the NSBA subjects. In the SBA subjects, the PC, PG, PS, SM, and TG levels were similar to the levels observed in the NC group. Using differentially expressed lipid species (p value < 0.05, FDR < 0.1 and VIP score of PLS-DA > 1), 34 lipid biomarker candidates with high prediction performance between asthmatics and controls were identified (AUROC > 0.9). These novel findings revealed specific characteristics of lipid phenotypes in asthmatic patients and suggested the importance of future research on the relationship between lipid levels and asthma.

Survivin as a potential mediator to support autoreactive cell survival in myasthenia gravis: a human and animal model study.

The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer cells in the thymuses of corticosteroid-treated patients. Application of a survivin vaccination strategy in mouse and rat models of myasthenia gravis demonstrated improved motor assessment, a reduction in acetylcholine receptor specific autoantibodies, and a retention of acetylcholine receptor at the neuromuscular junction, associated with marked reduction of survivin-expressing circulating CD20+ cells. These data strongly suggest that survivin expression in cells with lymphocyte and plasma cell markers occurs in patients with myasthenia gravis and in two animal models of myasthenia gravis. Survivin expression may be part of a mechanism that inhibits the apoptosis of autoreactive B cells in myasthenia gravis and other autoimmune disorders.

Topical Corticosteroids Do Not Revert the Activated Phenotype of Eosinophils in Eosinophilic Esophagitis but Decrease Surface Levels of CD18 Resulting in Diminished Adherence to ICAM-1, ICAM-2, and Endothelial Cells

Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients' eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.

Treatment with corticosteroids and the risk of anastomotic leakage following lower gastrointestinal surgery: a literature survey

Background Anastomotic leakage is a serious complication in colorectal surgery. Treatment with corticosteroids is known to impair wound healing but their effect on the healing of a colorectal anastomosis remains unclear, and studies have reported conflicting results. Objective The aim of this study was to evaluate the current evidence regarding the effect of corticosteroids on the risk of anastomotic leakage following colorectal surgery. Search strategy A systematic review was conducted following a search of PubMed and Embase. Selection criteria Inclusion criteria were studies published in English and involving humans. A minimum cohort of 50 patients was required and anastomoses involving the ileum, colon and rectum were included. Studies that investigated corticosteroids as a risk factor for anastomotic leakage were included regardless of the duration and the dose of corticosteroids. Data Collection and analysis A comparison was conducted between anastomotic leakage in noncorticosteroid- and corticosteroid-treated patients. The main outcome measure was the risk of anastomotic leakage. Twelve studies with a total of 9564 patients were included in the review. In total, 1034 patients received corticosteroids in the preoperative period, and 344 patients were diagnosed with anastomotic leakage, 70 of whom had received corticosteroids. Six of the 12 studies showed an increased risk for anastomotic leakage in the corticosteroid group. Overall, the anastomotic leakage rate was 6.77% (95% CI: 5.48-9.06) in the corticosteroid group and 3.26% (95% CI: 2.94-3.58) in the noncorticosteroid group. Caution should be shown in patients scheduled for lower gastrointestinal surgery with anastomosis.

Review article: the prevention and reversal of hepatic fibrosis in autoimmune hepatitis

Immunosuppressive treatment of autoimmune hepatitis can prevent or reverse hepatic fibrosis, but these anti-fibrotic effects are inconsistent secondary gains. To describe the anti-fibrotic effects of current therapies for autoimmune hepatitis, discuss the pathogenic mechanisms of hepatic fibrosis that might be targeted by anti-fibrotic interventions, indicate the non-invasive diagnostic tests of hepatic fibrosis that must be validated in autoimmune hepatitis and to suggest promising treatment opportunities. Studies cited in PubMed from 1972 to 2013 for autoimmune hepatitis, hepatic fibrosis, cirrhosis, anti-fibrotic therapy and non-invasive tests of hepatic fibrosis were selected. Hepatic fibrosis improves in 53-57% of corticosteroid-treated patients with autoimmune hepatitis; progressive fibrosis slows or is prevented in 79%; and cirrhosis may be reversed. Progressive hepatic fibrosis is associated with liver inflammation, and the inability to fully suppress inflammatory activity within 12 months is associated with progression to cirrhosis (54%) and death or need for liver transplantation (15%). Liver tissue examination remains the gold standard for assessing hepatic fibrosis, but laboratory and radiological tests may be useful non-invasive methods to measure the fibrotic response. Severe liver inflammation can confound radiological assessments, and the preferred non-invasive test in autoimmune hepatitis is uncertain. Individualised treatment adjustments and adjunctive anti-fibrotic therapies are poised for study in this disease. The prevention and reversal of hepatic fibrosis are achievable objectives in autoimmune hepatitis. Strategies that evaluate individualised therapies adjusted to the rapidity and completeness of the inflammatory response, and the use of adjunctive anti-fibrotic interventions, must be evaluated.

A Prospective, Randomized, Noninferiority Trial of Steroid Dosing After Major Colorectal Surgery

To evaluate the safety of perioperative low-dose steroids (LDS) versus high-dose steroids (HDS) in steroid-treated patients with inflammatory bowel disease (IBD) undergoing major colorectal surgery. Corticosteroid-treated patients undergoing major colorectal surgery are commonly prescribed HDS to prevent perioperative adrenal insufficiency and cardiovascular collapse. There is little evidence to support this practice. We performed a single-blinded noninferiority trial to compare perioperative hemodynamic instability in 92 steroid-treated IBD patients undergoing major colorectal surgery. Patients were randomly assigned to receive perioperative high-dose corticosteroids (HDS; hydrocortisone, 100 mg, intravenously 3 times daily, followed by taper) or low-dose corticosteroids (LDS; intravenous hydrocortisone equivalent to presurgical oral dosing, followed by taper). The primary outcome was the absence of postural hypotension on postoperative day 1, defined as a decrease in systolic blood pressure by 20 mm Hg after sitting from a supine position. The primary outcome, absence of postural hypotension on postoperative day 1, occurred in 95% of those randomized to receive high doses of corticosteroids compared with 96% of those who received low doses (noninferiority 95% confidence interval=-0.08 to 0.09; P=0.007). In IBD patients undergoing abdominal surgery, the incidence of postural hypotension or adrenal insufficiency is similar among those receiving high doses or low doses of corticosteroids in the perioperative period. To reduce complications associated with unnecessarily high doses of steroids, steroid-treated IBD patients undergoing major colorectal surgery should be treated with low doses of steroids in the perioperative period. (Clinicaltrials.gov ID# NCT01559675).

Anti-TNF Therapy and Radiation Exposure in Ulcerative Colitis

Purpose: Patients with ulcerative colitis [UC] may be exposed to radiation for evaluation of disease with inherent risks from protracted exposure. Bolder definitions of disease control have changed treatment paradigms with earlier introduction of biological therapy. Our aim was to compare the effective radiation dose prior to, a year after, and 3 years after initiating anti-TNF therapy or corticosteroid. Methods: We performed a retrospective review of UC patients treated with anti-TNF therapy (infliximab or adalimumab) or corticosteroids at our institution from 2005 to 2013. Clinical data (demographics, disease characteristics, treatment) were obtained from case notes and electronic patient records. All instances of imaging in the previous year, 1 year after, and 3 years after initiation of anti-TNF therapy were recorded. The effective and cumulative radiation doses were calculated from published tables [Royal College of Radiologists, UK]. Results: We analyzed 87 patients with ulcerative colitis (57 anti-TNF and 30 corticosteroidtreated). In the anti-TNF group, 70% were males with median age 48 years (range 25-76) and mean disease duration 9.2 years. Forty-seven percent had left-sided disease, and 53% had pancolitis. Of 30 corticosteroid-treated patients, 57% were males (median age 51 years; range 17-90; mean disease duration 7.7 years). Proctitis, left-sided disease, and pancolitis were seen in 10%, 47%, and 43%, respectively. The anti-TNF cohort had a significant reduction in the number of imaging studies (4.0 +/3.9 vs. 1.5 +/-2.9, p<0.0001) and cumulative radiation dose (4.1 +/-7.0 vs. 1.2 +/-3.9 mSv, p<0.0001) a year after treatment. The corticosteroid group had no significant change in the number of imaging studies (1.9 +/-2.0 vs. 1.3 +/-2.4, p=0.1) or cumulative radiation dose (3.2 +/-5.2 vs. 1.0 +/-3.1 mSv, p=0.5). There was a significant reduction in the median number of imaging studies in the anti-TNF cohort (three studies in the year before vs. one study in the year after) compared to the steroid cohort (one study in the year before and after) [p=0.01]. In 22 patients, after 3 years of anti-TNF, there was no significant change in the cumulative radiation dose (1.6 vs. 1.0 mSv, p=0.3) or number of imaging studies (2.7 vs.1.9, p=0.3). In the corticosteroid group, there was no significant change in the cumulative radiation dose (2.5 vs. 1.1 mSv, p=0.3) or number of imaging studies (1.6 vs. 1.7, p=0.5) at the end of 3 years. The cumulative radiation dose between the year preceding, and 3 years following, therapy showed no significant difference between the groups. Conclusion: Anti-TNF, but not corticosteroid, therapy is associated with a significant reduction in diagnostic imaging studies a year after therapy. This difference was not borne out at 3 years.

Enhancing Angiogenesis in Invasive Aspergillosis: A Novel Therapeutic Approach

Invasive aspergillosis is one of the most devastating opportunistic infections in immunocompromised hosts, such as those with hematologic malignancies and those undergoing hematologic cell transplantation (HCT). Despite the recent availability of potent antifungal agents, mortality rates remain unacceptably high for invasive aspergillosis in these 2 patient groups, at 42% and 58%–72%, respectively [1–3]. One of the reasons for this lack of improvement in outcomes with current therapeutic regimens may lie in the pathogenesis of invasive aspergillosis. The major risk factors for invasive aspergillosis are neutropenia (ie, chemotherapy-induced neutropenia in patients with hematologic malignancies and HCT recipients in the early, preengraftment phase) and corticosteroid treatment (ie, for graft-versus-host disease during the postengraftment phase of HCT). The immunosuppression induced by these agents and the resulting pathogenesis of invasive aspergillosis may differ between these 2 immunosuppressive states. Aspergillus conidia are inhaled through the sinopulmonary tract and land in the pulmonary alveoli. In the immunocompetent host, the first lines of defense are the alveolar macrophage and the neutrophil. If the patient is immunosuppressed, either with cytotoxic agents (inducing neutropenia) or corticosteroids (impairing macrophage function), conidia survive and go on to germinate into hyphae. These hyphae then proceed to invade the alveolar endothelial cells and extend into the pulmonary arterioles, the final act of angioinvasion. Penetration of endothelial cells results in endothelial cell damage, proinflammatory cytokine release, activation of the coagulation cascade, and intravascular coagulation [4]. These events, in turn, lead to tissue hypoperfusion and tissue necrosis. Intravascular coagulation, tissue hypoperfusion, and necrosis lead to an ideal state for the survival and progression of Aspergillus hyphae, a sequestered infection in a privileged site without access to fungicidal macrophages or neutrophils or antifungal agents. There are differences, however, between the responses in neutropenic and corticosteroid-treated hosts. While the pulmonary lesions in neutropenic patients consist predominantly of angioinvasion and intravascular hemorrhage, the lesions in corticosteroid-treated patients consist mainly of neutrophilic and monocytic infiltrates and inflammatory necrosis [5]. Thus, although the result, tissue necrosis, is the same in both types of immunosuppression, the mechanisms, coagulative vs inflammatory necrosis, differ. Angiogenesis, the formation of new blood vessels from existing blood vessels, is a physiologic response to tissue inflammation and ischemia [6]. Thus, it is not surprising that Aspergillus infection induces angiogenesis. It was demonstrated that Aspergillus fumigatus hyphae stimulate the production of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 8 (IL-8) by endothelial cells [7] and that these are potent inducers of proangiogenic signaling pathways involving vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) [8]. A. fumigatus, however, produces many metabolites, including fumagillin and gliotoxin, that demonstrate antiangiogenic activity [9–12]. Thus, to determine the balance between proangiogenic and antiangiogenic factors in invasive aspergillosis, Ben-Ami et al [13] studied angiogenesis in a neutropenic model of cutaneous invasive aspergillosis. They noted that angiogenesis was suppressed by Aspergillus-infected mice, when compared to uninfected mice. The antiangiogenic effect was completely abolished Received and accepted 10 December 2012; electronically published 9 January 2013. Correspondence: James I. Ito, MD, Division of Infectious Diseases, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 ( jito@coh.org). The Journal of Infectious Diseases 2013;207:1031–3 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/infdis/jis944

A comparative study of the immune modulating properties of antifibrinolytics in cardiac surgery

PurposeAntifibrinolytics, used in cardiac surgery to abate postoperative blood loss, share anti-inflammatory properties by suppression of pro-inflammatory D-dimer and plasmin levels. Additional drug specific immune modulating qualities are often mentioned in the discussion on which antifibrinolytic can best be used. To determine the extent and relevance of these effects, we investigated cytokine and growth factor plasma levels in cardiac surgery patients randomized to receive either tranexamic acid, aprotinin, or placebo. Corticosteroid-treated patients served to put the effects in perspective. MethodsUsing a biochip immunoassay, plasma of 36 cardiac surgery patients was quantified for 12 cytokines and growth factors, assessed preoperatively and 6, 12, 24, and 48h after the start of cardiopulmonary bypass. Eight patients were treated with tranexamic acid, nine with aprotinin, and nine received placebo. Ten placebo-treated patients received corticosteroids. ResultsIL-1ß, IL-6, IL-8, IL-10, IFN-γ, TNF-α, VEGF, MCP-1, and EGF plasma concentrations significantly changed over time across all patients. Aprotinin-treated patients showed decreased pro-inflammatory TNF-α and peak MCP-1 plasma levels when compared with placebo. However, corticosteroids attenuated the inflammatory response to a much larger extent, lowering postoperative IL-6, IL-10, IFN-γ, and VEGF concentrations also. ConclusionsAprotinin attenuates postoperative pro-inflammatory levels TNF-α and MCP-1 whereas tranexamic acid does not. The majority of plasma proteins studied, however, were not affected by the use of antifibrinolytics when compared with placebo. A clinically relevant common anti-inflammatory effect through inhibition of fibrinolysis seems therefore unlikely.

INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

Infectious complications have been known to be a major cause of morbidity and mortality in Chronic Lymphocytic Leukemia (CLL) patients who are prone to infections because of both the humoral immunodepression inherent to the hematologic disease and to the immunosuppression related to the therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The subsequent introduction of monoclonal antibodies in therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles.Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

Corticosteroid-Induced Osteoporosis

Long-term corticosteroid treatment is the most common secondary cause of bone loss. Patients treated with long-term corticosteroid therapy may develop osteopenia or osteoporosis, and many have fractures. It is difficult to predict which corticosteroid-treated patients will develop significant skeletal complications because of variability in the underlying diseases treated with corticosteroids, and because of variation in corticosteroid dose over time. Corticosteroid therapy causes an alteration in the ratio between osteoprotegerin (OPG) and receptor activator of nuclear factor κ B (RANK) ligand (RANKL), which leads to early increased bone resorption for the first 3-6 months, with long-term treatment leading primarily to suppression of bone formation. Recently published recommendations advise the use of bisphosphonates or teriparatide in high-risk patients, depending on fracture risk assessed by bone mineral density testing. This article gives an update of current knowledge regarding the pathophysiology, clinical presentation and evaluation, and prevention and treatment of patients with corticosteroid-induced osteoporosis.

Infliximab and complications after colectomy in patients with ulcerative colitis

BackgroundInfliximab treatment may increase the risk of subsequent postoperative complications in patients with ulcerative colitis. The main purpose of the present study therefore was to assess postoperative complications in patients who have undergone colectomy for ulcerative colitis with and without previous infliximab treatment. MethodsThrough a database search within a five-year period ulcerative colitis patients in a single highly specialized department, who had undergone colectomy, were identified. In total 71 ulcerative colitis patients were identified and analyzed according to pretreatment with infliximab or not. Twenty patients who had received infliximab within 12weeks prior to colectomy were compared to 51 patients on standard treatment. Data on patient background, concomitant medication, endoscopic and the laboratory results, clinical activity, and complications within 30days after colectomy were recorded. ResultsAt primary surgery, patient groups were similar with respect to distribution on gender, age, smoking behavior and concomitant medication. There were significant differences in partial Mayo-scores (7,95 (IFX) vs. 7,64, P=0.032); preoperative CRP-levels (42,72 (IFX) vs. 63,2, P=0.05); postoperative hospitalization time (10,9 (IFX) vs. 11,3days, P=0.039); and in number of patients who underwent elective surgery (10% vs. 37,3%, P=0.015). There was no short-term mortality in either group and no significant difference in terms of postoperative complications between patients treated with IFX or not. However, the number of postoperative infectious complications was increased in corticosteroid-treated patients irrespective of IFX or not (45,8% in CS group vs. 13,0%, P=0.028). ConclusionsThe use of infliximab does not seem to associate with an increased risk of short-term postoperative complications in ulcerative colitis.

Three-dimensional models of 14α-sterol demethylase (Cyp51A) from Aspergillus lentulus and Aspergillus fumigatus: an insight into differences in voriconazole interaction

Aspergillus lentulus, an Aspergillus fumigatus sibling species, is increasingly reported in corticosteroid-treated patients. Its clinical significance is unknown, but the fact that A. lentulus shows reduced antifungal susceptibility, mainly to voriconazole, is of serious concern. Heterologous expression of cyp51A from A. fumigatus and A. lentulus was performed in Saccharomyces cerevisiae to assess differences in the interaction of Cyp51A with the azole drugs. The absence of endogenous ERG11 was efficiently complemented in S. cerevisiae by the expression of either Aspergillus cyp51A allele. There was a marked difference between azole minimum inhibitory concentration (MIC) values of the clones expressing each Aspergillus spp. cyp51A. Saccharomyces cerevisiae clones expressing A. lentulus alleles showed higher MICs to all of the azoles tested, supporting the hypothesis that the intrinsic azole resistance of A. lentulus could be associated with Cyp51A. Homology models of A. fumigatus and A. lentulus Cyp51A protein based on the crystal structure of Cyp51p from Mycobacterium tuberculosis in complex with fluconazole were almost identical owing to their mutual high sequence identity. Molecular dynamics (MD) was applied to both three-dimensional protein models to refine the homology modelling and to explore possible differences in the Cyp51A–voriconazole interaction. After 20ns of MD modelling, some critical differences were observed in the putative closed form adopted by the protein upon voriconazole binding. A closer study of the A. fumigatus and A. lentulus voriconazole putative binding site in Cyp51A suggested that some major differences in the protein's BC loop could differentially affect the lock-up of voriconazole, which in turn could correlate with their different azole susceptibility profiles.

Urinary interleukin-6 (IL-6) and transforming growth factor (TGF-β) levels in corticosteroidtreated patients with IgA nephropathy

Interleukin-6 (IL-6) and transforming growth factor-β (TGF-β) are implicated in the progression of IgA nephropathy, which is usually treated with corticosteroids. Urinary IL-6 and TGF-β were measured in 21 proteinuric patients with IgA nephropathy, before and after treatment with corticosteroids, to estimate the activity of the disease after remission of proteinuria. Urinary IL-6 and TGF-β levels at diagnosis were significantly higher in patients with IgA nephropathy compared to healthy subjects. TGF-β levels, were significantly higher in patients with proteinuria > 1 g/24 h and/or severe mesangial proliferation. Although a significant reduction of proteinuria was observed with corticosteroid treatment, urinary IL-6 and TGF-β levels remained elevated. Deterioration of renal function over a period of 5 years was observed in 3 patients. High urinary IL-6 levels at diagnosis represent a significant parameter distinguishing patients with progressive course in comparison to those with favorable clinical outcome (p = 0.01). Treatment of patients with IgA nephropathy with corticosteroids is followed by remission of proteinuria but still increased urinary IL-6 and TGF-β excretion. This may be related to an ongoing inflammatory process within the kidney, and further research is required to estimate the value of urinary IL-6 and TGF-β as markers of activity of the disease.

Evaluation of B-cell activating factor in corticosteroid-treated systemic lupus erythematosus patients

Evaluation of B-cell activating factor in corticosteroid-treated systemic lupus erythematosus patients

The effectiveness of narrow-band phototherapy, corticosteroid, and methotrexate on clinical picture and serum level of soluble interleukin-2 receptors among vitiligo patients

Objective Vitiligo is a specific type of leukoderma characterized by depigmentation of the epidermis. This study aimed to compare the effectiveness of methotrexate, narrow-band phototherapy, and corticosteroid as three different treatment modalities for vitiligo. Patients and methods The study included 52 patients suffering from nonsegmental vitiligo and 20 healthy participants that served as the control group. They were recruited from the Dermatology Outpatient Clinic, National Research Center (Cairo, Egypt). The patients were randomly divided into three groups according to the treatment modalities (narrow-band ultraviolet radiation, methrotrexate, and corticosteroids). Clinical evaluation and serum level of soluble interleukin-2 receptor (sIL-2R) estimation were performed before and after treatment with follow-up duration of 6 months. Results The serum level of sIL-2R was significantly higher among patients compared with controls. The study also showed a highly statistically significant lowering of serum level of sIL-2R among both narrow-band-treated and corticosteroid-treated patients, whereas the decrease was not statistically significant among those treated with methotrexate. No statistically significant difference was detected between the three groups of patients regarding clinical response to treatment or severity of the disease. However, regarding patient satisfaction it was significantly higher among both narrow-band-treated and corticosteroid-treated patients compared with those belonging to the methotrexate group. A statistically significant negative correlation between patient satisfaction and serum level of sIL-2R after treatment was detected. Conclusion No statistically significant difference was detected between the three modalities of treatment (narrow-band ultraviolet radiation, methrotrexate, and corticosteroids) regarding clinical response or severity of the disease. However, only narrow band and corticosteroid significantly decreased the serum level of sIL-2R. Patients receiving methotrexate reported the least satisfaction compared with the other two groups.

Cognition and dorsolateral prefrontal cortex volume in corticosteroid‐treated patients given lamotrigine

AbstractIn addition to changes in declarative memory and the hippocampus, corticosteroid excess is associated with prefrontal cortex changes. We previously reported that patients receiving exogenous corticosteroid therapy had impaired performance on prefrontal cortex‐related tasks, including working memory and executive functioning tasks. Glutamate release inhibitors attenuate corticosteroid‐effects on the hippocampus in both animal and human models. Twenty‐eight outpatients receiving chronic prednisone therapy for transplant rejection or other medical conditions were randomized to lamotrigine (a glutamate release inhibitor) or placebo for 24 weeks. Dorsolateral prefrontal cortex (DLPFC) volume was manually traced from MRI scans by trained staff members. Cognition was examined using the Stroop Color Word Test (SCWT), Delis‐Kaplan Executive Function System (D‐KEFS) and the Trail Making Test. Groups were compared using analysis of covariance. Consistent with prior findings in corticosteroid‐treated patients, baseline cognitive function was in the low normal range. At baseline, prednisone duration showed a trend towards negative correlation with SCWT and D‐KEFS inhibition switching time error scores, and DLPFC volume showed a trend towards a positive correlation with SCWT scores. No significant between‐group differences in outcomes were observed following lamotrigine therapy. Thus, this study found lamotrigine to not be associated with either positive or negative effects on cognition or DLPFC volume. Copyright © 2010 John Wiley &amp; Sons, Ltd.

A Short Burst of Oral Corticosteroid for Children with Acute Asthma: Is There an Impact on Immunity?

Background: We wished to examine the impact of a short course of oral corticosteroids on the immune function of children with acute asthma and explore the mechanism of immune suppression, if any. Methods: We conducted a prospective cohort study of children aged 3–17 years presenting with acute asthma to the emergency department. The exposure of interest was a short course of systemic corticosteroids. In emergency department, corticosteroid-treated and nonexposed children were immunized with 3 antigens, namely, a neoantigen (Bacteriophage φX 174) and 2 recall antigens (diphtheria and tetanus). After 5 ± 1 weeks, children were reimmunized with Bacteriophage φX 174. Antibody titers were measured 1, 2 (peak), and 5 weeks after the primary immunization, and 1 week (peak) after the secondary one. Results: We enrolled 41 children, 27 treated with and 14 unexposed to oral corticosteroids. Corticosteroid-treated children displayed an 85% lower adjusted total (IgG and IgM) peak titers to the primary Bacteriophage immunization compared to controls [ratio of geometric means (95% confidence interval): 15% (5% to 43%)]. There were no group differences in the rise of diphtheria or tetanus antibodies. After the secondary Bacteriophage immunization, corticosteroid-treated patients showed no significant group difference in peak total titers [ratio of geometric means (95% confidence interval): 1.84% (0.66%, 5.10%)], amplification and absolute, and percent IgG titers as compared to unexposed children. Conclusions: In children with acute asthma, a short course of oral corticosteroids may be associated with depressed immune response to a new antigen, with recovery within 6 weeks and no apparent impact on response to known antigens.