Chronic Corticosteroid Use Research Articles

Rate of Cataracts Across the Eltrombopag Clinical Studies in Patients with Chronic Immune Thrombocytopenia

Abstract 1164▪▪This icon denotes a clinically relevant abstract Introduction:Systemic corticosteroids, a common first-line treatment for chronic immune thrombocytopenia (ITP), are known to be associated with an increased risk of cataracts. Feudjo-Tepie et al (2009) determined that the rate of cataracts was higher in patients treated with oral corticosteroids (14.0/1000 patient years [PYs] vs 6.0/1000 PY). Eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, is approved for the treatment of chronic ITP, a disease characterized by low platelet counts. Preclinical studies of eltrombopag in young rodents showed the potential for cataract development at doses ≥4 times the human clinical exposure. The potential for an association between treatment with eltrombopag and an increased risk for cataracts was assessed in 5 clinical trials in chronic ITP. Methods: Ocular data from 5 trials were analyzed: 2 placebo-controlled, 6-week studies, TRA100773A (phase 2) and TRA100773B (phase 3); a 6-month, placebo-controlled phase 3 study (RAISE); a phase 2 study with 3 intermittent treatment cycles of up to 6 weeks (REPEAT); and an ongoing extension study (EXTEND, data from June 2006-February 2010). Ocular monitoring included assessment of ocular health history and cataract risk factors such as chronic corticosteroid use, and a complete ophthalmologic exam, including assessment of the lens using the Age-Related Eye Disease Study (AREDS) lens opacity grading protocol (AREDS Research Group, 2001). Ocular exams were performed at baseline, frequently during treatment, and 6 months following discontinuation of treatment. A Clinical Events Committee (CEC) composed of 3 external ophthalmologists was assembled to provide external medical review of the ocular data across the eltrombopag program. The CEC adjudicated the presence or absence of cataracts from treatment-blinded data and, where possible, made attributions of potential relatedness to study medication. Results: At baseline, 47/392 patients (12%) had pre-existing cataracts or were aphakic/pseudophakic. Across the trials, chronic corticosteroid use was the most commonly reported cataract risk factor, reported in 62% of patients with risk factor assessment. After CEC adjudication, in the two 6-week trials, 2/49 placebo-treated patients (4%) and 6/112 eltrombopag-treated patients (5%) had an incident cataract or progression of cataracts. All 8 patients reported prior use of corticosteroids, and 7/8 reported at least 1 risk factor for cataracts at their first ocular exam. In RAISE, 6/61 placebo-treated patients (10%) and 11/135 eltrombopag-treated patients (8%) had incident cataract or progression of cataracts. All 17 patients reported prior use of corticosteroids, identified as a risk factor at the baseline ocular exam. In REPEAT, the CEC identified 2/66 patients with potential cataract findings; given the additional risk factors in both patients, the CEC concluded there was no evidence of a drug-related increased risk of cataracts in the study. In the ongoing eltrombopag extension study, 25/299 patients (8%) had incident cataract or progression of cataracts. Twenty patients reported at least 1 cataract risk factor, and 24 patients had documented use of corticosteroids. The CEC noted variability in the AREDS lens grading, in which there was apparent progression followed by apparent regression to a lower, less severe grade on the AREDS scale. Conclusion: The CEC adjudication of the ocular data from the placebo-controlled eltrombopag studies in chronic ITP showed that a similar proportion of patients in the placebo- and eltrombopag-treatment groups had incident cataract or progression of cataracts. In the extension study, with patients exposed to eltrombopag for over 3 years, the proportion of patients with cataracts is similar to that observed in the placebo-controlled studies (despite the significant difference in exposure to eltrombopag). The noted variability in the AREDS lens grading reflects the inherent challenges for the clinician in implementing this scale in a consistent manner. Based upon the ocular data reviewed to date by the CEC, there is no evidence of an increased risk of cataract or cataract progression in chronic ITP patients treated with eltrombopag. The possibility of a relationship between eltrombopag and cataracts has not been completely excluded and is still being monitored in clinical trials. Disclosures:Cooper:GlaxoSmithKline: Honoraria. Wong:Biogen Idec: Honoraria, Research Funding; Sanofi: Research Funding; Bayer: Honoraria, Research Funding; GSK: Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Pfizer Inc: Research Funding; Roche: Research Funding; Leo Pharma: Honoraria; Johnson & Johnson: Research Funding. Brainsky:GlaxoSmithKline: Employment, Equity Ownership. Bailey:GlaxoSmithKline: Employment, Equity Ownership.

Outcomes after thyroidectomy and parathyroidectomy

Previous reports on postoperative outcomes following thyroid and parathyroid surgery are limited by relatively small sample size. We report 30-day outcomes following thyroid and parathyroid surgery and analyze factors affecting length of stay (LOS) and postoperative adverse events (AEs). The multicenter, prospective, National Surgical Quality Improvement Program (NSQIP) datasets (2007/2008) were used. Multivariable logistic regression and analysis of covariance (ANCOVA) were performed. Patients undergoing thyroidectomy, parathyroidectomy, or both were identified (n = 13,380, 6154, 1535, respectively). Thirty-day mortality was 0.08%, 0.16%, and 0.2%, respectively; 30-day morbidity was 3.50%, 3.02%, and 4.04%, respectively. Mean LOS values were 1.1 ± 1.4, 1.1 ± 2.1, and 1.4 ± 3.1 days, respectively. Congestive heart failure, dependent functional status, dialysis dependence, and chronic corticosteroid use were significantly associated with increased LOS and postoperative AE. Morbidity and mortality rates following thyroid and parathyroid surgery are low. These data could be used by third-party interests, and surgeons should be aware of them to ensure their outcomes are in the national norm.

Safety of investigative bronchoscopy in the Severe Asthma Research Program

Investigative bronchoscopy was performed in a subset of participants in the Severe Asthma Research Program to gain insights into the pathobiology of severe disease. We evaluated the safety aspects of this procedure in this cohort with specific focus on patients with severe asthma. To evaluate prospectively changes in lung function and the frequency of adverse events related to investigative bronchoscopy. Bronchoscopy was performed by using a common manual of procedures. A subset of very severe asthma was defined by severe airflow obstruction, chronic oral corticosteroid use, and recent asthma exacerbations. Subjects were monitored for changes in lung function and contacted by telephone for 3 days after the procedure. A total of 436 subjects underwent bronchoscopy (97 normal, 196 not severe, 102 severe, and 41 very severe asthma). Nine subjects were evaluated in hospital settings after bronchoscopy; 7 of these were respiratory-related events. Recent emergency department visits, chronic oral corticosteroid use, and a history of pneumonia were more frequent in subjects who had asthma exacerbations after bronchoscopy. The fall in FEV₁ after bronchoscopy was similar in the severe and milder asthma groups. Prebronchodilator FEV₁ was the strongest predictor of change in FEV₁ after bronchoscopy with larger decreases observed in subjects with better lung function. Bronchoscopy in subjects with severe asthma was well tolerated. Asthma exacerbations were rare, and reduction in pulmonary function after the procedure was similar to that in subjects with less severe asthma. With proper precautions, investigative bronchoscopy can be performed safely in severe asthma.

Impact of Systemic Corticosteroids on Healthcare Utilization in Patients With Sarcoidosis

IntroductionPractical complications of chronic systemic corticosteroid (SC) use in patients with sarcoidosis are poorly characterized. The objective of this study was to determine the impact of SC use in patients with sarcoidosis on unscheduled sarcoidosis-attributed and nonsarcoidosis-attributed healthcare utilization (SHCU and NSHCU, respectively). MethodsRetrospective analysis of patient-reported HCU between clinic visits at a university hospital sarcoidosis outpatient clinic. ResultsA total of 441 included patients had a mean (standard deviation) of 2.4 (1.2) organs involved, were followed up for a mean of 2.9 (2.4) years and received a median cumulative dose of 2680 mg of prednisone. Patients in the higher 50th percentile of cumulated SC reported a higher unadjusted mean annual SHCU (0.33 versus 0.22, P < 0.0001 by Wilcoxon rank-sum test) but a similar mean annual NSHCU (0.83 versus 1.00, P = 0.88). After adjustment for age, race and sex, persons in the higher 50th percentile of corticosteroid exposure had a similar odds of overall NSHCU (adjusted odds ratio = 1.03, 95% CI = 0.74-1.44) but a 2.2 (95% CI = 1.5-3.3) odds of greater nonsarcoidosis attributable emergency department visits. in separate analysis of the reasons for NSHCU, persons with greater SC use had a 1.74 (95% CI = 1.16-2.62) odds of more infectious disease-related complaints and a trend toward more visits for cardiovascular problems (OR = 1.49, 95% CI = 0.96-2.32). ConclusionsGreater SC use is associated with small but significant increase in HCU related to infection and increased unscheduled emergency department visits for complaints not directly attributable to sarcoidosis.

Rare case of intracranial Salmonella enteritidis abscess following glioblastoma resection: Case report and review of the literature

Background:Worldwide, Salmonella enteritidis (SE) is becoming a common cause of gastrointestinal infections by contaminated food products, mainly eggs. Extra-intestinal manifestations such as brain abscess are more commonly associated with Salmonella typhimurium and are rare in adults. We report the clinical features, treatment outcomes and risk factors predisposing our patient to Salmonella enteritidis brain abscess and discuss relevant literature.Case Description:A 57-year-old-man developed SE subdural empyema, abscess and possible ventriculitis following reoperation for progression of a right temporal glioblastoma. He initially presented with rapidly worsening headaches over a few days, with a wound discharge and associated meningeal signs. An emergent wound washout revealed pus in the epidural, subdural space and resection cavity. An external ventricular drain (EVD) was placed and cultures revealed gram negative rods. Timely intervention, EVD, and antibiotics resulted in complete resolution. Nine cases of Salmonella abscess associated with primary brain tumor have been reported in literature, most frequently caused by SE in association with glioblastoma multiforme (GBM). We describe our management and outcome in addition to discussing neurosurgical literature on the reported cases.Conclusions:Re-operative tumor surgery has a higher incidence of post-operative infections, with Gram positive cocci being the most common pathogens. Predisposing factors reported for intracranial salmonellosis include compromised immunity, diabetes, HIV, and recent travel. Chronic corticosteroid use, multiple regimens of chemotherapy, and regions of tumor necrosis likely potentiate this rare infection in GBM patients.

Screening for Osteoporotic Fractures in the Elderly: Current Guidelines and Future Directions.

Osteoporotic fragility fractures are a major health concern causing increased morbidity and mortality in the elderly population. Major risk factors for fragility fractures include, but are not limited to, advanced age, low Bone Mineral Density (BMD), and a personal or familial history of a prior adult fragility fracture. Additional factors, such as chronic oral corticosteroid use and a history of recurrent falls, have also been identified to be important risk factors in the development of fragility fractures in the elderly. Current Canadian screening and treatment guidelines are based on regular BMD testing to identify individuals at risk; however, emerging evidence continues to emphasize the importance of analysis of the many risk factors for fragility fractures in combination with BMD measurements. Risk factor assessment tools, such as the FRAXâ„¢ tool developed by the World Health Organization, are promising new methods for screening and preventative care of the elderly. In addition, changes in screening methodology within the family practice setting, such as the utilization of specific electronic medical record templates for the elderly, are potential directions for improving screening of fragility fractures in the elderly patient population.

Validation of a case definition for osteoporosis disease surveillance

A simple case definition for osteoporosis case diagnosis is feasible based upon administrative health data. This may facilitate implementation of a population-based osteoporosis surveillance program, providing information that could help to inform and guide screening, prevention, and treatment resources. Our aim was to construct and validate a simplified algorithm for osteoporosis case ascertainment from administrative databases that would be suitable for disease surveillance. Multiple classification rules were applied to different sets of hospital diagnosis, physician claims diagnosis, and prescription drug variables from Manitoba, Canada. Algorithms were validated against results from a regional bone mineral density testing program that identified bone mineral density (BMD) measurements in 4,015 women age 50years and older with at least one BMD test between April 1, 2000 and March 31, 2001. Sensitivity as high as 93.3% was achieved with 3years of data. Specificity ranged from 50.8% to 91.4% overall, and from 81.2% to 99.1% for discriminating osteoporotic from normal BMD. Sensitivity and overall accuracy were generally lower for algorithms based on diagnosis codes alone than for algorithms that included osteoporosis prescriptions. In the subgroup without prior osteoporotic fractures or chronic corticosteroid use, one simple algorithm (one hospital diagnosis, physician claims diagnosis, or osteoporosis prescription within 1year) gave accuracy measures exceeding 90% for discriminating osteoporosis from normal BMD across a wide range of disease prevalence. A relatively simple case definition for osteoporosis surveillance based upon administrative health data can achieve an acceptable level of sensitivity, specificity, and accuracy. Performance is enhanced when the case definition includes osteoporosis medication use in the formulation.

Risk of Cataract Development among Children with Juvenile Idiopathic Arthritis-Related Uveitis Treated with Topical Corticosteroids

We sought to investigate the risk of cataract development among patients with juvenile idiopathic arthritis (JIA)-associated uveitis treated with topical corticosteroids. Retrospective cohort study. We included 75 patients with JIA-associated uveitis observed from July 1984 through August 2005 at a single academic center. Clinical data on these patients were collected by chart review and were analyzed. Incidence of new-onset cataract. Risk factors for cataract development were assessed with attention paid to the use of topical corticosteroids. Over a median follow-up of 4 years, the incidence of new-onset cataract was 0.04/eye-year (EY; 95% confidence interval [CI], 0.02-0.09). Of the 60 eyes in 40 patients who received topical corticosteroid therapy, there was a dose-dependent increase in the rate of cataract development among eyes receiving topical corticosteroids. The incidence of cataract was 0.01/EY for eyes treated with < or = 3 drops daily and 0.16/EY (P = 0.0006 for log-rank test) for eyes treated with >3 drops daily. Among eyes receiving < or = 2 drops daily, the incidence of cataract was 0/EY (95% CI [1 sided], 0.03/EY). Presence of posterior synechiae, active uveitis, and use of topical corticosteroids at presentation were significantly associated with cataract development after controlling for confounding variables. Use of topical corticosteroids was associated with cataract formation independent of uveitis activity. Using longitudinal data analysis and controlling for duration of uveitis, presence and degree of active uveitis, and concomitant use of other forms of corticosteroids in a time-updated fashion, treatment with < or = 3 drops daily of topical corticosteroid was associated with an 87% lower risk of cataract formation compared with eyes treated with >3 drops daily (relative risk, 0.13; 95% CI, 0.02-0.69; P = 0.02). In our cohort, topical corticosteroid use was associated with an increased risk of cataract formation independent of active uveitis or presence of posterior synechiae. However, chronic use of topical corticosteroids dosed at < or = 3 drops daily seemed to be associated with a lower risk of cataract development relative to eyes receiving higher doses over follow-up in the setting of suppressed uveitis. Proprietary or commercial disclosure may be found after the references.

Nocardia cyriacigeorgica: a case of endocarditis with disseminated soft-tissue infection

Nocardia cyriacigeorgica is a common environmental organism. It has been isolated from clinical samples in Europe, Asia and North America, predominantly from respiratory samples but also from samples from several other sites. We present a case report of an 85-year-old female patient in the UK who was found to have a multi-focal soft-tissue infection from which N. cyriacigeorgica was isolated. She had a background history of chronic obstructive pulmonary disease and corticosteroid use for polymyalgia rheumatica. During the course of her treatment echocardiography showed the presence of a mobile heart mass attached to a valve leaflet, a major Dukes criterion for endocarditis. We suggest that in cases of disseminated Nocardia infection, endocarditis should be tested for, particularly in cases failing to respond to treatment. We also review previous reports of both N. cyriacigeorgica infection, and of endocarditis due to Nocardia species and related genera.

AGA Medical Position Statement on the Diagnosis and Management of Colorectal Neoplasia in Inflammatory Bowel Disease

The AGA Institute Medical Position Panel consisted of the authors of the technical review, a community-based gastroenterologist (Robert P. McCabe, MD, Minnesota Gastroenterology), academic-based gastroenterologists (Themistocles Dassopoulos, MD, James D. Lewis, MD, and Thomas A. Ullman, MD), an insurance provider representative (Tom James III, MD Physician Advisor, Strategic Advisory Group, Humana), a colon and rectal surgeon (Robin McLeod, MD, Mount Sinai Hospital-Canada), a pathologist (Lawrence J. Burgart, MD, Minnesota Gastroenterology), chair of the AGA Institute Clinical Practice and Quality Management Committee (John Allen, MD, Minnesota Gastroenterology), and chair of the Practice Management and Economics Committee (Joel V. Brill, MD, Predictive Health, LLC) .

Measuring exacerbations in obstructive lung disease

Using hospitalization always has been seen as a solid measurement for exacerbation in pharmacoepidemiology, but might lead to an underestimation of disease exacerbation because of a trend towards outpatient care. The aim of this study was to quantify the incidence of different exacerbation markers in obstructive lung disease and to identify predictors for these exacerbation markers. We conducted a cohort study using the PHARMO record linkage system, including demographic details and complete medication histories of more than two million community-dwelling residents in the Netherlands from 1985 onwards. Eligible patients were adult users of inhaled corticosteroids (ICS). Outcome parameters were hospitalization and short courses of systemic corticosteroids. Patients were allowed to have multiple exacerbations during follow-up. We identified 5327 patients. During follow-up, 8635 exacerbations occurred in 2332 patients with a trend in time towards treating exacerbations out of the hospital (p-value 0.003). Of all patients with exacerbations, 73% was not hospitalized during follow-up. Exacerbations were associated with high-dose ICS use (adjusted RR 1.4; 95% CI 1.2-1.7) and chronic systemic corticosteroid use (adjusted RR 1.9; 95%CI 1.6-2.2). Using hospitalization only as exacerbation marker leads to underestimating the exacerbation rate, because of exacerbation treatment out of the hospital. Patients with obstructive lung disease using chronic systemic corticosteroids or high-dose ICS use are more prone to exacerbations. This implies that these patients should be monitored carefully to prevent recurrent exacerbations which are detrimental for their prognosis and quality of life.

Repeat Contrast Medium Reactions in Premedicated Patients: Frequency and Severity

To determine the frequency, type, and severity of breakthrough and repeat breakthrough reactions to iodinated low-osmolality contrast medium (LOCM) in patients who were premedicated with corticosteroids and antihistamines. Institutional review board approval was obtained, and informed consent was waived for this retrospective HIPAA-compliant analysis. One hundred ninety breakthrough allergic-like reactions to intravenous LOCM in 175 patients with a history of contrast medium reactions were reviewed. The repeat breakthrough reactions that resulted from 197 additional LOCM-enhanced examinations performed in 58 patients after the initial breakthrough reaction were also reviewed. The Fisher exact test was used to determine if certain risk factors were associated with an increased risk of a moderate or severe breakthrough reaction. Subgroup analysis was performed to determine if the contrast medium type, contrast medium volume, and/or time between the initial (index) and breakthrough reactions affected the breakthrough reaction severity. Of 128 breakthrough reactions in which the index reaction severity was known, 103 (81%) were of a severity similar to that of the index reaction, 15 (12%) were less severe, and 10 (8%) were more severe. The severity of the breakthrough reactions in the patients with a mild index reaction was usually (in 94 [91%] of 103 reactions) mild. When the index reaction was severe, the breakthrough reaction was usually moderate or severe (in eight [42%] of 19 cases and four [67%] of six cases, respectively). The majority (174 [88%] of 197) of LOCM injections after the initial breakthrough reaction did not result in a repeat breakthrough reaction. Breakthrough reactions were significantly more likely to be moderate or severe in patients with a history of chronic oral corticosteroid use (P = .01), drug (P = .04) or severe (P < .001) allergies, or allergies to four or more allergens (P = .01). Breakthrough reactions are usually similar in severity to the index reaction, and subsequent contrast medium injections usually do not induce repeat breakthrough reactions. Breakthrough reactions are more likely to be moderate or severe in patients with certain risk factors.

Current Controversies in Critical Illness-related Corticosteroid Insufficiency and Glucocorticoid Supplementation

The stress response, which is triggered by a number of factors, including surgery, results in activation of the hypothalamic pituitary adrenal axis and subsequent release of cortisol from the adrenal glands. Critical illness-related corticosteroid insufficiency is an inadequate corticosteroid response relative to a patient's illness; patients with critical illness-related corticosteroid insufficiency have both insufficient circulating cortisol and impaired cellular use of glucocorticoids. Corticosteroids, such as hydrocortisone, have been cited to improve survival, oxygenation, duration of mechanical ventilation, and intensive care unit-free days in critically ill patients. Perioperative glucocorticoid supplementation is also recommended in patients with secondary adrenal insufficiency due to chronic corticosteroid use.

Vasculitis working group: Selected unanswered questions related to giant cell arteritis and anti-neutrophil cytoplasmic antibody-associated vasculitis

Evidence to guide assessment and management of patients with vasculitis is lacking for many important clinical questions. The evidence surrounding several common questions about management of vasculitis was reviewed. Patients with giant cell arteritis (GCA) are at risk for developing extra-cranial large vessel inflammation. Clinicians should be aware of this complication and search for large vessel involvement in patients with GCA who have ischemic symptoms. Research is needed to define optimal strategies to identify patients with such complications. Because of the hazards of chronic corticosteroid use, alternative therapies for patients with GCA have been sought but thus far no clear alternatives have been identified. Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with small-vessel vasculitis, including Wegener's granulomatosis and microscopic polyangiitis, but changes in ANCA titers should not be used as a surrogate biomarker for disease activity. Several immunosuppressive agents can be used for maintenance therapy after induction of remission in patients with ANCA-associated vasculitis, with no firm evidence that one agent is superior to others. Collectively, this review shows that more research is needed to provide a firmer body of evidence to support clinical decision-making for patients with vasculitis.

Polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is a common chronic inflammatory rheumatic disease with unknown aetiology, affecting predominately people of middle age and older. Besides clinical symptoms and diagnostics, imaging techniques including sonography and magnetic resonance imaging may provide evidence of typical inflammatory lesions with bilateral bursitis subdeltoidea or subacromialis, tenosynovitis of the biceps tendon sheath and/or synovitis of the shoulder joints and thus may support the diagnosis of this disease in difficult cases. Corticosteroids are the cornerstone of treatment of PMR, but adverse events because of chronic corticosteroid use are observed in more than 50% of treated patients. Whether immunosuppressants, such as methotrexate and tumour necrosis factor-alpha inhibitors are effective in the therapy of PMR has still not yet been clarified.

Autoantibodies in the Autoimmune Disease Pemphigus Foliaceus Induce Blistering via p38 Mitogen-Activated Protein Kinase-Dependent Signaling in the Skin

Pemphigus foliaceus (PF) is a human autoimmune blistering disease in which a humoral immune response targeting the skin results in a loss of keratinocyte cell-cell adhesion in the superficial layers of the epidermal epithelium. In PF, desmoglein-1-specific autoantibodies induce blistering. Evidence is beginning to accumulate that activation of signaling may have an important role in the ability of pathogenic pemphigus IgGs to induce blistering and that both p38 mitogen-activated protein kinase (MAPK) and heat shock protein (HSP) 27 are part of this signaling pathway. This study was undertaken to investigate the ability of PF IgGs to activate signaling as well as the contribution of this signaling pathway to blister induction in an in vivo model of PF. Phosphorylation of both p38 MAPK and HSP25, the murine HSP27 homolog, was observed in the skin of PF IgG-treated mice. Furthermore, inhibition of p38 MAPK blocked the ability of PF IgGs to induce blistering in vivo. These results indicate that PF IgG-induced blistering is dependent on activation of p38 MAPK in the target keratinocyte. Rather than influencing the immune system, limiting the autoantibody-induced intracellular signaling response that leads to target end-organ damage may be a more viable therapeutic strategy for the treatment of autoimmune diseases. Inhibition of p38 MAPK may be an effective strategy for the treatment of PF.

Risk Factors for Late Staphylococcus Aureus Bacteremia after Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Institution, Nested Case-Controlled Study

We report on the incidence, risk factors, and outcome of late Staphylococcus aureus bacteremia (SAB) in a cohort of 709 adult and pediatric patients at Memorial Sloan-Kettering Cancer Center between September 1999 and December 2006. The SAB cases were identified by prospective surveillance and examination of a computerized database. Late SAB was defined as SAB occurring > 50 days post-hematopoietic stem cell transplantation (HSCT). A nested case-controlled study was conducted to identify predictors of late SAB. The incidence of late SAB was 6/100,000 patient-days. The median time from stem cell infusion to incident blood culture was 137 days (range, 55 to 581 days). Eighty-four percent of the cases were community acquired; 40% involved a focal infection. Bacteremia was persistent (>3 days) despite removal of endovascular access in > 50% of cases. Risk factors for late SAB were acute graft-versus-host disease (aGVHD) flare, acute or chronic skin GVHD (cGVHD), corticosteroid use, liver dysfunction, and prolonged hospital length of stay (LOS) post-HSCT. In multivariate models, skin GVHD ( P = .002) and LOS ( P = .02) remained significant. The median survival post-SAB was 135 days (range, 1 to 1765 days). Late SAB occurred mainly in the setting of GVHD or corticosteroid therapy. Clinical manifestations were highly variable. Multiple comorbidities, indicated by organ dysfunction and hospitalization, likely contributed to persistence and increased morbidity and mortality. We recommend a high index of suspicion and empiric antistaphylococcal treatment pending culture results in high-risk patients undergoing HSCT.

Steroid-Free Maintenance Immunosuppression With Rapamune and Low-Dose Neoral in Pancreas Transplant Recipients

Steroid-free immunosuppression is an attractive option because it avoids the many side effects of chronic corticosteroid use. It is especially attractive in pancreas recipients because it avoids the diabetogenic effects of steroids. We evaluated the outcome of a steroid-free maintenance immunosuppressive protocol in pancreas transplant recipients. Between August 2003 and May 2006, a total of 97 pancreas transplant recipients received steroid-free maintenance immunosuppression, consisting of induction with thymoglobulin and prednisone for the first 5 days. Patients were maintained on sirolimus adjusted to a target rapamycin trough level and reduced-dose cyclosporine adjusted to target C2 levels. All pancreas transplants (n=124) performed in the previous 3 years and maintained on a steroid-based immunosuppressive protocol with cyclosporine and mycophenolate mofetil were used for comparison. One-year patient and death censored pancreas graft survival were 93.8% and 94.8% for the steroid free group versus 95.2% and 87.9% for the comparator group, respectively. The incidence of acute rejection was 9.3% in the steroid-free group versus 28.3% in the comparator group (P<0.01). No pancreas loss in the steroid-free group was caused by acute rejection, whereas seven (5.6%) patients in the comparator group lost their pancreases because of acute rejection (P<0.05). At 1 year after transplant, the mean serum glucose and creatinine levels were not different between the two groups. We conclude that excellent graft survival with a significantly lower incidence of acute rejection can be achieved using a steroid-free maintenance immunosuppressive protocol consisting of sirolimus and cyclosporine.

Thymoglobulin induction and steroid avoidance in cardiac transplantation: results of a prospective, randomized, controlled study

Chronic use of corticosteroids (CS) following transplantation is associated with significant long-term morbidities. Minimizing exposure to CS to improve long-term outcomes, without compromising allograft function, remains an important goal in transplantation. This single-center, prospective, randomized, open-label study was designed to evaluate the efficacy of Thymoglobulin as part of a CS-sparing regimen in cardiac transplantation. Thirty-two low-risk cardiac transplant patients were randomized in a 1:1 ratio to receive either a Thymoglobulin-based CS-avoidance regimen (CS-avoidance group; n = 16) or a long-term CS-based regimen with no antibody induction (control group; n = 16). Pulse CS therapy was used for the treatment of acute cellular rejection in both groups. Baseline characteristics were similar between groups. At one yr, there was no significant difference in the mean incidence of acute cellular rejection (>or=3A) episodes between the CS-avoidance and control groups, 0.81+/-1.05 and 1.07+/-1.03, respectively. Importantly, the CS-avoidance patients had significant improvement in muscle strength and less bone loss compared with the control patients during the first six months post-transplant. CS-avoidance regimen with Thymoglobulin induction appeared to be safe and effective in cardiac transplantation. Further studies are required to demonstrate the long-term safety and benefits of such a regimen.

Efeitos do uso crônico da dexametasona na cicatrização de feridas cutâneas em ratos

FUNDAMENTOS: Acredita-se que os glicocorticóides prejudiquem a cicatrização, causando decréscimo da proliferação celular, da neovascularização e da produção de matriz. OBJETIVO: Investigar os efeitos do uso crônico dos corticoesteróides na cicatrização de feridas cutâneas. MÉTODOS: Após injeções de dexametasona (0,1mg/kg/dia) por 30 dias, fez-se incisão no dorso de ratos e estudou-se a cicatrização no terceiro, sétimo e 14o dias. A resistência da cicatriz, a densidade do colágeno e a reação inflamatória foram avaliadas pela histometria. RESULTADOS: As cicatrizes do grupo tratado com dexametasona eram menos resistentes à tração em todos os tempos (p=0,008) e apresentavam menor densidade de colágeno. A do colágeno tipo III foi menor em todos os tempos estudados (p&lt;0,0001), e a do colágeno tipo I foi menor apenas no 14º dia (p&lt;0,0001). A infiltração de células inflamatórias foi menor no grupo tratado com dexametasona nas duas primeiras avaliações (p=0,001 e p=0,016), não sendo significativa a diferença no 14º dia (p=0,367). CONCLUSÕES: Verificou-se diminuição da resistência da cicatriz e baixa densidade do colágeno total em todos os tempos estudados. No início do processo observou-se baixa densidade do colágeno tipo III e mais tarde também baixa densidade do colágeno tipo I. Nos tempos iniciais houve redução do número de células inflamatórias.