Long-term Steroid Administration Research Articles

Mechanism of Actions, Efficacy, and Long-term Use of Steroids in Autoimmune Hemolytic Anemia (AIHA)

Autoimmune hemolytic anemia (AIHA) is a rare condition in which autoantibodies cause the loss of red blood cells. Steroids have been used to treat several illnesses, including AIHA. For now, steroids remain as the first line of treatment for AIHA. In AIHA, especially warm AIHA (wAIHA), steroids suppress autoantibody production and downregulate Fcγ receptors' expression on monocytes to prevent hemolysis. The type of steroids chosen for first-line therapy for wAIHA in pediatrics and adults are Prednisone (Prednisolone) and Methylprednisolone. At the same time, Dexamethasone is used as an alternative treatment in AIHA. Steroids show better therapeutic outcomes in the first 2-3 weeks of administration, but the proportion of patients who remain in remission after steroid discontinuation are still quite low. Long-term administration of steroids may affect bone, blood glucose metabolism, and hypothalamic-pituitary-adrenal axis (HPAA). However, steroids which have a linear pharmacokinetic profile, intermediate-acting glucocorticoids such as Prednisone (Prednisolone) or Methylprednisolone, and also tapering dose of steroids after 2-4 weeks administration will be safe for long term use as AIHA treatment.Keywords: steroids, glucocorticoid, corticosteroid, autoimmune hemolytic anemia, AIHA, mechanism of action, efficacy

A multicenter, randomized, placebo-controlled phase IIb trial of an autologous formalin-fixed tumor vaccine for newly diagnosed glioblastomas.

An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV. Eligible patients were adults with supratentorial GBMs, 16-75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration. An AFTV comprising fixed paraffin-embedded tumor tissue with immune adjuvants or an identical placebo without fixed tumor tissue was injected intradermally over three courses before and after chemoradiotherapy. The primary and secondary end points were overall survival (OS), progression-free survival (PFS), and 3-year survival rate. Sixty-three patients were enrolled. The average patient age was 61 years. The median KPS score was 80%, and the median resection rate was 95%. The full analysis set of 57 patients indicated no significant difference in OS (p = 0.64) for the AFTV group (median OS 25.6 months, 3-year OS rate 38%) compared with the placebo group (31.5 months and 41%, respectively) and no difference in PFS (median PFS 13.3 months in both groups, p = 0.98). For patients with imaging-based total tumor removal, the 3-year PFS rate was 81% in the AFTV group versus 46% in the placebo group (p = 0.067), whereas the 3-year OS rate was 80% versus 54% (p = 0.16), respectively. Similar results were obtained in the p53-negative subgroups. Severe adverse effects were not observed. The AFTV may have potential effects in certain patient subgroups. A phase III study for patients with total tumor removal remains warranted to confirm these findings. Clinical trial registration no.: UMIN000010602 (UMIN Clinical Trials Registry).

Precision Delivery of Steroids as a Rescue Therapy for Gastrointestinal Graft-versus-Host Disease in Pediatric Stem Cell Transplant Recipients

Graft versus host disease (GVHD) is one of the most serious complications following stem cell transplant in children and is a major cause of morbidity and mortality. Corticosteroids remain the mainstay of treatment, and although a majority of children respond to systemic steroids, those refractory to or dependent upon corticosteroids suffer from complications secondary to long-term steroid administration. This problem has prompted consideration of steroid-sparing treatment strategies, although the time to clinical remission can be variable. Intraarterial corticosteroid delivery has been used in adults as a rescue therapy in steroid-resistant patients, but its use in children has been limited. We investigated the feasibility of intraarterial steroid administration into the bowel and/or liver in a cohort of six pediatric patients with acute GVHD. All patients successfully underwent treatment with no serious adverse effects. Five of five (100%) patients with gastrointestinal bleeding due to GVHD had rapid symptom improvement by 48 h, which was durable up to three weeks. Three of four (75%) patients with hepatic GVHD had improved cholestasis following intraarterial steroid administration. Our experience with this small cohort preliminarily demonstrated the feasibility and safety of intraarterial steroid administration in children with acute GVHD. This approach warrants consideration as a rescue therapy in steroid-refractory cases and as a “bridge” therapy for children with severe acute GVHD who are transitioning to steroid-sparing regimens.

Development of triamcinolone acetonide-hyaluronic acid conjugates with selective targeting and less osteoporosis effect for rheumatoid arthritis treatments

Rheumatoid arthritis (RA) is a common systemic autoimmune disease in developed countries. In clinical treatment, steroids have been used as bridging and adjunctive therapy after disease-modifying anti-rheumatic drug administration. However, the severe side effects caused by the nonspecific targeting of organs followed by long-term administration have limited their usage in RA. In this study, poorly water-soluble triamcinolone acetonide (TA), a highly potent corticosteroid for intra-articular injection, is conjugated on hyaluronic acid (HA) for intravenous purposes with increased specific drug accumulation in inflamed parts for RA. Our results demonstrate that the designed HA/TA coupling reaction reveals >98 % conjugation efficiency in the dimethyl sulfoxide/water system, and the resulting HA-TA conjugates show lower osteoblastic apoptosis compared with that in free TA-treated osteoblast-like NIH3T3 cells. Furthermore, in a collagen-antibody-induced arthritis animal study, HA-TA conjugates enhanced the initiative targeting ability to inflame tissue and reduce the histopathological arthritic changes (score = 0). Additionally, the level of bone formation marker P1NP in HA-TA-treated ovariectomized mice (303.6 ± 40.6 pg/mL) is significantly higher than that in the free TA-treated group (143.1 ± 3.9 pg/mL), indicating the potential for osteoporotic reduction using an efficient HA conjugation strategy for the long-term administration of steroids against RA.

SURG-10. The evolving role of neurosurgery for central nervous system metastases in the era of personalized medicine

BackgroundNovel therapies translating into improved survival of patients with advanced cancer have emerged. The number of metastases in the central nervous system is therefore seen to increase. Neurosurgery assumes an expanding role within multi-disciplinary care structures for such patients.MethodsWe performed a comprehensive literature review on the current status of neurosurgery for brain metastases patients. Based on the extracted data, we developed a review from experts in the field on the role of brain metastasis surgery in the era of personalized medicine.ResultsTraditionally, three metastases were considered the cutoff to offer surgical resection. With respect to the clinical status, the resection of a symptomatic mass may nowadays be considered even in presence of multiple tumors in a multimodal setting: surgical resection of brain metastasis provides immediate relief from mass effect-related symptoms and histology in case of unknown primary tumor; surgery may help stabilizing the disease, thus enabling further therapy; and in situations where immunotherapy is considered and non-surgical management would require long-term steroid administration, surgery may also provide expeditious relief of edema and reduction of needs for steroids. In patients with multiple brain metastasis and mixed response to non-surgical therapy, tumor resampling may allow tissue analysis for expression of molecular tumor targets. In patients with leptomeningeal dissemination and consecutive hydrocephalus, ventriculo-peritoneal shunting improves quality of life but also allows for time to administer more therapy thus prolonging survival. Addressing the limited efficacy of many oncological drugs for brain metastases, clinical trial protocols in which surgical specimens are analyzed for pre-surgically administered agents may offer pharmacodynamic insights.ConclusionComprehensive neurosurgical care will have to be an integral element of multi-disciplinary oncological centres providing care to patients with brain metastases to improve on therapy and tumour biology research.

Efficacy of hydroxychloroquine for treating annular erythema associated with Sjögren's syndrome.

Annular erythema is one of the cutaneous manifestations of Sjögren's syndrome (SS). Topical corticosteroids and tacrolimus, and oral corticosteroids, have been used as treatments for this condition. However, the safety and efficacy of these treatments remains unsatisfactory, and further development of therapies are desired. In this study, we performed a retrospective analysis of 16 annular erythema associated with SS (AESS) patients treated with hydroxychloroquine (HCQ). Disease activity was assessed using a modified version of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), which we termed the modified CLASI (m-CLASI). HCQ treatment improved AESS lesions in all 16 patients. The mean m-CLASI score was reduced by 85.6% at the 12-week follow-up relative to baseline (p<0.01). Notably, 60% (6/10 cases) of patients with AESS lesions limited to the facial area achieved complete remission within 4weeks. In the analysis of six patients who had taken oral prednisolone before starting HCQ, all were able to reduce the dose within 52weeks without relapse. Particularly, 75% (3/4 cases) of patients with prednisolone dose of more than 5mg/day could reduce their dose to less than 5mg/day in combination with HCQ. For the safety concerns, two patients experienced grade 1 diarrhea during the 52-week observation period. However, neither serious adverse events nor adverse events requiring discontinuation of treatment occurred. The results of the present study suggest that HCQ may not only be highly effective as a single agent, but may also be useful as a steroid-sparing agent in refractory case requiring long-term steroid administration, making it a good treatment option for AESS.

Ruxolitinib Alleviates Uveitis Caused by Salmonella typhimurium Endotoxin.

Uveitis is characterized by inflammatory lesions of intraocular structures. It is one of the important manifestations in patients with Reiter’s syndrome, an inflammatory arthritis, which is caused by enteric infection with bacteria, including Salmonella typhimurium. Corticosteroids remain the most frequently used therapies against uveitis associating with inflammatory arthritis. However, the long-term administration of steroids results in many side effects, and some uveitis patients do not respond to steroid treatment. Non-steroidal treatments are needed for uveitis patients. Our previous study found that Janus kinase (JAK) 1/2 inhibitor, ruxolitinib could suppress the expression of proinflammatory mediators in the ciliary body and iris. However, the impacts of ruxolitinib on ophthalmic features in uveitic eyes are still unknown. In this study, Salmonella typhimurium endotoxin-induced uveitis (EIU) was induced in Sprague Dawley rats by the injection of lipopolysaccharide (LPS). Compared with LPS-induced rats treated with water, ruxolitinib significantly attenuated the clinical manifestations, infiltrating cells and protein exudation in the aqueous humor, and retina–choroid thickening. Amplitudes of b-wave in both scotopic and photopic electroretinogram (ERG), and the amplitude of a-wave in scotopic ERG in EIU animals were alleviated by ruxolitinib. Collectively, we propose ruxolitinib could attenuate endotoxin-induced uveitis and rescue visual functions in rats by inhibiting the JAK2-STAT3 pathway.

Update in immunosuppressive therapy of myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Immunosuppressive treatments are part of the therapeutic armamentarium in MG. Long-term systemic steroid administration carry considerable risks and adverse events. Consequently, steroid-free immunosuppressive therapy is necessary to reduce the dose or discontinue steroids. First immunosuppressive drug trials in MG, were performed in the mid-60s, using standard and nonspecific immunosuppression. Since then, only few randomized controlled clinical trials were developed in MG, showing inconclusive results; and drug efficacy was assessed in terms of its steroid-sparing capacity and the ability to reduce myasthenic signs and symptoms. Treatment strategy in MG is quite challenging, mainly due to the disease heterogeneity in terms of clinical presentation, immunopathogenesis and drug response. To solve this dilemma, emerging treatment are based on biological drugs and use new targets of the immune pathway.

Rituximab versus cyclophosphamide for the treatment of children with steroid resistance nephrotic syndrome; a clinical trial study

Introduction: The most common complications of the nephrotic syndrome (NS) are the frequent relapses, steroid resistance, and long-term steroid administration. Objectives: This study aimed to compare the therapeutic effect of rituximab versus cyclophosphamide in the prevention of relapses and the complications of treatment in children with steroid-resistant NS. Patients and Methods: This clinical trial study was performed on 50 patients with resistant steroidal NS referred to Masoumeh hospital in Qom, Iran. Patients were randomly divided into the two groups including intervention (n=20) and control groups (n=30). In addition to the prednisolone, the intervention group received 375 mg/m2/weekly rituximab intravenously for 4 weeks. The control group received oral doses of cyclophosphamide 2 mg/kg/d for 3 months. During treatment, the frequency of relapses, the mean dose of steroid and the complications of treatment were compared with a paired t-test, independent t-test, and chi-square test. Results: A significant decrease in the mean dose of steroids and the mean number of relapses were seen in patients after administration of rituximab and cyclophosphamide (P&lt;0.001). However, rituximab reduced the dose of steroid administration by 12.25 mg/d, while cyclophosphamide reduced only 2.83 mg/d (P&lt;0.001). Rituximab reduced the relapse rate two times on average, while cyclophosphamide reduced only 0.5 times (P&lt;0.001). The incidence of complications in the cyclophosphamide group was found to be more severe than the rituximab group. Conclusion: To compare rituximab versus cyclophosphamide regarding lower the frequency of recurrence after treatment, we found rituximab is a more suitable drug for the treatment of steroid-resistant NS than cyclophosphamide.

Periodically repeated rituximab administrations in children with refractory nephrotic syndrome: 2-year multicenter observational study.

Rituximab (RTX) is effective in maintaining remission in patients with nephrotic syndrome (NS), but a standard protocol of RTX administration has not been established. This study was a 2-year multicenter observational study, in which consistent treatments and evaluations were performed. We enrolled pediatric patients with refractory NS between January 2015 and December 2015. RTX infusion was performed four times at 6-month intervals, followed by mizoribine pulse therapy with early discontinuation of calcineurin inhibitor (CNI). Primary endpoints were the relapse-free survival rate and the number of relapses after RTX administration. Secondary endpoints were changes in side effects associated with long-term steroid administration. Twenty-two patients were analyzed. The relapse-free survival rate at 1year and 2years was 50 and 46%, respectively. Twenty-one patients accomplished our protocol and the frequency of relapse was reduced under the discontinuation of CNI. Although two patients were diagnosed with frequent relapse and/or steroid dependency during the observation period, the frequency of relapse decreased with each rituximab dose. Statistically significant improvements in all steroid complications were observed in the final examination, but no significant improvements were observed from 1 to 2years after RTX administration. One patient had agranulocytosis, and three patients showed electrocardiographic abnormalities. Our protocol was useful and safe for refractory NS. However, RTX administration four times might have been excessive in patients who had no relapse by 1year after the initial RTX administration. Further investigation of the most appropriate method of RTX administration is required.

352 The Effect of Epidural Steroid Injections on Bone Mineral Density and Vertebral Fracture Risk

Abstract INTRODUCTION Epidural steroid injections (ESIs) are a common treatment for the management of patients with radicular back pain. It is also known that the long-term enteral administration of exogenous steroids disrupts bone health and skeletal micro-architecture METHODS A systematic and critical review of recent literature was conducted in accordance with PRISMA guidelines. RESULTS &gt;A total of 8 studies were included in the analysis (6 retrospective, 2 prospective). A total of 7233 patients with a mean age ranging between 49 and 74 years and an average follow-up between 6 and 60 months were studied. Steroids that were used included triamcinolone, dexamethasone, and methylprednisolone (MP), with a mean number of injections ranging from 1 to 14.7 and average cumulative dose in MP equivalents between 80 and 8130 mg. A single ESI was shown to decrease BMD as measured at the femoral neck by 1.8%, and increase the risk of vertebral fracture by 21%. Significant reductions in BMD were associated with a cumulative MP dose of 200 mg over a one year period and 400 mg over three years, but not in doses of less than 200 mg of MP equivalents for postmenopausal women and at least 3 g for healthy men. The risk of osteopenia and osteoporosis was lower in patients that were receiving anti-osteoporotic medication during the treatment course. CONCLUSION ESIs can decrease BMD, both locally (lumbar spine) and systemically (femoral neck) and increase the risk of vertebral fracture. Therefore, ESIs should be recommended with caution, especially in patients at risk for osteoporotic fractures, such as women of postmenopausal age. Anti-osteoporotic medication might be considered prior to ESI.

Clinical Course of Oral Squamous Cell Carcinoma in Patients on Immunosuppressant and Glucocorticoid Therapy

Depressed immune function is a serious adverse effect of long-term immunosuppressant or steroid administration at doses that exceed the physiologically required amount. The purpose of this study was to determine the effects of immunosuppression on carcinogenesis, particularly malignant tumor development, in patients with oral squamous cell carcinoma who had immunosuppression because of immunosuppressant therapy with or without steroid therapy administered for different underlying diseases. In this retrospective chart review, 886 patients with oral squamous cell carcinoma who received treatment at the authors' department from April 2001 through December 2011 were included. Their clinical characteristics; tumor, node, and metastasis (TNM) stage; initial treatment for the primary cancer; mode of cervical lymph node metastasis; incidence rate of distant metastases; white blood cell, neutrophil, and lymphocyte counts on initial examination; and therapeutic outcomes were evaluated and compared between patients on and those not on immunosuppressant therapy with or without steroid therapy. Survival rates were calculated using the Kaplan-Meier method. Fourteen eligible patients (5 men, 9 women; mean age, 65.2yr) were identified who were on immunosuppressant therapy with or without steroid therapy. They exhibited considerably more metastases, extracapsular spread, and distant metastases, and the number of metastases and extracapsular spread were statistically significant (P= .0213, P= .042, respectively). In 9 patients, total lymphocyte count in the peripheral blood was no higher than 1,500/μL, indicating the lower limit of the normal range. One patient died of recurrence of the primary tumor. Another patient died of cervical lymph node recurrence. Distant metastases occurred in 2 patients. The cumulative disease-specific 5-year survival rate of patients receiving immunosuppressive therapy was 62.3% and that of patients with cervical lymph node metastasis was 25%. The results of this study suggest that patients with oral squamous cell carcinoma on immunosuppression therapy show progression of cervical lymph node metastasis and extracapsular spread and are at high risk of developing distant metastases.

How I manage Evans Syndrome and AIHA cases in children.

The management of Evans Syndrome in children is challenging due to the lack of evidence-based data on treatment. Steroids, the first-choice therapy, are successful in about 80% of cases. For children who are resistant, relapse or become steroid-dependent, rituximab is considered a valid second-line treatment, with the exception of those with an underlying diagnosis of autoimmune lymphoproliferative syndrome who may benefit from other options such as mycophenolate mofetil and sirolimus. Better knowledge of the immunological mechanisms underlying cytopenias and the availability of new immunosuppressive drugs can be helpful in the choice of more targeted therapies that would enable the reduction of the use of long-term steroid administration or other more aggressive options, such as splenectomy or stem cell transplantation. This manuscript provides an overview of the pathogenic background of the disease, and suggests a clinical approach to diagnosis and treatment with a particular focus on the management of relapsing/resistant disease.

ABSTRACT 859

Background and aims: Lithium battery ingestion can cause corrosive esophageal ulcer. Aims: The aim of this study is to assess the appropriateness of treatment for corrosive ulcer, especially using steroids for preventing esophageal stricture. Methods: A 20 month-old boy presented to the emergency room 1.5 hour after swallowing a lithium battery 20mm in diameter. By esophagoscopy the battery was found at the bottom of pyriform sinusitis but it could not be removed. Under direct laryngoscopy, the Otorhinolaryngologist finally removed the battery 7.5 hour after ingestion using long forceps. The posterior wall of the esophagus had a 3rd degree alkali burn and the patient suffered from larygeal edema. We performed (i) endotracheal intubation, (ii) insertion of nasogastric tube for tube feeding and preventing esophageal stricture, (iii) administration of dexamethasone for preventing esophageal scarring and stricture with an initial dose of 1mg/kg/day. Results: Nine days later, laryngoscopy revealed that the esophageal ulcer had improved and there was no longer any laryngeal edema. The dose of dexamethasone was reduced to 0.75mg/kg/day for 7 days, following 0.5mg/kg/day for the next 7 days, 0.35mg/kg/day for the next 7 days, 0.25mg/kg/day for the next 7 days and 0.15mg/kg/day for the next 7 days. Upper digestive tract test revealed no evidence of leakage nor stricture. The patient started to eat minced meal and nasal gastric tube was removed 30 days after admission. Four months later, he was able to eat normally. Conclusions: In this case, long term administration of steroids may prevent esophageal stricture. Further studies are needed to decide the appropriate dose and period of steroid administration.

Intra-Erythrocyte Infusion of Dexamethasone Reduces Neurological Symptoms in Ataxia Teleangiectasia Patients: Results of a Phase 2 Trial

BackgroundAtaxia Teleangiectasia [AT] is a rare neurodegenerative disease characterized by early onset ataxia, oculocutaneous teleangiectasias, immunodeficiency, recurrent infections, radiosensitivity and proneness to cancer. No therapies are available for this devastating disease. Recent observational studies in few patients showed beneficial effects of short term treatment with betamethasone. To avoid the characteristic side effects of long-term administration of steroids we developed a method for encapsulation of dexamethasone sodium phosphate (DSP) into autologous erythrocytes (EryDex) allowing slow release of dexamethasone for up to one month after dosing. Aims of the study were: the assessment of the effect of EryDex in improving neurological symptoms and adaptive behaviour of AT patients; the safety and tolerability of the therapy.MethodsTwenty two patients (F:M = 1; mean age 11.2 ± 3.5) with a confirmed diagnosis of AT and a preserved or partially supported gait were enrolled for the study. The subjects underwent for six months a monthly infusion of EryDex. Ataxia was assessed by the International Cooperative Ataxia Rating Scale (ICARS) and the adaptive behavior by Vineland Adaptive Behavior Scales (VABS). Clinical evaluations were performed at baseline and 1, 3, and 6 months.ResultsAn improvement in ICARS (reduction of the score) was detected in the intention-to-treat (ITT) population (n = 22; p = 0.02) as well as in patients completing the study (per protocol PP) (n = 18; p = 0.01), with a mean reduction of 4 points (ITT) or 5.2 points (PP). When compared to baseline, a significant improvement were also found in VABS (increase of the score) (p < 0.0001, ITT, RMANOVA), with statistically significant increases at 3 and 6 months (p < 0.0001). A large inter-patient variability in the incorporation of DSP into erythrocytes was observed, with an evident positive effect of higher infusion dose on ICARS score decline. Moreover a more marked improvement was found in less neurologically impaired patients. Finally, a 19 month-extension study involving a subgroup of patients suggested that Erydex treatment can possibly delay the natural progression of the disease.EryDex was well tolerated; the most frequent side effects were common AT pathologies.ConclusionsEryDex treatment led to a significant improvement in neurological symptoms, without association with the typical steroid side effects.Trial registrationCurrent Controlled Trial 2010-022315-19SpA

Steroid-induced Spinal Epidural Lipomatosis after Suprasella Tumor Resection.

Spinal epidural lipomatosis (SEL) is an abnormal localized accumulation of fat tissues in the epidural space. It is strongly related with steroid administration. The symptoms of SEL are various and range from back pain to paraplegia. In severe cases, decompressive laminectomy is the choice of treatment. A 32-year-old woman who had been under long-term steroid administration after suprasellar tumor resection was admitted for both leg radiating pain and weakness. She was diagnosed with SEL and had a decompressive laminectomy. During the operation, we found the nerve roots were compressed by epidural fat tissues and engorged vessels. After the operation, her radiating pain was relieved and motor weakness was improved.

Avascular necrosis of both femoral heads following short-term high-dose steroid treatment for acute severe asthma - A rare presentation: Case report and review of literature

A 50-year-old patient who had acute severe asthma presented with avascular necrosis (AVN) of both femoral heads 6 months after short-term high-dose steroid therapy. The use of steroids on a long-term basis can cause AVN of the bone which also occurs in various diseases. A variety of traumatic and nontraumatic factors contribute to the etiology of AVN although long-term exogenous steroid administration and alcoholism are among the most common nontraumatic causes. AVN of both femoral heads presenting after short-term high-dose steroid treatment for acute severe asthma is rare in medical literature; thus, prompting the present case report.

Exclusion of internal iliac artery aneurysm in high-risk patients

The purpose of this retrospective study was to assess the long-term results after exclusion of an internal iliac artery aneurysm (IIAA) to patients with high-risk conditions. From 1993 to 2000, sixteen patients (15 men and one woman, mean age 75.1 years) with 22 internal iliac artery aneurysms underwent exclusion surgery. Only two patients had solitary IIAA and the remaining fourteen had IIAA associated with abdominal aortic aneurysm (AAA) or common iliac artery aneurysm (CIAA). Of the 16 patients, there were 7 with ruptured aneurysm (43.8%) and the other 9 patients, who had underwent an elective operation, were at high risk for surgery because of existence of advanced cancer in 3, cerebrovascular disease in 2, severe chronic obstructive lung disease in 2, and liver cirrhosis or rheumatoid arthritis with long-term steroid administration in 1 each. The sacs of all IIAA (6 bilateral and 10 unilateral) were excluded without internal iliac artery reconstruction. The operative mortality was 6.3%. Non-fatal ischemic colitis occurred in one patient. Buttock claudication was not recognized. Only one excluded aneurysm expanded and underwent complete resection of the sac 45 months after the initial exclusion surgery. Delayed rupture was not observed in the follow-up periods (mean, 37.9 months). The 3-year and 5-year survival rate was 66.7% and 41.7%, respectively. The exclusion method minimizes surgical intervention and yields an acceptable outcome. This method could be the procedure of choice for high-risk patients.

Wegener 肉芽腫症による軟口蓋全欠損に対しスピーチエイドを装着した1例

We report a case of a total soft palate defect caused by Wegener’s granulomatosis, treated by application of a speech aid. The patient was a 25-year-old man with a tumor accompanied by an ulcer and tenderness of the soft palate. The ulceration was extensive, and the soft palate was perforated. Finally, the soft palate became totally involved and showed an extensive defect. We obtained a biopsy specimen from the granulomatous reddish gingiva, so called “strawberry gums.” Clinical appearance, a positive finding for PR3-ANCA, and histopathological findings led to a diagnosis of the upper respiratory tract-limited form of Wegener’s granulomatosis. Although the symptoms such as ulceration and tenderness were improved by administration of steroids and immunosuppressants, nasal leakage of food and hypernasality were severe. We decided to apply a speech aid. The obturator was adjusted by functional impression of the pharyngeal area, so that the space between the obturator and pharyngeal posterior wall would be narrowed. It took only 2 weeks to complete the speech aid fabrication. Remarkable improvement of velopharyngeal function and speech intelligibility was confirmed on logopedic and phoniatric evaluation. We considered application of a speech aid to be effective for a patient with a total soft palate defect caused by Wegener’s granulomatosis who had vascular abnormalities and required long-term administration of steroids and immunosuppressants, because it could be fabricated and applied within a short time, without an invasive procedure.

Patient Outcomes in Two Steroid-Free Regimens Using Tacrolimus Monotherapy After Daclizumab Induction and Tacrolimus With Mycophenolate Mofetil in Liver Transplantation

Long-term steroid administration may predispose liver transplant recipients to infectious and metabolic complications. Maintaining effective immunoprophylaxis while minimizing the negative consequences of steroid therapy could be a key factor in improving clinical outcomes. Six hundred two patients were randomized to receive tacrolimus (TAC) immunosuppression with a single-steroid bolus and two doses of daclizumab (DAC) or mycophenolate mofetil (MMF). The incidence of biopsy-proven acute rejection was 19.7% in the TAC/DAC group and 16.2% in the TAC/MMF group (ns). Three-month patient and graft survival were similar. Steroid use at month-3 was low at 5.5% in the TAC/DAC group and 3.9% in the TAC/MMF group. Significantly higher incidences of causally related adverse events (AEs) and significantly more dose modifications, interruptions, or discontinuations due to an AE were reported with TAC/MMF. Study withdrawal due to leucopenia was significantly higher with TAC/MMF (0.0% vs. 1.7%. P<or=0.05). AEs were generally reported less frequently in the TAC/DAC group. However, specifically headache and supraventricular arrhythmia were significantly higher with TAC/DAC, whereas leucopenia and bacterial infection were significantly higher with TAC/MMF. Laboratory indices of renal function were similar, and increases in serum lipids were negligible in both groups. Incidences of de novo diabetes mellitus (>or=2 fasting plasma glucose values >or=7.0 mmol/L) were low at 9.5% (TAC/DAC) and 11.0% (TAC/MMF). Both TAC-based regimens allowed optimization of immunoprophylaxis while eliminating some of the negative consequences associated with steroids. Efficacy outcomes were comparable; however, TAC monotherapy after DAC induction was associated with significantly less leucopenia and less bacterial infection than a dual regimen incorporating MMF.