Use Of High-dose Dexamethasone Research Articles

Nocardia caishijiensis infection: a case report and review of the literature

BackgroundNocardia caishijiensis is a rare soil actinomycete first described in Anhui province, China, in 2003. There has been only one reported instance of human infection caused by this species in the current literature.Case presentationWe present a case of pulmonary nocardiosis caused by Nocardia caishijiensis in a fifty-two-year-old man with human immunodeficiency virus infection and concomitant use of high-dose dexamethasone for cervical myelopathy, treated successfully with amikacin and thrimetroprim-sulfametoxazole, antibiotic resistance pattern was obtained, although interpretation may be limited.ConclusionTo our knowledge, this is the first reported case of Nocardia caishijiensis infection in humans in North America and the second one in the literature, this pathogen should be recognized as a potentially rising etiology of nocardiosis, especially in solid organ transplant recipients. This has a rising importance as the survival for solid organ recipients continue to rise with advance in transplant medicine leading to increased life expectancy in this particularly susceptible group.

Comparative study of intravenous high-dose dexamethasone versus intravenous methylprednisolone as an emergent therapy in severe primary immune thrombocytopenia

Background In severe immune thrombocytopenia (ITP), high-dose methylprednisolone (MP) alone or combined with intravenous immunoglobulin showed some efficacy. Reports of use of high-dose dexamethasone (HD-DXM) in this setting are lacking.Objectives To compare between the efficacy and safety of HD-DXM versus MP as an emergency therapy in patients with severe ITP.Patients and methods A total of 50 adult patients with primary severe ITP were divided into two groups (25 in each): HD-DXM was given 40 mg/day intravenous for 4 days, and MP was given 1 g/day intravenous for 3 days. Platelet count was compared on admission and on days 3 and 5 of therapy. After 1 week, response was defined as platelet count more than 30×109/l and complete response when platelet more than 100×109/l.Results The baseline characteristics of the two groups are well balanced. Mean platelet count on third day showed no significant difference between the two groups (P=0.19). On day 5, HD-DXM group achieved significantly higher platelet count (90.13±11.41×106/ml vs. 65.11±10.38×106/ml) than in MP group (P≤0.001). Response and complete response rates after 1 week of therapy were statistically significant higher in HD-DXM group than in MP group (92 vs. 76%; P≤0.001). Hypertension and hyperglycemia were more significant in MP group (28 and 40%, respectively) than in HD-DXM group (8 and 12%, respectively; P=0.01 and 0.01, respectively).Conclusion HD-DXM alone could provide an effective and well-tolerated corticosteroid modality in emergency setting of patients with severe ITP. Prospective randomized trials of HD-DXM alone or in combination with intravenous immunoglobulin for higher efficacy are warranted.

MON-LB035 Adrenal Venous Sampling in the Lateralization of Acth-Independent Cushing Syndrome With Bilateral Adrenal Masses: A Case With a 5-Year Follow-Up

Background Nearly 25% of adrenal Cushing syndrome (CS) patients with bilateral adrenal masses have unilateral hypercortisolism, making localization crucial for surgical planning. Since there is no standardized protocol for adrenal venous sampling (AVS) in lateralizing adrenal hypercortisolism, we share our experience with a case of CS with bilateral adrenal masses in which lateralization via AVS permitted unilateral adrenalectomy. Clinical Case A 59-year-old woman with hypertension, hyperlipidemia, and prediabetes was hospitalized for worsening back pain and hypertension. Her BMI was 26.5 kg/m2, BP 173/93 mmHg, HR 73/min, she was anxious, diaphoretic, and hirsute. Glucose was 118 mg/dL and HbA1c 6.6%. Abdominal computed tomography revealed a type B aortic dissection with both right (6.1 x 3.1cm and 3.6 x 2.4cm), and left (largest 1.7 cm) sided adrenal masses. Plasma and 24 hour-urine metanephrine, normetanephrine and catecholamines, as well as plasma renin and aldosterone levels, were normal. AM cortisol on three different occasions was 21.30, 20.70, and 21.30 mcg/dL. Midnight cortisol was 17.8 mcg/dL, and 24-hour urine free cortisol on two occasions was 163 mcg (urine volume 3.4L with creatinine 1.14) and 99.2 mcg (urine volume 1.15L). After 1mg dexamethasone her AM ACTH and cortisol were <5 and 18.70 mcg/dL, respectively. Preoperative AVS was performed and 8mg of dexamethasone was administered the night prior to ensure ACTH suppression during the procedure, and epinephrine was measured to ascertain adequate adrenal vein cannulation. Cortisol levels (in mcg/dL) from the common iliac, right and left adrenal veins were 14.7, 61.5, and 23.5 at 0 minute and 15.2, 61.0, and 22.7 at 2 minutes, respectively. Epinephrine levels (in pg/dL) from the common iliac, right and left adrenal veins were 42, 577, and 3225 at 0 minutes, and 46, 718, and 2989 at 2 minutes. Despite higher epinephrine levels from the left adrenal, the cortisol ratio of the right adrenal vein to peripheral vein was 4.18 with the right-to-left ratio of 2.59 and 2.68 at 0 and 2 minutes, suggesting hypersecretion of cortisol from the right adrenal gland. Unilateral right adrenalectomy revealed a 5.6 cm adrenal adenoma arising in a background of adrenal cortical hyperplasia. Morning postoperative cortisol was 2.2 mcg/dL. She was placed on hydrocortisone and tapered over a 10-month period with remission maintained for more than 3.5 years post-operatively. Conclusion This case demonstrates the safety, usefulness, and necessity, of AVS in localizing cortisol production when bilateral adrenal masses are present. In addition, this case suggests that the use of high dose dexamethasone and measurement of catecholamines may be helpful for more accurate interpretation. More data on AVS in CS patients with bilateral adrenal masses is needed so a well-validated and standardized CS-specific ACS protocol can be developed.

Effects of high-dose dexamethasone in postpartum women with class 1 haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome

This study was performed to investigate the effectiveness of dexamethasone in the management of postpartum women with class 1 haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. This retrospective study was conducted on 18 women with class 1 HELLP syndrome at the Shiga University of Medical Science. They were divided into two groups: Group A comprised participants who did not receive dexamethasone, and Group B comprised participants that intravenously received dexamethasone. The main outcomes were the serum laboratory values, mortality and morbidity. The only significant difference between the two groups in baseline characteristics was the aspartate aminotransferase levels. The linear regression analysis showed a significant difference between the two groups in the recovery of platelet counts (p = .046) and aspartate aminotransferase (p = .009). These findings support the use of high-dose dexamethasone to promote recovery of the platelet counts and aspartate aminotransferase levels in postpartum women with class 1 HELLP syndrome.Impact statementWhat is already known on this subject? Haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is one of the most dangerous complications that can occur during pregnancy and is considered a particularly serious variant of severe preeclampsia. Several clinical trials have been performed since 1994 because it was expected that corticosteroid therapy, primarily with dexamethasone, accelerates recovery after delivery. However, the effect of dexamethasone therapy on class 1 HELLP syndrome is unclear.What do the results of this study add? In this retrospective study, we demonstrated that dexamethasone administration significantly improved the recovery of the platelet count in postpartum women with class 1 HELLP syndrome, and did not increase the rate of maternal postpartum complications.What are the implications of these findings for clinical practice and/or further research? The use of high-dose dexamethasone in postpartum women with class 1 HELLP syndrome might be effective to promote recovery of the platelet count, and contributes a shorter duration of hospitalisation. Because the number of patients with class 1 HELLP syndrome is small, it is important to confirm these findings with well-designed multicentre prospective studies.

Effect of high-dose dexamethasone on patients without diabetes during elective neurosurgery: a prospective study.

The peri-operative use of high-dose dexamethasone to reduce cerebral oedema may result in worsening glycaemic control in people with diabetes and glucocorticoid-induced diabetes in susceptible individuals. This study aims to examine the incidence of glucocorticoid-induced diabetes in a cohort of neurosurgical patients receiving high-dose dexamethasone peri-operatively. Adult non-diabetic neurosurgical patients receiving high-dose dexamethasone were prospectively studied. Exclusion criteria included pregnancy, HbA1c > 6.0%, and use of anti-diabetes therapies. The following data were collected: Family history of diabetes, body mass index, fasting glucose, insulin, C-peptide, and HbA1c (prior to surgery and 6 weeks after last dose of dexamethasone). Homeostatic model assessment values were calculated. Peri-operative glucose readings were recorded and 75g oral glucose tolerance tests performed at the end of 6weeks. Paired student t tests and multiple linear regressions were used. Data from 21 participants (11 women) were available. The mean total dose of dexamethasone was 96 ± 34mg, and treatment duration was 17 ± 7days. A total of 105 random blood glucose levels were documented peri-operatively (mean 7.0 ± 1.0mmol/L). Six weeks following cessation of dexamethasone course, none of the participants developed diabetes, defined either by fasting glucose or by 75g OGTT. There was a statistically significant increase in the mean HOMA-β from 81.5 to 102.1% (p = 0.01) and a significant decrease in the mean fasting glucose from 5.7 to 4.8mmol/L (p = 0.001). The use of high-dose dexamethasone in this cohort of neurosurgical patients did not result in glucocorticoid-induced diabetes. Hyperglycaemia was transient and had resolved by 6weeks.

OVERCOMING TREATMENT RESISTANCE IN A PATIENT WITH PSYCHOTIC MAJOR DEPRESSION AND SEVERE HYPERCORTISOLEMIA: A CLINICAL CASE PRESENTATION AND A LITERATURE REVIEW

In patients with major depression, there is well-known dysregulation of the HPA axis, including GR resistance, hypercortisolism, aberrant negative cortisol feedback, presenting itself as positive standard 1 mg dexamethasone suppression test, absence of nighttime cortisol suppression. Those HPA axis disturbances are more pronounced in cases with severe depression, and/or with melancholic features or psychosis, and in cases where treatment resistance is documented or suspected. Severe HPA axis disturbances may themselves predispose patients to treatment resistance or be the main reason for it. One method to overcome treatment resistance in such cases is using antiglucocorticoid therapy (for example, inhibitors of cortisol biosynthesis, like ketoconazole, or GR antagonist mifepristone, or a short course of high-dose synthetic glucocorticoid dexamethasone to suppress the HPA axis overactivity). In this article, we present a case in which the treatment resistance in a patient with severe psychotic major depression and severe hypercortisolemia was successfully overcomed by sequential use of high-dose dexamethasone (20 mg/day x 4 days) and high-dose mifepristone (600 mg/day for 14 days).

Oral melphalan and dexamethasone grants extended survival with minimal toxicity in AL amyloidosis: long-term results of a risk-adapted approach

The combination of oral melphalan and dexamethasone is considered standard therapy for patients with light-chain amyloidosis ineligible for autologous stem cell transplantation. However, previous trials reported different rates of response and survival, mainly because of the different proportions of high-risk patients. In the present study, including a total of 259 subjects, we treated 119 patients with full-dose melphalan and dexamethasone (dexamethasone 40 mg days 1-4), and 140 patients with advanced cardiac disease with an attenuated dexamethasone schedule (20 mg). Hematologic response rates were 76% in the full-dose group and 51% in the patients receiving the attenuated schedule; the corresponding complete response rates were 31% and 12%, respectively. The median survival was 7.4 years in the full-dose group and 20 months in the attenuated-dose group. Use of high-dose dexamethasone, amino-terminal pro-natriuretic peptide type-B >1800 ng/L, a difference between involved and uninvolved free light chains of >180 mg/L, troponin I >0.07 ng/mL, and response to therapy were independent prognostic determinants. In relapsed/refractory subjects bortezomib combinations granted high hematologic response rates (79% and 63%, respectively), proving the most effective rescue treatment after melphalan and dexamethasone. In summary, melphalan plus dexamethasone was highly effective with minimal toxicity, confirming its central role in the treatment of AL amyloidosis. Future randomized trials will clarify whether bortezomib is best used in frontline combination with melphalan and dexamethasone or as rescue treatment.

Administration of high dose dexamethasone impairs the function of thymus cells

This study was purposed to investigate the effects of high-dose dexamethasone on structure and function of thymic epithelial cells (TEC). Male C57BL/6 mice aged 6 to 8 weeks were used as experimental animals. The mice were injected intraperitoneally with dexamethasone (20 mg/kg), and the other mice treated with saline were used as controls. Thymus was harvested at day 5 after treatment. The histological changes of the treated thymus were monitored by HE staining and in situ immunofluorescence staining. The ratio of each subset in the thymus were analyzed by using flow cytometry, and quantitative PCR was applied to detect the expression levels of IL-22 and Foxn1, which represent the regenerative function of thymus. The results showed that compared with control mice, the structure of TEC in mice treated with high-dose dexamethasone was damaged and the thymic cell number was declined dramatically (P < 0.05); the ratios of thymus cell subsets were changed, the number of double positive (DP) thymus cells among these subsets declined sharply (P < 0.05); the expression levels of Foxn1 and IL-22 increased by 34 and 8 folds respectively. It is concluded that the use of high-dose dexamethasone can lead to damage of the structure and function of TEC, and induce up-regulation of the expression of genes related to thymus repair.

Cost-Effectiveness of Targeted Cancer Therapies for Hematological Malignancies.

Abstract 4547Targeted cancer therapies for hematological malignancies have rapidly gained uptake in different types of indications, and some have become gold standard of treatment. However, the high cost of these therapies poses challenges for payers, patients and physicians. MethodsTo understand the cost-effectiveness of these new classes of drugs we reviewed the published cost-effectiveness studies and analyzed their cost/QALY, time horizon, comparators, indications and model approaches. ResultsTargeted therapies for hematological cancers have much lower and less variable cost/QALY than branded drugs indicated for solid tumors. For example, incremental cost effectiveness ratio (ICER) for imatinib ranges from $40,000 to $45,000/QALY, while ICER for bevacizumab ranges from $125,000 to $325,000/QALY. Secondly, the choice of comparator in some occasions may depend on the country of use, therefore models are required to be customized to local regimens. In one of the cost-effectiveness analysis for bortezomib for refractory multiple myeloma patients, NICE questioned the use of high dose dexamethasone (HDD) as comparator. Third, there is also some variability in methods used by different manufacturers, some used cost/QALY whereas others used cost/LYG. Conclusion: This analysis shows the range, variability and methods used for calculation of ICER values for these targeted cancer therapies and provides lessons for executives and policy makers. Disclosures:No relevant conflicts of interest to declare.

FDA Warns Claims for Pharmacy-Made “Bio-identical” Hormones Are Misleading

tolerated—plus high-dose dexamethasone is indicated for the treatment of patients with multiple myeloma who have received at least one prior therapy. “We’ve been using high-dose corticosteroids for myeloma just because that’s the way it’s always been done,” said first author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minn. “This is the first randomized study that looked at steroid dose.” The study revealed that lenalidomide plus low-dose dexamethasone is associated with longer survival and less toxicity than lenalidomide plus highdose dexamethasone. For patients given lenalidomide plus low-dose dexamethasone, the 1-year survival rate was 96% compared with 87% in the group receiving high-dose dexamethasone. The 18-month survival rate was 91% vs 80%, respectively. To date, 42 deaths have occurred in the high-dose group and 16 in the low-dose group. The increased mortality in the former group was due to disease progression as well as increased toxicity. The investigators reported that the superiority of the lower dose of steroid in this trial reflected not only greater safety, but also fewer adverse effects, which allowed patients to continue treatment at effective doses for a longer period. “Either regimen is excellent. However, lenalidomide and low-dose dexamethasone is safer and more effective in terms of overall survival,” said Rajkumar. “We believe our study has major implications for the continued use of high-dose dexamethasone in multiple myeloma, including in regimens that use high-dose dexamethasone in combination with other chemotherapy drugs or novel agents,” he added. Rajkumar and colleagues concluded that lenalidomide and lowdose dexamethasone should be considered for first-line therapy because the 1-year survival rate in this study is better than the rate reported in two phase 3 trials with thalidomide plus dexamethasone, an FDA-approved regimen (Rajkumar SV et al. J Clin Oncol. 2006;24[3]:431-436; Rajkumar SV et al. J Clin Oncol. In press).

A Randomized Trial of Lenalidomide Plus High-Dose Dexamethasone (RD) Versus Lenalidomide Plus Low-Dose Dexamethasone (Rd) in Newly Diagnosed Multiple Myeloma (E4A03): A Trial Coordinated by the Eastern Cooperative Oncology Group.

Aim: A phase III trial of lenalidomide plus high (standard) dose dex (RD) versus lenalidomide plus low dose dex (Rd) in newly diagnosed myeloma (MM).Methods: Pts with untreated, symptomatic MM were eligible. Pts in the RD arm (Arm A) received lenalidomide 25 mg/day PO days 1–21 every 28 days plus dex 40 mg days 1–4, 9–12, and 17–20 PO every 28 days; pts in the Rd arm (Arm B) received lenalidomide at the same dose plus dex 40 mg days 1, 8, 15, and 22 PO every 28 days. The primary endpoint was response rate at 4 months, with the null hypothesis being that the response rates in the two 2 arms are equivalent. Planned sample size was 196 eligible pts per arm with one-sided 0.10 Type I and 0.05 Type II error rate. All analysis were performed on an intent to treat basis. An independent DMC recommended release of study results.Results: 445 pts (median age, 65 yrs) were accrued; 223 randomized to RD, 222 to Rd. Median follow-up time is 17 months. Arms were well balanced for age, gender, stage, bone lesions, hemoglobin, beta-2 microglobulin, performance status, bone marrow plasma cells, and M protein levels at baseline. Major grade 3 or higher toxicities, including DVT/PE and infections, were significantly higher in the high dose dex arm (see Table). Overall survival (OS) at the second pre-planned interim analysis was significantly superior with lenalidomide plus low dose dex, P<0.001; one year survival 96% (Rd) versus 87% (RD). The 18 month survival rate is 91% versus 80%, respectively. OS differences in favor of the low dose dex arm were seen in pts <65 (P=0.022; one year rate 97% vs 92%) as well as pts 65 and older (P=0.002; one year rate 94% vs 83%), respectively. Sixty-one patients have died; 42 in the RD arm and 16 in Rd arm. The cause of death has been verified by detailed chart review in 38 patients. Of 29 verified deaths in the RD arm, 13 were due to disease progression, 6 thrombosis/embolism, 3 infection, 3 cardiac ischemia, 1 stroke, and 1 respiratory failure. Of 9 verified deaths in the Rd arm, 5 were due to disease progression, 2 infection, 1 thrombosis/embolism, and 1 cardiac arrest. Response rate data are expected to be available at the time of the meeting.Conclusions: Lenalidomide plus low-dose dexamethasone (Rd) is associated with superior OS compared to lenalidomide plus high-dose dexamethasone (RD) in newly diagnosed MM. The increased mortality in Arm A is due to disease progression (myeloma deaths) as well as increased toxicity. This study has major implications for the use of high-dose dexamethasone in the treatment of newly diagnosed MM.Major Grade 3 or Higher Adverse EventsToxicityArm A %Arm B %P valueNeutropenia10190.01DVT/PE259<0.001Infections166<0.001Any grade 3 or higher non-hematologic4932<0.001Any grade 4 or higher non-hematologic209<0.001Deaths in first 4 months50.50.006

Phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): A trial coordinated by the Eastern Cooperative Oncology Group

LBA8025 Background: We compared lenalidomide plus high (standard) dose Dex (R+HighD) versus lenalidomide plus low dose Dex (R+LowD) in newly diagnosed MM. Methods: Pts with untreated, symptomatic MM were eligible. Pts in both arms received lenalidomide 25 mg/day PO days 1–21 every 28 days. In addition, pts in the R+HighD arm received Dex 40 mg days 1–4, 9–12, and 17–20 PO every 28 days; pts in the R+LowD arm received Dex 40 mg days 1, 8, 15, and 22 PO every 28 days. The primary null hypothesis was that response rates at 4 months on the 2 arms are equivalent. Planned sample size was 196 eligible pts per arm with one-sided 0.10 Type I and 0.05 Type II error rate. Pre-planned interim analysis is performed by an independent DMC when full information is available on 25%, 50% and 75% of accrual. All analysis were intent to treat. Results: 445 pts (median age, 65 yrs) were accrued; 223 randomized to R+HighD, 222 to R+LowD. Arms were well balanced for age, gender, stage, bone lesions, hemoglobin, beta-2 microglobulin, performance status, bone marrow plasma cells, and M protein levels at baseline. Major grade 3 or higher toxicities included thromboembolism (22.1% with R+HighD vs 6.1% in R+LowD), infection/pneumonia (15.7% vs 7.5%) and hyperglycemia (9.7% vs 6.6%). Grade 3 or higher non-hematologic toxicities occurred in 65.9% (R+HighD) versus 54.9% (R+LowD) respectively; corresponding grade 4 or higher rates were 20.3% vs 13.1% respectively. Overall survival (OS) at first interim analysis was significantly superior with R+LowD, P&lt;0.001; one year survival 96.5% (R+LowD) versus 86% (Rev+HighD). OS differences in favor of R+LowD were seen in pts &lt;65 (P=0.015; one year rate 98% vs 90%) and pts 65 and older (P=0.004; one year rate 95% vs 83%), respectively. DMC recommended release of survival results, and recommended switching all pts to R+LowD. DMC also recommended closure of an expansion phase trial of R+HighD investigating optimal thromboprophylaxis. Conclusions: Lenalidomide plus low-dose dexamethasone is associated with superior OS compared to lenalidomide plus high-dose dexamethasone. This study has major implications for future use of high-dose dexamethasone in the treatment of MM. No significant financial relationships to disclose.

There Is No Dose-Escalation Response to Dexamethasone (0.0625–1.0 mg/kg) in Pediatric Tonsillectomy or Adenotonsillectomy Patients for Preventing Vomiting, Reducing Pain, Shortening Time to First Liquid Intake, or the Incidence of Voice Change

Tonsillectomy is associated with postoperative nausea and vomiting (PONV) if no prophylaxis is administered. Previous studies have shown that a single dose of dexamethasone decreases the incidence of PONV. The most effective dose of dexamethasone to affect clinical outcome is yet to be defined. One-hundred-twenty-five children were enrolled in a double-blind, prospective, randomized, dose-escalating study of dexamethasone: 0.0625, 0.125, 0.25, 0.5, or 1 mg/kg, maximum dose 24 mg. Nonparametric ANOVA was used to analyze the incidence of vomiting by treatment group for 0 to < or =5 h, >5 to 24 h. The Cox Proportional Likelihood Ratio Test was used to compare the time of first vomit and time to first pain medication across treatment groups. There was no difference in the incidence of vomiting for the five escalating doses of dexamethasone in the time period. There were no differences in secondary outcomes (analgesic requirements, time to first liquid, and change in voice) across treatment groups. We conclude that the lowest dose of dexamethasone (0.0625 mg/kg) was as effective as the highest dose of dexamethasone (1.0 mg/kg) for preventing PONV or reducing the incidence of other secondary outcomes following tonsillectomy or adenotonsillectomy. There is no justification for the use of high-dose dexamethasone for the prevention of PONV in this cohort of children.

The Feasibility of High-Dose Dexamethasone (HD-DEX) in Idiopathic Thrombocytopenic Purpura (ITP) in Adults; a Multi-Center Study in Korea.

Short term use of HD-DEX has shown less adverse effects (AEs) than PDS maintenance but its success rates reported differently by several studies. The objective of this study was to determine HD-DEX effectiveness in adult ITP with newly diagnosed (group 1) and relapsed after other treatments(Tx) (group 2). 71 (median age; 45, 20~82) with ITP with a platelet counts (PC) 20,000/uL or less than 50,000/uL and clinically significant bleeding were enrolled. DEX a dose of 40 mg/day for 4 consecutive days was tried. A response was defined as an increase in the PC of at least 30,000/uL, PC of more than 50,000/uL by day 10 (D10) after DEX. A maintenance was defined as a PC of more than 50,000/uL 6 ms after Tx. The number of group 1 and 2 were 54, 17, retrospectively. In group 2, previous regimens included;oral PDS and/or IVIG (16)and splenectomy (4). Median PC before Tx were 8,500(1,000~45,000/uL) and 9,000(100~33,000/uL) in group 1 and 2, retrospectively (p=0.80). 27(50%) and 6(35.3%) in group 1, 2 showed good initial response to 1st course of DEX, retrospectively (p=0.40). After 1st course of DEX, 11(20.3%) in group 1 and 1(5.9%) in group 2 could maintain response for 3 ms (p=0.27). By 6 ms, 8 (14.8%) in group 1 and 1 (5.9%) in group 2 kept first response (p=0.68). Among 33 patients bearing initial response, 12 (44.4%)and 2 (33.3%) in group 1, 2 relapsed (p=1.0). Good correlation revealed between PC (D10) and response rate (RR) (p<0.05). Of 21 with PC (D10) above 100,000/uL, 6(28.6%) experienced relapse. On the other hand, nine of 11 patients (81.8%) in whom PC (D10) were less than 100,000/uL relapsed after all. There was no significant difference in relapse-free survival (RFS) after 1st DEX between 2 groups (p=0.9). 13 of 14 relapsed received 2nd DEX and then maintained PDS without interruption. After several weeks of maintenance, PDS tapered according to the PC. 9(75.0%) in group 1 and 2(100%) in group 2 showed response in 2nd DEX. Of these 11 patients, 2 in group 1 relapsed 10 ms after receiving 2nd DEX. After 1st DEX, 12 (16.9%), 5(7%) and 6 (8.5%) temporarily suffered from vague generalized sx., facial edema, and mild liver function abnormality, retrospectively. During the 2nd DEX and consecutive oral PDS, 4(30.7%), 3(23.1%) and 1(7.7%) experienced same AEs, retrospectively. Additionally, of these 13, overt DM requiring hypoglycemic agents appeared in 2(15.4%) and 1(7.7%) experienced duodenal ulcer bleeding. In conclusion, 1 course of HD-DEX revealed good initial response in group 1 but in group 2, the RR was lower than in historical results of oral PDS. However, it has an advantage for the patients to have a good compliance to the Tx because of few AEs and no need to maintain long-term daily medication. Furthermore, although the 2nd DEX and PDS maintenance showed good response, it revealed no benefit compared as a previously established oral PDS regimen because of frequently occurrence of AEs and poor compliance. Therefore, the proper DEX schedule remained to be determined according to the early achieved platelet counts (eg. D10) with 1st course DEX or to the presence of previous Tx.

High-dose dexamethasone in scleromyxedema: Report of 2 additional cases

To the Editor: In the August 2004 issue of the Journal, Horn et al1 reported the successful use of high-dose dexamethasone in scleromyxedema. A 63-year-old man received 3 consecutive weekly cycles each month of high-dose dexamethasone (40 mg/d for 4 days) resulting in a complete resolution of cutaneous manifestation. Encouraged by this report, we initiated the same regimen in two of our patients with scleromyxedema who had not benefited from prior treatment with methotrexate and extracorporeal photopheresis.

Emergency treatment of malignant extradural spinal cord compression: an evidence-based guideline.

To review the literature for malignant extradural spinal cord compression (MSCC), produce evidence-based recommendations based on the criteria used by the Canadian Task Force on the Periodic Health Examination, and make suggestions regarding future research directives. A systematic review of the literature with explicit study selection and evaluation criteria was performed. Primary outcome measure was posttreatment ambulation rate. There is good evidence to support the use of high-dose dexamethasone (96 mg/d), but inconclusive evidence for the use of moderate-dose steroids (16 mg/d) in conjunction with radiotherapy (RT) for the treatment of MSCC. Fair evidence exists for not using steroids in patients who are nonparetic and ambulatory pretreatment, and to give radiation to patients with subclinical spinal cord compression (SCC). The remainder of the recommendations are based on inconclusive evidence: RT alone should be the first-line treatment for ambulatory patients except when there is spinal instability, bony compression, or paraplegia on presentation, in which case surgery should be performed. Either modality can be used for paraparetic patients who are nonambulatory. Postoperative RT should be considered for tumor in residua. Ambulatory, undiagnosed patients should have needle biopsy attempted first. Patients should be aggressively screened and educated about SCC. In general, there were very few papers of high methodologic quality found in the literature. More studies are needed to satisfy the validity of many of the clinical decisions that are made today with regard to the management of MSCC.

A dose-response study of dexamethasone in a model of spinal cord compression caused by epidural tumor.

In order to assess the clinical and biological effects of glucocorticoids in the therapy of epidural spinal cord compression, the T8-10 epidural space of 50 rats was implanted with Walker 256 tumor. The rats were studied 10 to 20 days later when they became paraparetic. The regional blood-spinal cord transport constant (K, a function of the blood-spinal cord barrier) of 14Carbon-labeled aminoisobutyric acid was measured with quantitative autoradiography 6 hours after intravenous injection of low-dose (0.1 mg/kg), intermediate dose (1 mg/kg), and high-dose (10 mg/kg) dexamethasone. The effects of dexamethasone in these doses on the clinical signs and water content of the compressed cord were also evaluated 40 hours after treatment began. The K factor increased 730% in compressed compared with noncompressed spinal cords (p less than 0.001). Dexamethasone induced a dose-related reduction of both K (p = 0.007) and water content of the compressed cord (p less than 0.0001). Stabilization or, more rarely, improvement of weakness at 24 and 40 hours posttreatment correlated with the dose of dexamethasone (r = 0.88, p less than 0.001). This study demonstrates that dexamethasone has a dose-related beneficial clinical effect associated with an improvement of blood-spinal cord barrier breakdown and a reduction of the water content of the compressed cord. This study supports the use of highdose dexamethasone for the initial treatment of epidural spinal cord compression.