High-dose Methylprednisolone Group Research Articles

Predictors of Coronavirus Disease 2019 Severity: A Retrospective Study of 64 Cases.

This study aimed to analyze the clinical characteristics and potential predictors of disease severity in patients with coronavirus disease 2019 (COVID-19). We retrospectively analyzed the clinical data from 64 (37 male and 27 female) patients with COVID-19. Their mean age was 47.8 years; 43 (67.2%) cases were non-severe, 21 (32.8%) were severe, and 2 patients (3.1%) died. Age and serum ferritin levels were significantly associated with COVID-19 severity. There were no significant differences in the duration of severe illness or the number of days on high-level respiratory support between the low-dose and high-dose methylprednisolone groups. The mean number of days in hospital in the high-dose group was higher than that in the low-dose group. Repeated monitoring of ferritin, interleukin-6, C-reactive protein, lactic acid dehydrogenase, and erythrocyte sedimentation rate during COVID-19 treatment may assist in the prediction of disease severity and evaluation of treatment effects.

Mortality and morbidity after high-dose methylprednisolone treatment in patients with acute cervical spinal cord injury: a propensity-matched analysis using a nationwide administrative database

ObjectiveTo examine the magnitude of the adverse impact of high-dose methylprednisolone treatment in patients with acute cervical spinal cord injury (SCI).MethodsWe examined the abstracted data from the Japanese Diagnosis Procedure...

Effect of glucocorticoid on expression of vascular endothelial growth factor, FLT-1 and FLK-1 after gamma knife surgery in rats

Objective To investigate the effect of methylprednisolone (MP) on the expression of vascular endothelial growth factor (VEGF) and its receptors in rats after gamma knife surgery (GKS),and elucidate the mechanism of the unique benecial effect of glucocorticoid therapy on brain edema after GKS.Methods Male Wistar rats were subjected to GKS and given MP (5-30 mg/kg body weight) 12 weeks after GKS.Blood-brain barrier permeability and brain water content were detected at 12th and 13th week after irradiation.The protein and mRNA expression of VEGF and its receptors was determined by using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR).Results The brain water content and EB extravasations were significantly reduced in MP-treated rats as compared with the controls.High dose MP downregulated the protein expression of VEGF ( 12.40 ±0.88 cells/high power field vs.30.20 ± 1.20 cells/high power field),but upregulated the protein expression of Flt-1 ( 25.40 ± 0.86vs.11.80 ± 0.50) as compared with the controls.The relative level of VEGF mRNA in high dose MP group was 70％ of the controls,whereas the level of Flt-1 mRNA significantly increased,showing a 1.8 fold difference.Conclusion Glucocorticoid therapy for brain edema induced by GKS is associated with differential regulation of VEGF and its receptors. Key words: Brain edema; Radiosurgery; Vascular endothelial growth factor

Methylprednisolone exacerbates acute critical illness-related corticosteroid insufficiency associated with traumatic brain injury in rats

Emerging evidence demonstrates that severe illness could induce critical illness-related corticosteroid insufficiency (CIRCI) and cause poor prognosis. The purpose of this study was to test the hypothesis that methylprednisolone (MP), a synthetic glucocorticoid, promotes post-traumatic apoptosis in both the hypothalamus and pituitary, resulting in acute CIRCI and increased mortality in the acute phase of traumatic brain injury (TBI). We tested this hypothesis by measuring acute CIRCI in rats subjected to fluid percussion injury (FPI) and treated with MP (5–30mg/kg). The corticosteroid response to TBI was evaluated using the corticosterone increase index (CII), where values less than 2.5 were considered indicative of acute CIRCI. The CII of MP treated rats was comparable to that of saline treated control rats before injury but was significantly decreased in injured rats receiving high-dose MP on post-injury day 7. Similarly, the incidence of acute CIRCI was significantly higher in the high-dose MP group on post-injury day 7. Furthermore, the CII of rats that did not survive post-injury was significantly lower compared to that of survival and was indicative of acute CIRCI. We also examined apoptosis in the paraventricular nucleus (PVN) of the hypothalamus and the adenohypophysis of the pituitary, using a TUNEL assay and transmission electron microscopy (TEM). The number of TUNEL-positive cells was significantly higher in injured rats treated with high-dose MP. No TUNEL-positive cells were detected in the adenohypophysis across experimental groups at either 7 or 14days after TBI. However, autopsies performed on rats that did not survive post-injury revealed obvious apoptotic cells in the adenohypophysis. Moreover, TEM revealed morphological changes characteristic of apoptosis in both the PVN and adenohypophysis of high-dose MP treated rats. These data suggest that MP therapy for TBI could increase neuronal apoptosis in both the hypothalamus and pituitary and consequently exacerbate acute CIRCI and mortality induced by TBI.

Treatment of Steroid-Resistant Acute GvHD with OKT3 and High-Dose Steroids Versus High-Dose Steroids Alone.

Despite new conditioning regimens and introduction of novel immunosuppressants in hematopoietic cell transplantation (HCT), acute graft-versus-host disease (aGvHD) remains an often life threatening complication. Methylprednisolone (MP) 2 mg/kg body weight (BW) per day is the initial standard treatment with escalation to high-dose MP (10 mg/kg BW per day) for non-responders. Recently, we demonstrated OKT3 muromonab to be an effective second-line and subsequent salvage treatment. Response duration, however, was frequently short-lived in those extensively pretreated patients and inversely correlated with duration from allografting. In the current randomized multicenter trial we investigated high-dose MP (HD-MP) versus OKT3 5 mg per day plus HD-MP. Primary endpoints were response to treatment after 100 days and survival at one year from HCT. Secondary endpoints were side effects and incidence of infectious complications. Patients with resistant °II to IV aGvHD on standard MP following allogeneic HCT were randomized to HD-MP or OKT3 + HD-MP after exclusion of other severe HCT-related complications. Eighty patients from 6 transplant centers were enrolled. Median age for the 40 patients who received OKT3 + HD-MP was 40 (range, 19 – 65) years and for the 40 patients who received HD-MP 39 (range, 19 – 56) years. There was no statistical significant difference between the groups for severity of aGvHD (°II vs. °III/IV); stem cell source (bone marrow vs. peripheral blood progenitor cells); GvHD prophylaxis (CSA vs. ATG+CSA); and conditioning regimen (TBI/Cy vs. Bu-Cy). However, significantly fewer HCTs in the OKT3 + HD-MP group were from HLA-identical siblings. Currently, 62 subjects are evaluable for response. In both arms, reduction of severe and proportional increase of moderately-severe aGvHD was observed with resolution of all °IV cases until day +30. However, significantly more patients in the OKT3 + HD-MP became disease-free (°0) by day +100 when compared to patients treated with HD-MP alone: 39.3 % vs. 20.6 % (p=0.03). In the OKT3 + HD-MP group relative increase of disease-free patients was higher for all organ systems at all time points when compared to patients on HD-MP treatment without reaching statistical. With respect to infectious complications, the incidence of both bacterial and viral infections was slightly and for invasive aspergillosis significantly higher in the HD-MP when compared to the OKT3 + HD-MP group (20.6 vs. 10.7 %; p=0.025). Treatment related mortality was higher in the HD-MP group when compared to the OKT3 + HD-MP group by days +30 (32.3 vs. 10.7 %) and +100 (55. 9 vs. 39.3 %). However, this did not translate into a significantly better one-year survival with the currently evaluable patients: one-year survival for the HD-MP group was 32.4 % and for the OKT3 + HD-MP group 46.4 %. (p=0.72). We conclude that OKT3 + HD-MP results in higher response rates for patients with steroid-resistant aGvHD and thus leads to a better immune reconstitution after HCT what is reflected by reduced incidence and mortality of infectious complications. Final results of the trial will be presented.

Myeloprotective effect of short‐course high‐dose methylprednisolone treatment before consolidation therapy in children with acute myeloblastic leukemia

In our previous studies, short-course high-dose methylprednisolone (HDMP) has been shown to shorten the chemotherapy-induced neutropenic period by stimulating the CD34(+) hematopoietic progenitor cells in children with acute leukemia. In this study, we investigate the role of short-course HDMP on induction of a myeloprotective effect when administered before consolidation therapy consisting of high-dose cytosine arabinoside and daunorubicin. Thirty-four consecutive newly diagnosed children with acute myeloblastic leukemia (AML) who received 64 courses of consolidation regimen were entered into the study. The patients received HDMP (group A) at a daily dose of 30 mg/kg methylprednisolone starting 4 days before the initiation of consolidation therapy. The control group did not receive HDMP (group B). There were no differences in the white blood cell (WBC) and absolute neutrophil counts (ANC) between group A (at day -4) and group B (at day 0) at the beginning of the study (medians: 3 x 10(9)/L vs. 3.2 x 10(9)/L and 1.5 x 10(9)/L vs. 1.7 x 10(9)/L, respectively). The WBC count increased significantly from 3 x 10(9)/L to 6.4 x 10(9)/L, and ANC increased from 1.5 x 10(9)/L to 3.9 x 10(9)/L after 4 days of HDMP treatment in group A (P < 0.01). Following high-dose chemotherapy, the median values of WBC and ANC also remained higher than the control values during the 16 days of the follow-up period. The neutropenic period was significantly shorter in the HDMP group than in the control group (9 +/- 5.2 days vs. 22 +/- 4.7 days) (P < 0.05). The duration of hospitalization and the interval between two chemotherapy cycles were significantly decreased in group A when compared group B (9 +/- 2.7 vs. 14 +/- 2.7 days; 22 +/- 4.7 vs. 26 +/- 4.2 days, respectively) (P < 0.05). Moreover, following consolidation therapy, the number of patients with ANC values below 0.5 x 10(9)/L was lower in group A when compared the group B. In conclusion, the administration of short-course (4 days) HDMP before high-dose chemotherapy has been found to be beneficial for reducing the duration and severity of neutropenia. Further studies with short-course HDMP are required to evaluate its myeloprotective effects in patients with other malignancies.

Long‐term effects of intravenous high dose methylprednisolone pulses on bone mineral density in patients with multiple sclerosis

To determine the effects of high dose methylprednisolone (HDMP) pulses on bone mineral density (BMD) in patients with multiple sclerosis (MS), we studied 25 MS patients who received regular pulses of HDMP as well as pulses of HDMP for relapses, 18 MS patients who received HDMP at the same dose schedule only for relapses, and 61 healthy controls. We measured BMDs at lumbar spine and femoral neck and we assessed biochemical markers of bone metabolism and turnover. The average lifetime dosage of MP was 75.4 (SD 11.9) g in the pulsed HDMP group and 28.6 (SD 18.3) g in the HDMP for relapses group (P < 0.0001). Two MS patients (4.7%) and four controls (6.6%) had osteoporosis (P = NS), whereas 25 patients with MS (58.1%) and 21 controls (34.4%) had osteopenia (P = 0.016). BMDs measured at lumbar spine and femoral neck and biochemical indices of bone metabolism did not differ in MS patients and controls. BMD measures were not associated with lifetime methylprednisolone dosage. In partial correlation analysis, controlling for age, gender and menopausal status there was a significant inverse correlation between BMD at femoral neck and Expanded Disability Status Scale (EDSS) score (r = -0.31, P = 0.05). In conclusion, treatment with repeated HDMP pulses was not associated with osteoporosis in patients with MS who participated in a trial of methylprednisolone. However, osteopenia was observed more frequently in MS patients than healthy controls. Our data are reassuring, as them suggest that repeated pulses of methylprednisolone do not result in substantially increased risk of osteoporosis in MS patients. Moreover, osteopenia was found only in patients treated for relapses, who had a significantly higher EDSS score than patients in the HDMP group, suggesting that decreased mobility may contribute to bone loss more than corticosteroid use. BMD should be monitored in patients with MS, regardless of the use of methylprednisolone.

The effect of short course high dose methylprednisolon therapy on fibrinogen level in children with acute lymphoblastic leukemia: A preliminary study

In order to investigate the effects of short term high dose methylprednisolone (HDMP) on fibrinolytic system in patients with ALL, 16 of newly diagnosed 32 ALL patients were given HDMP alone (20 mg/kg per day) for 5 days and the rest 16 patients received conventional dose methylprednisolone (CDMP, 2 mg/kg per day) prior to a combination chemotherapy consisting of methylprednisolone, vincristin, daunorubicin and 9 doses of l-Asparaginase. Fibrinogen levels decreased in both groups at day 5 which was statistically significant in the HDMP group. Baseline d-dimer levels of both groups were significantly higher than those of the control group including 24 healthy children. d-dimer levels significantly decreased after initiation of combination therapy in both groups. There was a significant rise in PAI-1 levels after combination therapy both in HDMP and CDMP groups.

Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial

Treatment of adults with autoimmune thrombocytopenic purpura (AITP) is based more on individual experience than on results of controlled studies. We compared intravenous immunoglobulin with high-dose methylprednisolone in untreated adults with severe AITP and assessed efficacy of subsequent oral steroids compared with placebo. Primary outcome was number of days with platelet count greater than 50 x 10(9)/L within the first 21 days. We did a randomised multicentre trial based on a 232 design. 122 adults with severe AITP (platelet count < or =20 x 10(9)/L) were randomly assigned to receive either intravenous immunoglobulin or high-dose methylprednisolone on days 1-3 (randomisation A), and then to receive either oral prednisone or placebo (randomisation B) on days 4-21. Analysis was by intention to treat. Six patients were excluded from the analysis. The number of days on which platelet counts were above 50 x 10(9)/L was 18 in 56 patients receiving intravenous immunoglobulin and 14 in 60 receiving high-dose methylprednisolone (p=0.02). Percentage of patients who had platelet counts over 50 x 10(9)/L on days 2 and 5 was 7% and 79%, respectively, in the intravenous immunoglobulin group compared with 2% and 60%, respectively, in the high-dose methylprednisolone group (p=0.04). During the second treatment period, prednisone was more effective than placebo for all short-term endpoints. Patients who received intravenous immunoglobulin and prednisone had platelet count greater than 50 x 10(9)/L for 18.5 days (p=0.005), and those treated with high-dose methylprednisolone and prednisone had this count for 17.5 days. Intravenous immunoglobulin and oral prednisone seems to be more effective than high-dose methylprednisolone and oral prednisone in adults with severe AITP, although the latter treatment is effective and well tolerated.

Anti-Rejection Therapy in Renal Transplantation: Use of the Monoclonal Antibody OKT3

The success of anti-rejection therapy was evaluated in 65 cadaveric renal allografts immunosuppressed with cyclosporin. All first rejection episodes were treated with 0.5 g methylprednisolone given daily for 3 days. Second rejection episodes were treated with either a further identical 3-day course of methylprednisolone or a 10-14-day course of the monoclonal antibody OKT3. The peak creatinine during second rejection episodes was higher in patients treated with OKT3 (481 +/- 54 mumol/l; mean +/-SEM) than in those treated with methylprednisolone (320 +/- 59 mumol/l) (P = 0.036), suggesting more severe rejection in the OKT3 group. Despite this the rejection reversal rate was higher in the OKT3-treated group (100%) when compared to the high-dose methylprednisolone group (64%) (P less than 0.05) and the creatinine at 6 months was less in the OKT3 group (162 +/- 17 mumol/l) than in the methylprednisolone group (230 +/- 22 mumol/l). These data suggest that OKT3 is a very effective treatment for second rejection episodes following renal transplantation and yields improved renal functions in comparison with high-dose steroids.