A questionnaire survey.
To characterize surgeons' current perspectives on the administration of methylprednisolone for acute spinal cord injury (SCI) and determine how this has changed during the ...last 7 years.
The determinants of and complications associated with off-label steroid use for acute SCI remain controversial.
A survey was sent to surgeon members of the Cervical Spine Research Society requesting information regarding their use of steroids for acute SCI. Determinants included surgeons' specialty, trauma center level, number of SCIs treated per year, severity of injury, and location of injury. These results were compared across groups as well as with a historical control.
In the case of cervical complete and incomplete SCIs, 47.4% and 56.4% of respondents, respectively, reported using steroids. For complete and incomplete thoracolumbar spine injuries, the usage rate was 46.2% and 55.1%, respectively. There has been a significant (P < 0.0001) decrease in the number of surgeons using high-dose steroids in the treatment of acute SCIs when compared with a previous report in 2006 (56% vs. 89%).More than 80% of respondents reported sepsis, active gastrointestinal bleeding, and SCI occurring earlier than 8 hours as contraindications. Seventy-one percent of respondents reported observing complications from the use of steroids, and 76.3% thought that the complications were severe enough to limit steroid use. Of the surgeons who used steroids for SCI, 26% thought that steroids improved neurological recovery, 19.2% used steroids to adhere to institutional protocol, and 25.6% stated they did not think steroids were beneficial but used them because of medicolegal concerns.
There has been a significant decrease in the number of surgeons using high-dose steroids for acute SCIs. Sepsis, gastrointestinal bleeding, and an injury occurring more than 8 hours prior to presentation were agreed upon as contraindications to steroid use.
The plasma and tissue binding properties of two corticosteroids, dexamethasone (DEX) and methylprednisolone (MPL), were assessed in the rat in anticipation of developing physiologically based ...pharmacokinetic and pharmacokinetic/pharmacodynamic models. The tissue-to-plasma partition coefficients (
) of DEX and MPL were measured in liver, muscle, and lung in vivo after steady-state infusion and bolus injection in rats. Since
is often governed by reversible binding to macromolecules in blood and tissue, an attempt was made to assess
values of DEX and MPL by in vitro binding studies using rat tissue homogenates and to compare these estimates to those obtained from in vivo kinetics after dosing. The
values of both steroids were also calculated in rat tissues using mechanistic tissue composition-based equations. The plasma binding of DEX and MPL was linear with moderate binding (60.5% and 82.5%) in male and female rats. In vivo estimates of steroid uptake appeared linear across the tested concentrations and
was highest in liver and lowest in muscle for both steroids. Assessment of hepatic binding of MPL in vitro was severely affected by drug loss at 37°C in male liver homogenates, whereas DEX was stable in both male and female liver homogenates. With the exception of MPL in liver, in vitro-derived
estimates reasonably agreed with in vivo values. The mechanistic equations modestly underpredicted
for both drugs. Tissue metabolism, saturable tissue binding, and active uptake are possible factors that can complicate assessments of in vivo tissue binding of steroids when using tissue homogenates. SIGNIFICANCE STATEMENT: Assuming the free hormone hypothesis, the ratio of the unbound drug fraction in plasma and in tissues defines the tissue-to-plasma partition coefficient (
), an important parameter in physiologically based pharmacokinetic modeling that determines total drug concentrations within tissues and the steady-state volume of distribution. This study assessed the plasma and tissue binding properties of the synthetic corticosteroids, dexamethasone and methylprednisolone, in rats using ultrafiltration and tissue homogenate techniques. In vitro-in vivo and in silico-in vivo extrapolation of
was assessed for both drugs in liver, muscle, and lung. Although the extrapolation was fairly successful across the tissues, in vitro homogenate studies severely underpredicted the
of methylprednisolone in liver, partly attributable to the extensive hepatic metabolism.
The efficacy and safety of methylprednisolone in mechanically ventilated patients with acute respiratory distress syndrome resulting from coronavirus disease 2019 (COVID-19) are unclear. In this ...study, we evaluated the association between use of methylprednisolone and key clinical outcomes.
Clinical outcomes associated with the use of methylprednisolone were assessed in an unmatched, case-control study; a subset of patients also underwent propensity-score matching. Patients were admitted between 1 March and 12 April, 2020. The primary outcome was ventilator-free days by 28 days after admission. Secondary outcomes included extubation, mortality, discharge, positive cultures, and hyperglycemia.
A total of 117 patients met inclusion criteria. Propensity matching yielded a cohort of 42 well-matched pairs. Groups were similar except for hydroxychloroquine and azithromycin use, which were more common in patients who did not receive methylprednisolone. Mean ventilator-free days were significantly higher in patients treated with methylprednisolone (6.21 ± 7.45 vs 3.14 ± 6.22; P = .044). The probability of extubation was also increased in patients receiving methylprednisolone (45% vs 21%; P = .021), and there were no significant differences in mortality (19% vs 36%; P = .087). In a multivariable linear regression analysis, only methylprednisolone use was associated with a higher number of ventilator-free days (P = .045). The incidence of positive cultures and hyperglycemia were similar between groups.
Methylprednisolone was associated with increased ventilator-free days and higher probability of extubation in a propensity-score matched cohort. Randomized, controlled studies are needed to further define methylprednisolone use in patients with COVID-19.
A slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) ...high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE.
We prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA- cells; and (3) non-suppressive FoxP3lowCD45RA- cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score.
Seventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53-8.43) at day 0 to 2.80% (0.83-14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50-12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02-20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20-17.70) at day 0 to 4.74% (1.03-9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2.
IV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE.
Total knee arthroplasty (TKA) is associated with severe pain and inflammation despite an extensive multimodal analgesic approach, but the effect of high-dose glucocorticoid administration has not ...been studied.
Forty-eight patients undergoing unilateral TKA were included in a randomized, double-blind, placebo-controlled trial receiving preoperative methylprednisolone (MP) 125 mg i.v. or saline. All surgery was performed under lumbar spinal anaesthesia and patients received a standardized, multimodal analgesic regime. The primary endpoint was pain during walking 24 h after surgery, and secondary endpoints were pain at rest, pain upon hip flexion, and pain upon knee flexion. Pain assessments were performed repeatedly for the first 48 h after surgery, in a questionnaire from days 2 to 10, and at follow-up on days 21 and 30. Tertiary endpoints were postoperative nausea and vomiting (PONV), plasma C-reactive protein (CRP) concentrations, fatigue, sleep quality, and rescue analgesic and antiemetic requirements.
Pain during walking was significantly lower in the MP group up to 32 h after operation. Overall pain and cumulative pain scores (2–48 h) were lower for all pain assessments (P<0.04). Consumption of rescue oxycodone was lower from 0 to 24 h (P=0.02) and PONV, consumption of ondansetron reduced (P<0.05), and CRP concentrations were lower at 24 h (P<0.000001). Fatigue throughout the day of surgery was lower (P=0.02), but sleep quality was worse on the first night (P=0.002). No side-effects or complications were observed in other respects.
MP 125 mg before surgery improves analgesia and immediate recovery after TKA, even when combined with a multimodal analgesic regime. These findings call for further studies on safety aspects.
Registered with ClinicalTrails.gov under the US National Library of Medicine (registration number: NCT00968578).
•As Add-on therapy, IFN β-1b shortened the time to clinical improvement.•IFN β-1b significantly increased the discharge rate at day 14.•IFN β-1b reduced overall 28-day mortality.•IFN β-1b related ...adverse effects were mild and did not cause treatment interruptions.
In this study, efficacy and safety of interferon (IFN) β-1b in the treatment of patients with severe COVID-19 were evaluated.
Among an open-label, randomized clinical trial, adult patients (≥18 years old) with severe COVID-19 were randomly assigned (1:1) to the IFN group or the control group. Patients in the IFN group received IFN β-1b (250 mcg subcutaneously every other day for two consecutive weeks) along with the national protocol medications while in the control group, patients received only the national protocol medications (lopinavir/ritonavir or atazanavir/ritonavir plus hydroxychloroquine for 7–10 days). The primary outcome of the study was time to clinical improvement. Secondary outcomes were in-hospital complications and 28-daymortality.
Between April 20 and May 20, 2020, 80 patients were enrolled and finally 33 patients in each group completed the study. Time to clinical improvment in the IFN group was significantly shorter than the control group (9(6–10) vs. 11(9–15) days respectively, p = 0.002, HR = 2.30; 95% CI: 1.33–3.39). At day 14, the percentage of discharged patients was 78.79% and 54.55% in the IFN and control groups respectively (OR = 3.09; 95% CI: 1.05–9.11, p = 0.03). ICU admission rate in the control group was significantly higher than the IFN group (66.66% vs. 42.42%, p = 0.04). The duration of hospitalization and ICU stay were not significantly different between the groups All-cause 28-day mortality was 6.06% and 18.18% in the IFN and control groups respectively (p = 0.12).
IFN β-1b was effective in shortening the time to clinical improvement without serious adverse events in patients with severe COVID-19. Furthermore, admission in ICU and need for invasive mechanical ventilation decreased following administration of IFN β-1b. Although 28-day mortality was lower in the IFN group, further randomized clinical trials with large sample size are needed for exact estimation of survival benefit of IFN β-1b.
COVID‐19 in posttransplant patients—report of 2 cases Huang, Jiaofeng; Lin, Heng; Wu, Yinlian ...
American journal of transplantation,
July 2020, 2020-Jul, 2020-07-00, 20200701, Letnik:
20, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Coronavirus Disease 2019 (COVID‐19) has become a pandemic since March 2020. We describe here 2 cases of COVID‐19 infection in a posttransplant setting. First one is a 59‐year‐old renal transplant ...recipient; the second is a 51‐year‐old allogeneic bone marrow transplant recipient. Both patients were on immunosuppressant therapy and had stable graft function before COVID‐19 infection. After the diagnosis of COVID‐19, immunosuppressive agents were discontinued and methylprednisolone with prophylactic antibiotics were initiated, however, the lung injury progressed. The T cells were extremely low in both patients after infection. Both patients died despite the maximal mechanical ventilatory support. Therefore, the prognosis of COVID‐19 pneumonia following transplantation is not optimistic and remains guarded. Lower T cell count may be a surrogate for poor outcome.
This report presents the clinical features, treatment, and outcome of two posttransplant patients with COVID‐19.
Immunomodulants have been proposed to mitigate severe acute respiratory syndrome coronavirus 2–induced cytokine storm, which drives acute respiratory distress syndrome in coronavirus disease 2019 ...(COVID-19).
We sought to determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation.
A secondary analysis of prospective observational cohort studies was carried out at an Italian tertiary health care facility. COVID-19 patients consecutively hospitalized (February 25, 2020, to March 30, 2020) with hyperinflammation (ferritin ≥1000 ng/mL and/or C-reactive protein >10 mg/dL) and respiratory failure (oxygen therapy from 0.4 FiO2 Venturi mask to invasive mechanical ventilation) were evaluated to investigate the effect of high-dose anakinra plus methylprednisolone on survival. Patients were followed from study inclusion to day 28 or death. Crude and adjusted (sex, age, baseline PaO2:FiO2 ratio, Charlson index, baseline mechanical ventilation, hospitalization to inclusion lapse) risks were calculated (Cox proportional regression model).
A total of 120 COVID-19 patients with hyperinflammation (median age, 62 years; 80.0% males; median PaO2:FiO2 ratio, 151; 32.5% on mechanical ventilation) were evaluated. Of these, 65 were treated with anakinra and methylprednisolone and 55 were untreated historical controls. At 28 days, mortality was 13.9% in treated patients and 35.6% in controls (Kaplan-Meier plots, P = .005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared with controls (hazard ratio, 0.33, 95% CI, 0.15-0.74, P = .007, and HR, 0.18, 95% CI, 0.07-0.50, P = .001, respectively). No significant differences in bloodstream infections or laboratory alterations were registered.
Treatment with anakinra plus methylprednisolone may be a valid therapeutic option in COVID-19 patients with hyperinflammation and respiratory failure, also on mechanical ventilation. Randomized controlled trials including the use of either agent alone are needed to confirm these results.
INTRODUCTION: The use of glucocorticosteroids (GCs) through oral, intravenous, intramuscular, or rectal routes is prohibited in sports. Its use is permitted through inhalation, topical and ...intra-articular route of administration. Methylprednisolone (MP) is available for use by different routes for anti-inflammatory and immunosuppressive purposes. To discriminate its intake by permitted & forbidden routes, a reporting level of 30 ng/ml is set by World Anti-Doping Agency. The aim of this study was to compare MP's excretion profile following oral & intra-articular administration & to evaluate its effect on endogenous GCs profile.
MATERIALS & METHODS: The MP was administered through oral and intra-articular route to different patients & urine samples were collected up to 100 h. The urine samples were hydrolyzed, extracted, and analyzed on Liquid chromatography-mass spectrometry/MS.
RESULTS: MP levels in urine exceeded the reporting limit of 30 ng/ml after oral (8 mg) and intra-articular administration (80 mg) routes. After oral intake (8 mg), MP levels exceeded the reporting level up to 24 h. However, after intra-articular injection (80 mg), the MP could be detected above the reporting level up to 80 h.
CONCLUSION: The findings reveal that the MP can exceed the reporting level in urine even after administration by permitted route (i.a.). Further analysis of four endogenous GCs (Cortisol, Cortisone, TH Cortisone, and 11-deoxycortisol) showed a decreased excretion following administration of MP by oral & intra-articular routes.
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