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Intensive Care Medicine Aug 2022Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes.
METHODS
This double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72-96 h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40 mg loading bolus was followed by 40 mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1 year of follow-up.
RESULTS
Between January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57-1.40). There were no significant differences in secondary outcomes or complications.
CONCLUSIONS
In patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.
Topics: Adult; Community-Acquired Infections; Critical Illness; Humans; Methylprednisolone; Pneumonia; Respiration, Artificial; Treatment Outcome
PubMed: 35723686
DOI: 10.1007/s00134-022-06684-3 -
JAMA May 2022The effect of glucocorticoids on major kidney outcomes and adverse events in IgA nephropathy has been uncertain. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The effect of glucocorticoids on major kidney outcomes and adverse events in IgA nephropathy has been uncertain.
OBJECTIVE
To evaluate the efficacy and adverse effects of methylprednisolone in patients with IgA nephropathy at high risk of kidney function decline.
DESIGN, SETTING, AND PARTICIPANTS
An international, multicenter, double-blind, randomized clinical trial that enrolled 503 participants with IgA nephropathy, proteinuria greater than or equal to 1 g per day, and estimated glomerular filtration rate (eGFR) of 20 to 120 mL/min/1.73 m2 after at least 3 months of optimized background care from 67 centers in Australia, Canada, China, India, and Malaysia between May 2012 and November 2019, with follow-up until June 2021.
INTERVENTIONS
Participants were randomized in a 1:1 ratio to receive oral methylprednisolone (initially 0.6-0.8 mg/kg/d, maximum 48 mg/d, weaning by 8 mg/d/mo; n = 136) or placebo (n = 126). After 262 participants were randomized, an excess of serious infections was identified, leading to dose reduction (0.4 mg/kg/d, maximum 32 mg/d, weaning by 4 mg/d/mo) and addition of antibiotic prophylaxis for pneumocystis pneumonia for subsequent participants (121 in the oral methylprednisolone group and 120 in the placebo group).
MAIN OUTCOMES AND MEASURES
The primary end point was a composite of 40% decline in eGFR, kidney failure (dialysis, transplant), or death due to kidney disease. There were 11 secondary outcomes, including kidney failure.
RESULTS
Among 503 randomized patients (mean age, 38 years; 198 [39%] women; mean eGFR, 61.5 mL/min/1.73 m2; mean proteinuria, 2.46 g/d), 493 (98%) completed the trial. Over a mean of 4.2 years of follow-up, the primary outcome occurred in 74 participants (28.8%) in the methylprednisolone group compared with 106 (43.1%) in the placebo group (hazard ratio [HR], 0.53 [95% CI, 0.39-0.72]; P < .001; absolute annual event rate difference, -4.8% per year [95% CI, -8.0% to -1.6%]). The effect on the primary outcome was seen across each dose compared with the relevant participants in the placebo group recruited to each regimen (P for heterogeneity = .11): full-dose HR, 0.58 (95% CI, 0.41-0.81); reduced-dose HR, 0.27 (95% CI, 0.11-0.65). Of the 11 prespecified secondary end points, 9 showed significant differences in favor of the intervention, including kidney failure (50 [19.5%] vs 67 [27.2%]; HR, 0.59 [95% CI, 0.40-0.87]; P = .008; annual event rate difference, -2.9% per year [95% CI, -5.4% to -0.3%]). Serious adverse events were more frequent with methylprednisolone vs placebo (28 [10.9%] vs 7 [2.8%] patients with serious adverse events), primarily with full-dose therapy compared with its matching placebo (22 [16.2%] vs 4 [3.2%]).
CONCLUSIONS AND RELEVANCE
Among patients with IgA nephropathy at high risk of progression, treatment with oral methylprednisolone for 6 to 9 months, compared with placebo, significantly reduced the risk of the composite outcome of kidney function decline, kidney failure, or death due to kidney disease. However, the incidence of serious adverse events was increased with oral methylprednisolone, mainly with high-dose therapy.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01560052.
Topics: Administration, Oral; Adult; Disease Progression; Double-Blind Method; Female; Glomerulonephritis, IGA; Humans; Kidney; Male; Methylprednisolone; Proteinuria; Renal Dialysis; Renal Insufficiency
PubMed: 35579642
DOI: 10.1001/jama.2022.5368 -
Arquivos de Neuro-psiquiatria Jun 2017Spinal cord injury (SCI) affects 1.3 million North Americans, with more than half occurring after trauma. In Brazil, few studies have evaluated the epidemiology of SCI... (Review)
Review
Spinal cord injury (SCI) affects 1.3 million North Americans, with more than half occurring after trauma. In Brazil, few studies have evaluated the epidemiology of SCI with an estimated incidence of 16 to 26 per million per year. The final extent of the spinal cord damage results from primary and secondary mechanisms that start at the moment of the injury and go on for days, and even weeks, after the event. There is convincing evidence that hypotension contributes to secondary injury after acute SCI. Surgical decompression aims at relieving mechanical pressure on the microvascular circulation, therefore reducing hypoxia and ischemia. The role of methylprednisolone as a therapeutic option is still a matter of debate, however most guidelines do not recommend its regular use. Neuroprotective therapies aiming to reduce further injury have been studied and many others are underway. Neuroregenerative therapies are being extensively investigated, with cell based therapy being very promising.
Topics: Decompression, Surgical; Humans; Methylprednisolone; Neuroprotective Agents; Spinal Cord Injuries; Trauma Severity Indices
PubMed: 28658409
DOI: 10.1590/0004-282X20170048 -
ACS Nano Nov 2023Spinal cord injury (SCI) can cause permanent loss of sensory and motor function, and there is no effective clinical treatment, to date. Due to the complex pathological...
Spinal cord injury (SCI) can cause permanent loss of sensory and motor function, and there is no effective clinical treatment, to date. Due to the complex pathological process involved after injury, synergistic treatments are very urgently needed in clinical practice. We designed a nanofiber scaffold hyaluronic acid hydrogel patch to release both exosomes and methylprednisolone to the injured spinal cord in a non-invasive manner. This composite patch showed good biocompatibility in the stabilization of exosome morphology and toxicity to nerve cells. Meanwhile, the composite patch increased the proportion of M2-type macrophages and reduced neuronal apoptosis in an in vitro study. In vivo, the functional and electrophysiological performance of rats with SCI was significantly improved when the composite patch covered the surface of the hematoma. The composite patch inhibited the inflammatory response through macrophage polarization from M1 type to M2 type and increased the survival of neurons by inhibition neuronal of apoptosis after SCI. The therapeutic effects of this composite patch can be attributed to TLR4/NF-κB, MAPK, and Akt/mTOR pathways. Thus, the composite patch provides a medicine-exosomes dual-release system and may provide a non-invasive method for clinical treatment for individuals with SCI.
Topics: Rats; Animals; Methylprednisolone; Exosomes; Spinal Cord Injuries; Macrophages; Neurons; Spinal Cord
PubMed: 37948097
DOI: 10.1021/acsnano.3c08046 -
The New England Journal of Medicine Dec 2022Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown.
METHODS
We conducted a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (<1 year of age) undergoing heart surgery with cardiopulmonary bypass at 24 sites participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Registry data were used in the evaluation of outcomes. The infants were randomly assigned to receive prophylactic methylprednisolone (30 mg per kilogram of body weight) or placebo, which was administered into the cardiopulmonary-bypass pump-priming fluid. The primary end point was a ranked composite of death, heart transplantation, or any of 13 major complications. Patients without any of these events were assigned a ranked outcome based on postoperative length of stay. In the primary analysis, the ranked outcomes were compared between the trial groups with the use of odds ratios adjusted for prespecified risk factors. Secondary analyses included an unadjusted odds ratio, a win ratio, and safety outcomes.
RESULTS
A total of 1263 infants underwent randomization, of whom 1200 received either methylprednisolone (599 infants) or placebo (601 infants). The likelihood of a worse outcome did not differ significantly between the methylprednisolone group and the placebo group (adjusted odds ratio, 0.86; 95% confidence interval [CI], 0.71 to 1.05; P = 0.14). Secondary analyses (unadjusted for risk factors) showed an odds ratio for a worse outcome of 0.82 (95% CI, 0.67 to 1.00) and a win ratio of 1.15 (95% CI, 1.00 to 1.32) in the methylprednisolone group as compared with the placebo group, findings suggestive of a benefit with methylprednisolone; however, patients in the methylprednisolone group were more likely than those in the placebo group to receive postoperative insulin for hyperglycemia (19.0% vs. 6.7%, P<0.001).
CONCLUSIONS
Among infants undergoing surgery with cardiopulmonary bypass, prophylactic use of methylprednisolone did not significantly reduce the likelihood of a worse outcome in an adjusted analysis and was associated with postoperative development of hyperglycemia warranting insulin in a higher percentage of infants than placebo. (Funded by the National Center for Advancing Translational Sciences and others; STRESS ClinicalTrials.gov number, NCT03229538.).
Topics: Humans; Methylprednisolone; Prospective Studies; Cardiac Surgical Procedures; Insulin
PubMed: 36342116
DOI: 10.1056/NEJMoa2212667 -
Neurology Aug 2019Due to the continuing debates on the utility of high-dose methylprednisolone (MP) early after acute spinal cord injury (ASCI), we aimed to evaluate the therapeutic and... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
Due to the continuing debates on the utility of high-dose methylprednisolone (MP) early after acute spinal cord injury (ASCI), we aimed to evaluate the therapeutic and adverse effects of high-dose MP according to the second National Acute Spinal Cord Injury Study (NASCIS-2) dosing protocol in comparison to no steroids in patients with ASCI by performing a meta-analysis on the basis of the current available clinical trials.
METHODS
We searched PubMed and Cochrane Library (to May 22, 2018) for studies comparing neurologic recoveries, adverse events, and in-hospital costs between ASCI patients who underwent high-dose MP treatment or not. Data were synthesized with corresponding statistical models according to the degree of heterogeneity.
RESULTS
We enrolled 16 studies (1,863 participants) including 3 randomized controlled trials (RCTs) and 13 observational studies. Pooled results indicated that MP was not associated with an increase in motor score improvement (RCTs: = 0.84; observational studies: = 0.44) and incidence of recovery by at least one grade on the American Spinal Injury Association Impairment Scale or Frankel ( = 0.53). Meanwhile, MP did not lead to better sensory recovery ( = 0.07). However, MP was associated with a significantly higher incidence of gastrointestinal hemorrhage ( = 0.04) and respiratory tract infection ( = 0.01). The difference in the overall in-hospital costs between MP and control groups was not statistically significant ( = 0.78).
CONCLUSIONS
Based on the current evidence, high-dose MP treatment, in comparison to controls, does not contribute to better neurologic recoveries but may increase the risk of adverse events in patients with ASCI. Therefore, we recommend against routine use of high-dose MP early after ASCI.
Topics: Adolescent; Adult; Clinical Trials as Topic; Female; Humans; Male; Methylprednisolone; Middle Aged; Neuroprotective Agents; Recovery of Function; Spinal Cord Injuries; Young Adult
PubMed: 31358617
DOI: 10.1212/WNL.0000000000007998 -
Intensive Care Medicine Dec 2023Patients who are successfully resuscitated following out-of-hospital cardiac arrest (OHCA) are still at a high risk of neurological damage and death. Inflammation and... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Patients who are successfully resuscitated following out-of-hospital cardiac arrest (OHCA) are still at a high risk of neurological damage and death. Inflammation and brain injury are components of the post-cardiac arrest syndrome, and can be assessed by systemic interleukin 6 (IL-6) and neuron-specific enolase (NSE). Anti-inflammatory treatment with methylprednisolone may dampen inflammation, thereby improving outcome. This study aimed to determine if prehospital high-dose methylprednisolone could reduce IL-6 and NSE in comatose OHCA patients.
METHODS
The STEROHCA trial was a randomized, blinded, placebo-controlled, phase II prehospital trial performed at two cardiac arrest centers in Denmark. Resuscitated comatose patients with suspected cardiac etiology were randomly assigned 1:1 to a single intravenous injection of 250 mg methylprednisolone or placebo. The co-primary outcome was reduction of IL-6 and NSE-blood levels measured daily for 72 h from admission. The main secondary outcome was survival at 180 days follow-up.
RESULTS
We randomized 137 patients to methylprednisolone (n = 68) or placebo (n = 69). We found reduced IL-6 levels (p < 0.0001) in the intervention group, with median (interquartile range, IQR) levels at 24 h of 2.1 pg/ml (1.0; 7.1) and 30.7 pg/ml (14.2; 59) in the placebo group. We observed no difference between groups in NSE levels (p = 0.22), with levels at 48 h of 18.8 ug/L (14.4; 24.6) and 14.8 ug/L (11.2; 19.4) in the intervention and placebo group, respectively. In the intervention group, 51 (75%) patients survived and 44 (64%) in the placebo group.
CONCLUSION
Prehospital treatment with high-dose methylprednisolone to resuscitated comatose OHCA patients, resulted in reduced IL-6 levels after 24 h, but did not reduce NSE levels.
Topics: Humans; Out-of-Hospital Cardiac Arrest; Coma; Methylprednisolone; Interleukin-6; Inflammation; Emergency Medical Services; Biomarkers; Phosphopyruvate Hydratase
PubMed: 37943300
DOI: 10.1007/s00134-023-07247-w -
Archivos de La Sociedad Espanola de... Jun 2022Trochleitis is usually a transient and non-disabling inflammation of the trochlea of superior oblique. The case is presented of a difficult to manage bilateral...
Trochleitis is usually a transient and non-disabling inflammation of the trochlea of superior oblique. The case is presented of a difficult to manage bilateral trochleitis in a 29-year-old woman. After an exhaustive aetiological study with neuro-imaging tests, as well as an analysis of autoimmunity and infection, no underlying cause was found. Multiple injections of corticosteroids were required in both eyes, with a partial effect. Surgical intervention was finally decided in order to visually examine the trochlea, take biopsies, and inject methylprednisolone. These were effective in relieving the symptoms. This case is exceptional due to it involving both eyes and its severity, and represented a therapeutic challenge for the clinical team.
Topics: Adult; Biopsy; Eye; Female; Humans; Methylprednisolone; Oculomotor Muscles
PubMed: 35676027
DOI: 10.1016/j.oftale.2020.12.018 -
The Journal of the American Academy of... Sep 2023Spinal cord injury (SCI) is a leading cause of disability worldwide, and effective management is necessary to improve clinical outcomes. Many long-standing therapies... (Review)
Review
Spinal cord injury (SCI) is a leading cause of disability worldwide, and effective management is necessary to improve clinical outcomes. Many long-standing therapies including early reduction and spinal cord decompression, methylprednisolone administration, and optimization of spinal cord perfusion have been around for decades; however, their efficacy has remained controversial because of limited high-quality data. This review article highlights studies surrounding the role of early surgical decompression and its role in relieving mechanical pressure on the microvascular circulation thereby reducing intraspinal pressure. Furthermore, the article touches on the current role of methylprednisolone and identifies promising studies evaluating neuroprotective and neuroregenerative agents. Finally, this article outlines the expanding body of literature evaluating mean arterial pressure goals, cerebrospinal fluid drainage, and expansive duroplasty to further optimize vascularization to the spinal cord. Overall, this review aims to highlight evidence for SCI treatments and ongoing trials that may markedly affect SCI care in the near future.
Topics: Humans; Spinal Cord Injuries; Decompression, Surgical; Methylprednisolone; Pressure; Spinal Cord
PubMed: 37432977
DOI: 10.5435/JAAOS-D-23-00281 -
Continuum (Minneapolis, Minn.) Apr 2018This article provides an update on the acute and subacute management and prognostication of patients with traumatic spinal cord injury. (Review)
Review
PURPOSE OF REVIEW
This article provides an update on the acute and subacute management and prognostication of patients with traumatic spinal cord injury.
RECENT FINDINGS
Immobilization of the spine and spine clearance should be individualized depending on the ability to perform a reliable neurologic examination, the presence of neck pain, and the imaging findings. Early surgery (within 24 hours) to achieve definitive cord decompression and spine stabilization may be beneficial. Ensuring adequate oxygenation and perfusion and avoiding secondary systemic complications remain the goals of the critical care of these patients. No neuroprotective treatment has been shown to improve outcomes. In fact, the use of high-dose methylprednisolone is now generally discouraged because of its major systemic adverse effects. Survivors of severe cervical traumatic spinal cord injury typically sustain substantial long-term functional impairment. Advances in our understanding of neuroregenerative strategies, especially stem cell transplantation, can offer the future hope of functional improvement to the many patients currently living with the consequences of traumatic spinal cord injury. Yet, at present, these therapies remain strictly investigational.
SUMMARY
The treatment of traumatic spinal cord injury remains supportive, and prognosis is still poor for patients who are severely affected. While much remains to be learned about how to optimize the acute management of these patients, future efforts would be most useful if focused on injury prevention and the development of effective neuroregenerative therapies.
Topics: Decompression, Surgical; Humans; Methylprednisolone; Neurologic Examination; Neuroprotective Agents; Prognosis; Spinal Cord Injuries
PubMed: 29613899
DOI: 10.1212/CON.0000000000000581