Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial.

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

Traumatic Spinal Cord Injury.

OBJECTIVE: This article provides a review of the initial clinical and radiologic evaluation and treatment of patients with traumatic spinal cord injuries. It specifically highlights essential knowledge for neurologists who encounter patients with these complex injuries. LATEST DEVELOPMENTS: There has been improvement in the care of patients with traumatic spinal cord injuries, particularly in the prehospital evaluation, approach for immediate immobilization, standardized spinal clearance, efficient triage, and transportation of appropriate patients to traumatic spinal cord injury specialized centers. Advancements in spinal instrumentation have improved the surgical management of spinal fractures and the ability to manage patients with spinal mechanical instability. The clinical evidence favors performing early surgical decompression and spine stabilization within 24 hours of traumatic spinal cord injuries, regardless of the severity or location of the injury. There is no evidence that supports the use of neuroprotective treatments to improve outcomes in patients with traumatic spinal cord injuries. The administration of high-dose methylprednisolone, which is associated with significant systemic adverse effects, is strongly discouraged. Early and delayed mortality rates continue to be high in patients with traumatic spinal cord injuries, and survivors often confront substantial long-term physical and functional impairments. Whereas the exploration of neuroregenerative approaches, such as stem cell transplantation, is underway, these methods remain largely investigational. Further research is still necessary to advance the functional recovery of patients with traumatic spinal cord injuries. ESSENTIAL POINTS: Traumatic spinal cord injury is a complex and devastating condition that leads to long-term neurologic deficits with profound physical, social, and vocational implications, resulting in a diminished quality of life, particularly for severely affected patients. The initial management of traumatic spinal cord injuries demands comprehensive interdisciplinary care to address the potentially catastrophic multisystem effects. Ongoing endeavors are focused on optimizing and customizing initial management approaches and developing effective therapies for neuroprotection and neuroregeneration to enhance long-term functional recovery.

Safety of non-standard regimen of systemic steroid therapy in patients with Graves' orbitopathy: a single-centre experience.

BACKGROUND: Graves' orbitopathy (GO) is an autoimmune disorder of the orbit and retro-ocular tissues and the primary extrathyroidal manifestation of Graves' disease. In moderate-to-severe and active GO iv glucocorticoids (GCs) are recommended as first-line treatment. The aim was to assess the safety profile of methylprednisolone administered intravenously for three consecutive days at 1 g in patients with active, moderate-to-severe or sight-threatening Graves' orbitopathy. METHODS: We retrospectively evaluated 161 medical records of patients with GO treated with high-dose systemic GCs in the Department of Endocrinology, Metabolic Disorders, and Internal Medicine in Poznan between 2014 and 2021. Clinical data included age, gender, laboratory results, activity and severity of GO, smoking status, disease duration, and presented side effects. RESULTS: The presence of mild side effects was observed during 114 (71%) hospitalizations. The most common complications were hyperglycemia (n = 95) and elevated aminotransferases (n = 31). Increased levels of aminotransferases were more likely observed in smokers and GO duration above 12 months. Based on the multivariate logistic regression, higher TRAb and CAS values were significantly associated with lower odds of hyperglycemia. In turn, the increased odds of elevated aminotransferases were significantly correlated with higher initial ALT levels, female gender, and GO duration above 12 months. In addition, the multidimensional correspondence analysis (MPA) showed that GO patients who declared smoking and had not L-ornithine L-aspartate applied demonstrated a higher probability of elevated aminotransferases. CONCLUSIONS: Active GO treatment with high-dose systemic GCs is not associated with serious side effects. Hyperglycemia is the most common steroid-induced complication.

Cumulative pulse methylprednisolone and its relation to disease activity, damage and mortality in systemic lupus erythematosus patients: A post hoc analysis of COMOSLE-EGYPT study.

OBJECTIVE: To investigate the relation between cumulative intravenous methylprednisolone dose and disease activity, damage, and mortality among a group of Egyptian SLE patients. PATIENTS AND METHODS: This is a post hoc analysis of a retrospective multicenter COMOSLE study. Cumulative pulse methylprednisolone dose was abstracted from COMOSLE database. Patients with cumulative pulse dose of ≤ 3.0 g (median dose) were compared to those with cumulative dose of > 3.0 g regarding demographic data, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and The Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC) score as well as treatment received. Additionally, at 1.5, 3, 6, and 9 g of cumulative methylprednisolone, patients were compared regarding SLICC score and risk of mortality. RESULTS: Patients who received > 3 g of methylprednisolone were statistically significantly younger at disease onset, had longer disease duration, higher SLEDAI score at last visit, and higher SLICC score (p = 003, p = 0.002, p = 0.004 and p = < 0.001, respectively). Additionally, with every gram increase in the cumulative methylprednisolone, there was a significant increase in SLICC score by 0.169 (B = 0.169, CI = 0.122-0.216, p-value = < 0.001) and an increased risk of mortality by 13.5% (hazard ratio (HR) = 1.135, CI = 1.091-1.180, p-value = 0.001). The best cutoff value of methylprednisolone dose at which damage may occur, ranged between 2.75 (with sensitivity of 81.4% and specificity of 33.9%) and 3.25 g (with sensitivity of 48.3% and specificity of 71.5%). CONCLUSION: With every gram increase in the cumulative methylprednisolone, there may be increase in damage and mortality, especially in doses exceeding the range of 2.75-3.25 g. Key Points • Treatment of systemic lupus erythematosus should be with the least possible dose of steroids to decrease the risk of damage and mortality. • With every gram increase in the cumulative intravenous methylprednisolone there may be increase in damage and mortality.

The effect of different types of oral or intravenous corticosteroids on capillary blood glucose levels in hospitalized inpatients with and without diabetes.

PURPOSE: This study investigated: (1) the type of corticosteroid associated with the greatest degree of hyperglycemia, assessed using bedside capillary blood glucose monitoring, in hospitalized patients; and (2) the pattern of hyperglycemia throughout the day with the use of each type of corticosteroid. METHODS: This single-center, retrospective study used data from 964 adult inpatients receiving oral or IV corticosteroids. Data on capillary blood glucose concentrations and time taken over 7 days were collected. A mixed model for repeated measures was applied to investigate changes in glucose concentration over time with the use of four different corticosteroids. An autoregressive covariance structure was used to model correlations between repeated measurements. FINDINGS: Across all 7 days, the mean blood glucose concentration was greater with dexamethasone compared to that with hydrocortisone (mean difference, 16.6 mg/dL [95% CI, 8.1-24.8] [0.92 mmol/L (95% CI, 0.45-1.38)]) or prednisolone (mean difference, 20.0 mg/dL [95% CI, 14.2-25.7] [1.11 mmol/L (95% CI, 0.79-1.43)]). The mean blood glucose concentration was greater with methylprednisolone compared to that with hydrocortisone (mean difference, 23.9 mg/dL [95% CI, 11.3-36.4] [1.33 mmol/L (95% CI, 0.63-2.02)]), and with methylprednisolone versus prednisolone (mean difference, 27.4 mg/dL [95% CI, 16.4-38.3] [1.52 mmol/L (95% CI, 0.91-2.13)]). There were no significant differences in the patterns of hyperglycemia at six time points of the day with each type of corticosteroid. IMPLICATIONS: Treatment with oral or IV dexamethasone or methylprednisolone was associated with greater hyperglycemia in comparison to prednisolone and hydrocortisone. More vigorous monitoring and intervention, when necessary, are suggested in adult inpatients receiving corticosteroids, in particular dexamethasone and methylprednisolone.

The Efficacy, Adverse Effects and Economic Implications of Oral Versus Intravenous Methylprednisolone for the Treatment of Optic Neuritis: A Systematic Review.

INTRODUCTION: Optic neuritis may occur in a variety of conditions, including as a manifestation of multiple sclerosis. Despite significant research into the efficacy of corticosteroids as a first-line treatment, the optimal route of administration has not been well defined. This review aims to explore the efficacy, adverse effects and economic implications of using oral versus intravenous methylprednisolone to treat acute optic neuritis. METHODS: A systematic search of the databases PubMed/MEDLINE, Embase and CENTRAL was performed to July 2022, prior to data collection and risk of bias analysis in accordance with the PRISMA guidelines. RESULTS: Six articles fulfilled the inclusion criteria. The results showed that in the treatment of acute optic neuritis, oral methylprednisolone has a non-inferior efficacy and adverse effect profile in comparison to intravenous methylprednisolone. In a cost analysis, oral methylprednisolone to be more cost-effective than intravenous methylprednisolone. CONCLUSIONS: Oral methylprednisolone has comparable efficacy and adverse effect profiles to intravenous methylprednisolone for the treatment of optic neuritis. The analysis suggests oral administration is more cost-effective than intravenous administration; however, further analyses of the formal cost-benefit ratio are required.

Pulse Methylprednisolone-Induced Sinus Bradycardia: A Case Report.

Corticosteroids have a wide range of uses. The most commonadverse side effectsofhigh-dosepulse steroids are hyperglycemia, gastrointestinal intolerance, and psychiatric symptoms. Cardiac arrhythmias have been reported in patients who receive high-dose steroid therapy. Bradycardia is a rare adverse side effect of pulse steroid therapy. We present the case of a 57-year-old male patient who developed symptomatic sinus bradycardia after he received pulse methylprednisolone therapy as treatment for graft-versushost disease. The patient's pulse steroid therapy was discontinued, and the dose of methylprednisolone was reduced to 100 mg/day. He was treated conservatively and with close observation; the patient's heart rate increased to 68 beats/min after 1 day, and then to 78 beats/min. The diagnosis of methylprednisolone-induced bradycardia was made after exclusion of other common etiologies of sinus bradycardia. This case report demonstrates the importance of careful cardiovascular monitoring in patients who receive high-dose methylprednisolone because of dose-related cardiovascular risks.

Efficacy and safety of glucocorticoids use in patients with COVID-19: a systematic review and network meta­analysis.

BACKGROUND: Currently, some meta-analyses on COVID-19 have suggested that glucocorticoids use can reduce the mortality rate of COVID-19 patients, utilization rate of invasive ventilation, and improve the prognosis of patients. However, optimal regimen and dosages of glucocorticoid remain unclear. Therefore, the purpose of this network meta-analysis is to analyze the efficacy and safety of glucocorticoids in treating COVID-19 at regimens. METHODS: This meta-analysis retrieved randomized controlled trials from the earliest records to December 30, 2022, published in PubMed, Embase, Cochrane Library, CNKI Database and Wanfang Database, which compared glucocorticoids with placebos for their efficacy and safety in the treatment of COVID-19, Effects of different treatment regimens, types and dosages (high-dose methylprednisolone, very high-dose methylprednisolone, Pulse therapy methylprednisolone, medium-dose hydrocortisone, high-dose hydrocortisone, high-dose dexamethasone, very high-dose dexamethasone and placebo) on 28-day all-caused hospitalization mortality, hospitalization duration, mechanical ventilation requirement, ICU admission and safety outcome were compared. RESULTS: In this network meta-analysis, a total of 10,544 patients from 19 randomized controlled trials were finally included, involving a total of 9 glucocorticoid treatment regimens of different types and dosages. According to the analysis results, the 28-day all-cause mortality rate was the lowest in the treatment with pulse therapy methylprednisolone (OR 0.08, 95% CI 0.02, 0.42), but the use of high-dose methylprednisolone (OR 0.85, 95% CI 0.59, 1.22), very high-dose dexamethasone (OR 0.95, 95% CI 0.67, 1.35), high-dose hydrocortisone (OR 0.64, 95% CI 0.34, 1.22), medium-dose hydrocortisone (OR 0.80, 95% CI 0.49, 1.31) showed no benefit in prolonging the 28-day survival of patient. Compared with placebo, the treatment with very high-dose methylprednisolone (MD = -3.09;95%CI: -4.10, -2.08) had the shortest length of hospital stay, while high-dose dexamethasone (MD = -1.55;95%CI: -3.13,0.03) and very high-dose dexamethasone (MD = -1.06;95%CI: -2.78,0.67) did not benefit patients in terms of length of stay. CONCLUSIONS: Considering the available evidence, this network meta­analysis suggests that the prognostic impact of glucocorticoids in patients with COVID-19 may depend on the regimens of glucocorticoids. It is suggested that pulse therapy methylprednisolone is associated with lower 28-day all-cause mortality, very high-dose methylprednisolone had the shortest length of hospital stay in patients with COVID-19. TRIAL REGISTRATION: PROSPERO CRD42022350407 (22/08/2022).

The effects of prophylactic tadalafil use on VEGF expression in the rabbit model of steroid-induced femoral head avascular necrosis.

OBJECTIVE: The purpose of this study was to examine the effect of prophylactic tadalafil use on a steroid-induced femoral head avascular necrosis model in terms of microscopic, imaging, and molecular biological changes. METHODS: Twenty-four New Zealand rabbits were divided into 3 equal groups. Eight rabbits were designated as the control group and did not receive treatment. Rabbits in group 1 (G1) received 0.1 mg/kg Escherichia coli lipopolysaccharide (LPS) intravenously and 40 mg/ kg methylprednisolone sodium succinate (MP) was administered intramuscularly for 3 days consecutively. Rabbits in group 2 (G2) were given 5 mg/kg tadalafil orally for 10 consecutive days. Starting on the eighth day, 0.1 mg/kg LPS was given, and following this 40 mg/kg MP injections were administered for 3 days. All animals were sacrificed 3 weeks after the final MP injection. Magnetic resonance imaging was performed, and bilateral femora were harvested. Half of the femoral head was stored for Vascular Endothelial Growth Factor (VEGF) examination with Western blot analysis. The other half was examined microscopically for the presence of osteonecrosis. RESULTS: In G1, 15 out of 16 hips (93%) of the 8 rabbits had osteonecrosis compared to 8 out of 12 hips (67%) of 6 rabbits in G2 (P > .05). The VEGF expression in G2 was significantly higher than in the control group and G1 (P < .05 and P < .001, respectively). There was no significant difference in VEGF expression between the control group and G1 (P > .05). CONCLUSION: This study has shown us that femoral head osteonecrosis can be reliably induced with LPS and corticosteroid, as described in the literature. Prophylactic tadalafil use did not decrease the occurrence of osteonecrosis significantly. However, it significantly increased VEGF expression in the femoral head independent of the effects of steroids and LPS.

Methylprednisolone therapy induces differential metabolic trajectories in severe COVID-19 patients.

IMPORTANCE: The SARS-CoV-2 virus infection in humans induces significant inflammatory and systemic reactions and complications of which corticosteroids like methylprednisolone have been recommended as treatment. Our understanding of the metabolic and metabolomic pathway dysregulations while using intravenous corticosteroids in COVID-19 is limited. This study will help enlighten the metabolic and metabolomic pathway dysregulations underlying high daily doses of intravenous methylprednisolone in COVID-19 patients compared to those receiving placebo. The information on key metabolites and pathways identified in this study together with the crosstalk with the inflammation and biochemistry components may be used, in the future, to leverage the use of methylprednisolone in any future pandemics from the coronavirus family.

The influence of calcitriol and methylprednisolone on podocytes function in minimal change disease in vitro model.

Minimal change disease (MCD), considered one of the major causes of nephrotic syndrome, is a complex pathological condition with disturbances in podocytes' foot processes. Numerous studies suggested the essential role of vitamin D3 in maintaining proper glomerulus function. However, the data on direct potential of that compound in reference to podocytes are scarce. Thus, here we assessed the influence of calcitriol (active vitamin D3) on podocyte function, apart from commonly used steroids (methylprednisolone). CIHP-1 podocyte cell line was used to implement the LPS-PAN-induced MCD in vitro model. Viability, podocyte-related slit diaphragm proteins, morphology, function as a barrier was evaluated using flow cytometry, RT-PCR, confocal microscopy, and TEER analysis. Calcitriol or methylprednisolone did not affect cell viability. Podocyte-related proteins demonstrated different responses to in vitro treatment compared to previously reported changes in total glomeruli. Podocyte morphology was partially restored in the presence of the tested compounds. In addition, TEER analysis revealed improvement of LPS-PAN-induced cells' function as a barrier when vitamin D3 or steroid was used. In conclusion, a significant potential for modulation of MCD in vitro model podocytes with calcitriol or selected steroids was reported. Further studies on vitamin D3 in context of podocyte-related phenomenon accompanying MCD are of great importance.

A Randomized Clinical Trial of Intravenous Methylprednisolone With 2 Protocols in Patients With Graves Orbitopathy.

CONTEXT: Intravenous glucocorticoid (IVGC) is an accessible and affordable treatment for Graves orbitopathy (GO); the 4.5-g protocol is well studied, but many details of treatment protocols need to be clarified. OBJECTIVE: To compare the efficacy and safety of weekly and monthly protocol of IVGC in GO. METHODS: A prospective, randomized, observer-masked, single-center clinical trial, followed up to week 24, at the third affiliated hospital of Southern Medical University; 58 patients with active and moderate to severe GO, aged 18-60 years old, who had not received relevant treatment were included. The intervention was weekly protocol or monthly protocol of IVGC; both received a cumulative dose of methylprednisolone 4.5 g and had a duration of 12 weeks. The overall effective rate, improvement of quality of life (QOL) and signal intensity ratio (SIR) were measured. RESULTS: There was no significant difference in the effective rate between the 2 groups at week 12 and week 24 (86.21% vs 72.41%, P = .195; 86.21% vs 82.61%, P = .441), there was no significant difference in the improvement of clinical activity score, exophthalmos, soft tissue involvement, diplopia, and QOL. At week 24, the mean SIR and maximum SIR of the 2 groups were lower than those before treatment, and there were no statistically significant difference between the 2 groups. There was no significant difference in the incidence of adverse events between the 2 groups (31.03% vs 27.59%, P = .773). CONCLUSION: The efficacy and safety of the 2 protocols are comparable; the monthly protocol could be used as an alternative to the weekly protocol.

Corticosteroid-Associated Avascular Necrosis of the Femoral Head in Patients with Severe COVID-19: A Single-Center Study.

BACKGROUND Avascular necrosis (AVN) of the femoral head can result from high-dose corticosteroid therapy. Given that severe COVID-19 pneumonia patients respond positively to corticosteroids, this study aimed to explore the incidence of femoral head AVN associated with corticosteroid therapy in 24 patients diagnosed with severe COVID-19 at a single center. MATERIAL AND METHODS The study included 24 patients who were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through real-time reverse transcription polymerase chain reaction test (rRT-PCR) and with COVID-19 pneumonia via high-resolution computed tomography (HRCT). Moderate cases received 2×4 mg Dexamethasone while severe cases were also administered with 3×40 mg Methylprednisolone. Diagnosis of femoral head AVN was confirmed with magnetic resonance imaging (MRI) and radiographs, which was subsequently treated by a total hip arthroplasty (THA) or a core decompression surgery (CDS) in line with the Ficat and Arlet classifications RESULTS Among the patients, 8 had a moderate infection course, while 16 were severe. The mean corticosteroid duration was 15±5 days for Dexamethasone and 30 days for Methylprednisolone. Severe patients presented with higher grade femoral head AVN and greater pain levels compared to moderate cases (p<0.05). Four patients developed bilateral AVN. The treatment resulted in 23 THAs and 5 CDSs CONCLUSIONS The data from this study corroborate earlier studies and case reports, suggesting an increased occurrence of AVN of the femoral head during the COVID-19 pandemic due to the high-dose corticosteroid therapy employed for patients hospitalized with severe COVID-19 pneumonia.

The steroid-sparing effects of a mycophenolate mofetil-based regimen in the management of immunoglobulin A nephropathy in patients with histologically active lesions: A comparison with a control cohort receiving conventional therapy.

INTRODUCTION: While the use of different immunosuppressants has been investigated in immunoglobulin A nephropathy, further investigation is needed to assess the effect of a regimen of mycophenolate mofetil combined with a short course of glucocorticosteroids in the subset of patients with histologically active features. We compared the efficacy and safety of a combined regimen of mycophenolate mofetil and glucocorticosteroids to a conventional regimen of glucocorticosteroids alone in patients with immunoglobulin A nephropathy who have active lesions and major urinary abnormalities. METHODS: This retrospective study involved 30 immunoglobulin A nephropathy patients with active histological lesions, 15 of whom were treated with both mycophenolate mofetil 2 g/day for 6 months and 3 pulses of 15 mg/kg methylprednisolone, followed by a short tapering schedule of oral prednisone. The control group was made up of the remaining 15 clinically- and histologically-matched patients treated with glucocorticosteroids alone according to a validated schedule, i.e., 1 g of methylprednisolone given intravenously for 3 consecutive days, followed by oral prednisone 0.5 mg/kg every other day for 6 months. At diagnosis, all patients had urinary protein excretion > 1 g/24 h and microscopic hematuria. RESULTS: At the end of the first year of follow-up (30 patients) and after 5 years (17 patients), there were no differences between the two groups in terms of urinary abnormalities and functional parameters. Both regimens achieved a statistically significant decrease in 24-h urinary protein excretion (p < 0.001) and a reduction of microscopic hematuria. However, the mycophenolate mofetil-based regimen allowed a cumulative sparing dose of 6 g of glucocorticosteroids. CONCLUSION: In this single center study on immunoglobulin A nephropathy patients with active lesions and major urinary abnormalities and at increased risk of glucocorticosteroid-related complications, a mycophenolate mofetil-based regimen demonstrated similar outcomes in terms of complete response and relapse (at 1 and 5 years) compared to a conventional glucocorticosteroid-based protocol, while achieving a consistent reduction of glucocorticosteroid cumulative dose.

Comparison of triamcinolone and methylprednisolone efficacy and steroid flare reaction rates after shoulder corticosteroid injection: a prospective interrupted time series study.

BACKGROUND: A corticosteroid flare reaction is a well-described phenomenon that causes significant pain and dysfunction. The paucity of literature impedes decision making regarding which corticosteroid to use for shoulder injection. The purpose of this study was to compare methylprednisolone acetate (MPA) and triamcinolone acetonide (TA) injections in the glenohumeral joint and/or subacromial space in terms of efficacy and the incidence of steroid flare reactions. METHODS: In this prospective, interrupted time series, parallel study, patients received injections in the glenohumeral joint and/or subacromial space. MPA and TA were used during 2 discrete 3-month periods. The injections consisted of 2 mL of lidocaine, 2 mL of bupivacaine, and 80 mg of either MPA or TA. Visual analog scale (VAS) pain scores were recorded immediately before injection; 1-7 days after injection; and 3, 6, and 12 months after injection. The primary outcome was the incidence of a steroid flare reaction, defined as a post-injection increase in the VAS score by ≥2 points. The secondary outcome was injection failure, defined as a post-injection VAS score greater than the baseline score or the need for another intervention. We used linear mixed models with a patient-level random intercept to identify the mean VAS score change for TA injections in the first week after injection. RESULTS: MPA or TA shoulder injections were administered in 421 patients; of these patients, 15 received bilateral-joint injections whereas 406 received a single-joint injection, for a total of 436 injections (209 MPA and 227 TA injections). Pain scores in the first week after injection were available for 193 MPA and 199 TA injections. Significantly more patients in the MPA cohort reported flare reactions compared with the TA cohort (22.8% vs. 4.0%, P < .001) during the first week after injection. In the first week after injection, the mean VAS score of patients receiving TA injections was 1.05 (95% confidence interval, 0.47-1.63) lower than that of patients receiving MPA injections when adjusted for age, sex, race, pain type, surgeon type, and injection site. At 3 months, surveys for 169 MPA and 172 TA injections were completed, with no significant difference in the rate of injection failure for MPA vs. TA (42.6% vs. 36.1%, P = .224). Treatment failure rates were significantly higher for MPA than for TA at 6 months (78.44% vs. 62.5%, P < .001) but not at 12 months (81.18% vs. 81.42%, P = .531.) CONCLUSION: TA injections resulted in a >5-fold reduction in steroid flare reactions, with statistically superior 6-month efficacy rates, compared with MPA injections. This study supports TA as a more viable corticosteroid option for shoulder injection.

Inmunoglobulina humana para el tratamiento de pacientes pediátricos con encefalitis autoinmune, que no mejoran con respuesta a pulsos de metilprednisolona y/o plasmaféresis / Human immunoglobulin for the treatment of pediatric patients with autoimmune encephalitis, who do not improve with response to pulses of methylprednisolone and/or plasmapheresis

INTRODUCCIÓN: Este informe de ETS-R corta se realizó a solicitud del Seguro Integral de Salud; el cual motivó la formulación de la pregunta PICO conjuntamente con médicos y especialistas del Instituto Nacional del Niño de Breña, P: pacientes pediátricos con encefalitis autoinmune que no mejoran con respuesta a pulsos de metilprednisolona y/o plasmaféresis; I: IgIV más metilprednisolona; C: mejor terapia de soporte (continuar con pulsos de metilprednisolona); O: mejoría clínica, recaída, calidad de vida, numero de crisis convulsivas, tiempo de estancia hospitalaria, frecuencia de infecciones y eventos adversos. a. Cuadro clínico: La encefalitis autoinmune incluye un grupo heterogéneo de trastornos de tipo autoinmunitario en los que el sistema inmune reacciona frente a antígenos propios expresados en el sistema nervioso central. Los anticuerpos anti neuronales pueden estar dirigidos a la superficie celular (antígenos sinápticos en neuronas y glía) o a antígenos intracelulares. Los principales autoanticuerpos presenten en la encefalitis autoinmune son aquellos contra las moléculas NMDAR, GABAa, GABAb, AMPA, receptores de glicina, LGI1, CASPR2, GAD, entre otros. Las manifestaciones clínicas incluyen convulsiones, trastornos del movimiento, cambios de comportamiento y estado de ánimo, psicosis, deterioro cognitivo, disfunción autonómica y alteración del nivel de conciencia. La encefalitis por anticuerpos anti-NMDAR es la más prevalente en la población pediátrica. Las opciones terapéuticas consideradas como primera línea incluyen a los corticoides, la inmunoglobulina humana intravenosa (IgIV) y/o la plasmaféresis. b. Tecnología sanitária: La IgIV es una solución estéril de inmunoglobulinas humanas concentradas derivadas de donantes sanos; más del 90% de la preparación de IgIV corresponde a la IgG siendo el componente principal requerido para el efecto terapéutico. El mecanismo de acción de la IgIV aún no está claro, pero se presume que tienen un efecto inmunomodulador y antinflamatorio. Los efectos secundarios graves incluyen meningitis aséptica, shock anafiláctico, trombosis, accidente cerebrovascular y deterioro de la función renal; y el 6 % de los pacientes reportan eventos adversos serios. Dado su potencial mecanismo de acción, la IgIV ha sido utilizada en indicaciones fuera de etiqueta, tales como la encefalitis autoinmune. Actualmente, la IgIV cuenta con la aprobación de la Food and Drug Administration (FDA) para el tratamiento de inmunodeficiencia humoral primaria (IgIV al 5 %) y/o para el tratamiento de púrpura trombocitopénica inmune crónica en pacientes de 15 años o más; o polineuropatía desmielinizante inflamatoria crónica en adultos (IgIV al 10 %). A pesar de no contar con indicación para el uso en encefalitis autoinmune, se ha reportado su uso en pacientes pediátricos con esta condición. La dosis de IgIV para el tratamiento de la encefalitis autoinmune se establece empíricamente en 2 mg/kg seguido de una dosis mensual de mantenimiento de 1 g/kg que se ajusta según la respuesta clínica del paciente; o en 0.4 g/kg/día durante 5 días con o sin esteroides. OBJETIVOS: Describir la evidencia científica disponible sobre la eficacia y seguridad de la Inmunoglobulina Intravenosa (IgIV) para el tratamiento de encefalitis autoinmune en pacientes pediátricos que no mejoran con respuesta a pulsos de metilprednisolona y/o plasmaféresis. METODOLOGÍA: Se realizó una búsqueda sistemática en Medline/PubMed, The Cochrane Library y LILACS utilizando la estrategia de búsqueda descrita en el Anexo 01. Ésta se complementó con la búsqueda de evidencia en páginas institucionales de agencias gubernamentales y buscadores genéricos. Se priorizó la identificación y selección de ensayos clínicos aleatorizados controlados (ECA), revisiones sistemáticas (RS) de ECA, estudios observacionales comparativos, guías de práctica clínica (GPC), evaluaciones de tecnología sanitaria (ETS) y evaluaciones económicas (EE) de América Latina. La calidad de la evidencia se valoró usando: AMSTAR 2 para revisiones sistemáticas, la herramienta de la colaboración Cochrane para ensayos clínicos, la escala Newcastle-Ottawa para estudios no aleatorizados incluyendo cohortes y estudios de casos y controles, y AGREE II para valorar el rigor metodológico de las GPC. RESULTADOS: Tras la búsqueda sistemática se identificaron 207 artículos de los cuales 11 pararon a revisión a texto completo. De estos 11 documentos solo uno (GPC) correspondió con la pregunta PICO de interés. No se identificaron ECA o estudios observacionales comparativos, evaluaciones económicas, ni ETS que respondieran a la pregunta PICO de interés. CONCLUSIONES: Se revisó la mejor evidencia disponible sobre la eficacia y seguridad de la IgIV más metilprednisolona en pacientes pediátricos con encefalopatía autoinmune no mejoran con respuesta a pulsos de metilprednisolona y/o plasmaféresis (población objetivo). Se identificó solo una GPC que brinda recomendaciones para la población objetivo basada únicamente en consenso de expertos. Esta guía recomienda tanto la intervención como el comparador (prolongar el uso de metilprednisolona). No se cuenta con evidencia procedente de estudios tipo ECA u observacionales comparativos que evalúen la eficacia y seguridad de IgIV más metilprednisolona en la población objetivo, incluso ni en el contexto de primera línea. No se disponen de ETS ni evaluaciones económicas que respondan a la pregunta PICO de la presente revisión. Se espera que los resultados de ensayos clínicos en curso puedan brindar nueva información que permita responder a la pregunta de la presente revisión.

An Analysis of Medical Malpractice Litigation due to Intravenous Steroid Treatment for Acute Spinal Cord Injury.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the incidence of litigation due to using or foregoing methylprednisolone (MP), naloxone, or tirilazad for treatment of acute spinal cord injury (ASCI) through querying the Westlaw and VerdictSearch databases. SUMMARY OF BACKGROUND DATA: There is historic controversy regarding the use of intravenous steroids for treatment of ASCI. Many highlight that MP continues to be used for ASCI treatment mainly as a defensive medicine tactic due to the fear of malpractice litigation. METHODS: Westlaw and VerdictSearch were queried for cases involving steroid treatment for ASCI between the years 1998 and 2021. Collected data for each case included year of case hearing, verdict ruling, location of filed claim, and the plaintiff's basis of litigation. Cases were reviewed and categorized by two independent reviewers based on the grievance(s) levied by the plaintiff. Inclusion criteria for topic relevance was defined as a plaintiff's basis of litigation resting on a claim of medical malpractice due to the use, or lack thereof, of MP, naloxone, or tirilazad for treatment of ASCI. RESULTS: Upon review of 238 cases, case claims were grouped into five categories based on reason for litigation: Social Security benefits (171), lawsuit due to vaccination (25), medical malpractice unrelated to steroid use (16), fungal infections due to MP injections (4), and other (22). Zero cases were found to be related to lawsuits filed due to steroid use or lack thereof for ASCI treatment. CONCLUSION: Our findings suggest there is limited risk of malpractice litigation due to steroid use or lack thereof in the treatment of ASCI. As such, steroid-related treatment decisions for ASCI should be informed by evidence-based approaches to care not influenced by medicolegal concerns.

Methylprednisolone alleviates cognitive functions through the regulation of neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and linked to abnormal deposition of amyloid-ß (Aß), neurofibrillary tangles (NFTs), synaptic dysfunction, and neuroinflammation. Despite significant progress in unravelling the pathogenesis of AD, currently main therapeutic interventions is limited to symptomatic alleviation. Methylprednisolone (MP), a synthetic glucocorticoid, is recognized for its extensive anti-inflammatory properties. Our study assessed the neuroprotective effect of MP (25 mg/kg) administration to an Aß1-42-induced AD mouse model. Our findings demonstrate that MP treatment can ameliorate cognitive impairment in Aß1-42-induced AD mice and suppress microglial activation in the cortex and hippocampus. RNA-Sequencing analysis reveals that MP ultimately rescues cognitive dysfunction through improving the synapse function and inhibiting the immune and inflammatory processes. Our study suggests that MP could be a promising drug alternative for the treatment of AD, either alone or in combination with other existing drugs.

Oral or pulse glucocorticoid use at the onset of giant cell arteritis and its influence on the risk of relapse: a retrospective study.

The objective is to investigate whether initial therapy with intravenous methylprednisolone pulses (ivMTP) or oral glucocorticoid (OG) influences the relapse rate in giant cell arteritis (GCA) patients. This is a retrospective observational study of patients with GCA from 2004 to 2021. Demographics, clinical and laboratory variables, cumulative glucocorticoid dose and relapse rate at 6-month follow-up defined according to EULAR recommendations were recorded. Univariate and multivariate logistic regression models were used to determine possible risk factors for relapse. A total of 74 GCA patients were included for analysis (54 (73%) female, mean (SD) age 77.2 (7.4) years). Overall, 47 (63.5%) patients received ivMTP at disease onset and 27 (36.5%) OG. Mean (SD) cumulative prednisone dose (mg) at 6-month follow-up was 3790.7 (1832.7) for patients with ivMTP vs 4298.1 (2930.6) for the OG group, p = 0.37. A total of 15 (20.3%) relapses occurred at 6-month follow-up. Relapse rates did not differ according to the initial therapy (19.1 vs 22.2%, respectively, p = 0.75). In the multivariate analysis, fever at disease onset (OR 4.837; CI 1.1-21.6) and dyslipidemia (OR 5.651; CI 1.1-28.4) were independent predictors for relapse. Initial therapy with ivMTP or OG does not influence the relapse rate of GCA patients. Fever at disease onset and dyslipidemia are independent predictors of disease relapse.