ABSTRACT
INTRODUCTION: Intratympanic corticosteroids are commonly used in the treatment of Menière's disease (MD). However, few and small randomised controlled trials (RCT) on the effectiveness of intratympanic corticosteroids have been performed. A recent Cochrane review suggested that a well-conducted placebo-controlled RCT with a large study population is required to evaluate the effectiveness of the use of intratympanic corticosteroids in MD. The following protocol describes a phase-3 multicentre, double-blinded, randomised, placebo-controlled trial to compare the effectiveness of methylprednisolone (62.5 mg/mL) to a placebo (sodium chloride 0.9%). METHODS AND ANALYSIS: We aim to recruit 148 patients with unilateral MD from six hospitals in the Netherlands. Patients will be randomly assigned to either the methylprednisolone or the placebo group. Two injections will be given, one at baseline and one after 2 weeks. Follow-up assessments will be done at 3, 6, 9 and 12 months. The primary outcome will be the frequency of vertigo attacks. Attacks will be evaluated daily with the DizzyQuest app. Secondary outcomes include hearing loss, tinnitus, health-related quality of life, use of co-interventions and escape medication, (serious) adverse events and cost-effectiveness. These will be evaluated with audiometry and multiple commonly used, validated questionnaires. For the primary and secondary outcomes mixed model analysis, generalised estimating equation analysis and logistic regression analysis will be used. ETHICS AND DISSEMINATION: This study was submitted via the Clinical Trials Information System, reviewed and approved by the Medical Research Ethics Committee Leiden The Hague Delft and the local institutional review board of each participating centre. All data will be presented ensuring the integrity and anonymity of patients. Results will be published in scientific journals and presented on (inter)national conferences. TRIAL REGISTRATION NUMBER: This study is registered at ClinicalTrials.gov Protocol Registration and Results System, with the registration ID: NCT05851508.
Subject(s)
Injection, Intratympanic , Meniere Disease , Methylprednisolone , Vertigo , Humans , Clinical Trials, Phase III as Topic , Double-Blind Method , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Meniere Disease/drug therapy , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Multicenter Studies as Topic , Netherlands , Quality of Life , Randomized Controlled Trials as Topic , Treatment Outcome , Vertigo/drug therapyABSTRACT
A rare subtype of autoimmune encephalitis consists of antibodies targetting the alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid receptor in the central nervous system. We describe the clinical presentation and autoimmune profile of the first case of alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis with concurrent anti-acetylcholine receptor antibodies in Pakistan. The patient was a 58-year-old male who presented with the characteristic symptoms of limbic encephalitis with memory loss, irritability, agitation, and confusion. Antibodies against the alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid receptor were detected in both serum and cerebrospinal fluid by indirect immunofluorescence. Computerised tomography of the chest showed an anterior mediastinal mass. The patient was treated with high dose Methylprednisolone and five sessions of plasma exchange. There was a short period of improvement; however, the patient now continues to exhibit irritability, aphasia, confusion, and memory loss. Video-assisted thoracoscopic surgery for mediastinal mass resection and histological testing was planned, however after review by the interventional radiologist the associated risks were deemed too high to proceed with the procedure and biopsy was not done.
Subject(s)
Myasthenia Gravis , Humans , Male , Middle Aged , Myasthenia Gravis/diagnosis , Myasthenia Gravis/complications , Receptors, AMPA/immunology , Autoantibodies/blood , Encephalitis/immunology , Encephalitis/diagnosis , Methylprednisolone/therapeutic use , Methylprednisolone/administration & dosage , Limbic Encephalitis/immunologyABSTRACT
BACKGROUND: Acute respiratory distress syndrome (ARDS), are respiratory diseases with high morbidity and mortality. Clinical trials investigating the efficacy of corticosteroids in the treatment of ARDS often yield contradictory results. We hereby conducted a systematic review and meta-analysis to investigate the efficacy of corticosteroids in ARDS management. MATERIALS AND METHODS: We conducted a search for randomized clinical trials (RCT) and observational studies that utilized corticosteroids for patients with ARDS in Web of Science, PubMed, and Embase. The primary outcome was mortality. Risk of bias was assessed using Cochrane or NOS scales. Statistical effect size was analyzed using the Mantel-Haenszel method. RESULTS: A total of 20 studies, comprising 11 observational studies and 9 RCTs, were eligible for analysis. In RCTs, corticosteroids were associated with a reduction of mortality in ARDS patients (relative risk [RR] = 0.80, 95%CI: 0.71-0.91, p = 0.001). Further subgroup analysis indicated that specific variables, such as low-dose (RR = 0.81; 95%CI: 0.67-0.98; p = 0.034), methylprednisolone (RR = 0.70; 95%CI: 0.49-0.98; p = 0.035), and dexamethasone (RR = 0.82; 95%CI: 0.69-0.98; p = 0.029) were associated with mortality among patients receiving corticosteroids. However, in observational studies, corticosteroids increased the risk of death (RR = 1.16, 95%CI: 1.04-1.29; p = 0.001). Subgroup analysis showed that the use of high-dose corticosteroids was associated with higher patient mortality (RR = 1.20; 95%CI: 1.04-1.38; p = 0.001). CONCLUSIONS: The efficacy of corticosteroids on the mortality of ARDS differed by the type and dosage of corticosteroids used, as well as the etiologies. Current data do not support routine use of corticosteroids in ARDS since protective effects were observed in RCTs but increased mortality was found in observational studies. More well designed and large clinical trials are needed to specify the favorable subgroups for corticosteroid therapy.
Corticosteroid use may reduce the risk of death in patients with acute respiratory distress syndrome (ARDS) according to randomized controlled trials.Observational studies indicate that corticosteroid use may increase the risk of death in non-COVID-19 ARDS patients but not in COVID-19 ARDS patients.Both regular and low-dose corticosteroids show benefits in reducing mortality in RCTs, but observational studies associate these doses with increased mortality.
Subject(s)
Adrenal Cortex Hormones , Dexamethasone , Observational Studies as Topic , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/mortality , Humans , Adrenal Cortex Hormones/therapeutic use , Dexamethasone/therapeutic use , Treatment Outcome , Methylprednisolone/therapeutic use , Methylprednisolone/administration & dosageABSTRACT
PURPOSE: The primary objective of this study was to identify predictive factors linked to the normalization of thyroid-stimulating immunoglobulin (TSI) levels in patients diagnosed with active, moderate-to-severe Graves' orbitopathy (GO). The study also tracked the longitudinal changes in TSI levels over a 36-month period following treatment. METHODS: The study population consisted of individuals who were recently diagnosed with active, moderate-to-severe GO and received a 12-week course of intravenous methylprednisolone (IVMP) treatment. A subgroup of patients who did not respond to the initial treatment received an additional 20 Gy of radiation therapy (RTx). TSI levels were monitored at the time of diagnosis, after treatment, and subsequently every 6 months for 36 months. Normalization was defined as a TSI level below 140%. Patients were divdied into two groups with success and failure group depending on whether TSI became normal or not. RESULTS: Out of 83 patients, 36 (43.4%) achieved normalized TSI levels within two years post-IVMP treatment. Lower initial TSI levels (< 425%), absence of additional RTx, and early treatment initiation were associated with a higher likelihood of TSI normalization (P = 0.035, P = 0.028, P < 0.001, respectively). Notably, significant differences in TSI level reduction were observed from 18 months post-treatment between the two groups (P = 0.031). A TSI cutoff value of 413% was identified as predictive for normalization at 24 months (P = 0.002). CONCLUSION: This study is the first to identify key factors that influence normalization of TSI levels in moderate-to-severe Graves' Orbitopathy. It highlights the importance of early treatment decisions, particularly for patients with initial TSI levels above 425%. Despite the treatment, less than half of the patients achieved TSI normalization within 24 months, underscoring the need for additional research to explore the relationship between TSI levels and the clinical manifestations of chronic GO.
Subject(s)
Glucocorticoids , Graves Ophthalmopathy , Immunoglobulins, Thyroid-Stimulating , Methylprednisolone , Humans , Graves Ophthalmopathy/drug therapy , Graves Ophthalmopathy/diagnosis , Graves Ophthalmopathy/blood , Female , Male , Middle Aged , Prognosis , Adult , Methylprednisolone/therapeutic use , Methylprednisolone/administration & dosage , Glucocorticoids/therapeutic use , Immunoglobulins, Thyroid-Stimulating/blood , Longitudinal Studies , Follow-Up Studies , Aged , Severity of Illness Index , Retrospective StudiesABSTRACT
BACKGROUND: Acute exacerbation of fibrosing interstitial lung diseases (AE-ILD) is a serious life-threatening event per year. Methylprednisolone and/or immunosuppressive agents (ISA) are a mainstay in any regimen, under the premise that pulmonary infection has been promptly identified and controlled. We investigated the value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) on the treatment adjustment of AE-ILD. METHODS: We conducted a cross-sectional observational study. All data were collected prospectively and retrospectively analyzed. We included fifty-six patients with AE-ILD and nineteen stable ILD who underwent BALF mNGS at the beginning of admission. RESULTS: Patients with a variety of ILD classification were included. Connective-tissue disease related ILD (CTD-ILD) occupy the most common underlying non-idiopathic pulmonary fibrosis (non-IPF). The infection-triggered AE accounted for 39.29%, with the majority of cases being mixed infections. The microorganisms load in the AE-ILD group was significantly higher. After adjusted by mNGS, the therapy coverage number of pathogens was significantly higher compared to the initial treatment (p < 0.001). After treatment, the GGO score and the consolidation score were significantly lower during follow up in survivors (1.57 ± 0.53 vs. 2.38 ± 0.83 with p < 0.001, 1.11 ± 0.24 vs. 1.49 ± 0.47 with p < 0.001, respectively). Some detected microorganisms, such as Tropheryma whipplei, Mycobacterium, Aspergillus, and mixed infections were difficult to be fully covered by empirical medication. BALF mNGS was also very helpful for excluding infections and early administration of methylprednisolone and/or ISA. CONCLUSIONS: mNGS has been shown to be a useful tool to determine pathogens in patients with AE-ILD, the results should be fully analyzed. The comprehensive treatment protocol based on mNGS has been shown crucial in AE-ILD patients.
Subject(s)
Bronchoalveolar Lavage Fluid , High-Throughput Nucleotide Sequencing , Lung Diseases, Interstitial , Humans , Female , Bronchoalveolar Lavage Fluid/microbiology , Male , Middle Aged , Aged , Lung Diseases, Interstitial/microbiology , Lung Diseases, Interstitial/drug therapy , Cross-Sectional Studies , Retrospective Studies , Immunosuppressive Agents/administration & dosage , Metagenomics/methods , Methylprednisolone/administration & dosage , Disease ProgressionABSTRACT
A woman in her 20s presented with 6 weeks of fever, persistent vomiting and 28% loss of body weight. Symptoms were refractory to treatment with antiemetics and broad spectrum antibiotics.Further investigation via oesophageogastroduedenoscopy revealed a large gastric ulcer and pyloric stricture, causing gastric outlet obstruction (GOO). Biopsies of the stomach and duodenum showed plasma cell infiltration with a large proportion being IgG4 positive.Treatment with methylprednisolone, and later prednisolone, quickly improved inflammatory markers and symptoms. Balloon dilatation of the pyloric stricture also improved vomiting, allowing eventual re-establishment of oral nutrition. The patient made a full recovery with maintenance treatment on mycophenolate mofetil.IgG4-related disease (IgG4-RD) is a multisystem disorder with unpredictable presentation. The case highlights diagnostic challenges in IgG4-RD and identifies it as a rare differential in upper gastrointestinal symptoms. To our knowledge this is the first published case of IgG4-RD in the duodenum causing GOO.
Subject(s)
Gastric Outlet Obstruction , Immunoglobulin G4-Related Disease , Humans , Female , Gastric Outlet Obstruction/etiology , Gastric Outlet Obstruction/diagnosis , Immunoglobulin G4-Related Disease/complications , Immunoglobulin G4-Related Disease/diagnosis , Adult , Diagnosis, Differential , Immunoglobulin G/blood , Methylprednisolone/therapeutic use , Methylprednisolone/administration & dosage , Prednisolone/therapeutic use , Stomach Ulcer/complications , Stomach Ulcer/diagnosis , Vomiting/etiology , Pyloric Stenosis/diagnosis , Pyloric Stenosis/complications , Duodenum/pathologyABSTRACT
BACKGROUND: Particulate steroids are thought to exert their effects for long durations at injection sites. However, these types of steroids carry higher risks when used in epidural steroid injections. Catastrophic spinal cord complications, including sudden-onset paraplegia, have been reported due to intravascular particulate steroid preparations that cause embolisms and occlusion of blood vessels, resulting in spinal cord infarctions. Clinicians, therefore, recommend nonparticulate steroids to mitigate these adverse events. To our knowledge, this is the first retrospective study that addresses the effectiveness and safety of methylprednisolone, dexamethasone, and betamethasone when used in transforaminal epidural steroid injections (TFESIs) for the treatment of lumbar radiculopathy. OBJECTIVES: The primary goal of this study was to compare the proportion of patients who received injections of particulate steroids and required zero repeat injections within 12 months of their initial injection to the proportion of patients who received injections of nonparticulate steroids and also required zero repeat injections, as well as to compare the number of patients in the particulate cohort who required one or more repeat injections within 12 months of their initial injection to the number of patients in the nonparticulate cohort who required the same. The secondary goal was to evaluate the proportion of patients ultimately requiring surgery. STUDY DESIGN: This is a single-center, IRB-approved, retrospective study evaluating the safety and effectiveness of nonparticulate as compared to particulate steroid medications when used in TFESIs as minimally invasive treatments for chronic lumbar radiculopathy. SETTING: This study captured data (n = 1717) over a 4-year time frame (01/15/2018 to 01/15/2022). METHODS: The following data were collected from each patient's chart: age, gender, BMI, race, date of initial injection, number of repeat injections at the same lumbosacral level and on the same side within 12 months of the initial injection, and lumbar surgery date (if applicable). Inclusion criteria included: 1) having chronic low back pain of radicular etiology; 2) being at least 18 years old; 3) having experienced the failure of conservative therapy after 12 weeks (including physical therapy and/or medications); 4) having positive physical exam findings supporting nerve impingement (straight leg raise, slump test); and 5) showing lumbar MRI evidence of nerve impingement from disc herniation. Exclusion criteria included: 1) having received prior lumbar surgery at any level (L1-S1); 2) having been given prior TFESIs fewer than 6 months prior to initial injection; 3) having contracted a systemic infection at the proposed injection site; 4) undergoing active cancer treatment; and 5) having gotten any other spine injections. RESULTS: A significantly greater proportion of patients in the nonparticulate steroid cohort received 0 repeat injections (87.5% vs 71.4%, P < 0.001). The particulate steroid cohort demonstrated a significantly greater proportion of patients who received repeat injections within 12 months after the initial injections (12.5% vs 29.6%, P < 0.001). There were no significant differences among patients requiring surgery between the 2 cohorts. Other outcome measures included the identification of risk factors significantly associated with repeat injections. There was a statistically significant weak positive correlation between age and repeat injections (Pearson corr = 0.102; P < 0.001) and a weak negative correlation between ethnicity/race and repeat injections (point-biserial corr = -0.093; P < 0.001). No adverse events were reported. LIMITATIONS: Not all clinicians included in this study used each of the 3 steroid types, and all clinicians used either particulate or nonparticulate steroids exclusively. CONCLUSIONS: Our study demonstrates that the clinical outcomes associated with TFESIs of nonparticulate steroids are superior to those associated with TFESIs of particulate steroids when either variety of medication is used to treat lumbar radiculopathy. This is the first study to include a clinically useful predictive model using information on laterality, age, and steroid type.
Subject(s)
Betamethasone , Dexamethasone , Methylprednisolone , Radiculopathy , Humans , Injections, Epidural/methods , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Retrospective Studies , Betamethasone/administration & dosage , Methylprednisolone/administration & dosage , Methylprednisolone/adverse effects , Radiculopathy/drug therapy , Male , Female , Middle Aged , Adult , Aged , Anti-Inflammatory Agents/administration & dosage , Lumbar VertebraeABSTRACT
Objective: The prognostic factors and outcomes of Turkish children with newly diagnosed acute lymphoblastic leukemia (ALL), treated with the Modified St. Jude Total XV Protocol, which was adjusted by adding high-dose methylprednisolone (HDMP) before induction in the original protocol, were assessed in this study. Materials and Methods: The Modified St. Jude Total XV Protocol was administered to 183 newly diagnosed ALL patients, aged 1-18 years, between 1 January 2008 and 30 January 2016. HDMP was applied at doses of either 10 mg/kg/day (Group A) or 20 mg/kg/day (Group B) for 7 days before induction and then tapered over the next 7 days to 5 or 10 mg/kg/day, and continued at 2 mg/kg/day for 2 weeks during the induction phase. Absolute blast count (ABC) in peripheral blood and minimal residual disease (MRD) in bone marrow were assessed at the end of the initial 7-day HDMP treatment. MRD in the bone marrow was evaluated on day 15 and at the end of the induction period. The follow-up for these patients ended on 15 July 2019. Results: The 5-year event-free (EFS) and overall survival (OS) rates for all patients were 85.6±2.6% and 89.2±2.3%, respectively. The rate of good response to steroids (defined as ABC in peripheral blood of less than 1000/mm3 on day 7) was 88% and 97% of children achieved complete remission after induction. The survival rate and infection frequency did not show statistically significant differences between Group A and B. EFS and OS correlated with initial leukocyte count, age of 10-18 years at diagnosis, CD20 positivity at diagnosis, and gram-negative bacterial infection during remission induction. Conclusion: The remarkable response rates on days 7 and 15, along with the promising EFS and OS results in childhood ALL patients treated with the Modified St. Jude Total XV Protocol, highlight the early and substantial response effect of HDMP. At the onset of induction, short-term HDMP can be initiated, preferably at 10 mg/kg/day for the first 7 days, to minimize potential side effects.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Methylprednisolone , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Child , Female , Male , Child, Preschool , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Retrospective Studies , Infant , Turkey/epidemiology , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Treatment Outcome , Neoplasm, Residual/diagnosis , Prognosis , Remission InductionABSTRACT
Neuromyelitis optica spectrum disorders (NMOSD) is one of autoimmune inflammatory diseases and is characterized by area postrema syndrome, brainstem syndrome, optic neuritis, and/or myelitis. Typical myelitis is longitudinally extended transverse myelitis (LETM) which extends over three vertebral bodies. Several previous case reports have suggested association between cancer and NMOSD. A 50-year-old woman had breast cancer and underwent mastectomy and, 10 months later, she had developed acutely progressive dysbasia. Spine MRI showed LETM in 13 vertebrae length and blood test revealed positive anti-aquaporin 4 (anti-AQP4) antibody based on enzyme-linked immunosorbent assay with index of over 40. She was treated by intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulin, followed by oral prednisolone. The condition had mostly recovered after the treatment. A small population of NMOSD has the aspect of paraneoplastic neurological syndrome. The age of onset in patients with cancer-associated NMOSD tends to be higher than that in individuals with NMOSD due to any causes of NMOSD.
Subject(s)
Aquaporin 4 , Autoantibodies , Breast Neoplasms , Methylprednisolone , Neuromyelitis Optica , Plasma Exchange , Humans , Female , Middle Aged , Neuromyelitis Optica/etiology , Neuromyelitis Optica/complications , Neuromyelitis Optica/diagnostic imaging , Aquaporin 4/immunology , Methylprednisolone/administration & dosage , Autoantibodies/blood , Breast Neoplasms/complications , Immunoglobulins, Intravenous/administration & dosage , Magnetic Resonance Imaging , Prednisolone/administration & dosage , Biomarkers/blood , Treatment Outcome , Mastectomy , Pulse Therapy, Drug , Paraneoplastic Syndromes, Nervous System/etiology , Administration, OralABSTRACT
BACKGROUND: Because lateral epicondylitis is a common musculoskeletal disorder that affects the forearm's extensor tendons, an effective therapeutic approach should reverse the degeneration and promote regeneration. This study aimed to compare the efficacies of autologous blood (AB) injection, corticosteroid (CS) injection, and a combined injection of both in treating lateral epicondylitis (LE), hypothesizing that the combined approach might offer immediate symptom resolution and a lower recurrence. MATERIALS AND METHODS: A total of 120 patients diagnosed with lateral epicondylitis were systematically distributed among three distinct therapeutic injection groups. Those in the AB group were administered 1 ml of autologous venous blood mixed with 2 ml of 2% prilocaine HCl. Participants in the CS category were given 1 ml of 40 mg methylprednisolone acetate mixed with 2 ml of 2% prilocaine HCl. Meanwhile, patients in the combined group received a mixture containing 1 ml each of autologous venous blood and 40 mg methylprednisolone acetate along with 1 ml of 2% prilocaine HCl. Prior to receiving their respective injections, a comprehensive assessment of all participants was carried out. Follow-up assessments were subsequently conducted on days 15, 30, and 90 utilizing metrics of the patient-rated tennis elbow evaluation (PRTEE) and measurements of hand grip strength (HGS). RESULTS: One patient dropped out from the combined group, and 119 patients completed the trial. No complications were recorded during the course of follow-up. By day 15, all groups had demonstrated significant PRTEE improvement, with CS showing the most pronounced reduction (p = 0.001). However, the benefits of CS had deteriorated by day 30 and had deteriorated further by day 90. The AB and AB + CS groups demonstrated sustained improvement, with AB + CS revealing the most effective treatment, achieving a clinically significant improvement in 97.4% of the patients. The improved HGS parallelled the functional enhancements, as it was more substantial in the AB and AB + CS groups (p = 0.001), corroborating the sustained benefits of these treatments. CONCLUSIONS: The study concluded that while AB and CS individually offer distinct benefits, a combined AB + CS approach optimizes therapeutic outcomes, providing swift and sustained functional improvement with a lower recurrence rate. These findings have substantial clinical implications, suggesting a balanced, multimodal treatment strategy for enhanced patient recovery in LE. LEVEL OF EVIDENCE: Randomized clinical trial, level 1 evidence. TRIAL REGISTRATION: NCT06236178.
Subject(s)
Blood Transfusion, Autologous , Methylprednisolone Acetate , Methylprednisolone , Prilocaine , Tennis Elbow , Humans , Tennis Elbow/therapy , Tennis Elbow/drug therapy , Male , Female , Blood Transfusion, Autologous/methods , Middle Aged , Adult , Methylprednisolone/administration & dosage , Treatment Outcome , Prilocaine/administration & dosage , Methylprednisolone Acetate/administration & dosage , Anesthetics, Local/administration & dosage , Glucocorticoids/administration & dosage , Pain MeasurementABSTRACT
BACKGROUND: This study explored the relationship between inflammatory markers and glucocorticoid dosage upon admission. METHODS: We conducted a retrospective analysis of 206 patients with refractory Mycoplasma pneumoniae pneumonia (RMPP) admitted to a Children's Hospital from November 2017 to January 2022. Patients were categorized into three groups based on their methylprednisolone dosage: low-dose (≤ 2 mg/kg/d), medium-dose (2-10 mg/kg/d), and high-dose (≥ 10 mg/kg/d). We compared demographic data, clinical manifestations, laboratory findings, and radiological outcomes. Spearman's rank correlation coefficient was used to assess relationships between variables. RESULTS: The median age was highest in the low-dose group at 7 years, compared to 5.5 years in the medium-dose group and 6 years in the high-dose group (P < 0.001). The body mass index (BMI) was also highest in the low-dose group at 16.12, followed by 14.86 in the medium-dose group and 14.58 in the high-dose group (P < 0.001). More severe radiographic findings, longer hospital stays, and greater incidence of hypoxia were noted in the high-dose group (P < 0.05). Additionally, significant increases in white blood cells, C-reactive protein, procalcitonin, lactate dehydrogenase (LDH), alanine transaminase, aspartate transaminase, ferritin, erythrocyte sedimentation rate, and D-dimer levels were observed in the high-dose group (P < 0.05). Specifically, LDH and ferritin were markedly higher in the high-dose group, with levels at 660.5 U/L and 475.05 ng/mL, respectively, compared to 450 U/L and 151.4 ng/mL in the medium-dose group, and 316.5 U/L and 120.5 ng/mL in the low-dose group. Correlation analysis indicated that LDH and ferritin levels were significantly and positively correlated with glucocorticoid dose (Spearman ρ = 0.672 and ρ = 0.654, respectively; P < 0.001). CONCLUSIONS: Serum LDH and ferritin levels may be useful biomarkers for determining the appropriate corticosteroid dosage in treating children with RMPP.
Subject(s)
Biomarkers , Ferritins , L-Lactate Dehydrogenase , Pneumonia, Mycoplasma , Humans , Female , Male , Pneumonia, Mycoplasma/drug therapy , Pneumonia, Mycoplasma/blood , Pneumonia, Mycoplasma/diagnosis , Child , Ferritins/blood , Retrospective Studies , Child, Preschool , Biomarkers/blood , L-Lactate Dehydrogenase/blood , Dose-Response Relationship, Drug , Adolescent , Mycoplasma pneumoniae/drug effects , Methylprednisolone/administration & dosage , Glucocorticoids/administration & dosageABSTRACT
Multisystem inflammatory syndrome in children (MIS-C) is a known complication of COVID-19. There is still limited knowledge about this condition. Here, we report the case of a previously healthy toddler boy, who presented with acute liver failure and duodenal lesions resulting in severe haematemesis and haemorrhagic shock, requiring intensive care unit care. The patient had persistent transaminitis, a deranged coagulation profile, inflammatory markers were elevated, and laboratory tests were negative for common infectious hepatitis aetiologies as well as COVID-19 Reverse transcription polymerase chain reaction. His COVID-19 antibody was reactive. Upper gastrointestinal endoscopy revealed a Forrest grade III duodenal ulcer. Looking into the constellation of symptoms and laboratory findings a confirmed diagnosis of acute viral hepatitis caused by MIS-C was made. Hence, he was given intravenous methylprednisolone along with intravenous immunoglobulins, after which he improved clinically and transaminitis resolved. The patient was discharged on clinical improvement and was doing fine on follow-up up to 6 months.
Subject(s)
COVID-19 , Gastrointestinal Hemorrhage , Liver Failure, Acute , Methylprednisolone , Systemic Inflammatory Response Syndrome , Humans , Male , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/complications , COVID-19/complications , Liver Failure, Acute/diagnosis , Liver Failure, Acute/etiology , Liver Failure, Acute/complications , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/diagnosis , Methylprednisolone/therapeutic use , Methylprednisolone/administration & dosage , Immunoglobulins, Intravenous/therapeutic use , Hematemesis/etiology , Duodenal Ulcer/complications , Duodenal Ulcer/diagnosis , SARS-CoV-2 , Child, PreschoolABSTRACT
Hyperinflammatory Coronavirus disease 2019 (COVID-19) and rapidly-progressive interstitial lung diseases (RP-ILD) secondary to inflammatory myopathies (IIM) present important similarities. These data support the use of anti-rheumatic drugs for the treatment of COVID-19. The aim of this study was to compare the efficacy of combining baricitinib and pulse steroids with the Standard of Care (SoC) for the treatment of critically ill COVID-19 patients. We retrospectively enrolled consecutive patients admitted to the Intensive Care Unit (ICU) with COVID-19-pneumonia. Patients treated with SoC (dexamethasone plus remdesivir) were compared to patients treated with baricitinib plus 6-methylprednisolone pulses (Rheuma-group). We enrolled 246 patients: 104/246 in the SoC and 142/246 in the Rheuma-group. All patients presented laboratory findings suggestive of hyperinflammatory response. Sixty-four patients (26.1%) died during ICU hospitalization. The mortality rate in the Rheuma-group was significantly lower than in the SoC-group (15.5 vs. 40.4%, p < 0.001). Compared to the SoC-group, patients in the Rheuma-group presented significantly lower inflammatory biomarker levels after one week of treatment. Higher ferritin levels after one week of treatment were strongly associated with mortality (p < 0.001). In this large real-life COVID-19 cohort, baricitinib and pulse steroids led to a significant reduction in mortality, paralleled by a prompt reduction in inflammatory biomarkers. Our experience supports the similarities between hyperinflammatory COVID-19 and the IIM-associated RP-ILD.
Subject(s)
Azetidines , COVID-19 Drug Treatment , COVID-19 , Drug Therapy, Combination , Intensive Care Units , Methylprednisolone , Purines , Pyrazoles , SARS-CoV-2 , Sulfonamides , Humans , Purines/therapeutic use , Purines/administration & dosage , Male , Female , Azetidines/therapeutic use , Azetidines/administration & dosage , Sulfonamides/therapeutic use , Sulfonamides/administration & dosage , Pyrazoles/therapeutic use , Pyrazoles/administration & dosage , Middle Aged , Aged , Retrospective Studies , Methylprednisolone/therapeutic use , Methylprednisolone/administration & dosage , COVID-19/mortality , COVID-19/complications , Dexamethasone/therapeutic use , Dexamethasone/administration & dosage , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adenosine Monophosphate/administration & dosage , Treatment Outcome , Alanine/analogs & derivatives , Alanine/therapeutic use , Alanine/administration & dosageABSTRACT
Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressant medications and remain the cornerstone of systemic lupus erythematosus (SLE) therapy. However, ongoing exposure to GCs has the potential to elicit multiple adverse effects. Considering the irreplaceability of GCs in SLE therapy, it is important to explore the optimal regimen of GCs. Here, we compared the long-term efficacy and safety of pulsed and oral GC therapy in a lupus-prone mouse model. Mice were grouped using a randomized block design. We monitored survival rates, proteinuria, serum autoantibodies, and complement 3 (C3) levels up to 28 weeks of age, and assessed renal damage, bone quality, lipid deposition in the liver and marrow, glucose metabolic parameters, and levels of hormones of the hypothalamic-pituitary-adrenal (HPA) axis. Finally, we explored the mechanisms underlying the superior efficacy of the pulse regimen over oral prednisone regimen. We found that both GC regimens alleviated the poor survival rate, proteinuria, and glomerulonephritis, while also reducing serum autoantibodies and increasing the level of C3. The pulsed GC regimen showed less resistance to insulin, less suppression of the HPA axis, less bone loss, and less bone marrow fat deposition than the oral GC regimen. Additionally, GC-induced leucine zipper (GILZ) was significantly overexpressed in the GC pulse group. These results suggest that the GC pulse regimen ameliorated symptoms in lupus-prone mice, with fewer side effects, which may be related to GILZ overexpression. Our findings offer a potentially promising GC treatment option for SLE.
Subject(s)
Glucocorticoids , Lupus Erythematosus, Systemic , Methylprednisolone , Mice, Inbred MRL lpr , Prednisone , Animals , Lupus Erythematosus, Systemic/drug therapy , Methylprednisolone/pharmacology , Methylprednisolone/administration & dosage , Glucocorticoids/pharmacology , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Prednisone/pharmacology , Prednisone/adverse effects , Prednisone/administration & dosage , Mice , Female , Mice, Inbred C57BL , Disease Models, Animal , Autoantibodies/blood , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/metabolism , Complement C3/metabolism , Pituitary-Adrenal System/drug effects , Pituitary-Adrenal System/metabolism , Proteinuria/drug therapyABSTRACT
RATIONALE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that damages multiple organs and systems, including the lungs, kidneys, and heart. The respiratory system is commonly affected by SLE, leading to problems such as pleurisy, pleural effusion, and interstitial lung disease (ILD). In addition, SLE can involve the heart, with pericarditis being the most common manifestation. Notably, pericardial effusion frequently accompanies pericarditis involved by SLE, and aspects such as thickened pericardium (TP) can be challenging to detect early on. There are limited reports on TP and even fewer reports on the treatment of ILD with TP. This study investigates the clinical treatment of SLE complicating ILD and TP and reports on a successful case treated with tofacitinib, offering new strategies for managing such patients. PATIENT CONCERNS: A 35-year-old female patient presented to the hospital with polyarticular swelling and pain that had been ongoing for over 4 years, as well as recurrent chest pain for 2 years that worsened over the course of 1 day. DIAGNOSES: The patient was diagnosed with SLE complicating ILD and TP, with hematologic involvement. INTERVENTIONS: Treatment involved the administration of tofacitinib in combination with low-dose methylprednisolone (MP) and mycophenolate mofetil (MMF). OUTCOMES: The patient experienced recurrent chest pain and difficulty in reducing glucocorticoids (GCs), but the patient conditions were improved upon the addition of tofacitinib. The patient has been followed up for 16 months, and the patient MP dosage has been reduced to 6 mg once daily. The patient condition remains stable without recurrence, and the patient quality of life has improved. LESSONS: In cases of SLE complicating ILD and TP, when tapering GCs is difficult, treatment with tofacitinib can be effective in achieving remission and maintaining stability.
Subject(s)
Lung Diseases, Interstitial , Lupus Erythematosus, Systemic , Piperidines , Pyrimidines , Humans , Pyrimidines/therapeutic use , Piperidines/therapeutic use , Piperidines/administration & dosage , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Female , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/etiology , Adult , Pericardium/pathology , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/administration & dosage , Mycophenolic Acid/therapeutic use , Methylprednisolone/therapeutic use , Methylprednisolone/administration & dosageSubject(s)
Myelin-Oligodendrocyte Glycoprotein , Myelitis, Transverse , Humans , Myelitis, Transverse/drug therapy , Myelitis, Transverse/immunology , Myelitis, Transverse/diagnosis , Myelin-Oligodendrocyte Glycoprotein/immunology , Female , Autoantibodies/blood , Autoantibodies/immunology , Magnetic Resonance Imaging , Methylprednisolone/therapeutic use , Methylprednisolone/administration & dosage , Male , Treatment Outcome , AdultABSTRACT
BACKGROUND: The efficacy of rituximab in steroid-resistant nephrotic syndrome (SRNS) is controversial. We previously reported that rituximab in combination with methylprednisolone pulse therapy (MPT) and immunosuppressants was associated with favorable outcomes. We determined risk factors for poor response following rituximab treatment, which remains unknown. METHODS: This retrospective study included 45 patients with childhood-onset SRNS treated with rituximab across four pediatric kidney facilities. Treatment effects were categorized as complete remission (CR), partial remission (PR), and no remission (NR) at one year after rituximab treatment. The primary outcome was the rate of CR, PR, and NR. Risk factors for non-CR were calculated with multivariate logistic regression. Adverse events and the relationship between disease status at one year and long-term prognosis were also evaluated. RESULTS: The rates of CR, PR, and NR at one year were 69%, 24%, and 7%, respectively. The median time from rituximab administration to CR was 90 days. The median follow-up period after rituximab administration was 7.4 years. In multivariate analysis, significant risk factors for poor response were the pathologic finding of focal segmental glomerular sclerosis and a long interval between SRNS diagnosis and rituximab administration. The rates of CR were 90.3% and 21.4% in patients receiving rituximab within and after 6 months following SRNS diagnosis, respectively (p < 0.001). Five patients developed chronic kidney disease stage G5, including 2 of the 11 patients with PR and all 3 patients with NR, whereas none of the 31 patients with CR developed chronic kidney disease stage G5. CONCLUSION: Early administration of rituximab in combination with MPT and immunosuppressants might achieve favorable outcomes in patients with SRNS.
Subject(s)
Immunosuppressive Agents , Nephrotic Syndrome , Rituximab , Humans , Rituximab/administration & dosage , Rituximab/therapeutic use , Rituximab/adverse effects , Nephrotic Syndrome/drug therapy , Male , Retrospective Studies , Female , Child , Risk Factors , Child, Preschool , Prognosis , Treatment Outcome , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Adolescent , Remission Induction/methods , Drug Resistance , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Infant , Drug Therapy, Combination/methods , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Glucocorticoids/adverse effectsABSTRACT
Background: The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms through which corticosteroid treatment impacts acute neuroinflammation in people with MS (pwMS) remain not fully understood. In particular, the changes induced by glucocorticoids (GCs) on cells of the innate immune system and the differences between patients with distinct immunotherapies have received little attention to date. Methods: We conducted immunophenotyping using flow cytometry on peripheral blood mononuclear cells of pwMS who received IVMP treatment during a relapse. We compared the impact of an IVMP treatment on a broad variety of immune cell subsets within three groups: twelve patients who were treatment-naïve to disease modifying therapies (wDMT) to ten patients on platform therapies (PT) and eighteen patients on fingolimod therapy (FTY). Results: We observed pronounced interindividual short- and intermediate-term effects of IVMP on distinct immune cells subsets. In addition to the well-documented decrease in T-helper cells (Th cells), we detected significant alterations after the first IVMP infusion within the innate immune response among neutrophil, eosinophil and basophil granulocytes, monocytes and plasmacytoid dendritic cells (pDCs). When comparing patients wDMT to the PT and FTY cohorts, we found that IVMP had a similar impact on innate immune cells across all treatment groups. However, we did not observe a significant further decline in T lymphocyte counts during IVMP in patients with pre-existing lymphopenia under FTY treatment. Although T cell apoptosis is considered the main mechanism of action of GCs, patients with FTY still reported symptom improvement following IVMP treatment. Conclusion: In addition to T cell suppression, our data suggests that further immunoregulatory mechanisms of GC, particularly on cells of the innate immune response, are of greater significance than previously understood. Due to the regulation of the adaptive immune cells by DMTs, the impact of GC on these cells varies depending on the underlying DMT. Additional studies involving larger cohorts and cerebrospinal fluid samples are necessary to gain a deeper understanding of the immune response to GC in pwMS with different DMTs during relapse to define and explain differences in clinical response profiles.
Subject(s)
Multiple Sclerosis , Humans , Female , Male , Adult , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Fingolimod Hydrochloride/therapeutic use , Fingolimod Hydrochloride/administration & dosage , Immunity, Innate/drug effects , Methylprednisolone/therapeutic use , Methylprednisolone/administration & dosage , Immunophenotyping , Leukocytes, Mononuclear/immunology , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Immunosuppressive Agents/therapeutic use , Glucocorticoids/therapeutic use , Glucocorticoids/administration & dosageABSTRACT
A man in his 40s with end-stage kidney disease due to IgA nephropathy and receiving peritoneal dialysis presented with a 1-week history of breathlessness, cough and nosebleeds. CT scan of the chest revealed ground glass changes while blood tests indicated elevated inflammatory markers and a negative vasculitis screen. This included negative ANCA and anti-GBM antibodies. Initial treatment for suspected atypical pneumonia with antibiotics yielded no clinical improvement.Over the course of the admission, his symptoms progressively worsened, leading to oxygen dependency with a FiO2 of 40% and episodes of haemoptysis. Suspicions of pulmonary vasculitis arose due to clinical deterioration, prompting consultation with a tertiary vasculitis centre. It was subsequently concluded that the clinical and radiological findings correlated with ANCA-negative pulmonary vasculitis or a rare case of IgA-associated pulmonary capillaritis. Treatment with methylprednisolone and rituximab led to significant improvement, allowing rapid oxygen withdrawal. The patient was discharged with a tapering prednisolone regimen.