Low-dose Corticosteroids Research Articles

Outcomes Associated with the use of High Dose Corticosteroids and IL-6 Inhibitors for the Treatment of Acute Respiratory Distress Syndrome Secondary to SARS COV-2.

During the COVID-19 pandemic, treatment strategies evolved rapidly. The RECOVERY trial established corticosteroids as the standard care for reducing mortality in COVID-19 patients. However, some critical care clinicians began using doses higher than those recommended in RECOVERY. To characterize the use of high-dose corticosteroids and IL-6 inhibitors in critically ill COVID-19 patients and examine their association with adverse drug events (ADEs). A retrospective cohort study of 320 electronic health records (January 1, 2020 - June 30, 2022) was conducted on COVID-19 patients requiring high-flow oxygen or mechanical ventilation. Patients were categorized based on corticosteroid dose: "high dose dexamethasone" (daily dose greater than 12 mg and/or for longer than 10 days), "low dose dexamethasone" (daily dose 12 mg or less for 10 days or less), and "no dexamethasone" (no corticosteroid therapy). Subgroups were created based on IL-6 inhibitor use. High-dose dexamethasone was associated with increased odds of ADEs compared to low dose (OR 2.55, 95% CI 1.45 to 4.49) and no dexamethasone (OR 6.29, 95% CI 2.08 to 19.03). No additional efficacy benefit was observed in patients receiving high dose corticosteroids when compared to low dose corticosteroids. Patients receiving both an IL-6 inhibitor and high-dose dexamethasone had further increased odds of ADEs. High-dose dexamethasone was also associated with increased mortality compared to low dose (OR 3.78, 95% CI 1.97-7.25) and no dexamethasone (OR 15.22, 95% CI 3.27-70.74). Acknowledging the risk for residual confounding, higher doses of dexamethasone were associated with increased ADEs and mortality. These findings highlight the need for careful consideration of the use of high-dose dexamethasone.

Clinical Predictors of Mood Disorders and Prevalence of Neuropsychiatric Symptoms in Patients with Systemic Lupus Erythematosus.

Background/Objectives: We aimed to determine the prevalence and clinical correlations of mood disorders in a sample of systemic lupus erythematosus (SLE) patients. Hence, we hypothesized that the prevalence of mood disorders would be lower than reported in the literature and that patients would remain clinically stable and show less damage accrual despite low-dose corticosteroid prescription. Methods: In total, 92 SLE outpatients gave informed consent to participate in this cross-sectional study. Psychiatric and autoimmune clinical data were obtained, and a structured psychiatric interview was performed. The main clinical scales for the assessment of clinical symptomatology were included. To examine the potential relationships of presenting a mood disorder in SLE, clinical correlations and multivariate analyses were performed. Results: Mood disorders were the most prevalent disorder reported by SLE patients (16%), followed by adjustment disorders (5%). A significant proportion of patients presented psychosocial disturbances that did not meet the ICD-10 criteria for psychiatric diagnosis. According to the cut-off criterion for the Montgomery-Åsberg Depression Rating Scale (MADRS), up to 27% of the sample met the clinical criteria for depression. The multivariate analysis revealed a relationship between the presence of a mood disorder with total scores of the MADRS and the Young Mania Rating Scale (YMRS). Conclusions: The prevalence of mood disorders in patients with SLE was lower than previously reported. Although self-report clinical scales are useful for assessing clinical symptomatology, they should not be used in place of a comprehensive standardized interview conducted by a trained mental health specialist. Multidisciplinary teamwork is required for the early identification and therapeutic management of autoimmune patients with neuropsychiatric disorders.

Predictive value of perilesional edema volume in melanoma brain metastasis response to stereotactic radiosurgery.

Stereotactic radiotherapy (SRT) is an established treatment for melanoma brain metastases (MBM). Recent evidence suggests that perilesional edema volume (PEV) might compromise the delivery and efficacy of radiotherapy to treat BM. This study investigated the association between SRT efficacy and PEV extent in MBM. This retrospective study reviewed medical records from January 2020 to September 2023. Patients with up to 5 measurable MBMs, intracranial disease per RANO/iRANO criteria, and on low-dose corticosteroids were included. MRI scans assessed baseline neuroimaging, with PEV analyzed using 3D Slicer. SRT plans were based on MRI-CT fusion, delivering 18-32.5Gy in 1-5 fractions. Outcomes included intracranial objective response rate (iORR) and survival measures (L-iPFS and OS). Statistical analysis involved decision tree analysis and multivariable logistic regression, adjusting for clinical and treatment variables. Seventy-two patients with 101 MBM were analyzed, with a mean age of 68.83 years. The iORR was 61.4%, with Complete Response (CR) in 21.8% and Partial Response (PR) in 39.6% of the treated lesions. PEV correlated with KPS, BRAF status, and treatment response. Decision tree analysis identified a PEV cutoff at 0.5cc, with lower PEVs predicting better responses (AUC = 0.82 sensitivity: 86.7%, specificity:74.4%,). Patients with PEV ≥ 0.5cc had lower response rates (iORR 44.7% vs. 63.8%, p < 0.001). Median OS was 9.4 months, with L-iPFS of 27 months. PEV significantly impacted survival outcomes. A more extensive PEV was associated with a less favorable outcome to SRT in MBM.

Corticosteroid Prescribing Patterns in the Emergency Department for Acute COPD Exacerbations: A Retrospective Analysis Following an Educational Intervention.

COPD is a progressive lung disease with marked airflow limitation. It has a large global prevalence and is managed with antibiotics, bronchodilators, and corticosteroids. Despite the prevalence, corticosteroid prescribing regimens differ widely amongst providers. This study aims to evaluate baseline corticosteroid prescribing patterns, the ability to change corticosteroid prescribing patterns with the utilization of an educational initiative, and to evaluate the effect of corticosteroid dose on length of stay, 30-day hospital readmission, mortality, and total hospital insulin dosing. This study was conducted via a retrospective observational study. Providers at a single institution answered a baseline questionnaire on COPD corticosteroid prescribing patterns and subsequently received an educational presentation regarding evidence-based corticosteroid recommendations. Data were then retrospectively obtained and analyzed evaluating corticosteroid prescribing patterns both pre- and post-educational intervention. Data were analyzed using IBM SPSS Version 25. The provider survey revealed that most (95.3%) administered 125 mg of methylprednisolone to patients treated for AECOPD. The most common reason a particular dose of corticosteroid was administered was due to previous teaching or practice patterns. The mean initial steroid dose of methylprednisolone decreased following the educational initiative from 114.24 mg to 72.8 mg (p < 0.01). This corresponded to a 69% (n=41) decrease of providers using 125 mg methylprednisolone (p < 0.01), and increased prescribing of 62.5 mg methylprednisolone by 42.6% (n=66). The mean LOS following hospital admission for AECOPD in the pre-intervention group was 5.80 days, while the mean LOS following the targeted educational intervention decreased to 4.82 days (p = 0.01). The implementation of an educational intervention may change provider corticosteroid prescribing patterns. Additionally, lower corticosteroid dose in the Emergency Department may decrease patient length of stay. Keywords: Corticosteroid, COPD, LOS, recommendations, steroid.

Radiological and spirometric changes in relation to drugs used in post COVID pulmonary fibrosis in a cohort of COVID-19 survivors

BackgroundIt has been proposed that prolonged use of anti-inflammatory and anti-fibrotic drugs diminish the probability of development of lung fibrosis. Prolonged low-dose corticosteroid may prevent remodeling of the lung in survivors. Pirfenidone and colchicine may exhibit anti-fibrotic and anti-inflammatory properties as well.MethodsThis retrospective observational study was conducted at post COVID-19 clinic, Mansoura University Hospitals, during the period between October 2020 and March 2022. This study included 104 patients who had COVID-19 pneumonia confirmed either by RT-PCR or radiologically by CT scan and divided into 3 groups; group A (corticosteroids only) included 33 (31.7%) patients, group B (corticosteroids and colchicine) included 56 (53.8%) patients, and group C (corticosteroids, colchicine, and pirfenidone) included 15 (14.4%) patients. All patients were assessed during follow-up visits in post COVID-19 clinic 1 and 3 months after discharge by evaluation of resting SpO2, spirometry, and radiological assessment. Patients’ data during hospitalization was collected from hospital electronic systems.ResultsThere was non-statistically significant improvement in FEV1 in group A while there was statistically significant improvement in FEV1 in groups B and C (P value = 0.002 and 0.041, respectively) 1 month and 3 months after discharge. Group B exhibited more statistically significant improvement in FVC as well compared to group C (P value = 0.003 and 0.025, respectively) while group A showed non-statistically significant improvement in FVC. There was a statistically significant decrease in CT severity score in all the groups during follow-up with P value < 0.001 in groups A and B and to less extent less statistically significant decrease in group C comparing the 3 groups to each other.ConclusionThe use of colchicine added to corticosteroids after acute phase of COVID-19 pneumonia resulted in statistically significant improvement regarding functional and radiological changes during follow-up when compared to corticosteroids alone. The addition of pirfenidone (which is a relatively expensive drug) to corticosteroids and colchicine did not add more statistically significant improvement in functional or radiological changes.

Role of Low Dose Intravenous Methylprednisolone in Pulmonary Hemorrhage Associated with Severe Leptospirosis

Leptospirosis, an emerging zoonosis endemic in Malaysia, presents with diverse clinical manifestations, ranging from mild to potentially fatal illness. Pulmonary involvement in leptospirosis, particularly pulmonary hemorrhage, poses a significant risk of mortality, prompting exploration of various treatment strategies. While high-dose corticosteroid therapy has demonstrated efficacy in some studies, data on the use of low-dose corticosteroids in pulmonary leptospirosis remain scarce. Here, we report a case of successful treatment with low-dose methylprednisolone in a patient diagnosed with Weil’s disease and pulmonary hemorrhage. The patient, initially presenting with fever, vomiting and hemoptysis, rapidly deteriorated, necessitating intubation due to respiratory distress. Prompt initiation of low-dose methylprednisolone alongside antibiotic therapy resulted in clinical improvement, resolution of pulmonary hemorrhage, and normalization of laboratory parameters. This case highlights the potential efficacy of low-dose corticosteroid therapy in managing severe pulmonary involvement in leptospirosis, offering insights into alternative treatment modalities for this challenging condition. Further studies are warranted to elucidate the optimal dosing and timing of corticosteroid therapy in leptospirosis-associated pulmonary complications.

Corticosteroids for Immune-Related Adverse Events and Checkpoint Inhibitor Efficacy: Analysis of Six Clinical Trials.

Retrospective studies suggest that immunosuppressive treatment of immune-related adverse events (irAEs) impairs survival in patients with melanoma who received immune checkpoint inhibitors. Here, we study this association across tumor types using data from six international phase II/III registrational trials. A post hoc analysis was performed on individual patient data from the anti-programmed cell death-1 (anti-PD-1) + anti-cytotoxic T lymphocyte-associated protein-4 (anti-CTLA-4) treatment arms of six clinical trials (CheckMate-067, -142, -214, -648, -743, and -9LA). Among patients who received systemic immunosuppression for treatment-related adverse events (trAEs), associations of peak and cumulative corticosteroid dose, and use of second-line immunosuppression with overall survival (OS) and progression-free survival (PFS) were assessed using multilevel Cox regression with adjustment for age and sex. Of the 1,959 patients who received anti-PD-1 + anti-CTLA-4 therapy, 834 patients who were treated with immunosuppression for trAEs were included. Eight hundred and thirty-two patients (100%) received corticosteroids and 81 patients (10%) received second-line immunosuppressants. High corticosteroid peak dose was associated with worse PFS: adjusted hazard ratio (HRadj), 1.15 (95% CI, 1.02 to 1.29) for 1 versus 0.5 mg/kg prednisolone and HRadj, 1.43 (95% CI, 1.05 to 1.96) for 2 versus 0.5 mg/kg. Similar effects were observed for OS: HRadj, 1.21 (95% CI, 1.06 to 1.39) and HRadj, 1.66 (95% CI, 1.17 to 2.37) for 1 and 2 versus 0.5 mg/kg, respectively. Cumulative corticosteroid dose was not associated with survival. HRadj of use of second-line immunosuppression was 1.23 (95% CI, 0.90 to 1.68) for PFS and 1.25 (95% CI, 0.88 to 1.77) for OS. Higher corticosteroid peak dose for trAEs is associated with worse survival across tumor types, while cumulative dose is not. Too few patients received second-line immunosuppressants to confirm or reject an association with survival. These data argue for a reconsideration of irAE management approaches, starting with lower corticosteroid dose whenever feasible.

Orbital Myositis Leading to Compressive Optic Neuropathy after COVID-19 mRNA Vaccination: A Case Report

Purpose: We present a case of bilateral compressive optic neuropathy secondary to orbital myositis after COVID-19 messenger ribonucleic acid (mRNA) vaccination.Case summary: A 51-year-old man developed acute bilateral visual loss and painful ophthalmoplegia shortly after receiving the second dose of the BNT162b2 COVID-19 mRNA vaccine (Comirnaty, Pfizer®, New York, NY, USA). His best-corrected visual acuity was counting fingers at 30 cm and 50 cm in the right and left eyes, respectively. Bilateral eyelid swelling, erythema, conjunctival injection, and color vision deficit were observed. Orbital magnetic resonance imaging revealed diffuse enhancement and hypertrophy of the bilateral extraocular muscles. The patient had no significant ophthalmic history and systemic work-up revealed no evidence of underlying inflammatory disease. Based on the clinical presentation and imaging findings, he was tentatively diagnosed with bilateral compressive optic neuropathy secondary to orbital myositis after COVID-19 mRNA vaccination. He was treated with intravenous corticosteroids for 3 days followed by low-dose oral corticosteroids. One month later, his visual acuity and color vision improved; moreover, the inflammatory signs in the eyelids, conjunctiva, and extraocular muscles resolved. However, after developing COVID-19, he experienced a recurrence of symptoms and was retreated with corticosteroids. Radiotherapy was administered to address persistent color vision deficit in the right eye and recurrent eyelid edema, erythema, and conjunctival injection. This treatment effectively resolved all inflammatory signs and color vision deficits, without signs of recurrence.Conclusions: Acute fulminant orbital myositis with associated compressive optic neuropathy can manifest after COVID-19 mRNA vaccination and onset of COVID-19. Anti-inflammatory treatment measures can effectively control these manifestations.

Changing clinical practice and prognosis for severe respiratory failure over time: A nationwide inpatient database study

BackgroundSevere respiratory failure requires numerous interventions and its clinical implementation changes over time. We aimed to clarify the clinical practice and prognosis of severe respiratory failure and its changes over time. MethodsIn a nationwide Japanese administrative database from 2016 to 2019, we identified nonoperative patients with severe respiratory failure without congestive heart failure as the main diagnosis who received mechanical ventilation (MV) for more than four days. We examined trends in patient characteristics, adjunctive interventions, and prognosis. ResultsAmong 66,905 patients included in this study, patients received antibiotics (90%), high-dose corticosteroids (14%), low-dose corticosteroids (18%), and 51% were admitted to the critical care unit. Hospital mortality was 35%. Median mechanical ventilation lasted 10 days. Tracheostomy occurred in 23% of cases. Median critical care and hospital stays were 10 and 25 days, respectively. Among survivors, 23% had mechanical ventilation dependency at hospital discharge. Large relative changes in adjunctive therapies included fentanyl (30%–38%), rocuronium (4.4%–6.7%), vasopressin (3.8%–6.0%), early rehabilitation (27%–38%), extracorporeal membrane oxygenation (0.7%–1.2%), dopamine (15%–10%), and sivelestat (8.6%–3.5%). No notable changes were seen in mechanical ventilation duration, tracheostomy, critical care unit stay, hospital stay, or ventilator dependency at discharge, except for a slight reduction in hospital mortality (36%–34%). ConclusionsSeveral adjunctive therapies for severe respiratory failure changed from 2016 to 2019, with an increase in evidence-based practices and a slight decrease in hospital mortality.

The Effectiveness of High versus Low Dose Corticosteroid therapy in Pediatric Patients with Acute Respiratory Distress Syndrome

Abstract Background When the lungs fill with fluid as a result of an infection or injury, acute respiratory distress syndrome ensues. Inflamed and fluid-filled lungs occur. They become rigid as a result, making it difficult for them to breathe fully. Blood oxygen levels will fall, endangering the health of other organs. Patients will require a ventilator to help them breathe while their lungs mend. The aim of this study was: to evaluate safety and efficacy of high dose therapy in acute respiratory distress syndrome pediatric patients and to compare safety and efficacy of high dose versus low dose therapy in Acute respiratory distress syndrome patients. Patients and Methods A Prospective open label randomized trial included 15 patients as group1 received high dose corticosteroid therapy for 3 consequent days, high dose Methyl prednisone 30 mg/kg/day and 15 patients as group 2 received low dose corticosteroid therapy for 3 consequent days, low dose Methyl prednisone 2 mg/kg/day. Clinical and laboratory data chest ultrasound and bronchoalveolar lavage to measured pre collagen peptide were studied in each group before and after corticosteroid therapy. Results In the present study 15(50%) patients received high dose steroid and 15 (50%) patients received low dose steroid, male 23 (70%), female 7 (30%), age 7 (3.0-30.0), weight (9.55 ± 6.63), there was no significant difference in prognosis and total days in pediatric intensive care unit between high and low dose corticosteroid therapy as prognosis improving 17 patients (55%), death 13(45%) and As regards total days in pediatric intensive care unit median in high dose corticosteroid therapy 24.0 (15.50-33.0) and median in low dose corticosteroid therapy 18.50 (11.0-23.50) less days in pediatric intensive care unit in low dose steroid therapy group than high dose steroid therapy group but no significant difference between two groups as regarding decrease in chest ultrasound (BLUE Score) and increase in pre collagen peptide in bronchoalveolar lavage between study groups . Conclusion there was no significant difference in prognosis and total days in pediatric intensive care unit between high and low dose corticosteroid therapy as regarding change in chest ultrasound (BLUE Score) and change in pre collagen peptide in bronchoalveolar lavage between study groups.

Risk Factors Associated with Cutaneous Reactions Following COVID-19 Vaccine Immunisation: A Registry-Based Case-Control Study.

In Malaysia, following extensive COVID-19 vaccination, Hospital Kuala Lumpur reported an increase in cutaneous reactions post-immunisation. To understand this, a case-control study was initiated to identify potential risk factors. This registry-based, unmatched case-control study encompasses all adverse event following immunisation (AEFI) reports associated with COVID-19 vaccines, received by the Department of Pharmacy at Hospital Kuala Lumpur through the Malaysian Adverse Drug Reactions Advisory Committee (MADRAC) AEFI reporting forms. Twenty-four potential risk factors were evaluated, including demographic information, medical history, food allergies, COVID-19 vaccination history and prior SARS-CoV-2 infection, were evaluated using MADRAC AEFI reporting forms. Odds ratio (OR) with 95% confidence interval (CI) were estimated using univariable and multivariable logistic regression. Cutaneous reactions were more frequent in middle-aged females, especially after the first COVID-19 vaccine dose. These reactions, primarily mild and generalised, included pruritus and urticaria. Notably, 52% were delayed reactions (more than 4 h post-vaccination). Factors associated with increased risk of cutaneous reaction following COVID-19 immunisation included history of seafood and shellfish allergy (adjusted odds ratio [adjOR]: 2.11; 95% CI: 1.12, 3.96; P = 0.020), history of vaccine allergy (adjOR: 4.07; 95% CI: 1.44, 11.54; P = 0.008), past dermatological diseases (adjOR: 5.48; 95% CI: 2.03, 14.78; P = 0.001), and past medication allergy (adjOR: 2.12; 95% CI: 1.36, 3.31; P = 0.001). Self-reported histories of allergies to vaccines, foods or medications were found to increase the likelihood of cutaneous reactions following COVID-19 vaccination. These reactions, which were predominantly mild, did not hinder the administration of the second vaccine dose. The majority of reactions occurred after the first dose, manifesting as generalised pruritus and urticaria. They were effectively managed with oral antihistamines and low-dose corticosteroids, thereby avoiding the need for hospitalisation.

The impact of cotrimoxazole in idiopathic granulomatous mastitis treatment

Introduction and importanceIdiopathic granulomatous mastitis (IGM) is a benign inflammatory breast disease, commonly presented with a sensitive breast lump and developing scars. Currently, there is no definitive treatment for IGM but Antibiotics, steroids, immunosuppressive drugs or a surgical treatments are the usual options. This case series aimed to evaluate the effectiveness of cotrimoxazole in treatment of IGM as there is no clinical consensus on the best and most widely acknowledged therapeutic management for IGM. Case presentationAll IGM patients were treated by Cotrimoxazole (800 mg BD for one week), and they were assessed at a month, 3 months, and 6 months after that. The primary outcome was an improvement in presenting complaints and symptoms such as palpable mass, bulging, pain, erythema and hypersensitivity of breast skin, breast discharge and fluctuation. The secondary outcome was the refractory rate within 6 months. Number of 20 patients were included. At the baseline, participants exhibited various symptoms such as bulging, pain and erythema (100 %), breast discharge (80 %), and fluctuation (30 %). After the intervention, there was a significant decrease in the prevalence of symptoms over the study period. The prevalence of bulging and pain, erythema, discharge, and fluctuation symptoms were decreasedto 5 %, 0 %, and 0 %, respectively. The refractory rate of IGM within six months of cotrimoxazole treatment was estimated 30 %. Clinical discussionIn this study, the treatment approach did not involve corticosteroids and invasive procedures and the recurrence rate of IGM within the six months was lower than in similar studies that employed steroids alone or any more invasive treatments. Additionally, our study showed a high healing rate with resolution of inflammation, pain, discharge, and fluctuation. These results suggest that cotrimoxazole may be a more favorable option than high-dose corticosteroids and a comparable alternative to low-dose corticosteroids regarding recurrence rates. ConclusionCotrimoxazole may be an effective treatment option for idiopathic granulomatous mastitis. However, further research is needed on different treatment options.

Anti-sulfatide antibody associated GBS with headache and abdominal pain: a case report

BackgroundGuillain‒Barre syndrome (GBS) is an acute inflammatory peripheral neuropathy caused by autoimmunity. Gangliosides and sulfatides are important components of peripheral nerves. Anti-sulfatide antibody-mediated complement is associated with acute sensorimotor peripheral neuropathy in GBS, which is characterized by pain and paresthesias.Case presentationThe child was a 7-year-old girl with headache and abdominal pain, followed by limb numbness and pain. Cranial imaging showed ventricular dilatation, peripheral nerve function conduction examination showed polyradiculopathy, and cerebrospinal fluid tests showed normal cell counts but elevated protein levels, all of which led to the diagnosis of GBS. After treatment with intravenous immunoglobulin (400 mg/kg × 5 days), the symptoms did not improve, and muscle strength progressively worsened, accompanied by paroxysmal complexion flushing, heart rate fluctuation, hyperhidrosis, and a progressive increase in cerebrospinal fluid protein (up to 3780.1 mg/L). On the basis of these findings combined with serum anti-sulfatide IgM positivity, anti-sulfatide antibody-related GBS was considered, and treatment with low-dose prednisolone (1 mg/kg/d) led to symptom improvement.ConclusionsAnti-sulfatide antibody-associated GBS is associated with small fiber peripheral neuropathy. The main manifestations are pain, paresthesias and autonomic dysfunction. In addition to the dysfunction of spinal nerve root absorption caused by increased cerebrospinal fluid protein, autonomic dysfunction may be involved in pain. When the therapeutic effect of immunoglobulin is not satisfactory, a low dose and short course of corticosteroids can be considered, and the prognosis is good.

Investigating risk factors and treatment options for severe, partially steroid responsive, and steroid-refractory checkpoint inhibitor pneumonitis.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer care with incredible reductions in mortality. One of the most devastating complications of treatment is ICI-related pneumonitis (ICI-p). Despite this, little is known regarding risk factors for severe pneumonitis and treatment effectiveness of various therapeutic options for steroid-refractory disease. To address this, we conducted a retrospective study on patients with cancer who developed ICI-p. We examined consecutive patients who received ICIs and developed ICI-p. Risk factors of interest for severe disease and steroid-refractory ICI-p, including pre-treatment pulmonary function tests (PFTs) and chest imaging, were compared between patients with severe (grades 3-5) and mild (grades 1-2) pneumonitis. The clinical and treatment courses for patients with steroid-refractory ICI-p were recorded. A total of 132 patients developed ICI-p, with 60 patients having mild and 72 with severe disease. We found that lower forced vital capacity percent predicted (66.24 vs 85.05, P = .05), lower total lung capacity percent predicted (85.23 vs 99.71, P = .13), and specific radiographic patterns on pre-treatment chest imaging were predictors of severe disease. Initial corticosteroid dose of less than 1 milligram per kilogram prednisone equivalent (P = .14) was correlated with partially steroid-responsive or steroid-refractory ICI-p. Ten patients had steroid refractory ICI-p, and those who received IVIG alone as the immune suppressant beyond corticosteroids had improved survival (P = 05). We are the first to identify pre-treatment PFTs and chest imaging abnormalities as risk factors for severe ICI-p. We also found that lower corticosteroid doses were associated with partially steroid-responsive and steroid-refractory ICI-p. Larger, prospective studies are needed to validate our results.

СРАВНИТЕЛЬНЫЙ АНАЛИЗ РАННЕГО И ПОЗДНЕГО НАЗНАЧЕНИЯ БИОАНАЛОГА РИТУКСИМАБА BCD020 ПРИ СИСТЕМНОЙ КРАСНОЙ ВОЛЧАНКЕ У ДЕТЕЙ: РЕЗУЛЬТАТЫ ОДНОЦЕНТРОВОГО РЕТРОСПЕКТИВНОГО КОГОРТНОГО ИССЛЕДОВАНИЯ

Juvenile systemic lupus erythematosus (jSLE) is a severe life-threatening disease with an immunoinflammatory pathogenesis and possible involvement of several organs or organ systems, both sequentially and simultaneously. Early initiation of biological therapy may improve disease outcomes. The purpose of this research was to evaluate the benefits of early initiation of genetically engineered biological therapy for jSLE with the Rituximab biosimilar BCD020. Materials and methods used: a single-center retrospective cohort study performed at the Saint Petersburg State Pediatric Medical University (Saint Petersburg, Russia) in 2012-2022 that included information on 36 patients with early Rituximab prescription (ERP; within less than 6 months from the jSLE diagnosis) and late Rituximab prescription (LRP; after over one year). The main characteristics of the disease were compared at the onset, at the time of initiation of Rituximab therapy and at 12 months after that. Results: the main baseline differences between the groups were statistically significantly higher disease activity according to the SLEDAI scale (p=0.003) and a higher incidence of macrophage activation syndrome (p=0.096), a higher average daily dose of glucocorticosteroids (GCS) in the ERP group (p=0.027). At the end of the study there were no statistically significant differences in the main outcomes of SLE between the compared groups. The main advantages of ERP were a statistically significantly shorter time to achieve a low daily dose of GCS (&lt;0.2 mg/kg) - 1.2 (0.9; 1.4) years compared to 2.8 (2.3; 4 .0) years (p&lt;0.001) and a higher likelihood of achieving a low dose of corticosteroids (RR=57.8 [95% CI: 7.2; 463.2], p&lt;0.001) and achieving remission (SLEDAI=0); RR=37.6 [95% CI: 4.45; 333.3], p&lt;0.001). During the research there were no statistically significant differences in the incidence of adverse events, including severe adverse events, between the compared groups of patients. Conclusion: ERP makes it possible to improve the control over the activity of jSLE and minimize the volume of GCS drugs with similar treatment outcomes and safety profile. Further research is required in order to determine the indications for biological therapy for jSLE.

Yellow bronchoalveolar lavage from chronic eosinophilic pneumonia

A 64-year-old female was admitted to our hospital for non-resolving pneumonia. Chest imaging demonstrated persistent, primarily right-sided pulmonary infiltrates despite two courses of oral antibiotics. Bloodwork was notable for peripheral eosinophilia (1.0 x 109/L). A bronchoscopy was completed demonstrating bright yellow bronchoalveolar lavage (BAL) fluid with a cell count differential of 27% eosinophils. A diagnosis of chronic eosinophilic pneumonia was made, with the patient having a dramatic clinical and radiographic improvement following treatment with low-dose oral corticosteroids.

Safety and efficacy of low dose versus high dose corticosteroid for graft versus host disease (GVHD): A systematic review.

e24047 Background: Graft-versus-host disease (GVHD) is an immune-mediated complication of allogeneic hematopoietic stem cell transplantations. Current standard dose of corticosteroids used by the most hospitals for GVHD patients is 1-2 mg/kg/day. The prednisone dose used in the treatment of a GVHD has been a matter of debate. In this systematic review, we aimed to compare low dose prednisone to high/standard dose prednisone in terms of multiple prognostic outcomes of the patients undergoing allogenic hematopoietic stem-cell transplantations. Methods: We searched the databases PubMed, Cochrane library, and clinicaltrials.gov for all studies investigating the efficacy and safety of low dose and high dose steroid for GVHD. We set the search strategy incorporating the search terms, Graft-versus-host disease," "low dose cortico-steroid," and "high dose corticosteroid", and operated using the Boolean operators ‘AND’, and ‘OR’. Thus, retrieved articles were then exported on an Excel sheet, and duplicates were removed. After selecting the study based on inclusion criteria, data on study characteristics and biomarker description was extracted on a pre-determined data extraction table on the Microsoft Excel. Results: The search revealed 547 studies and 3 studies that met the eligibility criteria of this review have been included.During relapse, chronic GVHD, mortality, and malignancy outcomes were generally similar between doses, low-dose prednisone showed benefits for leukemia-free, relapse-free, and overall survival. Overall, the randomized trial by Chang et al. found lower risks of HZV and pulmonary infections with low-dose prednisone compared to standard-dose. (Table 1) Other infections were similar between groups. Conclusions: Low-dose prednisone showed similar efficacy to standard-dose for most GVHD outcomes (relapse risk, mortality), with potential benefits on survival, reduced HZV/pulmonary infections, and reduced adverse effect of higher cumulative dose of corticosteroids. [Table: see text]

High-Dose or Low-Dose Corticosteroids - Which Regimen is More Effective in Patients with Moderate to Severe COVID-19? A Retrospective Study.

Although several studies have assessed corticosteroid therapy as a pivotal treatment for SARS-CoV-2, the net effectiveness of corticosteroids in the treatment of COVID-19 remains controversial. This study aimed to compare the conventional use of methylprednisolone and pulse therapy to determine the best method of administration of corticosteroids in patients with SARS-CoV-2. A total of 52 patients with a diagnosis of moderate to severe COVID-19 with the same conditions were retrospectively enrolled in the present study. Participants were divided into two groups based on the corticosteroid therapy regimen received during hospitalization: low-dose and high-dose methylprednisolone. Clinical outcomes, including laboratory tests, improvement of oxygen saturation, the need for invasive mechanical ventilation, length of hospital stay (LOHS) and mortality, were compared between the two groups. The distribution of sex, age, oxygen saturation on admission, pattern and location of lung involvement, and other medical conditions were similar between the two groups to avoid the effect of any possible confounding factor. There were no differences in laboratory tests (P=0.389), LOHS (P=0.107), improvement of oxygen saturation (P=0.721), the need for invasive mechanical ventilation and mortality (P=0.695) between groups. Based on the results of this study, there was no significant difference in clinical outcomes of patients with COVID-19 between low- and high-dose corticosteroid regimens. Further research is warranted to determine the best method of administration of corticosteroids in these patients.

Immune responsiveness in stable kidney transplantation patients: Complete inhibition of T-cell proliferation but residual T-cell activity during maintenance immunosuppressive treatment.

The recommended immunosuppressive treatment after kidney transplantation consists of tacrolimus, mycophenolate mofetil, and low-dose corticosteroids. Drug concentrations are monitored using therapeutic drug monitoring (TDM), which does not necessarily correlate with pharmacodynamic activity. To find the balance between optimal efficacy and minimal toxicity, it might be more informative to monitor patients' immunological status rather than drug concentrations. We selected a panel of T-cell-based immune assays, which were used for immunomonitoring of 14 stable kidney transplantation patients. Whole blood was incubated with a T-cell stimulus, after which T-cell proliferation, T-cell activation marker expression and cytokine production were measured to study residual immune activity invitro (before drug intake; drug added to the incubation) and exvivo (after drug intake). T-cell proliferation was completely suppressed in all patients over the full day, while IL-2, IFN-γ, CD71, and CD154 showed fluctuations over the day with a strong inhibition (75%-25%) at 2 h post-dose. The level of inhibition was variable between patients and could not be related to pharmacokinetic parameters or the presence of regulatory or senescence immune cells. Moreover, the level of inhibition did not correlate with the invitro tacrolimus drug effect as studied by incubating pre-dose blood samples with additional tacrolimus. Overall, IL-2, IFN-γ, CD71, and CD154 seem to be good markers to monitor residual immune activity of transplantation patients. To evaluate the correlation between these pharmacodynamic biomarkers and clinical outcome, prospective observational studies are needed.

In-hospital survival of critically ill COVID-19 patients treated with glucocorticoids: a multicenter real-world data study

The COVID-19 pandemic has posed a major challenge to healthcare systems globally. Millions of people have been infected, and millions of deaths have been reported worldwide. Glucocorticoids have attracted worldwide attention for their potential efficacy in the treatment of COVID-19. Various glucocorticoids with different dosages and treatment durations have been studied in patients with different severities, with a suitable dosage and treatment duration not yet defined. This study aimed to investigate whether in-hospital survival differs between critically ill patients treated with low-dose glucocorticoids, high-dose glucocorticoids or no glucocorticoids. All critically ill patients admitted to the intensive care unit of the Charité Hospital—Universitätsmedizin Berlin between February 2020 and December 2021 with COVID-19 pneumonia receiving supplemental oxygen were eligible to participate in this multicenter real-world data study. Patients were retrospectively assigned to one of three groups: the high corticosteroid dose (HighC) group (receiving 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), the low corticosteroid dose (LowC) group (receiving less than 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), or the no corticosteroid (NoC) group. Overall survival and risk effects were compared among groups within the total observation period, as well as at 35 days after the onset of COVID-19 symptoms. Adjusted multivariable Cox proportional hazard regression analysis was performed to compare the risk of death between the treatment groups. Out of 1561 critically ill COVID-19 patients, 1014 were included in the baseline analysis. In the survival study, 1009 patients were assigned to the NoC (n = 346), HighC (n = 552), or LowC group (n = 111). The baseline characteristics were balanced between groups, except for age, BMI, APACHE II score, SOFA and SAPS II. While the 35-day survival did not show any differences, a landmark analysis of the patients surviving beyond 35 days revealed differences between groups. The restricted mean survival time was 112 days in the LowC group [95% CI: 97 – 128], 133 days in the HighC group [95% CI: 124 – 141] and 144 days in the NoC group [95% CI: 121 – 167]. The multivariable-adjusted Cox proportional hazard analysis indicated that, regardless of age, sex, health status or invasive oxygenation, a low-dose treatment increased the hazard of death of critically ill COVID-19 patients by a factor of 2.09 ([95% CI: 0.99, 4.4], p = 0.05) and a high-dose corticosteroid treatment increased the risk by a factor of 1.07 ([95% CI: 0.53, 2.15], p = 0.85) compared to no treatment with glucocorticoids. The analysis reveals that corticosteroid treatment does not influence the survival of critically ill COVID-19 patients in the intensive care unit within 35 days. Our evaluations further suggest that regardless of ventilation status, the decision-making process for administering corticosteroid therapy should account for the individual severity of the illness.