Low-dose Methylprednisolone Research Articles

Corticosteroid effects on IL-10 and IL-1β in U937-derived macrophages: A model for Kawasaki disease-associated inflammation

BackgroundKawasaki disease (KD) is a pediatric vasculitis that has a predilection for coronary artery involvement. Activated macrophages play an important role in the destruction of the coronary arteries in KD. Although intravenous immunoglobulin (IVIG) is standard therapy, corticosteroids are sometimes given to patients at a higher risk of IVIG non-responsiveness. In this study, we examined the effect of IVIG and corticosteroids in U937 derived M1 and M2 a macrophages. MethodsA total of 40 children with KD and 30 healthy controls were enrolled. U937-derived macrophages were stimulated with patient plasma to examine its effect on macrophage polarization. U937 derived M1 and M2 macrophages were then stimulated with IVIG and methylprednisolone. RNA was extracted from cell cultures and the expression levels of STAT1, interleukin (IL)-1β, PPARγ and IL-10 were determined by RT-PCR. ResultsIVIG was effective at suppressing IL-10 expression in M2 macrophages (relative mRNA expression mean ± SE, high dose IVIG Vs. untreated 0.304 ± 0.095 Vs. 2.541 ± 0.157, p = 0.002), but did not suppress the production of IL-1β in M1 macrophages. In contrast, methylprednisolone both suppressed the IL-1β in M1 macrophages and also enhanced IL-10 in M2 macrophages even at low doses (relative mRNA expression mean ± SE, low dose methylprednisolone Vs. untreated IL-1β 6.353 ± 0.414 Vs. 93.838 ± 1.321, p < 0.001, IL-10 61.117 ± 2.319 Vs. 46.867 ± 2.893, p = 0.005). DiscussionIn this study we found that methylprednisolone was effective at suppressing the inflammatory cytokine IL-1β in M1 macrophages, and enhanced the production of anti-inflammatory IL-10 in M2 macrophages, an effect that could not be produced by IVIG. Our findings provide further mechanistic evidence that corticosteroid therapy, even at low doses may be a cost-effective adjuvant to IVIG therapy in patients with high-risk KD.

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.

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.

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. 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. 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. 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. 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. 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. ChiCTR.org.cn Identifier: ChiCTR2100051729.

Effect of methylprednisolone in reducing severe COVID-19 and mortality in high-risk patients: A retrospective study.

The treatment of COVID-19 patients, especially high-risk patients, remains a large challenge. Glucocorticoids have been accepted as effective medicines for severe COVID-19. However, the glucocorticoid usage guidelines do not cover all the indications for high-risk patients. To identify more effective treatments for high-risk patients with COVID-19, this retrospective study analyzed routine epidemiological, clinical, and laboratory data from 33 high-risk patients with COVID-19 in Beijing Gobroad Boren Hospital, Beijing, China, most of whom responded well to treatment. Severe acute respiratory syndrome coronavirus-2 infection was confirmed via real-time reverse transcriptase polymerase chain reaction assays. Outcome measures such as duration of mechanical ventilation, intensive care unit length of stay, and 28-day mortality were analyzed. Patients were divided into two groups: mild to moderate COVID-19 (n = 26) and severe COVID-19 (n = 7). Chest computed tomography images were used to guide methylprednisolone administration or withdrawal. Upon intensive care unit admission, 12.1% of patients were mechanically ventilated with an average partial pressure of oxygen/fraction of inspired oxygen(PaO2/FiO2) ratio of 279 ± 146. No coinfections with other endemic viruses were observed. The duration of mechanical ventilation was 16 days (interquartile range: 8-28); the intensive care unit length of stay was 11 (interquartile range: 2-33) days; and the 28-day total mortality was 3.0%. Multivariate regression analysis revealed that low-dose, timely methylprednisolone administration was associated with a lower severe COVID-19 rate and mortality in high-risk patients. For high-risk patients, once there are ground-glass opacities (GGO) in the computed tomography image, continuous and low-dose methylprednisolone administration promotes inflammation remission and protects them from severe COVID-19 or mortality.

Targeted drug delivery into glial scar using CAQK peptide in a mouse model of multiple sclerosis.

In multiple sclerosis, lesions are formed in various areas of the CNS, which are characterized by reactive gliosis, immune cell infiltration, extracellular matrix changes and demyelination. CAQK peptide (peptide sequence: cysteine-alanine-glutamine-lysine) was previously introduced as a targeting peptide for the injured site of the brain. In the present study, we aimed to develop a multifunctional system using nanoparticles coated by CAQK peptide, to target the demyelinated lesions in animal model of multiple sclerosis. We investigated the binding of fluorescein amidite-labelled CAQK and fluorescein amidite-labelled CGGK (as control) on mouse brain sections. Then, the porous silicon nanoparticles were synthesized and coupled with fluorescein amidite-labelled CAQK. Five days after lysolecithin-induced demyelination, male mice were intravenously injected with methylprednisolone-loaded porous silicon nanoparticles conjugated to CAQK or the same amount of free methylprednisolone. Our results showed that fluorescein amidite-labelled CAQK recognizes demyelinated lesions in brain sections of animal brains injected with lysolecithin. In addition, intravenous application of methylprednisolone-loaded nanoparticle porous silicon conjugated to CAQK at a single dose of 0.24 mg reduced the levels of microglial activation and astrocyte reactivation in the lesions of mouse corpus callosum after 24 and 48 h. No significant effect was observed following the injection of the same dose of free methylprednisolone. CAQK seems a potential targeting peptide for delivering drugs or other biologically active chemicals/reagents to the CNS of patients with multiple sclerosis. Low-dose methylprednisolone in this targeted drug delivery system showed significant beneficial effect.

Local steroid injection in severe idiopathic granulomatous mastitis as a new first-line treatment modality with promising therapeutic efficacy.

Intralesional steroid injection has recently evolved as a novel treatment modality for localized idiopathic granulomatous mastitis (= IGM). We aimed to explore the therapeutic efficacy of local steroid injections (LSI) in patients with severe IGM. Fifty-one patients diagnosed with severe IGM were included in the study and treated with either local steroid injection (LSI) alone (n = 25) or combined LSI with systemic oral steroid treatment (OST) (n = 26). The local steroid injection protocol included an intralesional triamcinolone acetonide injection into the palpable granulomas every 4-week, and topical administration of steroid-containing pomades twice a day on the affected surface of the breast. Patients with a combined LSI and OST received low-dose oral methylprednisolone (<16 mg). Patients with LSI alone required more LSI applications than those in the combined LSI with OST group (LSI: 5 ± 2.9; vs. LSI/OST: 3.5 ± 2.5; p = 0.080) to obtain an effective optimum therapeutic response. At a median of 12 months (range, 4-42), no difference was found in complete response rates between patients in the LSI group and the combined LSI group with OST (52 vs. 53.9%, p = 0.999). However, steroid-related systemic side effects were lower in the LSI alone group (p < 0.008). Local steroid injection could be considered as the first-line treatment in patients with severe IGM until a therapeutic response has been obtained either as the sole treatment modality or combined with oral steroids. Compared with systemic oral steroid therapy, local steroid administration can be considered a new treatment modality with fewer side effects.

The Role of Long-term Low-dose Methylprednisolone Treatment on Long Covid Patients

The Role of Long-term Low-dose Methylprednisolone Treatment on Long Covid Patients

Major Publications in the Critical Care Pharmacotherapy Literature: 2022.

A number of trials related to critical care pharmacotherapy were published in 2022. We aimed to summarize the most influential publications related to the pharmacotherapeutic care of critically ill patients in 2022. PubMed/Medical Literature Analysis and Retrieval System Online and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2022, and December 31, 2022, were included in this article. Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included and stratified into clinical domains based upon consistent themes. Consensus was obtained on the most influential publication within each clinical domain utilizing an a priori defined three-round modified Delphi process with the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature. The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update yielded a total of 704 articles, of which 660 were excluded. The remaining 44 articles were stratified into the following clinical domains: emergency/neurology, cardiovascular, gastroenterology/fluids/nutrition, hematology, infectious diseases/immunomodulation, and endocrine/metabolic. The final article selected from each clinical domain was summarized following a three-round modified Delphi process and included three randomized controlled trials and three systematic review/meta-analyses. Article topics summarized included dexmedetomidine versus other sedatives during mechanical ventilation, beta-blocker treatment in the critically ill, restriction of IV fluids in septic shock, venous thromboembolism prophylaxis in critically ill adults, duration of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia, and low-dose methylprednisolone treatment in severe community-acquired pneumonia. This concise review provides a perspective on articles published in 2022 that are relevant to the pharmacotherapeutic care of critically ill patients and their potential impact on clinical practice.

Low-Dose Intravenous Methylprednisolone in Remission Induction Therapy for ANCA-Associated Vasculitis.

Glucocorticoids (GC) remain integral to the management of ANCA associated vasculitis (AAV), but are associated with significant adverse effects. Recent studies have shown reduced oral GC dosing to be safe and effective, however data guiding the use of intravenous (IV) methylprednisolone (MTP) is limited. A single centre, retrospective cohort of patients with AAV were divided into two groups; low-dose GC (patients receiving 250mg IV MTP followed by a tapering course of 30mg prednisolone daily) versus high-dose GC (1.5g IV MTP followed by tapering course of 40-60mg prednisolone daily). Primary outcomes included; end stage kidney disease (ESKD) and mortality, secondary outcomes; glucocorticoid related toxicity, remission and relapse rates. This study was applied to patients with newly diagnosed AAV, including those with severe or life-threatening disease. Sixty-five patients were included in the final analysis, 34 in the high dose and 31 in the low-dose treatment group. At diagnosis, more advanced renal impairment and histological disease was present in the low-dose cohort. The rate of ESKD was similar between groups at 6 and 12 months (P=0.22, P=0.60 respectively). More deaths occurred in the high-dose group (26.5% vs 6.5%, P=0.05) although on multivariable analysis this was not significant (P=0.06). Remission rates were comparable and there was no significant difference in relapses. Adverse events were seen in both groups but the high dose patients experienced a higher number of severe infections, weight gain and steroid induced diabetes. We demonstrate that markedly reduced dose IV MTP with a lower overall cumulative dose GC is safe and effective in the management of severe AAV disease, with no significant difference in primary outcomes.

The Efficacy of High-Dose Pulse Therapy vs. Low-Dose Intravenous Methylprednisolone on Severe to Critical COVID-19 Clinical Outcomes: A Randomized Clinical Trial.

It remains unclear which formulation of the corticosteroid regimen has the optimum efficacies on COVID-19 pneumonia. The aim of this study was to compare the clinical outcomes of 2 different regimens in the treatment of acute respiratory distress syndrome (ARDS) caused by COVID-19: Methylprednisolone at a dose of 1 mg/kg every 12 hours (low-dose group) and 1000 mg/day pulse therapy for 3 days following 1 mg/kg methylprednisolone every 12 hours (high-dose group). In this randomized clinical trial, patients with mild to moderate ARDS due to COVID-19 were randomly assigned to receive either low-dose (n = 47) or high-dose (n = 48) intravenous methylprednisolone regimens. Two groups were matched for age, gender, body mass index (BMI), comorbidities, leukocytes, lymphocytes, neutrophil/lymphocyte, platelet, hemoglobin, and inflammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and ferritin). Both regimens were initiated upon admission and continued for 10 days. The clinical outcome and secondary complications were evaluated. Evaluating in-hospital outcomes, no difference was revealed in the duration of intensive care unit (ICU) stays (5.4 ± 4.6 vs. 4.5 ± 4.9; P = 0.35), total hospital stays (8 ± 3.1 vs. 6.9 ± 3.4; P = 0.1), requirement rate for invasive ventilation (29.2% vs. 36.2%; P = 0.4) or non-invasive ventilation (16.6% vs 23.4%; P = 0.4), and hemoperfusion (16.6% vs 11.3%; P = 0.3) between the low- and high-dose groups. There was no significant difference in fatality due to ARDS (29.2% vs. 38.3%; P = 0.3) and septic shock (4.2% vs. 6.4%; P = 0.3) between the low- and high-dose groups. Patients in the high-dose group had significantly higher bacterial pneumonia co-infection events compared with those in the low-dose group (18.7% vs 10.6%; P = 0.01). The use of adjuvant pulse therapy with intravenous methylprednisolone did not result in improved in-hospital clinical outcomes among patients with mild to moderate ARDS due to COVID-19. A higher risk of bacterial pneumonia should be considered in such cases as receiving a higher dose of steroids.

Robotic-assisted mobilization for an effective mobilization in a COVID-19 patient with ECMO treatment

An effective (early) mobilization in COVID-19 intensive care patients with ECMO treatment is very important. Sedation, extracorporeal procedures with the danger of circuit malfunction, large lumen ECMO cannulas with a risk of dislocation and a very severe neuromuscular weakness are factors that could deem mobilization beyond stage 1 of the ICU mobility score (IMS) in some cases difficult or impossible; however, early mobilization is a key point of the ABCDEF bundle to counteract pulmonary complications, neuromuscular dysfunction and enable recovery. The case of a 53-year-old, previously healthy and active male patient with a severe and complicated course of COVID-19 and pronounced ICU-acquired weakness is described. While receiving ECMO the patient could be mobilized using a robotic system. Due to severe and rapidly progressing pulmonary fibrosis, additional low-dose methylprednisolone therapy (Meduri protocol) was implemented. Under this multimodal treatment the patient was successfully weaned from the ventilator and decannulated. Robotic assisted mobilization has the potential to be a novel and safe therapeutic option for a customized and highly effective mobilization in ECMO patients.

The Effect of Short-term Methylprednisolone on Clinical Outcome and Lung CT Scan in Severe COVID-19: In-hospital and Six Weeks Later Follow-up

Background: The severe coronavirus disease 2019 (COVID-19) induces widespread inflammatory responses that are attempted to be managed by the administration of anti-inflammatory drugs, along with antiviral drugs and respiratory support. This clinical trial study investigated the effect of short-term and low-dose methylprednisolone on the clinical outcome and radiological improvement of admitted patients with severe COVID-19. Methods: In this randomized clinical trial, two strains of patients with severe pneumonia of COVID-19 were evaluated before and after the use of corticosteroids. Inclusion criteria were age over 18 years, definitive case of COVID-19 based on positive reverse transcription polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), and arterial oxygen saturation (SaO2 )&lt;93%; furthermore, at least 7 days and 5 days should be passed since the onset of symptoms and antiviral treatment, respectively. Exclusion criteria were similar to contraindications to the administration of methylprednisolone for short-term injections and pregnancy. Patients received intravenous methylprednisolone succinate (1-1.75 mg/kg/day) for 5 days in addition to treatment based on the World Health Organization (WHO) approved protocol for COVID-19. Finally, demographic characteristics, dyspnea, peripheral oxygen saturation (SpO2), number of lymphocytes, and computed tomography (CT) scan of the patient’s chest before and after taking corticosteroids were evaluated. Results: The average oxygen saturation of patients increased significantly after taking methylprednisolone succinate (P&lt;0.001). Moreover, dyspnea and pulmonary insufficiency in CT scans improved significantly (P&lt;0.001), and among hematological parameters, only lymphocytes increased significantly (P=0.01). Furthermore, methylprednisolone succinate use had no effect on mortality and length of hospitalization. Conclusion: Methylprednisolone succinate use during the treatment period of COVID-19 improves clinical conditions, CT scan findings, and hematological parameters affected by inflammation, but it does not affect the mortality and length of hospitalization of patients.

Efficacy of initial high- versus low-dose intravenous corticosteroid therapy in patients with acute exacerbation of idiopathic interstitial pneumonia: A nationwide observational study.

Acute exacerbation of idiopathic interstitial pneumonias (AE-IIPs) has a high mortality. However, there is no established treatment for AE-IIPs. Therefore, we aimed to compare the efficacy of high- and low-dose corticosteroid therapies in AE-IIPs patients. Data were retrospectively collected from the Japanese Diagnosis Procedure Combination database from July 2010 to March 2018. Adult patients with AE-IIPs who received high-dose (methylprednisolone at a dose of 500-1000 mg/day for 3 days starting within 4 days after admission) or low-dose (methylprednisolone at a dose of 100-200 mg/day for at least 5 days starting within 4 days after admission) corticosteroid therapy were identified. Eligible patients (n = 17,317) were divided into the high-dose (n = 16,998) and low-dose (n = 319) groups. A stabilized inverse probability of treatment weighting using propensity scores was performed to compare outcomes between the groups. The primary outcome was in-hospital mortality, and the secondary outcomes were 28-day mortality, infections during hospitalization, length of hospitalization, duration of steroid use, and discharge to home. The in-hospital mortality rates of the high- and low-dose corticosteroid groups were 50.6% and 47.0%, respectively. In-hospital mortality did not significantly differ between the two groups after stabilized inverse probability of treatment weighting, and the odds ratio in the low-dose corticosteroid group was 0.86 (95% confidence interval: 0.64-1.16; p = 0.33). The secondary outcomes also did not significantly differ between the groups. There was no significant difference in outcomes between patients with AE-IIPs who received high- and low-dose corticosteroid therapies.

Hydroxychloroquine, azithromycin and methylprednisolone and in hospital survival in severe COVID-19 pneumonia

Introduction: Severe COVID-19 pneumonia has two phases that are not mutually exclusive. Repurposed drugs target only one phase and the association of combination therapy to survival is unknown. Objective: To determine the association of hydroxychloroquine, azithromycin, and methylprednisolone versus methylprednisolone only to in hospital survival. Methods: This is a secondary analysis of a retrospective cohort of patients admitted for severe covid-19 in 13 hospitals in New Jersey, United States from March–June 2020. Propensity score match with 11 variables was constructed between those who received no methylprednisolone and methylprednisolone. Multivariate Cox regression was used for risk of in hospital mortality. Measurements and main results: There were 759 patients, 380 in no methylprednisolone and 379 with methylprednisolone. Multivariate Cox regression shows that methylprednisolone, hydroxychloroquine, and azithromycin had prolonged survival compared to methylprednisolone alone [HR 0.45 (95% CI 0.22,0.91 p < 0.03)]. In patients who received hydroxychloroquine and azithromycin, those who also received high dose methylprednisolone were associated with worse survival compared to those who received low dose methylprednisolone (HR = 1.642; 95% CI 1.053 to 2.562; p = 0.0287). Nursing home residents [HR 2.77 (95% CI 1.67, 4.59 p < 0.0001)], coronary artery disease [HR 2.93 (95% CI 1.31, 3.15 p = 0.001), and invasive mechanical ventilation [HR 3.02 (95% CI 1.71,5.34 p = 0.0001)] were independently associated with worse survival. Conclusion: Combination therapy was associated with improved survival compared to monotherapy. However, nursing home residents, coronary artery disease, and mechanical ventilation were independently associated with mortality. Larger randomized controlled studies are needed to confirm conclusions.

Saponins from Panax notoginseng ameliorate steroid resistance in lupus nephritis through regulating lymphocyte-derived exosomes in mice.

Lupus nephritis (LN) is the most common and severe type of organ damage and an important primary disease in end-stage renal failure in patients with systemic lupus erythematosus (SLE). Clinical guidelines recommend steroid treatment, but steroid resistance has become a major factor leading to treatment failure and affecting prognosis. Our previous study demonstrated that Saponins from Panax Notoginseng (Panax ginseng saponins, PNS) could reverse steroid resistance of lymphocytes by downregulating P-glycoprotein (P-gp) expression and provide renal protection in LN mice, but the mechanism by which lymphocytes transmit these related messages to renal lamina propria cells is not clear. Therefore, we further elucidated this mechanism through holistic experiments. In this study, low-dose methylprednisolone (0.8 mg/kg/day, MP) was used to induce a steroid-resistant lupus nephritis (SR-LN) mouse model in weeks one to four, and a therapeutic steroid dosage (MP 12 mg/kg/day) or a combined PNS (PNS 100 mg/kg/day) treatment was administered from week five to eight. Lymphocyte-derived exosomes (Lyme-Exos) were isolated from the spleens of mice and injected into untreated homozygous LN mice for 14 days via the tail vein. At the end of the experiment, the efficacy and mechanism of action of different groups of Lyme-Exos on LN mice were observed. The results revealed that exogenously injected Lyme-Exos were effectively taken up by the kidney and affected the progression of kidney disease. Steroid-resistant lymphocyte-derived exosomes intervented with PNS significantly downregulated the levels of silent information regulator-related enzyme 1 (Sirt1), multidrug resistance gene 1 (MDR1), and P-gp in the renal cortex and glomerular endothelial cells (GECs); reduced serum autoantibody [antinuclear antibody (ANA) and anti-double-stranded DNA (dsDNA)] levels and inflammatory markers (WBC, PCR, and PCT); improved renal function; and attenuated urinary microalbumin excretion. Additionally, renal histopathological damage (HE staining) and fibrosis (Masson staining) were improved, and immune complex (IgG) deposition and membrane attack complex (C5b-9) production were significantly reduced; the gene levels of inflammatory factors (INF-γ, MCP-1, IL-8, IL-17, vWF, VCAM-1, IL-1β, IL-6, PTX3) in the renal cortex were downregulated. Taken together, this study showed that PNS may alleviate steroid resistance in GEC by interfering with steroid-resistant Lyme-Exos to ameliorate LN progression, which will likely provide insights into developing a new LN treatment.

Retrospective analysis of leflunomide and low-dose methylprednisolone for the treatment of diabetic nephropathy combined with membranous nephropathy.

Diabetic kidney disease (DKD) combined with Membranous Nephropathy (MN) was observed in some patients with the increasing of Diabetic patients. However, no treatment guidelines are available for DKD combined with MN. In this study, we for the first time analyzed the safety and efficacy of leflunomide (LEF) combined with low-dose glucocorticoid methylprednisolone (MP) in the treatment of DKD with MN. We retrospectively collected the clinical data of patients with the highest number of DKD combined with MN diagnosed by renal biopsy between December 2016 and December 2020. The inclusion criteria were a history of diabetes for more than 20 months, no glucocorticoid therapy or immunosuppressant therapy for at least 6 months, urine protein level greater than 3.5 g, and a follow-up time of 16 months. In addition to conservative treatment, the patients received LEF monotherapy (LEF, n = 38) or LEF combined with low-dose methylprednisolone (LEF+MP, n = 26). After 16 months of treatment, the complete remission rate was 2.6%, and the remission rate was 15.8% in the LEF group; in the LEF+MP group, the complete remission rate and the remission rate were 23.1% and 34.6%, respectively. At month 16, the urine protein level was lower than the baseline value in both groups (p < 0.05) and was significantly lower in the LEF+MP group than in the LEF group (p < 0.05). Serum albumin levels were higher than the baseline value in both groups (p < 0.05), with no significant between-group difference (p > 0.05). No inter- or intragroup difference in serum creatinine or glycated hemoglobin was observed. During treatment, the relapse rate was lower in the LEF+MP group than in the LEF group (p < 0.05). No irreversible adverse events were observed. In summary, LEF+MP is more effective than LEF monotherapy for DKD combined with MN. Large, long-term, randomized, double-blind, controlled studies are needed to further validate the clinical efficacy of LEF+MP.

A clinical study of mycophenolate mofetil combined with low-dose steroids in the management of pediatric systemic lupus erythematosus

Purpose: To investigate the efficacy and safety of mycophenolate mofetil (MMF) combined with lowdose steroids in the treatment of pediatric systemic lupus erythematosus (pSLE).Methods: A total of 76 children were diagnosed and admitted with SLE, lupus nephritis (LN) and type IV diffuse proliferative glomerulonephritis at Hainan Women and Children’s Medical Center, Haikou, China from March 2017 to December 2018, had their clinical data analyzed retrospectively. Among them, 38 children received methylprednisolone pulse combined with MMF and intermittent oral low-dose glucocorticoids (GC), labelled MMF group, while the remaining 38 children, which served as control group, were treated with oral GC and transitional reduction. Pertinent biochemical parameters were evaluatedResults: Compared with control group, MMF group showed a notably lower level of erythrocyte sedimentation rate (ESR), a higher level of complement C3, lower level of serum creatinine (Scr) and 24-h urine protein level 6 months after treatment (p &lt; 0.05). Albumin level was higher in MMF group at 6 months and 12 months after treatment than in the control group. Compared to control group, the SLEDAI score in MMF group was significantly lower at 6 months and 12 months after treatment (p &lt; 0.05). Body mass index, triglyceride, fasting blood glucose and intraocular pressure levels in the MMF group were significantly lower than those in the control group (p &lt; 0.05). Post-treatment, peripheral blood CD3+ and CD4+ T lymphocytes, CD4+/CD8+ ratio and NK cell levels in the two groups were significantly increased, while CD8+ T lymphocyte level declined.Conclusion: MMF combined with low-dose methylprednisolone controls symptoms early and mitigates renal injury in the treatment of pSLE. It is also safe, and effectively regulates the patient's cellular immune function.

Dupilumab combined with low-dose systemic steroid therapy improves efficacy and safety for bullous pemphigoid.

Routine systemic therapy for bullous pemphigoid (BP) has been challenged due to the inevitably adverse effects. According to the successful applications of dupilumab in BP cases reported, therefore, we investigate the real-life efficacy and safety of dupilumab combined with low-dose oral steroid for BP. A cohort of BP patients who received either dupilumab plus low-dose methylprednisolone (dupilumab group) or merely methylprednisolone (control group) was retrospectively reviewed. The time to disease control was investigated. Additionally, the control dose and cumulative dosage of steroids, Bullous Pemphigoid Disease Area Index (BPDAI) scores, pruritus scores, and adverse events were assessed. A total of 40 patients, with 20 in each group, were retrospectively studied. The time to disease control was shorter in the dupilumab group than the control group (14 days vs. 19 days, p=0.043). When the disease was controlled, the control dose and cumulative dosage of methylprednisolone in the dupilumab group were substantially lower than those of the control (24.6mg vs. 48.8 mg, 376.8mg vs. 985.6 mg, both p < 0.01). Compared with the control, the percentage change from baseline in BPDAI scores and pruritus scores were both significantly reduced, and the adverse events were also less frequent in the dupilumab group. The combination therapy of dupilumab plus low-dose methylprednisolone exhibits superior efficacy and safety in comparison with the current first-line systemic therapy for BP.

Evaluation of personalized methylprednisolone therapy in critically ill COVID-19 patients: an observational comparative study using real-life data.

Methylprednisolone is commonly used to attenuate the cytokine storm and prevent mortality in COVID-19 pneumonia. However, the optimal methylprednisolone dose and duration are unclear. Additional data are required on the effectiveness of methylprednisolone in reducing mortality in COVID-19. This real-life retrospective study aimed to analyze the data of a COVID-19 dedicated ICU and compare the mortality rates of standard care, low-dose, and pulse-dose methylprednisolone in patients requiring mechanical ventilatory support. Methylprednisolone's indication, dose, and duration were determined according to the severity of COVID-19 pneumonia based on the patient's demographic parameters, comorbidities, laboratory data, radiology, and arterial blood gas analysis results. 867 patients were grouped as: no methylprednisolone (standard care), low-dose (0.5-1 mg/kg/day) methylprednisolone or pulse-dose (250-1,000 mg/day) methylprednisolone. The overall mortality rate was 63.78%. Adjusting the dose of methylprednisolone according to the severity of the disease resulted in statistically similar mortality rates despite the increase in disease severity. Mortality was 62.71% in standard treatment, 65.76% in low-dose, and 62.10% in pulse-dose methylprednisolone groups (p = 0.633). Invasive mechanical ventilation at admission was associated with increased mortality (HR: 1.826 [95% CI: 1.542-2.161]; p < 0.001). Hematologic disorders and malignancies, arterial blood pH and HCO3, neutrophil count, and NLR at admission were also associated with mortality. Personalizing the dose and duration of methylprednisolone according to the patient's disease severity assessed with demographic, clinical, and laboratory results may benefit mortality in severe COVID-19 patients receiving ventilatory support in the ICU. Hematologic disorders and malignancies, arterial blood pH and HCO3, neutrophil count, and NLR at admission were associated with mortality in our patient cohort.