Conventional Steroid Research Articles

Late-Onset Asthma: A Review

Asthma is a chronic respiratory condition with a growing global prevalence, affecting millions of individuals annually. While asthma can develop at any age, late-onset asthma is a specific phenotype that begins in adulthood, as recognized by the Global Initiative for Asthma (GINA) in its 2024 guidelines. This form of asthma is often associated with several predisposing factors, including gender, obesity, occupational exposure, rhinitis, respiratory infections, smoking, stress, and diminished lung function. Unlike early-onset asthma, which frequently involves a history of allergies, late-onset asthma tends to lack allergic triggers, making it a distinct and challenging form of the disease. Managing late-onset asthma is often more complex, as it typically requires higher doses of corticosteroids and demonstrates a reduced responsiveness to standard steroid treatments. The exact mechanisms and pathophysiological processes contributing to the increased severity and poorer clinical outcomes in late-onset asthma remain largely unclear. This uncertainty often leads to underdiagnosis and inadequate management, further complicating patient care. Phenotypic analysis is recommended to improve treatment outcomes. This includes assessing clinical features and utilizing biomarkers, such as inflammatory markers and immunoglobulin E (IgE) levels, to guide targeted therapy when conventional steroid treatments are insufficient. However, there is a significant need for further research to elucidate the underlying mechanisms of late-onset asthma. This literature review is essential to develop more effective, personalized treatment strategies that can address the unique challenges posed by this asthma phenotype, ultimately leading to better management and improved patient outcomes.

Association of early steroid withdrawal with kidney transplant outcomes in first-transplant and retransplant recipients.

Early steroid withdrawal (ESW) is often preferred over conventional steroid maintenance (CSM) therapy for kidney transplant recipients with low immunological risks because it may minimize immunosuppression-related adverse events while achieving similar transplant outcomes. However, the risk-benefit balance of ESW could be less favorable in retransplant recipients given their unique immunological risk profile. We hypothesized that the association of ESW with transplant outcomes would differ between first-transplant and retransplant recipients. To assess whether the impact of ESW differs between first and retransplant recipients, we studied 210 086 adult deceased-donor kidney transplant recipients using the Scientific Registry of Transplant Recipients. Recipients who discontinued maintenance steroids before discharge from transplant admission were classified with ESW; all others were classified with CSM. We quantified the association of ESW (vs. CSM) with acute rejection, death-censored graft failure, and death, addressing retransplant as an effect modifier, using logistic/Cox regression with inverse probability weights to control for confounders. In our cohort, 26 248 (12%) were retransplant recipients. ESW was used in 30% of first-transplant and 20% of retransplant recipients. Among first-transplant recipients, ESW was associated with no significant difference in acute rejection (aOR=1.04 [95% CI=1.00-1.09]), slightly higher hazard of graft failure (HR=1.09 [95% CI=1.05-1.12]), and slightly lower mortality (HR=0.93 [95% CI=0.91-0.95]) compared to CSM. Nonetheless, among retransplant recipients, ESW was associated with notably higher risk of acute rejection (OR=1.42 [95% CI=1.29-1.57]; interaction p<0.001) and graft failure (HR=1.24 [95% CI=1.14-1.34]; interaction p=0.003), and similar mortality (HR=1.01 [95% CI=0.94-1.08]; interaction p=0.04). In retransplant recipients, the negative impacts of ESW on transplant outcomes appear to be non-negligible. A more conservatively tailored approach to ESW might be necessary for retransplant recipients.

Intravenous methylprednisolone for nephrotic syndrome with minimal change lesions in adults: a randomized controlled trial.

Patients with minimal change nephrotic syndrome (MCNS) usually experienced severe edema which can affect the absorption of oral corticosteroid during the first 2 weeks. We conducted a randomized controlled trial to compare the efficacy of intravenous isovalent methylprednisolone induction followed by oral prednisone therapy with conventional oral prednisone therapy in highly edematous MCNS patients, aiming to provide a better therapy for MCNS patients. A single-center, open-label, parallel-arm randomized controlled trial was performed in the Nephrology Department of the Affiliated Hospital of Guangdong Medical University. Patients who met the inclusion were enrolled in our study from May 2015 to October 2020, and were randomized to receive conventional oral steroid or 2 weeks intravenous methylprednisolone followed by oral prednisone. 117 patients were enrolled and randomly assigned to either the sequential group (N=57) or the oral group (N=60). Total remission rate in the sequential group was higher than the oral group after treatment for 2 weeks and 4 weeks (P=0.032, P=0.027). Complete remission rate was higher in the sequential group than in the oral group (63.3% vs. 41.5%, P=0.031) after treatment for 2 weeks. The time to achieve CR is shorter in the sequential group than the oral group, with a statistically significant difference (14.0 days, 95% CI [13.5 to 14.5] vs. 16.0 days, 95% CI [12.7 to 19.3], P=0.024). There were no significant difference in relapse rate (24.5% vs 28.3%, P=0.823) and time to relapse (155±103 days vs 150.7±103.7 days, P=0.916) between two groups. This study suggested that highly edematous MCNS patients received intravenously isovalent methylprednisolone induction therapy follow by oral prednisone achieved earlier remission than the conventional oral prednisone regimen without differences in relapse rates or adverse effects. Short-term intravenous methylprednisolone followed by oral prednisone may be a better choice for MCNS patients with highly edema.

The Enhancement of Regulatory T Cell Maturation and Th1/Th2 Balance through FOXP3 Expression by Lactobacillus paracasei in an Ovalbumin-Induced Allergic Skin Animal Model.

Chronic allergic skin conditions, including atopic dermatitis (AD), are characterized by pruritus, erythema, xerosis, desquamation, and inflammation, significantly impacting quality of life. Long-term steroid use, while common in treatment, carries the risk of adverse effects. Previous studies have demonstrated the potential of Lactobacillus paracasei subsp. paracasei NTU 101 (NTU 101) in alleviating AD symptoms from a preventive perspective. This study, however, focuses on exploring NTU 101's therapeutic potential by investigating its effects on regulatory T cell (Treg) maturation and Th1/Th2 balance. The results revealed that NTU 101 administration effectively reduced serum IgE levels and inflammatory cell infiltration in the skin, leading to a significant improvement in both epidermal and dermal thickness in the AD model. Additionally, NTU 101 modulated the immune response by increasing the proportion of CD4+/IL-4+ (Th2) cells in the spleen and concurrently enhancing FOXP3 expression in CD4+/CD25+ cells, which is critical for Treg cell development. This immune modulation was further associated with a rebalancing of the Th1/Th2 ratio, achieved by increasing the proportion of CD4+/IFN-γ+ (Th1) cells. Moreover, NTU 101 influenced the proportion of CD4+IL-17+ (Th17) cells, thereby supporting neutrophil maturation and promoting allergen clearance, ultimately mitigating AD symptoms. These findings underscore the potential of NTU 101 not only in managing AD symptoms but also in modulating key immune pathways involved in the pathogenesis of the disease, offering a promising alternative or adjunct to conventional steroid therapies.

Conventional steroids vs. dual-release hydrocortisone on metabolic, cardiovascular and bone outcomes in adrenal insufficiency: a 10-year study.

Adrenal insufficiency (AI) is characterized by increased mortality compared to general population, mainly due to cardiovascular disease. Conventional glucocorticoid (GC) replacement therapy has a role in determining the increased mortality risk. Primary outcome of the current study was to evaluate the impact of 10 years of conventional GCs and DR-HC on body weight changes in treatment-naïve patients with AI. Secondary outcomes were changes from baseline to 5 and 10 years in anthropometric and metabolic profile, insulin sensitivity, cardiovascular and bone parameters. We prospectively randomised 42 patients to conventional GCs (cortisone acetate or hydrocortisone) and 44 to DR-HC (1:1). Anthropometric, metabolic, cardiovascular and bone parameters were evaluated at baseline and after 5 and 10 years of follow-up. This trial is registered at ClinicalTrials.gov NCT06260462. At 10 years of follow-up, patients with conventional GCs had significantly higher values ​​of BMI (p=0.031), waist circumference (p=0.047), systolic blood pressure (p=0.039), total and LDL cholesterol (p=0.041 and p=0.042), HbA1c (p=0.040), HOMA-IR (p=0.006), AUC2h of glucose (p<0.001), thickness of the interventricular septum in diastole and of the posterior wall (both p<0.001) and significantly lower values ​​of oral disposition index (p=0.001) and ISI-Matsuda (p<0.001), lumbar spine T score (p=0.036) and femoral neck Z score (p=0.026), compared to patients treated with DR-HC. In patients with treatment-naïve AI, 10 years of conventional GC treatment is associated with a worsening of metabolic, insulin-sensitivity, cardiac and bone outcomes, while DR-HC had no impact on them achieving a lower risk of developing comorbidities.

Audiovestibular outcomes in adult patients with cogan syndrome: a systematic review.

To determine factors associated with steroid responsiveness and efficacy of biologic disease-modifying anti-rheumatic (DMARD) use in patients with Cogan Syndrome (CS). A systematic search of Cochrane Library, PubMed, CINAHL, and Scopus was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Any study describing audiometric or vestibular data and pharmacologic treatment in patients with CS was included. Due to limited literature, only case reports/case series were included. Seventy case reports or case series studies comprising 79 individual cases of CS were included. A difference in vestibular symptoms with a higher prevalence in the steroid-resistant group than the steroid-responsive group was found (79.5% vs 57.9%, p = 0.04). Eighteen (60.0%) patients treated only with oral steroids had no audiological improvement, while twelve (n = 12; 85.7%) patients treated with biologic DMARD showed audiological improvement. The steroid-responsive group had an overall better response to DMARDs than the steroid-resistant group (62.1% vs 45.0%; 100.0% vs 77.8%). Our study synthesized the available literature to better characterize steroid resistance in patients with Cogan syndrome and treatment outcomes. Vestibular symptoms were noted to be more prevalent in patients who were eventually labeled as steroid resistant. There were higher rates of audiological improvement in patients given biologic DMARDs rather than conventional DMARDs or steroids only. Further studies are needed to characterize each individual vestibular symptom and investigate the utility and timing of biologic DMARDs in managing patients with Cogan syndrome.

Association of PLCE1 (rs7922612) and COL4A3 (rs375290088) Genetic Variants with the Risk of Nephrotic Syndrome in Egyptian Pediatric Patients.

Nephrotic syndrome is one of the most prevalent pediatric kidney illnesses seen in pediatric nephrology clinics. Steroid resistance in children with nephrotic syndrome is a primary cause of renal failure and is characterized by nephrotic range proteinuria that does not respond to conventional steroid therapy. The current work was intended to investigate the possible role of the Phospholipase C epsilon 1 (rs7922612) and collagen4 alpha 3 (rs375290088) single nucleotide polymorphisms as risk factors for developing nephrotic syndrome among Egyptian children. The study was conducted on 100 children with nephrotic syndrome and 100 age- and sex-matched healthy individuals. Geno typing was performed by two methods of polymerase chain reaction for the analysis of PLCE1 (rs7922612) and COL4A3 (rs375290088) variants. We observed a higher percentage of the heterozygous and homozygous variant genotypes of PLCE1 (rs7922612) SNP in NS patients in comparison with the controls (P < 0.001 for both). The frequencies of the PLCE1 (rs7922612) variant showed a statistically significant elevated risk of NS using several genetic models, including the dominant (OR = 9.12), recessive (OR = 2.31), and allelic (OR = 1.62) models (P < 0.001 for each). In addition, the PLCE1 (rs7922612) genotypes and alleles frequencies did not differ significantly between SRNS compared to SSNS cases. Furthermore, there was no significant difference regarding COL4A3 (rs375290088) polymorphism, neither between the NS and control groups nor between SDNS and SRNS. PLCE1 (rs7922612) is considered an independent risk factor for nephrotic syndrome in Egyptian pediatrics.COL4A3 (rs375290088) polymorphism is not correlated to Egyptian NS patients.

P21 Advancing dermatological care: a comprehensive evaluation of the steroid-free GL-1 formulation

Abstract Introduction and aims The prolonged use of topical steroids introduces notable dermatological risks, including the onset of permanent stretch marks, bruising, discoloration and vascular abnormalities. This study presents an innovative strategy by formulating GL-1, a steroid-free treatment amalgamating seaweed bioactives, sesame oil and naturally occurring salts and minerals. The objective of this study was to address the limitations of conventional topical steroids and introduce pioneering solutions to dermatological care. Methods To assess the safety and efficacy of GL-1 (product 1), a comprehensive battery of in vitro tests was employed. The skin corrosion test (OECD 431) established the noncorrosive nature of GL-1, validating its safety on reconstructed human epidermis. The skin irritation test (OECD 439) demonstrated the nonirritating attributes of GL-1, aligning with the United Nations Globally Harmonized System of Classification and Labelling guidelines. Additionally, the bovine corneal opacity and permeability test (OECD 437) affirmed the noninducing nature of GL-1 in relation to eye irritation or serious eye damage. Results Preliminary outcomes from dermal clinical trials indicate promising Results for GL-1. In vitro experiments on HaCaT and human dermal fibroblasts, adult (HDFa) cell lines highlighted the noncytotoxicity of GL-1, contrasting with the ‘Cortopin’, which exhibited cytotoxicity. GL-1 exhibited a proliferative effect in HDFa cells, signifying its potential for regenerative applications. Furthermore, both GL-1 and ‘Cortopin’ displayed antioxidant activity in HaCaT cells, underscoring the additional merits of our formulation. Conclusions Our steroid-free formulation, GL-1, demonstrates exceptional safety and efficacy through a meticulous series of in vitro assessments and initial clinical trials. These findings position GL-1 as a promising candidate for diverse dermal applications, offering a secure alternative to traditional topical steroids. The potential impact of GL-1 transcends its therapeutic efficacy, emphasizing its robust safety profile validated through multiple in vitro evaluations.

Impact of 10 years of conventional steroids vs dual-release hydrocortisone on metabolic, cardiovascular, and bone outcomes in treatment-naive patients with adrenal insufficiency

Impact of 10 years of conventional steroids vs dual-release hydrocortisone on metabolic, cardiovascular, and bone outcomes in treatment-naive patients with adrenal insufficiency

Effectiveness of Intracameral Tissue Plasminogen (r-tPA) Activator in Resolution of Fibrinous Reaction in Refractory Toxic Anterior Segment Syndrome (TASS)

Purpose: To evaluate the effectiveness of tissue plasminogen activator (r-tPA) in resistant toxic anterior segment syndrome (TASS) after Phacoemulsification. Study Design: Quasi experimental. Place and Duration of Study: Khyber Teaching Hospital, Peshawar from August 2021 to August 2023. Methods: Forty-six patients (46 eyes) with an anterior chamber fibrin reaction after cataract surgery were treated with intra-cameral injection of t-PA (30µg/0.1cc) following failure to respond to conventional treatment with intensive topical and subconjunctival steroids. Outcome measures were best corrected visual acuity (BCVA), clearance/recurrence of the fibrin reaction and complications. Results: Intra-cameral t-PA was injected2 to 6 weeks post Phacoemulsification in TASS cases. Mean post-operative injection time was 18.5± 10.2 days. After 1st day post injection, we observed total abolition of fibrinous exudate in 36(78.2%) cases and subtotal resolution in 10 (21.7%) cases. After 6 weeks the TASS was completely settled in 43(93.4%)cases. Mean BCVA improved from 0.59 ± 0.40 log MAR pre-injection to 0.38 ± 0.40 log MAR at 6th week post-injection (p=0.07). There was no statistically significant difference in BCVA and rate of fibrinolysis between the two groups after post r-tPA injections. Intra-cameral r-tPA was not associated with adverse effects like raised IOP or endophthalmitis. Conclusion: Intra-cameral t-PA injection (30µg/0.1cc)appears to be a safe and effective treatment option for resolving anterior chamber fibrin reaction refractory to conventional steroid therapy following cataract surgery.

P572 Evaluation of safety, pharmacokinetics and efficacy of oral treatment with OST-122 in patients with moderate to severe ulcerative colitis: A Phase Ib/IIa, randomized, double blind, placebo controlled clinical trial

Abstract Background OST-122 is an orally administered, GI-targeted and non-systemic JAK3/TYK2 inhibitor. In preclinical models and in healthy volunteers, OST-122 has demonstrated excellent safety and tolerability with minimal systemic exposure, thereby reducing the risk of causing serious systemic toxicities associated with current JAK inhibitors. The aim of this study was to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of OST-122 in moderate to severe ulcerative colitis (UC) patients. Methods This randomized, double blind, placebo controlled, multicenter proof of concept trial enrolled patients aged 18 to 75 years with moderate to severe UC (Total Mayo score 5-10, Endoscopic score ≥2) and with inadequate/loss of response, or intolerance to conventional (steroids and immunomodulators) and/or advanced therapy (ie. anti-TNFα, anti-integrin, anti-interleukin 12/23) in a 3:1 ratio to receive oral OST-122 400 mg (n=28) or placebo (n=9) for 28 days. The main objective of this study was to evaluate the safety and tolerability of OST-122 in patients with moderate to severe UC over 28 days by assessing the number, severity and type of adverse events. The pharmacokinetic profile was determined to confirm the compound’s low exposure in plasma (Cmax, AUC) previously observed in healthy volunteers and preclinical model. Another objective was to explore preliminary efficacy by assessing clinical parameters including rectal bleeding score and clinical response. Results A total of thirty-seven patients, 59.5% males, mean age of 44.8 years were included. The patients in the OST-122 group (n=28) had a mean Total Mayo Score at baseline of 8.1 compared to TMS = 6.7 in the placebo group (n=9). Safety analysis revealed no significant differences in the number of reported adverse events between the two treatment groups, nor did serious adverse events occur (Table 1). There were no clinically relevant changes in vital signs, laboratory values or ECG parameters which raise any safety concerns. After 28 days of treatment, 63% of patients taking OST-122 showed an improvement in rectal bleeding (vs 33% in the placebo group), 44% achieved a clinical response (vs 11% on placebo) and 22% reached clinical remission (Figure 1). Statistical significance was not achieved due to the small study size and patient variability. Pharmacokinetic data indicated minimal plasma concentrations (Cmax,ave. Day28 0.92 ng/mL) and therapeutically relevant levels in colon tissue (Cave.,Day28 15.5 ug/g tissue). Conclusion GI-restricted OST-122 was well tolerated during the 4-week treatment. Its excellent safety profile, limited systemic absorption and promising trends of clinical activity may provide a safer therapeutic option for patients with moderate to severe UC.

Topical sodium valproate-loaded nanospanlastics versus conventional topical steroid therapy in alopecia areata: a randomized controlled study

BackgroundA myriad of therapeutic modalities for alopecia areata are available; however, none is of high level of evidence, creating an immense need for the evaluation of other treatment modalities, of which topical sodium valproate is of potential role via proposed decrease in beta-catenin breakdown, despite its well-known side effect of hair fall as an oral therapy.ObjectiveEvaluating the efficacy and the safety of sodium valproate (SV)-loaded nanospanlastics, in comparison to topical corticosteroids, this is the currently available gold standard topical treatment for patchy AA.MethodologyA total of 66 patients with patchy AA were randomly assigned to receive either topical mometasone furoate lotion or topical SV applied twice daily to all patches except a control patch, which was left untreated. Clinical, trichoscopic and biochemical assessments of beta-catenin tissue levels and Axin-2 gene expression were carried out at baseline and after 3 months.ResultsBoth therapeutic modalities were comparable. Potential efficacy was highlighted by significant improvement in the representative patch, the largest treated patch, to the control patch, the smallest untreated patch in both steroid and valproate groups (p = 0.027, 0.003 respectively). Both beta-catenin levels and Axin-2 gene expression were reduced after treatment, pointing to the inhibitory effect of dominating uncontrolled inflammatory milieu. Baseline beta-catenin was found to significantly negatively correlate with improvement in the representative patch in patients with baseline level above 0.42 ng/ml (p = − 0.042).ConclusionBoth topical SV and steroids are of comparable modest efficacy. Thus, further evaluation of SV is due in combination with intralesional steroids and other anti-inflammatory treatment modalities, together with developing individualized approaches based on baseline beta-catenin level.ClinicalTrials.gov IdentifierNCT05017454, https://clinicaltrials.gov/ct2/show/NCT05017454.

The impact of novel inflammation-preserving treatment towards lumbar disc herniation resorption in symptomatic patients: a prospective, multi-imaging and clinical outcomes study.

We performed a prospective one-year multi-imaging study to assess the clinical outcomes and rate of disc resorption in acute lumbar disc herniation (LDH) patients undergoing inflammation-preserving treatment (i.e. no NSAIDS, steroids). All patients received gabapentin to relieve leg pain, 12 sessions of acupuncture. Repeat MRI was performed, every 3months, after 12 sessions of treatment continued for those without 40% reduction in herniated disc sagittal area. Disc herniations sizes were measured on sagittal T2W MRI sequences, pre-treatment and at post-treatment intervals. Patients were stratified to fast, medium, slow, and prolonged recovery groups in relation to symptom resolution and disc resorption. Ninety patients (51% females; mean age: 48.6years) were assessed. Mean size of disc herniation was 119.54 ± 54.34mm2, and the mean VAS-Leg score was 6.12 ± 1.13 at initial presentation. A total of 19 patients (21.1%) improved at the time of the repeat MRI (i.e. within first 3months post-treatment). 100% of all patient had LDH resorption within one year (mean: 4.4. months). There was no significant difference at baseline LDH between fast, medium, slow, and prolonged resorption groups. Initial LDH size was weakly associated with degree of leg pain at baseline and initial gabapentin levels. Surgery was avoided in all cases. This is the first study to note inflammation-preserving treatment, without conventional anti-inflammatory and steroid medications, as safe and effective for patients with an acute LDH. Rate of disc resorption (100%) was higher than comparative recent meta-analysis findings (66.7%) and no patient underwent surgery.

Long-term Outcomes after Steroid Pulse Therapy in Patients with Type 1 Autoimmune Pancreatitis.

Objective Steroid pulse therapy is a regimen involving the intravenous administration of supra-pharmacological doses of corticosteroids in the short term. It is used to treat various inflammatory and autoimmune conditions. However, the strengths and limitations of steroid pulse therapy for induction of remission in type 1 autoimmune pancreatitis (AIP) are unknown. Methods Depending on the steroid therapy regimen administered, the 104 patients with type 1 AIP included in this retrospective study were divided into three groups: conventional oral prednisolone (PSL) regimen (PSL group), intravenous methylprednisolone (IVMP) pulse followed by oral PSL regimen (Pulse+PSL group), and IVMP pulse-alone regimen (Pulse-alone group). We then examined the relapse rate and adverse events among the three groups. Results The Kaplan-Meier estimates of the relapse rate at 36 months after steroid therapy were 13.6% in the PSL group, 13.3% in the Pulse+PSL group, and 46.2% in the Pulse-alone group. The log-rank test revealed that the relapse-free survival in the Pulse-alone group was significantly shorter than that in the PSL (p=0.024) and Pulse+PSL groups (p=0.014). The exacerbation of glucose tolerance after steroid therapy was less frequently observed in the Pulse-alone group (0%) than in the PSL group (17%, p=0.050) and Pulse+PSL groups (26%, p=0.011). Conclusion Although treatment with IVMP pulse alone resulted in unsatisfactory relapse prevention outcomes compared with conventional steroid therapy, the IVMP pulse-alone regimen might be an alternative treatment strategy for type 1 AIP from the perspective of avoiding adverse events from steroids.

THU207 11-oxygenated Androgens Are Strongly Associated With Treatment Quality In Children With Congenital Adrenal Hyperplasia Due To 21-Hydroxylase Deficiency

Abstract Disclosure: O. Abawi: None. T. Du Toit: None. G. Sommer: None. C.D. Vögel: None. M. Groessl: None. U. Halbsguth: None. S.E. Hannema: None. C. de Bruin: None. E. Charmandari: None. E.L. van den Akker: None. C.E. Flueck: None. Introduction: Treatment of children with Congenital Adrenal Hyperplasia (CAH) aims at balancing steroid replacement, hyperandrogenism and hypercortisolism. Optimal treatment and its assessment however remain a conundrum. Currently, specialists integrate clinical and conventional laboratory parameters such as 17-hydroxyprogesterone (17OHP) and androstenedione (A4). In recent years, 11-oxygenated androgens (11oxyAs) have been proposed as promising biomarkers, but their merit in treatment monitoring is not yet established. Aim: To investigate potential biomarkers of treatment quality in children with CAH by comprehensive serum steroid profiling. Methods: This prospective, observational cohort study was conducted at 4 academic pediatric endocrinology outpatient clinics and included children with genetically confirmed 21-hydroxylase deficiency. At 2 consecutive visits (mean 4.1 ± 0.7 months apart), a targeted and untargeted panel of conventional adrenal and additional peripheral steroids was analysed in serum using liquid chromatography-mass spectrometry. This included 11β-hydroxy (11OH)-androstenedione (11OHA4), 11keto-A4 (11KA4), 11OH-testosterone (11OHT), and 11keto-T (11KT). At each visit, the pediatric endocrinologist classified patients as undertreated, optimally treated or overtreated based on detailed clinical and endocrinologic evaluation, including serum 17OHP and A4 profiling. Mixed-effects logistic regression analyses on log-steroid concentrations adjusted for age, sex, BMI-z, pubertal status, CAH subtype (classic vs non-classic) and random effects for unique patients were performed to investigate odds ratios (OR) of being undertreated vs optimally treated. False discovery rate adjusted P&amp;lt;0.05 was considered significant. Results: We included 138 visits (86 [62%] optimal treatment, 52 [38%] undertreatment) from 72 patients, of whom 31 (43%) girls, 59 (82%) had classic CAH, and 31 (43%) were prepubertal. Mean age at first visit was 10.6 ± 5.2 years, mean BMI-z was 0.6 ± 1.1. Ten out of 17 conventional steroids, including 17OHP and 21-deoxycortisol but not A4, were associated with undertreatment. All 11oxyAs were associated with undertreatment: 11OHA4 (OR 3.64, SE 1.42, P=0.008), 11OHT (OR 2.91, SE 1.09, P=0.012), 11KT (OR 2.77, SE 1.00, P=0.01), and 11KA4 (OR 2.64, SE 0.84, P=0.009). The strongest association with undertreatment was found for the sum of 11oxyAs (OR 4.04, SE 1.70, P=0.008). Discussion: We show that 11oxyAs have the strongest association with undertreatment in children with CAH. This study supports the inclusion of 11oxyAs in the biochemical work-up of CAH to improve treatment monitoring and underscores the importance of analysing unconventional steroids in CAH by comprehensive steroid profiling. Following on, our steroid profiling can now be extended to characterise other forms of CAH and cases of suspected overtreatment. Presentation: Thursday, June 15, 2023

Remdesivir, dexamethasone and angiotensin-converting enzyme inhibitors use and mortality outcomes in COVID-19 patients with concomitant troponin elevation.

There are indications that viral myocarditis, demand ischemia, and renin-angiotensin-aldosterone system pathway activation play essential roles in troponin elevation in coronavirus disease 2019 (COVID-19) patients. Antiviral medications and steroids are used to treat viral myocarditis, but their effect in patients with elevated troponin, possibly from myocarditis, has not been studied. To evaluate the effect of dexamethasone, remdesivir, and angiotensin-converting enzyme (ACE) inhibitors (ACEI) on mortality in COVID-19 patients with elevated troponin. Our retrospective observational study involved 1788 COVID-19 patients at seven hospitals in Southern California, United States. We did a backward selection Cox multivariate regression analysis to determine predictors of mortality in our study population. Additionally, we did a Kaplan Meier survival analysis in the subset of patients with elevated troponin, comparing survival in patients that received dexamethasone, remdesivir, and ACEI with those that did not. The mean age was 66 years (range 20-110), troponin elevation was noted in 11.5% of the patients, and 29.9% expired. The patients' age [hazard ratio (HR) = 1.02, P < 0.001], intensive care unit admission (HR = 5.07, P < 0.001), and ventilator use (HR = 0.68, P = 0.02) were significantly associated with mortality. In the subset of patients with elevated troponin, there was no statistically significant difference in survival in those that received remdesivir (0.07), dexamethasone (P = 0.63), or ACEI (P = 0.8) and those that did not. Although elevated troponin in COVID-19 patients has been associated with viral myocarditis and ACE II receptors, conventional viral myocarditis treatment, including antiviral and steroids, and ACEI did not show any effect on mortality in these patients.

JAAD Game Changer: Inhibition of tumor necrosis factor improves conventional steroid therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis in a cohort of patients

JAAD Game Changer: Inhibition of tumor necrosis factor improves conventional steroid therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis in a cohort of patients

Infection prevention and vaccination in the rheumatic diseases.

Patients with chronic inflammatory rheumatisms (CIR) have a higher risk of infections compared to healthy subjects. Viral and bacterial pneumonia are the most frequent infections observed in CIR with targeted disease modifying anti-rheumatic drugs (DMARDs). Moreover, drugs used to treat CIR (especially biologic and synthetic targeted DMARDs) increase the risk of infection and expose CIR patients to opportunistic infections such as tuberculosis reactivation. To limit the risk of infection, the risk-benefit ratio should be evaluated for each patient based on their characteristics and comorbidities. To prevent infections, an initial pre-treatment work-up must be performed, especially before the initiation of conventional synthetic DMARDs or biological and synthetic targeted DMARDs. This pre-treatment assessment includes the case history, laboratory and radiology findings as well. The physician must make sure a patient's vaccinations are up-to-date. The vaccines recommended for patients with CIR being treated with conventional synthetic DMARDs, bDMARDs, tsDMARDs and/or steroids should be given. Patient education is also very important. During workshops, they learn how to manage their drug treatments in at-risk situations and learn which symptoms require treatment discontinuation.

#3418 DISAPPEARANCE OF GLOMERULAR C3 DEPOSITION MIGHT BE A PROGNOSTIC MARKER IN MEMBRANOUS NEPHROPATHY AFTER TREATMENT

Abstract Background and Aims Membranous nephropathy (MN) is the most common cause of nephrotic syndrome (NS) in adults. In about 80% is primary and remaining 20% are secondary due to medications or other diseases. Treatment of primary MN remains controversial, and the prognosis is still difficult to predict despite the introduction of anti phospholipase A2 receptor (PLA2R) antibody. We evaluated pathological changes for predicting prognosis in patients of MN after methyprednisolone (MPD) pulse therapy. Method We performed 1,649 renal biopsies at the OPD during last 9 years, of which 31 subjects were MN. We performed follow up biopsy who showed normal urinary findings after treatment with MPD pulse therapy in 11 subjects of MN. Indications of the initial biopsy in MN were oral steroid resistant NS (9 subjects), massive proteinuria associated with hematuria (2 subjects). Among the 11 subjects of MN, 3 subjects were lupus nephritis (LN), 8 subjects were primary MN. One cycle of MPD consist of 10-20 mg/kg (max 1.0 g)/day for 3 consecutive days, performing every 10 to 14 days. Mean MPD pulse therapy were done 13 cycles Results Among the 11 cases of MN, male to female ratio was 6 to 5. Age distribution from 1 year old to 61years old (mean 40.8 y/o), Mean spot urine protein to creatinine before treatment was 4,182.5 mg/g and 189.4 mg/g after treatment. 9 subjects showed glomerular C3 deposition were noted at the initial biopsy and 2 subjects showed no C3 deposition. After treatment glomerular C3 deposition were disappeared in 8 subjects, and showed no relapse during 5.3 years follow up. However, 3 subjects who showed glomerular C3 deposition were lupus nephritis, relapsed during follow up period. Conclusion MPD pulse therapy might be still promising therapeutic modality in conventional oral steroid resistant MN. Although further larger number of studies are mandatory, disappearance of glomerular C3 deposition might be a prognostic marker for treatment response, instead of disappearance of proteinuria in MN.

#3045 EFFICACY AND SAFETY OF MONTHLY-STEROID PULSE THERAPY AND TONSILLECTOMY IN PATIENTS WITH IGA NEPHROPATHY

Abstract Background and Aims In Japan, tonsillectomy and corticosteroid therapy is widely performed in patients with IgA nephropathy, to improve kidney outcomes and reduce proteinuria and hematuria. Over the last decade, patients with IgA nephropathy with ≥1g/day of proteinuria are treated with corticosteroid globally. However, after the results of the STOP-IGA and TESTING trials regarding efficacy and safety, the KDIGO 2021 clinical practice guideline suggest the use of immunosuppressive drugs only in patients who remain at high-risk for progressive chronic kidney disease despite maximal supportive care, after considering the risks and benefits. The TESTING trial showed that even in the reduced-dose group, severe adverse events occurred. In order to reduce steroid-induced toxicity, we administrated steroid pulse therapy monthly for 3 consecutive months and tonsillectomy without post-treatment. Thereafter, the effects and adverse events were evaluated. Method Forty-two patients diagnosed with IgA nephropathy on biopsy at our hospital, with ≥0.3g/day of proteinuria, and who had undergone tonsillectomy and steroid pulse therapy were included in the study. Of these patients, 16 were treated with three months of consecutive steroid pulse therapy without follow-up steroid administration (MSP); the remaining patients were administrated the conventional steroid pulse therapy (SP), including modified Pozzi's (Lancet 1999) and Hotta's (AJKD 2001) regimens. We evaluated and compared the time to proteinuria remission and both hematuria and proteinuria remission between the two groups using Kaplan-Meier curve and log-rank test. Remission of proteinuria was defined as three consecutive urinary protein results of &amp;lt;0.3g/day over 6 months, and that of hematuria was defined as three consecutive results of &amp;lt;5 RBCs/high-power field in the urinary sediment. In addition to efficacy, we compared the incidence rates of adverse events between the two groups. Results There were no significant differences in the age, sex, time to diagnosis, histopathological findings according to the Oxford classification, or RAS inhibitor use between the MSP and SP groups. The eGFR(ml/min/1.73m2) was 81.3 and 78.5, and the urinary protein excretion (g/day) was 1.01 and 1.18, in the MSP and SP groups, respectively. The proteinuria remission rates in the MSP and SP groups were 81% and 69% after one year and 94% and 81% after two years, respectively, with no significant difference. The remission rates of both hematuria and proteinuria were 47% and 46% after one year and 77% and58% after two years, respectively, with no significant differences. The incident rates of adverse events, including diabetes and infections, was 13% and 54% in the MSP and SP groups, respectively, and was significantly lower in the MSP group (p = 0.005). Conclusion Tonsillectomy with monthly steroid pulse therapy was effective and safer than the conventional steroid pulse therapy in patients with IgA nephropathy.