Steroid Response Research Articles

IgM deposition is a risk factor for delayed remission and early relapse of the pediatric minimal change disease.

Minimal change disease (MCD) is the most common pathological subtype of pediatric idiopathic nephrotic syndrome (INS). It has been suggested that IgM deposition might predict kidney function deterioration in the course of MCD. However, the specific role of IgM deposition in the prognosis of MCD is still controversial. This study aims to investigate the clinical significance of IgM deposition on delayed remission and early relapse in a pediatric population. This study enrolled 283 children diagnosed with MCD by renal biopsy in a single center from 2010 to 2022. These cases were divided into two groups according to the histopathological deposition of IgM. Patients' demographics, clinical parameters, and follow-up data were collected and analyzed. The primary and secondary outcomes were defined as the time to the first remission and the first relapse. The IgM-positive group had a weaker response to steroids (steroid-sensitive: 23.5% vs. 40.8%; steroid-dependent: 74.0% vs. 51.0%; steroid-resistant: 18.4% vs. 8.2%, P = 0.001), and showed more recurrent cases (47.2% vs. 34.4%, P = 0.047) compared with the IgM-negative group. The Kaplan-Meier analysis showed that the IgM-positive group had a lower cumulative rate of the first remission (Log-rank, P < 0.001) and a higher rate of the first relapse (Log-rank, P = 0.034) than the IgM-negative group. Multivariate Cox analysis showed that IgM deposition was independently associated with the delayed first remission (hazard ratio [HR] = 0.604, 95% confidence interval [CI] = 0.465-0.785, P < 0.001) and the early first relapse (HR = 1.593, 95% CI = 1.033-2.456, P = 0.035). IgM deposition was associated with a weaker steroid response. MCD children with IgM deposition were prone to delayed first remission and early first relapse.

Pediatric Autoimmune Pancreatitis: A Single-Center Retrospective Case Series.

Autoimmune pancreatitis (AIP) is a rare form of a chronic, immune-mediated, inflammatory pancreatic condition. There is limited data regarding presentation and outcome in the pediatric population. We described a single-center case series of 4 pediatric patients with AIP to better understand the presentation, symptoms, and outcomes of this rare condition. Data collected included demographics, serology markers, symptoms at presentation, imaging, additional organ involvement, histology, treatment methods, and outcomes. The diagnosis of AIP was made by a combination of serology, pancreatic imaging, histology, extrapancreatic manifestations, and steroid response. All patients were diagnosed with type 2 AIP. Abdominal pain, emesis, and obstructive jaundice were the most common symptoms at presentation. Autoimmune markers were negative. Cross-sectional abdominal imaging showed diffuse/focal pancreatic gland enlargement and common bile duct stricture universally and main pancreatic duct irregularity in half of the patients. Biopsies showed lymphoplasmacytic infiltration with associated pancreatic fibrosis and atrophy. Treatment with an 8-week tapering course of prednisone showed prompt response with resolution of symptoms and normalization of laboratory test results. Our case series shows that AIP in children is a rare entity with a distinct clinical presentation, classical radiographic and histological features with good long-term prognosis.

370 - Evaluating Diversity of Tcrvb Repertoire and Steroid Responsiveness in Acute Graft Versus Host Disease

370 - Evaluating Diversity of Tcrvb Repertoire and Steroid Responsiveness in Acute Graft Versus Host Disease

Urinary Neutrophil Gelatinase Associated Lipocalin: A Novel Biomarker Determining Steroid Responsiveness in Nephrotic Syndrome.

Urinary Neutrophil Gelatinase Associated Lipocalin (uNGAL) has been demonstrated to be a powerful marker of progression in chronic kidney disease. The present study was done to find out the ability of uNGAL as a biomarker to differentiate steroid-sensitive nephrotic syndrome (SSNS), steroid-dependent nephrotic syndrome (SDNS), and steroid-resistant nephrotic syndrome (SRNS) from each other. The cross-sectional study included 45 patients with Idiopathic Nephrotic Syndrome (INS) (15 each of SSNS, SDNS, and SRNS). uNGAL was measured by ELISA. Demographic profile of patients with INS, lab parameters including Serum albumin, cholesterol, urinary albumin, creatinine, etc., were estimated using standard laboratory methods. Various statistical methods were used to assay the usefulness of NGAL as a diagnostic marker. Among the three groups, the median value of uNGAL was 8.68 ng/ml in SSNS, higher in SDNS (32.8 ng/ml), and highest in the SRNS group (50 ng/ml). The receiver operating curve (ROC) was generated for uNGAL to differentiate between SDNS and SSNS. Cut-off 13.26 ng/ml had a sensitivity of 86.7% and specificity of 97.4%, PPV 92.9%, and NPV 87.5 % with an area under the curve (AUC) of 0.958. Another ROC was generated for uNGAL to differentiate between SRNS and SDNS, and cut-off 40.02 ng/ml had a sensitivity of 80% and specificity of 86.7% with an AUC of 0.907. A similar result was observed when ROC was generated to differentiate SRNS from SSNS and SDNS combined. uNGAL can distinguish between SSNS, SDNS, and SRNS.

Factors related to steroid treatment responsiveness in thyroid eye disease patients and application of SHAP for feature analysis with XGBoost.

The primary treatment for active thyroid eye disease (TED) is immunosuppressive therapy with intravenous steroids. In this study, we attempted to predict responsiveness to steroid treatment in TED patients using eXtreme Gradient Boosting (XGBoost). Factors associated with steroid responsiveness were also statistically evaluated. Clinical characteristics and laboratory results of 89 patients with TED who received steroid treatment were retrospectively reviewed. XGBoost was used to explore responsiveness to steroid treatment, and the diagnostic performance was evaluated. Factors contributing to the model output were investigated using the SHapley Additive exPlanation (SHAP), and the treatment response was investigated statistically using SPSS software. The eXtra Gradient Boost model showed high performance, with an excellent accuracy of 0.861. Thyroid-stimulating hormone, thyroid-stimulating immunoglobulin (TSI), and low-density lipoprotein (LDL) cholesterol had the highest impact on the model. Multivariate logistic regression analysis showed that less extraocular muscle limitation and high TSI levels were associated with a high risk of poor intravenous methylprednisolone treatment response. As a result of analysis through SHAP, TSH, TSI, and LDL had the highest impact on the XGBoost model. TSI, extraocular muscle limitation, and LDL cholesterol levels may be useful in predicting steroid treatment response in patients with TED. In terms of machine learning, XGBoost showed relatively robust and reliable results for small datasets. The machine-learning model can assist in decision-making for further treatment of patients with TED.

The role of the glucocorticoid receptor and its impact on steroid response in moderate-severe COVID-19 patients

The effect of corticosteroid therapy in COVID-19 patients is mediated by its suppressive effect on the regulations of inflammatory response. However, its clinical outcome is often unpredictable. This study aimed to explore the role of glucocorticoid receptors in corticosteroid response in Moderate-Severe COVID-19 patients. In this cross-sectional study, we attempted to find the relationship between the expression of the glucocorticoid receptor (encoded by NR3C1), the variation of glucocorticoid receptors isoform, and the mutations of glucocorticoid receptors exon with clinical response to corticosteroids. In addition, the relationship between glucocorticoid receptors expression and the expression of IκBα (encoded by NFKBIA) and glucocorticoid-induced leucine zipper protein (GILZ; encoded by TSC22D3) as steroid pathways was also evaluated. Thirty-four COVID-19 patients were studied. Blood was drawn before and on day 5 of corticosteroid treatment. Glucocorticoid receptors expression, isoform, and mutation were determined by RNA sequencing from white blood cells. Based on the improvement of clinical and oxygen status, patients were classified into responder and non-responder groups. Of thirty-four patients, 23 (67.6%) showed excellent responses to corticosteroids, and 11 (32.4%) were non-responders. The NR3C1 gene expression was significantly higher in the responsive group at baseline and after five days of glucocorticoid treatment. Isoform variant and mutation of glucocorticoid receptors did not correlate with clinical response. The expression of IκBα and GILZ correlated positively with glucocorticoid receptors expression. This study elucidates the relationship between glucocorticoid receptor expression with therapeutic responses to corticosteroids in moderate-severe COVID-19.

P176 Clinical features of acute severe ulcerative colitis according to steroid dependency: A KASID multicenter study

Abstract Background Intravenous steroid therapy is the main initial treatment for acute severe ulcerative colitis (ASUC). However, steroid dependence in patients who were treated with intravenous steroid therapy for ASUC is not fully evaluated. We aimed to determine the prevalence and risk factors of corticosteroid dependence after treatment of ASUC. Methods Adult patients who were admitted for the treatment of ASUC satisfying Truelove-Witts criteria from January 2015 to December 2020 were included in the study. Steroid dependence was defined as a failure to taper steroids below 10 mg within 3 months from initiating intravenous therapy or relapse within 3 months after steroid discontinuation. Results Among a total of 140 patients who received intravenous steroids as initial treatment for ASUC, 105 (75.0%) showed a response while 35 (25.0%) were refractory to steroids. Of 105 patients who responded to intravenous steroid therapy, 21 (20.0%) showed steroid dependence during the follow-period. Demographic and clinical variables were not significantly different between steroid-dependent and steroid response groups. However, initial C-reactive protein (CRP) levels in steroid-dependent groups were numerically lower compared with those in the steroid response group with statistical significance (4.4 ± 4.6 mg/dL versus 7.0 ± 6.4 mg/dL, p = 0.04). Conclusion A total of 20.0% of responders to intravenous steroid treatment for ASUC had a steroid dependency during follow-up. The demographic and clinical features of ASUC according to the presence or absence of steroid dependency were similar. Initial CRP levels were low in patients with steroid dependence.

P002 Exclusive Enteral Nutrition, the gut microbiome and corticosteroid response in patients with acute severe colitis

Abstract Background Supplementation with exclusive enteral nutrition (EEN) in addition to standard of care with intravenous corticosteroids (SOC) augments the steroid response in patients with acute severe ulcerative colitis (ASUC). EEN is known to alter gut microbial composition. The present study identifies changes in gut microbiota driven by EEN in patients with ASUC receiving standard steroid therapy and examines correlations between EEN-associated bacteria and response to corticosteroid therapy. Methods Stool samples were collected at baseline (Day0) and post-therapy (Day 7) from 44 patients with ASUC who received either SOC (n=24) or SOC supplemented with EEN (n=20) for a period of 7 days, at baseline (Day 0) and post-therapy (Day-7). Microbiome characterization was carried out using 16S rRNA gene sequencing followed by data processing using QIIME2 and R packages to analyze diversity and differentially abundant taxa. Results Seven-day EEN supplementation of SOC in patients with ASUC resulted in enhanced proportions of Methylobacterium, Sphingomonas, Limosilactobacillus, Megamonas, Thermus, Viellonella, with a reduction in Ruminococcus gnavus, Gemmiger, Pseudomonas, and Enterococcus. EEN-mediated enhancement in specific taxa correlated positively with patients’ day-7 serum albumin levels and negatively with day-3 faecal calprotectin levels (FCal) (Fig.1). Gut microbial composition of patients who responded to EEN-augmented SOC showed an enhanced abundance of Coprococcus, Megamonas, Oribacterium, Sediminibacterium, Acidibacter, and Thermus, and reduction in Sutterella, R. gnavus, Collinsella, Dorea, and Morganella, when compared to non-responders (Fig.2). Baseline gut microbiome signature in patients with ASUC predicts a potential response to both SOC and EEN-supplemented SOC in patients with ASUC (Fig.3). Conclusion Augmentation of clinical response by EEN-conjugated corticosteroid therapy is accompanied by specific gut microbial changes in patients with ASUC.

Machine learning models for predicting steroid-resistant of nephrotic syndrome.

In the absence of effective measures to predict steroid responsiveness, patients with nonhereditary steroid-resistant nephrotic syndrome (SRNS) have a significantly increased risk of progression to end-stage renal disease. In view of the poor outcomes of SRNS, it is urgent to identify the steroid responsiveness of idiopathic nephrotic syndrome (INS) early. To build a prediction model for SRNS, we collected 91 subjects; 57 of them had steroid-sensitive nephrotic syndrome, and the others had SRNS. For each subject, 87 clinical variables were measured. In general, only a small part of these variables is informative to SRNS. Thus, we proposed a new variable selection framework including a penalized regression approach (named MLR+TLP) to select variables having a linear effect on the SRNS and a nonparametric screening method (MAC) to select variables having a nonlinear marginal (joint) effect on the SRNS. Thereafter, considering the correlation between selected clinical variables, we used a stepwise method to build our final model for predicting SRNS. In addition, a statistical testing procedure is proposed to test the overfitting of the proposed model. Twenty-six clinical variables were selected to be informative to SRNS, and an SVM model was built to predict SRNS with a leave-one-out cross-validation (LOO-CV) accuracy of 95.2% (overfitting p value<0.005). To make the model more useful, we incorporate prior medical information into the model and consider the correlation between selected variables. Then, a reduced SVM model including only eight clinical variables (erythrocyte sedimentation rate, urine occult blood, percentage of neutrophils, immunoglobulin A, cholesterol, vinculin autoantibody, aspartate aminotransferase, and prolonged prothrombin time) was built to have a LOO-CV accuracy of 92.8% (overfitting p value<0.005). The validation cohort showed that the reduced model obtained an accuracy of 94.0% (overfitting p value<0.005), with a sensitivity of 90.0% and a specificity of 96.7%. Notably, vinculin autoantibody is the only podocyte autoantibody included in this model. It is linearly related to steroid responsiveness. Finally, our model is freely available as a user-friendly web tool at https://datalinkx.shinyapps.io/srns/. The SRNS prediction model constructed in this study comprehensively and objectively evaluates the internal conditions and disease status of INS patients and will provide scientific guidance for selecting treatment methods for children with nonhereditary SRNS.

Does Urinary Vitamin D-Binding Protein Have a Role in the Prediction of Steroid Resistance in Nephrotic Syndrome? A Cohort Study on Egyptian Children

Background: Nephrotic syndrome (NS) is a common glomerular disease in children, for which there are currently no noninvasive markers for predicting responsiveness to steroid treatment. Objectives: This study aimed to analyze the relationship between clinical-laboratory presentations and subsequent response to steroid therapy and to evaluate the role of urinary vitamin D binding protein (uVDBP) as a predictor of steroid resistance (SR). Methods: This was a prospective longitudinal study on 60 children with active NS (30 patients with newly diagnosed NS and 30 with relapsed NS). In addition, 30 control subjects served as a reference group for uVDBP values. The patients were evaluated before starting steroid therapy, and response to steroid therapy was monitored 4 - 8 weeks later. Results: The levels of uVDBP were elevated in patients with NS (33.33 ± 15.6 ng/mL) compared to control subjects (17.35 ± 5.5 ng/mL, P &lt; 0.001). Also, the levels of uVDBP were significantly higher in patients with relapsed NS (37.93 ± 16.2 ng/mL) than in newly diagnosed NS patients (28.73 ± 13.67 ng/mL, P = 0.014). The level of uVDBP on presentation did not significantly differ between patients who had steroid-sensitive nephrotic syndrome (SSNS) (34.91 ± 15.01 ng/mL) and patients who had steroid-resistant nephrotic syndrome (SRNS) after 4 - 8 weeks of steroid treatment (32.60 ± 15.94 ng/mL, P = 0.417). Steroid resistance was significantly associated with a younger age of onset, specifically below 2.1 years (P = 0.023), a longer duration of the illness (P = 0.007), having more relapses (P = 0.002), total leucocytic count on presentation &gt; 8.05 × 103/mm3 (P = 0.031), and platelet counts on presentation &gt; 516.5 × 103/mm3 (P = 0.044). Conclusions: In this study, we found that uVDBP levels could reflect disease severity rather than predict the pattern of steroid responsiveness. Younger age of onset, longer duration of illness, previous relapses, and increased total leukocyte and platelet counts on presentation were associated with SRNS.

HSP70 mediates a crosstalk between the estrogen and the heat shock response pathways

Cells respond to multiple signals from the environment simultaneously, which often creates crosstalk between pathways affecting the capacity to adapt to the changing environment. Chaperones are an important component in the cellular integration of multiple responses to environmental signals, often implicated in negative feedback and inactivation mechanisms. These mechanisms include the stabilization of steroid hormone nuclear receptors in the cytoplasm in the absence of their ligand. Here, we show using immunofluorescence, chromatin immunoprecipitation, and nascent transcripts production that the heat shock protein 70 (HSP70) chaperone plays a central role in a new crosstalk mechanism between the steroid and heat shock response pathways. HSP70-dependent feedback mechanisms are required to inactivate the heat shock factor 1 (HSF1) after activation. Interestingly, a steroid stimulation leads to faster accumulation of HSF1 in inactive foci following heat shock. Our results further show that in the presence of estrogen, HSP70 accumulates at HSF1-regulated noncoding regions, leading to deactivation of HSF1 and the abrogation of the heat shock transcriptional response. Using an HSP70 inhibitor, we demonstrate that the crosstalk between both pathways is dependent on the chaperone activity. These results suggest that HSP70 availability is a key determinant in the transcriptional integration of multiple external signals. Overall, these results offer a better understanding of the crosstalk between the heat shock and steroid responses, which are salient in neurodegenerative disorders and cancers.

Management of Post-Keratoplasty Glaucoma: A Literature Review

Glaucoma is the second leading cause of graft failure after graft rejection. Sustained elevations in intraocular pressure (IOP) can lead to corneal endothelial decompensation, graft failure and vision loss. Causes of glaucoma post-keratoplasty include steroid response, pupillary block, retained viscoelastic material, distortion of the trabecular meshwork or Schlemm’s canal, haemorrhage, lens protein leakage, secondary angle-closure from peripheral anterior synechiae, and pre-existing glaucoma. Close monitoring, coupled with prompt diagnosis and appropriate treatment of post-keratoplasty glaucoma are vital to the preservation of optic nerve function and a successful graft outcome.

Corticosteroids and glaucoma

Corticosteroid use is a major risk factor in the development of glaucoma and its aggravation. This is due to the augmentation of the intraocular pressure (IOP) induced by the corticoids. This augmentation is different between individuals: we called it steroid responsiveness, for which multiple risk factors have been identified, the most important being personal or family history of primary open angle glaucoma. The secondary augmentation of IOP depends also on the type of preparation, the mode of administration, the dosage and the duration of the therapy. Prevention and management are essentials to avoid this adverse effect. Among the most important measures, there are the education of the patient and the practitioner, IOP follow-ups after the use of corticoids and IOP-lowering medications.

Association of the rs1128503 and rs1045642 polymorphisms in the MDR-1 gene with steroid responsiveness in Iraqi children with idiopathic nephrotic syndrome

Association of the rs1128503 and rs1045642 polymorphisms in the MDR-1 gene with steroid responsiveness in Iraqi children with idiopathic nephrotic syndrome

Descemet membrane endothelial keratoplasty in eyes with glaucoma.

Endothelial keratoplasty has become the standard for the treatment of endothelial dysfunction. In Descemet membrane endothelial keratoplasty (DMEK), only the endothelium and Descemet membrane are transplanted, providing superior outcomes compared to Descemet stripping endothelial keratoplasty (DSEK). A substantial subset of patients who require DMEK have comorbid glaucoma. Even in eyes with complex anterior segment such as eyes with previous trabeculectomy or tube shunts, DMEK can restore meaningful vision and outperforms DSEK in terms of visual recovery, decreased rejection rate, and the need for high dose of topical steroids. However, accelerated endothelial cell loss and secondary graft failure have been described in eyes with previous glaucoma surgery, namely trabeculectomy and drainage device. During DMEK and DSEK procedures, raised intraocular pressure is required to attach the graft, which could worsen preexisting glaucoma or cause de novo glaucoma. Mechanisms of postoperative ocular hypertension include delayed air clearance, pupillary block, steroid response, and damage to angle structures. Medically treated glaucoma has increased risk for postoperative ocular hypertension. By understanding these additional complications and making appropriate modifications in surgical techniques and postoperative management, DMEK can be performed successfully and achieve very good visual outcome in eyes with glaucoma. Such modifications include precisely controlled unfolding technique, iridectomies that can help avoid pupillary block, tube shunts that can be trimmed to facilitate graft unfolding, air fill tension that can be adjusted, and postoperative steroid regimens that can be modified to decrease the risk for steroid response. Long-term survival of the DMEK graft, however, is shorter in eyes with previous glaucoma surgery than those without, as observed after other types of keratoplasty.

Prognostic significance of steroid response in pediatric acute lymphoblastic leukemia: The CCCG-ALL-2015 study.

Whether steroid response is an independent risk factor for acute lymphoblastic leukemia (ALL) is controversial. This study aimed to investigate the relationship between response to dexamethasone and prognosis in children with ALL. We analyzed the data of 5,161 children with ALL who received treatment in accordance with the Chinese Children's Cancer Group ALL-2015 protocol between January 1, 2015, and December 31, 2018, in China. All patients received dexamethasone for 4 days as upfront window therapy. Based on the peripheral lymphoblast count on day 5, these patients were classified into the dexamethasone good response (DGR) and dexamethasone poor response (DPR) groups. A peripheral lymphoblast count ≥1× 109/L indicated poor response to dexamethasone. The age, white blood cell counts, prevalence of the BCR/ABL1 and TCF3/PBX1 fusion genes, and rates of recurrence in the central nervous system were higher in the DPR than in the DGR group (P<0.001). Compared to the DPR group, the DGR group had a lower recurrence rate (18.6% vs. 11%) and higher 6-year event-free survival (73% vs. 83%) and overall survival (86% vs. 92%) rates; nevertheless, subgroup analysis only showed significant difference in the intermediate-risk group (P<0.001). Response to dexamethasone was associated with an early treatment response in our study. In the intermediate-risk group, dexamethasone response added a prognostic value in addition to minimal residual disease, which may direct early intervention to reduce the relapse rate.

Steroid Response after Trabeculectomy-A Randomized Controlled Trial Comparing Dexamethasone to Diclofenac Eye Drops.

This prospective randomized controlled trial aimed to compare changes in intraocular pressure in three different anti-inflammatory regimens following trabeculectomy. Sixty-nine patients were randomized to receive either postoperative prophylaxis with topical preservative-free dexamethasone (DEX), diclofenac (DICLO), or their combination (DEX+DICLO). Our main outcome measure was an intraocular pressure (IOP) change of a minimum 4 mmHg following the withdrawal of anti-inflammatory prophylaxis 9 weeks after trabeculectomy. We found that the IOP decreased ≥ 4 mmHg in 18.6% of eyes after cessation of the topical steroid DEX (n = 3/22) and DEX+DICLO (n = 5/21), whereas a decrease in IOP was not observed in the DICLO group. In conclusion, IOP decreased in nearly 1/5 of patients after cessation of topical steroidal anti-inflammatory prophylaxis after trabeculectomy. This points toward a steroid-induced increase in IOP even after trabeculectomy. Thus, increased postoperative IOP may be related to steroid use, and the success or failure of a trabeculectomy cannot be fully evaluated before anti-inflammatory prophylaxis with steroids is stopped or changed to non-steroidal eye drops.

Myosin Mutations and Sudden Sensorineural Hearing Loss: Results of Whole Exome Sequencing.

Idiopathic sudden sensorineural hearing loss (ISSNHL) affects 66,000 patients per year in the United States. Genetic mutations have been associated with progressive hearing loss; however, genetic mutations associated with ISSNHL have not been identified. A prospective cohort study of adults older than 18 years presenting with ISSNHL at a tertiary academic medical center. Whole exome sequencing (WES) was conducted using Genome Analysis Toolkit best practices. An automated diagnostic screen employing a variety of models for pathogenicity was conducted across all genes with no specific targets. Candidate pathogenic variants were reviewed by a team of geneticists and clinicians. Variants were crossed-referenced with 92 known hearing loss associated genes. Twenty-nine patients with SSNHL were screened using WES. The average age of patients was 53 ± 17.1 years, and most patients were White (62%) and men (55%). The mean pure tone average was 64.8 ± 31.3 dB for the affected ear. Using a 0.1% allele frequency screen, 12 (41%) cases had a mutation in any of the nine selected myosin genes. When we restrict to singletons (allele frequency = 0%), 21% (n = 6) of cases have qualifying variants, whereas only 3.8% (n = 481) of 12,577 healthy controls carry qualifying variants (p < 0.01). Most mutations (80%) were missense mutations. Of the novel mutations, one was a frameshift mutation, and two were a stop-gained function. Three were missense mutations. Myosin mutations may be associated with ISSNHL. However, larger population screening is needed to confirm the association of myosin mutation with ISSNHL and steroid responsiveness.

Comparison of Dexamethasone Versus Prednisolone Prephase in Induction Therapy of Pediatric Acute Lymphoblastic Leukemia: A Single-Center, Randomized Controlled Study from India

Background: Acute lymphoblastic leukemia (ALL) is the commonest cancer in children. Despite advances in treatment, approximately 20% of pediatric ALL patients still relapse. Although the use of dexamethasone in induction regimen has been reported to significantly decrease CNS relapse risk & improve event-free survival (EFS) compared to prednisolone, there are concerns of significant toxicities like infection & osteonecrosis with dexamethasone. Objectives: The aim of this single-center randomized study was to compare the efficacy and safety of dexamethasone prephase versus prednisolone prephase during the initial seven days (days 1 - 7) of induction chemotherapy in newly diagnosed pediatric ALL patients treated with ALL IC-BFM 2009 protocol,in terms of day 8 steroid response, day 15 bone marrow minimal residual disease (MRD) response, and day 33 morphological complete remission (CR) rates. Methods: The study enrolled total 62 newly diagnosed pediatric ALL patients (age > 1 year & ≤ 18 years) between June 2019 and April 2021, after obtaining informed consent and with institutional ethics committee approval. Patients with lymphoblastic lymphoma (LBL) and infantile ALL (age < 1 year) were excluded. Patients who were randomized to dexamethasone prephase group received intravenous dexamethasone 10 mg/m2/day on days 1-7 of induction,& those in prednisolone prephase group received prednisolone 60 mg/m2/day p.o. in three divided doses on days 1-7 of induction therapy .All the patients subsequently received prednisolone 60 mg/m2/day p.o. in three divided doses on days 8 - 28 of induction, followed by prednisolone taper over next 7 days. Induction regimen of ALL IC-BFM 2009 protocol was given. The cut-off values for day 15 BM Flow-MRD were <0.1%, 0.1-10%, and >10% as per ALL IC-BFM 2009 protocol. Morphological complete remission on day 33 was defined as bone marrow blasts < 5% of total nucleated cells, with normocellular or mildly hypocellular marrow. Steroid-related toxicities in the two treatment groups were compared as per NCI-CTCAE version 5. Results: Out of total 62 patients, 33 patients (53%) received dexamethasone prephase and 29 patients (47%) received prednisolone prephase. Forty-six patients (75%) had B-cell ALL, and 25% had T-cell ALL. The distribution of patients in standard-risk, intermediate-risk & high-risk groups as per ALL IC-BFM 2009 protocol risk stratification were 18%, 34% and 48% respectively. Twenty-nine out of 33 patients (88%) in dexamethasone prephase group achieved good steroid response on day 8 (peripheral blood absolute blast count < 1000/µl) compared to 17/29 patients (59%) in prednisolone prephase group [p = 0.018]. Day 15 bone marrow MRD assessment by flowcytometry was available in 57 patients (31/33 in dexamethasone prephase group & 26/29 in prednisolone prephase group). Nineteen out of 31 patients (61%) in dexamethasone prephase group achieved day 15 MRD < 0.1% compared to 6/26 patients (23%) in prednisolone prephase group [p = 0.02]. Twenty-eight out of 30 patients (93%) in dexamethasone group achieved morphological CR on day 33 of induction compared to 18/24 patients (75%) in prednisolone prephase group [p = 0.135]. Day 33 bone marrow Flow-MRD < 0.1% in the dexamethasone & prednisolone prephase groups were 82% and 50% respectively [p = 0.12]. At the time of analysis, 3/30 patients (10%) in dexamethasone group who achieved CR has disease relapse, compared to 8/24 patients (33%) in prednisolone prephase group [p = 0.04]. The event-free survival (EFS) at the end of study (18 months) was found to be significantly higher in the dexamethasone prephase group compared to prednisolone prephase group (p = 0.002). The incidence of steroid-related toxicities of any grade was similar in the two treatment groups. Conclusion: In the present study, the replacement of prednisolone with dexamethasone for a relatively shorter duration in the 7-day steroid prephase of ALL IC-BFM 2009 induction regimen was associated with significantly improved day 8 steroid response, day 15 bone marrow Flow-MRD response, day 33 morphological CR rates, and EFS at 18 months, without significant increase in steroid-related toxicity in induction. To our knowledge, this is the only study to compare dexamethasone versus prednisolone prephase in pediatric ALL induction, in the context of ALL IC-BFM 2009 regimen. Long-term follow up and enrollment of larger number of patients is planned. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Steroid treatment response combined with serological mark in differentiating type-1 autoimmune pancreatitis from pancreatic cancer.

Autoimmune pancreatitis (AIP) and pancreatic cancer (PC) are two different diseases. Their diagnosis, treatment, and prognosis are different, and it is difficult to differentiate them. This study aimed to explore the role of steroid treatment response combined with serological mark in distinguishing type-1 AIP from PC. Clinical data were collected and compared from 50 cases of AIP (group 1) and 100 cases of PC (group 2). The diagnostic value of serum IgG4, CA19-9, globulin, and eosinophil cell (EC) were evaluated. The response of steroid treatment of 28 patients with atypical imaging in group 1 was analyzed. After 2 weeks, the patients were classified as positive and negative steroid response according to the manifestations and/or the radiological changes. The positive response cases (n = 20) were confirmed as AIP, whereas negative ones (n = 8) were finally diagnosed as PC after complete resection. Serum globulin, IgG4, and EC levels in group 1 were significantly higher than those in group 2 (P < .01), and CA19-9 levels were distinctly lower in group 1 (P < .01). The level of serum IgG4 was related to the accuracy of diagnosis of AIP on the basis of the result of logistic regression analysis. Two-weeks steroid therapy response combined with serum IgG4 levels contribute to the differential diagnosis AIP and PC. However, regular and long-term follow-up were important for the differential diagnosis. There was an urgent need to explore the specific markers that distinguish these 2 entities.