Steroid Responders Research Articles

Risk factors of pediatric steroid-induced ocular hypertension.

Steroid-induced ocular hypertension (SIOH) is a significant ocular complication of pediatric steroid administration. In this study, we analyzed the risk factors associated with pediatric SIOH. We retrospectively collected data from 78 children under 20 years of age who received systemic steroids during hospitalization. The data included age, gender, primary disease, intraocular pressure (IOP) before and one month after administration, total monthly steroid dose adjusted for body weight (BW), and one-month changes in red blood cell, white blood cell, and platelet counts. A multivariate analysis was used to identify risk factors related to steroid responsiveness. Thirty patients (38.5%) were classified as steroid responders, and 48 as non-responders. The median IOP during the first month of steroid treatment was 24.0 mmHg (IQR; 23.0-28.3) for responders and 15.0 mmHg (IQR; 12.3-18.0) for non-responders. The Generalized Estimating Equations analysis revealed that younger age, male sex, primary disease, increase the amount of white blood cell (WBC) and total steroid dose per BW in one month were independently associated variables. The receiver operating characteristic analysis also revealed that the cutoff values for age, total monthly steroid dose, the increase amount of WBC were 11.0 years, 40.7mg/kg and 3.40 × 10²/µl respectively. High-dose steroid administration, especially in male, younger patients, necessitates careful monitoring for IOP changes during treatment. WBC count also needs to be monitored during IOP follow-ups. What is known Steroid-induced ocular hypertension (SIOH) is one of the essential complicationsduring steroid administration,but onlylimited analyses have been performed in children. What is new A comprehensive analysis of multiple factors was performed that are predicted to be associated with pediatric SIOH from previous literature. Younger age, male sex, primary disease, increase the amount of WBC, and highertotal monthly steroid dose were extracted as risk factors of SIOH. This study can contribute to the prediction of cases in which ophthalmologic examinations are particularly important during systemic steroid administration in children.

Incidence of Steroid-Related Ocular Hypertension and Cataract Formation After Subtenon Triamcinolone in Non-Uveitic Pediatric Patients.

To describe intraocular pressure (IOP) changes after injection of subtenon triamcinolone (STT) during examination under anesthesia (EUA) for pediatric patients. Multicenter, retrospective case series of pediatric patients STT from three tertiary care ophthalmic services between November 2018 and October 2023. Of 392 patients identified, 59 eyes of 41 patients (10.5%) were included. Laser was administered in 95.1% of the cases. STT dose ranged from 4 to 20 mg. The most common diagnosis was retinopathy of prematurity (43.9%). Two eyes (3.4%) of 2 patients (4.9%) were mild steroid responders. One eye (1.7%) of 1 patient (2.4%) was a moderate responder. There were no high steroid responders, and all eyes with steroid response showed a return of IOP to normal range at next visit without needing any IOP-lowering medications. No patients were diagnosed with glaucoma or required glaucoma surgery. Only 1 eye (1.7%) developed trace posterior subcapsular cataract, while no optic disc cupping or inflammation were noted. Subtenon triamcinolone injection is commonly used to prevent inflammation at the time of retinal photocoagulation treatment in pediatric patients. It has a favorable safety profile in relation to IOP elevation and cataract formation. There was no requirement for IOP lowering medications or surgical interventions.

"CYP3A4 Poor and Intermediate Metabolizers Have a Higher Rate of Steroid-Induced Intraocular Pressure Response".

Evaluate the relationship between CYP3A4 phenotype, the gene encoding the enzyme that metabolizes exogenous steroid, and the rate of steroid-induced intraocular pressure (IOP) response. Lymphocyte-derived DNA sequencing of CYP3A4 from 10073 patients was completed using the PGRN-Seq assay. Subjects with CYP3A4 intermediate metabolizer or slower phenotypes were identified and compared with controls matched by age, race and sex. All subjects had at least three eye exams with at least an exam while on topical/systemic/local steroid in any body location except the eye. Patients with pre-existing glaucoma or glaucoma suspect were excluded. Of the 10073 patients, there were 63 patients who had CYP3A4 poor or intermediate metabolizer phenotype. Of the 63 patients, 22 had documented steroid use. Fifty-nine percent (13/22) of patients with CYP3A4 poor/intermediate metabolizer had a steroid-induced IOP response of 3 mmHg or more, significantly higher compared to 23% (5/22) of matched controls (P=0.031). Although more poor /intermediate metabolizers were steroid responders, the average IOP elevation in steroid responders in both groups were similar (5.0 ± 2.5 mmHg in CYP3A4 poor/intermediate metabolizers compared to 4.1 ± 2.1mmHg in controls, P=0.327). Family history of glaucoma was similar in both groups (7/22 vs. 8/22, P=1.0). Reduced CYP3A4 phenotypes may help identify patients at a higher risk of steroid-induced IOP elevation. This retrospective study examined patients with sequenced CYP3A4, a gene encoding an enzyme that metabolizes exogenous steroids. When compared to normal metabolizers, CYP3A4 poor or intermediate metabolizers have a higher steroid-induced IOP response rate.

Expansion of effector regulatory T cells in steroid responders of severe alcohol-associated hepatitis.

While steroid therapy is the preferred treatment for severe alcohol-associated hepatitis, the role of effector regulatory T (eTreg) cells and their association with steroid response and clinical outcomes in these patients remains to be elucidated. We prospectively enrolled 47 consecutive patients with alcohol-associated hepatitis, consisting of severe alcohol-associated hepatitis treated with steroids (n=18; steroid-treated group) and mild alcohol-associated hepatitis (n=29; nontreated group). After isolating peripheral blood mononuclear cells from the patients at enrollment and again 7 days later, the frequency of eTreg cells was examined using flow cytometry. Single-cell RNA sequencing analysis was conducted using paired peripheral blood mononuclear cells. In vitro experiments were also performed to assess phenotype changes and the suppressive function of Treg cells following steroid treatment. The steroid-treated group exhibited significantly higher Model for End-Stage Liver Disease scores than the nontreated group ( p < 0.01). Within the steroid-treated group, the proportion of eTreg cells significantly expanded in the steroid responders (n=13; p = 0.01). Furthermore, a significant positive correlation was observed between the decrease in the Model for End-Stage Liver Disease score and the increase in eTreg cells ( p < 0.05). Single-cell RNA sequencing using paired peripheral blood mononuclear cells (pre-steroid and post-steroid therapy) from a steroid responder revealed gene expression changes in T cells and monocytes, suggesting enhancement of Treg cell function. In vitro results showed an elevation in the proportion of eTreg cells after steroid therapy. In conclusion, our findings suggest that the efficacy of steroid therapy in patients with severe alcohol-associated hepatitis is mediated by an increase in the number of eTreg cells.

Intestinal ultrasound scan predicts corticosteroid failure and colectomy risk in patients with ulcerative colitis.

Intestinal ultrasound (IUS) is an emerging modality for assessing disease activity, extent, and treatment response in ulcerative colitis. This study aimed to evaluate the potential of IUS in predicting severe flares, the need for rescue therapy (corticosteroid failure), and colectomy in patients with ulcerative colitis. We conducted a retrospective review of medical records, collecting clinical and IUS data. The Milan Ultrasound Criteria (MUC) score was used to assess ulcerative colitis severity. Group comparisons were performed to identify differences in MUC scores between mild-to-moderate and severe ulcerative colitis, between steroid responders and nonresponders, and between patients who underwent colectomy and those who did not. Receiver operating characteristic (ROC) analysis was used to predict outcomes in patients with ulcerative colitis. This analysis included 102 patients with ulcerative colitis categorized as mild/moderate (60) or severe (42). MUC scores were significantly higher in the severe ulcerative colitis group compared with the mild/moderate group ( P < 0.001). Analysis (using ROC) identified a cutoff MUC score of >8.54 to indicate severe ulcerative colitis with good sensitivity (64.29%) and excellent specificity (93.33%). Similarly, a cutoff of MUC > 10.54 showed promise in predicting corticosteroid failure, with acceptable sensitivity (50%) and high specificity (90.91%). Finally, a cutoff MUC score >12.5 demonstrated potential for predicting colectomy, exhibiting moderate sensitivity (55.56%) but excellent specificity (96.97%). IUS may be useful for differentiating severe ulcerative colitis from mild-to-moderate disease, identifying early stage failure of corticosteroid therapy, and predicting the potential need for colectomy.

The Impact of Steroid Responder Status on Long-Term Outcomes in Critically Ill Patients With Acute Respiratory Distress Syndrome Receiving High-Dose Glucocorticoids.

Background and objective High-dose intravenous pulsed glucocorticosteroids (GCS) are not part of the standard treatment in acute respiratory distress syndrome (ARDS), and the evidencesupporting their use is conflicting. In clinical practice, however, they are used in specialist settings when clinico-patho-radiological features suggest a potentially steroid-responsive pattern, or as a last resort in cases where patients are unable to be weaned off mechanical ventilation. This study aimed to investigate if an early objective response to high-dose GCS treatment in selected critically ill patients is predictive of survival in ARDS. Methods This study involved a case series of 63 patients treated at a tertiary specialist respiratory ICUbetween 2009 and 2017 who received high-dose GCS for ARDS following a multidisciplinary board agreement. Patients were stratified according to the change in their modified lung injury score (mLIS) between days 0 and 10 following GCS initiation. Changes in mLIS (range: 0-4)were grouped as follows - full responders: ≥2, partial responders: ≥1 and <2, and non-responders: <1. Mortality on discharge and at 6, 12, 18, and 24 months post-ICU discharge was assessed for each group. Data were analysed using logistic regression and a receiver operating curve (ROC) to determine a statistically significant association between the change in mLIS and survival. Results Of the 63 patients, there were seven full responders, 12 partial responders, and 44 non-responders to high-dose GCS. Overall mortality at ICU discharge and 6, 12, 18 and 24 months post-discharge was 29/63 (46.0%), 33/63 (52.4%), 34/63 (54.0%), 34/63 (54.0%), and 35/63 (55.6%) respectively. Mortality was significantly lower in the partial and full-response groups than in the non-response group at all time frames. Logistic regression showed a significant association between the change in mLIS and survival (p<0.001), and a ROC demonstrated that categorising the change in mLIS was a good predictive model for survival (c-statistic 0.86). Conclusions Measuring the change in mLIS by day 10 following high-dose GCS administration for ARDS may beclinically useful in prognosticating such patients. Further research using mLIS as a measure of response to GCS, and larger datasets to enable the evaluation of prognostic factors, may assist clinicians in predicting which patients with persistent ARDS are likely to respond to GCS therapy.

To determine the effectiveness of Tofacitinib on treatment outcome in patients hospitalised with COVID-19 pneumonia- A longitudinal observational study in a tertiary care Hospital Mandya

The effectiveness of Tofacitinib, a Janus kinase inhibitor, in patients who are hospitalised with coronavirus disease 2019 (COVID-19) pneumonia are unclear hence this study is conducted to evaluate the efficacy of Tofacitinib on treatment outcome in patients hospitalised with COVID-19 pneumonia.All diagnosed cases of SARS COV2 who required O2 therapy at the start of the study will be undergoing routine investigations according to COVID 19 management guidelines and will be treated with adequate immunosuppression with corticosteroids. Those patients whose inflammatory markers (CRP, S LDH, D DIMER) are not decreasing after 48 hours of corticosteroids therapy may be given Tab Tofacitinib 10mg bid for a period of 14 days or till the decrease in inflammatory markers, whichever is earlier. Oxygen requirement and inflammatory markers were assessed every 3 day. Out of 27 patients who didn’t respond for corticosteroids 20 were given the drug tab tofacitinb 10mg BD. CRP in the both the steroid non responders and steroid responders groups was high till day 9, on day 14 the CRP levels were normal in 50% of steroid non responders. S LDH levels in the steroid non responders group was in the decreasing trend i.e., on day 14 it was normal in 70% of patients.. The levels of D DIMER in tofacitinib group was high till day 6, and on day 14 the D-DIMER levels were normal in 40% patients. Oxygen requirement showed drastic changes in the steroid non responders group. Among patients hospitalized with COVID-19 pneumonia, addition of Tofacitinib to steroid non responders group showed early improvement in their clinical and biochemical levels. Hence, Tab tofacitinib can be recommended an adjunct to steroids for early clinical and biochemical improvement for treatment of moderate to severe cases of COVID-19.

Paradoxical eosinophilic and cytokine responses to oral corticosteroid treatment in patients with asthma exacerbations

BackgroundThymic stromal lymphopoietin (TSLP) orchestrates eosinophilic inflammation, which may increase in asthma exacerbations. On the contrary, miR-1 inhibits TSLP-mediated eosinophil trafficking in lung endothelium. Whether the balance of TSLP and miR-1 levels determines the response to oral corticosteroids during the treatment of asthma exacerbations remains unknown. ObjectiveTo investigate the involvement of TSLP/miR-1 axis in inflammatory response to OCS treatment for asthma exacerbations. MethodsWe measured the concentrations of TSLP and other inflammatory cytokines and miR-1 expression during acute asthmatic exacerbations treated with standard oral corticosteroids (OCS) in a real-life setting. Twenty eight consecutive patients with acute asthma exacerbations treated with OCS for 1 week at the Emergency Department (ED) were studied prospectively. Steroid responders (SR) were identified by a significant reduction in blood eosinophils, whereas paradoxical responders (PR) showed no markedly decreased or even increased absolute blood eosinophil counts after OCS treatment. Differential white blood cell counts, blood cytokine levels and miR-1 expression within and between groups were compared before and after OCS treatment. The baseline cytokine concentrations in both groups were compared with those of stable asthmatics (SA). ResultsOCS treatment significantly reduced TSLP levels in steroid responders whereas this effect did not occur in paradoxical responders (P = 0.006 and P = 0.742, respectively). In contrast, miR-1 expression was unchanged in steroid responders in response to OCS, whereas it was markedly reduced in the paradoxical responders, despite higher expression at baseline compared with stable asthmatics, which may account for slower resolution of the exacerbation. ConclusionsIn some asthmatic patients with acute exacerbations who do not suppress eosinophils after a course of OCS, there is a paradoxical decrease in plasma miR-1 and increase in TSLP compared with steroid responders, which may result in slower clinical recovery.

P972 Short and long-term outcomes after acute severe ulcerative colitis in children: A Canadian single centre experience

Abstract Background The short and long-term course of ulcerative colitis (UC) following an episode of acute severe UC (ASUC) in children is insufficiently characterized. We aimed to assess contemporary outcomes in children hospitalized with ASUC. Methods This was a retrospective cohort study of children aged 2-17 years hospitalized with ASUC between 2010 and 2022 at a tertiary center in London, Ontario, Canada. All data were recorded using standardised Case Report Forms, de-identified, and entered into a central database registry using Research Electronic Data Capture (REDCap) Steroid non-response was defined as requirement of medical rescue therapy or colectomy. Results A total of 58 children hospitalized with ASUC were included (male: 55.2% [n =32], mean age at admission: 12.2 ± 3.5 years). The majority had extensive colitis (82.4% [n = 42]) at the time of diagnosis. 74% (n = 43) presented within one year of symptom onset and 31% (n = 18) had ASUC as their index presentation with UC. 15.5% (n = 9) of patients had prior purine analogues and 20.7% (n = 12) had received biologics prior to ASUC presentation. Median Pediatric Ulcerative Colitis Activity Index (PUCAI) score on admission was 65.0 (IQR: 60.0 – 75.0). After intravenous corticosteroid therapy 68.9% (n = 40) responded to steroids. Of the patients with steroid non-response (31% [n = 18]), 3.4% (2/58) underwent colectomy and 27.6% (16/58) patients received infliximab rescue therapy. Median PUCAI score was significantly lower on day 3 between steroid responders and steroid non-responders (37.5 vs 60, p &amp;lt;0.01). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 7.4% (4/54) and 8% (4/50) respectively. Short term and long-term hospitalization rates for UC exacerbation following discharge was 25.9% (14/54) and 16% (8/50) respectively. Similar rates of long-term colectomy and hospitalizations were observed between steroid responders and non-responders. On univariate analysis, no statistically significant factors associated with steroid non-response were identified. Conclusion 17% of patients hospitalized for ASUC required colectomy within 12 months of presentation. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates are still high. Future research should focus on earlier identification and treatment of children at high risk of exacerbation to prevent complications.

P228 Predictors of steroid therapy refractoriness in admitted Acute Severe Ulcerative Colitis patients

Abstract Background One third of acute severe ulcerative colitis (ASUC) patients are steroid refractory and require colectomy or rescue therapy. Risk stratifying ASUC patients who are steroid non responders to facilitate early initiation of rescue therapy or consideration of colectomy remains an unmet needs in the management of ASUC. Methods Records of admitted patients with ASUC over a 5-year period were included. Clinical (diagnosis history, previous medications, disease extent) laboratory (FBC, CRP and albumin at admission and day 3, CRP/albumin ratio) and endoscopic scores (Mayo and UCEIS) at admission were recorded. The primary outcome was response to IV steroids. Secondary outcomes were the proportion of patients requiring re admission or initiation of advanced therapy (biologics or small molecules) within 1 year. Results Our study included 103 ASUC patients (44/103 male, median age: 41 years(Min:18, Max:84, range:66, IQR:27). 53 patients were steroid responders, 50 patients were non responders. Among non responders 48 had rescue therapy and 5 had colectomy at index admission (3 after rescue therapy and 2 without rescue therapy). There was no statistical significant difference between both groups in age, gender, disease extent and duration, haemoglobin level, platelets, CRP level, Mayo score of sigmoid, UCEIS score of rectum and sigmoid. There was statistically significant difference between both groups in being on oral steroids at entry, duration of hospital stay, albumin at admission, day 3 albumin, CRP/Albumin ratio at day 3 and Mayo score of rectum. On univariate analysis, albumin at admission and at day 3, CRP/Albumin ratio at day 3 and being on oral steroids at entry predicted non response to steroids while on multivariate analysis, being on steroids at admission was the only factor independently associated with steroid non-response(OR= 4.695, 95% CI: 1.79-12.34, P=0.002). Among steroid responders, 13(24.5%) required readmission within 1 year while only 3(6.7%) of the steroid non responders who received rescue therapy required readmission. Twenty five(47.2%) of steroid responders required initiation of advanced therapies within 1 year of index admission while 28 didn’t. Patients who required initiation of advanced therapy have statistically significant lower hemoglobin and higher platelets than who didn’t. Hemoglobin was the only factor to predict initiation of advanced therapy in multivariate regression analysis(-0.043, P=0.029) Conclusion Being on oral steroids at admission for ASUC can predict non response to IV steroids with majority may benefit from upfront advanced therapies at Day 1 of admission. Nearly half of the admitted ASUC patients who respond to steroids require treatment escalation to advanced therapies at 1 year.

P550 Short and long-term outcomes after acute severe ulcerative colitis in adults: A 12 year Canadian experience in the post biologic era

Abstract Background Patients with acute severe ulcerative colitis (ASUC) are at increased risk of colectomy following an episode of acute severe exacerbation. Medical rescue therapy in steroid non-responders has reduced the need for emergency colectomy. However, impact of biologics on longer-term colectomy risk is unclear. Methods A retrospective cohort study of adult patients aged ≥18 years hospitalized with acute exacerbation of UC requiring hospitalization and managed with intravenous corticosteroids between 2010 and 2022 at two regional hospitals in London, Ontario, Canada. Steroid non-response was defined as requirement of medical rescue therapy or colectomy. Results A total of 264 adults hospitalized with ASUC were included in the analysis (male: 51.1% [n=136], mean age at admission: 40.8±17.8 years). The majority had extensive colitis (71.3% [n=169]) at the time of diagnosis. 46.3% (n=118/255) presented within one year of disease onset and 23% (n=61) had ASUC as their first presentation with UC. 25.7% (n=66/257) of patients had prior purine analogues and 23.3% (60/257) had previous biologics prior to ASUC presentation. After admission, 55.7% (n=147) responded to intravenous corticosteroids. Of the steroid non-responders, 37.5% (n=99) patients were managed with infliximab rescue therapy and only one patient received tofacitinib rescue therapy. Median CRP, stool frequency and Lindgren index score were statistically significant between steroid responders and non-responders (Table 1). A higher proportion of steroid non-responders had prior exposure to biologics or tofacitinib compared to steroid responders (31.9% vs 16.3%, p&amp;lt;0.01). On multivariate analysis for various factors predicting steroid non-response, assessment by Oxford criteria on day 3 was the only factor that was statistically significant (odds ratio 4.70 (95% CI 1.06-20.8), p = 0.04). Oxford criteria on day 3 had a sensitivity, specificity of 58.6% and70.8%, respectively for predicting steroid non-response. 8% (n=21) required colectomy during index admission. An additional 13% (n = 32) underwent colectomy within 12 months of discharge, for which there was no difference between steroid responders and non-responders (12.2% vs 14.7%). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 8% (20/245) and 5.4% (12/223) respectively. Hospitalization with UC exacerbation rate following discharge was 17% (38/223). Conclusion 8% of patients admitted for ASUC require colectomy during the same admission and additional 13% required colectomy within 12 months of discharge. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates remain high.

Safety and efficacy profile of intravitreal ranibizumab vs dexamethasone in treatment of naïve diabetic macular edema.

To compare the safety and efficacy parameters of intravitreal ranibizumab vs intravitreal dexamethasone (IVD) in the treatment of patients with naïve diabetic macular edema (DME) in terms of best-corrected visual acuity (BCVA), central macular thickness (CMT), and possible complications like intraocular pressure (IOP) rise and cataract progression. A hospital-based prospective and comparative study of naïve DME patients was conducted between November 2020 and October 2021 with a minimum follow-up (F/U) period of 6 months. Thirty phakic patients received one dose of IVD implant (Group A) and the other 30 (Group B) received three consecutive monthly doses of ranibizumab. The main exclusion criteria were steroid responders and the presence of ocular inflammation. The mean pre-injection CMT in Group A was 405µ and reduced to 297.07µ at 3 months and 278.35µ at 6 months. Mean increase in logMAR BCVA was 0.55. The mean pre-injection IOP was 16.28 and 17.64 mm of Hg at 6 months. In Group B, the mean pre-injection CMT was 401.07µ and reduced to 276.1µ at 3 months and 292.9µ at 6 months. Mean BCVA increased to 0.37. The mean pre-injection IOP was 17.28 mm Hg and 16.42 mm Hg at 6 months. There was no significant progression of cataract in both groups. The mean decrease in CMT was comparable in both the groups at 6 months F/U with an improvement of BCVA with no significant IOP fluctuation or cataract progression. Hence, IVD appears to be noninferior to ranibizumab in the treatment of naïve DME.

Early Postoperative Complications of Trabeculectomy and Their Management: A Hospital Based Study

Purpose: To study the early post operative complications of trabeculectomy, Phaco trabeculectomy and their management in a tertiary care center. Study Design: Interventional case series. Place and Duration of Study: Al-Ehsan Welfare Eye Hospital from 1st November 2020 to 30th January 2022. Methods: One hundred and two patients who underwent glaucoma filtration surgery were selected through convenient sampling. The patients were followed up for 12 weeks and early post-operative complications, if any, were noted and managed. Results: There were 58 (56.86%) males and 44 (43.14%) females. The age ranged from 35 to 70 years. There were 48 (47.06%) pseudophakic and 54 (52.94%) phakic patients. Mean pre-operative IOP was (31.99 ± 5.66 mm Hg) which reduced to 12.35 ± 4.30 mm Hg one month after surgery. Trabeculectomy with 5-Fluorouracil (5-FU) was performed in 48 patients (47.06%) while trabeculectomy combined with phacoemulsification and IOL implantation was performed in 54 patients (52.94%). Primary open angle glaucoma (POAG) was present in 94 patients (92.16%) while 8 patients (7.84%) had chronic angle closure glaucoma. The early postoperative complications were shallow anterior chamber in 17.6%, pupillary membrane in 2.9% and choroidal detachment in 2.9%. Six patients (5.9%) were steroid responder and these patients were shifted to topical Loteprednol from topical prednisolone. Conclusion: Majority of early post operative complications of trabeculectomy are transient and settled in first two to three weeks without any surgical intervention. Anticipation, timely diagnosis and early intervention is the key to success in management of complications of trabeculectomy.

A Nationwide Clinical Trial ALL-B12: An Optimized Therapy for Pediatric B-Precursor Acute Lymphoblastic Leukemia with Excellent Overall Survival and Minimal Non-Relapse Mortality: A Report from the Japan Children's Cancer Group

Background: Advancements in treatment have significantly improved therapeutic outcomes for pediatric acute lymphoblastic leukemia (ALL) and relapsed ALL. However, there remains a need for therapies that minimize relapse in high-risk groups and avoid long-term complications. To address this gap. we conducted the nationwide clinical trial ALL-B12, aimed at newly diagnosed B-precursor ALL aged 1-18 years. Methods: ALL-B12 enrolled participants from November 2012 to November 2017. Patients were stratified based on the NCI classification (age and WBC count at diagnosis). Those with NCI-SR and NCI-HR were assigned to the standard risk group (SR) and the intermediate group (IR), respectively. Poor steroid responders and those with high-risk genomic abnormalities were assigned to the high risk group (HR). A treatment regimen, including 4-drug remission induction, early consolidation, HD-MTX-containing intensification, re-induction, and maintenance, was implemented. Anthracycline dose in the induction therapy was reduced in SR patients. In contrast, early consolidation was intensified with L-ASP for a part (randomized) of the IR and the entire HR. Patients classified as CNS3 were treated as high risk, receiving 12 Gy cranial irradiation; prophylactic cranial irradiation was avoided in non-CNS3 groups. Allogeneic hematopoietic cell transplantation (allo-HCT) during the first remission was restricted to those in the very high-risk group with specific genomic abnormalities (e.g., hypodiploid &amp;lt;44 and TCF3-HLF) and residual MRD above 10^-3 at the end of early consolidation. A randomized comparison was carried out within each risk group to identify the optimal treatment. We assessed the effectiveness of intensification with VCR/DEX pulses for the SR, the impact of L-ASP intensification for the IR, and compared block-type treatment and HD-MTX intensified with VCR and L-ASP (HD-MTX/VL) for the HR. The primary outcome measure was the 5-year event-free survival (EFS) rate. Results: In total, 1,936 patients were enrolled, with 1,804 patients receiving protocol treatment after excluding ineligible patients such as those with BCR-ABL1 positivity. The percentage of patients achieving remission at the end of early consolidation was 98.9%. The overall 5-year EFS and OS probability were 85.2% (95%CI 83.5-86.8%) and 94.3% (95%CI 93.1-95.3%), respectively. Only 1.7% of patients underwent allo-HCT during the first remission. The mortality rate during induction was just 0.6%, with non-relapse mortality (NRM) after remission at 0.6%. The overall relapse incidence was 13.2%, and the overall CNS relapse rate was 1.9%. Among patients assigned to risk groups, 1,107 (62.7%) were assigned to the SR, 459 (26.0%) to the IR, and 200 (11.3%) to the HR. The 5yEFS for the SR was 89.9%. The post-randomization EFS rates for those with and without VCR/DEX intensification were 90.7% and 90.1%, respectively, indicating nearly identical survival curves (p = 0.73). The EFS for the IR was 79.7%, but L-ASP intensification was expected to be effective, the EFS for groups with and without ASP intensification was 82.1% and 77.9%, respectively, failing to reach statistical significance (p = 0.31). The EFS for the HR was 75.5%, with overlapping survival curves for block treatment (75.7%) and HD-MTX/VL (74.2%) (p = 0.92). MRD dynamics were associated with prognosis, and early consolidation therapy enhanced by ASP resulted in better MRD clearance. MRD of 10^-4 was associated with poor prognosis at both the end of induction and the end of early consolidation. Conclusion: In our multi-center clinical trial, we observed excellent outcomes in a diverse group of patients nationwide. Using the NCI criteria for stratification, a significant number of patients were categorized into the SR. Additionally, introducing L-ASP during early consolidation decreased the number of MRD-positive patients, which subsequently reduced the subset needing allo-HCT. This strategic adjustment in treatment intensity resulted in both high EFS rates and low NRM. Given the rise of immunotherapy and its promising results for recovery even post-relapse, there's a pressing need to enhance overall outcomes while minimizing non-relapse mortality. We anticipate refining our stratification further and integrating immunotherapy and other innovative treatments into our approach.

Intraocular pressure changes following small-incision cataract surgeries in a tertiary care center: a prospective study

Aim This study aims to identify the pattern of intraocular pressure (IOP) changes after uneventful small-incision cataract surgery (SICS) in previously normotensive eyes, to know the cause for these postoperative changes, and to correlate the preoperative anterior chamber depth (ACD) to the postoperative IOP change. Patients and methods A prospective study was conducted at Yenepoya Medical College, Mangalore, India on 87 non-glaucomatous eyes that underwent an uneventful SICS with posterior chamber intraocular lens implantation. The IOP was measured preoperatively and postoperatively on days 1, 3, and weeks 1, 3, and 6. We tried to identify the cause of the IOP change. The preoperative and postoperative ACD change was also noted and correlated with the IOP change. Results The mean preoperative IOP was 14±1.81 mm Hg. On the first postoperative day (POD-1), 54% of the eyes showed a statistically significant rise in IOP (mean IOP=17.03±7.17 mm Hg, P=0.0002), and 28% showed a mean fall in IOP of 9.28 mm Hg. On the third postoperative day (POD-3), the IOP showed a statistically significant rise (14.82±3.93 mm Hg, P=0.028) compared with the preoperative value. At the end of the first postoperative week (POW-1), the IOP showed a statistically nonsignificant rise (P=0.66). By the third postoperative week (POW-3), the IOP decreased to 13.82±2.83 mm Hg, with a statistically nonsignificant difference compared with the preoperative IOP (P=0.45). However, there was a statistically significant decrease in the IOP (P=0.0001) in the sixth postoperative week (POW-6). Postoperatively, there was a statistically significant increase in ACD from 3.01±0.31 to 3.23±0.36 mm (P=0.0001) by the POW-3. The preoperative ACD showed a statistically significant moderate negative correlation with late postoperative IOP (r=−0.7394, P&lt;0.0001). Conclusion After SICS, at the end of 6 weeks, there was a statistically significant decrease in the mean IOP with an increase in the ACD. A moderate negative correlation existed between the preoperative ACD and late postoperative IOP. It was found that 2.3% of the eyes were steroid responders and showed a rise in IOP at POW-3.

A very early steroid responder after cataract surgery: a case report

BackgroundIncreased intraocular pressure (IOP), a side effect of corticosteroid eye drops, typically develops during the first few weeks of administration, and steroid response is not generally considered a cause of increased IOP immediately after cataract surgery.Case presentationHere, I report a rare case of increased IOP due to steroid eye drops immediately after surgery. A man in his 80s presented with vision loss. Bilateral cataracts and pseudoexfoliation syndrome were confirmed. Postoperative eye drops including steroid eye drops were started immediately after cataract surgery in the right eye. High IOP was observed at the next and subsequent morning visits, but IOP normalized when steroid eye drops were discontinued. After surgery on the left eye, steroids were not administered postoperatively, and no increase in IOP was observed.ConclusionThis case report highlights that a very early steroid response may be potential cause of elevated IOP immediately after cataract surgery.

Rapamycin Restores Different Patterns of Cytokine Expression to Dexamethasone Treatment on CD14++CD16+ Monocytes from Steroid-Resistant Asthma Patients.

We aimed to investigate the differences in interleukin (IL)-10, IL-1β, IL-6, and tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated CD14++CD16+ monocytes obtained from asthmatics after dexamethasone or dexamethasone plus rapamycin treatments between clinical steroid responders (R) and non-responders (NR). Cytokine expressions in LPS-stimulated CD14++CD16+ p-mammalian target of rapamycin (mTOR) monocytes from R and NR were determined using flow cytometry. IL-10high CD14++CD16+ p-mTOR population following LPS stimulation increased in the R group although decreased in the NR group with dexamethasone treatment. IL-1βhigh population decreased in the R group although increased in the NR group. Rapamycin treatment after LPS and dexamethasone resulted in a significant increase in the IL-10high population and a significant decrease in the IL-1βhigh population in the NR group. Dexamethasone treatment resulted in different patterns of change in cytokine expressions in LPS-stimulated CD14++CD16+ p-mTOR monocytes between the R and NR. mTOR inhibition can restore steroid responsiveness involving IL-10 and IL-1β in CD14++CD16+ p-mTOR monocytes.

Peripheral lymphocyte fluctuation as an indicator of severe immune-related adverse events in patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have proven to be effective treatments for various cancers, but can also elicit immune-related adverse events (irAEs). Given that severe irAEs can be life-threatening, biomarkers that can predict the occurrence of irAEs are of paramount importance. ICIs affect the dynamics of lymphocytes, and alterations in these dynamics may play a role in the development and severity of irAEs. The aim of this study was to investigate the correlation between irAEs and changes in lymphocyte counts. Information on irAEs was collected from 226 ICI cases from 2014 to 2020. We compared lymphocyte counts before treatment and at the onset of irAE and investigated the association between lymphocyte count fluctuations and the presence and severity of irAE, the course after steroid treatment, and overall survival. Of the 226 cases, 27 patients developed grade 3 or higher irAE. Compared to the other groups, the lymphocyte count in this group was significantly decreased at the time of irAE (p < 0.01). There was a trend toward a rapid increase in lymphocyte count in the steroid responder group compared to the non-responder group. Regarding overall survival, patients with irAE had significantly longer survival than those without irAE (p=0.0025). However, there was no association between changes in lymphocyte count and survival in patients with irAE. The percentage change in lymphocyte count was found to correlate with the incidence of severe irAEs. Close monitoring of the patient's condition is crucial when the lymphocyte count decreases during ICI treatment.

Response to Preoperative Dexamethasone Predicts Postoperative Neurological Improvement of Focal Neurological Deficits in Patients With Brain Metastases.

Steroids are used ubiquitously in the preoperative management of patients with brain tumor. The rate of improvement in focal deficits with steroids and the prognostic value of such a response are not known. To determine the rate at which focal neurological deficits respond to preoperative corticosteroids in patients with brain metastases and whether such an improvement could predict long-term recovery of neurological function after surgery. Patients with brain metastases and related deficits in language, visual field, or motor domains who received corticosteroids before surgery were identified. Characteristics between steroid responders and nonresponders were compared. Ninety six patients demonstrated a visual field (13 patients), language (19), or motor (64) deficit and received dexamethasone in the week before surgery (average cumulative dose 43 mg; average duration 2.7 days). 38.5% of patients' deficits improved with steroids before surgery, while 82.3% of patients improved by follow-up. Motor deficits were more likely to improve both preoperatively ( P = .014) and postoperatively ( P = .010). All 37 responders remained improved at follow-up whereas 42 of 59 (71%) of nonresponders ultimately improved ( P < .001). All other clinical characteristics, including dose and duration, were similar between groups. A response to steroids before surgery is highly predictive of long-term improvement postoperatively in brain metastasis patients with focal neurological deficits. Lack of a response portends a somewhat less favorable prognosis. Duration and intensity of therapy do not seem to affect the likelihood of response.

Practice patterns and opinions in the treatment of allergic eye disease: A survey among Indian ophthalmologists.

Management of allergic eye disease is seldom straightforward and often challenging. We conducted an online survey to elicit opinions on the preferred practice pattern in the treatment of allergic eye disease. An online survey questionnaire was sent to all practicing ophthalmologists using social media platforms. The respondents were asked about their clinical experience and preferred treatment in various scenarios such as mild-moderate vernal keratoconjunctivitis (VKC), chronic VKC, refractory VKC, steroid responders, giant papillae, and shield ulcer. Respondents were asked about the newer molecule (alcaftadine) and reservations regarding systemic immuno-suppressants and ordering allergy tests in their practice. Ninety - one participants responded to the survey. About 57.1% of ophthalmologists reported coming across more than 10 cases per week in their practice. The most common age group was 5-10 years (61.1%), but adult onset VKC was also reported at 41.6% (1-2 per month), 37.1% (3-5 per month), and 13.5% (more than 10 per month). The disease is perennially present (36.7%), and a mixed form has been reported by 47.8% of ophthalmologists. Dual-acting agents were preferred by 40% in mild-moderate clinical variants. Topical steroids in slow tapering dosage were preferred by 86.7% in their prescription. Tacrolimus 0.03% was preferred by 65.9% and given for at least 3 months of continuous usage by 47.6% of ophthalmologists. High-dose topical steroids were preferred for giant papillae (67.8%) and Shields ulcers (68.3%) in our survey. Supratarsal steroid injection was preferred by 50% in treating refractory VKC in our survey. Allergic eye disease is a common yet annoying disease. The signs and symptoms can vary from subtle, innocuous forms to devastating variants affecting vision and day-to-day work. This survey aims to elicit responses from clinicians spreading across different geographical areas and compares responses based on experience in practice.