Initial Steroid Research Articles

Clinical characteristics and prognosis of steroid-resistant nephrotic syndrome in children: a multi-center retrospective study.

This study investigated the factors influencing the prognosis of children with steroid-resistant nephrotic syndrome (SRNS) in patients from the Guangxi region. We retrospectively analyzed clinical and pathological data of 279 patients with SRNS from six tertiary hospitals in Guangxi. Clinical data were compared between initial (I-SRNS) and secondary (S-SRNS) steroid resistance subgroups and Cox regression analysis was used to determine risk factors for chronic kidney disease (CKD) and CKD stage 5 (CKD5) in patients with SRNS. The median age of onset was 54 months. Thirty-three patients had extra-kidney manifestations. Fifty-two, 24, 57, 33, and 41 patients had hypertension, acute kidney injury, vitamin D deficiency, high intraocular pressure, and dwarfism, respectively. One hundred eighty-two and 92 patients had I-SRNS and S-SRNS, respectively. There were significant differences in sex, ethnicity, family history, incidence of hematuria, clinical classification, efficacy of immune agents, and prognosis between groups (P < 0.05). Among the 279 cases of SRNS, 239 had normal kidney function, 37 developed CKD, and 16 had CKD5. An increase in serum creatinine level (HR = 1.003) was significantly associated with CKD in children with SRNS, and effective immunosuppressant therapy decreased the CKD risk (HR = 0.168). Patients with increased serum creatinine levels (HR = 1.003) and acute kidney injury (HR = 4.829) were more likely to progress to CKD5. Children with S-SRNS showed a higher response to immunosuppressants than those with I-SRNS. Effective immunosuppressant therapy was found to protect against CKD, whereas increased acute kidney injury was an independent risk factor for CKD5.

Results of a New Treatment Protocol for Sudden Sensorineural Hearing Loss Using Betamethasone for Intratympanic Therapy.

Introduction Sudden sensorineural hearing loss (SSNHL) is defined as a rapid sensation of hearing impairment in one or both ears. Based on its personal impact on patients, the present study advances the analysis of new treatments for the prompt recognition and management of SSNHL, with higher chances of improvements in terms of hearing recovery and quality of life of the patients. Objective To describe the intratympanic (IT) corticoid infiltration technique, to demonstrate the efficacy of betamethasone injection as a sequential treatment in patients whose initial systemic steroid treatment failed, as well as to compare its use in different treatment periods. Methods The present clinical trial was conducted with 37 patients referred to our office with the diagnosis of SSNHL, from September 2019 to May 2022, who provided informed consent to participate. Results Even dividing the analysis of increasing the pure tone average (PTA) or speech recognition threshold (SRT) between the difference into initiation of the salvage therapy in up to 15 days of the sudden deafness event, and between 15 days and 3 months of the event, we did not find any difference in hearing improvement. Conclusion Intratympanic corticosteroid therapy is prescribed when conventional therapy fails or when there is a limitation to the use of corticosteroids due to the presence of systemic disorders. As such, new drugs, such as bethametasone, are studied and show promising results.

Managing RS3PE: Diagnostic approach, initial steroid response, and long-term management with DMARDs

Background. RS3PE, or Remitting Seronegative Symmetrical Synovitis with Pitting Edema, is a unique and relatively rare form of inflammatory arthritis that predominantly affects older adults. It is distinguished by its hallmark features: symmetrical swelling of the joints, significant pitting edema in the extremities, and a negative serological profile for common markers associated with rheumatoid arthritis, such as rheumatoid factor (RA factor) and anti-citrullinated protein antibodies (anti-CCP). This condition is often characterized by a remitting course, meaning that symptoms may improve or resolve over time, particularly with appropriate treatment. The condition usually affects older adults and can sometimes be associated with other underlying health issues, such as malignancies or infections. The “remitting” aspect of RS3PE refers to the fact that the symptoms often improve or resolve over time, particularly with appropriate treatment, which usually involves corticosteroids or other anti-inflammatory medications. Case report. This case study details the clinical presentation, diagnosis, and management of a 56-year-old female patient with known hypertension who presented with bilateral dorsal hand swelling, pain, and early morning stiffness over a 15-day period. The patient’s initial examination revealed bilateral pitting edema and active arthritis in the proximal interphalangeal joints, with significant warmth and tenderness. Laboratory tests showed elevated ESR and CRP, normocytic normochromic anemia, and negative rheumatoid factor and anti-CCP antibodies. Imaging studies, including X-ray, ultrasound, and mammogram, showed no erosive changes or malignancy, while a Pap smear and serum CA-125 levels were within normal limits. The clinical picture, combined with the exclusion of other conditions, supported the diagnosis of RS3PE. Treatment commenced with intravenous low-dose dexamethasone, which led to significant symptomatic improvement. This was followed by a transition to oral prednisolone, and the patient initially showed complete resolution of symptoms. However, recurrence of symptoms occurred upon discharge, prompting the introduction of steroid-sparing agents: methotrexate and hydroxychloroquine, alongside continued oral steroid treatment. Over a two-month follow-up period, the patient experienced no signs of relapse. This case fits the clinical and investigative criteria for RS3PE. The patient showed symptomatic improvement after treatment with low-dose steroids.

Perfusion Steroid via Ventilation Tube as Salvage Treatments for Sudden Sensorineural Hearing Loss.

Objectives: Intratympanic steroid injection (ISI) for sudden sensorineural hearing loss (SSNHL) is a relatively popular and effective method, but there is no standardized method for intratympanic steroids for the treatment of SSNHL and no consensus on how to deliver steroids to the middle ear. The purpose of this study was to compare 2 means of intratympanic steroid delivery as therapy for SSNHL. Methods: A retrospective chart review was performed for the period from November 2018 to October 2022 at our Department of Otorhinolaryngology-Head and Neck Surgery. Sixty patients with profound SSNHL who have failed initial steroid therapy were divided into the continuously transtympanic steroid perfusion (TSP) therapy and the intermittent ISI therapy. Results: Posttreatment pure-tone average was 60.3 ± 18.2 dB in the TSP group and 67.5 ± 22.6 dB in the ISI group, 70.0% of subjects in the TSP group, and 46.7% of subjects in the ISI group had improved by 15 dB or more after the therapy. The increased hearing threshold of the TSP group (24.6 ± 14.1 dB) was better than the ISI group (16.6 ± 14.9 dB), and the hearing recovery was significantly different (P < .05) in the 2 groups. Besides the hearing improvement was most obvious in low-frequency areas in the TSP group, the most significant hearing improvement was at 250 Hz, reaching 30.8 ± 3.3 dB. Conclusions: In SSNHL patients who have failed initial steroid therapy, TSP therapy via a ventilation tube can achieve good hearing outcomes and serve as a salvage therapy for patients with SSNHL.

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

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

Cushing's Syndrome and Topical Corticosteroids in Pediatrics: A Systematic Review

Introduction Despite the increasing number of pediatric cases of iatrogenic Cushing's syndrome (CS) due to topical corticosteroids, systematic reviews are lacking to provide comprehensive insights into the disease. This study aims to provide a systematic overview of the disease. Methods Relevant literature was identified using Google Scholar and PubMed. The search strategy was restricted to studies on human published in English. The inclusion criteria encompassed confirmed pediatric cases of iatrogenic CS induced by topical corticosteroids. Results The mean age of the cases was 38.8 months, with a female gender predominance (57.1%). Abnormalities in growth patterns were observed in approximately 75% of the cases. The most common clinical presentation was a "moon face" appearance (74.6%), followed by weight gain (55.5%). Clobetasol propionate was the most frequently used topical steroid (54%), followed by betamethasone types (35%). The mean duration of steroid use was 25.4 weeks. The primary indications for steroid use were dermatitis (47.6%), psoriasis (17.5%), and scabies (15.9%). Laboratory tests for adrenocorticotropic hormone and cortisol levels revealed low levels in 73% and 78% of cases, respectively. All cases had their initial steroid discontinued. Oral hydrocortisone was the primary replacement therapy (39.7%), followed by sulfur cream (12.7%). Fifty-one cases (81%) recovered from the disease. Partial recovery was observed in 2 cases (3.2%), while four cases (6.3%) did not survive. Conclusion A specialist should supervise topical corticosteroid administration, and parents need to be fully informed about the proper usage and potential side effects to avoid iatrogenic CS and other complications.

Optimal management of radiation pneumonitis: Findings of an international Delphi consensus study

PurposeRadiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) for lung cancer, however, the optimal practice for diagnosis, management, and follow-up for RP remains unclear. We thus sought to establish expert consensus recommendations through a Delphi Consensus study. MethodsIn Round 1, open questions were distributed to 31 expert clinicians treating thoracic malignancies. In Round 2, participants rated agreement/disagreement with statements derived from Round 1 answers using a 5-point Likert scale. Consensus was defined as ≥ 75 % agreement. Statements that did not achieve consensus were modified and re-tested in Round 3. ResultsResponse rate was 74 % in Round 1 (n = 23/31; 17 oncologists, 6 pulmonologists); 82 % in Round 2 (n = 19/23; 15 oncologists, 4 pulmonologists); and 100 % in Round 3 (n = 19/19). Thirty-nine of 65 Round 2 statements achieved consensus; a further 10 of 26 statements achieved consensus in Round 3. In Round 2, there was agreement that risk stratification/mitigation includes patient factors; optimal treatment planning; the basis for diagnosis of RP; and that oncologists and pulmonologists should be involved in treatment. For uncomplicated radiation pneumonitis, an equivalent to 60 mg oral prednisone per day, with consideration of gastroprotection, is a typical initial regimen. However, in this study, no consensus was achieved for dosing recommendation. Initial steroid dose should be administered for a duration of 2 weeks, followed by a gradual, weekly taper (equivalent to 10 mg prednisone decrease per week). For severe pneumonitis, IV methylprednisolone is recommended for 3 days prior to initiating oral corticosteroids. Final consensus statements included that the treatment of RP should be multidisciplinary, the uncertainty of whether pneumonitis is drug versus radiation-induced, and the importance risk stratification, especially in the scenario of interstitial lung disease. ConclusionsThis Delphi study achieved consensus recommendations and provides practical guidance on diagnosis and management of RP.

Immune-related adverse event-associated sclerosing cholangitis due to immune checkpoint inhibitors: imaging findings and treatments.

Immune-related adverse event-sclerosing cholangitis caused by treatment with immune checkpoint inhibitors is rare, and the diagnostic criteria and treatment strategy remain unclear. In this study, we confirmed the clinicopathological features of immune-related adverse event-sclerosing cholangitis and clarified its diagnosis and appropriate management. We retrospectively evaluated 10 patients diagnosed with immune-related adverse event-sclerosing cholangitis and identified by electronic database searches. Blood tests revealed liver dysfunction with a predominance of biliary tract enzymes in all patients; however, jaundice was present in only one patient. Contrast-enhanced computed tomography revealed diffuse hypertrophy of the extrahepatic bile duct wall as the most frequent finding; however, endoscopic retrograde cholangiopancreatography showed various imaging features, such as the pruned-tree appearance of intrahepatic bile ducts, in all patients. Transpapillary bile duct biopsy showed inflammatory cell infiltration using immunostaining, with a predominance of cluster of differentiation 8-positive T cells in 63% of the cases. Initial steroid therapy was effective in two cases. Mycophenolate mofetil and tacrolimus were used in steroid-refractory cases. Although six patients showed improvements, all of the remaining patients died owing to immune-related adverse event-sclerosing cholangitis. Various bile duct imaging findings of immune-related adverse event-sclerosing cholangitis were revealed; transpapillary bile duct biopsy may be useful in the diagnosis of immune-related adverse event-sclerosing cholangitis. Despite the combination of multiple immunosuppressive agents, prognosis of immune-related adverse event-sclerosing cholangitis remains poor. Longer follow-up and larger clinical studies are necessary to establish its treatment strategy.

Association between the time of initial relapse and subsequent relapses in patients with childhood-onset idiopathic nephrotic syndrome.

Nephrotic syndrome relapse within 6months is a known risk factor for steroid-dependent nephrotic syndrome/frequently relapsing nephrotic syndrome (SDNS/FRNS), but the risk of early development of SDNS/FRNS and initiation of immunosuppression therapy remains unknown. Patients with childhood-onset idiopathic nephrotic syndrome who had the first relapse within 6months were enrolled. We analyzed the relationship between the time of the first relapse or the time of initial remission and incidence of SDNS/FRNS or initiation of immunosuppression therapy. Forty-five patients were enrolled. Twenty out of 23 patients (87%) with the first relapse within 30days after discontinuing initial steroid therapy experienced a second relapse within 30days after discontinuing steroid therapy. Additionally, most patients in this group (96%) experienced a second relapse within 6months after the onset and were diagnosed as SDNS/FRNS at this time. In this group, the incidence of SDNS/FRNS development within 6months was 96%. In contrast, the incidence of SDNS/FRNS development within 6months was 18% in patients with the first relapse more than 30days after steroid discontinuation. The incidence of initiation of immunosuppressive agents within 6months was 83% in the former group and 14% in the latter group. Most patients with the first relapse within 30days after discontinuing steroid therapy developed SDNS/FRNS and were administered immunosuppressive agents within 6months. Thus, it might be reasonable to start immunosuppression therapy in this group without waiting for the second relapse.

Safety andeffectiveness ofdenosumab inJapanese patients with rheumatoid arthritis: A 2-year post-marketing surveillance study.

To investigate the 2 year safety and effectiveness of denosumab 60 mg in patients with rheumatoid arthritis (RA) in clinical practice in Japan. This 2 year, prospective, observational cohort study included patients who initiated treatment with denosumab 60 mg for the progression of bone erosion associated with RA. Key endpoints were adverse drug reactions (ADRs), progression of bone erosion, and 28-joint Disease Activity Score based on C-reactive protein or erythrocyte sedimentation rate. Univariate and multivariate analyses were conducted to determine the risk factors for ADRs and the progression of bone erosion. In the safety analysis set (n = 1239), the incidence of ADRs was 3.0%; the most common ADRs were hypocalcaemia (1.2%) and osteonecrosis of jaw-related events (0.6%). A history of any drug allergy was a statistically significant risk factor associated with the occurrence of ADRs. In the effectiveness analysis set (n = 815), the incidence of progression of bone erosion was 8.7%. Steinbrocker stage and initial steroid dose were statistically significant risk factors associated with the progression of bone erosion. Denosumab demonstrated safety and effectiveness over a 2 year period in RA patients without any new safety concerns.

Meperfluthrin poisoning from mosquito repellent fumes in a 14-year-old Nigerian male adolescent- a case report

Mosquito coils, common in resource-constraint countries where mosquito-borne diseases are endemic, are slow- burning sticks that emit smoke containing mosquito repellents, commonly pyrethroids like meperfluthrin. In humans, the documented side effects of inhaled meperfluthrin are few. We report a case of meperfluthrin toxicity following exposure to mosquito coil fumes. A 14-year-old male adolescent developed multiple episodes of vomiting, respiratory distress, and altered consciousness following exposure to mosquito- repellent fumes containing 0.25% meperfluthrin. He had slept on a floor mat CC –BY 4.0 with the burning coil 20cm from his face before the onset of symptoms. He received initial oxygen, steroids, and antibiotics care at a private hospital before being referred to the teaching hospital. At presentation, his Glasgow Coma Score was 12, otherwise normal CNS finding. He developed irrational talk, violent behaviour and insomnia three days later. He recovered fully with supportive care. Excessive inhalation of meperfluthrinfumes maylead to neurotoxicity and pulmonary toxicity.

Baseline predictors of disease severity in immune checkpoint inhibitor-induced inflammatory arthritis.

The objective of this study was to determine baseline risk factors for requiring immunosuppression and having persistent arthritis in patients with immune checkpoint inhibitor-induced inflammatory arthritis (ICI-inflammatory arthritis). Participants were adults with rheumatologist diagnosed ICI-inflammatory arthritis. The primary outcome was requirement of conventional synthetic (cs) or biologic (b) DMARDs; other outcomes were persistence of inflammatory arthritis >6 months after ICI cessation and requirement of CSs. Logistic regression models evaluated associations between clinical features and primary and secondary outcomes, with adjustment for potential confounders, as appropriate. One hundred and twenty-six patients with ICI-inflammatory arthritis were included; 53 patients (42%) required a csDMARD/bDMARD. In the univariate logistic regression analysis, higher clinical disease activity index (CDAI), tenosynovitis, longer symptom duration before first rheumatology visit and longer ICI duration were significantly associated with a higher likelihood of requiring DMARDs; in addition, there was a trend towards those treated with prior chemotherapy being less likely to need DMARDs. After adjustment, tenosynovitis, longer symptom duration and higher CDAI remained associated with requiring DMARDs, while those with prior chemotherapy were significantly less likely to require DMARDs. Combination anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein-4)/PD-1 (Programmed cell death protein-1) therapy and CS use at baseline were associated with a higher risk of persistent inflammatory arthritis. Higher levels of disease activity, tenosynovitis and longer symptom duration prior to rheumatology referral were associated with requiring DMARDs for ICI-inflammatory arthritis, while those treated previously with chemotherapy were less likely to require additional immunosuppression. The presence of risk factors for severe disease at baseline may indicate a role for higher initial CS dose, earlier rheumatology referral, and adoption of immunosuppression beyond CSs to improve outcomes.

Anti-Vascular Endothelial Growth Factor Therapy with or Without Initial Steroid Therapy for Macular Edema in Branch Retinal Vein Occlusion.

In branch retinal vein occlusion (BRVO), administering steroid injections to inhibit expression of inflammatory factors in the first phase of macular edema may reduce recurrence of the edema. The purpose of our study was to investigate the functional and morphological prognosis and frequency of recurrence after injection of an anti-vascular endothelial growth factor (VEGF) with and without initial steroid therapy to treat macular edema with BRVO. Patients with BRVO and macular edema (41 eyes) received intravitreal ranibizumab injection (IRI) alone (IRI group, 21 eyes) or subtenon triamcinolone (STTA) injection and IRI (combination group, 20 eyes). Patients in both groups with recurrent macular edema received further IRI as appropriate. A laser flare meter was used to assess aqueous flare values, and an optical coherence tomography device was used to measure central macular thickness (CMT). Before the first treatment, we obtained samples of aqueous humor and analyzed them by the suspension array method to evaluate VEGF, placental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, IL-8, and interferon-inducible 10-kDa protein (IP-10). The two groups were not significantly different with regard to levels of VEGF, PlGF, PDGF-AA, sICAM-1, MCP-1, IL-6, IL-8, or IP-10. Best-corrected visual acuity, CMT, and aqueous flare value (IRI group, baseline 8.69 ± 4.55 photon counts/ms; combination group, baseline 9.21 ± 3.72 photon counts/ms) improved significantly in both groups without significant intergroup differences. Analyses showed no significant intergroup differences in the mean number of IRIs during the 12-month follow-up, but the proportion of patients without recurrence (ie, who received only one IRI) was significantly higher in the combination group than in the IRI group (P = 0.032). Furthermore, the time to initial recurrence was significantly longer in the combination group than in the IRI group (P = 0.003). These findings suggest that initial STTA injection and IRI may have a synergistic effect in patients with BRVO and macular edema in that they increase the time between anti-VEGF treatments.

Circulatory shock in adults in emergency department.

Circulatory shock is a common condition that carries high morbidity and mortality. This review aims to update the critical steps in managing common types of shock in adult patients admitted to medical emergency and intensive care units. A literature review was performed by searching PubMed, EMBASE Ovid, and Cochrane Library, using the following search items: ("shock" OR "circulatory shock" OR "septic shock" OR "cardiogenic shock") AND ("management" OR "treatment" OR "resuscitation"). The review emphasizes prompt shock identification with tissue hypoperfusion, knowledge of the underlying pathophysiological mechanism, initial fluid resuscitation with balanced crystalloids, norepinephrine as the preferred vasopressor in septic and profound cardiogenic shock, and tailored intervention addressing specific etiologies. Point-of-care ultrasound may help evaluate an undifferentiated shock and determine fluid responsiveness. The approach to septic shock is improving; however, confirmatory studies are required for many existing (e.g., amount of initial fluids and steroids) and emerging (e.g., angiotensin II) therapies. Knowledge gaps and wide variations persist in managing cardiogenic shock that needs urgent addressing to improve outcomes.

Factors predicting the occurrence of disease-causing variants on next-generation sequencing in children with steroid-resistant nephrotic syndrome - implications for resource-constrained settings.

Enhanced availability of high-throughput sequencing (at progressively reducing costs) has revolutionized the identification of monogenic SRNS. However, in resource-poor settings, it may not be possible to perform next-generation sequencing (NGS) in all children wherein monogenic SRNS is suspected. Besides, the optimal strategy of genetic evaluation (in patients with SRNS) in routine clinical practice in resource-limited settings is unknown. Patients with newly diagnosed SRNS were recruited from our center and followed up prospectively. We analyzed the factor(s) independently predicting the occurrence of disease-causing variants in these patients. In our study, 36 children/adolescents with SRNS were included (initial steroid resistance in 53%). On targeted NGS, pathogenic/likely pathogenic variants were identified in 31% (n = 11). These included homozygous or compound heterozygous variants in the following genes: ALOX12B, COL4A3, CRB2, NPHS1, NPHS2, PLCE1, and heterozygous variant in WT1 gene. Overall, 14 variants were identified of which 5 (36%) were novel. Age of < 1 or < 2years and presence of family history of nephrotic syndrome independently predicted the occurrence of monogenic SRNS on multivariate analysis. While NGS-based genetic testing in SRNS is increasingly being incorporated in routine clinical practice the world over, the scenario is far from optimal in resource-limited settings. Our study highlights that resources for genetic testing in SRNS should be prioritized for patients with early age at disease onset and presence of family history. Larger studies composed of diverse multi-ethnic cohorts of patients with SRNS are required to further delineate the optimal strategy of genetic evaluation in resource-poor settings. A higher resolution version of the Graphical abstract is available as Supplementary information.

A242 DELAYED STEROID TAPER MAY REDUCE RISK OF RELAPSE IN PATIENTS WITH IMMUNE CHECKPOINT INHIBITOR ASSOCIATED HEPATOTOXICIT

Abstract Background Immune checkpoint inhibitors (ICI) have become the cornerstone of treatment of certain malignancies. However, they can result in systemic toxicities including hepatitis. Societal guidelines recommend initial management with high dose steroids, then a slow taper as hepatitis resolves. However, there is significant variation in steroid response with some patients experiencing a relapse of hepatitis as steroid doses are tapered (“steroid relapse”). Purpose Identify clinical features that predict relapse, and to explore variations in steroid management, in patients with ICI hepatotoxicity. Method Patients receiving ICI in early phase clinical trials at Princess Margaret Cancer Centre, or treated at the Toronto Centre for Liver Disease for ICI hepatotoxicity, were included. Patients with CTCAE Grade (G)3 ICI hepatotoxicity (ALT &amp;gt;5 x ULN) were identified and clinical records reviewed for management and outcomes. Patients with an alternate cause for ALT elevation; who did not receive corticosteroids; or with HCC or viral hepatitis, were excluded. Result(s) Between August 2012 and December 2021, 36 patients with G3 ICI hepatotoxicity were identified. Most (23; 64%) had metastatic melanoma. Thirteen received anti-CTLA-4/PD-1; 18 anti-PD-1 or anti-PD-L1, and 5 anti-CTLA-4 monotherapy. All patients initially received corticosteroids (1-2mg/kg/day methylprednisone equivalent). Thirteen patients (36%) were steroid relapsers. Consistent steroid response was seen in 18 (50%). Age, sex, liver metastases, prior ICI exposure, peak ALT or starting dose of steroids (≤1.5 vs &amp;gt;1.5mg/kg/day methylprednisolone equivalents) did not predict relapse, although relapsers were more likely to have been treated with combination anti-CTLA-4/PD-1 (7 (54%) relapsers, vs 3 (16%) responders, p = 0.02). Relapse occurred after a median of 14.5 days (range 8-111), and after taper to median 54% (5-100) of initial steroid dose. In responders, ALT normalisation occurred after median 14 days (range 3-56). In 27 patients where sufficient data were available, societal guidelines on ALT thresholds to initiate steroid taper were followed in 13 (48%; 6 relapsers and 7 responders). However, initiation of steroid taper was delayed in responders compared to relapsers (after median 7 days (2-15) in responders vs 4 days (range 2-9) in relapsers, p = 0.04). Overall, 5 relapsers responded to re-escalation of steroids. Eight required additional treatment with MMF, and 4 required 3rd line therapy with Tacrolimus. Ultimately, hepatitis resolved in all patients. Conclusion(s) In patients with ICI hepatotoxicity, combination ICI therapy confers a higher risk of steroid relapse than monotherapy. There is significant heterogeneity in management of steroid dosing in patients with ICI hepatotoxicity. Delayed initiation of steroid taper may be associated with a reduced risk of relapse and warrants prospective evaluation as part of a standardised management algorithm. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

P621 Combination treatment of biologics with immunomodulator increases risk of infection after discharge in biologics naive steroid refractory acute severe ulcerative colitis patient: A KASID multicenter study

Abstract Background Biologics such as infliximab is the main treatment for steroid refractory acute severe ulcerative colitis (ASUC), However, there are only a few studies on the effectiveness and safety of biologics in steroid refractory ASUC. In this study, we evaluated the effectiveness and safety of biologics as a rescue therapy for biologics naïve steroid refractory ASUC patient in Korea. Methods We retrospectively included patients who were hospitalized at seven tertiary medical centers for ASUC management between January 2015 to December 2020, and data on the demographic and clinical variables, disease activity, treatment method, treatment response, adverse event, readmission due to any reasons were checked Results A total of 230 ASUC patients were included, of which 220 were biologic naïve patient. The response rate of steroid in these patients was 74%, and infliximab was administered as rescue therapy to 53 patients who failed initial steroid treatment. The response rate to infliximab as rescue therapy was 96%, and 2 patients who did not respond received colectomy. One of the two patients who underwent colectomy died of sepsis. There was no infliximab-related adverse event during hospitalization. Although infliximab itself was not a factor associated with infection after discharge (10% vs. 16%, p=0.355), combination therapy with thiopurine was a risk factor for infection after discharge. (Odd ratio 7.302, 95% CI 2.101-25.372, p=0.002). A total of 12 infections occurred in patients treated with infliximab after discharge (3 pneumonia, 1 skin infection, 3 cytomegalovirus colitis, 4 Clostridium difficile infection) and were associated with readmission. (40.1% vs. 75%, p=0.031) Conclusion As a rescue therapy in biologics naive steroid refractory ASUC, infliximab showed a 96% therapeutic response. Although infliximab itself did not increase the risk of infection after discharge, the combination with thiopurine increased the risk of infection after discharge

Effects of a QI intervention on pediatric asthma treatment using patient outcomes and workflow in an emergency department

Objective Evaluate a nurse-initiated quality improvement (QI) intervention aimed at enhancing asthma treatment in a pediatric emergency department (ED), utilizing outcomes and workflow. Methods We evaluated the impact of QI interventions for pediatric patients presenting to the ED with asthma with pre-post analysis. A pediatric asthma score (PAS) of >8 indicated moderate to severe asthma. This secondary analysis of the electronic health record (EHR), evaluated on 1) patient outcomes (time to clinical treatment, ED length of stay [EDLOS], admissions and discharges home), 2) clinical workflow. Results We compared 886 visits occurring between 01/01/2015 and 09/27/2015 (pre-implementation period) with 752 visits between 01/01/2016 and 09/27/2016 (post-implementation). Time to first documentation of PAS was decreased post-intervention (p<.001) by >30 min (75 ± 57 to 39 ± 54 min). There were significant decreases in time to treatment with both steroid and bronchodilator administration (both p<.001). EDLOS did not significantly change. Based on acuity level, those discharged home from the ED with high acuity (PAS score ≥8), had a significant decrease in time to initial PAS, steroid and bronchodilator use and EDLOS. Of those with high acuity who were admitted to the hospital, there was a difference pre- to post-implementation, in time to first PAS (p<.05), but not to treatment. Workflow visualization provided additional insights and detailed (task level) comparisons of the timing of ED activities. Conclusions Nurse-initiated ED interventions, can significantly improve the timeliness of pediatric asthma evaluation and treatment. Examining workflow along with the outcomes, can better inform QI evaluations and clinical management.

Bilateral Extensive Syphilitic Punctate Inner Retinitis Triggering Macular Ischemia after Intravitreal Triamcinolone Injections

Purpose: To report a case of extensive syphilitic punctate inner retinitis (SPIR) triggering bilateral macular ischemia after intravitreal triamcinolone injections, and the multimodal retinal imaging findings.Case summary: A 69-year-old male patient with nonproliferative diabetic retinopathy was transferred to our hospital because of bilateral visual deterioration (to counting fingers) after the first intravitreal triamcinolone injection. Fundus examination revealed numerous yellow punctate precipitates in the superficial retinae, retinal arteriolitis, and vitritis. The punctate lesions and surrounding retinal regions showed decreased vascular density on optical coherence tomography angiography, and focal hypofluorescence on fluorescein angiography. The patient was positive for all of the Venereal Disease Research Laboratory test, the fluorescent treponemal antibody-absorption test, and &lt;i&gt;Treponema pallidum&lt;/i&gt; hemagglutination; we diagnosed bilateral SPIR. After treatment with aqueous crystalline penicillin solutions (24 million units per day for 14 days), the punctate lesions reduced but arteriolitis progressed to obliterative vasculitis. After 6 months, the bilateral SPIR and vitritis resolved, and the bilateral visual acuity improved to 20/100. However, inner retinal and macular ischemia persisted because of capillary nonperfusion attributable to obliterative vasculitis.Conclusions: Extensive SPIR can develop after an initial intravitreal steroid injection; the inner retinal ischemia and visual loss may persist after treatment because obliterative vasculitis develops. Therefore, patients scheduled for intravitreal steroid injections should be screened for syphilis infection.

The M-ANNHEIM-AiP-Activity-Score is useful for predicting relapse in patients with type 1 autoimmune pancreatitis

Background/ObjectivesProper assessment of disease activity and prediction of relapse are crucial for the management of autoimmune pancreatitis (AIP). The M-ANNHEIM-AiP-Activity-Score (MAAS) has been proposed to determine disease activity and predict relapse in German and Swedish patients with AIP. MAAS is calculated using six categories: pain report, pain control, exocrine insufficiency, endocrine insufficiency, imaging, and complications. This study aimed to clarify the usefulness of MAAS to predict relapse in Japanese patients with type 1 AIP. MethodsWe retrospectively analyzed 117 patients with type 1 AIP undergoing initial and maintenance steroid treatments at our institute between April 2006 and March 2021. AIP was diagnosed according to the Japanese Diagnostic Criteria for AIP 2018. We examined the association of MAAS with relapse during and after maintenance treatment. ResultsMAAS (median, 8 points) at the start of the initial treatment was reduced after treatment (median, 4 points; P < 0.001). A MAAS ≥11 points at the start of the initial treatment was associated with relapse. The initial treatment-induced reduction of MAAS<60% was more frequent in patients with relapse (75.0%) than in patients without relapse (37.6%; P = 0.007). MAAS at the start of maintenance treatment was higher for patients with relapse (median, 5 points) than that for patients without relapse (median, 4 points; P = 0.007). MAAS ≥4 points at the start of maintenance treatment was associated with subsequent relapse. ConclusionsMAAS is useful for predicting relapse in patients with type 1 AIP undergoing maintenance therapy.