Chronic Corticosteroid Therapy Research Articles

Influential Factors Affecting Intestinal Anastomotic Leakage and Their Predictive Significance

Background: The occurrence of anastomotic leakage following intestinal surgery stands as a significant contributor to postoperative complications and fatalities. This prospective study was conducted with the aim of assessing different factors associated with the risk of anastomotic leakage. Methods: This study was carried out within the Department of Surgery over the course of one year. It encompassed patients who underwent intestinal anastomosis, whether in emergency situations or as part of routine surgical procedures. The study encompassed a total of 150 patients. Results: Anastomotic leakage was identified in 18.02% of cases, with a higher incidence among males and individuals from a lower socioeconomic background. However, age, gender, and socioeconomic status were not found to be significant risk factors for anastomotic leakage. The incidence of leaks was elevated in patients with chronic illnesses such as malignancy, chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM), and those on chronic corticosteroid therapy. Additionally, malnourished patients and those with sepsis, as indicated by their blood investigation reports, had a notably higher leak rate. After conducting logistic regression analysis, several independent predictors for anastomotic leaks were identified, including peritonitis (\(p< 0.05;\) odds ratio \(2.156\)), bowel obstructions (\(p< 0.05\); odds ratio \(2.864\)), receiving more than 2 units of blood transfusion (\(p< 0.05\); odds ratio \(2.334\)), serum albumin levels \(< 3.0\) gm/dL (\(p< 0.001\); odds ratio \(8.873\)), corticosteroid therapy (\(p< 0.001\); odds ratio \(4.877\)), serum creatinine levels \(>1.2\) mg/dL (\(p< 0.001\); odds ratio 11.785), surgery duration exceeding 4 hours (\(p< 0.01\); odds ratio 3.0251), and ASA Grading (III & IV) (\(p< 0.01\); odds ratio 3.707). Conclusion: This study has successfully identified key risk factors that influence the occurrence of anastomotic leakage. The findings from this research are expected to be valuable in efforts to mitigate the incidence of anastomotic leakage following surgery.

Abstract 17159: Chronic Corticosteroid Immunosuppression in African American Pediatric Heart Transplant Recipients Does Not Improve Outcomes

Introduction: Previous studies consistently demonstrate worse outcomes for African American (AA) pediatric heart transplant (HT) recipients when compared to non-AA counterparts. Medical and social factors have been implicated in this discrepancy. As such, chronic corticosteroid use as maintenance immunosuppression for AA HT patients may be beneficial, though this has not been studied. Hypothesis: Chronic maintenance corticosteroid therapy does not decrease rejection or graft failure in AA pediatric HT recipients. Methods: We performed a retrospective analysis of the Pediatric Heart Transplant Society (PHTS) database for all HT recipients <18 y.o. from January 1 st , 2007 to June 30 th , 2021. Retransplants and multiorgan transplants were excluded. Chronic steroid use was defined as taking oral steroids at one-year post-HT in the absence of rejection past 60 days post-HT to exclude patients who were on steroids for-cause. We used Kaplan-Meier and log-rank analyses for outcome comparisons among cohorts after the first year post-HT. Results: A total of 4099 patients were included, of which 780 (19%) were AA. Of the cohort, 756 (18.4%) were on chronic steroids. Within that group, 157 (20.1%) were AA. Patients on chronic steroids at individual centers ranged 0%-64.7% (median 11.5%, SD 16.9%), with no collective difference between steroid use in AA and non-AA patients. Freedom from rejection was worse in AA compared to non-AA patients, both in steroid and no steroid groups (p<0.01). In the non-AA cohort, freedom from rejection was better in the no steroid group (p<0.01). In the AA cohort, there was no statistical difference in rejection between the steroid and no steroid groups (p=0.20). Analyses of graft survival resulted in the same pattern. Conclusion: Use of Chronic steroids varies widely across pediatric HT centers, with no difference between AA and non-AA patients. AA patients have worse rejection and graft failure, and chronic steroid use did not affect these outcomes.

Corticosteroid Use and Adherence in Patients Treated with Acthar Gel for Advanced Sarcoidosis.

Long-term corticosteroid use in immune-mediated diseases is associated with increased risk of adverse events (AEs) and worsened health-related quality of life (HRQoL). Previous studies report chronic high-dose corticosteroid therapy results in higher rates of healthcare resource use and AE-related medical costs. Recent studies suggest Acthar® Gel (repository corticotropin injection) is an effective steroid-sparing therapy for sarcoidosis. This study compares the corticosteroid-sparing effect between Acthar Gel and comparators and evaluates the impact of Acthar Gel adherence on reduction of corticosteroid burden. A retrospective analysis of a large administrative pharmacy and medical claims database (Symphony Health Solutions) was conducted. Patients were included with confirmed ICD-9/10 diagnosis for sarcoidosis in the study period (2014-2020), followed by ≥ 2 Acthar Gel claims or comparators (janus kinase inhibitor (JAKi)/rituximab), ≥ 18years old, with 12months coverage pre/post index. Outcomes were compared as change from baseline. Acthar Gel adherence was determined by proportion of days covered in the follow-up period. The Acthar Gel (n = 735) and comparator (n = 626) cohorts were mostly female (68-72%) between 55 and 58years old. Compared to the comparator cohort at baseline, Acthar Gel patients had greater any corticosteroid use (80% vs. 56%, p < 0.001), extended use (61% vs. 32%, p < 0.001), and mean average daily dose (6.72 vs. 3.03, p < 0.001). After treatment, Acthar Gel patients had greater reduction from baseline in any corticosteroid use (-9.0% vs. -3.2%) and extended use (-10.0% vs. -3.0%). In the Acthar Gel adherence cohorts, patients with above average adherence had greater reduction in both measures (-11.2% vs. -6.1%; -11.6% vs. -7.6%, respectively) than patients with below average adherence. Acthar Gel patients had greater reduction of extended use at all dose levels. Acthar Gel is associated with reductions in corticosteroid use compared to alternatives. Better adherence is associated with greater reduction in corticosteroid exposure. Key Summary Points.

FTP6.4 Management and Outcomes of Acute Diverticulitis in Immunosuppressed Patients

Abstract Aims Previous studies have suggested that immunosuppressed patients with acute diverticulitis are at high risk of failing conservative management and many will require urgent surgical intervention. Some series have shown mortality rates as high as 39% and 56% with medical and surgical management respectively. The aim of this study was to analyse the management and outcomes of immunosuppressed patients presenting with acute diverticulitis. Methods Data were collected on patients admitted as an emergency with acute diverticulitis over a 2-year period (1st January 2018 to 31st December 2019). Immunosuppressed patients were identified and divided into 5 groups according to the cause: group 1, chronic corticosteroid use; group 2, transplant patients; group 3, malignant neoplasm; group 4 chronic kidney disease; group 5, other immunosuppressant treatments. Outcomes were recorded. Results Sixty-one patients with immunosuppression were admitted with acute diverticulitis. The number of patients in groups 1-5 were 23, 2, 11, 16 and 9 respectively. Fifty-one patients (83.6%) had a CT during their admission and thirteen (21.3%) presented with complicated diverticulitis. Two patients (3.3%) underwent emergency surgery, both of whom were on chronic corticosteroid therapy and were alive at 1-year post-op. All fifty-nine patients (96.7%) managed conservatively survived admission. Conclusions This study has shown a lower rate of emergency surgery than previously observed and lower mortality with both medical and surgical management. Conservative management appears to be safe for the majority of immunosuppressed patients with acute diverticulitis.

Primary antibody deficiencies represent an underestimated comorbidity in asthma patients: efficacy of immunoglobulin replacement therapy in asthma control

Objective Primary antibody deficiencies (PAD) are an underestimated comorbidity in asthma and its treatment could improve disease control. Methods a retrospective cohort of asthmatics, affected by IgG subclass deficiency or unclassified antibody deficiency and treated with low-dose intravenous immunoglobulin replacement therapy (IRT) was recruited. Demographic and clinical data, chest CT scan, blood eosinophils, atopy, chronic oral corticosteroid (OCS) therapy were evaluated at baseline. Asthma exacerbations, lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI) and asthma-related hospitalizations were assessed after one and two years of IRT. Results 57 moderate-to-severe asthmatics were enrolled, mostly affected by T2 low asthma (39/57, 68.4%). After one year, IRT was effective in improving, irrespective of bronchiectasis, atopy, eosinophils and PAD type: 1) trough IgG (826.9 ± 221.3 vs 942.2 ± 195.1 mg/dl; p < 0.0001) and IgG subclasses (IgG1 355.4 ± 88.4 vs 466.7 ± 122.3, p < 0.0001; IgG2 300.1 ± 130.1 vs 347.6 ± 117.3, p < 0.0005) serum levels. 2) asthma exacerbations (6.4 ± 4.1 vs 2.4 ± 1.9, p < 0.0001), LRTI (4.3 ± 3.9 vs 1.3 ± 1.5, p < 0.0001) and hospitalization rate (0.26 ± 0.7 vs 0.05 ± 0.2, p < 0.01). These results persisted after 2 years of therapy. Estimated mean cumulative OCS exposure was reduced by 4500 mg over the 2-year period. Conclusions low-dose IRT is effective in improving asthma control and lessening OCS burden in asthmatics affected by PAD.

Steroid Sparing Immunosuppression in Management of Cardiac Sarcoidosis: A Systematic Review

• There is a lack of high-quality evidence for drug-modifying anti-sarcoidosis drugs (DMASD) in management of cardiac sarcoidosis. • Methotrexate is the most commonly used DMASD, followed by mycophenolate mofetil and azathioprine. • Tumour necrosis factor-α inhibitors use has primarily been described for refractory cardiac sarcoidosis. • Randomized controlled trials are needed to assess the efficacy of DMASDs in long-term management of cardiac sarcoidosis. Cardiac sarcoidosis (CS) is frequently treated with corticosteroids. However, given the complications associated with chronic corticosteroid therapy, disease modifying anti-sarcoidosis drugs (DMASDs) are frequently prescribed. We conducted a systematic review to evaluate use of DMASDs in CS. We conducted a systematic review of Cochrane Central Register of Controlled Trials, and Ovid (MEDLINE and EMBASE). We included randomized controlled trials, clinical trials, and cohort studies examining outcomes in patients with CS managed with DMASDs. Two authors independently used predetermined criteria to perform initial screening, full text screening, and risk of bias assessment. Due to heterogeneity in study design and outcomes we summarized the data without meta-analysis. Sixteen studies met our inclusion criteria. Fifteen papers were retrospective cohort studies and one was an open label comparative study. Studies had at least moderate risk of bias in all domains. The most commonly described DMASD was methotrexate (MTX). Most studies reported improvement or lack of disease progression with DMASDs. The most commonly reported side effects were infection and hepatotoxicity. Although DMASDs are frequently prescribed for CS, there is no high-quality evidence to support this practice. Multi-center randomized trials are warranted to evaluate the efficacy of different immunosuppression strategies.

Chronic systemic corticosteroid therapy influences the development of pulp necrosis and experimental apical periodontitis, exacerbating the inflammatory process and bone resorption in rats.

The main aim of the study was to evaluate the inflammatory response and development of apical periodontitis in rats chronically treated with glucocorticoids. Male Wistar rats (Rattus novergicus) were randomly divided into two groups: the experimental group, which was treated with prednisone (5mg/kg/day) and a control group, which was administered saline solution for 30days before induction of apical periodontitis, continuing until the day of euthanasia days 0, 7, 14 and 28 after injury induction. The mandibles were subjected to histological evaluation to determine the size of the lesion, was also performed for the presence and absence of pulp necrosis, bone resorption and micro abscesses, and histomorphometric analyses were performed based on the number of polymorphonuclear cells and mononuclear cells. Histochemical analysis was also performed to assess the percentage of collagen fibres and their typification, in addition to immunohistochemistry for the inflammatory markers interleukin IL-1β, IL-6, TNF-α and TRAP. Despite after 7days, there was no differences between groups, a significant increase in the root pulp necrosis (p=.001), micro-abscesses (p=.026) and the size of the apical lesion on the 14th day of treatment with prednisone (p=.008). On the same day, there was also an increase in the number of polymorphonuclear cells (p=.042) and cells immunostained for IL-1β (p=.006), IL-6 (p<.001) and TRAP (p=.002) in animals treated with prednisone. The numbers of mononuclear cells also increase in 28days (p=.025) and TNF-α ± increases in the prednisone group on the 7th day (p=.041). The prednisone group also showed a decrease in collagen after 14 (both type I [p=.041] and type III [p=.046]) and 28 type III (p=.002) days after the coronary opening. The glucocorticoids modified the development of experimental apical periodontitis induced in rats, causing an early increase in periapical bone resorption and pulp necrosis. These effects are associated with alterations in cytokine levels, in the inflammatory response and in collagen deposition, in the 14th day after injury induction.

Influence of chronic use of corticosteroids and calcineurin inhibitors on COVID-19 clinical outcomes: analysis of a nationwide registry

ObjectivesThe aim of this study was to analyze whether subgroups of immunosuppressive (IS) medications conferred different outcomes in COVID-19.MethodsThe study involved a multicenter retrospective cohort of consecutive immunosuppressed patients (ISPs) hospitalized with COVID-19 from March to July, 2020. The primary outcome was in-hospital mortality. A propensity score-matched (PSM) model comparing ISP and non-ISP was planned, as well as specific PSM models comparing individual IS medications associated with mortality.ResultsOut of 16 647 patients, 868 (5.2%) were on chronic IS therapy prior to admission and were considered ISPs. In the PSM model, ISPs had greater in-hospital mortality (OR 1.25, 95% CI 0.99–1.62), which was related to a worse outcome associated with chronic corticoids (OR 1.89, 95% CI 1.43–2.49). Other IS drugs had no repercussions with regard to mortality risk (including calcineurin inhibitors (CNI); OR 1.19, 95% CI 0.65–2.20). In the pre-planned specific PSM model involving patients on chronic IS treatment before admission, corticosteroids were associated with an increased risk of mortality (OR 2.34, 95% CI 1.43–3.82).ConclusionsChronic IS therapies comprise a heterogeneous group of drugs with different risk profiles for severe COVID-19 and death. Chronic systemic corticosteroid therapy is associated with increased mortality. On the contrary, CNI and other IS treatments prior to admission do not seem to convey different outcomes.

Nutritional Supplements, Ginseng and Leucine, Increase Erythropoiesis in Diamond Blackfan Anemia Models through Inhibition of Nemo-like Kinase

Diamond Blackfan Anemia (DBA) is an inherited bone marrow failure syndrome that is typically associated with mutations in one of at least 20 ribosomal genes and is associated with anemia, congenital abnormalities, and cancer predisposition. The current treatment for DBA is associated with toxicities including iron overload from repeated transfusions, immune suppression from chronic corticosteroid therapy or consequences from stem cell transplantation. Developing new therapies for DBA remains a challenge, since it is a rare disease and the connection between faulty ribosomes and defects in erythropoiesis is still being explored. As such, repurposing existing, approved drugs is one approach to find new ways to treat this disease.We recently identified that Nemo-like Kinase (NLK) is hyper-activated and contributes to disease pathogenesis in the erythroid progenitors of patients with DBA, irrespective of the genetic mutation. NLK is an atypical member of the MAPK family of kinases. Due to a high degree of conservation, kinase inhibitors that specifically target NLK are not currently available, although several small molecules inhibit NLK as an off-target. We are actively pursuing a number of these compounds as potential therapies for DBA. In addition to known kinase inhibitors, we have examined the active components of widely available nutritional supplements. Although rigorous clinical evaluation is required, these supplements are well tolerated and offer an alternative or a complement to conventional drug therapy for DBA.Ginsenoside Rb1, an active component of ginseng, increases erythropoiesis in in vitro models of DBA (2.6-fold) at 50mM (p=0.048) with an EC 50 of 2.3mM. Importantly, ginsenoside Rb1 does not impact healthy erythropoiesis or other hematopoietic lineages and is nontoxic to normal cells. Our results demonstrate that ginsenoside Rb1 does not inhibit NLK kinase activity directly, but rather induces a microRNA (miR-208) that binds to NLK mRNA leading to degradation of transcript by 35.9% (p=0.007) before the protein can be translated.Another nutritional supplement that has been indicated to improve erythropoiesis (in DBA and non-diseased models) and is currently in clinical trials is the amino acid leucine. In DBA progenitors, 5mM leucine increases erythropoiesis from 8.8 to 16.3% of healthy controls. Leucine acts by stimulating the activity of mTORC1 but similar to erythropoiesis, mTORC1 activity is only stimulated from 26.4 to 57.2% of controls in DBA progenitors.Our results demonstrate that leucine does not impact NLK expression or activity directly. Aberrantly activated NLK phosphorylates and inhibits the activation of mTORC1 (target of leucine). The suppression of NLK by 50mM ginsenoside Rb1 restored mTORC1 activity to basal (94.7% of non-diseased control) but also restored leucine sensitivity (from 57.2 to 88.1% of non-diseased controls). Importantly, combining 5mM leucine and 50mM ginsenoside Rb1 increased erythropoiesis from 1.9-fold and 2.6-fold when used alone, to 8.9-fold (or 78.3% of healthy controls) together in our in vitro models of DBA (CI=0.31).Ginseng and leucine offer promising alternatives to steroids and other immunosuppressive drugs for DBA patients. The goal of these studies is to raise the hemoglobin in DBA patients to avoid the need for red cell transfusions. As nutritional supplements are widely available and well tolerated, this class of compounds provides alternatives to currently approved drugs to treat DBA. DisclosuresGlader: Agios: Consultancy.

Comparison of the impact of chronic corticosteroid therapy on critical care outcomes of COVID-19 patients with and without history of chronic liver disease

There is a paucity of studies investigating the impact of chronic corticosteroid use for coexisting conditions in patients with Coronavirus Disease 2019 (COVID-19). Additionally, the information regarding the impact of chronic liver disease (CLD) on COVID-19 outcomes is evolving. Our study aims to investigate hospitalization outcomes of patients with COVID-19 on long term corticosteroids for coexisting conditions while also seeking to compare outcomes between such patients with a history of CLD to analyze the impact on mortality. We conducted a retrospective chart review across our 10-hospital network identifying patients on chronic corticosteroids (Prednisone ≥ 5 mg daily dose or equivalent dose of another steroid, for a duration of 30 days or more) who were hospitalized with COVID-19 from March 1, 2020 to June 30, 2020. Of these patients who met inclusion criteria, patients were then divided into groups based upon their history of CLD. Primary outcomes of the study looked to investigate the hospitalization outcomes of patients with a history of CLD and comorbid conditions requiring chronic corticosteroid use. Secondary outcomes sought to further investigate risk factors for mortality in our study sample. 837 charts were reviewed. 139 patients met inclusion criteria of which 34 patients had a history of CLD. Statistical analysis demonstrated no difference in length of hospital stay but increased ICU admission rate in the CLD group (41.2% vs 23.8%). No statistically significant difference was seen in between the CLD and non-CLD groups in term of complication rates and 28-day mortality. However, chronic corticosteroids patients were found to have higher rates of ICU admission and overall 28-day and ICU mortality in comparison to patients who were not on chronic corticosteroids prior to COVID-19 hospitalization. The larger contributor to COVID-19 severity was likely chronic corticosteroid use rather than CLD and thus chronic corticosteroid use should be limited throughout the COVID-19 pandemic especially in patients with additional speculated risk factors for COVID-19 such as CLD.

Clinical case of preiser disease, bilateral femoral head and humeral head osteonecrosis associated with chronic corticosteroid therapy

Osteonecrosis is a pathologic process that is associated with numerous conditions and therapeutic interventions. Most commonly the hip is involved but almost any bone can develop osteonecrosis. It can occur in the femoral head, but also affect the femoral condyles, humeral heads, proximal tibia, vertebrae, and small bones of the hand and foot. The most frequent etiological factors are trauma, alcoholism, and chronic corticosteroid therapy; the latter causing the most devastating form of osteonecrosis. Glucocorticoid-induced osteonecrosis is a known toxicity in pediatric and young adult patients treated for Acute Lymphoblastic Leukemia (ALL) and Non-Hodgkin Lymphoma (NHL). Osteonecrosis of the shoulders and weight-bearing joints of the lower extremities has emerged as a major adverse effect of modern ALL therapy. Pain in the absence of activity (ie, rest pain) occurs in approximately two-thirds of patients, and nocturnal pain occurs in one-third. MRI continues to be the gold standard for diagnosis in symptomatic and asymptomatic patients, especially in early-stage disease. Respectively to Preiser disease, this condition is a rare disease of unknown etiology characterized by Avascular Necrosis (AVN), also known as osteonecrosis, of the scaphoid bone and the clinical manifestations include insidious and progressive pain lasting from months to years, edema, loss of strength and reduced range of motion in the wrist. The treatment of non-traumatic osteonecrosis remains one of the most controversial subjects in the orthopedic literature. The purpose of this case report is to bring to attention osteonecrosis as a potential side effect of corticosteroid use in the pediatric population, as a delayed or missed diagnosis can lead to several joints destruction.

Utilization of chronic lung disease treatment before the respiratory syncytial virus season as palivizumab prophylaxis qualifier in the American Academy of Pediatrics Guidelines.

Guidelines from the American Academy of Pediatrics recommend palivizumab immunoprophylaxis for children with CLD in their second year of life if they continue to need treatment within 6 months before the RSV season. The utilization patterns of treatment (chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) are not well understood. We examined variations in CLD treatment for ten consecutive 20-day segments preceding RSV season onset. Among infants and children with CLD (n = 19,026), 35.2% received one or more medical treatments for CLD any time within 200 days before entering the second RSV season: 8.6%, 3.2%, and 29.7% received supplemental oxygen, diuretics, and corticosteroids, respectively. Utilization decreased as infants’ age increased with corticosteroids surpassing oxygen and diuretics. To avoid the capture of intermittent use of corticosteroids for acute infections, we found requiring a minimum of 45 days cumulative exposure was reasonable to determine chronic use. What is Known:• Guidelines from the American Academy of Pediatrics recommend palivizumab immunoprophylaxis for children with CLD in their second year of life if they continue to need treatment within 6 months before the RSV season.• The utilization patterns of treatment (chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) are not well understood. A definition of chronic corticosteroid therapy in this setting is not available.What is New:• Among infants and children with CLD of prematurity, 35.2% received one or more medical treatments for CLD any time within 200 days before entering the second RSV season: 8.6%, 3.2%, and 29.7% received oxygen, diuretics, and corticosteroids, respectively. Utilization decreased as infants’ age increased with corticosteroids surpassing oxygen and diuretics.• A minimum of 45 days cumulative corticosteroid use within the past 90 days would accurately capture chronic use to fulfill criteria for immunoprophylaxis while limiting the inclusion of intermittent use of corticosteroids for acute infections.

Clinical and peculiar immunological manifestations of SARS-CoV-2 infection in systemic lupus erythematosus patients.

ObjectivesThe impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with systemic lupus erythematosus (SLE) remains unclear and data on clinical manifestations after infection are lacking. The aim of this multicentre study is to describe the effect of SARS-CoV-2 in SLE patients.MethodsSLE patients referring to 4 Italian centres were monitored between February 2020 and March 2021. All patients with SARS-CoV-2 infection were included. Disease characteristics, treatment, disease activity, and SARS-CoV-2 related symptoms were recorded before and after the infection.ResultsFifty-one (6.14%) SLE patients were included among 830 regularly followed-up. Nine (17.6%) had an asymptomatic infection. Five (9.8%), out of 42 (82.6%) symptomatic, developed interstitial pneumonia (no identified risk factor). The presence of SLE major organ involvement (particularly renal involvement) was associated with asymptomatic SARS-CoV-2 infection (p-value = 0.02). Chronic corticosteroid therapy was found to be associated with asymptomatic infection (p-value = 0.018). Three SLE flares (5.9%) were developed after SARS-CoV-2 infection: one of them was characterized by MPO-ANCA positive pauci-immune crescentic necrotizing glomerulonephritis and granulomatous pneumonia.ConclusionsSARS-CoV-2 infection determined autoimmune flares in a small number of our patients. Our data seem to confirm that there was not an increased risk of SARS-CoV-2 in SLE. Patients with asymptomatic SARS-CoV-2 infections were those having major SLE organ involvement. This may be explained by the high doses of corticosteroids and immunosuppressive agents used for SLE treatment.

Clinical evolution of a severe asthmatics group in the use of immunobiological therapy in a Brazilian Public Hospital.

A small portion of the asthmatic population (3.6%) has severe asthma (SA), presenting high morbimortality rates and demanding more financial resources than other asthmatic populations. The use of immunobiological therapy is an effective tool in controlling symptoms, decreasing the number of exacerbations, and reducing the use of systemic corticosteroids in these patients. In Brazil, epidemiological data regarding this asthmatic population using immunobiologicals and their evolution are scarce. This is an observational, analytical, cross-sectional, and retrospective study. The sample consisted of adult patients with SA in follow-up at the pulmonology service of the Complexo Hospital de Clínicas of the Federal University of Paraná, from January 2011 to August 2019. The analyzed variables were as follows: the number of exacerbations that required hospitalization in the previous year, forced expiratory volume in one second (FEV1), and asthma control test (ACT) scores before and after the start of immunobiological therapy. We studied 20 patients with SA using omalizumab or mepolizumab. We observed an increase in the mean ACT score of 4.8 points, a nonsignificant reduction in the number of exacerbations that required hospitalization, and a slight improvement in the FEV1. Regarding the patients using chronic systemic corticosteroid therapy, 14.2% (n=1) of patients had the medication discontinued and 57% (n=4) of patients had the dose reduced by half. The use of omalizumab and mepolizumab as additional therapy in SA provided a significant improvement in the ACT and allowed the dose reduction of systemic corticosteroids, without significant improvement in FEV1 and in the frequency of severe exacerbations.

Do Short Oral Corticosteroid Bursts Have Adverse Effects

Unlike with chronic corticosteroid therapy, short bursts of oral corticosteroids in children have not been associated with adverse effects, but few

POS-130 EXPERIENCE WITH LEVAMISOLE IN CHILDREN WITH FREQUENTLY RELAPSING AND STEROID DEPENDENT NEPHROTIC SYNDROME HAVING FOLLOW UP AT TIKUR ANBESSA SPECIALIZED HOSPITAL, ADDIS ABABA, ETHIOPIA

Nephrotic syndrome is characterized by nephrotic range proteinuria, and hypoalbuminemia,most commonly associated with hyperlipidemia and edema. Without treatment,nephrotic syndrome in children is associated with high risk of death,most commonly from infections. Corticosteroids are the treatment of choice for idiopathic nephrotic syndrome (INS). Although about 80-90% of children with INS respond to corticosteroids, 20-30% become steroid dependent. Chronic corticosteroid therapy in patients with steroid dependent or frequently relapsing NS (FRNS or SDNS) is associated with numerous side effects. Levamisole is an anti helminthic agent with immunomodulatory effect. Levamisole has been considered the least toxic and least expensive steroid sparing drug for preventing relapses of steroid sensitive idiopathic nephrotic syndrome (SSINS). Though FDA doesn’t approve it for this purpose many researches done so far have shown that Levamisole is effective in treatment of children with FR/SDNS. We are using Levamisole in our Hospital but we have no data supporting or negating the use of levamisole as a good choice for treatment of children with SDNS/ FRNS to date. To determine the outcome of pediatric FR/SDNS treated with levamisole among children who had follow up at TASH pedaitric renal clinic. Methods: Retrospective cohort study on clinical records of patients with FR/SDNS having follow up at Tikur Anbessa Specialized Hospital from January 2016 to January 2019 . Charts of 80 patients reviewed and using exclusion criteria 33 patients were excluded from the study. Patient charts were retrieved using patients MRN and type of their disease from registration book at pediatrics renal clinic having follow up at our Hospital during the study period .The collected data was cleaned, Coded and analyzed using SPSS Version 25. Inclusion and Exclusion Criteria: Inclusion criteria: All patients who had FR/SD idiopathic nephrotic syndrome age between 1yr and 18 years attending follow up at TASH pediatric renal clinic. Exclusion criteria: All patients with steroid resistant nephrotic syndrome. All patients of Congenital or Infantile nephrotic syndrome. All patients with CKD. Nephrotic syndrome secondary to systemic illness Among 47 patients with FR/SDNS 32 were males and 15 were females, 21 (44.5%) were FRNS and 26 (55.5%) were SDNS. The duration of Nephrotic Syndrome was 8.75 3.7 yrs, the number of relapses before Levamisole treatment was 3, relapse after Levamisole was 0.7. The duration of Levamisole treatment was 19.9 during levamisole treatment. Levamisole is associated with significant reduction in relapses of FRNS/SDNS.It also significantly reduces adverse effects associated with corticosteroid treatment. The medication is not available in hospital pharmacies and treating those patients who have indications is difficult and the drug should be available at Hospital pharmacies.

Non-steroidal anti-inflammatory drugs (NSAIDs) – exacerbated respiratory disease: epidemiology, pathogenesis, clinical findings and management

Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) are characterized by non-allergic hypersensitivity (intolerance) to NSAIDs and aspirin in patients with asthma and/or eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP). Asthma in N-ERD patients is usually characterized by eosinophilic inflammation, tends to become severe and intractable, and needs chronic oral corticosteroid therapy. For some patients recurrent CSwNP is more significant problem due to nasal congestion, anosmia, and multiple repeated surgeries. Intolerance to aspirin and other NSAIDs limits the choice of pain relievers and antipyretics. Accidental use of these medications can lead to dangerous consequences, including anaphylaxis. This review presents the current understanding of the N-ERD pathogenesis and perspective trends in therapy.

S3455 Non-Survivable GI Bleed in a Patient on Chronic Steroid Therapy

INTRODUCTION: Steroid therapy has been established as a risk factor for peptic ulcer disease. (1) Chronic corticosteroid therapy also suppresses the hypothalamic pituitary adrenal (HPA) axis. We present a case of rapid deterioration of a patient who developed a GI bleed (GIB) on chronic steroid therapy. CASE DESCRIPTION/METHODS: A 68 year-old African-American male with a past medical history of a CVA with residual left-sided weakness and dysarthria, HTN, spinal stenosis and hemolytic anemia presented with dysarthria and right-sided weakness. Due to his autoimmune hemolytic anemia, months prior, he was started on a 1mg/kg dose of prednisone with plans for a long taper (65mg daily). He had been admitted to inpatient rehabilitation after undergoing laminectomy when a rapid response was called due to hypotension. No GIB was reported by bedside nursing, and his pressure normalized initially after IV fluid boluses. Another rapid response was called shortly afterwards, again for hypotension, and the patient was transferred to the general medicine wards. An episode of hematemesis was reported. His hemoglobin was 7.6 mg/dL from his baseline of 9.8. He was transfused 1 unit of pRBCs, and GI was consulted for presumed UGIB. DAPT and prednisone were discontinued and IV PPI was initiated. Upon arrival to general medicine wards, he was profoundly hypotensive and was immediately transferred to the ICU on pressors. In the ICU he was intubated for airway protection. Prior to attempting an EGD, he developed monomorphic V tach, and the procedure was aborted. Now on amiodarone, he continued to require increasing vasopressors. He received 12 units of whole blood, 6 units pRBCs, 1 pool platelets, and 2 units FFP. Despite the large volume resuscitation efforts and vasopressors, the patient remained hypotensive with minimal overt GI bleeding. Massive upper GI bleed with perforation and intra-peritoneal bleeding was suspected. Shortly after, the patient expired. Post-mortem examination showed minimal blood in the GI tract and limited blood in the peritoneal cavity without significant lesion or ulceration of the GI tract. The cause of death was listed as hemorrhagic shock. DISCUSSION: Along with added risk of GIB, corticosteroids cause relative adrenal insufficiency. Stress dose replacement therapy should be considered in hypotensive patients even with suspected GI bleeding.

Invasive Pulmonary Aspergillosis in Chronic Obstructive Pulmonary Disease Exacerbations.

Nowadays, reports in the literature support that patients with severe chronic obstructive pulmonary disease (COPD) are at higher risk to develop invasive pulmonary aspergillosis (IPA). However, the interpretation of Aspergillus-positive cultures from the airways in critically ill COPD is still a challenge. Indeed, as the patient could be merely colonized, tissue samples are required to ascertain IPA diagnosis but they are rarely obtained before death. Consequently, diagnosis is often only suspected on the basis of a combination of three elements: clinical characteristics, radiological images (mostly thoracic CT scan), and microbiological, and occasionally serological, results. To facilitate the analysis of these data, several algorithms have been developed, and the best effectiveness has been demonstrated by the Clinical algorithm. This is of importance as IPA prognosis in these patients remains presently very poor and using such an algorithm could promote prompter diagnosis, early initiation of treatment, and subsequently improved outcome.While the most classical presentation of IPA in critically ill COPD patients features a combination of obstructive respiratory failure, antibiotic-resistant pneumonia, recent or chronic corticosteroid therapy, and positive Aspergillus cultures from the lower respiratory tract, the present article will also address less typical presentations and discuss the most appropriate treatments which could alter prognosis.

Progressive myelopathy associated with spinal epidural lipomatosis in three non-obese patients with type 1 diabetes mellitus

BackgroundSpinal epidural lipomatosis (SEL) is a rare condition defined as pathological overgrowth of the normally present epidural fat within the spinal canal. SEL is associated with Cushing disease, obesity and chronic corticosteroid therapy. Diabetes mellitus type 1 (DM1) has not known to be a risk factor for SEL. The neurological symptoms of SEL are attributed mainly to mechanical compression on the spinal cord and the cauda equina. MethodsA retrospective chart review of patients evaluated at NYU Multiple Sclerosis Care Center identified three diabetic patients with progressive myelopathy associated with SEL. We report the clinical course, diagnostic workup and outcomes in these three patients with SEL-associated myelopathy. ResultsThree patients (2 females and 1 male) had long-standing DM1 and developed progressive myelopathy in their early 40's. All were found to have thoracic SEL (extensive extradural T1, T2 hyperintense signal; biopsy confirmed in one case) with associated extensive abnormal cord signal in lower cervical/upper thoracic spinal cord. A comprehensive evaluation for metabolic, infectious, autoimmune and vascular causes of myelopathy that included serologies, cerebrospinal fluid analyses, and spinal angiography did not reveal an alternative cause for myelopathy. One of the patients underwent a surgical decompression of SEL with subsequent clinical and radiologic improvement. ConclusionsOur case series suggest that patients with DM1 and myelopathy of unknown cause should be evaluated for SEL. Timely diagnosis and appropriate intervention may forestall progression of neurological disability and even result in neurologic improvement. SEL should be considered on the short list of diagnoses that cause potentially reversible progressive myelopathy.