Initial Steroid Research Articles

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

BackgroundSystemic steroid therapies for Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have been challenged because of their limited benefits. Whether additional tumor necrosis factor (TNF) α inhibition provides an optimized approach remains unexplored. ObjectiveTo investigate the efficacy of TNF-α inhibition combined with a steroid to treat SJS/TEN and to identify potential biomarkers. MethodsTwenty-five patients with SJS/TEN were recruited and divided into 2 groups: 10 patients received methylprednisolone and 15 patients received etanercept plus methylprednisolone. Serum levels of granzyme B, perforin, interferon-γ, interleukin (IL) 6, IL-15, IL-18, macrophage inflammatory protein 1α, macrophage inflammatory protein 1β, and TNF-α were measured by multiplex cytokine analysis kits during the acute and resolution phases. ResultsCompared with the steroid monotherapy, the combination therapy significantly shortened the course of the initial steroid treatment and the duration of the acute stage, hospitalization stay, and skin re-epithelialization. Although both therapies significantly reduced IL-15 levels; the combination therapy also decreased IL-6 and IL-18 levels. While the level of IL-15 was positively correlated with skin re-epithelialization time in both groups, the level of IL-6 served as an additional marker for the course of the disease in the combination therapy group. LimitationsThe cohort size is relatively small. ConclusionAdditional TNF-α inhibition to steroid treatment appeared to improve outcomes for SJS/TEN.

P319 Incorporating HLADQA1*05 in pre-biologic screening in IBD patients initiating biologic therapies

Abstract Background The PANTS study reported high risk of immunogenicity and loss of response in anti Tumor Necrosis Factor (anti-TNFs) treated Crohn’s disease (CD) patients carrying HLADQA1*05 allele. The proposed biomarker stratified trial to evaluate the usefulness of HLA testing prior to initiation of anti-TNFs is not yet available. We aimed to evaluate the use of HLADQA1*05 as part of pre-biologic screening in IBD patients initiating biologics on MDT decision on drug choice and disease outcomes Methods We prospectively included all IBD patients who had HLADQA1*05 tested prior to initiation of biologics over a period of, 12 months. Patients with definitive indication for one class of drug or drug strategy (perianal fistula, acute severe colitis, contraindications to infliximab, co-existent EIMs) were excluded. Primary outcome was treatment persistence at, 6 and, 12 months. Secondary outcomes were steroid free remission at, 6 and, 12 months, use concomitant immunosuppression and proportion needing dose escalation. Results Seventy-six patients were included in analysis (UC=, 32, CD=43, IBD-U =1). HLADQA1*05 was positive in, 46.7% of patients. The therapy class choice was as recorded in figure 1. Concomitant immunosuppression was used in, 44% of the whole cohort and in, 100% of HLADQA1*05 positive patients started on anti-TNF agents. Primary non-response was recorded in, 8 patients and secondary loss of response in, 3 patients. Among patients started on anti-TNFs, anti-drug antibodies were detected in, 10 (15.6%) patients with, 7 out of, 10 positive for HLADQA1*05. However, only, 3 (4.6%) had undetectable drug levels in the presence of antibody and all three were HLADQA1*05 positive. Two patients had reactions during induction therapy both were HLADQA1*05 positive and were on combination therapy with Infliximab. Therapy persistence with initial drug strategy and steroid free remission at, 6 months was recorded in, 77.1% and, 78% respectively. There was no significant difference in drug persistence rates at, 6 months and, 12 months in patients with HLADQA1*05 variant or those with variant absent (Figure, 2). Steroid free remission at, 6 and, 12 months was also similar irrespective of the variant status (Figure 3) Conclusion Choice of therapy incorporating HLADQA1*05 status may allow anti-TNF monotherapy and tailoring of therapy in IBD patients. A randomised stratified biomarker trial is required to determine the utility of pre-treatment testing.

Salvage intratympanic steroid therapy for sudden sensorineural hearing loss: our real-life experience in 32 patients

To examine the role of salvage intratympanic steroid injections in patients presenting with idiopathic sudden sensorineural hearing loss following a poor response to initial oral steroid treatment. A retrospective analysis of patient records over the course of four years was conducted, and pure tone thresholds were reviewed before treatment, after oral steroid therapy and six weeks after intratympanic steroid injection therapy. After oral steroid therapy alone, there was a mean average threshold change of 6.2 dB HL (range, -13.8-33.8 dB). This change was statistically significant for severely affected patients (those with an average presenting threshold of over 71 dB). The mean average threshold improvement following intratympanic steroid injection therapy was 2.9 dB (range, -22.5-61.3 dB); this was not statistically significant. Some patients experienced moderate improvement following intratympanic steroid injection therapy; however, no specific subgroup was identified to benefit more from intratympanic steroid injection therapy.

Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Nationwide, Multicenter, Retrospective Cohort Study.

BackgroundCoronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated.MethodsThis multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model.ResultsAmong 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03–13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26–14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P = 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089).ConclusionOur study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

Influenza associated acute necrotizing encephalopathy and COVID-19 encephalopathy; a comparative review

Acute necrotizing encephalopathy (ANE) is influenza-associated encephalopathy (IAE) that mostly occurs in younger age groups following an acute viral illness with a very low recovery rate. It is a rare but rapidly progressive neurodegenerative disorder which pathogenesis is still not clear. There are some cases reported where the virus can directly invade the central nervous system (CNS) through the peripheral nervous system. Several pathogenic conditions like rising levels of proinflammatory cytokines, dissolving the blood-brain barrier (BBB), etc can trigger the viral infection. There are no specific treatments available but initial steroid therapy in combination with antivirals and hypothermia therapy were found efficacious in some cases. Similarly, coronavirus disease 2019 (COVID-19) encephalopathy is caused by a novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2). Having a very low recovery rate, and still unknown pathophysiology, this condition is proved to be fatal for immunocompetent adults. Treatments are not available but drugs like remdesivir, hydroxychloroquine, tocilizumab, and losartan were used to reduce the viral infection. No recurrent cases have been reported so far, but reinfection of the virus can trigger hypoxic encephalopathy. This review mainly focuses on a comparative study to understand the pathophysiology to help for discovering a new area of drug development.

Association between HLA alleles and sub-phenotype of childhood steroid-sensitive nephrotic syndrome

BackgroundFew studies have addressed the effects of human leukocyte antigen (HLA) alleles on different clinical sub-phenotypes in childhood steroid-sensitive nephrotic syndrome (SSNS), including SSNS without recurrence (SSNSWR) and steroid-dependent nephrotic syndrome/frequently relapse nephrotic syndrome (SDNS/FRNS). In this study, we investigated the relationship between HLA system and children with SSNSWR and SDNS/FRNS and clarified the value of HLA allele detection for precise typing of childhood SSNS.MethodsA total of 241 Chinese Han individuals with SSNS were genotyped using GenCap-WES Capture Kit, and four-digit resolution HLA alleles were imputed from available Genome Wide Association data. The distribution and carrying frequency of HLA alleles in SSNSWR and SDNS/FRNS were investigated. Additionally, logistic regression and mediating effects were used to examine the relationship between risk factors for disease process and HLA system.ResultsCompared with SSNSWR, significantly decreased serum levels of complement 3 (C3) and complement 4 (C4) at onset were detected in SDNS/FRNS (C3, P < 0.001; C4, P = 0.018). The average time to remission after sufficient initial steroid treatment in SDNS/FRNS was significantly longer than that in SSNSWR (P = 0.0001). Low level of C4 was further identified as an independent risk factor for SDNS/FRNS (P = 0.008, odds ratio = 0.174, 95% confidence interval 0.048–0.630). The HLA-A*11:01 allele was independently associated with SSNSWR and SDNS/FRNS (P = 0.0012 and P = 0.0006, respectively). No significant HLA alleles were detected between SSNSWR and SDNS/FRNS. In addition, a mediating effect among HLA-I alleles (HLA-B*15:11, HLA-B*44:03 and HLA-C*07:06), C4 level and SDNS/FRNS was identified.ConclusionsHLA-I alleles provide novel genetic markers for SSNSWR and SDNS/FRNS. HLA-I antigens may be involved in steroid dependent or frequent relapse in children with SSNS as mediators of immunoregulation.

Effect of corticosteroid dosing on outcomes in high-grade immune checkpoint inhibitor hepatitis.

Consensus guidelines recommend high-dose corticosteroids (1-2 mg/kg/day methylprednisolone equivalents) for treating grade ≥3 immune checkpoint inhibitor (ICI) hepatitis. We examined the effect of corticosteroid dosing on time to alanine aminotransferase (ALT) normalization, need for additional immunosuppression, and steroid-related complications. We conducted a retrospective cohort study of 215 ICI-treated patients from 2010 to 2020 who developed grade ≥3 (ALT>200 U/L) ICI hepatitis. Patients were grouped by initial corticosteroid dose (≥1.5 mg/kg or <1.5 mg/kg methylprednisolone equivalents). Propensity scores were calculated predicting the risk of receiving the higher steroid dose and used in inverse probability of treatment weighted (IPTW) logistic or Cox regression. The 87 patients in the ≥1.5 mg/kg group received higher initial (2.0 vs. 0.8 mg/kg/day, p<0.001) and maximum (2.0 vs. 1.0 mg/kg/day, p<0.001) steroid doses than the 128 patients in the <1.5 mg/kg group. There was no difference between the higher versus lower-dose groups in development of steroid-refractory hepatitis (OR 1.22, 95% CI 0.79-1.89, p=0.365) on IPTW-logistic regression. In patients with steroid-responsive disease, there was no difference between the two groups in time to ALT normalization using either standard Cox regression (HR 1.02, 95% CI 0.72-1.45, p=0.903) or IPTW-Cox regression (HR 1.09, 95% CI 0.78-1.51, p=0.610). The ≥1.5 mg/kg group had longer exposure to corticosteroids (median 60 vs. 44 days, p=0.005) and higher incidences of infection (18.4% vs. 7.0%, relative risk [RR] 2.6, 95% CI 1.2-5.6, p=0.011) and hyperglycemia requiring treatment (23.3% vs. 7.8%, RR 3.0, 95% CI 1.5-6.0, p=0.001). In patients with high-grade ICI hepatitis, initial treatment with 1 mg/kg/day methylprednisolone equivalents provides similar hepatitis outcomes with reduced risk of steroid-related complications when compared with higher-dose regimens.

돌발성 난청에서 발병 후 2주 이상 지연된 스테로이드 복합 치료의 이점

Objectives: We evaluated hearing recovery rates in sudden sensorineural hearing loss (SSNHL) according to a delay from onset to treatment. Materials and Methods: 281 subjects with SSNHL, who received steroid combination treatment as an initial treatment, were included in this study. We divided the patients into groups of the delay from onset to treatment: ≤48 hours, ≤7 days, ≤14 days, ≤21 days, ≤30 days, and 31–60 days groups. Results: Complete recovery (CR) rates were 21.2% in ≤48 hours group, 25.3% in ≤7 days group, and 7.9% in ≤14 days group. The CR was not found in groups with treatment delayed group after 14 days. The CR rate in ≤14 days group had 0.019-fold (95% CI: 0.051–0.769) decreased odds than the ≤48 hours group. Meaningful hearing recovery (MR) rates were 36.9%–47.1% in groups that received treatment within 14 days, and those of 17.7%–21.1% were observed in groups with a delay between 14 and 30 days. Of patients with treatment delays more than 31 days, hearing recovery of any type was not found. The MR rate in ≤30 days group had 0.234-folds decreased odds than ≤48 hours group (95% CI 0.061–0.906). Conclusions: Hearing recovery rates according to the delay of initial steroid treatment in SSNHL patients were identified. Clinicians can provide patients with information for hearing outcomes of delayed initiation of steroid treatment. Shared information facilitates better making decision with regard to their treatment plan. (J Clinical Otolaryngol 2021;32:212-220)

Short Versus Long Steroid Therapy in Nephrotic Syndrome

Source: Pasini A, Bertulli C, Casadio L, et al. Childhood idiopathic nephrotic syndrome: does the initial steroid treatment modify the outcome? A multicentre, prospective cohort study. Front. Pediatr. 2021;9:627636; doi.10.3389/fped.2021.627636Investigators from multiple institutions in Italy conducted a prospective study comparing relapses in children with idiopathic nephrotic syndrome (INS) treated with different steroid regimens, with treatment based on time to remission (TTR). Study patients were children >6 months to <18 years old with a first episode of INS, defined as proteinuria >40 mg/m2/hr or urine protein/creatinine ration (uPr/UCr) >2 mg/mg, and serum albumin <2.5 g/dL who were treated at 49 different pediatric units in Italy between 2011 and 2016. Children with congenital or secondary nephrotic syndrome were excluded. TTR was defined as first day of negative/trace protein on daily dipstick assessment after initiation of treatment. Study patients with a TTR of ≤10 days received prednisone, 60 mg/m2/day for 4 weeks, while those with a TTR >10 days were treated with the same prednisone dose for 6 weeks. Both groups had the same steroid-tapering dose regimen. Study patients who did not achieve remission within 8 weeks were classified as steroid-resistant and excluded.Study participants were followed for 24 months, with relapses defined as 3 days of ≥2+ protein on urine dipstick confirmed by a uPr/UCr >2 mg/mg. Primary outcomes included any relapse, time to first relapse and number of relapses. These outcomes were compared between those with a TTR ≤10 days (group A) and those with a TTR >10 days (group B) using chi-square or non-parametric (Wilcoxon, Krukal-Wallis) tests. A Kaplan Meier analysis was used to compare relapse-free survival in patients in groups A and B.A total of 184 children were enrolled in the study, but 21 steroid-resistant and 20 non-compliant patients were excluded from the analyses. Among the remaining 143 participants, 100 (70%) had a TTR ≤10 days (group A) and 43 had a longer TTR (group B). Children in group A were significantly older (mean ages 4.73 and 4.14 years, respectively; P = 0.01) and had a lower mean uPr/UCr than those in group B. A relapse occurred in 118 (78%) participants, including 77% of those in group A and 79% of group B patients (P = 0.91). There was also no difference in number of relapses between participants in group A and B (mean number 1.8 and 2, respectively; P = 0.43). Mean time to first relapse was longer for children in group A than group B (206 vs 167 days; P = 0.05), but relapse-free survival was not significantly different between groups.The authors conclude that in children with INS, different steroid regimens, based on TTR, were not associated with risk of relapse.Dr Sanchez-Kazi has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Nephrotic syndrome is one of the most common glomerular disorders in children.1 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend treatment of the initial episode with 60 mg/m2 or 2 mg/kg daily for 4–6 weeks (maximum 60 mg) followed by alternate day prednisone at 40 mg/m2 or 1.5 mg/kg x 2–5 months with tapering of the dose.2 The current investigators assessed whether induction therapy of 4 weeks vs 6 weeks with the same duration of weaning will alter the frequency of relapses and development of frequently relapsing INS.There may be an inherent fault in the trial since the investigators used TTR as the randomization criterion. The results of previous studies demonstrated that TTR is not a significant factor in the prediction of the number of relapses in steroid sensitive INS.1 It would have been better if the randomization was done based on age. As reported in the current study, the younger age group had a higher number of relapses despite longer induction. Similar findings were reported in a meta-analysis of European children less than 4 years of age.1,3 Multiple randomized controlled studies in different countries also have shown that the standard therapy and further extension of the standard therapy did not alter the risk of frequent relapses in steroid sensitive INS (See AAP Grand Rounds. 2020;43:32.)4-7Shorter steroid therapy was not only cost-effective but associated with fewer adverse effects on growth and behavior due to lower cumulative dose.5–6 In the future, biomarkers may be useful in risk stratification of patients with steroid-sensitive INS and modifying the frequency of relapses.Duration and dose of steroid induction therapy do not modify the number of relapses in steroid-sensitive INS in children.

Dexamethasone Versus Prednisone in Children Hospitalized for Acute Asthma Exacerbations.

Extensive literature supports using dexamethasone (DEX) in children presenting to the emergency department (ED) with mild-to-moderate asthma exacerbations; however, only limited studies have assessed this in hospitalized children. In this study, we evaluate the outcomes of DEX versus prednisone/prednisolone (PRED) use in children hospitalized for mild-to-moderate asthma exacerbations. This multisite retrospective cohort study included children between 3 and 21 years of age hospitalized to a tertiary care children's hospital system between January 1, 2013, and December 31, 2017, with a primary discharge diagnosis of acute asthma exacerbation or status asthmaticus. Primary study outcome was mean hospital length of stay (LOS). Secondary outcomes included PICU transfers during initial hospitalization and ED revisits and hospital readmissions within 10 days after discharge. Generalized linear models were used to model logged LOS as a function of steroid and demographic and clinical covariates. The analysis was stratified by initial steroid timing. Of the 1410 children included, 981 received only DEX and 429 received only PRED. For children who started oral steroids after hospital arrival, DEX cohort had a significantly shorter adjusted mean hospital LOS (DEX 24.43 hours versus PRED 29.38 hours; P = .03). For children who started oral steroids before hospital arrival, LOS did not significantly differ (DEX 26.72 hours versus PRED 25.20 hours; P = .45). Rates of PICU transfers, ED revisits, and hospital readmissions were uncommon events. Children hospitalized with mild-to-moderate asthma exacerbations have significantly shorter hospital LOS when starting DEX rather than PRED on admission.

Impact of initial steroid response on transplant outcomes in children with steroid-resistant nephrotic syndrome.

Limited data suggest children with secondary steroid-resistant nephrotic syndrome (secondary SRNS) have increased risk of recurrence post transplantation. There are no data on the association between secondary steroid resistance and risk of transplant loss. Children who received kidney transplantation between 2000 and 2019 for either primary or secondary SRNS in Australia and New Zealand were included. Children presenting with nephrotic syndrome before 12months were excluded. Data were gathered from chart reviews and ANZDATA. Transplant survival was estimated using the Kaplan-Meier estimator with Cox modelling used to explore predictors of survival. There wereseventy children, 38 (55%) male, median age at presentation 4years (IQR 2-7) and 46 (66%) Caucasian. Median age at transplant was 11years (IQR 7-15) and 39 (55%) received living donor transplant. Secondary SRNS occurred in 20/70 (29%). For those with secondary SRNS, 18/20 (90%) had recurrence post-transplant, compared to 18/50 (36%) with primary SRNS (p = 0.001). Every child with history of atopy (n = 11) or with hypoalbuminaemia at time of transplant (n = 13) experienced immediate recurrence. For children with secondary SRNS, 8/18 (44%) with post-transplant recurrence had no response to therapy. For children with primary SRNS, 4/18 (22%) with recurrence had no response to therapy (p = 0.3). Overall, 10-year transplant survival was 47% (95%CI 29-77%) for those with secondary SRNS, compared to 71 (95%CI 57-88%) for those with primary SRNS (p = 0.05). Secondary steroid resistance is strongly associated with SRNS recurrence. Atopy and hypoalbuminaemia at transplant may be novel risk factors for recurrence. Further research is needed to assess if secondary steroid resistance is associated with poorer transplant outcomes. "A higher resolution version of the Graphical abstract is available as Supplementary information".

Pulse steroid treatment for hospitalized adults with COVID-19

High-dose steroid has been shown to reduce the mortality rate in Corona virus disease 2019 (COVID-19) patients who need oxygen support. Here, we evaluated the effectiveness of pulse-steroid in case of unresponsiveness to treatment with high dose steroid. The study is a retrospective controlled trial. We divided the patients in 3 groups: standard-care therapy alone, high-dose steroid treatment (6 mg/day dexamethasone equivalent), and pulse-steroid treatment (250 mg/day methyl-prednisolone). One hundred and fifty patients were enrolled in each group. All patients were hospitalized and needed oxygen support. We matched the patients according to disease severity at the onset of hypoxia, weight of co-morbidities, age, and sex. We then compared 3 groups in terms of mortality, length of hospitalization, need for intensive care unit (ICU) admission and mechanical ventilation (MV), length of stay in ICU, and duration of MV. The pulse-steroid group had shorter ICU stay. The median ICU stay was 9.0 (CI 95% 6.0–12.0) days in standard-care group, 8.0 (CI 95% 5.0–13.0) days in high-dose steroid group and 4.5(CI %95 3.0–8.0) days in pulse-steroid group. Moreover, although patients in pulse-steroid group were initially unresponsive to high dose steroid therapy, they achieved similar results compared to the high-dose steroid group in other outcomes except for length of hospital stay. Pulse-steroid treatment would be an option for COVID-19 patients who do not respond to the initial high-dose steroid treatment.

CAVITATION DUE TO COVID-19: A CASE OF SECONDARY ATYPICAL MYCOBACTERIAL INFECTION POST-COVID-19

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: The novel Coronavirus disease 2019 pandemic has caused over 2 million deaths worldwide. Two recent systematic reviews and 1 meta-analysis reviewing the CT chest findings of COVID-19 did not reveal cavitation as a common finding with a recent retrospective review estimating the prevalence to be around 3.3%. Among the published examples, about half are solitary cavitary lesions. Most common causative organisms include staphylococcus aureus, klebsiella, and Enterobacter cloacae complex. A recently published case series described 6 cases of co-infection of Mycobacterium tuberculosis with COVID-19 causing cavitary lung disease. We report a case of Mycobacterium Avium Complex (MAC) infection causing cavitary lung disease as a complication of COVID-19 pneumonia. CASE PRESENTATION: 39 year old female with type 2 diabetes and hypothyroidism with a recent diagnosis of COVID-19 and pulmonary embolism. She presented with worsening cough, hemoptysis and left sided chest pain.CT Chest on admission showed a 7cm left lower lobe abscess with an associated pleural effusion and a left lower lobe pulmonary embolism along with scattered ground glass and consolidative opacities. Initial hospital treatment included prednisone, levofloxacin, and apixaban. One week after discharge she was readmitted with worsening left sided chest pain with scant hemoptysis.On readmission, workup included mycobacterial, fungal, auto-immune and HIV tests which were all negative. Patient improved significantly on broad-spectrum antibiotics which included Cefepime and Metronidazole. Laboratory work-up was significant for ESR > 100, CRP of 6 mg/dl. Patient continued to be on room air with improved symptoms and was discharged on oral Augmentin for 4 weeks with plans for outpatient follow-up CT chest. On follow-up, CT chest showed no significant difference in the cavity size and continued to have significant left sided pleuritic chest pain. Her antibiotic course was extended due to the persistence of the cavity and symptoms. At the conclusion of 8 weeks of antibiotics with persistent symptoms, a bronchoscopy was done with a BAL performed in the left lower lobe. AFB cultures grew Mycobacterium Avium Complex. DISCUSSION: Lung cavitation in COVID-19 is an uncommon and so far under-reported consequence/complication. Considering that it might present as a late complication, as in the above case, it is imperative to follow-up these patients closely and consider a broad and appropriate workup. The mechanism of lung cavitation is probably multifactorial, including lung necrosis from the initial pulmonary embolism, effect of initial SARS-CoV2 infection, secondary bacterial, fungal or mycobacterial infection and immunosuppression from initial steroid course. CONCLUSIONS: We report this case to add a secondary atypical mycobacterial infection causing cavitary lung disease to the ever increasing list of late complications of COVID-19 pneumonia. REFERENCE #1: Zoumot, Z. et al. Pulmonary cavitation: an under-recognized late complication of severe COVID-19 lung disease. Bmc Pulm Med 21, 24 (2021). REFERENCE #2: Teng, E., Bennett, L., Morelli, T. & Banerjee, A. An unusual presentation of pulmonary embolism leading to infarction, cavitation, abscess formation and bronchopleural fistulation. Bmj Case Reports 2018, bcr-2017-222859 (2018) REFERENCE #3: Selvaraj, V. & Dapaah-Afriyie, K. Lung cavitation due to COVID-19 pneumonia. Bmj Case Reports 13, e237245 (2020). DISCLOSURES: No relevant relationships by Benjamin Bevill, source=Web Response No relevant relationships by Milind Bhagat, source=Web Response

Calcineurin inhibitors and renal biopsy in children with idiopathic nephrotic syndrome.

Idiopathic nephrotic syndrome (NS) is common in children, and most patients respond to corticosteroid therapy. Patients who relapse may need additional immunosuppression with cyclophosphamide, mycophenolate mofetil, calcineurin inhibitors (CNI), or rituximab. Many such patients undergo protocol renal biopsies before and after the initiation of CNI therapy. The main objective of our study was to assess the role of protocol renal biopsies in the monitoring of CNI-induced nephrotoxicity in patients with steroid-dependent (SD)/frequent relapse (FR) NS. We did an Institutional Review Board (IRB)-approved retrospective chart review of patients who were diagnosed with NS at the Children's Hospital of Michigan from January 2000 to June 2019. Study inclusion criteria were a diagnosis of NS, age 1 - 21 years at initial diagnosis, SD/FR clinical course, patients with initial steroid resistance with renal biopsy showing minimal change disease, and renal biopsy before and after CNI initiation. The data is presented on 24 patients who met study inclusion criteria. Only 3 patients (12.5%) showed evidence of chronic CNI nephrotoxicity after a median treatment 66.5 months (range 12 - 153 months). Our study revealed that a baseline renal biopsy before starting CNI therapy for children with FR/SDNS is not necessary. A renal biopsy may be considered after 2 - 3 years of CNI administration in selected few cases in whom the diagnosis of CNI nephrotoxicity might help change the management.

Endocrine Disruptors-(estrone and β-estradiol) removal from water by Nutshell activated carbon: Kinetic, Isotherms and Thermodynamic studies

A large number of substances in the environment designated as endocrine-disrupting chemicals (EDCs) are amongst the most intoxicating compounds found in environmental waters. The removal of two EDCs: estrone (E1) and β-estradiol (E2) by activated carbon was examined in an agitated non-flow batch adsorption studies. The macadamia nutshell activated carbon (MAC) was characterized by TGA, FTIR, and SEM. Properties such as contact time, adsorbent dosage, pH, initial steroids concentration, and temperature were examined. Mathematical models like pseudo-first-order and pseudo-second-order kinetics, thermodynamic, the Freundlich, and Langmuir isotherms model were used to describe the steroids adsorption phenomenon. From the Langmuir isotherm, maximum adsorption capacity was found to be 22.0 mg/g. Thermodynamic factors: ∆G° values of –1.223 to –1.308 kJ/mol, ∆H° = –11.72 kJ/mol, and ∆S° = 37.34 J/mol k of steroids adsorbed onto MAC indicate that the adsorption was spontaneous, proceeded favourably at lower temperature and exothermic in nature, demonstrating that physisorption mechanism predominates. The distinctive data and adsorption intensity disclosed that MAC could be engaged as a substitute for effective adsorbents for the removal of endocrine disruptors-steroids from water.

De Novo Cancer Incidence after Kidney Transplantation in South Korea from 2002 to 2017.

Advances in patient care and immunosuppressive drugs have improved graft survival, resulting in an increase in kidney transplantation (KT); however, persistent immunosuppression is thought to cause late occurrence of cancer. This population-based study consisted of a total of 14,842 patients whose data from the years 2002 to 2017 were collected from the National Health Information Database in South Korea. Malignancies occurred in 7.6% of the total KT patients. Prostate and thyroid cancers were the most common in males and females, respectively. From the age-adjusted incidence analysis, Kaposi’s sarcoma showed the highest standardized incidence ratio in both male and female patients. According to the linear regression model, cancer incidence in KT recipients under immunosuppressive conditions increased by approximately 0.1% each month. Patients’ age over 39 and the use of prednisolone as an initial steroid regimen were associated with increased risk of cancer development after KT. Our regression and proportional hazards models will help clinicians to predict the approximate cancer incidence risk when monitoring KT recipients. Based on the largest available national database, screening or monitoring methods for cancer detection and prevention can be established for KT patients by considering the factors involved in cancer development.

Association of initial prednisolone dose with remission, relapse, and infectious complications in adult-onset minimal change disease

BackgroundA dose of 0.5–1 mg/kg/day of prednisolone (PSL) is administered for the initial treatment of minimal change disease (MCD). However, little is known about the optimal PSL dose for the initial treatment of MCD.MethodsWe conducted a retrospective multicenter cohort study of treatment-naive adult patients with MCD diagnosed by renal biopsy from 1981 to 2015 in whom PSL monotherapy was performed as the initial treatment. The exposure of interest was an initial median PSL dose of < 0.63 mg/kg/day (Group L) compared to ≥ 0.63 mg/kg/day (Group H). Cumulative remission and relapse after remission were compared between these groups using Cox regression adjusted for baseline characteristics.ResultsNinety-one patients met the inclusion criteria. During a median follow-up of 2.98 years, 87 (95.6%) patients achieved complete remission, and 47.1% relapsed after remission. There was no significant difference in the remission rate between the groups at 4 weeks of follow-up (66.7 vs. 82.6%). The median time to remission in Group L was comparable to that in Group H (17.0 vs. 14.0 days). A multivariable Cox hazard model revealed that the initial PSL dose was not a significant predictor of remission. The cumulative steroid doses at 6 months, 1 year, and 2 years after treatment initiation were significantly lower in Group L than in Group H.ConclusionThe initial PSL dose was not associated with time to remission, remission rate, time to relapse, or relapse rate. Therefore, a low initial steroid dose may be sufficient to achieve remission.

Response to steroid and immunosuppressive therapies may predict post-transplant recurrence of steroid-resistant nephrotic syndrome.

Recurrence of SRNS is a major challenge in KT. Several clinical factors, including initial steroid sensitivity, have been associated with increased post-transplant SRNS recurrence risk. However, conflicting data have been reported, possibly due to the heterogeneous pathophysiology of SRNS and the lack of genetic testing of SRNS patients. Furthermore, the response to immunosuppressive therapies has not been evaluated. Seventy patients aged 1-15years at SRNS onset who underwent KT between 2002 and 2018 were enrolled. Patients with secondary, familial, syndromic, and genetic forms of SRNS and those who were not treated with steroid were excluded. This study aimed to assess the risk factors for post-transplant recurrence, including treatment responses to initial steroid therapy and additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A. Data from 36 kidney transplant recipients were analyzed. Twenty-two (61%) patients experienced post-transplant SRNS recurrence, while 14 patients did not. The proportion of patients who achieved complete or partial remission with initial steroid therapy and/or additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A was significantly higher in the SRNS recurrence group (19/22, 86%) than in the group without SRNS recurrence (6/14, 43%; p=.01). This study suggests that the response to steroid treatment, other immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A may predict post-transplant SRNS recurrence.

Childhood Idiopathic Nephrotic Syndrome: Does the Initial Steroid Treatment Modify the Outcome? A Multicentre, Prospective Cohort Study.

Background: A great majority of children with idiopathic nephrotic syndrome will relapse after successful treatment of the initial episode. The possibility that different steroid dosing regimens at onset, adjusted for risk factors, can reduce the rate of relapse represents an interesting option to investigate.Objectives: To evaluate the effect of the initial steroid regimen, adjusted for time to remission (TTR), on the frequency of relapses and steroid dependence, and to verify the influence of prognostic factors on disease course.Methods: A multicentre, prospective, cohort study. Children with nephrotic syndrome, with TTR ≤ 10 days (Group A), were given a 20-week prednisone regimen (2,828 mg/m2) and those with a TTR >10 days, a 22-week regimen (3,668 mg/m2) (Group B). Previously published retrospective data from the same centers were also evaluated. Main outcomes were: relapse rate, number of frequent relapsers + steroid dependent children and total prednisone dose after induction.Results: 143 children were enrolled. Rate of relapsed subjects (77 vs. 79%) and frequent relapsers + steroid dependent subjects (40 vs. 53%) did not differ between Groups A and B, or between the retrospective and prospective cohorts. The cumulative prednisone dose taken after the induction treatment was similar in both groups and in the retrospective and prospective cohorts. TTR was not associated with relapse risk. Age at onset and total serum protein were significantly lower in relapsing patients. At ROC analysis, the best cut-off was 5.3 years for age at onset and 4.2 g/dL for total serum protein. According to these cut-offs, older children with higher total serum protein had a higher relapse free survival rate (58%) than younger children with lower total serum protein (17%).Conclusions: TTR was not found to be a prognostic factor of relapse; because of this, different steroid regimens, adjusted for TTR, did not modify the relapse rate in any relevant measure. Conversely, younger age and low total serum protein were independent predictors of relapse risk, however this outcome was not modified by higher prednisone regimens.Clinical Trial Registration:https://www.ClinicalTrials.gov/, identifier: NCT01386957 (www.nefrokid.it).

Optimal First-Line Therapy for Acute Low-Tone Sensorineural Hearing Loss

Background and ObjectivesWe aimed to analyze treatment outcomes following different initial management approaches and confirm treatment regimens for acute low-tone sensorineural hearing loss (ALHL) that would yield the best results.Subjects and MethodsWe retrospectively analyzed the medical records of 106 patients with ALHL who visited a university hospital’s otology clinic from March 2013 to June 2019. Pure-tone averages at the initial visit and at 2 and 4 weeks after the initial visit were evaluated.ResultsForty-nine patients were enrolled in this study; of them, 41 (83.7%) exhibited complete recovery (CR) at 2 weeks and 43 (87.8%) exhibited CR at 1 month after the initial visit. Regression analysis revealed that CR at 2 weeks after the initial visit was associated with diuretic use [Exp(B): 10.309, 95% confidence interval (CI): 1.007-100]. An initial daily low-dose steroid use was marginally significant [Exp(B): 1.042, 95% CI: 0.997-1.092; p=0.066]. Isolated diuretic use [Exp(B): 25.641, 95% CI: 1.121-90.909; p=0.039] was an independent, good prognostic factor at 1 month after the initial visit. However, other treatment regimens did not affect the final results.ConclusionsA combination of initial daily administration of ≤30 mg prednisolone plus diuretics was sufficient as the first-line treatment for ALHL. High-dose steroids and salvage intratympanic steroid injections can be applied as a second choice; however, the predicted outcome would not be good in that case.