Steroid Duration Research Articles

Recent Infection With Black Fungus Associated With COVID-19: A Review

Recently, an emergency health problem erupted that worried the world, which is the black fungus infection associated with Covid-19, especially in India and some regions of the Middle East. The members of genus Rhizopus or Mucor resulted the common mucormycosis. Humans become infected by inhaling and depositing the spores of fungi in the tissues of the body. Rhinocerebral is the site most susceptible to infection . Several factors may have contributed to an increase in the incidence of mucormycosis in patients with COVID-19, including hypoxia, steroid-induced elevated blood glucose levels, and diminished phagocytic action of leukocytes due to immunosuppression, and non-sterile medical supplies. In addition, there is an unsanitary phenomenon resorting to some people in India, it is smearing the body with cow dung and urine, which may have a role in the spread of the black fungus infection. Proper use of both the dose and duration of steroids is essential to avoid an increase in cases of mucormycosis, especially when caring for critically ill COVID-19 patients. Keywords : Black fungus, infection, health problem.

Multicentre retrospective assessment of toxicity and response to immunotherapy in elderly patients with metastatic melanoma.

9565 Background: The incidence of melanoma increases with age, however, elderly patients remain under-represented in landmark immunotherapy trials for metastatic melanoma. This study aims to investigate the impact of age on efficacy and toxicity of immunotherapy, and complications of immunosuppression to treat toxicity. Methods: A multicentre retrospective study involving centres in Australia [Gold Coast University Hospital, Cairns Base Hospital, Townsville University Hospital] was performed to compare the efficacy and toxicity of immunotherapy in metastatic melanoma in patients ≥70 years versus patients < 70 years treated between 2015 and 2019. Data collected included: baseline demographics, PFS, OS, Grade 3 or higher (Gr3+) adverse events as per CTCAEv5, adverse events leading to discontinuation, duration of steroids used to treat toxicity and complications secondary to steroids. Comparison of survival outcomes between the groups was calculated using Kaplan Meier, Log rank test and multivariate Cox regression analysis. Fisher exact test was used to determine differences in toxicity between the two groups. Results: A total of 229 patients were included with 106 patients ≥70years and 123 patients < 70 years. Baseline demographics were similar. Dual immunotherapy (ipilimumab + nivolumab) was less commonly used in patients ≥70years [13 v 38% p < 0.001]. Although the median PFS was numerically higher amongst ≥70years [10.8 v 6.9months p = 0.99], the landmark PFS was not [3yr PFS: 31 v 39%; 4yr PFS: 22 v 39%]. The median OS was similar in patients ≥70 years v < 70years [27.5 v 28.7 months p = 0.91], with similar landmark survival [3yr OS: 46 v 49%; 4yr OS: 42 v 49%]. Age was not associated with a difference in overall survival on multivariate analysis. There was no increase in Gr3+ adverse events in patients ≥70 years [22 v 21% p = 1.00] or discontinuation rates [26 v 20% p = 0.35]. There was one death in a patient < 70years secondary to colitis. There was a significantly higher rate Gr3+ adverse events in ≥70years patients receiving dual immunotherapy [71 v 35% p = 0.029] and a similar rate of Gr3+ adverse events with PDL1 inhibitors [13 v 11% p = 0.7]. Median duration of steroids was similar in both group [15 v 17wks], as was the median duration of high dose steroids defined as greater than 10mg of prednisone [5 v 6wks]. Complications of steroids was numerically higher in the elderly population [42 v 25% p = 0.15]. The most common adverse event to immunosuppression was infection. Conclusions: Patients ≥70years received similar benefit from immunotherapy in comparison to their younger counterparts. Toxicity related to PDL1 inhibitors was similar in both groups and was higher in patients ≥70years receiving dual immunotherapy. Patients ≥70 years had a clinically significant higher rate of complications secondary to steroids.

Chronic immune checkpoint inhibitor (ICI) pneumonitis in patients (pts) with non-small cell lung cancer (NSCLC).

9103 Background: ICI pneumonitis is an immune-related adverse event (irAE) of the lung and often requires discontinuation of ICI. While some pneumonitis cases resolve within the recommended 4-6-week period of corticosteroid therapy, others either fail to improve or have multiple flares necessitating longer or repeated courses of steroids. We investigated the clinical features and courses of pts with chronic pneumonitis. Methods: We analyzed 869 pts with NSCLC initiated on ICIs at our institution between 2011 and 2019 for development of ICI pneumonitis. Chronic pneumonitis was defined as any pneumonitis requiring a total of ≥12 weeks of steroids, given either continuously or over multiple courses of treatment. Cases of chronic pneumonitis in which the initial course of steroids lasted ≥12 weeks without interruption were termed “primary refractory pneumonitis”. Subsequent episodes of pneumonitis were categorized as either “recurrent pneumonitis” from ICI rechallenge or “pneumonitis flare” after steroid taper without ICI rechallenge. Chest CT scans were analyzed to classify the imaging patterns. Results: Of the 869 pts analyzed, 44 developed ICI pneumonitis (5.1%) and 22 of the 44 (50%) experienced chronic pneumonitis (Grade 2 in 11, Grade 3 in 9, and Grade 4 in 2). A cryptogenic organizing pneumonia (COP) pattern was the most common CT pattern among all pneumonitis cases (30/44) and in chronic pneumonitis cases (14/22). Among chronic pneumonitis cases, the median number of total weeks on corticosteroid therapy was 25.9 (range: 12.4 – 114.4 weeks). Four pts required additional immunosuppressive agents including mycophenolate or infliximab. Fourteen of 22 pts with chronic pneumonitis had primary refractory pneumonitis, while the remaining 8 pts were weaned off of steroids within 12 weeks but later developed additional episode(s) of pneumonitis, ultimately resulting in a total steroid duration of ≥12 weeks. The 14 pts with primary refractory pneumonitis had significantly shorter time to pneumonitis onset compared to the other 8 pts (median time to onset: 1.8 vs. 5.5 months, Wilcoxon ranksum p = 0.04). Seventeen of 22 patients had their ICI permanently discontinued; of these, 9 pts subsequently experienced pneumonitis flare after steroid taper, necessitating additional course(s) of steroid therapy. 5 of the 22 patients were rechallenged with ICI, and 4 of them had recurrent pneumonitis with ICI rechallenge. Conclusions: Half of the pts diagnosed with pneumonitis developed chronic pneumonitis requiring at least 12 weeks in aggregate of glucocorticoid therapy. Some patients had an initial prolonged steroid course while others initially improved and then flared, even after ICI discontinuation. Recognition of chronic pneumonitis as a distinct and common clinical entity is important in management of pts with ICI pneumonitis.

Patients with steroid-refractory toxicity following immune checkpoint inhibitors: Frequent hospitalizations and long duration of illness.

2655 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer with significantly improved outcomes, but these agents have a unique spectrum of toxicities known as immune-related adverse events (irAEs). The recommended treatment for non-endocrine toxicities is steroid based. However, a subset of patients (pts) is steroid-refractory and requires second-line immunosuppression. There is very little evidence regarding this population. In this retrospective study we report the 1) incidence 2) type of treatment used 3) natural history and 4) potential predictors of steroid-refractory irAE at a major academic medical center. Methods: The Research Patient Database Registry at Mass General Brigham was used to identify pts treated with an ICI from 1/5/2017 to 6/1/2019. Pharmaceutical records identified a subset of the cohort received a second-line immunosuppressive agent within a 15-month period after ICI. For pts with steroid-refractory irAE additional information was collected: demographics, ICI regimen, type/#/and severity of irAE, clinical characteristics, # of admissions, length of stay (LOS), amount and duration of steroid therapy, second line immunosuppression type, treatment discontinuation rates, response, and outcome of re-challenge. Multivariate logistic regressions were used to predict risk of refractory toxicity and study the association of different variables (age, sex, race, marital status, cancer and ICI types) with refractory toxicities. Results: We identified 61 pts (1.4%) with steroid-refractory irAEs (48 colitis, 4 myocarditis, 6 pneumonitis, 3 neurologic) out of the total ICI cohort (N=4,325). 60.7% received ICI monotherapy. 24.6% received ICI in the adjuvant setting. Median length of steroid duration was 68 days with max of 1135 days. Despite use of second line immunosuppression, 25.8% of pts were never able to discontinue steroids. Majority of pts (72.1%) had at least one hospitalization with median LOS of 7.5 days. 93.4% of pts permanently discontinued the ICI responsible for the irAE. Thirteen pts (21.3%) were later re-challenged with ICI and 7 (53.8%) of these developed a subsequent irAE. Anti-CTLA-4 therapy was associated with a 10-fold risk of refractory toxicity compared to PD-1 (p<.05). Best tumor response was complete response in 21.3% and partial response in 26.2%. Among different cancer types, melanoma was most strongly associated with refractory events (OR 2.97 in comparison to thoracic malignancy). Conclusions: Refractory toxicity is uncommon but leads to high rates of ICI discontinuation, frequent hospitalizations, and a long duration of illness with exposure to prolonged and high-doses of steroids. There is an urgent need for further investigation into predictive factors for steroid-refractory toxicity given that ICI is being used more frequently and in earlier lines of treatment.

Treating Pediatric Myocarditis with High Dose Steroids and Immunoglobulin

Purpose Though many pediatric centers use immunotherapy including immunoglobulin (IVIG) and corticosteroids to treat patients with acute myocarditis, given a lack of evidence supporting its efficacy there is considerable variability in practice. We report our approach using high dose steroids with IVIG to treat acute myocarditis. Methods This is a single center retrospective observational study of children diagnosed with myocarditis treated with high dose steroids and IVIG from January 2004-April 2020. Diagnostic criteria for myocarditis included positive endomyocardial biopsy, MRI meeting Lake Louise criteria, or clinical diagnosis including an elevated troponin, LVEDD Z score Results ty one patients met inclusion criteria. Median age at diagnosis was 10.7 years (1 wk-20 yrs). The majority were male (65%). Diagnosis was made clinically in 68% of cases (N=21), MRI in 16% (N=5) and biopsy in 16% (N=5). Ten patients had positive respiratory viral PCR, 6 had positive plasma viral PCR and 0 had positive biopsy viral PCR. Median EF at diagnosis was 41% (IQR 10-65). Mean duration of steroids received was 74 days (SD 13) with IV steroids for 7 days (IQR 3-13) prior to transition to an enteral regimen. The mean cumulative dose of steroids for first 7 days was 38 mg/kg. All patients received IVIG; median cumulative dose was 2 g/kg. Seven patients (23%) required mechanical circulatory support (5 ECMO, 1 Centrimag LVAD and 1 Centrimag BiVAD). There were no serious secondary bacterial. In-hospital mortality was 0%. Mean follow up was 2 years (SD=2yr); 1 patient died 2 years after discharge; 1 patient underwent transplant during initial hospitalization; no others were listed. Five required re-admission for cardiovascular reasons. Six patients (19%) had steroid course altered due to suspected side effects such as weight gain or hypertension which resolved at follow up. By 3 months from diagnosis, 84% (N=26) of patients regained normal LV function. Conclusion Our study demonstrates that use of high dose steroids with IVIG to treat myocarditis can be safe without significant infections or side effects. Our cohort had excellent recovery of ventricular function and survival without transplant (94%). Prospective comparison of a combination of high dose steroids with IVIG versus either therapy alone is needed.

The combined use of steroids and immune checkpoint inhibitors in brain metastasis patients: a systematic review and meta-analysis.

Immune checkpoint inhibitors (ICI) have been a breakthrough for selected cancer patients, including those with brain metastases (BMs). Likewise, steroids have been an integral component of symptomatic management of BM patients. However, clinical evidence on the interaction between ICI and steroids in BM patients is conflicting and has not adequately been summarized thus far. Hence, the aim of this study was to perform a systematic literature review and meta-analysis on the association between steroid use and overall survival (OS) in BM patients receiving ICI. A systematic literature search was performed. Pooled effect estimates were calculated using random-effects models across included studies. After screening 1145 abstracts, 15 observational studies were included. Fourteen studies reported sufficient data for meta-analysis, comprising 1102 BM patients of which 32.1% received steroids. In the steroid group, median OS ranged from 2.9 to 10.2 months. In the nonsteroid group, median OS ranged from 4.9 to 25.1 months. Pooled results demonstrated significantly worse OS (HR = 1.84, 95% CI 1.22-2.77) and systemic progression-free survival (PFS; HR = 2.00, 95% CI 1.37-2.91) in the steroid group. Stratified analysis showed a consistent effect across the melanoma subgroup; not in the lung cancer subgroup. No significant association was shown between steroid use and intracranial PFS (HR = 1.31, 95% CI 0.42-4.07). Administration of steroids was associated with significantly worse OS and PFS in BM patients receiving ICI. Further research on dose, timing, and duration of steroids is needed to elucidate the cause of this association and optimize outcomes in BM patients receiving ICI.

Safety and efficacy outcomes in immune checkpoint inhibitor (ICI)-treated metastatic urothelial carcinoma (mUC) patients (pts) requiring treatment interruption (TI) due to immune-related adverse events (irAEs).

411 Background: Most patients (pts) with metastatic urothelial carcinoma (mUC) will receive immune checkpoint inhibitors (ICI) at some point during treatment. As such, understanding of immune-mediated toxicity is integral to optimal patient management. We describe the clinical characteristics, treatment, and outcomes of ICI-treated mUC pts who experienced irAEs requiring treatment interruption (TI). Methods: ICI-treated mUC pts who developed > grade 2 (per CTCAEv5) irAEs leading to >2 week TI were retrospectively reviewed. Patient-, disease-, treatment-, and toxicity-related data were evaluated. Toxicity was graded per CTCAEv5. Time to treatment interruption (TTI), treatment-free interval (TFI), time to next treatment (TTNT), and duration of response (DoR) were assessed descriptively. Results: Of 200 ICI-treated mUC pts, 18 (9%) experienced irAEs necessitating TI. 12 (43%) were male; median age at diagnosis was 72.5 (range, 45-80); 15 (83%) had KPS > 80. 8 (44%) had pure UC histology, 14 (78%) had prior cystectomy or nephroureterectomy, and 11 (61%) received platinum-based chemotherapy in the perioperative setting. 4 (22%) received 1L platinum-based Tx for mUC. ICI therapy was distributed evenly between atezolizumab (50%, n = 9) and pembrolizumab (50%, n = 9). Median TTI was 6.5 months (mos) (range, 1-19). The most common irAEs were dermatitis (22%, n = 4), colitis (17%, n = 3), and transaminitis (17%, n = 3); the majority were grade 2 (72%, n = 13). No grade 4/5 events occurred. 14 pts (78%) were treated with methylprednisolone and/or prednisone. Median initial prednisone-equivalent steroid dose was 45 mg/day (range, 30-1,250) with a median steroid duration of 42 days (range, 4-198). ICI were held and later re-challenged in 10 pts (56%), permanently discontinued in 7 pts (39%), and transitioned to a subsequent Tx in 1 pt (5%). Of 10 pts re-challenged with ICI, 7 (70%) experienced an irAE upon re-challenge (4 with recurrent irAEs, 3 with new irAEs); ICI was permanently discontinued in 3 of these pts. For pts receiving subsequent Tx, median TFI was 1 month (range, 0-12) and median TTNT was 5 mos (range, 2-31). Median DoR among all pts with initial response to ICI therapy was 15.5 mos (range, 2-52). Of 7 pts who permanently discontinued ICI and received no further Tx, 6 (86%) demonstrated an ongoing sustained therapy response with median DoR of 22.5 mos (range, 12-52). Conclusions: In this cohort, ICI-treated mUC pts who developed irAEs requiring treatment interruption had a high rate of subsequent irAEs upon ICI re-challenge. Importantly, pts who discontinue ICI due to irAE can have durable responses off treatment, consistent with data from other cancers.

Methotrexate in the Treatment of Idiopathic Granulomatous Mastitis

Even though idiopathic granulomatous mastitis (IGM) is a benign breast lesion of the mammary grand, it poses a problem of diagnosis as it is a rare entity. Because it resembles breast abscess or inflammatory carcinoma, patients undergo surgical excision leading to breast scarring and disfigurement. In this work, we carried a prospective study of cases of IGM managed over the past 7 years from 2009 to 2015. Among 4200 patients who were treated for breast swelling, 40 cases of IGM were diagnosed. We present the clinical data of our IGM patients and results of treatment with corticosteroids and methotrexate. The mean age of presentation was 33 years, and the median duration of steroid and methotrexate treatment was 3 and 6–9 months, respectively. The diagnosis of IGM was confirmed by core needle biopsy in all the patients. With this combination therapy, all the patients showed complete resolution of IGM and the recurrence was observed in only 2 patients. Our study demonstrates that a combination of corticosteroids (prednisolone) and methotrexate is an ideal choice of treatment for IGM rather than the surgical excision. The combination of low doses of corticosteroids with methotrexate could significantly prevent the side effects of high doses of corticosteroids.

Evaluating tertiary adrenal insufficiency in rheumatology patients on long-term systemic glucocorticoid treatment.

Patients with rheumatic diseases are often treated with prolonged, high-dose systemic glucocorticoids which can cause hypothalamic-pituitary-adrenal (HPA) axis suppression and development of tertiary adrenal insufficiency. Adrenal insufficiency carries the risk of serious, potentially life-threatening adrenal crisis. Our study evaluated the prevalence, characteristics and recovery of patients with underlying rheumatology conditions who had received prolonged glucocorticoid treatment. Retrospective, cross-sectional study. We evaluated 238 patients seen in outpatient rheumatology clinic, managed in accordance with current nationally and internationally accepted clinical guidelines. Data collected included patient demographics, historical steroid data, 09.00h cortisol/short synacthen test (SST) results and follow-up data on those with repeat assessments. Overall, 65% of our cohort had a 09.00h cortisol <350nmol/L. On SST, 43% of patients demonstrated evidence of possible tertiary adrenal insufficiency. Prednisolone equivalent dose at time of SST was significantly higher in the group who failed SST vs. those who passed; mean of 5.57mg vs. 3.59mg (p=.005). 09.00h cortisol result correlated with 30-min cortisol on SST (R2 =.20, p=.002). 0-min cortisol on SST correlated more strongly with 30-min cortisol than 09.00h cortisol (R2 =.59, p-value<.001). Patients with 0-min cortisol >350nmol/L, all passed their SST. Patients who remained on prednisolone were more likely to recover (71%) vs. those switched to hydrocortisone (27%), P=.02. Peak steroid dose was predictive of recovery; significantly lower in those who recovered (mean of 22.3mg vs. 33.8mg, P=.03). Steroid duration was not found to be a predictor of recovery [recovery (64.2months) vs. non-recovery (55.6months), P=.58]. There was no correlation found to outcome on SST with age, sex, peak steroid dose, steroid duration, underlying rheumatological condition, additional exogenous steroid use or serum sodium. Forty three percent of our patients demonstrated sub-optimal adrenal function on SST. Steroid dose at the time of SST was the only significant predictive risk factor for tertiary adrenal insufficiency. 09.00h cortisol demonstrated good correlation with outcome on SST and could represent a valid screening test to reduce need for SST if 09.00h >350nmol/L. Further prospective data are required to further characterize risk factors, predictive features of recovery and establish optimal management strategy of steroids (prednisolone vs hydrocortisone) to encourage adrenal recovery.

Effect of 6-12 Weeks of Systemic Glucocorticoids on Bone Mineral Density in Children

Introduction: Prolonged use of systemic steroids in children is associated with many side-effects including effect on Bone Mineral Density (BMD). Effect of more than three months of systemic steroids on BMD has been studied in children but not the effect of 6-12 weeks duration of steroid. Aim: To evaluate the effect of 6-12 weeks of systemic glucocorticoids on BMD in children. Materials and Methods: A longitudinal observational study was conducted at a Tertiary Care Hospital. Dual Energy X-ray Absorptiometry (DEXA) of Whole Body (WB), Lumbar Spine (LS) and Distal Radius (DR) were done at baseline, end of steroid therapy or third month whichever was earlier and end of six months, on 30 patients receiving systemic steroid (Nephrotic Syndrome (NS)-7, Systemic Onset Juvenile Idiopathic Arthritis (SOJIA)-12, Tubercular Meningitis-11). Age and sex adjusted values of Bone Mineral Content (BMC), BMD and Z scores were analysed. Bone densitometric parameters of Total Body Less the Head (TBLH) were derived from WB values. X-rays of whole spine (antero-posterior and lateral view) were done at baseline and follow-up. Equal number of age and sex matched healthy controls were subjected to biochemical and DEXA scans at baseline. Continuous and categorical variables were compared using Student’s t-test and Fisher-exact test, respectively. Pairwise comparison over period of time was done using Bonferroni correction. Results: Bone densitometric parameters of cases and controls were comparable at baseline. At follow-up statistically significant decrease in BMD was found at all three sites. A statistically significant negative correlation was found between cumulative dose of steroid and duration of steroid treatment with Z score of TBLH. No vertebral fractures were detected at baseline or follow-up. Conclusion: Use of systemic glucocorticoids for 6-12 weeks negatively affects bone mineralisation, not only during therapy but even three months after stopping it.

COVID-19 and Rheumatic Diseases in Tamil Nadu – A multicenter retrospective observational study

Aim: To describe the clinical and demographic characteristics of rheumatic disease patients who were diagnosed with COVID-19 infection. To identify the risk factors associated with hospitalization of patients and find out differences if any between patients managed as in-patients and out-patients.Methods: This was a multi-center retrospective observational study done by the analysis of data collected from six tertiary care centers from April 1, 2020, to October 15, 2020. All consecutive patients with a confirmed diagnosis of rheumatic disease and with a recent history of COVID-19 illness were included in the study.Results: Our study had a total of 85 patients with 58 managed as inpatients and 27 as outpatients. Six patients needed intensive care management and two patients succumbed to the illness. The majority were females (62/85) and majority (80/85) tested positive by the Reverse transcriptase-polymerase chain reaction method. The common rheumatic disease was rheumatoid arthritis (51.7%) followed by systemic lupus erythematosus (15.2%), psoriatic arthritis (10.5%), and others. Thirty-seven patients were on steroids and 28 were on hydroxychloroquine. There was no statistical difference in the mean dose of disease-modifying drugs between the two groups. Out of hospitalized people, 84.4% were above 40 years. There was a higher prevalence of comorbidities among hospitalized patients which was statistically significant (Chi-square test, P = 0.029). There was a positive correlation between duration of stay and steroid dose (Spearman rank correlation, “r” = 0.232), which was statistically significant (P = 0.03). There was no association between stay duration and other disease-modifying agents.Conclusion: There was a positive and statistically significant correlation between steroid dose and duration of stay. The prevalence of comorbidities was higher among hospitalized patients. There was no correlation between other immunosuppressive drugs and stay duration nor was there any difference in mean dosages of these drugs between patients treated as in-patients and out-patients.

The need for extreme caution while stopping short term dexamethasone therapy in SARS-CoV-2 infection: An experience

The mental and physical impact of the SARS-CoV-2 pandemic has led to the indiscriminate and desperate use of medications with the intention of saving lives. Dexamethasone has come across as a key player in the treatment of the infection. Short term therapy of dexamethasone, up to 10 days does not usually require tapering while discontinuing the therapy. However, the dose and duration of steroid required to suppress the Hypothalamic-Pituitary-Adrenal Axis (HPAA) is unpredictable. Hence, extreme caution should be taken while stopping dexamethasone therapy irrespective of the duration or the dose of the drug.

The Use of Systemic Steroids in the Treatment of Herpes Zoster Ophthalmicus–Related Ophthalmoplegia: Case Report and Case Meta-analysis

The role of systemic steroids in the treatment of ophthalmoplegia in the setting of herpes zoster ophthalmicus (HZO) is controversial. We conducted a case report-based meta-analysis to investigate the role of systemic steroid in the recovery of efferent dysfunctions in HZO. Case-report based meta-analysis. We report a case of herpes zoster ophthalmicus-related ophthalmoplegia (HZORO) in which systemic steroid led to complete resolution of external ophthalmoplegia. We further identified subjects from published cases of HZO-related ophthalmoplegia by searching PubMed and Google Scholar, which elicited 42 articles (49 cases) after excluding those younger than 18 years or with incomplete follow-up data. With the present case, a total of 50 cases are included in the analysis. Main outcome measure is the recovery of efferent dysfunction at the last known follow-up, coded as 1 for complete recovery or 0 for noncomplete recovery. We performed multivariable linear regression and Cox proportional hazards analysis to determine the contribution of steroid duration on the status of complete recovery. Multivariable linear regression showed significant association between duration of steroid treatment and status of complete recovery (P < .001). Cox proportional hazards analysis showed a hazard ratio of 1.1 (P= .04), indicating that longer treatment duration increased chance of complete recovery. Age, gender, and initial steroid dose did not contribute significantly to recovery status. Our meta-analysis suggests that extended steroid taper may aid the recovery of ophthalmoplegia in the setting of HZO and should be investigated further in the future.

Characterizing e-cigarette vaping-associated lung injury in the pediatric intensive care unit.

Adolescent e-cigarette use has risen to epidemic levels in the US, revealing a new phenomenon of e-cigarette vaping-associated lung injury (EVALI). It is important to better characterize EVALI in critically ill adolescents as this is a vulnerable and rapidly growing demographic. This was a retrospective case series of patients ≤21 years old with confirmed or probable EVALI (as defined by the Centers for Disease Control) that resulted in admission to the pediatric intensive care unit (PICU) of a large tertiary academic children's hospital between August 2019 and January 2020. There were six eligible patients, with a median age of 17 years. All patients reported tetrahydrocannabinol as well as nicotine e-cigarette use. Half of the patients had a preexisting diagnosis of asthma and four patients had mental health comorbidities. All patients presented with respiratory alkalosis and chest radiography showing diffuse bilateral infiltrates; two patients had pneumomediastinum, subcutaneous air and/or pneumothorax. The lowest documented ratio of oxygen saturation to inspired oxygen (SpO2:FiO2 or S/F ratio) ranged from 146 to 296. Two patients required an arterial line, with the lowest ratio of arterial oxygen to inspired oxygen (PaO2:FiO2 or P/F ratio) of 197 and 165. Two patients tested positive for rhinovirus and respiratory cultures were negative for all patients. Four patients underwent chest computed tomography imaging, which showed diffuse ground-glass opacities. Every patient required noninvasive positive pressure ventilation, with one progressing to invasive ventilation. All patients received broad-spectrum intravenous antibiotics and steroids, though there was considerable variability in dose, frequency, and duration of steroids. The hospital length of stay ranged from 5 to 16 days (median 8.3 days) with PICU length of stay ranging from 4 to 10 days (median 5.5 days). Four patients had pulmonary function testing before discharge, two of which showed decreased diffusing capacity of the lung for carbon monoxide. There were no patient deaths. This single-center case series describes the presentation, course, and treatment of EVALI in a pediatric intensive care unit setting. Our results show nuanced differences in the presentation and management of the critically ill adolescent, and raise many questions about the long term implications on lung health, morbidity, and mortality. Importantly, these cases illustrate the critical care consequences of a public health phenomenon and should spur further research and policy to address the negative health effects of vaping.

Approach to prevention of non-alcoholic fatty liver disease after liver transplantation

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of liver disease and non-alcoholic steatohepatitis (NASH) related cirrhosis is third common indication for liver transplantation (LT). Patients who have NASH related cirrhosis and are candidates for LT often have multiple comorbidities. These comorbidities need to be addressed before and after transplantation as it affects overall survival. Like hepatitis B, hepatitis C, primary biliary cirrhosis, autoimmune hepatitis which recurs after transplantation, NASH also recurs after transplant however the impact of the recurrence on allograft and patient outcomes is unclear. Limited data suggests that it does not affect graft and patient survival. De novo NAFLD which is defined as occurrence of fatty liver in a patient who did not have fatty liver prior to LT can also occur in the allograft of patients transplanted for non-NAFLD liver disease. Obesity, hyperlipidemia, diabetes as well as steroid dose and duration after LT are common predictors of recurrence of NAFLD after transplantation. Studies on prevention and treatment of NASH in post-transplant patients are lacking. Prevention of weight gain, regular exercises, weight reducing surgery, limited steroid use or steroid free regimen have been tried with varying success. Future studies for the prevention of NAFLD/NASH are required especially in post liver transplant patient.

Intravenous vs intravenous plus aerosolized colistin for treatment of ventilator-associated pneumonia – a matched case–control study in neonates

ABSTRACT Background Recently intravenous (IV) and aerosolized (ASZ) colistin have been used for treating ventilator-associated pneumonia (VAP) due to colistin susceptible multidrug-resistant Gram-negative bacteria (MDR-GNB). Colistin has limited lung penetration. We compared the efficacy and safety of IV-alone versus IV+ASZ-colistin for treating VAP in neonates. Methods This retrospective matched case–control study was performed at NICU of the Aga Khan University Hospital, Pakistan between January 2015 and December 2018. Sixteen neonates with MDR-GNB associated VAP received IV-ASZ-colistin and were matched for date of birth, gestational age, birth weight, Apgar score, antenatal steroid history, disease severity, and duration of mechanical ventilation with 16 control neonates who received IV-colistin alone. Results Both groups had similar MDR-GNB isolates and Acinetobacter baumannii (78%) was the most common pathogen. No colistin-resistant strain was isolated. Duration of IV-colistin and concomitant antibiotics use was significantly (p < 0.05) shorter in the IV-ASZ-colistin group. Significantly (p < 0.05) higher clinical cure and microbial eradication, along with lower ventilatory requirements, mortality rate, and colistin induced nephrotoxicity and electrolyte imbalance was observed in the IV-ASZ-colistin group. Conclusions With better lung penetration, ASZ-colistin offers effective and safe microbiological and clinical benefits as adjunctive or alternate treatment of VAP due to colistin susceptible MDR-GNB in neonates.

Juvenile lupus and serum vitamin D levels: A cross-sectional study.

Juvenile systemic lupus erythematosus (JSLE) is usually associated with vitamin D deficiency and low bone mineral density. To evaluate serum levels of 25-OH vitamin D in JSLE patients and to correlate these findings with disease activity and bone density. This study was conducted on 100 patients with JSLE and 100 healthy children as controls. Disease duration and SLEDAI for disease activity were evaluated. CBC, anti-dsDNA, C3,C4,24hr urinary proteins, creatinine, estimated glomerular filtration rate(e-GFR),Ca,P,PTH, 25 (OH) D levels, and bone mineral density(BMD)Z score were measured. There were significant differences in mean 25(OH)D concentration between patients group (19.37 ± 9.72 ng/ml) and controls 35.90 ± 9.66 ng/ml(p < 0.05), with significant difference between active and inactive patients (p < 0.05).There were significant negative correlations between serum 25(OH)D and SLEDAI (r-0.545, p 0.001), steroid dose (r-0.561, p 0.001), anti-dsDNA (r-0.685, p 0.006), 24 hr-proteinuria (r-0.738, p 0.001) and PTH (r-0.335, p 0.001), significant positive correlations between 25(OH)D and C3 (r0.617, p 0.001),C4 (r0.544, p 0.001) serum Ca (r0.424, p 0.001) and Z score (r0.561, p 0.001),with non-significant correlations between 25(OH)D and serum P and both disease & steroid duration, (p > 0.05). Vitamin D deficiency is common in JSLE, it's correlated significantly with disease activity and bone mineral density.

72. THE COMBINED USE OF STEROIDS AND IMMUNE CHECKPOINT INHIBITORS IN BRAIN METASTASES PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS

INTRODUCTIONImmune checkpoint inhibitors (ICI) are increasingly being administered to cancer patients, including those with brain metastases (BMs). However, little is known about the interaction between ICI and steroids such as dexamethasone. The aim of this study was to perform a systematic literature review and meta-analysis on the association between steroid use and overall survival (OS) in BM patients receiving ICI.METHODSA systematic literature search was performed in PubMed, Embase, Web of Science, Cochrane, Academic Search Premier, and PsycINFO. Pooled effect estimates were calculated using random-effects models; analysis was performed across all included studies and stratified by tumor type.RESULTSAfter screening 978 abstracts, thirteen studies were included for systematic review. Ten studies reported sufficient data for meta-analysis, comprising 838 BM patients of which 335 (40%) had received steroids. In the steroid group, median OS ranged from 2.9 months to 10.2 months across studies. In the non-steroid group, median OS ranged from 4.9 to 25.1 months. Pooling results demonstrated significantly worse survival in the steroid group (HR 1.97; 95% CI 1.65–2.36); no significant heterogeneity (I2 = 0%) or publication bias (Egger’s p = 0.29) was identified. Stratified analysis showed a consistent effect across melanoma (HR 1.71, 95% CI 1.34–2.18) and non-small cell lung cancer (HR 2.26, 95% CI 1.49–3.43) subgroups.CONCLUSIONAdministration of steroids is associated with a significantly worse OS in BM patients receiving ICI. Further investigation on dose, timing and duration of steroids in this population is needed to elucidate the cause of this association and optimize outcomes in BM patients receiving ICI.

Vascularites associées aux ANCA avec atteinte rénale recevant un traitement d’induction par cyclophosphamide oral versus intraveineux : étude rétrospective multicentrique de la survie sans rechute (VaReCyS)

IntroductionANCA-vasculitis are associated with high morbidity and mortality. Large use of cyclophosphamide as induction immunosuppressive therapy is limited by its side effects. All recent literature trends in decreasing cumulative dose while optimizing maintenance therapy. MethodsThis retrospective multicentric analysis included ANCA-vasculitis patients with renal impairment and de novo diagnose followed in Rennes and Vannes hospitals for 2 years minimum. The primary endpoint was to analyze relapse free survival comparing oral and intravenous administration of cyclophosphamide. ResultsFrom 01/01/2003 to 01/03/2016, 91 patients were included (45 oral and 46 intravenous group). Patients in oral group were 10 years younger (P<0,001), with higher maintenance therapy (P<0,001) and steroids (P<0,001) duration. With a Cox model adjusted on age, steroid and maintenance therapy duration, oral cyclophosphamide showed no benefice in decreasing relapse free survival (OR 0,80; 95%IC 0,38–1,66; P=0,55). No difference was observed on either mortality or renal survival. Oral group at 1-year trends to achieve more leucopenia (40 vs 24%) and infection (30 vs 22%) episodes, but less hospitalization (40 vs 65%), without reaching statistical significance. ConclusionIn this retrospective multicentric analysis, oral cyclophosphamide induction was not associated with better relapse free survival after adjustment with age, steroid and maintenance therapy duration. Maintenance therapy duration is believed to better prevent ANCA-vasculitis relapse.

Bone Densitometry in a Cohort of Egyptian Children with Steroid Sensitive Nephrotic Syndrome.

Introduction Nephrotic syndrome is one of the most frequent glomerular diseases among children. Steroid therapy is still the standard treatment of this disease. Aim of the Study This study aims to assess bone density in children with steroid sensitive nephrotic syndrome (SSNS) and to correlate the degree of bone density affection to steroid dose and duration. Methods Fifty children with SSNS [25 steroid dependent/ frequent relapsing (SDNS/FRNS) and 25 infrequently relapsing (IFRNS) patients] were assessed clinically and laboratory. Bone mineral density (BMD) was measured to all included patients by Duel energy X-ray absorptiometry. Results BMD abnormality is significantly increased in SDNS/FRNS group than IFRNS group (p = 0.0001). BMD Z score negatively correlated with relapse frequency-/year [p = 0.001 and correlation coefficient (CC) = -0.586]. Bone ache was the only significant complaint in patients with abnormal BMD (p = 0.004). Significant negative correlation was found between BMD Z score and each of serum alkaline phosphatase (ALP) level and Levamisol therapy duration (p 8329.4 mg/m2 with sensitivity of 85% and specificity of 96.67% and area under curve (AUC) of 0.92. Conclusion Impaired BMD in SSNS children significantly correlates with frequency of relapses, serum alkaline phosphatase level, Levamisol therapy duration, steroid doses and duration. At a cumulative steroid dose > 8329.4 mg/m2, BMD impairment is predicted with sensitivity 85% and specificity 97%.