Use Of Glucocorticoids In Patients Research Articles

Glucocorticoid use in acute respiratory failure from pulmonary causes and association with early changes in the systemic host immune response

BackgroundGlucocorticoids are commonly used in patients with or at-risk for acute respiratory distress syndrome (ARDS), but optimal use remains unclear despite well-conducted clinical trials. We performed a secondary analysis in patients previously enrolled in the Acute Lung Injury and Biospecimen Repository at the University of Pittsburgh. The primary aim of our study was to investigate early changes in host response biomarkers in response to real-world use of glucocorticoids in patients with acute respiratory failure due to ARDS or at-risk due to a pulmonary insult. Participants had baseline plasma samples obtained on study enrollment and on follow-up 3 to 5 days later to measure markers of innate immunity (IL-6, IL-8, IL-10, TNFr1, ST2, fractalkine), epithelial injury (sRAGE), endothelial injury (angiopoietin-2), and host response to bacterial infections (procalcitonin, pentraxin-3). In our primary analyses, we investigated the effect of receiving glucocorticoids between baseline and follow-up samples on host response biomarkers measured at follow-up by doubly robust inverse probability weighting analysis. In exploratory analyses, we examined associations between glucocorticoid use and previously characterized host response subphenotypes (hyperinflammatory and hypoinflammatory).Results67 of 148 participants (45%) received glucocorticoids between baseline and follow-up samples. Dose and type of glucocorticoids varied. Regimens that used hydrocortisone alone were most common (37%), and median daily dose was equivalent to 40 mg methylprednisolone (interquartile range: 21, 67). Participants who received glucocorticoids were more likely to be female, to be on immunosuppressive therapy at baseline, and to have higher baseline levels of ST-2, fractalkine, IL-10, pentraxin-3, sRAGE, and TNFr1. Glucocorticoid use was associated with decreases in IL-6 and increases in fractalkine. In exploratory analyses, glucocorticoid use was more frequent in participants in the hyperinflammatory subphenotype (58% vs 40%, p = 0.05), and was not associated with subphenotype classification at the follow-up time point (p = 0.16).ConclusionsGlucocorticoid use varied in a cohort of patients with or at-risk for ARDS and was associated with early changes in the systemic host immune response.

Glucocorticoid Use in Patients Hospitalized with Chronic Obstructive Pulmonary Disease Exacerbations.

Systemic glucocorticoid therapy can improve the outcomes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The study tried to investigate the use of glucocorticoids in AECOPD patients and the factors associated with the physicians' choice. Patients with AECOPD over two periods were divided by the year of 2017 when GOLD and ERS/ATS Guideline for COPD were updated. Data of patients regarding the study was retrieved from medical records. Descriptive statistical analysis was used for the illustration of glucocorticoids use, and hypothesis testing for comparison over the periods. Between 2010 and 2016, the proportion of ICS use was 522/640 (81.6%) and 341/452 (75.4%) between 2017 and 2020. COPD severity (GOLD C/D classification), bronchial asthma, percentage of neutrophils, and higher PaCO2 were factors associated with physicians' prescription of systemic glucocorticoids between 2010 and 2016. While the use of ICS at the stable stage, counts of neutrophils, and higher PaCO2 were influencing factors between 2017 and 2020. Over the two periods, 1-year recurrent rate decreased from 32.4% to 20.9%, with a significant statistical difference (P<0.001). The optimized use of glucocorticoids was found after the publishment of 2017 ERS/ATS Guideline for COPD, this improvement was associated with a decreased 1-year recurrence rate among AECOPD patients at our institution, underscoring the positive impact of guideline updates on patient outcomes.

Oral glucocorticoid use in patients with rheumatoid arthritis initiating TNF-inhibitors, tocilizumab or abatacept: Results from the international TOCERRA and PANABA observational collaborative studies

ObjectiveTo evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA). MethodsWe included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis. ResultsA total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was ≈2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48–0.87] for abatacept, and 1.04 [0.76–1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83–1.47] for abatacept, and 1.30 [0.96–1.78] for tocilizumab. ConclusionAfter initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guidelines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved.

The glucocorticoid receptor associates with RAS complexes to inhibit cell proliferation and tumor growth.

Mutations that activate members of the RAS family of GTPases are associated with various cancers and drive tumor growth. The glucocorticoid receptor (GR), a member of the nuclear receptor family, has been proposed to interact with and inhibit the activation of components of the PI3K-AKT and MAPK pathways downstream of RAS. In the absence of activating ligands, we found that GR was present in cytoplasmic KRAS-containing complexes and inhibited the activation of wild-type and oncogenic KRAS in mouse embryonic fibroblasts and human lung cancer A549 cells. The DNA binding domain of GR was involved in the interaction with KRAS, but GR-dependent inhibition of RAS activation did not depend on the nuclear translocation of GR. The addition of ligand released GR-dependent inhibition of RAS, AKT, the MAPK p38, and the MAPKK MEK. CRISPR-Cas9-mediated deletion of GR in A549 cells enhanced tumor growth in xenografts in mice. Patient samples of non-small cell lung carcinomas showed lower expression of NR3C1, the gene encoding GR, compared to adjacent normal tissues and lower NR3C1 expression correlated with a worse disease outcome. These results suggest that glucocorticoids prevent the ability of GR to limit tumor growth by inhibiting RAS activation, which has potential implications for the use of glucocorticoids in patients with cancer.

Real-world evidence of the use of glucocorticoids for severe COVID-19.

Introduction:Currently, only glucocorticoids have proved to impact adverse outcomes in COVID-19. However, their risk/benefit balance remains inconclusive and populations’ characteristics should be considered.Objective:The objective was to evaluate the real-life use of glucocorticoids in patients with severe COVID-19 hospitalized in a third-level referral center and to determine the type, accumulated doses, and the in-hospital outcomes related with their use.Methods:We evaluated a retrospective cohort of 737 patients with criteria for severe COVID-19 and a positive polymerase chain reaction (PCR) test for SARS-CoV-2. We extracted data for epidemiological analysis, medical history, and medications, as well as baseline laboratory tests. Data were analyzed using SPSS 21.0 and nonparametric tests, medians, and interquartile ranges (IQR). A p < 0.05 was considered significant.Results:A total of 65.3% were men, with a median age of 59 years (IQR 46–70) and a median of 10 days of hospital stay (IQR 6–16), more than 40% had diabetes, hypertension, and/or obesity, and 0.8% used steroids chronically. At the time of the study, 54.0% had been discharged due to improvement and 40.8% died. The most common treatment used was dexamethasone 6 mg/day/10 days (46.6%). Patients with a complete dexamethasone scheme [as proposed by the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study] had a lower mortality risk [hazard ratio (HR) 0.441, 95% confidence interval (CI) 0.232–0.840] in comparison with patients with lower doses (HR 1.803, 95% CI 1.080–3.012). Patients with methylprednisolone or several steroids tended to have higher cumulative doses (equivalent to >675 mg of prednisolone).Conclusion:The use of steroids in severe COVID-19 reduces mortality only at the dose proposed in the RECOVERY study in the younger population. No benefit of the use of steroids was observed in patients with older age or higher number of comorbidities.

Glucocorticoids and Risk of Venous Thromboembolism in Asthma Patients Aged 20-59 Years in the United Kingdom's CPRD 1995-2015.

BackgroundGlucocorticoids, the class of steroids used in management of asthma, have been observed to be associated with adverse events such as increased coagulation and inhibition of fibrinolysis. This study evaluated the risk of VTE in relation to the use of glucocorticoids in patients with asthma.MethodsWe conducted a nested case–control study among patients aged 20–59 years with asthma who received at least one glucocorticoid prescription during 1995–2015 in the UK-based Clinical Practice Research Datalink GOLD. We used descriptive analyses and conditional logistic regression to evaluate the risk of VTE associated with glucocorticoid use.ResultsThe adjusted ORs (aORs) (95% CI) for VTE in patients exposed to glucocorticoids were 1.9 (1.6–2.3), 1.4 (1.1–1.8), and 1.2 (0.9–1.5) for current, recent, and past glucocorticoid users, respectively, compared to the unexposed. The aORs (95% CI) for VTE in patients exposed to systemic glucocorticoid and inhaled glucocorticoids, compared to the unexposed, were 3.5 (2.7–4.5) and 1.5 (1.3–1.8), respectively.ConclusionCurrent and systemic glucocorticoid use was associated with a dose-response increased risk of incident idiopathic VTE.

Resolution of the Expert Council «The role of type I interferon inhibitor in the treatment of patients with systemic lupus erythematosus»

On April 28, 2021, a meeting of the Council of Experts was held with the participation of the leading experts in the field of rheumatic diseases, approaches to the treatment of patients with systemic lupus erythematosus (SLE) were discussed. The issues of medical care for patients with SLE and their routing, key points of Russian and international clinical guidelines for the management of patients with SLE, as well as the role of interferon (IFN) type I in the pathogenesis of the disease were discussed. It is noted that the management of patients with SLE requires a multidisciplinary approach. The basis of therapy is the use of glucocorticoids (GC), immunosuppressive drugs and their combinations. But long-term use of GC in patients with SLE leads to severe complications. Early prescription of biological disease-modifying antirheumatic drugs (bDMARDs) allows to achieve the greatest effect and prevent the development of irreversible organ damage associated with SLE. Currently data from three clinical trials on the efficacy and safety of the type I IFN inhibitor anifrolumab are available. During the discussion, experts defined the clinical profile of a patient with SLE, for whom administration of bDMARD therapy is indicated. According to experts, the use of a type I IFN inhibitor in routine clinical practice can improve disease outcomes in both short and long term.

Laboratory control of the osteoresorptive effects of glucorcorticoids in patients with purpose colitis.

The aim of the work was to develop an informative method for laboratory monitoring of osteoresorbent action during systemic administration of glucocorticoids in patients with ulcerative colitis. The study included 54 patients with ulcerative colitis aged 18 to 44 years: 35 (64,8%) men and 19 (35,2%) women. In patients of the clinical group before and after the first, second, third courses of glucocorticosteroids, as well as during the formation of steroid dependence, the concentration of the osteoresorption marker cathepsin K was determined simultaneously in the blood serum and gingival fluid by enzyme immunoassay. The concentration of the osteomarker was compared with the parameters of the densitometric density of the lumbar vertebrae L1-L4 during X-ray examination. It was found that with the systemic use of glucocorticoids in patients with ulcerative colitis, the concentration of cathepsin K in the gingival fluid increased earlier than in the blood serum. It was found that with an increase in the concentration of cathepsin K in the gingival fluid of more than 2,6 pmol/l in conditions of systemic administration of glucocorticosteroids, the risk of osteoporosis increased with a diagnostic sensitivity of 81,8% and a specificity of 74,4% (p=0,0001).The diagnostic accuracy was 78,1%. With an increase in the concentration of cathepsin K in the gingival fluid above the differential separation level (2,6 pmol/l), the risk of developing osteoporosis increased 3,2 times (p= 0,0001). The study developed a methodological and informational algorithm has been developed for the non-invasive control of steroidal osteoporosis in patients with ulcerative colitis with systemic use of glucocorticoids by assessing the concentration of cathepsin K in the gingival fluid.

Perspectives of Glucocorticoid Use in Patients with Rheumatoid Arthritis.

ObjectivePrednisolone is an effective oral glucocorticoid for managing symptoms of rheumatoid arthritis (RA) but has predictable and common adverse effects. We explored patient perspectives of prednisolone use in RA.MethodsPatients with RA registered with the Australian Rheumatology Association Database (ARAD) who had completed an ARAD questionnaire in the preceding 12 months were invited to participate in an online survey. Responses were linked to already collected respondent demographics, medication use, and patient‐reported outcome measures. The Beliefs about Medicine Questionnaire (BMQ) measured patient beliefs on medication necessity and concerns. Free‐text responses outlining reasons for stopping or declining prednisolone underwent thematic analysis using NVivo 12.ResultsThe survey response rate was 79.6% (804/1010), including 251 (31.2%) reporting current prednisolone use and 432 (53.7%) reporting previous use. Compared with previous users, current users were older (P = 0.0002) and had worse self‐reported pain, disease activity, health‐related quality of life, and function (all P < 0.001). Current users had higher BMQ scores for prednisolone‐specific necessity (3.6 versus 1.7; P <0.001) and concerns (2.7 versus 2.3; P <0.001). In previous prednisolone users (n = 432), the most frequent themes identified in free‐text responses for cessation were adequate disease control (30.3%), adverse effects (25.2%), and predetermined short courses (21.3%). Of respondents citing adverse effects for cessation (n = 131), weight gain (27.5%), osteoporosis (14.7%), and neuropsychiatric issues (13.8%) were most frequent.ConclusionsIn our cohort, patients with RA taking prednisolone believed it was necessary yet remained concerned about its use. Adequate disease control and adverse effects were important considerations for patients using prednisolone.

Glucocorticoid use in patients with adrenal insufficiency following administration of the COVID-19 vaccine: a pituitary society statement.

PurposeSide effects of the coronavirus disease 2019 (COVID-19) vaccines include pain at the injection site, fatigue, headache, myalgias, arthralgias, chills, and fever, all of which can be early indicators of an increased need for glucocorticoid replacement in patients with adrenal insufficiency. The Pituitary Society surveyed its membership to understand planned approaches to glucocorticoid management in patients with adrenal insufficiency who will receive a COVID-19 vaccine.MethodsMembers were asked to complete up to 3 questions regarding their planned approach for use of glucocorticoid replacement in patients with proven adrenal insufficiency.ResultsSurveys were sent to 273 members and 103 responded. Thirty-six percent plan to recommend that patients automatically increase glucocorticoid dosage with administration of the first vaccine injection. Of these, 84% plan to increase glucocorticoid dose on the day of vaccination, and 49% plan to increase glucocorticoid dose prior to vaccination. Of the 64% who do not plan to recommend automatic glucocorticoid dose increase with vaccine administration, 88% plan to increase the dose if the patient develops a fever, and 47% plan to increase the dose if myalgias and arthralgias occur.ConclusionsMost clinicians plan to maintain the current glucocorticoid dose with vaccine administration. The vast majority plan and to increase glucocorticoid dose in case of fever, and just under half in case of arthralgias and myalgias. These survey results offer suggested management guidance for glucocorticoid management in patients with adrenal insufficiency.

Thromboses and COVID-19: reducing inflammation in addition to thromboprophylaxis.

Thromboses and COVID-19: reducing inflammation in addition to thromboprophylaxis.

Diagnosis and Management Considerations in Steroid-Related Hyperglycemia in COVID-19: A Position Statement from the Endocrine Society of India.

The current coronavirus disease (COVID-19) pandemic is showing no signs of abatement and result in significant morbidity and mortality in the infected patients. Many therapeutic agents ranging widely between antivirals and anti-inflammatory drugs have been used to mitigate the disease burden. In the deluge of the drugs being used for COVID-19 infection, glucocorticoids (GCs) stand out by reducing mortality amongst in-hospital severe-to-critically ill patients. Health-care practitioners have seen this as a glimmer of hope and started using these drugs more frequently than ever in clinical practice. The fear of mortality in the short term has overridden the concern of adverse long-term consequences with steroid use. The ease of availability, low cost, and apparent clinical improvement in the short term have led to the unscrupulous use of the steroids even in mild COVID-19 patients including self-medication with steroids. The use of GCs has led to the increasing incidence of hyperglycemia and consequent acute complications of diabetic ketoacidosis and mucormycosis in COVID-19 patients. There is an urgent need to dissipate information about optimum management of hyperglycemia during steroid use. In view of this, the Endocrine Society of India has formulated this position statement about the diagnosis and management of hyperglycemia due to the use of GCs in patients with COVID-19 infection.

Dexamethasone and remdesivir: finding method in the COVID-19 madness

Dexamethasone and remdesivir: finding method in the COVID-19 madness

Use of glucocorticoids in patients with acute respiratory distress syndrome: a meta-analysis and trial sequential analysis

BackgroundAcute respiratory distress syndrome (ARDS) is a common and disabling disease with high rates of mortality and morbidity. The role of steroids in treating ARDS remains controversial. We aim to examine the evidence behind using glucocorticoids in the management of ARDS from the available studies.MethodsWe performed a literature review of major electronic databases for randomized controlled trials (RCTs) comparing glucocorticoids versus placebo in treating patients with ARDS. Our primary outcome was hospital mortality. Other outcomes included ICU mortality, number of ventilator-free days at day 28, incidence of nosocomial infections, and hyperglycemia. We performed a meta-analysis using a random effects model to calculate risk ratios (RR) and mean difference (MD) with their corresponding 95% confidence intervals (CI). A subsequent trial sequential analysis was performed to examine the strength of evidence and to guard against statistical type I and type II errors for our results.ResultsEight RCTs were included in the final analysis totaling of 1091 patients, with a mean age of 57 ± 16, and 56.2% were male. In our pooled analysis, use of glucocorticoids was associated with a significant reduction in hospital mortality (RR 0.79; 95% CI 0.64–0.98; P = 0.03) and ICU mortality (RR 0.64; 95% CI 0.42–0.97; P = 0.04). Furthermore, glucocorticoid use was associated with an increased number of ventilator-free days at day 28 (MD 4.06 days; 95% CI 2.66–5.45; P < 0.01). Regarding adverse events, glucocorticoids use was not associated with an increased risk for nosocomial infections (RR 0.82; 95% CI 0.68–1.00; P = 0.05); however, it was associated with an increased risk of hyperglycemia (RR 1.11; 95% CI 1.01–1.24; P = 0.04). In our trial sequential analysis, the required diversity-adjusted information size (sample size = 2692 patients) was not reached, and the evidence was insufficient from the available RCTs.ConclusionAmong patients with ARDS, use of glucocorticoids is associated with a significant reduction in mortality and duration of mechanical ventilation, without increased risk of hospital-acquired infections. However, based on a trial sequential analysis, these findings may be secondary to a false-positive (type I) error. Further studies are needed for a firm conclusion with guarding against possible statistical errors.

MO040LONG-TERM FOLLOW-UP OF IGA NEPHROPATHY PATIENTS AT HIGH RISK OF PROGRESSION ACCORDING TO THE THERAPEUTIC APPROACH EMPLOYED: A MULTICENTER RETROSPECTIVE STUDY OF 947 PATIENTS

Abstract Background and Aims IgA-nephropathy (IgA-N) is a frequent cause of CKD and ESRD. The optimal therapeutic approach and the role of glucocorticoids and immunosuppression is still debated. Aim of this study was to perform a survey across several Italian centers focusing on the long-term outcome of patients with IgA-N at high risk of progression stratified according to the therapeutic approach employed. Method All the consecutive patients affected by biopsy proven IgA-N, proteinuria &amp;gt;1g/day and a follow-up longer than 24 months have been collected across 48 centers. The population has been divided in three groups according to the therapeutic approach: group-1 received ACEi or ARBs alone, group-2 a six months course of glucocorticoids while group-3 glucocorticoids and immunosuppressive drugs. Primary endpoints have been ESRD free-survival, halving of the eGFR free-survival and rate of non-responders (NR, proteinuria &amp;gt;1 g/day). Secondary endpoints have been assessment of the prognostic role of the time average proteinuria (TAP) as well as of the time average slope of proteinuria (TASP) and rate of severe adverse events (SAEs). Results 947 patients have been included and followed for a median time of 60 months (IQR 24-96). Baseline eGFR and proteinuria in the three groups have been respectively 68.1 (95%CI 63.9-72.4)-67.8 (95%CI 65.3-70.3)-63.3 (95%CI 58.5-68.1) ml/min/1.73m2 (p=0.191) and 2.38 (95%CI 2-2.77)-2.65 (95%CI 2.49-2.82)-3.26 (95%CI 2.89-3.64) g/day (p&amp;lt;0.001). Respectively 76/586 (13%) and 28/167 (17%) of the patients in group-2 and 3 required re-treatment with glucocorticoids alone or in combination with immunosuppressive drugs after a median of 24 months from the first cycle. ESRD free-survival has been longer in the group-2 (p=0.004) (figure, panel A); at subgroup analysis this was restricted to the patients with a eGFR&amp;lt;50 ml/min (p=0.004) (figure, panel B) while only a trend was observed in the ones with eGFR ≥50 ml/min (p=0.0631). The halving of the eGFR free-survival has been longer in group-2 only when limiting the analyses to the subgroup with eGFR&amp;lt;50 ml/min (p=0.026) (figure, panel C). The proportion of NR has been significantly lower in group-2 compared to group-1 throughout the first 36 months of follow-up (figure, panel D); of note being NR during the first 36 months increased the risk of developing ESRD during the follow-up (OR 4 95%CI 2.2-7.3, p&amp;lt;0.0001). The TAP and TASP of the first 24 months have been higher in the patients developing ESRD (respectively, mean 2.48 95%CI 2.14-2.82 and 0.81 95%CI 0.70-0.92) compared to the other patients (mean 1.12 95%CI 1.2-1.32 and 0.59 95%CI 0.56-0.61) (p&amp;lt;0.0001 for both comparisons). Of note the 24 months TASP of group-2 was lower compared to group-1 (respectively mean 0.56 95%CI 0.54-0.59 and 0.79 95%CI 0.71-0.87) (p&amp;lt;0.0001). The rate of patients experiencing SAEs during the first 6 months of therapy in the three groups has been respectively 2%, 7% and 16%; of these withdrawn of the therapeutic approach employed has been necessary in 67%, 21% and 48%. During the whole follow-up the number of SAEs per 100 patients/years has been respectively 1.9-2.7 and 2.5 in the 3 groups. Conclusion In this large multicenter retrospective survey, the use of glucocorticoids in patients with IgA-N at high risk of progression has been associated to longer ESRD free-survival, longer time to the halving of the eGFR in the subgroup with eGFR &amp;lt;50 ml/min, lower rate of non-response during the first 36 months of follow-up as well as lower TASP during the first 24 months. The overall rate of SAEs has been low but higher in the group receiving glucocorticoids alone or in combination with immunosuppressors.

Glucocorticoid use and complications following immune checkpoint inhibitor use in melanoma

Immune checkpoint inhibitors have demonstrated benefit in the treatment of cancer, but are associated with toxicities, which often require treatment with glucocorticoids. We aimed to determine the prevalence of glucocorticoid use in patients treated with immune checkpoint inhibitors for melanoma in a single centre. We performed a retrospective review of patients with advanced melanoma treated with an immune checkpoint inhibitor between September 2010 and January 2017. Patients treated with glucocorticoids had a cumulative dose and duration of glucocorticoid treatment calculated. New onset hyperglycaemia was also identified. Of 412 patients receiving immune checkpoint therapy, 157 (38%) required glucocorticoids to treat toxicities. The median cumulative glucocorticoid dose was 2,795 mg (prednisolone equivalent) with a median duration of 61 days. Twenty-seven patients receiving glucocorticoids were noted to develop new onset hyperglycaemia. Immune-related adverse events frequently occur in patients treated with immune checkpoint inhibitors. Consequently, patients receive prolonged courses of glucocorticoids. Awareness of glucocorticoid-induced side effects is required.

NCMP-07. SECONDARY ADRENAL INSUFFICIENCY IN ADULT PATIENTS WITH GLIOMA: A CASE SERIES

Abstract Glucocorticoids (GC) are a mainstay in the treatment of gliomas to reduce cerebral edema and improving symptoms related to swelling. Prolonged GC use can lead to adrenal insufficiency (AI) due to the suppression of the hypothalamic-pituitary-adrenal axis. AI is challenging to diagnose as the tumor itself or the chemotherapy are blamed for the symptoms. This study aims to evaluate the risk factors predisposing patients with gliomas to develop AI during their treatment course. METHODS This is a retrospective case review. Charts in the neuro-oncology clinic from July 2018 to March 2018 were reviewed. Inclusion criteria include &gt; 18 y/o, diagnosis of glioma WHO Grade II to IV, and diagnosis of secondary AI. Demographic profile, tumor characteristics, radiation dose, exposure or proximity to HPA, current treatment, and dexamethasone dose and duration of treatment were tabulated and compared. RESULTS Nine of ten patients were started on high dose of dexamethasone (&gt; 8mg daily), and only one was started on a lower dose (&lt; 4mg daily). Majority of the patients (50%) were on dexamethasone for less than a year (4–8 months), and a significant portion (40%) of the patients remained on dexamethasone for &gt; 2 years, with one patient on steroids for 64 months. The minimum dose of dexamethasone needed to prevent symptoms ranged from 0.5mg to 2mg daily. Most received 60Gy of radiation, two received 59.4 Gy, and one received 54 Gy. Six patients had radiation exposure to the HP axis, while four didn’t. CONCLUSION Secondary adrenal insufficiency results from prolonged glucocorticoid use in patients with glioma. Dose and duration of GC are risk factors to its development. Radiation to the HPA axis may be a contributing factor to the development of AI in patients with glioma, although it can also be seen in patients with radiation distant from the HPA.

Effect of glucocorticoids on mortality in patients with acute respiratory distress syndrome: A meta-analysis.

To date, the efficacy of glucocorticoid therapy to reduce mortality in patients with acute respiratory distress syndrome (ARDS) has remained controversial among the studies available. The present meta-analysis study aimed to further clarify the impact of glucocorticoid therapy on mortality in patients with ARDS by performing a pooled analysis of the previous data. The PubMed, Chinese Knowledge Infrastructure, Wanfang and Cochrane trials databases were searched for relevant studies published between 1966 and 2016. Randomized controlled trials (RCTs) that included the use of glucocorticoids in patients with ARDS and had reported on mortality were included. Odds ratios (OR) and 95% confidence intervals (CI) for mortality were calculated. A total of 10 RCTs were included in the meta-analysis. Of these, 4 studies used high-dose glucocorticoid therapy, while 6 used low-dose glucocorticoid therapy. In the pooled analysis, glucocorticoids were indicated to significantly reduce ARDS-associated mortality (OR=0.64, 95% CI: 0.48-0.85, P=0.002). Further subgroup analysis indicated the following: i) Long-term low-dose glucocorticoid therapy reduced ARDS-associated mortality compared with that in the control group (OR=0.60, 95% CI: 0.44-0.82, P=0.001), whereas high-dose short-term glucocorticoid therapy did not reduce mortality (OR=0.82, 95% CI: 0.43-1.57, P=0.55). ii) Early initiation of glucocorticoid therapy was associated with reduced mortality compared with that in the control group (OR=0.60, 95% CI: 0.44-0.83, P=0.002); however, late initiation did not reduce mortality (OR=0.36, 95% CI: 0.03-3.76, P=0.39). iii) Therapeutic rather than preventive use of glucocorticoids reduced mortality (OR=0.65, 95% CI: 0.49-0.86, P=0.003). Overall, the present meta-analysis suggests that early initiation of long-term low-dose glucocorticoid therapy reduces mortality of patients with ARDS.

Survey on the use of glucocorticoids in severe community-acquired pneumonia in intensive care unit of forty-five hospitals in Zhejiang Province

To investigate the use of glucocorticoids in patients with severe community-acquired pneumonia (SCAP) in the intensive care unit (ICU) of Hospitals in Zhejiang Province and to provide a reference for guiding clinical use of SCAP patients. To draw up a questionnaire with reference to the Chinese and international guidelines, and to investigate the knowledge of community-acquired pneumonia (CAP) related guidelines and the use of glucocorticoids in patients with SCAP by doctors in hospitals above secondary level in Zhejiang Province by Email. Then the valid questionnaire was analyzed. In June 2016, 340 questionnaires were distributed, and all were returned after 2 months, with 333 of valid; 333 doctors from 45 ICUs in Zhejiang Province participated in the survey. (1) The knowledge of CAP-related guidelines in ICU doctors: 79.58% (265/333) of the doctors had read the CAP guidelines, and those who work over 10 years had a higher reading rate than those with 1-5 years and 6-10 years [93.07% (94/101) vs. 74.00% (111/150), 73.17% (60/82), both P < 0.05]. Post-graduates and above had higher reading rates than undergraduates [85.35% (134/157) vs. 74.43% (131/176), P < 0.05]. Senior doctors had higher reading rates than the junior and intermediate doctors [93.07% (94/101) vs. 71.43% (80/112), 75.83% (91/120), both P < 0.05]. The rate of understanding the clinical application of glucocorticoids was 13.81% (46/333). The doctors who work over 10 years and the seniorshad a relatively high awareness rate, 23.76% (24/101) and 20.79% (21/101) respectively. However, there was no significant difference in the awareness rate between doctors with different degrees and different levels of hospitals. (2) For the use of glucocorticoids in different causes of pneumonia, 44.74% (149/333) of doctors routinely used glucocorticoids in severe viral pneumonia. The proportion of glucocorticoids used in severe bacterial pneumonia, severe fungal pneumonia, severe pneumocystis pneumonia, chronic obstructive pulmonary disease (COPD) and severe pneumonia were 22.82% (76/333), 9.31% (31/333), 22.52% (75/333) and 18.32% (61/333), respectively. (3) The way of glucocorticoid usage: 79.58% (265/333) of doctors chose methylprednisolone, 4.20% (14/333) chose hydrocortisone, 1.20% (4/333) chose dexamethasone, and 15.02% (50/333) had not use glucocorticoids. The proportion of physicians who chose to use glucocorticoids within 24 hours of admission and 1-7 days after admission were 52.65% (149/283) and 47.35% (134/283), respectively. Glucocorticoids were used more in doctors with lower academic qualifications and hospitals within 24 hours. The undergraduate degree was 61.39% (97/158), and the second-grade class hospital was 67.50% (27/40). Among the doctors who chose methylprednisolone, 60.75% (161/265) prescribe the dose ≤ 80 mg/d; 79.15% (224/283) chose the course of ≤ 7 days. The number of years of work, education, professional title and hospital grade had no significant effect on the choice of methylprednisolone and the course of treatment. ICU doctors of 45 hospitals in Zhejiang Province have a high degree of heterogeneity in the understanding of the use and guidelines of glucocorticoids in SCAP. It is necessary to strengthen the ICU doctor's study of clinical guidelines at home and abroad and to develop a glucocorticoid use plan according to the specific conditions of patients, so that SCAP patients can benefit more.

Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma

BackgroundDupilumab is a fully human anti–interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. Its effectiveness in reducing oral glucocorticoid use in patients with severe asthma while maintaining asthma control is unknown.MethodsWe randomly assigned 210 patients with oral glucocorticoid–treated asthma to receive add-on dupilumab (at a dose of 300 mg) or placebo every 2 weeks for 24 weeks. After a glucocorticoid dose-adjustment period before randomization, glucocorticoid doses were adjusted in a downward trend from week 4 to week 20 and then maintained at a stable dose for 4 weeks. The primary end point was the percentage reduction in the glucocorticoid dose at week 24. Key secondary end points were the proportion of patients at week 24 with a reduction of at least 50% in the glucocorticoid dose and the proportion of patients with a reduction to a glucocorticoid dose of less than 5 mg per day. Severe exacerbation rates and the forced expiratory volume in 1 second (FEV1) before bronchodilator use were also assessed.ResultsThe percentage change in the glucocorticoid dose was −70.1% in the dupilumab group, as compared with −41.9% in the placebo group (P<0.001); 80% versus 50% of the patients had a dose reduction of at least 50%, 69% versus 33% had a dose reduction to less than 5 mg per day, and 48% versus 25% completely discontinued oral glucocorticoid use. Despite reductions in the glucocorticoid dose, in the overall population, dupilumab treatment resulted in a severe exacerbation rate that was 59% (95% confidence interval [CI], 37 to 74) lower than that in the placebo group and resulted in an FEV1 that was 0.22 liters (95% CI, 0.09 to 0.34) higher. Injection-site reactions were more common with dupilumab than with placebo (9% vs. 4%). Transient blood eosinophilia was observed in more patients in the dupilumab group than in the placebo group (14% vs. 1%).ConclusionsIn patients with glucocorticoid-dependent severe asthma, dupilumab treatment reduced oral glucocorticoid use while decreasing the rate of severe exacerbations and increasing the FEV1. Transient eosinophilia was observed in approximately 1 in 7 dupilumab-treated patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA VENTURE ClinicalTrials.gov number, NCT02528214.)