Use Of Corticosteroids In Patients Research Articles

Genetic factors associated with changes in muscle strength and mass during corticosteroid therapy

BACKGROUND: Corticosteroid use is associated with loss of muscle mass and strength, which is associated with an unfavorable prognosis of the underlying disease, as well as an increased risk of cardiovascular disease. Patients with multiple sclerosis (MS) have a higher baseline susceptibility to cardiovascular disease and a higher risk of adverse effects due to corticosteroid use. In clinical practice, different degrees of severity of side effects of corticosteroids are reported. This may be related to the presence of a genetic predisposition, the identification of which should allow a personalized approach to therapy. AIM: To evaluate the association of polymorphic variants of the glucocorticoid receptor gene NR3C1, the FTO gene, and the melatonin receptor genes MTNR1A, MTNR1B with the development of changes in muscle mass and strength in the context of corticosteroid use in patients with MS. MATERIALS AND METHODS: The study included 80 patients (mean age 36.3±10.0 years) with MS receiving pulse corticosteroid therapy: 4 (3; 4) g methylprednisolone. Patients were enrolled over the course of one year. To assess the primary endpoint (reduction in muscle mass and strength), muscle strength and mass were monitored before and after therapy using wrist dynamometry, the time-up-and-go test, and bioimpedancemetry. Polymorphic variants of the glucocorticoid receptor gene NR3C1, the FTO gene, and the melatonin receptor genes MTNR1A and MTNR1B were identified by real-time polymerase chain reaction. Intergenic interactions were evaluated using the multifactor dimensionality reduction (MDR) method. R (v. 3.2, R Foundation for Statistical Computing, Austria) was used for statistical analysis. RESULTS: In women with loss of muscle mass after corticosteroid therapy, there was an increased incidence of depression (p=0.01) for polymorphic variant BclI (rs41423247) of the NR3C1 gene (p=0.005). Reduced dominant arm strength in women was associated with a variant of the BclI gene (rs41423247) (p=0.02), genotypes including BclI (rs41423247) and N363S (rs56149945) (p=0.03). Men with decreased strength in the non-dominant arm were more likely to be smokers (p=0.03). Combinations of genotypes of the NR3C1, FTO, MTNR1B genes were identified with increased and decreased risk of muscle mass loss in women after corticosteroid therapy. Analysis of intergenic interactions showed a strong synergism between the polymorphic variant rs993960 of the FTO gene and rs10830963 of the MTNR1B gene. CONCLUSION: The presence of polymorphic variants BclI (rs41423247), N363S (rs56149945) of the glucocorticoid receptor gene NR3C1 is associated with loss of muscle strength and mass in women receiving corticosteroid therapy for MS. Combinations of genotypes of the NR3C1, FTO, MTNR1B genes have been identified with an increased risk of muscle mass loss in women after corticosteroid therapy. Modifiable factors associated with loss of muscle mass and strength and cardiovascular risk (depression, smoking) were identified. The data obtained can be used to personalize corticosteroid therapy and prevent cardiovascular and metabolic disorders.

Association of Ruxolitinib Cream Initiation With Continued Reduction in Use of Other Topical Treatments, Oral Corticosteroids, and Biologics for Atopic Dermatitis

The objective of this analysis was to examine the impact of ruxolitinib cream on the use of other treatments for atopic dermatitis (AD). This study used claims data from the Healthcare Integrated Research Database (HIRD®) to identify new users of ruxolitinib cream from October 1, 2021, to March 31, 2022. The index date was the date of the first claim for ruxolitinib cream. The baseline period was the 6-month period before the index date, and the follow-up period was 12 months after the index date, which was divided into months 1–6 and months 7–12. Use of other topical and systemic therapies for AD were descriptively analyzed. Among 556 ruxolitinib cream users with follow-up data, the mean number of ruxolitinib cream fills in the overall 12-month follow-up period was 2.1 (SD, 1.77; range, 1–12). The mean (SD) patient age was 40.3 (17.32) years. In months 1–6 and 7–12, 39.9% and 37.4% of patients were treated with ruxolitinib cream monotherapy, respectively; 72.5% and 73.9% of patients did not receive a new class of AD treatment during the respective follow-up periods. Topical corticosteroid use in patients was reduced from 53.4% at baseline to 31.3% in months 1–6 and 26.6% in months 7–12. Topical calcineurin inhibitor use decreased from 14.9% at baseline to 5.2% in months 1–6 and 5.0% in months 7–12. Similarly, topical phosphodiesterase 4 inhibitor use decreased from 6.7% at baseline to 3.4% in months 1–6 and 1.6% in months 7–12. The mean cumulative prednisone-equivalent dose was also reduced from 83.9 mg during the baseline period to 58.0 mg for months 1–6 and 47.3 mg for months 7–12. For patients who did not receive AD biologic therapy during the baseline period (n=431), 92.3% in months 1–6 and 91.4% in months 7–12 continued to remain off AD biologic therapy. Among patients who received AD biologics at baseline (n=125), 16.0% did not receive them in months 1–6 and 26.4% did not receive them in months 7–12. In conclusion, following initiation of ruxolitinib cream, there was a continued reduction in use of other topical therapies and oral corticosteroids for AD. Most biologic-naive patients (>90%) avoided biologics in the 12 months following ruxolitinib cream initiation. Approximately 1 in 4 patients who had biologic treatment during baseline did not continue biologic use in months 7–12. This 12-month analysis confirms earlier 6-month findings that indicated treatment with ruxolitinib cream may reduce the use of other topical therapies, oral corticosteroids, and biologics in patients with AD. (Funding, Incyte Corporation)

Profile of Oral Corticosteroid Use in Patients in Madison City Pharmacies

Hyperglycemia induced by corticosteroid use depends on the dose, indication and setting of use. The type of corticosteroid that causes a greater degree of hyperglycemia is the use of Deksametasonor metilprednisolonrednisolone compared to prednisolone or hydrocortisone. High risk of hyperglycemia due to the use of oral corticosteroids, especially Deksametasonor metilprednisolonrednisolone. The aim of this study was to determine the profile of oral corticosteroid use in Madiun City pharmacies. This research is an observational study using retrospective data. Where data was obtained from profile data on the use of oral corticosteroids in one of the pharmacies in Madiun City. Then the data is analyzed, percentages are calculated and presented in the form of tables, graphs and diagrams. The results obtained were that the number of oral corticosteroids used in Madiun City pharmacies in 2022 was 44,270 tablets and increased in 2023, namely 50,680 tablets. Meanwhile, the type of oral corticosteroid that is widely used is metilprednisolonrednisone 4 mg, namely 13,090 tablets (29.57%) in 2022 and 14,950 tablets (29.50%) in 2023. The increase in the use of metilprednisolonrednisolone 4mg from 2022-2023 is 1,860 tablets . The conclusion of this research is that the use of oral corticosteroids in Madiun City pharmacies in 2022 and 2023 will increase and the most common type of corticosteroid is metilprednisolonrednisolone 4 mg.

Outcomes of corticosteroid therapy in patients with viral community-acquired pneumonia

AimThe objective of this study was to assess the therapeutic effects of corticosteroids in adult patients hospitalized with viral community-acquired pneumonia.MethodsThis is a retrospective analysis of data collected prospectively from November 1996 to June 2024. All adult patients with viral community-acquired pneumonia were enrolled. The primary outcome was 30-day mortality. Secondary outcomes included all-cause in-hospital mortality, ICU admission, length of ICU and hospital stay, mechanical ventilation, and 1-year mortality. Propensity score matching (PSM) was used to obtain balance among the baseline variables in the two groups.ResultsOf the 524 patients with viral pneumonia, 30 (6%) received corticosteroids and 494 (94%) did not. Patients were primarily male (n = 299, 57%), with a median [Q1-Q3] age of 66.9 [55–81] years. The 3:1 propensity matching procedure identified 90 patients not treated with corticosteroid (CS-) as controls. After PSM, no difference in 30-day mortality was found [7% (95%CI 1 to 22%) vs. 4% (95%CI 1 to 11%), p = 0.639]. The risk of death at 30 days did not differ significantly in unmatched and matched cohorts [Hazard Ratio (HR) 1.33 (0.32–5.63), p = 0.695 vs. HR 1.51 (0.28–8.27), p = 0.632, respectively]. Nor were differences found in hospital length of stay, ICU admission and length of stay, or mechanical ventilation requirement and duration between matched and unmatched CS + and CS-.ConclusionsThere were no significant differences in the primary and secondary outcomes regarding the use of corticosteroids in patients with viral pneumonia.

No Impact of Prophylactic Corticosteroid Use in Patients Receiving Axicabtagene Ciloleucel for Large B-Cell Lymphoma

No Impact of Prophylactic Corticosteroid Use in Patients Receiving Axicabtagene Ciloleucel for Large B-Cell Lymphoma

CT-630 No Impact of Prophylactic Corticosteroid Use in Patients Receiving Axicabtagene Ciloleucel for Large B-Cell Lymphoma

CT-630 No Impact of Prophylactic Corticosteroid Use in Patients Receiving Axicabtagene Ciloleucel for Large B-Cell Lymphoma

Anifrolumab treatment improves patient-reported quality of life and decreases disease activity and corticosteroid use in patients with systemic lupus erythematosus: A qualitative study in Denmark.

Anifrolumab is a new therapeutic approach for individuals with systemic lupus erythematosus (SLE) directed at blocking the type 1 interferon pathway. Despite the expanding body of literature on Anifrolumab, an essential aspect remains absent: the subjective patient experience of treatment effects and implications on patients' health-related quality of life (HRQoL). The present study aimed to fill this void by elucidating the nuanced perspectives of SLE patients receiving Anifrolumab treatment by conducting qualitative in-depth interviews (IDIs). SLE patients at Aarhus University Hospital who had received at least three infusions of Anifrolumab were approached for inclusion in the study, which comprised two main elements: (1) qualitative IDIs and (2) collection of patient data from electronic medical records (EMRs). The IDIs were semi-structured and based on a discussion guide that included open-ended and close-ended questions. Verbatim transcripts were coded and analysed using qualitative software to understand concepts important to patients and to understand patients' own experiences before and after Anifrolumab therapy. A clinical chart review was conducted using EMR data at baseline, 3months, and 6months after Anifrolumab initiation. IDIs were completed with 14 patients, and EMR data was collected from 16 patients (treatment days range: 62-474). Of the 23 symptoms spontaneously reported by patients prior to Anifrolumab treatment, fatigue, joint pain, sun sensitivity, joint stiffness, skin rashes, and hair loss were the most common. Most symptoms improved, and none worsened during treatment. Patients reported significant impacts of disease on daily life before treatment: day-to-day activities, social life, emotional aspects, physical activity, concentration/memory, work/employment, and family/romantic relationships. Patients reported improvements in all aspects after treatment but were still impacted. From the EMR data, we observed a fall in disease activity after treatment initiation with a concomitant reduction in the use of corticosteroids. This study provides valuable insights into the subjective experiences of SLE patients treated with Anifrolumab, and the findings collectively contribute to a comprehensive understanding of the treatment's efficacy from the patients' perspective and its tangible effects on both subjective and objective parameters in SLE patients.

P.053 Concomitant corticosteroid use in ravulizumab-treated adults with anti-AChR antibody-positive gMG: results from the CHAMPION MG open-label extension

Background: Treatment of generalized myasthenia gravis (gMG) with reduced steroid dosages may minimize steroid-associated AEs. Corticosteroid dosage changes were not permitted during the 26-week, CHAMPION MG study of ravulizumab in adults with anti-acetylcholine receptor antibody-positive (AChRAb+) gMG. Participants who completed the study could receive ravulizumab in the open-label extension (OLE; NCT03920293); corticosteroid adjustments were permitted. Methods: Patients could receive intravenous ravulizumab (blind induction or bridging dose at Week 26 [OLE start] for those previously receiving placebo or ravulizumab, respectively, then 3000–3600 mg at Week 28 and every 8 weeks thereafter) for ≤4 years. Results: Among 161 patients (78 ravulizumab, 83 placebo) who entered the OLE and received ravulizumab for ≤164 weeks, 113 received oral or enteral corticosteroids during the OLE; the proportion treated with >10 mg/day corticosteroids decreased from 58% (n=66) at first OLE dose to 37% (n=42) (35 [31%] received ≤5 mg/day and 71 [63%] received ≤10 mg/day) at last reported dose. Fourteen patients (12%) discontinued corticosteroids. The mean (SD) corticosteroid dosage/patient decreased from 17.5 (11.9) mg/day at first OLE dose to 11.7 (10.9) mg/day at last assessment. Conclusions: Ravulizumab decreased corticosteroid use in patients with AChRAb+ gMG, suggesting a steroid-sparing role for ravulizumab.

EEG before chimeric antigen receptor T-cell therapy and early after onset of immune effector cell-associated neurotoxicity syndrome

BackgroundImmune effector cell-associated neurotoxicity syndrome (ICANS) is common after chimeric antigen receptor T-cell (CAR-T) therapy. ObjectiveThis study aimed to assess the impact of preinfusion electroencephalography (EEG) abnormalities and EEG findings at ICANS onset for predicting ICANS risk and severity in 56 adult patients with refractory lymphoma undergoing CAR-T therapy. Study designEEGs were conducted at the time of lymphodepleting chemotherapy and shortly after onset of ICANS. ResultsTwenty-eight (50%) patients developed ICANS at a median time of 6 days after CAR-T infusion. Abnormal preinfusion EEG was identified as a risk factor for severe ICANS (50% vs. 17%, P = 0.036). Following ICANS onset, EEG abnormalities were detected in 89% of patients [encephalopathy (n = 19, 70%) and/or interictal epileptiform discharges (IEDs) (n = 14, 52%)]. Importantly, IEDs seemed to be associated with rapid progression to higher grades of ICANS within 24 h. ConclusionsIf confirmed in a large cohort of patients, these findings could establish the basis for modifying current management guidelines, enabling the identification of patients at risk of neurotoxicity, and providing support for preemptive corticosteroid use in patients with both initial grade 1 ICANS and IEDs at neurotoxicity onset, who are at risk of neurological impairment.

Abstract 2647: Topical corticosteroids stimulate T cell-dependent melanoma growth control

Abstract Melanoma is the deadliest form of skin cancer. Treatment with immune checkpoint blockade (ICB) has transformed outcomes. However, half of melanoma patients do not derive long-term benefit. Side-effects of ICB are frequent, and typically managed by systemic or topical treatment with corticosteroids, widely known for their immunosuppressive effects. However, clinical data is contradictory as to the effect on prognosis of patients receiving ICB that also receive corticosteroids, with some studies suggesting a negative effect of steroid use, and others suggesting no effect or even positive outcomes with steroid use. Additionally, our lab recently showed that combining corticosteroids with ICB improves treatment responses in certain preclinical cancer models. Thus, understanding the role of corticosteroids in cancer progression, and their effect on the tumor immune microenvironment, is critical. In an intradermal murine melanoma model unresponsive to ICB, we found that topical corticosteroid treatment significantly impairs tumor growth. After just two doses, glucocorticoid-treated tumors shrank, whereas control-treated tumors doubled in volume. Intriguingly, this effect was lost in Rag1−/− mice (deficient in B and T cells) or in mice depleted of CD8+ T cells, uncovering a key role for T cells in corticosteroid-induced tumor growth control. Genetic ablation of the glucocorticoid receptor in tumor cells abrogated this effect, suggesting corticosteroids act directly on tumor cells to stimulate anti-tumor immunity. Analysis of TCGA RNA sequencing data showed melanoma patients with high glucocorticoid receptor expression have better overall survival than those with low expression, a finding repeated in a large, independent cohort of primary melanoma specimens of the Leeds Melanoma Cohort (n=703). Through cellular and molecular profiling using multiparametric flow cytometry and whole exome RNA sequencing, we have identified promising candidate pathways that might underlie the immune-dependent tumor control induced by steroids. Steroids induce tumor control in other, but not all, melanoma and non-melanoma tumor models studied, suggesting this may be a conserved immune-evasive pathway in a subset of tumors. Ongoing work aims to characterize the molecular and cellular effects of topical corticosteroid treatment, and to investigate their relevance in human melanoma. Given the widespread use of corticosteroids in patients receiving ICB, these unexpected findings may have significant clinical impact. Citation Format: Charles H. Earnshaw, Shih-Chieh Chiang, Agrin Moeini, Maria Koufaki, Eduardo Bonavita, Laetitia Nebot-Bral, Massimo Russo, Charlotte Bell, Theophile Bigirumurame, Jérémie Nsengimana, Julia Newton-Bishop, Christopher E. Griffiths, Santiago Zelenay. Topical corticosteroids stimulate T cell-dependent melanoma growth control [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2647.

Risk of fracture in patients with myasthenia gravis: a nationwide cohort study in Korea.

Myasthenia gravis (MG) is an autoimmune disorder that affects the neuromuscular junctions, resulting in muscle weakness and fatigue. Muscle weakness, restricted mobility, and frequent use of corticosteroids in patients with MG may predispose them to a higher risk of fractures. However, studies on the impact of MG on bone health and the associated fracture risk are scarce. Utilizing claim database of the Korean National Health Insurance Service collected between 2002 and 2020, we compared the risk of major osteoporotic fracture between 23 118 patients with MG and 115 590 individuals as an age- and sex-matched control group using multivariable Cox proportional hazard models. Over a median follow-up duration of 5.58years, the MG group (mean age 53.7years; 55% women) had higher risk of major osteoporotic fracture compared with controls (incidence rate 13.59 versus 9.74 per 10 000 person-years), which remained independent of age, sex, comorbidities, drug use including anti-osteoporotic agents, and previous fracture history (adjusted hazard ratio [aHR] 1.19, P < 0.001; subdistributed HR 1.14, P < 0.001 adjusted for mortality as competing risk). Subgroup analyses showed a greater association between MG and major osteoporotic fracture risk in younger (age 50 or younger) than older individuals (aHR 1.34 vs. 1.17) and in men compared with women (aHR 1.32 vs. 1.15; P for interaction < 0.05 for all). An imminent divergence of the fracture risk curve between MG and controls was observed for vertebral fracture, while there was time delay for non-vertebral sites, showing site-specific association. Factors associated with higher fracture risk in patients with MG were older age, female gender, high dose glucocorticoid use (>7.5mg/day), immunosuppressant use, and previous history of fracture. In summary, patients with MG had higher risk of major osteoporotic fracture compared with controls, which calls further preventive actions in this patient group.

2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia.

New evidence is available examining the use of corticosteroids in sepsis, acute respiratory distress syndrome (ARDS) and community-acquired pneumonia (CAP), warranting a focused update of the 2017 guideline on critical illness-related corticosteroid insufficiency. To develop evidence-based recommendations for use of corticosteroids in hospitalized adults and children with sepsis, ARDS, and CAP. The 22-member panel included diverse representation from medicine, including adult and pediatric intensivists, pulmonologists, endocrinologists, nurses, pharmacists, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines. We followed Society of Critical Care Medicine conflict of interest policies in all phases of the guideline development, including task force selection and voting. After development of five focused Population, Intervention, Control, and Outcomes (PICO) questions, we conducted systematic reviews to identify the best available evidence addressing each question. We evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach and formulated recommendations using the evidence-to-decision framework. In response to the five PICOs, the panel issued four recommendations addressing the use of corticosteroids in patients with sepsis, ARDS, and CAP. These included a conditional recommendation to administer corticosteroids for patients with septic shock and critically ill patients with ARDS and a strong recommendation for use in hospitalized patients with severe CAP. The panel also recommended against high dose/short duration administration of corticosteroids for septic shock. In response to the final PICO regarding type of corticosteroid molecule in ARDS, the panel was unable to provide specific recommendations addressing corticosteroid molecule, dose, and duration of therapy, based on currently available evidence. The panel provided updated recommendations based on current evidence to inform clinicians, patients, and other stakeholders on the use of corticosteroids for sepsis, ARDS, and CAP.

新型冠状病毒感染大流行期间慢性阻塞性肺疾病患者使用皮质类固醇进展

新型冠状病毒感染大流行期间慢性阻塞性肺疾病患者使用皮质类固醇进展

Optimizing inhaled corticosteroid use in patients with chronic obstructive pulmonary disease: assessing blood eosinophils, neutrophil-to-lymphocyte ratio, and mortality outcomes in US adults.

Accurate biomarkers for evaluating mortality rates in patients with chronic obstructive pulmonary disease (COPD) remain scarce. This study aimed to explore the relationships between mortality rates in patients with COPD and blood eosinophil counts, neutrophil counts, and lymphocyte counts, along with the neutrophil-to-lymphocyte ratio (NLR). Additionally, we sought to identify the optimal response values for these biomarkers when utilizing inhaled corticosteroids (ICS). Utilizing a nationally representative, multistage cross-sectional design and mortality correlation study, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 involving US adults aged 40 years or older with COPD. The primary endpoint was all-cause mortality, with Kaplan-Meier survival curves and restricted cubic splines applied to illustrate the relationship between leukocyte-based inflammatory markers and mortality. The analysis was conducted in 2023. Our analysis included 1,715 COPD participants, representing 6,976,232 non-institutionalized US residents [weighted mean age (SE), 62.09 (0.28) years; range, 40-85 years]. Among the participants, men constituted 50.8% of the population, and the weighted mean follow-up duration was 84.9 months. In the ICS use group, the weighted proportion of participants over 70 years old was significantly higher compared with the non-ICS use group (31.39% vs 25.52%, p < 0.0001). The adjusted hazard ratios for all-cause mortality related to neutrophil counts, lymphocyte counts, and NLR were 1.10 [95% confidence interval (CI), 1.04-1.16, p < 0.001], 0.83 (95% CI, 0.71-0.98; p = 0.03), and 1.10 (95% CI, 1.05-1.15; p < 0.0001), respectively. Optimal ICS response was linked with higher levels of eosinophil count (≥240 cells/μL), neutrophil count (≥3,800 cells/μL), NLR (≥4.79), and lower levels of lymphocyte count (<2,400 cells/μL). Adjusted baseline neutrophil, lymphocyte counts, and NLR serve as independent risk factors for all-cause mortality in patients with COPD. Further, ICS application appears to mitigate mortality risk, particularly when NLR levels reach 4.79 or higher, underlining the importance of ICS in COPD management.

Economic and clinical burden of chronic corticosteroid use in patients with Crohn[apos]s disease initiated on biologic or conventional therapies in the US: A retrospective claims study

BackgroundChronic corticosteroid (CS) use is associated with complications, but estimates of the economic and clinical burden in patients with Crohn’s disease (CD) are lacking. ObjectiveTo estimate the burden of chronic CS use in CD in the United States in terms of health care resource utilization (HRU), health care costs, and CS-related complications. MethodsThis was a retrospective study of adults with CD initiated on biologics or conventional therapies (index date). Patients from a deidentified insurance claims database (2004-2021) were classified as chronic CS users (>90 days of CS use) or nonchronic CS users based on a 12-month landmark period starting on the index date. Patient baseline characteristics were balanced, and outcomes (HRU, costs [2021 US dollars], and CS-related complications) 12 months after the landmark period were compared between CS groups using regressions with nonparametric bootstrap resampling to estimate confidence intervals and P values. ResultsBiologic initiators (mean age: 44 years, 55% female) included 3366 chronic and 3401 nonchronic CS users; conventional therapy initiators (mean age: 51 years, 59% female) included 3657 chronic and 3727 nonchronic CS users. Compared with nonchronic users, chronic users had significantly more inpatient days and outpatient visits (biologic initiators: 37% and 24% more, respectively; conventional therapy initiators: 36% and 17%, respectively; all P<0.05). Chronic users also had significantly higher mean all-cause total costs per-patient-per year (biologic: $72,967 vs. $63,100, mean cost difference [MCD] = $9867; conventional therapy: $40,144 vs. $26,426, MCD = $13,718; all P<0.001), as well as higher odds of infection (biologic: 14% higher; conventional therapy: 20% higher) and bone loss (63% and 41%, respectively) (all P<0.05). ConclusionChronic CS use in patients with CD is associated with a significant economic and clinical burden including higher HRU, health care costs, and prevalence of complications, suggesting unmet needs in the clinical management of this population.

Factors Affecting the Ability to Discontinue Oral Corticosteroid Use in Patients with EGPA Treated with Anti-Interleukin-5 Therapy

Introduction: Patients with eosinophilic granulomatosis with polyangiitis (EGPA) and some with severe eosinophilic asthma require continuous long-term oral corticosteroid (OCS) treatment for disease control. The anti-interleukin-5 agent, mepolizumab, has recently become available for the treatment of severe eosinophilic asthma and EGPA, with promising results and safety profiles. The proportion of patients with EGPA who discontinued oral steroids was 18% in the MIRRA trial. To compare patients with EGPA who were able to discontinue steroids with mepolizumab with those who could not. Methods: Twenty patients with EGPA treated with mepolizumab were evaluated at Osaka Habikino Medical Center. The OCS dose, asthma control test score, fractional exhaled nitric oxide levels, peripheral eosinophil count, and spirometric parameters were evaluated before and after treatment. Results: There was a significant reduction in the mean OCS dose from a prednisolone equivalent of 8.88 ± 4.99 mg/day to 3.18 ± 3.47 mg/day (p < 0.001). In this study, 40% of patients discontinued oral steroids. The most common reason for the failure to discontinue steroids in patients was poor asthma control. The percentage of predicted forced expiratory volume in 1 s significantly improved in patients with EGPA who could discontinue steroids after receiving mepolizumab. Conclusion: In this real-world study, treatment with mepolizumab for EGPA was associated with a significant reduction in OCS use; however, poor asthma control was identified as an inhibiting factor for steroid reduction.

Negative Prognostic Impact of High-Dose or Long-Term Corticosteroid Use in Patients with Relapsed or Refractory B-Cell Lymphoma Who Received Tisagenlecleucel

The prognostic impact of corticosteroid therapy in patients receiving tisagenlecleucel (tisa-cel) treatment who are more likely to develop cytokine release syndrome (CRS) remains unclear. This study aimed to evaluate the clinical impact and lymphocyte kinetics of corticosteroid administration for CRS in 45 patients with relapsed and/or refractory B cell lymphoma treated with tisa-cel. This was a retrospective evaluation of all consecutive patients diagnosed with relapsed and/or refractory diffuse large B cell lymphoma, follicular lymphoma with histologic transformation to large B cell lymphoma, or follicular lymphoma who received commercial-based tisa-cel treatment. The best overall response rate, complete response rate, median progression-free survival (PFS), and median overall survival (OS) were 72.7%, 45.5%, 6.6 months, and 15.3 months, respectively. CRS (predominantly grade 1/2) occurred in 40 patients (88.9%), and immune effector cell-associated neurotoxicity syndrome (ICANS) of all grades occurred in 3 patients (6.7%). No grade ≥3 ICANS occurred. Patients with high-dose (≥524 mg, methylprednisolone equivalent; n = 12) or long-term (≥8 days; n = 9) corticosteroid use had inferior PFS and OS to patients with low-dose or no corticosteroid use (both P < .05). The prognostic impact remained even in 23 patients with stable disease (SD) or progressive disease (PD) before tisa-cel infusion (P = .015). but not in patients with better disease status (P = .71). The timing of corticosteroid initiation did not have a prognostic impact. Multivariate analysis identified high-dose corticosteroid use and long-term corticosteroid use as independent prognostic factors for PFS and OS, respectively, after adjusting for elevated lactate dehydrogenase level before lymphodepletion chemotherapy and disease status (SD or PD). Lymphocyte kinetics analysis demonstrated that after methylprednisolone administration, the proportions of regulatory T cells (Tregs), CD4+ central memory T (TCM) cells, and natural killer (NK) cells were decreased, whereas the proportion of CD4+ effector memory T (TEM) cells was increased. Patients with a higher proportion of Tregs at day 7 had a lower incidence of CRS, but this did not affect prognosis, indicating that early elevation of Tregs may serve as a biomarker for CRS development. Furthermore, patients with higher numbers of CD4+ TCM cells and NK cells at various time points had significantly better PFS and OS, whereas the number of CD4+ TEM cells did not impact prognostic outcomes. This study suggests that high-dose or long-term corticosteroid use attenuates the efficacy of tisa-cel, especially in patients with SD or PD. Additionally, patients with high levels of CD4+ TCM cells and NK cells after tisa-cel infusion had longer PFS and OS.

Sepsis and Adrenal Insufficiency.

In sepsis, dysregulation of the hypothalamic-pituitary-adrenal axis, alterations in cortisol metabolism, and tissue resistance to glucocorticoids can all result in relative adrenal insufficiency or critical illness-related corticosteroid insufficiency (CIRCI). The symptoms and signs of CIRCI during sepsis are nonspecific, generally including decreased mental status, unexplained fever, or hypotension refractory to fluids, and the requirement of vasopressor therapy to maintain adequate blood pressure. While we have been aware of this syndrome for over a decade, it remains a poorly understood condition, challenging to diagnose, and associated with significantly diverging practices among clinicians, particularly regarding the optimal dosing and duration of corticosteroid therapy. The existing literature on corticosteroid use in patients with sepsis and septic shock is vast with dozens of randomized controlled trials conducted across the past 4 decades. These studies have universally demonstrated reduced duration of shock, though the effects of corticosteroids on mortality have been inconsistent, and their use has been associated with adverse effects including hyperglycemia, neuromuscular weakness, and an increased risk of infection. In this article, we aim to provide a thorough, evidence-based, and practical review of the current recommendations for the diagnosis and management of patients with sepsis who develop CIRCI, explore the controversies surrounding this topic, and highlight what lies on the horizon as new evidence continues to shape our practice.

The aqueous root extract of Withania somnifera ameliorates LPS-induced inflammatory changes in the in vitro cell-based and mice models of inflammation.

Introduction: Most critically ill COVID-19 patients have bronchitis, pneumonia, and acute respiratory distress syndrome (ARDS) due to excessive inflammatory conditions. Corticosteroids have largely been prescribed for the management of inflammation in these patients. However, long-term use of corticosteroids in patients with comorbidities such as metabolic, cardiovascular, and other inflammatory disorders is ideally not recommended due to safety issues. A potential and safer anti-inflammatory therapy is therefore the need of the hour. Withania somnifera (WS), a well-known herbal medicine used during the pandemic in India to prevent SARS-CoV2 infection, also possesses anti-inflammatory properties. Methods: In the present study, we, therefore, evaluated the effect of the aqueous extract of the roots of W. somnifera in the cell-based assays and in the experimental animal models of LPS-induced inflammation. Results: In the NCI-H460, A549 cells and human peripheral blood mononuclear cells (PBMCs) pre-treatment with W. somnifera reduced the LPS-induced expression of the pro-inflammatory cytokines. In addition, W. somnifera extract also showed potent anti-inflammatory activity in the lung tissues of BALB/c mice challenged intranasally with LPS. We observed a marked reduction in the neutrophil counts in the broncho-alveolar lavage (BAL) fluid, inflammatory cytokines, and fibrosis in the mice lungs pre-treated with W. somnifera. Results obtained thus suggest the potential utility of W. somnifera extract in reducing airway inflammation and recommend the clinical evaluation of W. somnifera extract in COVID-19 patients with a high propensity for lung inflammation.

Did the COVID-19 Pandemic Coincide With an Increase in Osteonecrosis as Indication for Total Hip Arthroplasty in Older Patients?

BackgroundOsteonecrosis of the femoral head is a common indication for total hip arthroplasty (THA). It is unclear to what extent the COVID-19 pandemic has impacted its incidence. Theoretically, the combination of microvascular thromboses and corticosteroid use in patients who have COVID-19 may increase the risk of osteonecrosis. We aimed to (1) assess recent osteonecrosis trends and (2) investigate if a history of COVID-19 diagnosis is associated with osteonecrosis. MethodsThis retrospective cohort study utilized a large national database between 2016 and 2021. Osteonecrosis incidence in 2016 to 2019 was compared to 2020 to 2021. Secondly, utilizing a cohort from April 2020 through December 2021, we investigated whether a prior COVID-19 diagnosis was associated with osteonecrosis. For both comparisons, Chi-square tests were applied. ResultsAmong 1,127,796 THAs performed between 2016 and 2021, we found an osteonecrosis incidence of 1.6% (n = 5,812) in 2020 to 2021 compared to 1.4% (n = 10,974) in 2016 to 2019; P < .0001. Furthermore, using April 2020 to December 2021 data from 248,183 THAs, we found that osteonecrosis was more common among those who had a history of COVID-19 (3.9%; 130 of 3,313) compared to patients who had no COVID-19 history (3.0%; 7,266 of 244,870); P = .001). ConclusionOsteonecrosis incidence was higher in 2020 to 2021 compared to previous years and a previous COVID-19 diagnosis was associated with a greater likelihood of osteonecrosis. These findings suggest a role of the COVID-19 pandemic on an increased osteonecrosis incidence. Continued monitoring is necessary to fully understand the impact of the COVID-19 pandemic on THA care and outcomes.