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OBJECTIVE: Despite limited safety and efficacy data, inhaled corticosteroids (ICS) are prescribed to premature infants in the neonatal intensive care unit (NICU). We examined contemporary use and risk factors for ICS use in the NICU. STUDY DESIGN: Infants

BACKGROUND: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The primary objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in a mouse model. A secondary objective was to identify shared transcriptomic features of pneumococcal pneumonia and steroid treatment in the mouse model and clinical samples. METHODS: We carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy. We also studied lower respiratory tract gene expression from a cohort of 15 mechanically ventilated patients (10 with Streptococcus pneumoniae and 5 controls) to compare with the transcriptional studies in the mice. RESULTS: In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden. Transcriptomic analyses identified effects of steroid therapy in mice that were also observed in the clinical samples. CONCLUSIONS: In combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The transcriptional studies in patients suggest that the mouse model replicates some of the features of pneumonia in patients with Streptococcus pneumoniae and steroid treatment. Overall, these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae.

IntroductionSymptomatic hip osteoarthritis (OA) causes significant morbidity and functional limitations. While corticosteroid injections (CSI) are commonly offered and administered for OA pain relief, it is unknown if they offer any clinically meaningful long-term benefit or reduce the overall need for surgical intervention.MethodsA cross-sectional retrospective cohort study was performed on primary hip osteoarthritis patients from a single academic tertiary-care center arthroplasty clinic from 2014 to 2019. Patients were divided into three groups. CSI + THA: hip CSI patients who underwent subsequent ipsilateral THA. CSI-noTHA: hip CSI who have not had ipsilateral THA to date. THA-noCSI: a control group of consecutive hip OA patients who underwent primary THA without prior CSI. Demographic variables, injection relief duration, and radiographic arthritis severity were recorded. Time from clinic presentation to injection and/or THA were compared.Results357 patients met inclusion criteria and underwent guided, arthroplasty provider-ordered CSI. Mean duration of relief was 6.7 weeks (SD 8.7). 244 injection patients (67.2%) subsequently underwent THA (CSI + THA). 150 of 390 patients have not undergone THA at mean of 25.5 months follow-up. Mean time from clinic presentation to THA was 8.6 months longer after CSI (16.3, SD 17.8) months in CSI patients compared to 7.7 (SD 10.6) months for patients without CSI (p

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four PICO questions (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.

PURPOSE: To summarize the evidence base on the use of topical corticosteroids for infectious keratitis. METHODS: Narrative review. RESULTS: Infectious keratitis is a painful condition that often results in visually significant corneal stromal scarring, even when antimicrobial therapy is successful. Corticosteroids may reduce inflammation and subsequent scar formation and while relieving the acute ocular pain associated with a corneal ulcer. However, corticosteroids also reduce the host immune response, which could hinder the ability to clear infection. The safety and effectiveness of corticosteroids depends to a large part on the efficacy of the antimicrobials being used to treat the underlying infection. Randomized trials have found that corticosteroids are safe and effective for herpetic keratitis when used with appropriate antiviral therapy, and are safe for bacterial keratitis when used with broad spectrum topical antibiotics. The effectiveness of corticosteroids for bacterial keratitis has not been shown conclusively, although more advanced bacterial corneal ulcers may do better with corticosteroids. No randomized trials have assessed the safety and effectiveness of steroids for fungal or acanthamoeba keratitis. Animal studies suggest corticosteroids may be harmful in fungal keratitis, and observational human studies have found that steroids are harmful for fungal and acanthamoeba keratitis when started prior to anti-amoebics. CONCLUSIONS: Topical corticosteroids, when used as an adjunct to antimicrobial therapy, may be beneficial if the antimicrobial being used can effectively clear or suppress the infection, such as in bacterial and herpetic keratitis. Randomized trials would be helpful to further delineate the role of corticosteroids for infectious keratitis.

BackgroundThe upper-airway microbiome is involved in asthma exacerbations despite inhaled corticosteroid (ICS) treatment. Although human genetics regulates microbiome composition, its influence on asthma-related airway bacteria remains unknown.ObjectiveWe sought to identify genes and biological pathways regulating airway-microbiome traits involved in asthma exacerbations and ICS response.MethodsSaliva, nasal, and pharyngeal samples from 257 European patients with asthma were analyzed. The association of 6,296,951 genetic variants with exacerbation-related microbiome traits despite ICS treatment was tested through microbiome genome-wide association studies. Variants with 1 × 10-4 -6 were examined in gene-set enrichment analyses. Significant results were sought for replication in 114 African American and 158 Latino children with and without asthma. ICS-response-associated single nucleotide polymorphisms reported in the literature were evaluated as microbiome quantitative trait loci. Multiple comparisons were adjusted by the false discovery rate.ResultsGenes associated with exacerbation-related airway-microbiome traits were enriched in asthma comorbidities development (ie, reflux esophagitis, obesity, and smoking), and were likely regulated by trichostatin A and the nuclear factor-κB, the glucocorticosteroid receptor, and CCAAT/enhancer-binding protein transcription factors (7.8 × 10-13 ≤ false discovery rate ≤ 0.022). Enrichment in smoking, trichostatin A, nuclear factor-κB, and glucocorticosteroid receptor were replicated in the saliva samples from diverse populations (4.42 × 10-9 ≤ P ≤ .008). The ICS-response-associated single nucleotide polymorphisms rs5995653 (APOBEC3B-APOBEC3C), rs6467778 (TRIM24), and rs5752429 (TPST2) were identified as microbiome quantitative trait loci of Streptococcus, Tannerella, and Campylobacter in the upper airway (0.027 ≤ false discovery rate ≤ 0.050).ConclusionsGenes associated with asthma exacerbation-related microbiome traits might influence asthma comorbidities. We reinforced the therapeutic interest of trichostatin A, nuclear factor-κB, the glucocorticosteroid receptor, and CCAAT/enhancer-binding protein in asthma exacerbations.

Abstract Background The aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them. Methods A two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis. Results A genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001–1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002–1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139–1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165–1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004–1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020–1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029–1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females. Conclusions Genetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE.

Background: The aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them. Methods: A two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis. Results: A genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001–1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002–1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139–1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165–1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004–1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020–1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029–1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females. Conclusions: Genetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE. [ABSTRACT FROM AUTHOR]

Background: During the Coronavirus Disease 2019 (COVID-19) pandemic, the demand for hospital beds has exceeded substantially. Thus, we aimed to conduct this study to identify factors associated with the risk of readmission in order to introduce the best discharge plan for patients with high risk of hospital readmission. Methods: This is a multicenter, case-control study including 1357 patients hospitalized with COVID-19 infection. Age-sex-matched case and control groups were paired at 1:2 ratios, and COVID-19 readmission rate was assessed. Moreover, the logistic regression analysis was applied to determine the factors associated with readmission. Results: Of the 1357 patients, 99 (7.29%) subjects were readmitted. The most common cause of readmission was respiratory distress. The median (interquartile) of the interval between hospital discharge and the second admission was 5 (2-16) days. Upon adjusting with the main risk factors, having at least one underlying disease and being treated with the corticosteroid were significantly associated with a higher rate of readmission (OR: 2.76, 95%CI: 1.30- 5.87) and (OR: 8.24, 95%CI: 3.72-18.22), respectively. Conclusion: Identification of risk factors of COVID 19 readmission will improve resource utilization and patient care. [ABSTRACT FROM AUTHOR]

ImportancePrescription drug prices are a leading concern among patients and policy makers. There have been large and sharp price increases for some drugs, but the long-term implications of large drug price increases remain poorly understood.ObjectiveTo examine the association of the large 2010 price increase in colchicine, a common treatment for gout, with long-term changes in colchicine use, substitution with other drugs, and health care use.Design, setting, and participantsThis retrospective cohort study examined MarketScan data from a longitudinal cohort of patients with gout with employer-sponsored insurance from 2007 through 2019.ExposuresThe US Food and Drug Administration's discontinuation of lower-priced versions of colchicine from the market in 2010.Main outcomes and measuresMean price of colchicine; use of colchicine, allopurinol, and oral corticosteroids; and emergency department (ED) and rheumatology visits for gout in year 1 and over the first decade of the policy (through 2019) were calculated. Data were analyzed between November 16, 2021, and January 17, 2023.ResultsA total of 2 723 327 patient-year observations were examined from 2007 through 2019 (mean [SD] age of patients, 57.0 [13.8] years; 20.9% documented as female; 79.1% documented as male). The mean price per prescription of colchicine increased sharply from $11.25 (95% CI, $11.23-$11.28) in 2009 to $190.49 (95% CI, $190.07-$190.91) in 2011, a 15.9-fold increase, with the mean out-of-pocket price increasing 4.4-fold from $7.37 (95% CI, $7.37-$7.38) to $39.49 (95% CI, $39.42-$39.56). At the same time, colchicine use declined from 35.0 (95% CI, 34.6-35.5) to 27.3 (95% CI, 26.9-27.6) pills per patient in year 1 and to 22.6 (95% CI, 22.2-23.0) pills per patient in 2019. Adjusted analyses showed a 16.7% reduction in year 1 and a 27.0% reduction over the decade (P

Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia often overlooked as a potential etiology of hemolysis and is challenging to diagnose because of the complicated testing methods required. We performed a systematic review of all reported cases to better assess the clinical, immunohematologic, and therapeutic characteristics of PCH. We systematically analyzed PubMed, Medline, and EMBASE to identify all cases of PCH confirmed by Donath-Landsteiner (DL) testing. Three authors independently screened articles for inclusion, and systematically extracted epidemiologic, clinical, laboratory, treatment, and outcomes data. Discrepancies were adjudicated by a fourth author. We identified 230 cases, with median presentation hemoglobin of 6.5 g/dL and nadir of 5.5 g/dL. The most common direct antiglobulin test (DAT) result was the presence of complement and absence of immunoglobulin G (IgG) bound to red blood cells, although other findings were observed in one-third of cases. DL antibody class and specificity were reported for 71 patients, of which 83.1% were IgG anti-P. The use of corticosteroids is common, although we found no significant difference in the length of hospitalization for patients with and without steroid therapy. Recent reports have highlighted the use of complement inhibitors. Among patients with follow-up, 99% (213 of 216) were alive at the time of reporting. To our knowledge, this represents the largest compilation of PCH cases to date. We discovered that contemporary PCH most commonly occurs in children with a preceding viral infection, corticosteroid use is frequent (but potentially ineffective), and DAT results are more disparate than traditionally reported.

Introduction: Currently, the application of intralesional triamcinolone with surgical excision is considered the most satisfactory treatment for keloids, with a low recurrence rate. Method: A case study was carried out covering reconstructive surgeries for patients with bilateral earlobe keloids, operated by the same plastic surgeon from July 2018 to January 2021 at the Hospital Regional de Sobradinho in Brasília-DF. The keloid scar (intralesional) was partially resected, leaving keloid margins in the surgical wound, and compared with the response after total resection (juxtalesional) of another scar in the same patient. Triamcinolone was applied preoperatively, with a total of 4 applications at intervals of 4 weeks between each session and in the immediate postoperative period, maintaining application every 30 days for 6 months. No patient had undergone previous treatments for keloids. Scars were evaluated postoperatively by the primary surgeon over a period of 12 months. Results: Four of 11 patients had some type of recurrence, totaling 36% of recurrence in our study. Total excision of the keloid (left ear) had more recurrences than the contralateral side where a 1mm margin of keloid was left in the scar (right ear). Conclusion: In the present study, we observed that when associated with treatment with triamcinolone pre-, intra-, and postoperatively, partial excision of the keloid presented lower rates of local recurrence when compared to total excision of the keloid.

We describe a rare case of acute mania in the setting of autoimmune adrenalitis. A 41-year-old male with no previous psychiatric diagnoses presented with impulsivity, grandiosity, delusions of telepathy, and hyperreligiosity following a previous hospitalization for an acute adrenal crisis and 2 subsequent days of low-dose corticosteroid treatment. Workups for encephalopathy and lupus cerebritis were negative, raising concern that this presentation might represent steroid-induced psychosis. However, discontinuation of corticosteroids for 5 days did not resolve the patient's manic episode, suggesting that his clinical presentation was more likely new onset of a primary mood disorder or a psychiatric manifestation of adrenal insufficiency itself. The decision was made to restart corticosteroid treatment for the patient's primary adrenal insufficiency (formerly known as Addison disease), coupled with administration of both risperidone and valproate for mania and psychosis. Over the following 2 weeks, the patient's manic symptoms resolved, and he was discharged home. His final diagnosis was acute mania secondary to autoimmune adrenalitis. Although acute mania in adrenal insufficiency is quite rare, clinicians should be aware of the range of psychiatric manifestations associated with Addison disease so that they can pursue the optimal course of both medical and psychiatric treatment for these patients.

Aim: To examine benefits of corticosteroids for Duchenne muscular dystrophy (DMD) by age and disease progression. Methods: Data from daily steroid users (placebo-treated) were pooled from four phase 2b/3 trials in DMD. Outcomes assessed overall and among subgroups included changes from baseline to 48 weeks in six-minute walk distance (6MWD), timed function tests and North Star Ambulatory Assessment total score. Results: Among 231 patients receiving deflazacort (n = 127) or prednisone (n = 104), observed differences in 6MWD favoring deflazacort over prednisone were significant for patients with relatively older age (≥8-years-old), greater disease progression (baseline timed stand from supine ≥5 s), or longer corticosteroid use (>3 years). Conclusion: Daily deflazacort had greater benefits than daily prednisone particularly among older/more progressed patients.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) considers blood eosinophil counts < 100 cells/μL (BEC≤100) in people with COPD to predict poor inhaled corticosteroid (ICS) responsiveness. However, the BEC≤100 phenotype is inadequately characterized, especially in advanced COPD. RESEARCH QUESTION: Are there differences between GOLD group D patients with high BEC and those with low BEC regarding baseline characteristics and longitudinal outcomes? STUDY DESIGN AND METHODS: We used multivariable mixed models and logistic regression to contrast clinical characteristics and outcomes of BEC≤100 vs BEC > 100 (BEC100+) in all subjects with COPD (n = 1,414) and GOLD group D subjects (n = 185) not receiving ICS. RESULTS: We identified n = 485 with BEC≤100 (n = 61 GOLD group D) and n = 929 people with BEC100+ (n = 124 GOLD group D). BEC≤100 status was stable at 6 weeks and approximately 52 weeks (intraclass correlations of 0.78 and 0.71, respectively). Compared with BEC100+, BEC≤100 comprised more women, with greater current smoking, and less frequent childhood asthma. Among all analyzed participants, the two BEC-defined subsets showed similar rates of lung function decline (mean slope, BEC≤100 vs BEC100+, -50 vs -39 mL/y; P = .140), exacerbations (0.40 vs 0.36/y; P = .098), subsequent ICS initiation (2.5% vs 4.4%; P = .071), and mortality (7.8% vs 8.4%; P = .715). However, in GOLD group D, people with BEC≤100 showed higher exacerbation rates within 365 days of enrollment (0.62 vs 0.33/y; P = .002) and total follow-up (1.16 vs 0.83/y; P = .014). They also had greater lung function decline (mean slope of -68 mL/y vs -23 mL/y; P = .036) and had greater emphysema at baseline (voxels < 950 Hounsfield units at total lung capacity of 7.46% vs 4.61%; P = .029). INTERPRETATION: In non-ICS-treated GOLD group D COPD, people with BEC≤100 had more baseline emphysema, prospective exacerbations, and lung function decline. Our analysis has identified a particularly vulnerable subpopulation of people with COPD, suggesting the need for studies focused specifically on their therapeutic treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01969344; URL: www. CLINICALTRIALS: gov.

Background and objectivesMyasthenia gravis (MG) is an autoimmune disease characterized by dysfunction at the neuromuscular junction. Treatment frequently includes corticosteroids (CSs) and IV immunoglobulin (IVIG). This study was conducted to determine whether immune globulin (human), 10% caprylate/chromatography purified (IGIV-C) could facilitate CS dose reduction in CS-dependent patients with MG.MethodsIn this randomized double-blind placebo-controlled trial, CS-dependent patients with MG (Myasthenia Gravis Foundation of America Class II-Iva; AChR+) received a loading dose of 2 g/kg IGIV-C over 2 days (maximum 80 g/d) or placebo at week 0 (baseline). Maintenance doses (1 g/kg IGIV-C or placebo) were administered every 3 weeks through week 36. Tapering of CS was initiated at week 9 and continued through week 36 unless the patient worsened (quantitative MG score ≥4 points from baseline). CS doses were increased (based on the current CS dose) in patients who worsened. Patients were withdrawn if worsening failed to improve within 6 weeks or if a second CS increase was required. The primary efficacy end point (at week 39) was a ≥50% reduction in CS dose. Secondary and safety end points were assessed throughout the study and follow-up (weeks 42 and 45). The study results and full protocol are available at clinicaltrials.gov/ct2/show/NCT02473965.ResultsThe primary end point (≥50% reduction in CS dose) showed no significant difference between the IGIV-C treatment (60.0% of patients) and placebo (63.3%). There were no significant differences for secondary end points. Safety data indicated that IGIV-C was well tolerated.DiscussionIn this study, IGIV-C was not more effective than placebo in reducing daily CS dose. These results suggest that the effects of IGIV-C and CS are not synergistic and may be mechanistically different.Trial registration informationThe trial was registered on clinicaltrialsregister.eu (EudraCT #: 2013-005099-17) and clinicaltrials.gov (identifier NCT02473965).Classification of evidenceThis study provides Class II evidence that IVIG infusions in adult patients with MG do not increase the percentage of patients achieving a ≥50% reduction in corticosteroid dose compared with placebo.

BACKGROUND: Duchenne muscular dystrophy (DMD) exhibits substantial variability in rates of disease progression and response to treatment. This has hindered treatment development and complicated interpretation of drug effects in clinical trials. OBJECTIVE: We hypothesized that a multivariate combination of early-age clinical outcome measurements can explain differential disease progression. METHODS: Data on boys with DMD (ages 4-

Administration of antenatal corticosteroids (AC) is the standard of care during pregnancy for women who are at risk of early delivery. Evidence indicates that AC improve survival and reduce morbidity for preterm infants. However, research suggests that infants whose mothers receive AC have an altered hypothalamic-pituitary-axis (HPA) response to stressors in early life. Results are mixed regarding the nature of these effects, with studies showing both suppressed and augmented HPA activity. In addition, research is very limited beyond the 4th month of life. The purpose of this study was to determine if AC exposure was associated with infant cortisol levels in a resting state or in response to a stressor at 1, 6 and 12 months postnatal. We also evaluated the moderating role of preterm birth in this association. 181 women and their infants participated in the study. Women were recruited during the 3rd trimester of pregnancy; at this time, they completed the Perceived Stress Scale and provided 8 salivary samples over a 2-day period for cortisol assay. They provided these data again at 6 and 12 months postnatal. At 1, 6, and 12 months postnatal, salivary samples were collected from infants to examine their cortisol levels before and after participation in a 'stressor protocol'. Data were extracted from the medical record on AC exposure, gestational age, maternal obstetric risk, and neonatal morbidity. Mixed effects multilevel regression modeling was used to examine the aims. Infants whose mothers received AC had significantly lower resting state (B = -2.47, CI: -3.691, -0.0484) and post-stressor (B = -2.51, CI: -4.283, -0.4276) cortisol levels across the first year of life than infants whose mothers did not receive AC. There was no moderating effect of preterm birth on the relationship between AC exposure and cortisol. Results indicate a state of dampened HPA activation and cortisol hypo-arousal that persists across the first year of life among infants who were exposed to corticosteroids in utero. Further research is needed to examine mechanisms responsible for any alterations that occur during development of the fetal HPA axis, including epigenetic and biochemical factors that control hormonal secretion, negative feedback, and glucocorticoid receptor function throughout the HPA axis. Findings warrant careful consideration by obstetric clinicians of the benefits and risks of prescribing AC.

Rationale: The use of hydrocortisone in adult patients with septic shock is controversial, and the effectiveness of adding fludrocortisone to hydrocortisone remains uncertain. Objectives: To assess the comparative effectiveness and safety of fludrocortisone plus hydrocortisone, hydrocortisone alone, and placebo or usual care in adults with septic shock. Methods: A systematic review and a Bayesian network meta-analysis of peer-reviewed randomized trials were conducted. The primary outcome was all-cause mortality at last follow-up. Treatment effects are presented as relative risks (RRs) with 95% credible intervals (CrIs). Placebo or usual care was the reference treatment. Measurements and Main Results: Among 7,553 references, we included 17 trials (7,688 patients). All-cause mortality at last follow-up was lowest with fludrocortisone plus hydrocortisone (RR, 0.85; 95% CrI, 0.72–0.99; 98.3% probability of superiority, moderate-certainty evidence), followed by hydrocortisone alone (RR, 0.97; 95% CrI, 0.87–1.07; 73.1% probability of superiority, low-certainty evidence). The comparison of fludrocortisone plus hydrocortisone versus hydrocortisone alone was based primarily on indirect evidence (only two trials with direct evidence). Fludrocortisone plus hydrocortisone was associated with a 12% lower risk of all-cause mortality compared with hydrocortisone alone (RR, 0.88; 95% CrI, 0.74–1.03; 94.2% probability of superiority, moderate-certainty evidence). Conclusions: In adult patients with septic shock, fludrocortisone plus hydrocortisone was associated with lower risk of all-cause mortality at last follow-up than placebo and hydrocortisone alone. The scarcity of head-to-head trials comparing fludrocortisone plus hydrocortisone versus hydrocortisone alone led our network meta-analysis to rely primarily on indirect evidence for this comparison. Although we undertook several sensitivity analyses and assessments, these findings should be considered while also acknowledging the heterogeneity of included trials. [ABSTRACT FROM AUTHOR]

To investigate the efficacy of corticosteroid (CS) injection methods for frozen shoulder. PubMed, Embase, and Cochrane Library were searched up to May 6, 2023. Randomized controlled trials (RCTs) that investigated CS injection methods for frozen shoulder were included. Data were extracted independently by 2 authors. Risk of bias was assessed using the RoB 2 tool. A random-effects network meta-analysis was performed within a frequentist framework. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. A total of 66 RCTs involving 4491 patients were included. For short-term outcomes, 4-site injection (vs placebo [PLA]: standardized mean difference [SMD]=−2.20, 95% confidence interval [CI], −2.81 to −1.59 in pain; SMD=2.02; 95% CI, 1.39-2.65 in global function) was the most effective (low certainty). Rotator interval injection was the optimal treatment with moderate to high certainty (vs PLA: SMD=−1.07, 95% CI, −1.51 to −0.64 in pain; SMD=0.94, 95% CI, 0.49-1.40 in global function). For midterm outcomes, 4-site injection was most effective (vs PLA: SMD=−1.71, 95% CI, −2.41 to −1.01 in pain; SMD=2.22, 95% CI, 1.34-3.09 in global function; low certainty). Distension via rotator interval (D-RI) was the optimal treatment with moderate to high certainty (vs PLA: SMD=−1.10, 95% CI, −1.69 to −0.51 in pain; SMD=1.46, 95% CI, 0.73-2.20 in global function). Distension and intra-articular injection via anterior or posterior approaches produced effects equivalent to those of rotator interval injection and D-RI. Rotator interval injection, distension, and intra-articular injection had equivalent effects on symptom relief. More RCTs are required to validate the superiority of multisite injections. [ABSTRACT FROM AUTHOR]

BackgroundNearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase III randomized CheckMate 548 study was to evaluate RT + TMZ combined with the immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in patients with newly diagnosed glioblastoma with methylated MGMT promoter (NCT02667587).MethodsPatients (N = 716) were randomized 1:1 to NIVO [(240 mg every 2 weeks × 8, then 480 mg every 4 weeks) + RT (60 Gy over 6 weeks) + TMZ (75 mg/m2 once daily during RT, then 150-200 mg/m2 once daily on days 1-5 of every 28-day cycle × 6)] or PBO + RT + TMZ following the same regimen. The primary endpoints were progression-free survival (PFS) and overall survival (OS) in patients without baseline corticosteroids and in all randomized patients.ResultsAs of December 22, 2020, median (m)PFS (blinded independent central review) was 10.6 months (95% CI, 8.9-11.8) with NIVO + RT + TMZ vs 10.3 months (95% CI, 9.7-12.5) with PBO + RT + TMZ (HR, 1.1; 95% CI, 0.9-1.3) and mOS was 28.9 months (95% CI, 24.4-31.6) vs 32.1 months (95% CI, 29.4-33.8), respectively (HR, 1.1; 95% CI, 0.9-1.3). In patients without baseline corticosteroids, mOS was 31.3 months (95% CI, 28.6-34.8) with NIVO + RT + TMZ vs 33.0 months (95% CI, 31.0-35.1) with PBO + RT + TMZ (HR, 1.1; 95% CI, 0.9-1.4). Grade 3/4 treatment-related adverse event rates were 52.4% vs 33.6%, respectively.ConclusionsNIVO added to RT + TMZ did not improve survival in patients with newly diagnosed glioblastoma with methylated or indeterminate MGMT promoter. No new safety signals were observed.

Rationale: The role of obesity-associated insulin resistance (IR) in airflow limitation in asthma is uncertain. Objectives: Using data in the Severe Asthma Research Program 3 (SARP-3), we evaluated relationships between homeostatic measure of IR (HOMA-IR), lung function (cross-sectional and longitudinal analyses), and treatment responses to bronchodilators and corticosteroids. Methods: HOMA-IR values were categorized as without (5.0). Lung function included FEV1 and FVC measured before and after treatment with inhaled albuterol and intramuscular triamcinolone acetonide and yearly for 5 years. Measurements and Main Results: Among 307 participants in SARP-3, 170 (55%) were obese and 140 (46%) had IR. Compared with patients without IR, those with IR had significantly lower values for FEV1 and FVC, and these lower values were not attributable to obesity effects. Compared with patients without IR, those with IR had lower FEV1 responses to β-adrenergic agonists and systemic corticosteroids. The annualized decline in FEV1 was significantly greater in patients with moderate IR (-41 ml/year) and severe IR (-32 ml/year,) than in patients without IR (-13 ml/year, P

STUDY OBJECTIVES: Although obesity, asthma, and sleep-disordered breathing are interrelated, there is limited understanding of the independent contributions of body-mass index and pulmonary function on polysomnography in children with asthma. METHODS: We conducted a retrospective chart review on 448 7- to 18-year-old children with asthma who had undergone polysomnography testing between 1/2007-12/2011 to elucidate the association between spirometry variables, body-mass index, and polysomnography parameters, adjusting for asthma and antiallergic medications. RESULTS: Obese children had poorer sleep architecture and more severe gas exchange abnormalities compared to healthy weight children. Multivariate analysis revealed an independent association of body-mass index with sleep efficiency, with more light and less deep sleep in both obese and healthy-weight children, and with baseline oxygen saturation and oxygen nadir in obese children. In obese children, forced vital capacity was independently associated with less deep sleep (time in N3 sleep) as well as with oxygen nadir, while among healthy-weight children, forced expiratory volume directly correlated but forced vital capacity inversely correlated with deep sleep. In obese children, inhaled corticosteroid was associated with baseline oxygen saturation, and montelukast was associated with lower end-tidal carbon dioxide. In healthy-weight children, inhaled corticosteroid was associated with arousal awakening index, and montelukast was associated with light sleep. Antiallergic medications were not independently associated with polysomnography parameters. CONCLUSIONS: Pulmonary function, body-mass index, and asthma medications have independent and differing influences on sleep architecture and gas exchange polysomnography parameters in obese and healthy-weight children with asthma. Asthma medications are associated with improved gas exchange in obese children and improved sleep architecture in healthy-weight children with asthma. CITATION: Conrad LA, Nandalike K, Rani S, Rastogi D. Associations between sleep, obesity, and asthma in urban minority children. J Clin Sleep Med. 2022;18(10):2377-2385.

PurposeTo determine the dose-dependent risk of systemic corticosteroids (SCs) and the risk of other immunosuppressive therapies on coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in patients with noninfectious uveitis (NIU).DesignA retrospective cohort study from January 20, 2020, to December 31, 2020 (an era before widespread COVID-19 vaccination), using the Optum Labs Data Warehouse, a US national de-identified claims database.ParticipantsPatients who had at least 1 NIU diagnosis from January 1, 2017.MethodsUnadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models, with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of SC exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models as a continuous variable, in addition to the dichotomous variable.Main outcome measuresIncidence rates of COVID-19 infection, COVID-19-related hospitalization, and COVID-19-related in-hospital death.ResultsThis study included 52 286 NIU patients of whom 12 000 (23.0%) were exposed to immunosuppressive medications during the risk period. In adjusted models, exposure to SCs was associated with increased risk of COVID-19 infection (HR, 2.66; 95% confidence interval [CI], 2.19-3.24; P < 0.001), hospitalization (HR, 3.26; 95% CI, 2.46-4.33; P < 0.001), and in-hospital death (HR, 1.99; 95% CI, 0.93-4.27; P = 0.08). Furthermore, incremental increases in the dosage of SCs were associated with a greater risk for these outcomes. Although tumor necrosis factor-α (TNF-α) inhibitors were associated with an increased risk of infection (HR, 1.48; 95% CI, 1.08-2.04; P = 0.02), other immunosuppressive treatments did not increase the risk of COVID-19 infection, hospitalization, or death.ConclusionsThis study from an era before widespread COVID-19 vaccination demonstrates that outpatient SC exposure is associated with greater risk of COVID-19 infection and severe outcomes in patients with NIU. Future studies should evaluate the impact of immunosuppression in vaccinated NIU patients. Limiting exposure to SCs and use of alternative therapies may be warranted.

BACKGROUND: Corticosteroids are the mainstay of treatment for immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI), but the optimal duration of therapy has not been established. Prolonged use of corticosteroids can cause numerous adverse effects and may decrease progression-free survival among patients treated with ICPis. We sought to determine whether a shorter duration of corticosteroids was equally efficacious and safe as compared with a longer duration. METHODS: We used data from an international multicenter cohort study of patients diagnosed with ICPi-AKI from 29 centers across nine countries. We examined whether a shorter duration of corticosteroids (28 days or less) was associated with a higher rate of recurrent ICPi-AKI or death within 30 days following completion of corticosteroid treatment as compared with a longer duration (29-84 days). RESULTS: Of 165 patients treated with corticosteroids, 56 (34%) received a shorter duration of treatment and 109 (66%) received a longer duration. Patients in the shorter versus longer duration groups were similar with respect to baseline and ICPi-AKI characteristics. Five of 56 patients (8.9%) in the shorter duration group and 12 of 109 (11%) in the longer duration group developed recurrent ICPi-AKI or died (p=0.90). Nadir serum creatinine in the first 14, 28, and 90 days following completion of corticosteroid treatment was similar between groups (p=0.40, p=0.56, and p=0.89, respectively). CONCLUSION: A shorter duration of corticosteroids (28 days or less) may be safe for patients with ICPi-AKI. However, the findings may be susceptible to unmeasured confounding and further research from randomized clinical trials is needed.

ObjectiveWe sought to determine if corticosteroid administration is associated with a SARS-CoV-2 nucleic acid test-positive result and to describe therapies administered to SARS-CoV-2 infected children.MethodsWe collected cross-sectional data from participants recruited in 41 pediatric emergency departments (ED) in 10 countries between March 2020 and June 2021. Participants were

Background and aims5-aminosalicylates (5-ASA) are frequently used in the management of Crohn's disease (CD). We used a de-identified administrative claims database to compare patterns and outcomes of continuing versus stopping 5-ASA in patients with CD who escalated to anti-metabolite monotherapy.MethodsPatients with CD on 5-ASA who were new users of anti-metabolite monotherapy and followed for at least 12 months from OptumLabs® Data Warehouse. Three patterns of 5-ASA use were identified: stopped 5-ASA, short-term 5-ASA (use for  6 months after starting anti-metabolites). Outcomes (need for corticosteroids, risk of CD-related hospitalization and/or surgery, treatment escalation to biologic therapy) were compared using Cox proportional hazard analysis adjusting for key covariates, with a 12-month immortal time period.ResultsOf 3036 patients with CD who were new-users of anti-metabolite monotherapy, 667 (21.9%), 626 (20.6%), and 1743 (57.4%) stopped 5-ASA, used 5-ASA transiently or persistently, respectively. Compared to patients who stopped 5-ASA after starting anti-metabolites, persistent 5-ASA use was associated with a higher risk of corticosteroid use (HR, 1.24 [1.08-1.42]), without an increase in risk of CD-related hospitalization (HR, 1.21 [0.98-1.49]), CD-related surgery (HR, 1.28 [0.90-1.80]) or treatment escalation (HR, 0.85 [0.62-1.20]). Sensitivity analyses using a 3-month window after initiation of anti-metabolites to classify patients as continuing vs. stopping 5-ASA showed similar results. Residual confounding by disease severity could not be excluded.Conclusion5-ASAs are frequently continued long-term even after escalation to anti-metabolite therapy in patients with CD but offer no clinical benefit over stopping 5-ASA.

BackgroundAlopecia areata (AA) is an autoimmune, nonscarring hair loss disorder with slightly greater prevalence in children than adults. Various treatment modalities exist; however, their evidence in pediatric AA patients is lacking.ObjectiveTo evaluate the evidence of current treatment modalities for pediatric AA.MethodsWe conducted a systematic review on the PubMed database in October 2019 for all published articles involving patients

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Background: Platelet-rich plasma (PRP) or corticosteroid injections may be used to conservatively treat mild-to-moderate carpal tunnel syndrome (CTS). We evaluated the cost-effectiveness of PRP injections versus corticosteroid injections for the treatment of mild-to-moderate CTS. Methods: Markov modeling was used to analyze the base-case 45-year-old patient with mild-to-moderate CTS, unresponsive to conservative treatments, never previously treated with an injection or surgery, treated with a single injection of PRP, or methylprednisolone/triamcinolone 40 mg/mL. Transition probabilities were derived from level-I/II studies, utility values from the Tufts University Cost-Effectiveness Analysis Registry reported using visual analog scale (VAS), Boston Carpal Tunnel Questionnaire Symptom severity (BCTQ-S), and Boston Carpal Tunnel Questionnaire Functional status (BCTQ-F), and costs from Medicare, published studies, and industry. Analyses were performed from healthcare/societal perspectives. Outcomes were incremental cost-effectiveness ratios (ICER) and net monetary benefits (NMB). Willingness-to-pay thresholds were $50 000 and $100 000. Deterministic/probabilistic sensitivity analyses were performed. Results: From a healthcare perspective, compared to PRP injections, the ICER for corticosteroid injections measured by VAS: -$13.52/quality-adjusted-life-years (QALY), BCTQ-S: -$11.88/QALY, and BCTQ-F: -$16.04/QALY. PRP versus corticosteroid injections provided a NMB measured by VAS: $428 941.12 versus $375 788.21, BCTQ-S: $417 115.09 versus $356 614.18, and BCTQ-F: $421 706.44 versus $376 908.45. From a societal perspective, compared to PRP injections, the ICER for corticosteroid injections measured by VAS: -$1024.40/QALY, BCTQ-S: -$899.95/QALY, and BCTQ-F: -$1215.51/QALY. PRP versus corticosteroid injections provided a NMB measured by VAS: $428 171.63 versus $373 944.39, BCTQ-S: $416 345.61 versus $354 770.36, and BCTQ-F: $420 936.95 versus $375 064.63. Conclusions: PRP injections were more cost-effective than methylprednisolone/triamcinolone injections from healthcare and societal perspectives for mild-to-moderate CTS. [ABSTRACT FROM AUTHOR]

Background: Dupilumab, a human monoclonal anti-interleukin (IL)-4Ra antibody blocks the shared receptor component of IL-4 and IL-13, drivers of type 2 inflammation. Dupilumab is approved for severe/refractory asthma inadequately controlled by existing therapies, but knowledge of its effect on real-world disease burden is lacking. This study investigates real-world effects of dupilumab on asthma exacerbation risk and oral corticosteroid (OCS) use in Japanese individuals with asthma. Methods: This retrospective, cohort study used a Japanese insurance claims database to identify patients who started dupilumab between 26 March 2019–31 May 2020. Patients were followed for ±365 days from dupilumab initiation. The study primarily assessed the annual incidence rate of severe asthma exacerbations occurring simultaneously with hospitalizations or OCS bursts. Secondary and exploratory endpoints assessed OCS dosage and duration, and healthcare resource utilization (HRU), respectively. Results: At dupilumab initiation (N = 215), mean age was 57.2 years, 41.9% of patients were aged ≥65 years, and 59.5% were female. Dupilumab significantly reduced the annual incidence of severe asthma exacerbations from 1.29 to 0.74 (95% confidence interval, 0.44–0.76) per patient per year. Mean OCS dosage decreased from 10.4 to 7.2 mg/day in chronic OCS users; median frequency of OCS bursts decreased from 3 to 0. Both unscheduled outpatient visits (35.8% vs 29.8%) and hospitalizations (21.9% vs 12.1%) decreased. Mean (standard deviation) duration of hospitalization also decreased from 6.7 (27.6) to 2.2 (8.1) days. Conclusions: Japanese patients with asthma who received dupilumab had reduced incidence rates of severe asthma exacerbations, OCS use, and HRU over 12 months.

Corticosteroids are most commonly used to treat HTLV-1-associated myelopathy (HAM); however, their clinical efficacy has not been tested in randomized clinical trials. This randomized controlled trial included 8 and 30 HAM patients with rapidly and slowly progressing walking disabilities, respectively. Rapid progressors were assigned (1:1) to receive or not receive a 3-day course of intravenous methylprednisolone in addition to oral prednisolone therapy. Meanwhile, slow progressors were assigned (1:1) to receive oral prednisolone or placebo. The primary outcomes were a composite of ≥1-grade improvement in the Osame Motor Disability Score or ≥30% improvement in the 10 m walking time (10 mWT) at week 2 for rapid progressors and changes from baseline in 10 mWT at week 24 for slow progressors. In the rapid progressor trial, all four patients with but only one of four without intravenous methylprednisolone achieved the primary outcome (p = 0.14). In the slow progressor trial, the median changes in 10 mWT were -13.8% (95% CI: -20.1--7.1; p < 0.001) and -6.0% (95% CI: -12.8-1.3; p = 0.10) with prednisolone and placebo, respectively (p for between-group difference = 0.12). Whereas statistical significance was not reached for the primary endpoints, the overall data indicated the benefit of corticosteroid therapy. (Registration number: UMIN000023798, UMIN000024085).

Background and aimsObesity has been reported to be one of the most frequent comorbidities in COVID-19 patients and associated with higher rates of in-hospital mortality compared to non-obese patients. Acute kidney injury (AKI) is also known to be a complication associated with obesity in critically-ill COVID-19 patients. We aimed to investigate whether obesity was associated with increased risk of in-hospital mortality and AKI among patients with COVID-19 treated with corticosteroids.MethodsWe utilized 9965 hospitalized COVID-19 patient data and divided patients who were treated with corticosteroids into 6 groups by body mass index (BMI) (less than 18.5, 18.5-25, 25-30, 30-35, 35-40, 40 kg/m2 or greater). The association between BMI and in-hospital mortality and between BMI and incidence rate of AKI during admission among COVID-19 patients receiving corticosteroids were retrospectively investigated.ResultsThere were 4587 study participants receiving corticosteroids (mean age 66.5 ± 15.5 years, men 56.6%, mean BMI 29.0 ± 7.2 kg/m2). The smooth spline curve suggested a J-shape association between BMI and in-hospital mortality. Patients with BMI above 40 kg/m2 exhibited a higher in-hospital mortality and higher incidence rate of AKI during admission compared to patients with BMI between 25 and 30 kg/m2. The differences in in-hospital mortality and the rate of AKI were larger among patients with severe COVID-19.ConclusionsClass III obesity was associated with high in-hospital mortality and AKI in patients with COVID-19 treated by corticosteroids. Clinicians must stay vigilant on the impact of class III obesity and development of AKI to disease trajectory of COVID-19 patients.

BackgroundPharmacogenetic studies in asthma cohorts, primarily made up of White people of European descent, have identified loci associated with response to inhaled beta agonists and corticosteroids (ICSs). Differences exist in how individuals from different ancestral backgrounds respond to long-acting beta agonist (LABA) and ICSs. Therefore, we sought to understand the pharmacogenetic mechanisms regulating therapeutic responsiveness in individuals of African descent.MethodsWe did ancestry-based pharmacogenetic studies of children (aged 5-11 years) and adolescents and adults (aged 12-69 years) from the Best African Response to Drug (BARD) trials, in which participants with asthma uncontrolled with low-dose ICS (fluticasone propionate 50 μg in children, 100 μg in adolescents and adults) received different step-up combination therapies. The hierarchal composite outcome of pairwise superior responsiveness in BARD was based on asthma exacerbations, a 31-day difference in annualised asthma-control days, or a 5% difference in percentage predicted FEV1. We did whole-genome admixture mapping of 15 159 ancestral segments within 312 independent regions, stratified by the two age groups. The two co-primary outcome comparisons were the step up from low-dose ICS to the quintuple dose of ICS (5 × ICS: 250 μg twice daily in children and 500 μg twice daily in adolescents and adults) versus double dose (2-2·5 × ICS: 100 μg twice daily in children, 250 μg twice daily in adolescents and adults), and 5 × ICS versus 100 μg fluticasone plus a LABA (salmeterol 50 μg twice daily). We used a genome-wide significance threshold of p

Rationale: Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with coronavirus disease (COVID-19) is unknown. Objectives: To identify clinically relevant, novel subgroups in COVID-19-related ARDS and compare them with previously described ARDS subphenotypes. Methods: Eligible participants were adults with COVID-19 and ARDS at Columbia University Irving Medical Center. Latent class analysis was used to identify subgroups with baseline clinical, respiratory, and laboratory data serving as partitioning variables. A previously developed machine learning model was used to classify patients as the hypoinflammatory and hyperinflammatory subphenotypes. Baseline characteristics and clinical outcomes were compared between subgroups. Heterogeneity of treatment effect for corticosteroid use in subgroups was tested. Measurements and Main Results: From March 2, 2020, to April 30, 2020, 483 patients with COVID-19-related ARDS met study criteria. A two-class latent class analysis model best fit the population (P = 0.0075). Class 2 (23%) had higher proinflammatory markers, troponin, creatinine, and lactate, lower bicarbonate, and lower blood pressure than class 1 (77%). Ninety-day mortality was higher in class 2 versus class 1 (75% vs. 48%; P

Background: The fractional exhaled nitric oxide (FENO) test is a point-of-care test that is used in the assessment of asthma. Objective: To provide evidence-based clinical guidance on whether FENO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered. Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FENO. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidence-based answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations. Main Results: After considering the overall low quality of the evidence, the panel made a conditional recommendation for FENO-based care. In patients with asthma in whom treatment is being considered, we suggest that FENO is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice. Conclusions: Clinicians should consider this recommendation to measure FENO in patients with asthma in whom treatment is being considered based on current best available evidence.

Acute respiratory distress syndrome is a heterogenous syndrome with many etiologies for which there are no definitive pharmacologic treatments, despite decades of research. We explore some adjunctive pharmacologic therapies, including neuromuscular blockade, corticosteroids, and inhaled pulmonary vasodilators. Additionally, we explore some investigative therapies, including Vitamin C, beta-agonists, statins, mesenchymal stromal cells, and granulocyte-macrophage colony stimulating factor. We do discuss the potential role of steroids in acute respiratory distress syndrome with severe acute respiratory syndrome coronavirus 2 as a trigger. The standard of care, however, remains supportive care.

BackgroundThe COVID-19 pandemic has caused substantial morbidity and mortality.ObjectiveTo describe monthly clinical trends among adults hospitalized with COVID-19.DesignPooled cross-sectional study.Setting99 counties in 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET).PatientsU.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during 1 March to 31 December 2020.MeasurementsMonthly hospitalizations, intensive care unit (ICU) admissions, and in-hospital death rates per 100 000 persons in the population; monthly trends in weighted percentages of interventions, including ICU admission, mechanical ventilation, and vasopressor use, among an age- and site-stratified random sample of hospitalized case patients.ResultsAmong 116 743 hospitalized adults with COVID-19, the median age was 62 years, 50.7% were male, and 40.8% were non-Hispanic White. Monthly rates of hospitalization (105.3 per 100 000 persons), ICU admission (20.2 per 100 000 persons), and death (11.7 per 100 000 persons) peaked during December 2020. Rates of all 3 outcomes were highest among adults aged 65 years or older, males, and Hispanic or non-Hispanic Black persons. Among 18 508 sampled hospitalized adults, use of remdesivir and systemic corticosteroids increased from 1.7% and 18.9%, respectively, in March to 53.8% and 74.2%, respectively, in December. Frequency of ICU admission, mechanical ventilation, and vasopressor use decreased from March (37.8%, 27.8%, and 22.7%, respectively) to December (20.5%, 12.3%, and 12.8%, respectively); use of noninvasive respiratory support increased from March to December.LimitationCOVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country.ConclusionRates of COVID-19-associated hospitalization, ICU admission, and death were highest in December 2020, corresponding with the third peak of the U.S. pandemic. The frequency of intensive interventions for management of hospitalized patients decreased over time. These data provide a longitudinal assessment of clinical trends among adults hospitalized with COVID-19 before widespread implementation of COVID-19 vaccines.Primary funding sourceCenters for Disease Control and Prevention.

Objective To investigate the effect of long-term dapagliflozin administration on sympathetic nervous activity in patients with diabetes and the underlying mechanism. Methods We included 100 patients with type 2 diabetes admitted to Heze Mudan People’s Hospital from June 2021 to July 2022. They were divided into diabetes group (50 cases) and dapagliflozin group (50 cases). The diabetes group received conventional treatment (metformin or acarbose), while the dapagliflozin group received conventional treatment plus dapagliflozin (10 mg, once daily). Both groups were treated for three months. We collected cli-nical data on body mass, body mass index, glucose metabolism, pancreatic islet function, renal function, cardiac function, and se-rum sympathetic nervous activity before and after treatment. The relationship between sympathetic activity and the protective effects of dapagliflozin on cardiac, renal and islet functions was analyzed. Results The two groups significantly differed in the differences in body mass, glucose metabolism, pancreatic islet function, and cardiac function (t=-5.57-4.65,P

Dupilumab, a human monoclonal anti-interleukin (IL)-4Ra antibody blocks the shared receptor component of IL-4 and IL-13, drivers of type 2 inflammation. Dupilumab is approved for severe/refractory asthma inadequately controlled by existing therapies, but knowledge of its effect on real-world disease burden is lacking. This study investigates real-world effects of dupilumab on asthma exacerbation risk and oral corticosteroid (OCS) use in Japanese individuals with asthma. This retrospective, cohort study used a Japanese insurance claims database to identify patients who started dupilumab between 26 March 2019–31 May 2020. Patients were followed for ±365 days from dupilumab initiation. The study primarily assessed the annual incidence rate of severe asthma exacerbations occurring simultaneously with hospitalizations or OCS bursts. Secondary and exploratory endpoints assessed OCS dosage and duration, and healthcare resource utilization (HRU), respectively. At dupilumab initiation (N = 215), mean age was 57.2 years, 41.9% of patients were aged ≥65 years, and 59.5% were female. Dupilumab significantly reduced the annual incidence of severe asthma exacerbations from 1.29 to 0.74 (95% confidence interval, 0.44–0.76) per patient per year. Mean OCS dosage decreased from 10.4 to 7.2 mg/day in chronic OCS users; median frequency of OCS bursts decreased from 3 to 0. Both unscheduled outpatient visits (35.8% vs 29.8%) and hospitalizations (21.9% vs 12.1%) decreased. Mean (standard deviation) duration of hospitalization also decreased from 6.7 (27.6) to 2.2 (8.1) days. Japanese patients with asthma who received dupilumab had reduced incidence rates of severe asthma exacerbations, OCS use, and HRU over 12 months. [Display omitted] [ABSTRACT FROM AUTHOR]

Background/Purpose of this study: It has been recommended that individuals with inflammatory bowel disease (IBD) be vaccinated against Coronavirus disease - 19 (COVID-19). Recently, we documented the incidence of side effects (SEs) after COVID-19 immunization among individuals with IBD in Japan. However, the study did not show differences between the types of IBD or the patients' clinical backgrounds. In this survey, we aimed at investigating whether the frequency of SEs differed among patients with IBD. Methods: A cross-sectional survey was conducted among adult patients with IBD at Kobe University between March 2022 and September 2022. Results: Total 195 patients, including 134 with ulcerative colitis (UC) and 61 with Crohn's disease (CD), completed the questionnaire and were included in the analysis. Of these, 92.3%, 91.3% and 44.1% received the initial, second and third dose of the COVID-19 vaccine, respectively. The frequency of local symptoms following the initial, second and third dose of the vaccine was comparable between patients with UC and CD (69.6% vs. 72.7%, 64.2% vs. 69.1% and 63.5% vs. 73.9%, respectively). Muscle pain after the initial and second doses of the COVID-19 vaccine was more common among patients treated with corticosteroids (58.1% vs. 37.6% and 60.0% vs. 31.8%, p < 0.05). Female sex, younger age and current or former smoking were associated with an increased incidence of fever or chills after the initial dose of the vaccine (p < 0.05). In contrast, corticosteroid use was identified as a factor associated with an increased incidence of muscle pain after the initial dose of vaccine (p < 0.05). Conclusion: The use of corticosteroids could increase the risk of muscle pain following COVID-19 vaccination. Additionally, factors such as female sex, younger age and current or former smoking can affect the incidence of fever or chills. This information should encourage patients with IBD to get vaccinated against COVID-19. [ABSTRACT FROM AUTHOR]

Sweet's Syndrome (SS), also known as acute febrile neutrophilic dermatosis, is one of several cutaneous inflammatory disorders classified as neutrophilic dermatoses. Respiratory complications are described in

ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2 × 106  CAR-T cells/kg (day 0) and once-daily oral dexamethasone [10 mg, day 0 (before axi-cel) through day 2]. Forty patients received axi-cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty-eight per cent of patients did not experience CRS or NEs within 72 h of axi-cel. With a median follow-up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.

MythCorticosteroid injection for the treatment of pain is known to decrease the efficacy of the adenovirus vector-based vaccines for COVID-19.FactThere is currently no direct evidence to suggest that a corticosteroid injection before or after the administration of an adenovirus vector-based COVID-19 vaccine decreases the efficacy of the vaccine. However, based on the known timeline of hypothalamic-pituitary-adrenal axis suppression following epidural and intraarticular corticosteroid injections, and the timeline of the reported peak efficacy of the Janssen and AstraZeneca vaccines, physicians should consider timing an elective corticosteroid injection such that it is administered no less than 2 weeks prior to and no less than 2 weeks following a COVID-19 adenovirus vector-based vaccine dose, whenever possible. We emphasize the importance of risk/benefit analysis and shared decision making in determining the timing of corticosteroid injections for pain indications in relation to receipt of a COVID-19 vaccine given that patient-specific factors will vary.

ObjectiveTo investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents.DesignMultinational network cohort study.SettingHospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea.Participants303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020.Main outcome measuresPrescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19.ResultsOf the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from

MythCorticosteroid injection for the treatment of pain and inflammation is known to decrease the efficacy of the messenger ribonucleic acid (mRNA) vaccines for coronavirus disease 2019 (COVID-19).FactThere is currently no direct evidence to suggest that a corticosteroid injection before or after the administration of an mRNA COVID-19 vaccine decreases the efficacy of the vaccine.However, based on the known timeline of hypothalamic-pituitary-adrenal (HPA) axis suppression following epidural and intraarticular corticosteroid injections, and the timeline of the reported peak efficacy of the Pfizer-BioNTech and Moderna vaccines, physicians should consider timing an elective corticosteroid injection such that it is administered no less than 2 weeks prior to a COVID-19 mRNA vaccine dose and no less than 1 week following a COVID-19 mRNA vaccine dose, whenever possible.

Patients exposed to pollutants are more likely to suffer from allergic rhinitis and may benefit from antioxidant treatment. Our study determined if patients diagnosed with grass-induced allergic rhinitis could benefit from broccoli sprout extract (BSE) supplementation. In total, 47 patients were confirmed with grass-induced allergic rhinitis and randomized to one of four groups: group 1 (nasal steroid spray + BSE), group 2 (nasal steroid spray + placebo tablet), group 3 (saline nasal spray + BSE) and group 4 (saline nasal spray + placebo tablet). Peak Nasal Inspiratory Flow (PNIF), Total Nasal Symptoms Scores (TNSS) and nasal mucus cytokine levels were analyzed in samples collected before and after the 3-week intervention. Comparing before and after the intervention, PNIF improved significantly when comparing Groups 1 and 2, vs. placebo, at various time points (p ≤ 0.05 at 5, 15, 60 and 240 min) following nasal challenge, while TNSS was only statistically significant at 5 (p = 0.03), 15 (p = 0.057) and 30 (p = 0.05) minutes. There were no statistically significant differences in various cytokine markers before and after the intervention. Combining nasal corticosteroid with BSE led to the most significant improvement in objective measures.

Rationale: It is unclear why select patients with moderate-to-severe asthma continue to lose lung function despite therapy. We hypothesized that participants with the smallest responses to parenteral corticosteroids have the greatest risk of undergoing a severe decline in lung function.Objectives: To evaluate corticosteroid-response phenotypes as longitudinal predictors of lung decline.Methods: Adults within the NHLBI SARP III (Severe Asthma Research Program III) who had undergone a course of intramuscular triamcinolone at baseline and at ≥2 annual follow-up visits were evaluated. Longitudinal slopes were calculated for each participant's post-bronchodilator FEV1% predicted. Categories of participant FEV1 slope were defined: severe decline, >2% loss/yr; mild decline, >0.5-2.0% loss/yr; no change, 0.5% loss/yr to

Corticosteroid therapy is now recommended as a treatment in patients with severe COVID-19. But one key question is how to objectively identify severely ill patients who may benefit from such therapy. Here, we assigned 12,862 COVID-19 cases from 21 hospitals in Hubei Province equally to a training and a validation cohort. We found that a neutrophil-to-lymphocyte ratio (NLR) > 6.11 at admission discriminated a higher risk for mortality. Importantly, however, corticosteroid treatment in such individuals was associated with a lower risk of 60-day all-cause mortality. Conversely, in individuals with an NLR ≤ 6.11 or with type 2 diabetes, corticosteroid treatment was not associated with reduced mortality, but rather increased risks of hyperglycemia and infections. These results show that in the studied cohort corticosteroid treatment is associated with beneficial outcomes in a subset of COVID-19 patients who are non-diabetic and with severe symptoms as defined by NLR.