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Objective: Our goal was to characterize a large group of children presenting to the emergency department (ED) with acute anaphylaxis, treated with intramuscular epinephrine (IM EPI) and a corticosteroid (CS), and to determine the impact of pharmacologic intervention on the rate and timing of biphasic reactions (BPR).Methods: We reviewed consecutive children diagnosed with acute anaphylaxis managed in three EDs during a six-year period. All received IM EPI and CS, followed by monitoring for 4–6 hours post-treatment. We analyzed the rate and timing of BPR, comparing the intervals of 0–4vs4–48 hours after initiating therapy.Results: During the study period, there were 371 cases of anaphylaxis, of which 357 (94%) received both IM EPI and CS. Of these, 49 (14%) manifested BPR [84% had received prehospital IM EPI] requiring at least one additional dose of IM EPI [14% required ≥2 additional doses]. All BPR episodes occurred within the 0–4 hour interval after initiating therapy, whereas no patient manifested a BPR requiring an additional dose of IM EPI during the 4–48 hours after initiating therapy (P =4 hours vs

Erdheim-Chester disease (ECD) is an exceedingly rare non-Langerhans cell CD68+ CD1a- S100- histiocytic multi-organ disease. Diagnosis of ECD is often delayed due to non-specific radiographic findings and heterogeneous lesional tissue. Increasingly, the role of genomic alterations is being recognized for both diagnosis and treatment of ECD. More than half of ECD patients harbor the BRAFV600E mutation. Evaluation for this mutation be can falsely negative on immunohistochemical staining and confirmation with molecular analyses is recommended. We present a case of the 44 year-old male with BRAFV600E-positive ECD treated successfully with steroids followed by single-agent dabrafenib.

Steroid-associated laminitis remains a major concern with use of corticosteroids in horses. Individual case factors such as joint pathology, pre-existing endocrinopathies, or corticosteroid type, dose, and timing influencing steroid-induced laminitis risk have not been investigated. This study aimed to determine if systemic absorption of triamcinolone acetonide (TA) varies between intrasynovial (antebrachiocarpal) and extrasynovial (sacroiliac) injection sites, and to determine the effects of TA absorption on glucose, insulin, cortisol, and adrenocorticotropic hormone (ACTH). Twenty adult horses were randomized into antebrachiocarpal or sacroiliac joint injection groups, and each horse received bilateral injections with a total dose of 18 mg triamcinolone. Blood was collected prior to injection and at 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 36, 48, 60, and 72 h post-injection. Peak TA absorption occurred at 8 h in both groups, and was significantly higher in the intrasynovial group compared to the extrasynovial group (1.397 ng/mL, 0.672 ng/mL, p 20 μU/mL) from both groups experienced a more marked hyperinsulinemia, reaching a mean peak insulin of 197.5 μU/mL as compared to 90.06 μU/mL in those with normal baseline insulin. Cortisol and ACTH were significantly decreased from baseline at timepoints from 4-72 h post-injection in both groups. This study is the first to evaluate drug absorption from the sacroiliac site and demonstrates that drug absorption varies between intrasynovial and extrasynovial injection sites. TA absorption causes metabolic derangements, most notably a marked hyperinsulinemia that is more severe in horses with elevated baseline insulin values. The influence of baseline endocrinopathies on response to corticosteroid administration as well as the effect of corticosteroid-induced metabolic derangements warrant further investigation as risk factors for corticosteroid-associated laminitis.

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.

BACKGROUND: Dexamethasone is routinely administered to horses but its effect on the antibody response to a commercial EIV/EHV vaccine is unclear. HYPOTHESIS: Horses receiving dexamethasone will have lower postvaccination antibody levels against EIV and EHV-1 than vaccinated controls. ANIMALS: Fifty-five healthy adult research horses. METHODS: Randomized cohort study. Control (no vaccine, group 1), vaccination only (EIV/EHV-1/EHV-4, Prestige 2, Merck Animal Health, group 2), vaccination and concurrent single intravenous dose of dexamethasone (approximately .05 mg/kg, group 3), vaccination and 3 intravenous doses of dexamethasone at 24 hours intervals (group 4). Serum SAA levels were measured on day 1 and day 3. Antibody levels against EIV (hemagglutination inhibition assay, Kentucky 2014 antigen) and EHV-1 (multiplex ELISA targeting total IgG and IgG 4/7) were measured on day 1 and day 30. RESULTS: Significantly increased mean antibody titers after vaccination were only noted against EIV and only after the vaccination alone (n = 14, prevaccine mean [prvm] 166.9, SD 259.6, 95% CI 16.95-316.8; postvaccine mean [povm] 249.1, SD 257.2, 95% confidence interval [CI] 100.6-397.6, P = .02) and the single dose dexamethasone (n = 14, prvm 93.14, SD 72.2, CI 51.45-134.8; povm 185.1, SD 118, CI 116.7-253.6, P = .01), but not after multiple doses of dexamethasone (n = 14, prvm 194.3, SD 258.3, CI 45.16-343.4; povm 240.0, SD 235.7, CI 103.9-376.1, P > .05). CONCLUSION: The effect of dexamethasone on the postvaccine antibody response varies depending on the dosing frequency and the antigen-specific antibody type.

PURPOSE: To determine the risk of coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in the era of COVID-19 vaccination among patients with noninfectious uveitis (NIU) taking immunosuppressive therapies. DESIGN: Retrospective cohort study from July 1, 2021, to June 30, 2022, using data from the Optum Labs Data Warehouse (OLDW) de-identified claims database. PARTICIPANTS: Patients with a diagnosis of NIU from January 1, 2017, and who had ≥ 1 year of continuous enrollment in the OLDW. METHODS: Incidence rates (IRs) were calculated for each COVID-19 outcome. Unadjusted 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 systemic corticosteroid (SC) exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models. MAIN OUTCOME MEASURES: Hazard ratios and IRs for COVID-19 infection, hospitalization, and death. RESULTS: This study included 62 209 patients with NIU. A total of 12 895 (20.7%) were exposed to SCs during the risk period. Incidence rates were increased when exposed to SCs versus unexposed for all COVID-19 outcomes. Incidence rates were also increased for all COVID-19 outcomes when exposed to SCs without COVID-19 vaccination versus exposed to SCs with ≥ 1 vaccination. In adjusted models, SCs were associated with increased risk of COVID-19 infection (HR, 3.57; 95% confidence interval [CI], 3.24-3.93; P

Purpose: Aim of this systematic review of preclinical evidence was to determine the effects of intra‐articular corticosteroid (CS) injections in joints affected by osteoarthritis (OA). Methods: A systematic review was performed on animal studies evaluating intra‐articular CS injections for OA joints. The search was performed on PubMed, Cochrane, and Web of Science databases. A synthesis of the results was performed investigating CS effects by evaluating studies comparing CS with control groups. Morphological, histological, immunohistochemistry evaluations, clinical outcomes, biomarkers and imaging results were evaluated. The risk of bias was assessed according to the Systematic Review Centre for Laboratory Animal Experimentation's tool. Results: Thirty‐two articles analysing CS effects in OA animal models were included (1079 joints), 18 studies on small and 14 on large animals. CS injections showed overall positive effects in at least one of the outcomes in 68% of the studies, while 16% reported a deleterious effect. CS improved cartilage and synovial outcomes in 68% and 60% of the studies, but detrimental effects were documented in 11% and 20% of the studies, respectively. Clinical parameters evaluated in terms of pain, lameness or joint swelling improved in 63% of the studies but deteriorated in 13%. Evidence is limited on imaging and biomarkers results, as well as on the best CS type, dose, formulation and injection protocol. The risk of bias assessment revealed a 28% low and an 18% high risk of bias. Conclusion: Intra‐articular CS injections induced a wide range of results on OA joints in experimental animal models, from disease‐modifying and positive effects on pain and joint function at short‐term evaluation to the lack of benefit or even negative effects. This underlines the need to identify more specific indications and treatment modalities to avoid possible detrimental effects while maximising the anti‐inflammatory properties and the benefits of intra‐articular CS in OA joints. Level of Evidence: Level II. [ABSTRACT FROM AUTHOR]

There are only a few clinical trials which address the treatment of acute urticaria (AU). Especially, the added value of systemic corticosteroids to antihistamines is unclear in treatment of severe AU. To review the existing evidence‐based approaches for AU treatment. A systematic electronic search was done in PubMed and Web of Science to retrieve all studies on the treatment of patients with AU. A descriptive synthesis was conducted based on the PRISMA statement. Quality assessment was independently performed by both reviewers ('Cochrane risk‐of‐bias tool' for RCTs). Ten randomized controlled trials (RCTs) (n = 857 participants) were included. Four studies assessed corticosteroid effectiveness added to antihistamines and six studies compared the efficacy of H1 and/ or H2‐antihistamines. The addition of corticosteroid (prednisone) to an antihistamine (levo)cetirizine did not improve symptoms of AU compared to antihistamine alone in two out of three RCTs. The combination of diphenhydramine (50 mg, IV) and ranitidine (50 mg, IV) or cimetidine (300 mg, IV) was most efficient for relief of urticaria in two out of five studies. Most frequent adverse effects were sedation and drowsiness. Recent guidelines on urticaria treatment mainly focus on chronic urticaria rather than on AU. Moreover, only few, small RCTs provide evidence for the management of AU. Thus, the state‐of‐the‐art management of this frequent condition remains unclear. The addition of corticosteroids to an antihistamine as treatment for AU needs to be further investigated. Well‐designed, high‐quality interventional trials are needed to establish evidence‐based treatment guidelines for AU. [ABSTRACT FROM AUTHOR]

We report two patients who displayed evidence of localized ocular inflammation after CAR T-cell infusion. To manage the resulting severe visual impairment, systemic corticosteroids were administered to both patients. This treatment led to a reduction in local inflammation and restored vision in one of the patients. [ABSTRACT FROM AUTHOR]

Intra‐articular corticosteroid injections, such as triamcinolone acetonide (TA), are commonly used by clinicians to manage joint synovial inflammation. However, due to conflicting evidence in literature, there is a fear among clinicians that the injections may be harmful to otherwise healthy cartilage in young patients. The purpose of this study was to evaluate the effects of TA on young, healthy chondrocytes. Articular cartilage samples were harvested from bovine knee joints (1–2 months old). In both healthy and inflammatory (interleukin‐1β) challenged cartilage, samples were treated with TA at doses ranging from 1 nM to 200 μM. Following a short‐ (2 days) or long‐term (10–14 days) treatment, chondrocyte viability, proliferation, and extracellular matrix (ECM) synthesis and degradation were evaluated with a click chemistry‐based technique. Chondrocyte viability, proliferation, and anabolic activity were all minimally affected by short‐term and long‐term TA treatment. After both acute and sustained inflammatory challenges, TA reduced the catabolic activities in cartilage, reducing nascent glycosaminoglycan loss and maintaining cartilage mechanical properties. Overall, at physiologically relevant doses, TA had minimal negative impact on chondrocytes when maintained within their native ECM. Clinical significance: The findings provide new insight for current clinical practices concerning the use of TA in intra‐articular injections, especially in young patients, and established a foundation for future investigations into the impact of corticosteroids on joint homeostasis. [ABSTRACT FROM AUTHOR]

Steroid hormone levels of patients may be monitored via dried blood spot (DBS) sampling at home. Stability of steroid hormones in DBS samples, however, needs to be established. DBS samples from healthy volunteers were collected and stored at various temperatures. Steroid hormone concentrations in DBS were measured directly, at day 2, day 7 and day 14 following storage at 37 °C and after 7 days, 14 days, 3 months and 6 months following storage at −20 °C, 4 °C and room temperature (RT). Cortisol, cortisone, corticosterone, testosterone, androstenedione, and 17-hydroxyprogesterone (17-OHP) were assessed using LC-MS/MS. All steroids were stable (±15 %) up to 14 days when stored at 37 °C, except for cortisone (only stable until 2 days). All steroids were stable up to 6 months when stored at −20 °C, 4 °C and RT. However, there were some exceptions, for androstenedione at RT (only stable until 7 days), for 17-OHP when stored at −20 °C (only stable until 3 months), for cortisone at RT and 4 °C (only stable until 14 days), and cortisol at RT (only stable until 3 months). Overall, we demonstrated stability of steroid hormone concentrations in DBS under various conditions which may be encountered during shipping to the diagnostic laboratory and during long-term storage before analysis. [ABSTRACT FROM AUTHOR]

[Display omitted] Mepolizumab is an anti-IL-5 mAb treatment for severe eosinophilic asthma that reduces asthma exacerbations. Residual airway inflammation with mepolizumab therapy may lead to persistent exacerbations. Oral corticosteroids remain the main treatment for these residual exacerbations. Our study aimed to explore the corticosteroid responsiveness of airway inflammation after mepolizumab treatment to find potentially treatable inflammatory mechanisms beyond the IL-5 pathway. The MAPLE trial was a multicenter, randomized, double-blind, placebo-controlled, crossover study of 2 weeks of high-dose oral prednisolone treatment at stable state in 27 patients treated with mepolizumab for severe eosinophilic asthma. We analyzed paired sputum (n = 16) and plasma (n = 25) samples from the MAPLE trial using high-throughput Olink proteomics. We analyzed additional sputum proteins using ELISA. In patients receiving mepolizumab, prednisolone significantly downregulated sputum proteins related to type 2 inflammation and chemotaxis including IL-4, IL-5, IL-13, CCL24, CCL26, EDN, CCL17, CCL22, OX40 receptor, FCER2, and the ST2 receptor. Prednisolone also downregulated cell adhesion molecules, prostaglandin synthases, mast cell tryptases, MMP1, MMP12, and neuroimmune mediators. Neutrophilic pathways were upregulated. Type 2 proteins were also downregulated in plasma, combined with IL-12, IFN-γ, and IP-10. IL-10 and amphiregulin were upregulated. At stable state, prednisolone has broad anti-inflammatory effects on top of mepolizumab. These effects are heterogeneous and may be clinically relevant in residual exacerbations. [ABSTRACT FROM AUTHOR]

Background: Oral corticosteroids (OCS) are effective anti-inflammatory agents used across a range of conditions. However, substantial evidence associates their use with increased risks for adverse events (AEs), causing high burden on healthcare resources. Emerging biologics present as alternative agents, enabling the reduction of OCS use. However, current modelling approaches may underestimate their effects by not capturing OCS-sparing effects. In this study, we present a modelling approach designed to capture the health economic benefits of OCS-sparing regimens and agents. Methods: We developed a disease-agnostic model using a UK health technology assessment (HTA) perspective, with discounting of 3.5% for costs and outcomes, a lifetime horizon, and 4-week cycle length. The model structure included type 2 diabetes mellitus, established cardiovascular disease, and osteoporosis as key AEs and drivers of morbidity and mortality, as well as capturing transient events. Quality-adjusted life-years (QALYs), life-years, and costs were determined for OCS-only and OCS-sparing treatment arms. Outcomes were determined using baseline 50% OCS-sparing, considering several OCS average daily doses (5, 10, 15 mg). Results: A treatment regimen with 50% OCS dose-sparing led to lifetime incremental cost savings per patient of £1107 (95% confidence interval £1014–£1229) at 5 mg, £2403 (£2203–£2668) at 10 mg, and £19,501 (£748–£51,836) at 15 mg. Patients also gained 0.033 (0.030–0.036) to 0.356 (0.022–2.404) QALYs dependent on dose. The benefits of OCS sparing were long-term, plateauing after 35–40 years of treatment. Conclusions: We present a modelling approach that captures additional long-term health economic benefits from OCS sparing that would otherwise be missed from current modelling approaches. These results may help inform future decision making for emerging OCS-sparing therapeutics by comparing them against the cost of such treatments. [ABSTRACT FROM AUTHOR]

Introduction: The Nucala Effectiveness Study (NEST) assessed the effectiveness of mepolizumab in patients with severe asthma (SA) in countries previously underrepresented in real-world studies. Methods: A multi-country, bi-directional, self-controlled, observational cohort study conducted in Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Historical and/or prospective data from patients with SA were assessed 12 months pre- and post-mepolizumab initiation. Primary endpoint: incident rate ratio (IRR) of clinically significant exacerbations (CSEs). Key secondary endpoints: healthcare resource utilisation (HCRU), oral corticosteroid (OCS) use, lung function and symptom control (Asthma Control Test [ACT] scores). Results: Overall, 525 patients with SA burden pre-initiation (geometric mean blood eosinophil count [BEC] 490.7 cells/µl; 31.4% prior biologic use; 37.3% obese) received at least one dose of mepolizumab 100 mg subcutaneously. Post-initiation, a significant reduction in CSEs was observed (76% [p < 0.001]; IRR [95% confidence interval] 0.24 [0.19–0.30]); 72.0% of patients had no CSEs. Mepolizumab treatment led to a reduction in OCS use (52.8% pre-initiation vs. 16.6% post-initiation) and a mean (standard deviation [SD]) change in OCS dose of − 18.1 (20.7) mg post-initiation; 36.1% of patients became OCS-free. Fewer patients were hospitalised post-initiation (22.5% pre-initiation vs. 6.9% post-initiation). Improvements in mean (SD) forced expiratory volume in 1 s (62.8 [20.2]% pre-initiation vs. 73.0 [22.7]% post-initiation) and ACT scores (15.0% pre-initiation vs. 64.5% of patients post-initiation with well-controlled asthma) were observed. Proportion of patients with BEC ≥ 500 cells/µl decreased from 84.4% pre-initiation to 18.1% post-initiation. Conclusion: Mepolizumab was effective in reducing the burden of SA by significantly reducing CSEs, reducing OCS use and HCRU, and improving lung function and asthma control, which could translate to improvements in health-related quality of life in patients with SA and high OCS dependency in the countries studied. A graphical abstract is available with this article. Plain Language Summary: Severe asthma occurs when asthma symptoms remain uncontrolled despite optimised treatment. In many low-middle income countries, and in some countries in the Middle East, Asia, Latin America and the Arab Gulf, the management and treatment of patients with severe asthma remain poor, with many patients having unscheduled hospital visits or admission, and use of steroids for a prolonged period. Mepolizumab is an injectable monoclonal antibody approved as an add-on treatment for severe asthma in patients ≥ 6 years of age. In clinical trials, mepolizumab has demonstrated reductions in the risk of clinically significant exacerbations (CSE; an asthma exacerbation that requires systemic corticosteroids and/or an emergency room visit and/or hospitalisation) and the need for oral corticosteroid (OCS) treatment in patients with severe asthma by reducing inflammation caused by eosinophil (a type of white blood cell) production. The Nucala Effectiveness Study (NEST) was performed to observe the effectiveness of mepolizumab in people with severe asthma in Colombia, Chile, India, Turkey, Saudi Arabia, United Arab Emirates, Kuwait, Oman and Qatar. The frequency of CSEs and other outcomes was compared 12 months pre- and post-mepolizumab initiation. Post-initiation, the risk of CSEs was significantly reduced by 76% (p < 0.001), and 72% of patients had no CSEs. Fewer patients were dependent on OCS, with 36.1% of patients not using OCS at all, and fewer patients were hospitalised. Lung function and asthma control also improved. NEST shows that mepolizumab could benefit people with severe asthma living in countries where disease-related burden and OCS use remain high. [ABSTRACT FROM AUTHOR]

Background: Prophylactic corticosteroids have been widely used to mitigate the inflammatory response induced by cardiopulmonary bypass (CPB). However, the impact of this treatment on clinically important outcomes in infants remains uncertain. Methods: We systematically searched databases (Medline, Embase, and Cochrane Central Register of Controlled Trials), Clinical Trials Registry, and Google Scholar from inception to March 1, 2024. Randomized controlled trials (RCTs) in which infants undergoing on-pump cardiac surgery received prophylactic corticosteroids or placebo were selected. The risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. Considering clinical heterogeneity between studies, the random-effects model was used for analysis. Subgroup analyses on the neonatal studies and sensitivity analyses by the leave-one-out method were also conducted. Results: Eight RCTs comprising 1,920 patients were included. Our analysis suggested no significant difference in postoperative mortality (2.1% vs. 3.3%, risk ratio (RR) = 0.71, 95% confidence interval (CI) [0.41, 1.21]). Significantly increased insulin treatment in infants (19.0% vs. 6.5%, RR = 2.78, 95% CI [2.05, 3.77]) and significantly reduced duration of mechanical ventilation in neonates (mean difference = -22.28 h, 95% CI [-42.58, -1.97]) were observed in the corticosteroids group. There were no differences between groups for postoperative acute kidney injury, cardiac arrest, extracorporeal membrane oxygenation support, low cardiac output syndrome, neurologic events, infection, or length of postoperative intensive care unit stay. Conclusions: Current evidence does not support the routine prophylactic use of corticosteroids in infants undergoing cardiac surgery with CPB. Further large-scale research is needed to investigate the optimal agent, dosing regimen, and specific impact on various types of cardiac surgery. Trial registration: This systematic review and meta-analysis was registered at the International Prospective Register of Systematic Reviews (CRD42023400176). [ABSTRACT FROM AUTHOR]

Background: Dexamethasone is currently administered for Coronavirus disease 2019(COVID-19); however, there are concerns about its effect on specific antibodies' production. The aim of this study was to evaluate whether specific antibodies were affected by COVID-19 severity and corticosteroid treatment. Methods: Of 251 confirmed COVID-19 patients admitted to our hospital between January 26 and August 10, 2020, the early period of the pandemic, 75 patients with sera within 1 month of onset and 1 month or longer were included in the research. A total of 253 serum samples from these patients were collected. The levels of specific antibodies for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), immunoglobulin G (IgG) and M (IgM), were measured retrospectively. The results were compared separately of each COVID-19 severity, and with or without corticosteroid treatment. Results: Among the 75 patients, 47, 18, and 10 had mild, moderate, and severe disease, respectively. The median age was 53.0 years and 22 (29%) were women. The most common comorbidities were hypertension and dyslipidemia. Corticosteroids were administered to 20 (27%) and 10 (53%), patients with moderate and severe disease, respectively. The positivity rates IgM increased first, and IgG was almost always positive after day 16, regardless of the severity of COVID-19. On days 6–10, both IgG and IgM positivity rates were higher in patients with moderate disease than in those with mild or severe disease. In patients with moderate disease, IgG positivity was similar over time, regardless of corticosteroid treatment. Conclusions: In COVID-19 patients, specific IgG is positive and maintained for a long period of time, even after corticosteroid treatment. The effect of corticosteroid treatment in a COVID-19 epidemiological study using specific IgG antibodies was considered minor. COVID-19 patients were more likely to receive oxygen if IgM was positive 1 week after onset, but not mechanical ventilation. IgM measurement 1 week after onset may predict COVID-19 severity. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Materials and Methods Results Conclusions The aim of this study was to compare the topical therapeutic efficacy of triamcinolone acetonide (TA) (0.2%) plus hyaluronic acid (HA) (0.1%) versus monotherapy in patients with symptomatic oral lichen planus (OLP), as well as to investigate the oxidative stress of saliva under the different treatments.Sixty OLP patients were included in a randomized, double‐blind, singlecenter study with a treatment duration of 28 days and 3‐month follow‐up period. Participants were randomized into three groups: Group I (TA + HA), Group II (TA), and Group III (HA). Treatment efficacy was assessed by means of Thongprasom scale, Oral Health Impact Profile‐14 (OHIP‐14), and visual analog scale (VAS). In addition, biochemical analyses were performed in order to determine the level of antioxidant biomarkers in saliva, including superoxide dismutase (SOD), glutathione (GSH), and total antioxidant capacity (TAC).All treatments seem to exhibit a significant effect in accordance with Thongprasom scale (p < 0.001), VAS reduction (p < 0.001), and OHIP14 (p < 0.05), which maintains over time. No significant changes in salivary oxidative stress in any of the three groups occurred.The results exhibited a significant improvement in the treated patients in all three groups. There were no significant changes in salivary stress biomarkers under treatment condition. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia (CAH) is a rare, inherited disorder of adrenal steroid synthesis. In many countries it is part of the neonatal screening program enabling early diagnosis and treatment. In case of an abnormal neonatal screening result or when other differences of sexual development (DSD) are suspected, measurement of serum steroid hormones using liquid chromatography coupled to mass spectrometry (LC-MS/MS) is needed for further diagnosis. However, reliable age- and sex-specific reference intervals (RIs) for serum steroid hormones during the neonatal period are missing. We therefore aimed to establish LC-MS/MS based RIs for serum steroid hormones in neonates.Serum was obtained from healthy term neonates at two time points: 130 samples at day 3–8 (T1, time of the neonatal screening) and 126 samples at day 13–15 (T2, two weeks old). Concentrations of cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, 11-deoxycorticosterone, testosterone, androstenedione, and 17-hydroxyprogesterone (17-OHP) were measured using LC-MS/MS.RIs (in nmol/L) were established for T1 and T2: cortisone (19.3–215;18.0–212), cortisol (10.0–407;8.4–446), corticosterone (<31;<50), 11-deoxycortisol (0.73–4.6;0.70–3.6), 17-OHP (<4.9;<5.1), androstenedione (0.3–1.8;0.3–2.7), 11-deoxycorticosterone (<0.2;<0.2), and 21-deoxycortisol (<1;<1), respectively. Testosterone differed between boys and girls: RIs at T1 and T2 for boys were 0.27–4.3 and 0.63–13.9, and for girls<0.30 and <0.47, respectively.We established LC-MS/MS based RIs for cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, 11-deoxycorticosterone, testosterone, androstenedione, and 17-OHP in neonates in the first and second week of life. [ABSTRACT FROM AUTHOR]

Oral corticosteroids represents the most prevalent treatment for idiopathic granulomatous mastitis. Ductal lavage with triamcinolone acetonide and antibiotics followed by observation (DL-OBS) has emerged as a novel strategy, but a comparison of them remains lacking. Here in this multicenter, open-label, non-inferiority, randomized trial (ClinicalTrials.gov identifier: NCT03724903), we assigned 140 patients to oral corticosteroids (N = 71) and DL-OBS (N = 69), stratified by baseline M-score. The primary outcome is complete Clinical Response rate at 1 year. The non-inferiority margin is −15%. The primary outcome is 85.5% in DL-OBS and 87.3% in oral corticosteroids (difference: −1.8%; 95%CI, 13.2 to 9.5; Pnon-inferiority =.01) in intention-to-treat population, and 92.6% vs 98.2% (difference −5.6%; 95%CI −13.4 to 2.2; Pnon-inferiority =.01) in per-protocol population, respectively. The most common (>15%) adverse events were Cushingoid, epigastric pain and arthralgia in oral corticosteroids, and irregular menstruation in DL-OBS, respectively. Here, we report that DL-OBS shows similar efficacy to oral corticosteroids but with better safety profile. Ductal lavage represents a treatment option for idiopathic granulomatous mastitis. Here, the authors report the results of a randomized clinical trial, indicating that ductal lavage followed by observation is non-inferior to oral corticosteroids [ABSTRACT FROM AUTHOR]

Background: The global effort to cure COVID-19 is still ongoing. Thus, a prospective, block-balanced, open-label, randomized controlled trial was conducted to evaluate how Tenofovir Alafenamide Fumarate affects hospitalized COVID-19 patients' outcomes. Methods: The intervention and control groups of 60 hospitalized COVID-19 patients were randomly allocated. Along with normal medication, the intervention group received 25 mg of tenofovir orally daily for seven days. The control group got normal therapy, including remdesivir and corticosteroids. ICU hospitalization duration, laboratory data, fever, dyspnea, arterial blood oxygen saturation with and without an oxygen face mask, mechanical ventilation, and mortality were the outcomes. Results: Sixty of 236 eligible patients between September 2020 and February 2021 were enrolled. The intervention group had a mean age (±SD) of 61.33 (±13.09) years and the control group 60.03 (±18.03). Sixteen (53.3%) intervention patients and 15 (50.0%) control patients were males. The intervention group had fewer mechanical ventilation and ICU days. Tenofovir Alafenamide Fumarate did not improve fever, dyspnea, oxygen saturation with or without a face mask or nasal cannula, or laboratory data including WBC, ESR, CRP, AST, ALT, AlkP, total and direct bilirubin, in COVID-19 patients. Conclusion: According to this pilot trial, Tenofovir Alafenamide Fumarate, along with conventional treatment, significantly reduced mechanical ventilation and ICU stay in COVID-19 patients. Further thorough research is necessary to verify this conclusion. [ABSTRACT FROM AUTHOR]

Corticosteroids have always been recommended for severe cases of COVID-19. However, the efficacy of treatment with corticosteroids for COVID-19 during the SARS-CoV-2 omicron outbreak in China has not been reported. Clinical data from 406 patients hospitalized for severe/critical COVID-19 from December 2022 to January 2023 at six hospitals in Chongqing were retrospectively analyzed. The primary outcome was all-cause mortality at 28 days in the groups with and without corticosteroids treatment after propensity score matching (PSM). Secondary outcomes were to compare in-hospital mortality and length of survival time with corticosteroids and those without corticosteroids. This study included 406 patients with severe or critical COVID-19, divided into the corticosteroids group (231, 56.9%) and non-corticosteroids group (175, 43.1%). After PSM, the use of corticosteroids did not reduce all-cause mortality at 28 days (42.5% vs. 39.1%). Univariate analysis showed that corticosteroids were not associated with improved all-cause mortality at 28 days [hazard ratio (HR), 1.019; 95% confidence interval (CI), 0.639–1.623; p = 0.938]. Multivariate analysis showed similar results (HR, 1.047; 95% CI, 0.633–1.732; p = 0.858). Among non-survivors, the survival time was significantly larger in those who received corticosteroids compared with the non-corticosteroid users [median 13 (IQR 6.5–15.5) vs. 6 (4-11.25), p = 0.007]. The use of systemic corticosteroids in severe/critical COVID-19 may provide certain potential survival benefits but does not improve prognosis. [ABSTRACT FROM AUTHOR]

Summary Intravenous immunoglobulin (IVIg) is the gold standard treatment for severe cases of immune thrombocytopaenia (ITP). However, its cost, limited duration of efficacy and market supply tension have led French guidelines to reserve IVIg for ITP patients with formal contra‐indications to corticosteroids, with French bleeding score (‘Khellaf score’) > 8, and corticosteroid‐resistant patients either with Khellaf score ≤ 8 or in preparation for an invasive procedure or during pregnancy. We studied the prescribing practices of IVIg for ITP in real‐life conditions and assessed their compliance with French guidelines. A monocentric retrospective study was conducted between 2016 and 2020 among 114 patients hospitalized in our unit, for a total of 208 IVIg treatments. In 37% of cases, the Khellaf score was >8, validating IVIg prescription according to French guidelines. In the remaining cases, reasons noted for use of IVIg included corticosteroid resistance (33.7%), preparation for an invasive procedure (8.5%), context of pregnancy (6.6%) and contra‐indication to corticosteroids (3.3%). After analysis, IVIg prescription was considered valid according to current French guidelines in 84.4% of cases. Non‐compliant IVIg prescription was more frequent in younger patients (p = 0.027). Concomitant anti‐coagulation was also noted as an argument for IVIg prescription outside of the current French guidelines. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusion Warm autoimmune hemolytic anemia (wAIHA) is a rare autoantibody‐mediated disorder, and first‐line treatment primarily relies on corticosteroids. This study assessed overall survival (OS) and treatment patterns of wAIHA in Sweden.Adults with ≥ 1 primary diagnosis code for wAIHA (or AIHA plus oral corticosteroids (OCS)/immunosuppressants as sensitivity analyses) between 2011 and 2022 were identified from five Swedish national registers and linked through each patient's unique identity number. Kaplan–Meier curves with log‐rank tests and Cox regressions were performed to assess OS for patients with primary versus secondary wAIHA and patients with wAIHA and long‐term versus short‐term (≥ 3 vs. < 3 months) OCS users.The main analysis included 292 patients; 1791 patients were included in the sensitivity analysis. At a median 3.7‐year follow‐up, a median OS in primary wAIHA was not reached versus 6.0 years for secondary wAIHA (log‐rank test: p = 0.003). Subgroup analyses showed no significant difference in risk of death between long‐term and short‐term OCS users; however, in the sensitivity analysis, long‐term OCS users showed significantly higher risk of death (adjusted hazard ratio: 1.45; 95% confidence interval: 1.180, 1.781; p < 0.001) versus short‐term OCS users.Secondary wAIHA or long‐term OCS use was associated with lower OS, underscoring the disease burden and unmet need for efficacious wAIHA treatments. [ABSTRACT FROM AUTHOR]

Background: Effective management of adverse events is required to maintain sufficient imatinib dosing when treating patients with gastrointestinal stromal tumors (GISTs). Skin rash is a common adverse event of imatinib, which can be effectively controlled by systemic steroid treatment without imatinib dose modification or interruption. However, the impact of the use of systemic steroids on the efficacy of imatinib treatment remains unclear. Methods: Between October 2014 and February 2022, 277 consecutive patients from a prospective registry of GIST patients were included as the study population. Patients who started systemic steroids due to grade ≥ 3 skin rash or grade 2 skin rash with grade 2 pruritis were classified as the steroid group, whereas patients who did not develop a skin rash or those who did not require steroids for a mild skin rash were classified as the control group. Efficacy outcomes were compared between the two groups. Results: Among the 277 patients, 30 (10.8%) were treated with systemic steroids for skin rash. There was no significant difference in progression free survival (PFS) or overall survival (OS) between the steroid and control groups (3-year PFS, 67.7% vs. 65.1%, p = 0.53; 3-year OS, 91% vs. 89.9%, p = 0.67, respectively). The use of systemic steroids was not an independent factor associated with PFS (hazard ratio 0.73, 95% confidence interval 0.36–1.49, p = 0.39) and OS (hazard ratio 0.37, 95% confidence interval 0.12–1.18, p = 0.09). In the steroid group, patients who successfully maintained the imatinib dosage showed a trend toward more favorable survival outcomes than those who did not (3-year PFS, 73.3% vs. 44.4%, p = 0.34; 3-year OS, 95.8% vs. 75.0%, p = 0.15, respectively). Conclusions: The use of systemic steroids for the control of imatinib induced severe skin rash did not adversely affect the efficacy outcomes of imatinib in patients with advanced GIST. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion To determine the duration of relapsing childhood idiopathic nephrotic syndrome (INS).In this population‐based study, we retrospectively analysed the computerised database of Israel's largest health maintenance organisation. Children (age 2–10 years) with a new INS diagnosis and a corticosteroid (CS) prescription between 2000 and 2010 were included. NS category was determined, according to CS and/or steroid‐sparing agents (SSA) purchases.Out of 1 669 977 eligible children, 608 fulfilled inclusion criteria. Patients in the fourth quartile of purchases (n = 132) had an older age at last relapse (17.9 ± 6.3 vs. 11.3 ± 5.9 years, p < 0.001) and more SSA use (78.8% vs. 20%, p < 0.001) compared to the remaining three quartiles. A single episode occurred in 84 patients. Of the remaining 524 patients (males 66%, diagnosis age: 4.8 ± 2.2 years, SSA prescribed: 35%) who were followed for 15.5 ± 5.1 years, 113 (21.6%) had a continuing disease at an age of 19.3 ± 6.3 years. The leftover 411 entered long‐lasting treatment‐free remission at age 11.2 ± 5.7 years.In this multicentre study, we identified INS disease course by medication delivery. NS long‐standing remission occurs at age 11.2 ± 5.7 years in most cases. However, the disease continues into adulthood in a fifth of the relapsing patients, implicating the need for proper transition to adult care. [ABSTRACT FROM AUTHOR]

Objectives Background Methods Results Discussion To compare the effectiveness of parenteral agents to reduce relapse in patients with acute migraine and identify factors that predict relapse.Following discharge from emergency settings, many patients with acute migraine will experience a relapse in pain; severe relapses may result in re‐visits to emergency settings.A comprehensive literature search, updated to 2023, was conducted to identify randomized controlled trials assessing the effectiveness of parenteral agents on relapse outcomes in patients with acute migraine discharged from emergency settings. Two independent reviewers completed study selection, quality assessment, and data extraction. A traditional meta‐analysis compared parenteral corticosteroids to placebo; a frequentist network analysis assessed direct and indirect comparisons. Results are reported as risk ratios (RRs) and 95% confidence intervals (CIs). The review protocol was registered with the International Prospective Register of Systematic Reviews (identifier: CRD42018099493).From 8949 citations, a total of 53 unique studies were included involving 6167 patients. Most studies had a high or unclear risk of bias. Corticosteroids significantly reduced relapses compared to placebo (RR 0.67, 95% CI 0.52–0.88; I2 = 0%). Patients receiving lidocaine (RR 0.10, 95% CI 0.01–0.82), sedatives/hypnotics (RR 0.33, 95% CI 0.14–0.75), ergot agents (RR 0.44, 95% CI 0.25–0.75), neuroleptics (RR 0.47, 95% CI 0.31–0.71), opioids (RR 0.58; 95% CI 0.35–0.94), or corticosteroids (RR 0.64, 95% CI 0.47–0.86) were significantly less likely to relapse. Lidocaine (RR 0.09, 95% CI 0.01–0.71), combination therapy (RR 0.12, 95% CI 0.02–0.74), or adding corticosteroids (RR 0.61, 95% CI 0.44–0.84) were more likely to reduce severe relapses. Longer duration of headache and residual pain at discharge were significantly associated with higher relapses.Corticosteroids remain the recommended first‐line option to reduce relapse outcomes. Some parenteral agents typically provided for pain relief including ergot agents, neuroleptics, or combination therapy may effectively reduce relapse; however, opioids are not recommended due to safety concerns. Additional research is needed for some lesser studied, albeit promising, agents including lidocaine and propofol. Effective pain control in emergency settings prior to discharge and duration of headache may play a role in the success of such treatments and further investigations could provide further insight regarding how and why some parenteral agents are effective in mitigating relapse events. [ABSTRACT FROM AUTHOR]

Cervical septic arthritis can lead to complications such as epidural abscess, which may result in respiratory failure. We present a case of a 78‑year‑old male with cervical septic arthritis complicated by epidural abscess, leading to severe diaphragm dysfunction. Ultrasound evaluation revealed dysfunction of the left hemidiaphragm and compensatory activation of accessory respiratory muscles. Treatment included antibiotic therapy and corticosteroids, alongside respiratory support. After 21 days, improvements were observed in diaphragmatic function and respiratory muscle activation. Our findings highlight the importance of assessing both diaphragm and accessory respiratory muscles in cases of cervical septic arthritis with respiratory complications. [ABSTRACT FROM AUTHOR]

The French Society of Pediatric Neurology and the FILNEMUS network created a working group on corticosteroid therapy in children with Duchenne muscular dystrophy in order to analyze the literature review and current French practices. The aim of this work was to produce guidelines regarding treatment initiation, pre-therapeutic interventions, choice between available compounds, and treatment monitoring (dosage, duration, and discontinuation). The treatment side effects and their management are also detailed: osteoporosis, endocrinological anomaly (growth delay, weight gain, pubertal delay), cataract, arterial hypertension, behavioral disorders, management of immunosuppression and vaccines, and management of gastrointestinal and metabolic complications. [ABSTRACT FROM AUTHOR]

Pharmaceutical drugs and other chemicals can impact organogenesis, either during pregnancy or by postnatal exposure of very preterm infants. Corticosteroids are administered to pregnant women at risk of preterm delivery in order to reduce neonatal morbidity and mortality. In addition, high-dose corticosteroid exposure of very preterm infants regularly serves to maintain blood pressure and to prevent and treat bronchopulmonary dysplasia, a form of chronic lung disease in prematurely born infants. Despite clinical benefits, there is increasing evidence of corticosteroid-mediated short- and long-term detrimental developmental effects, especially in the kidney. Here, we performed a detailed morphological and functional analysis of corticosteroid-mediated effects on pronephros development in larval zebrafish. About 24-h postfertilization (hpf) transgenic Tg(wt1b: EGFP) zebrafish larvae were exposed to a set of natural and synthetic corticosteroids (hydrocortisone, dexamethasone, 6α-methylprednisolone, betamethasone, prednisolone, fludrocortisone, 11-deoxycorticosterone) with varying glucocorticoid and mineralocorticoid potency for 24 h at different concentrations. A semiautomated, multiparametric in vivo workflow enabled simultaneous assessment of kidney morphology, renal FITC-inulin clearance, and heart rate within the same larva. All corticosteroids exerted significant morphological and functional effects on pronephros development, including a significant hypertrophy of the pronephric glomeruli as well as dose-dependent increases in FITC-inulin clearance as a marker of glomerular filtration rate. In conclusion, the present study demonstrates a significant impact of corticosteroid exposure on kidney development and function in larval zebrafish. Hence, these studies underline that corticosteroid exposure of the fetus and the preterm neonate should be carefully considered due to potential short- and long-term harm to the kidney. [ABSTRACT FROM AUTHOR]

Background/Objectives: Bacterial infections (BI) are a major cause of mortality in patients with alcohol-associated hepatitis (AH); however, only a few studies have investigated BI in AH in the last decade. Therefore, we aimed to assess the features and outcomes of BI in patients with AH. Methods: This observational descriptive study included patients with AH admitted to a tertiary academic hospital between 2016 and 2021. Clinical and complete microbiological data were recorded and complications, including acute-on-chronic liver failure (ACLF), and mortality over 90-days were compared between infected and noninfected patients. Results: Overall, 115 patients with AH were recruited and 75 had severe AH; among them, 66 started corticosteroid treatment. We identified 69 cases of BI in 44 patients; the incidence of BI upon hospital discharge was 32.2%, which reached 38.2% at 90 days. The predominant infection site was the chest (35%). Among the identified bacteria (52.1%), half were gram positive and half gram negative. A low rate of multidrug-resistant bacteria (14%) was also noted. Infected patients during hospitalization (n = 37) exhibited higher rates of hepatic decompensation and ACLF (p = 0.001) and lower survival (81.8% vs. 95.8%, p = 0.015) than did noninfected patients (n = 78). In-hospital infected patients (n = 22) exhibited worse survival (72.7%) than did those infected upon admission (93.3%) or noninfected patients (94.9%) (p = 0.009). Corticosteroid-treated patients displayed a nonsignificant increase in the total number of BI; however, without greater mortality. Conclusions: BI were common in our cohort of patients with AH. Patients with in-hospital infections commonly experienced serious complications, including high ACLF and death rates. Infections diagnosed upon admission were treated without affecting survival. [ABSTRACT FROM AUTHOR]

Introduction: Non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is heterogeneous in both phenotypes and endotypes. Due to insufficient head-to-head comparison studies, it is hard to decide which biological to initiate. This study aimed to compare the efficacy of omalizumab and mepolizumab which can be used in the treatment of patients with severe eosinophilic asthma diagnosed with N-ERD. Methods: The population of this observational, cross-sectional study comprised of N-ERD patients who received omalizumab or mepolizumab for at least 6 months for severe asthma. Outcomes included the asthma control test (ACT), and sino-nasal outcome test scores (SNOT-22), blood eosinophil counts at initiation of biological treatment (T0, baseline) and at the end of 6th months (T6). Adverse effects related to biological treatment and changes of oral corticosteroids dose was recorded. Results: The study included a total of 22 patients, of whom 11 received mepolizumab and 11 received omalizumab. The change in ACT, SNOT-22, eosinophil counts, and adverse effects related to biologicals were similar at T6 (p = 0.606, p = 0.168, p = 0.05, p = 0.053, respectively). However, when examining the SNOT-22 and ACT based on the cumulative distribution curve (SUCRA), mepolizumab (SUCRA value: 0.61, 0.72, respectively) demonstrated greater efficacy compared to omalizumab (SUCRA value: 0.19, 0.35, respectively). The oral corticosteroids discontinuation rate was similar between the two groups (p = 0.05). Conclusion: We found both omalizumab and mepolizumab to be effective in treatment; however, we determined that mepolizumab may have a potential superiority in efficacy. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR), commonly called hay fever, is primarily caused by the release of histamine after exposure to an allergen. This article reviews over-thecounter nasal spray options for the prevention and treatment of AR, including mechanisms of action, risks and benefits, and patient education. [ABSTRACT FROM AUTHOR]

Objective: To estimate the effectiveness and safety of tofacitinib in treating systemic lupus erythematosus (SLE) patients with arthritis. Methods: This research was a retrospective cohort study that focused on SLE patients who had arthritis and were treated with tofacitinib at the Department of Rheumatology and Immunology from January 2020 to January 2022. Clinical outcomes, disease activity, immunological parameters, and adverse events were systematically evaluated pre- and post-treatment at 4, 12, and 24 weeks. Results: Twenty-two patients were analyzed. At the 4-week mark, 5 (22.7%) patients were partially relieved, and 17 (77.3%) unalleviated. By the 12-week assessment, CR off corticosteroids was observed in four patients (18.2%), and CR on corticosteroids was seen in six patients (27.3%), with an additional six (27.3%) maintaining partial remission. At 24 weeks after treatment, three patients (13.6%) achieved CR off corticosteroids, ten patients (45.5%) achieved CR on corticosteroids, and all patients received remission. Compared to before treatment, The SLEDAI and PGA scores significantly improved. The level of C3 was increased significantly, and the absolute CD3+ T cell count, the 28-tender and the 28-swollen joint count, and the levels of serum IL-6 were significantly decreased at 24 weeks after treatment. Conclusion: Tofacitinib demonstrates significant therapeutic potential in SLE patients with arthritis, with a safety profile, and the therapeutic mechanism of tofacitinib may be related to reducing IL-6 expression and inhibiting T cell activation. Key Points • Tofacitinib demonstrates significant therapeutic potential in SLE patients with arthritis • The therapeutic mechanism of tofacitinib may be related to reducing IL-6 expression and inhibiting T cell activation [ABSTRACT FROM AUTHOR]

Idiopathic granulomatous mastitis (IGM) is a debilitating, chronic, inflammatory condition of the breast. Several studies have emerged evaluating intralesional steroid (ILS) injection and topical steroid administration as a treatment for IGM. However, there is a dearth of international consensuses with regards to the management of IGM. Therefore, we have systematically reviewed the effectiveness of ILS in the management of IGM. A systematic search was conducted in PubMed and Cochrane Library databases, the Google Scholar website and by citation searching up to June 15th, 2023. Eight articles were selected and analyzed. A total of 397 IGM patients were included in the review. The mean patient age was 35.7 years, ranging from 23-62 years. The mean pre-treatment diameter of lesions was 27.5 mm. A total of 184 patients were treated with ILS. The mean complete clinical response time was 2.6 months. The overall complete response rate was 92.8%. Complications following ILS were minor, with hematoma, skin atrophy and hyperemia being commonly described, while avoiding the systemic side effects of oral steroid use, such as weight gain and hirsutism, which were the most commonly reported side effects with oral steroids. The recurrence rates in the ILS group (6.6%) appear to be lower than in the oral steroid group (25.8%) and surgery group (26.3%). ILS seem to show a favorable outcome in terms of complete response rate, complete clinical response time and has a lower recurrence rate and complication rate when compared to other intervention strategies. However, more comparative studies with standardized protocols are necessary to ascertain the optimum type, dosage and frequency of ILS regimens. [ABSTRACT FROM AUTHOR]

Purpose: The index review aims to provide an update on the role of corticosteroids and steroid-sparing immunomodulatory therapy (IMT) in managing patients with infectious uveitis. Method: Narrative literature review. Results: Corticosteroids and immunomodulatory therapy (IMT) focus on the host defense system instead of the pathogen, adjusting exaggerated inflammatory reactions to reduce potential harm to ocular tissues. Systemic or local corticosteroids are primarily selected as adjunctive medication for infectious uveitis. Concomitant corticosteroids have also been used in cases of paradoxical worsening in ocular tuberculosis and immune recovery uveitis in cytomegalovirus (CMV) retinitis. While there is no well-established evidence to support the use of IMT in infectious uveitis, it is occasionally used in clinical settings to treat persistent inflammation following resolution of infection such as cases of ocular tuberculosis and ocular syphilis where an insufficient response is observed with corticosteroids. Conclusion: There is no consensus on the position of immunomodulatory therapy in the management of infectious uveitis with different etiologies. The index review provides an overview of available adjunctive corticosteroids and IMT options to assist clinicians in managing such disease entities more efficiently. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Approximately 1% of the UK population take oral corticosteroids for ≥ 28 days each year, for broadly two reasons: deficiency in corticosteroid requiring replacement; or therapeutic corticosteroid for inflammatory conditions. Acute deficiency can occur at times of physiological stress (e.g. surgery), potentially leading to major complications. The Association of Anaesthetists' 2020 consensus guideline provides detailed advice for the management of glucocorticoids during the peri‐operative period for patients with adrenal insufficiency. This national audit aimed to assess compliance with this guideline. Methods: Data were collected from 59 Trusts over 14 consecutive days for all eligible patients undergoing procedures under the care of an anaesthetist. Patients who were prescribed ≥ 5 mg oral prednisolone equivalents pre‐operatively, in whom supplementary corticosteroid would be indicated, were compared with those prescribed < 5 mg oral prednisolone equivalents. Results: Operations for 21,731 patients were audited: 277 (1.3%) patients were taking therapeutic corticosteroids. Detailed peri‐operative data were collected for all patients receiving therapeutic corticosteroids: 201/277 (73%) were ASA physical status ≥ 3; 184/277 (66%) underwent elective procedures; and 252/277 (91%) were prescribed prednisolone pre‐operatively, of whom 219/277 (79%) were prescribed ≥ 5 mg oral prednisolone equivalents. In the patients who were prescribed ≥ 5 mg oral prednisolone equivalents, 186/219 (85%) received pre‐operative glucocorticoid supplementation and 97/219 (42%) received it postoperatively; however, only 67/219 (31%) and 43/219 (20%) respectively received glucocorticoid supplementation according to the guidelines. Overall, peri‐operative prescribing was compliant in 19/219 (9%) patients. A similar proportion, 30/219 (14%), received no supplementation. In the patients taking < 5 mg oral prednisolone equivalents pre‐operatively, 28/58 (48%) received inappropriate supplementation. Conclusions: Despite 125/277 (45%) of anaesthetists reporting Association of Anaesthetists' guidelines use, compliance remained low, with adherence in only 27/125 (22%) patients. Further research is required to identify the correct peri‐operative strategy for patients taking therapeutic corticosteroids. [ABSTRACT FROM AUTHOR]

• SARS-CoV-2 S1 potentiated the neuroinflammatory response to LPS 7d and 9d later. • SARS-CoV-2 S1 potentiated the physiological response to LPS 7d later. • SARS-CoV-2 S1 potentiated the behavioral response to LPS 7d later. • SARS-CoV-2 S1 reduced basal corticosterone (CORT) levels in brain. • SARS-CoV-2 S1 might disinhibit/prime brain immune processes via reduced CORT. Long COVID is a major public health consequence of COVID-19 and is characterized by multiple neurological and neuropsychatric symptoms. SARS-CoV-2 antigens (e.g., spike S1 subunit) are found in the circulation of Long COVID patients, have been detected in post-mortem brain of COVID patients, and exhibit neuroinflammatory properties. Considering recent observations of chronic neuroinflammation in Long COVID patients, the present study explores the idea that antigens derived from SARS-CoV-2 might produce a long-term priming or sensitization of neuroinflammatory processes, thereby potentiating the magnitude and/or duration of the neuroinflammatory response to future inflammatory insults. Rats were administered S1 or vehicle intra-cisterna magna and 7d later challenged with vehicle or LPS. The neuroinflammatory, physiological, and behavioral responses to LPS were measured at various time points post-LPS. We found that prior S1 treatment potentiated many of these responses to LPS suggesting that S1 produces a protracted priming of these processes. Further, S1 produced a protracted reduction in basal brain corticosteroids. Considering the anti-inflammatory properties of corticosteroids, these findings suggest that S1 might disinhibit innate immune processes in brain by reducing anti-inflammatory drive, thereby priming neuroinflammatory processes. Given that hypocortisolism is observed in Long COVID, we propose that similar S1-induced innate immune priming processes might play role in the pathophysiology of Long COVID. [ABSTRACT FROM AUTHOR]

To assess and compare depression, anxiety, and cognitive impairments in juvenile systemic erythematous lupus (JSLE) children with lupus nephritis (LN) during the induction and maintenance phases of treatment and to investigate the association with disease activity, damage and immunosuppressive medications. This study included 33 patients diagnosed as JSLE with LN. Attention and working memory were assessed by the working memory index Wechsler Intelligence Scale (WISC). Depression and anxiety were assessed by the Children Depression Inventory (CDI) and the Spence Children Anxiety Scale respectively. The SLE disease activity index 2000 (SLEDAI-2 K) was recorded. The mean age of the children was 11.6 ± 2.2 years, 88 % were females and 12 % males with disease duration of 16.9 ± 9.2 months and age at onset of 10.2 ± 2.3 years. Mean anxiety scores were higher among patients during the induction phase than those during maintenance phase (62.1 ± 7.2 and 40.2 ± 8.8 respectively; p < 0.001). The depression score was higher in the induction (19 ± 5.5) than in the maintenance group (12.4 ± 5.6) (p = 0.002). Mean anxiety scores significantly correlated with SLEDAI-2 K and corticosteroids dose (r = 0.58 and r = 0.43, p = 0.0004 and p = 0.013 respectively) and a significant negative correlation with duration of corticosteroids and number of cyclophosphamide doses (r = 0.46 and r = 0.69, p = 0.008 and p = 0.0001 respectively). Depression and anxiety levels were higher in children with LN during the induction phase of treatment than those in the maintenance phase. Mental health problems must be screened among children with LN and treating these problems can improve the medical and psychosocial outcomes. [ABSTRACT FROM AUTHOR]

A 10-year-old male castrated Somali cat presented with neurologic signs, severe systemic hypertension, and hypokalemia. Abdominal ultrasonography demonstrated a left adrenal mass, and the serum aldosterone concentration was increased. Computed tomography and follow-up diagnostic testing confirmed a left adrenal mass consistent with functional adenocarcinoma; additional findings included chronic airway and parenchymal disease. Transthoracic echocardiography revealed biatrial enlargement, with abdominal and pericardial effusion, consistent with right-sided congestive heart failure. The cat was treated for congestive heart failure and adrenalectomy was performed. Cardiac structure and function returned to normal within 6 months postoperatively. This report highlights a case of reversible congestive heart failure secondary to primary hyperaldosteronism. [ABSTRACT FROM AUTHOR]

Introduction: Chronic obstructive pulmonary disease (COPD) is a common syndrome associated with smoking and environmental exposures coupled with genetic susceptibility. Recent major advancements in the treatment of COPD patients have become available. Areas covered: New data on the role of classic bronchodilators, including short-acting and long-acting beta2-agonists and anti-muscarinic antagonists, in the treatment of COPD patients are discussed. Data promoting a more targeted approach to inhaled and systemic corticosteroid use in COPD are reviewed. Phosphodiesterase (PDE) inhibitors, including the recently approved PDE 3/4 inhibitor inhaled ensifentrine, are noted. Selective use of antibiotics can play a role in complex COPD patients. COPD patients with evidence of asthma-COPD overlap syndrome and type-two lymphocytic inflammatory-mediated airway constriction appear to respond to biologics, particularly the anti-IL-4/IL-3 antagonist monoclonal antibody, dupilumab. Expert opinion: New therapeutic options have made the approach and treatment of the COPD patient much more complicated. These options tend to be very expensive. Attention to identifying the endotype and phenotype will help direct the pharmacotherapy. [ABSTRACT FROM AUTHOR]

Acute presentation of autoimmune hepatitis (AIH) occurs in 22–43% of all AIH cases, and is not a rare condition. Rather than constituting a single disease entity, it represents a clinical spectrum characterized by considerable variability in severity and the presence of preexisting chronic AIH. This spectrum ranges from acute AIH and acute severe AIH to AIH presenting as acute liver failure (ALF) or as acute-on-chronic liver failure (ACLF), contingent upon factors such as coagulopathy, hepatic encephalopathy, and underlying liver disease. Diagnosing acute presentation of AIH can be particularly challenging due to the frequent absence of classical serologic signatures such as autoantibodies and elevated IgG levels. Histopathological examination remains essential for diagnosis, typically necessitating percutaneous or transjugular liver biopsy. Corticosteroids (CS) are recommended for the management of acute AIH and acute severe AIH with coagulopathy. However, the therapeutic response to CS should be meticulously monitored. If a poor response is anticipated, liver transplantation (LT) should be promptly considered. For AIH presenting as ALF with encephalopathy or ACLF with advanced underlying liver disease, LT is generally advised. Nonetheless, there is potential for a trial of CS therapy in cases of ALF with low MELD scores or ACLF without encephalopathy. This review provides an overview of the latest findings concerning the definition, diagnosis, and management of acute presentation of AIH. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To examine the effectiveness and identify clinical response predictors of a short corticosteroid‐based regimen consisting of topical preservative‐free 0.1% dexamethasone (Monopex®, Théa Laboratories) in conjunction with artificial tears (AT) for dry eyes in a real‐life clinical setting.Patients were recruited from the Norwegian Dry Eye Clinic and were allowed to use ATs of their own choice in addition to the prescribed 14‐day topical dexamethasone course. Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire (DEQ‐5), Schirmer test (ST), fluorescein tear film break‐up time (FBUT), ocular surface staining (OSS), meibum expressibility (ME), meibum quality (MQ), number of expressible meibomian glands among the central eight glands in the lower lids (NMG) and intraocular pressure (IOP) were measured at baseline and at 1‐month follow‐up. The average values of clinical parameters from both eyes were used for analyses. A paired t‐test and a significance value of p < 0.05 were used for statistical analyses. Associations between sex, age, baseline values and the changes after the intervention (Δ) were explored using linear regression.A total of 167 patients (124 women, mean age 54 years ±17 (standard deviation)) were included. One month after initiation of intervention, OSDI and DEQ5 scores improved from 39.5 ± 22.1 to 31.4 ± 21.3 (p < 0.001) and from 12.6 ± 4.2 to 11.0 ± 4.6 (p < 0.001), respectively. OSS improved from 2.2 ± 1.4 to 1.8 ± 1.5 (p < 0.001), NMG increased from 4.8 ± 2.2 to 5.1 ± 2.2 (p < 0.05), while IOP decreased from 12.9 ± 3.3 to 12.4 ± 3.5 mmHg (p < 0.05). Significant associations were found between the change in symptoms and objective measures of DED (ΔOSDI, ΔDEQ5, ΔOSS, ΔFBUT, ΔNMG, ΔMQ) and their respective baseline values (OSDI, DEQ5, OSS, FBUT, NMG, MQ). The remaining tests did not show statistically significant changes.Improvement in dry eye symptoms and signs were observed following a short course of topical, preservative‐free 0.1% dexamethasone treatment in combination with AT. Individuals exhibiting more pronounced symptoms and signs witnessed the most profound improvements with the treatment regimen, suggesting that poor baseline parameters may serve as response predictors of the treatment regimen. While the real‐life data presented herein are valuable, the conclusions are limited by the inherent biases of a non‐controlled study. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common in critical cases of coronavirus disease 2019 (COVID-19) and associated with worse outcome. Dysregulated neutrophil extracellular trap (NET) formation is one of several suggested pathophysiological mechanisms involved in the development of COVID-19 associated AKI. The corticosteroid dexamethasone was implemented as a standard treatment for severe COVID-19 as of June 2020. A sub-analysis of a prospective observational single center study was performed to evaluate the effect of corticosteroid treatment on AKI development and NET markers in critical cases of COVID-19. Results: Two hundred and ten adult patients admitted to intensive care at a tertiary level hospital due to respiratory failure or shock secondary to SARS-CoV-2-infection between March 13th 2020 and January 14th 2021 were included in the study. Ninety-seven of those did not receive corticosteroids. One hundred and thirteen patients were treated with corticosteroids [dexamethasone (n = 98) or equivalent treatment (n = 15)], but the incidence of AKI was assessed only in patients that received corticosteroids before any registered renal dysfunction (n = 63). Corticosteroids were associated with a lower incidence of AKI (19% vs 55.8%, p < 0.001). Fewer patients demonstrated detectable concentrations of extracellular histones in plasma when treated with corticosteroids (8.7% vs 43.1%; p < 0.001). Extracellular histones and in particular non-proteolyzed histones were observed more frequently with increasing AKI severity (p < 0.001). MPO-DNA was found in lower concentrations in patients that received corticosteroids before established renal dysfunction (p = 0.03) and was found in higher concentrations in patients with AKI stage 3 (p = 0.03). Corticosteroids did not ameliorate established AKI during the first week of treatment. Conclusion: Corticosteroid treatment in severe COVID-19 is associated with a lower incidence of AKI and reduced concentrations of NET markers in plasma. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionSevere asthma presents significant management challenges, often requiring advanced treatments to control symptoms and reduce exacerbations. The use of monoclonal antibodies has revolutionized the clinical course of patients with severe asthma, showing a significant impact on exacerbations reduction, oral corticosteroids (OCS) cessation and on the improvement of lung function and quality of life. Tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody, has emerged as a potential therapeutic option for these patients.We conducted an observational, prospective, multicenter study including 20 patients with confirmed severe asthma according to ERS guidelines and GINA recommendations. Patients received Tezepelumab 210 mg every 4 wk due to uncontrolled asthma despite maximal inhalation treatment with ICS/LABA. Data were collected before treatment initiation (T0) and after three months from the first administration (T3).After three months of Tezepelumab treatment, we reported significant improvements in asthma symptoms and quality of life, as well as a consistent reduction in exacerbations and OCS use. We found no statistically meaningful differences among main clinical and functional outcomes according to inflammatory biomarkers, while lung function improved significantly in patients with less allergic sensitization. No serious adverse event was reported during the follow up, while the rates of mild adverse effects were comparable to those from registration trials.Tezepelumab demonstrated short-term efficacy in improving asthma control and quality of life, showing a favorable safety profile. Further studies with larger sample sizes and longer follow-up would confirm these findings and identify predictors of response to Tezepelumab. [ABSTRACT FROM AUTHOR]

Aim: The objective of this study was to assess the therapeutic effects of corticosteroids in adult patients hospitalized with viral community-acquired pneumonia. Methods: This 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. Results: Of 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-. Conclusions: There were no significant differences in the primary and secondary outcomes regarding the use of corticosteroids in patients with viral pneumonia. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion The management of acute exacerbations of chronic rhinosinusitis (AECRS) is understudied and the most cost‐effective management of AECRS has not been previously investigated. The aim of this study is to determine the most cost‐effective strategy for the initial management of AECRS.The study design consisted of a decision‐tree economic model comparing three different initial strategies for managing a patient perceived AECRS: observation, upfront rescue medications, or clinic visit with diagnostic nasal endoscopy (DNE). The primary study outcome was the disease burden of a single AECRS, which was determined by the health utility value and the duration of symptoms. Strategies with an incremental cost‐effectiveness ratio < $50,000/quality‐adjusted life year (QALY) or equivalently < $137/quality‐adjusted life day (QALD) were considered cost‐effective.Observation was the most cost‐effective strategy at a willingness to pay of $137 per QALD. One‐way sensitivity analysis demonstrated that observation was more effective than upfront rescue medications when the probability of bacterial infection as the cause of AECRS was <24.0%. Upfront rescue medications wer more cost effective than observation when the probability of bacterial infection exceeded 49.0%. Clinic visit with DNE was the most effective strategy to manage an AECRS, but it was not considered cost‐effective.Observation is the most cost‐effective strategy for the initial management of AECRS when there is a low likelihood of bacterial infection. When the probability of bacterial etiology of AECRS exceeds 49.0%, upfront rescue medications proved to be the most cost‐effective strategy. [ABSTRACT FROM AUTHOR]

Background: Early studies indicated that corticosteroids may limit the survival benefit from immunotherapy. We conducted this systematic review to evaluate the effect corticosteroids have on immunotherapy in patients with malignancy, when adjusted for potentially confounding effects of corticosteroids given for palliative indications. Methods: Three electronic databases (PubMed, Embase and Medline) were searched on 1 February 2023. Studies that measured response or survival to immunotherapy in people receiving corticosteroids for non‐cancer indications compared to either no corticosteroids or corticosteroids for cancer‐related indications were included. Studies exclusively evaluating the effect of corticosteroids administered for immune‐related adverse events (irAE) were excluded to avoid immortal time bias. Pooled odds and hazard ratios with 95% confidence intervals (CI) were calculated using a random effects model. Study heterogeneity was assessed using the I2 statistic, and publication bias was evaluated by funnel plot and Egger's regression model. Results: Eight thousand four hundred and twenty‐six titles were identified on our search. Eight studies met our inclusion criteria for meta‐analysis. Administration of corticosteroids does not have a statistically significant effect on survival and response to immunotherapy when administered for non‐cancer‐related indications, with a pooled odds ratio for overall response rate 1.01 (95% CI 0.64–1.60); pooled hazard ratio (HR) for progression free survival 0.87 (95% CI 0.68–1.12); and pooled HR for overall survival 0.79 (95% CI 0.59–1.05). Conclusion: This systematic review indicates that administration of corticosteroids does not affect response to immunotherapy nor survival outcomes, when removing confounding palliative corticosteroid indications. These results are limited by the retrospective nature of the studies included, small sample sizes, lack of information about corticosteroid dosing and the inclusion of irAE in two of the studies which could bias the results. [ABSTRACT FROM AUTHOR]

In this study, a new and straightforward process for the preparation of budesonide 21-phosphate (Bud-21P) and its disodium salt (Bud-21P-Na2) is described. The method results in a yield comparable to those obtained by diphosphoryl chloride, but it is more manageable, less expensive, and safer. The new compounds are characterized by better water solubility compared to the parent compound. Moreover, they have been evaluated for their anti-inflammatory activity and the obtained results clearly evidence that Bud-21P and Bud-21P-Na2 retained anti-inflammatory activity like the parent compound budesonide (Bud) in mice with cutaneous induced edema. [ABSTRACT FROM AUTHOR]

Myocarditis is a major cause of heart failure and death, particularly in young individuals. Current treatments are mainly symptomatic, but emerging therapies focus on targeting inflammation and fibrosis pathways. Natural bioactive compounds like flavonoids and phenolic acids show promising anti-inflammatory and antioxidant properties. Corticosteroids are frequently employed in the treatment of autoimmune myocarditis and appear to lower mortality rates compared to conventional therapies for heart failure. This study aims to explore the effects of Mangiferin on pro-inflammatory cytokine levels, nitro-oxidative stress markers, histopathological alterations, and cardiac function in experimental myosin-induced autoimmune myocarditis. The effects were compared to Prednisone, used as a reference anti-inflammatory compound, and Trolox, used as a reference antioxidant. The study involved 30 male Wistar–Bratislava rats, which were randomly divided into five groups: a negative control group (C−), a positive control group with induced myocarditis using a porcine myosin solution (C+), three groups with induced myocarditis receiving Mangiferin (M), Prednisone (P), or Trolox (T) as treatment. Cardiac function was evaluated using echocardiography. Biochemical measurements of nitro-oxidative stress and inflammatory markers were conducted. Finally, histopathological changes were assessed. At echocardiography, the evaluation of the untreated myocarditis group showed a trend toward decreased left ventricular ejection fraction (LVEF) but was not statistically significant, while all treated groups showed some improvement in LVEF and left ventricular fraction shortening (LVFS). Significant changes were seen in the Mangiferin group, with lower end-diastolic left ventricular posterior wall (LVPWd) by day 21 compared to the Trolox group (p < 0.001). In the first week of the experiment, levels of interleukins (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α were significantly higher in the myosin group compared to the negative control group (p < 0.001, p < 0.001, p < 0.01), indicating the progression of inflammation in this group. Treatment with Mangiferin, Prednisone, and Trolox caused a significant reduction in IL-1β compared to the positive control group (p < 0.001). Notably, Mangiferin resulted in a superior reduction in IL-1β compared to Prednisone (p < 0.05) and Trolox (p < 0.05). Furthermore, Mangiferin treatment led to a statistically significant increase in total oxidative capacity (TAC) (p < 0.001) and a significant reduction in nitric oxide (NOx) levels (p < 0.001) compared to the negative control group. Furthermore, when compared to the Prednisone-treated group, Mangiferin significantly reduced NOx levels (p < 0.001) and increased TAC levels (p < 0.001). Mangiferin treatment significantly lowered creatine kinase (CK) and aspartate aminotransferase (AST) levels on day 7 (p < 0.001 and p < 0.01, respectively) and reduced CK levels on day 21 (p < 0.01) compared to the untreated group. In the nontreated group, the histological findings at the end of the experiment were consistent with myocarditis. In the group treated with Mangiferin, only one case exhibited mild inflammatory infiltrates, represented by mononucleated leukocytes admixed with few neutrophils, with the severity graded as mild. Statistically significant correlations between the grades (0 vs. 1–2) and the study groups have been highlighted (p < 0.005). This study demonstrated Mangiferin's cardioprotective effects in autoimmune myocarditis, showing reduced oxidative stress and inflammation. Mangiferin appears promising as a treatment for acute myocarditis, but further research is needed to compare its efficacy with other treatments like Trolox and Prednisone. [ABSTRACT FROM AUTHOR]

Purpose To familiarize clinicians with the emerging concepts in critical care research of Bayesian thinking and personalized medicine through phenotyping and explain their clinical relevance by highlighting how they address the issues of frequent negative trials and heterogeneity of treatment effect. Summary The past decades have seen many negative (effect-neutral) critical care trials of promising interventions, culminating in calls to improve the field's research through adopting Bayesian thinking and increasing personalization of critical care medicine through phenotyping. Bayesian analyses add interpretive power for clinicians as they summarize treatment effects based on probabilities of benefit or harm, contrasting with conventional frequentist statistics that either affirm or reject a null hypothesis. Critical care trials are beginning to include prospective Bayesian analyses, and many trials have undergone reanalysis with Bayesian methods. Phenotyping seeks to identify treatable traits to target interventions to patients expected to derive benefit. Phenotyping and subphenotyping have gained prominence in the most syndromic and heterogenous critical care disease states, acute respiratory distress syndrome and sepsis. Grouping of patients has been informative across a spectrum of clinically observable physiological parameters, biomarkers, and genomic data. Bayesian thinking and phenotyping are emerging as elements of adaptive clinical trials and predictive enrichment, paving the way for a new era of high-quality evidence. These concepts share a common goal, sifting through the noise of heterogeneity in critical care to increase the value of existing and future research. Conclusion The future of critical care medicine will inevitably involve modification of statistical methods through Bayesian analyses and targeted therapeutics via phenotyping. Clinicians must be familiar with these systems that support recommendations to improve decision-making in the gray areas of critical care practice. [ABSTRACT FROM AUTHOR]