The Use of Azelastine Hydrochloride/Fluticasone Propionate in the Management of Allergic Rhinitis in Asia: A Review.

The incidence of allergic rhinitis (AR) in Asia and the world is steadily rising. Patients experience incomplete symptom relief despite existing treatment options, which warrants the need for new therapeutic regimes. Azelastine hydrochloride/fluticasone propionate (MP-AzeFlu), a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate has been indicated in the treatment of AR. The current review discusses the effects of MP-AzeFlu versus conventional therapies in achieving superior clinical improvement with a very rapid onset of action (5 minutes). The superiority of MP-AzeFlu in offering complete symptom control with sustained relief in patients with AR compared to the existing therapeutic options is also discussed. MP-AzeFlu has been shown to improve the quality of life for patients with AR, thereby enhancing patient adherence to therapy and establishing its preference for the treatment of AR. Currently, the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines recommend the use of a combination of intranasal corticosteroids and intranasal antihistamines as first-line treatment in patients with persistent AR with visual analog scores ≥5 or when prior treatment with single agents has been ineffective. Widely published data on the efficacy and safety of its prolonged use in adults and children have validated that effective treatment of AR can be achieved with MP-AzeFlu.

Differences in the effectiveness of single, dual, and triple inhaled corticosteroid therapy for reducing future risk of severe asthma exacerbation: A systematic review and network meta-analysis.

Importance: The effectiveness of different combinations of inhaled corticosteroid (ICS) therapies in reducing severe exacerbations of adult asthma remains unclear. Objective: This network meta-analysis (NMA) extensively evaluated the treatment effects of single ICS; dual ICS i.e., ICS/long-acting ß2-adrenergic agonists (LABA); ICS/LABA as single maintenance and reliever therapy (SMART); and triple ICS, i.e., ICS/LABA/long-acting muscarinic antagonists (LAMA) in preventing severe asthma exacerbations. Data sources: A systematic search of English databases, including PubMed and Web of Science, was conducted until December 31, 2022, using PRISMA-NMA. Study selection: Using the PICOS criteria, the questions for this study were carefully selected so that the correct keywords could be identified. Data extraction and synthesis: A pairwise meta-analysis was used to select trials based on the criteria for minimizing heterogeneity (I2). Subsequently, the "BUGSnet" package of R software was used to perform a Bayesian network meta-analysis. Main outcome measures: The main outcome measures were risk rate and annualized rate ratio of severe asthma exacerbations. Results: This review included 56 randomized control trials (RCTs; n = 78,171 patients). As the pairwise meta-analysis demonstrated that the annualized rate ratio of severe asthma exacerbation had moderate heterogeneity, we analyzed the risk rate of severe asthma exacerbation using a network meta-analysis. In terms of direct/indirect comparisons with non-ICS, single ICS, dual ICS, SMART, and triple ICS reduced severe asthma exacerbations by 34 %, 47 %, 58 %, and 57 %, respectively. SMART and triple ICS showed high effectiveness in reducing severe exacerbations. Conclusion: AND RELEVANCE: SMART and triple ICS were ranked higher in effectiveness in reducing severe asthma exacerbations in comparison with other therapies, indicating that these are the most effective treatments for reducing the future risk of severe asthma exacerbations.

Filgotinib induction-study baseline characteristics of patients with ulcerative colitis who achieve sustained corticosteroid-free remission: post hoc analysis of the phase 2b/3 SELECTION study.

Background/Aims: Obtaining and maintaining corticosteroid-free remission are important goals of treatment for ulcerative colitis (UC). Characteristics associated with achieving corticosteroid-free remission were assessed in filgotinib-treated patients in SELECTION, a 58-week, phase 2b/3 trial in moderately to severely active UC. Methods: This post hoc analysis used data from filgotinib-treated patients receiving corticosteroids at maintenance baseline in SELECTION. Univariate logistic regression was performed to assess induction baseline characteristics associated with 6 months of corticosteroid-free remission at week 58, defined as clinical remission without using corticosteroids for at least 6 months. Results: At maintenance baseline, 92 and 81 patients were receiving corticosteroids in the filgotinib 200 mg and filgotinib 100 mg groups, respectively. Age, body mass index, history of pancolitis, disease duration, fecal calprotectin levels, C-reactive protein levels, Mayo Clinic Score, concomitant corticosteroids, immunomodulators, and aminosalicylates had no statistically significant effect on the likelihood of achieving corticosteroid-free remission. Baseline characteristics associated with increased odds of corticosteroid-free remission were Mayo Clinic Endoscopic Subscore of 2 (vs. 3) in the filgotinib 200 mg and filgotinib 100 mg groups, and female (vs. male) sex, current (vs. former or never) smoking, and being biologic­naive (vs. experienced) in the filgotinib 200 mg group. Conclusions: Steroid tapering can be achieved in patients with UC receiving filgotinib 200 mg independently of baseline characteristics such as clinical activity and duration of illness. However, the likelihood of achieving corticosteroid-free remission was higher among patients who were biologic-naive, current smokers, had low endoscopic inflammatory burden and who were female.

Urban house finches are more resistant to the effects of artificial light at night.

Rapid urbanization of habitats alters the physical, chemical, auditory, and photic environments of human and wild animal inhabitants. One of the most widespread transformations is caused by artificial light at night (ALAN), but it is not clear the extent to which individuals acclimate to such rapid environmental change. Here, we tested the hypothesis that urban birds show increased resistance to harmful behavioral, parasitological, and physiological effects of ALAN. We captured house finches (Haemorhous mexicanus), a bird that commonly inhabits cities and their natural surroundings, from two urban and two rural sites in Phoenix, Arizona, USA, which differ by both degree of urbanization and by multiple orders of magnitude in ALAN intensity, and placed them in a common garden laboratory setting. We exposed half of the birds from each habitat type to ecologically relevant levels of night lighting during the subjective night and found that, while ALAN exposure reduced sleep in both urban and rural birds, ALAN-exposed urban birds were able to sleep longer than ALAN-exposed rural birds. We also found that ALAN exposure increased the proliferation rate of an intestinal coccidian parasite (Isospora spp.) in both urban and rural birds, but that the rate of proliferation was lower in urban relative to rural birds. We found that night lighting suppressed titers of feather corticosterone in rural but not urban birds, suggesting that light impairs HPA function through chronic stress or suppression of its circadian rhythmicity, and that urban birds were again resistant to this effect. Mediation analyses show that the effect of ALAN exposure in rural birds was significantly sleep-mediated for feather corticosterone but not coccidiosis, suggesting a diversity of mechanisms by which ALAN alters physiology. We contribute further evidence that animals from night-lit habitats can develop resistance to ALAN and its detrimental effects.

Sarcoidosis-associated pulmonary hypertension due to pulmonary arteries stenosis - a case report.

BACKGROUND: Sarcoidosis-associated pulmonary hypertension (SAPH) is listed in Group 5 of the clinical classification of pulmonary hypertension, due to its complex and multifactorial pathophysiology. The most common cause of SAPH development is advanced lung fibrosis with the associated destruction of the vascular bed, and/or alveolar hypoxia. However, a substantial proportion of SAPH patients (up to 30%) do not have significant fibrosis on chest imaging. In such cases, the development of pulmonary hypertension may be due to the lesions directly affecting the pulmonary vasculature, such as granulomatous angiitis, pulmonary veno-occlusive disease, chronic thromboembolism or external compression of vessels by enlarged lymph nodes. Based on the case of a 69-year-old female who developed SAPH due to pulmonary arteries stenosis, diagnostic difficulties and therapeutic management are discussed. CASE PRESENTATION: The patient, non-smoking female, diagnosed with stage II sarcoidosis twelve years earlier, presented with progressive dyspnoea on exertion, dry cough, minor haemoptysis and increasing oedema of the lower limbs. Computed tomography pulmonary angiography (CTPA) showed complete occlusion of the right upper lobe artery and narrowing of the left lower lobe artery, with post-stenotic dilatation of the arteries of the basal segments. The vascular pathology was caused by adjacent, enlarged lymph nodes with calcifications and fibrotic tissue surrounding the vessels. Pulmonary artery thrombi were not found. The patient was treated with systemic corticosteroid therapy and subsequently with balloon pulmonary angioplasty. Partial improvement in clinical status and hemodynamic parameters has been achieved. CONCLUSIONS: An appropriate screening strategy is required for early detection of pulmonary hypertension in sarcoidosis patients. Once SAPH diagnosis is confirmed, it is crucial to determine the appropriate phenotype of pulmonary hypertension and provide the most effective treatment plan. Although determining SAPH phenotype is challenging, one should remember about the possibility of pulmonary arteries occlusion.

Expedited liver transplantation as first-line therapy for severe alcohol hepatitis: ELFSAH; deferring corticosteroids in the sickest subset of patients.

BACKGROUND & AIMS: Severe alcohol-associated hepatitis (SAH) represents a lethal subset of alcohol-associated liver disease. Although corticosteroids are recommended by guidelines, their efficacy and safety remain questionable and so liver transplantation (LT) has been increasingly utilized. The timing and indication of corticosteroid use, specifically in patients being considered for LT requires further clarification. METHODS: A retrospective analysis was conducted on 256 patients with SAH between 2018 and 2022 at a single US center. RESULTS: Twenty of these patients underwent LT. Of the 256 patients, 38% had what we termed "catastrophic" SAH, defined as a MELD-Na ≥35 and/or discriminant function (DF) ≥100, which carried a mortality of 90% without LT. Compared with 100 matched controls, patients undergoing LT exhibited a one-year survival rate of 100% versus 35% (p < .0005). LT provided an absolute risk reduction of 65%, with a number needed to treat of 1.5. Steroid utilization in the entire cohort was 19% with 60% developing severe complications. Patients administered steroids were younger with lower MELD and DF scores. Only 10% of those prescribed steroids derived a favorable response. Sustained alcohol use post-LT was 20%. CONCLUSIONS: We propose ELFSAH: Expedited LT as First Line Therapy for SAH; challenging the current paradigm with recommendations to defer steroids in patients with "catastrophic" SAH (defined as: MELD-Na ≥35 and/or DF ≥100). Patients should be seen urgently by hepatology, transplant surgery, psychiatry and social work. Patients without an absolute contraindication should be referred for LT as first-line therapy during their index admission.

The Prevalence and Characteristics of Inflammatory Bowel Disease-related Ocular Involvement in Children.

BACKGROUND: Ocular manifestations (OMs) in patients with inflammatory bowel disease (IBD) are uncommon, particularly in children. We aimed to explore the prevalence and characteristics of IBD-associated OM in a large cohort study. METHODS: A cross-sectional study was performed using the Maccabi Healthcare Services (MHS) database. The eligible population included all patients diagnosed with IBD as children (<18 years) between January 2005 and July 2023. RESULTS: Out of 2567 children with IBD (males 55%, Crohn's disease 64%), 78 (3%) were diagnosed with OM at any time during the disease course. In 54 patients (69%), the ocular disease occurred after IBD diagnosis with a median time of 2.6 (0.47-7) years between the 2 events, whereas in 24 patients (31%), ocular involvement preceded IBD diagnosis with a median time of 2.1 (0.6-5.7) years. The presence of ocular involvement was associated with increased usage of systemic corticosteroids (P < .001) and biologic agents (P = .04). There were 55 patients with ocular involvement during childhood who were ever diagnosed with IBD. In this population, ocular involvement was also associated with increased usage of systemic corticosteroids (P < .001). The prevalence of OM among patients with IBD did not change significantly over time (P = .75), with a prevalence of 2.3% at the end of the study period. CONCLUSIONS: The prevalence of ocular involvement in children with IBD is rare and steady; it is also associated with a greater usage of systemic corticosteroids and biologic agents, potentially representing a more severe disease course.

The prevalence of ocular manifestations in children with inflammatory bowel diseases is 2.3%, steady over the years. Ocular manifestations were associated with systemic steroids and biologic agents treatment, potentially representing severe inflammatory bowel disease.

Chondrotoxicity of Intra-Articular Injection Treatment: A Scoping Review.

The purpose of this scoping review was to identify possible chondrotoxic effects caused by drugs usually used for intra-articular injections. PubMed, Scopus, Web of Science and Cochrane were searched. Inclusion criteria required randomized controlled trials written in English that evaluate the toxic effect that damages the cartilage. The literature search resulted in 185 unique articles. 133 full-text articles were screened for inclusion, of which 65 were included. Corticosteroids, with the exception of triamcinolone, along with local anaesthetics, potentially excluding ropivacaine and liposomal bupivacaine, and nonsteroidal anti-inflammatory drugs, exhibited insufficient safety profiles to warrant casual use in clinical settings. Hyaluronic acid, on the other hand, appears to demonstrate safety while also mitigating risks associated with concurrent compounds, thereby facilitating therapeutic combinations. Additionally, there remains a paucity of data regarding platelet-rich plasma, necessitating further evaluation of its potential efficacy and safety. Overall, it seems that results are significantly influenced by the dosage and frequency of injections administered, observed in both human and animal studies.

Betamethasone treatment-to-delivery interval, retreatment, and severe intraventricular hemorrhage in infants <28 weeks' gestation.

BACKGROUND: Antenatal corticosteroids decrease the incidence of severe intraventricular hemorrhages (grades 3,4) in preterm infants. It is unclear whether their beneficial effects on intraventricular hemorrhage wane with time (as occurs in neonatal respiratory distress) and if repeat courses can restore this effect. Prior randomized controlled trials of betamethasone retreatment found no benefit on severe intraventricular hemorrhage rates. However, the trials may have included an insufficient number of infants at risk for intraventricular hemorrhage to be able to adequately address this question. Severe intraventricular hemorrhages occur almost exclusively in infants born <28 weeks, whereas only 7% (0%-16%) of the retreatment trials' populations were <28 weeks. OBJECTIVE: To determine if the risk of severe intraventricular hemorrhage in infants delivered <28 weeks increases when the betamethasone treatment-to-delivery interval increases beyond 9 days and to determine if betamethasone retreatment prior to delivery decreases the rate of hemorrhage. STUDY DESIGN: Observational study examining the incidence of intraventricular hemorrhage before (epoch 1) and after (epoch 2) a practice change that encouraged obstetricians to retreat pregnant women still at high risk of delivery before 28 weeks' gestation when >9 days elapsed from the first dose of betamethasone. Multivariable analyses with logistic regression using generalized estimating equations techniques were conducted to examine the rates of intraventricular hemorrhage among 410 infants <28 weeks' gestation who either delivered between 1-9 days (n=290) after the first 2-dose betamethasone course or delivered ≥10 days (and eligible for retreatment) (n=120). RESULTS: After adjusting for potential confounding variables, infants who delivered ≥10 days after a single betamethasone course had an increased risk of either severe intraventricular hemorrhage alone or the combined outcome severe intraventricular hemorrhage or death before 4 days (OR (95%CI): 2.8 (1.2, 6.6)) compared with infants who delivered between 1-9 days after betamethasone. Among the 120 infants who delivered ≥10 days after the first dose of betamethasone, 64 (53%) received a second/retreatment course of antenatal betamethasone. The severe intraventricular hemorrhage rate in infants whose mothers received a second/retreatment course of betamethasone was similar to the rate in infants who delivered within 1-9 days and significantly lower than in those who delivered ≥10 days without retreatment (OR (95%CI): 0.10 (0.02, 0.65). Following the change in guidelines, the rate of retreatment in infants who delivered ≥10 days after the first betamethasone course (and before 28 weeks) increased from epoch 1 to epoch 2 (25% to 87%, p<0.001) and the rate of severe intraventricular hemorrhage decreased from 22% to 0% (p<0.001). In contrast, the rate of severe intraventricular hemorrhage in infants who delivered 1-9 days after the initial betamethasone dose (who were not eligible for retreatment) did not change between epochs 1 and 2 (12% and 11%, respectively). CONCLUSIONS: Although betamethasone's benefits on severe intraventricular hemorrhage appear to wane after the first dose, retreatment with a second course appears to restore its beneficial effects. Encouraging earlier retreatment of women at high risk of delivery before 28 weeks was associated with a lower rate of severe intraventricular hemorrhages among infants delivering <28 weeks.

Dexamethasone treatment influences tendon healing through altered resolution and a direct effect on tendon cells.

Inflammation, corticosteroids, and loading all affect tendon healing, with an interaction between them. However, underlying mechanisms behind the effect of corticosteroids and the interaction with loading remain unclear. The aim of this study was to investigate the role of dexamethasone during tendon healing, including specific effects on tendon cells. Rats (n = 36) were randomized to heavy loading or mild loading, the Achilles tendon was transected, and animals were treated with dexamethasone or saline. Gene and protein analyses of the healing tendon were performed for extracellular matrix-, inflammation-, and tendon cell markers. We further tested specific effects of dexamethasone on tendon cells in vitro. Dexamethasone increased mRNA levels of S100A4 and decreased levels of ACTA2/α-SMA, irrespective of load level. Heavy loading + dexamethasone reduced mRNA levels of FN1 and TenC (p < 0.05), while resolution-related genes were unaltered (p > 0.05). In contrast, mild loading + dexamethasone increased mRNA levels of resolution-related genes ANXA1, MRC1, PDPN, and PTGES (p < 0.03). Altered protein levels were confirmed in tendons with mild loading. Dexamethasone treatment in vitro prevented tendon construct formation, increased mRNA levels of S100A4 and decreased levels of SCX and collagens. Dexamethasone during tendon healing appears to act through immunomodulation by promoting resolution, but also through an effect on tendon cells.

Association between asthma and COVID-19 severity during Omicron epidemic: a retrospective cohort study using real-world data.

BACKGROUND: The available evidence presented inconsistencies and inconclusive findings regarding the associations between co-existing asthma and mortality among COVID-19 patients. The objective of the current study is to investigate the relationship between asthma and severe outcomes after SARS-CoV-2 Omicron infection in an infection-naïve population. METHODS: A retrospective cohort study using propensity score matching was conducted. The COVID-19 patients requiring hospitalisation in Hong Kong from January 1, 2022, to November 13, 2022, an Omicron-predominated period, were identified. Severe clinical outcomes were defined as ICU admission and inpatient death after the first positive PCR results as well as a composite outcome of both. RESULTS: Of the 74,396 hospitalised COVID-19 patients admitted, 1,290 asthma patients and 18,641 non-asthma patients were included in the matched cohort. The rates of death and the composite outcome were 15·3% and 17·2%, respectively, among the non-asthma patients,12·2% and 13·6%, respectively, among the asthma patients, with adjusted hazard ratios equal to 0·775 (95% CI: 0·660-0·909) and 0·770 (95% CI: 0·662-0·895), respectively. The negative association was more apparent in the elderly and female groups. Asthma remained a factor that lowered the risk of disease severity even though the patients were not fully vaccinated with at least two doses. CONCLUSIONS: We used real-world data to demonstrate that asthma was not a risk factor for COVID-19 severity of the infections of Omicron variant, even though the patients were not fully vaccinated.

A Distinct Instance of Palindromic Rheumatism Disguised as Polymyalgia Rheumatica.

In this case report, we highlight a rare case of palindromic rheumatism (PR) presenting as polymyalgia rheumatica (PMR). Many challenges and complexities are associated with diagnosing and treating PR. Literature reviews showed only a few case reports of this unique presentation. PR has a distinct presentation that often goes unnoticed and is misinterpreted by medical professionals. A more thorough clinical approach is required to identify and treat this condition. We hope sharing such uncommon cases will help the medical community better understand PR and develop improved diagnostic and therapeutic options. This case also demonstrates the need for further research to better understand the pathogenesis of this uncommon condition.

In Vivo Formation of Adrenal Organoids in a Novel Porcine Model of Adrenocortical Cell Transplantation.

Recognizing the limitations of current therapies for Addison's disease, novel treatments that replicate dynamic physiologic corticosteroid secretion, under control of ACTH, are required. The aim of these experiments was to evaluate the feasibility of adrenocortical cell transplantation (ACT) in a large animal model, adapting methods successfully used for intracutaneous pancreatic islet cell transplantation, using a fully biodegradable temporizing matrix. Autologous porcine ACT was undertaken by bilateral adrenalectomy, cell isolation, culture, and intracutaneous injection into a skin site preprepared using a biodegradable temporizing matrix (BTM) foam. Hydrocortisone support was provided during adrenocortical cell engraftment and weaned as tolerated. Blood adrenocortical hormone concentrations were monitored, and the transplant site was examined at endpoint. Outcome measures included cellular histochemistry, systemic hormone production, and hydrocortisone independence. Transplanted adrenocortical cells showed a capability to survive and proliferate within the intracutaneous site and an ability to self-organize into discrete tissue organoids with features of the normal adrenal histologic architecture. Interpretation of systemic hormone levels was confounded by the identification of accessory adrenals and regenerative cortical tissue within the adrenal bed postmortem. Corticosteroids were unable to be completely ceased. ACT in a large animal model has not previously been attempted, yet it is an important step toward clinical translation. These results demonstrate rhe potential for ACT based on the development of adrenal organoids at the BTM site. However, the inability to achieve clinically relevant systemic hormone production suggests insufficient function, likely attributable to insufficient cells through delivered dose and subsequent proliferation.

SARS-CoV-2 S1 subunit produces a protracted priming of the neuroinflammatory, physiological, and behavioral responses to a remote immune challenge: A role for corticosteroids.

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.

Ultrasonography of the superficial temporal and axillary arteries in giant cell arteritis diagnosis.

OBJECTIVES: Giant cell arteritis (GCA) is the main systemic vasculitis in individuals aged ≥ 50 years. Color Doppler ultrasound (CDS) has an established role in GCA diagnosis and management. This study aims to assess the clinical characteristics associated with a positive CDS evaluation and the impact of additional axillary artery examination on diagnostic sensitivity. MATERIAL AND METHODS: We conducted a retrospective analysis of patients undergoing CDS of the superficial temporal arteries, with or without axillary artery assessment, at our hospital, between 2009 and 2023. Patients meeting the new 2022 diagnostic criteria for GCA were included and their characteristics were analyzed according to the presence of the halo sign on CDS. RESULTS: Of the 135 included patients (54 % female, mean age 75 ± 8 years), the halo sign was observed in 57 %, correlating with higher systemic symptom prevalence (61 % vs 42 %, p = 0.035), lower hemoglobin (p < 0.001), and higher erythrocyte sedimentation rate (p = 0.028). The halo sign inversely related to prior corticosteroid therapy (p = 0.033). Patients with axillary halo sign had fewer external carotid symptoms and a higher vertebral halo sign prevalence. Vertebral halo sign was associated with posterior circulation ischemic stroke (65 %, p < 0.001). Axillary artery studies improved diagnostic sensitivity by 9 %. CONCLUSION: In our study, the halo sign correlated with higher systemic symptoms and analytical abnormalities. Axillary artery examination enhanced CDS sensitivity, linked to severe outcomes like stroke. Prior corticosteroid therapy reduced CDS sensitivity. The correlation of clinical, laboratory, and ultrasound findings provides a more comprehensive understanding of GCA pathogenesis and evolution.

Corticosteroids for improving patient-relevant outcomes in HELLP syndrome: a systematic review and meta-analysis.

BACKGROUND: We conducted this updated systematic review to assess the effects of corticosteroids vs. placebo or no treatment for improving patient-relevant outcomes in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. METHODS: CENTRAL, MEDLINE/PubMed, Web of Science, and Scopus, from the date of inception of the databases to February 3, 2024 were searched. Reference lists of included studies and systematic reviews were thoroughly searched. We included RCTs that enrolled women with HELLP syndrome, whether antepartum or postpartum, to receive any corticosteroid versus placebo or no treatment. No language or publication date restrictions were made. We used a dual independent approach for screening titles and abstracts, full text screening, and data extraction. Risk of bias was assessed in the included studies using Cochrane's RoB 2 tool. Pairwise meta-analyses were conducted, where two or more studies met methodological criteria for inclusion. GRADE approach was used to assess certainty of evidence for the pre-specified outcomes. RESULTS: Fifteen trials (821 women) compared corticosteroids with placebo or no treatment. The effect of corticosteroids is uncertain for the primary outcome i.e., maternal death (risk ratio [RR] 0.77, 95% confidence interval [CI] 0.25 to 2.38, very low certainty evidence). Out of 6 studies reporting maternal death, 5 were judged overall to have "low risk" of bias. The effect of corticosteroids is also uncertain for other important outcomes including pulmonary edema (RR 0.70, 95% CI 0.23 to 2.09), dialysis (RR 3, 95% CI 0.13 to 70.78), liver morbidity (hematoma, rupture, and failure; RR 0.22, 95% CI 0.03 to 1.83), or perinatal death (0.64, 95% CI 0.21 to 1.97) because of very low certainty evidence. Low certainty evidence suggests that corticosteroids have little or no effect on the need for platelet transfusion (RR 0.98, 95% CI 0.60 to 1.60) and may result in a slight reduction in acute renal failure (RR 0.67, 95% CI 0.40 to 1.12). Subgroup and sensitivity analyses showed results that were similar to the primary synthesis. CONCLUSIONS: In women with HELLP syndrome, the effect of corticosteroids vs. placebo or no treatment is uncertain for patient-relevant outcomes including maternal death, maternal morbidity, and perinatal death. These uncertainties regarding this critical question should be addressed by adequately powered rigorous trials. SYSTEMATIC REVIEW REGISTRATION: Center for Open Science, osf.io/yzku5.

Retroductal dexamethasone administration promotes the recovery from obstructive and inflammatory salivary gland dysfunction.

Introduction: Salivary gland dysfunction, often resulting from salivary gland obstruction-induced inflammation, is a prevalent condition. Corticosteroid, known for its anti-inflammatory and immunomodulatory properties, is commonly prescribed in clinics. This study investigates the therapeutic implications and potential side effects of dexamethasone on obstructive sialadenitis recovery using duct ligation mice and salivary gland organoid models. Methods: Functional and pathological changes were assessed after administering dexamethasone to the duct following deligation 2 weeks after maintaining ligation of the mouse submandibular duct. Additionally, lipopolysaccharide- and tumor necrosis factor-induced salivary gland organoid inflammation models were established to investigate the effects and underlying mechanisms of action of dexamethasone. Results: Dexamethasone administration facilitated SG function restoration, by increasing salivary gland weight and saliva volume while reducing saliva lag time. Histological evaluation revealed, reduced acinar cell atrophy and fibrosis with dexamethasone treatment. Additionally, dexamethasone suppressed pro-inflammatory cytokines IL-1ß and TNF expression. In a model of inflammation in salivary gland organoids induced by inflammatory substances, dexamethasone restored acinar markers such as AQP5 gene expression levels, while inhibiting pro-inflammatory cytokines TNF and IL6, as well as chemokines CCL2, CXCL5, and CXCL12 induction. Macrophages cultured in inflammatory substance-treated media from salivary gland organoid cultures exhibited pro-inflammatory polarization. However, treatment with dexamethasone shifted them towards an anti-inflammatory phenotype by reducing M1 markers (Tnf, Il6, Il1b, and Cd86) and elevating M2 markers (Ym1, Il10, Cd163, and Klf4). However, high-dose or prolonged dexamethasone treatment induced acino-ductal metaplasia and had side effects in both in vivo and in vitro models. Conclusions: Our findings suggest the effectiveness of corticosteroids in treating obstructive sialadenitis-induced salivary gland dysfunction by regulating pro-inflammatory cytokines.