Search Results (200)

Temporomandibular disorder (TMD) is recognized as a major public health problem, causing pain and physiological and psychosocial limitations. In this context, the present in vitro study investigated the synthesis of a hyaluronic acid (HA) hydrogel with hydrocortisone (Hyd), designed to enhance joint lubrication by reducing mechanical friction and delivering the anti-inflammatory drug. The hydrogels were prepared with 3% HA (30 mg/mL) and Hyd—0.125% (1.25 mg/mL), 0.250% (2.5 mg/mL), 0.500% (5 mg/mL), or 1% (10 mg/mL). Physicochemical analyses included Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TGA), rheological tests (frequency, amplitude, and temperature ramp scans), and field emission scanning electron microscopy (FESEM), performed before and after sterilization and cycling. In addition, cytocompatibility was evaluated by protocol OECD 129 and confocal microscopy, as well as genotoxicity (OECD487) in mouse macrophages (RAW 264.7 strain) per 24 h of exposure. FTIR demonstrated the spectral signatures of the compounds with no covalent interactions between the drugs, as well thermal stability on TGA. Rheology demonstrated that Hyd protected the HA structure after autoclaving, maintaining viscoelastic properties. SEM confirmed homogeneous porous morphology. Biological assays showed cell viability > 70%, but with a dose-dependent increase in genotoxicity (4–17 micronuclei). Confocal analysis revealed increasing cytotoxicity at high Hyd concentrations, indicating a balance between biocompatibility and adverse effects at concentrations ≤ 0.5%. Among the tested formulations, the 3% HA + 0.250% Hyd hydrogel provided the best balance of viscoelastic stability, cytocompatibility, and low genotoxicity, supporting its potential as a dual-function intra-articular candidate for TMD therapy. Full article

Background/Objectives: Non-classical congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency represents the mildest form of congenital adrenal hyperplasia and is frequently diagnosed only after the onset of clinical signs in childhood. Newborn screening programs for CAH are primarily designed to detect classical forms and show limited sensitivity for NCCAH. The clinical significance of neonatal 17-hydroxyprogesterone (17-OHP) values below recall thresholds remains incompletely defined. Methods: We retrospectively analyzed clinical, auxological, hormonal, and genetic data from pediatric patients diagnosed with NCCAH between 2018 and 2023 at a tertiary referral center. Neonatal screening 17-OHP concentrations, basal and ACTH-stimulated 17-OHP levels at diagnosis, bone age advancement, pubertal status, and hydrocortisone treatment were evaluated. Correlations between hormonal parameters, age at onset, and treatment dose were assessed. Results: Thirty-five patients (30 females) were included, with a mean age at clinical onset of 7.52 ± 0.36 years for females and 6.25 ± 0.29 years for males. Premature pubarche was the most frequent presenting sign (94.3%), and central precocious puberty was diagnosed in 31.4% of cases. The mean neonatal screening 17-OHP level was 4.53 ± 0.7 ng/mL; only two patients exceeded the screening recall cut-off. At diagnosis, mean basal and ACTH-stimulated 17-OHP levels were 15.1 ± 3.35 and 55.2 ± 11.3 ng/mL, respectively. Age at clinical onset was inversely correlated with both basal and stimulated 17-OHP levels, while hydrocortisone dose correlated positively with biochemical severity. Bone age advancement was observed in all patients. Conclusions: Most children with NCCAH display mildly elevated neonatal 17-OHP values that do not trigger screening recall. Higher biochemical severity is associated with earlier clinical presentation and higher glucocorticoid requirements. Neonatal 17-OHP concentrations, even when below cut-off values, may represent an early indicator of disease severity and warrant further investigation. Full article

Background/Objectives: Many products that claim to have anti-aging effects have been reported, but their relative potency is not clear. In this study, the in vitro replicative lifespan extension (RLE) activity of various groups of physiologically active substances was compared by using the updated “overlay method”. Methods: Human dermal and periodontal ligament fibroblasts (HDFa, HPLF) were inoculated into the inner 60 wells of 96-well microplate, surround by sterile water to prevent the water evaporation. At Day 1 and Day 8, the cells were overlayed with wide ranges of concentrations (0.01–100 µM) of samples without medium change. Viable cell number was measured by the MTT method at Day 15 and then corrected for the variation in cell growth due to the location of inoculated cells. The RLE value was calculated as the maximum cell proliferation rate relative to the control. Results: Cell density of HDFa and HPLFs at subculture decreased with the passage number, and their growth was stopped at 56 or 85 population doubling levels (PDLs), respectively. Hydrocortisone showed the highest RLE values among six hormones, followed by three plant extracts, sodium ascorbate and quercetin. On the other hand, other antioxidants, chlorogenic acid, phenylpropanoids, vanilloids, and bacterial products showed little or no RLE effects. However, for HPLF cells, hydrocortisone did not show RLE effects while oxytocin showed slight stimulation. Conclusions: When differences in proliferation due to cell seeding position were corrected, the biphasic dose response curve of most of the compounds significantly reduced. The present study suggests the significant role of hormones for the regulation of the long-term aging process. To confirm systemic or clinical anti-aging effects, further in vitro and in vivo experiments are needed. Full article

The physiological efficacy of plant-based matrices is often limited because bioactive compounds are sequestered within complex lignocellulosic architectures, restricting their release and downstream activity. Fermentation-driven enzymatic biotransformation can overcome these structural barriers; however, the mechanisms by which fermentation-derived, non-viable functional ingredients (postbiotics) confer benefits remain incompletely defined. Here, we examined whether a postbiotic-rich, co-fermented plant matrix enhances host resilience under metabolic stress and whether such effects are accompanied by a remodeling of gut microbial functional capacity. A functional plant matrix was produced by solid-state co-fermentation using two Lactobacillus plantarum strains selected for complementary lignocellulolytic profiles. Untargeted metabolomics and deep shotgun metagenomic sequencing were integrated with a hydrocortisone-induced murine metabolic stress model to quantify substrate remodeling, host neuroendocrine/behavioral outcomes, and microbiome functional reprogramming. Co-fermentation markedly remodeled the phytochemical landscape, increasing extractable flavonoids and generating distinct metabolite clusters. In vivo, administration of the postbiotic-rich matrix partially normalized stress-responsive neuroendocrine markers (ACTH, TRH, and testosterone) and improved behavioral outcomes in open-field and forced swim assays. These systemic changes were paralleled by a coordinated shift in microbial functional potential, including the enrichment of carbohydrate-active enzyme (CAZyme) families involved in complex polysaccharide utilization (e.g., AA9, GH129, CE14) and attenuation of phosphotransferase system modules and cytochrome P450-related functions. Enzymatic synergy-driven biotransformation yields a postbiotic-rich functional matrix that is associated with a selective remodeling of gut microbiome metabolic potential under stress and concomitant improvement in host physiological resilience. This study underscores microbial functional remodeling as a critical mechanistic interface linking fermentation-modified substrates to host physiological recovery, providing a molecular framework for the development of targeted postbiotic interventions. Full article

Background: Cerliponase alfa is an intracerebroventricular (ICV) enzyme replacement therapy (ERT) and the only approved treatment for neuronal ceroid lipofuscinosis type 2 (CLN2) disease. While generally well tolerated, infusion-associated reactions (IARs), including hypersensitivity events and anaphylaxis, remain a recognized safety consideration. Methods: This single-center, retrospective study describes the incidence and management of IARs in pediatric patients with CLN2 receiving long-term ICV cerliponase alfa at Great Ormond Street Hospital, London, United Kingdom. Results: Over a 10-year period (2014–2024), 31 patients received approximately 2705 ICV infusions. Eleven patients experienced at least one IAR. Most reactions were mild and transient, typically consisting of pyrexia, vomiting, or rash, and were managed conservatively with antipyretics and antihistamines. Four patients required steroid intervention following recurrent or more pronounced symptoms, which led to improved infusion tolerance. One patient experienced a single episode of anaphylaxis that required treatment with intramuscular adrenaline and intravenous hydrocortisone. Therapy was continued with a revised pre-medication regime, with no further severe reactions. Conclusions: These findings demonstrate that IARs to ICV cerliponase alfa are typically mild and readily manageable within a multidisciplinary framework. They highlight the importance of structured infusion protocols, vigilant monitoring strategies, and a coordinated management approach to ensure the long-term safety of ERT for children with CLN2 disease. Full article

Glucocorticoid (GC) residues present in aquatic products raise food safety concerns, as their chronic dietary intake may pose potential risks of endocrine and metabolic disruption. For the first time, a sensitive and reliable liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated herein for the simultaneous determination of 12 GCs residues, including critical isomeric pairs and acetate ester derivatives, in a variety of aquatic foods, employing deuterated isotopic internal standards. Key optimizations included using a pentafluorophenyl column for effective isomer separation, a synergistic extraction system for high recovery, and QuEChERS purification to mitigate matrix effects. The method exhibited excellent linearity (r² > 0.996) and high accuracy (recoveries 97.3–99.3%), and the intra- and inter-day precision values were below 3% in five representative aquatic matrices, with a limit of detection (LOD) and a limit of quantification (LOQ) of 0.5 μg/kg and 0.75 μg/kg, respectively. Animal experiments confirmed the in vivo retention of acetate derivatives, justifying their inclusion in monitoring. Real sample analysis of 18 market samples revealed the presence of cortisone and hydrocortisone in 17 samples. This represents the first reported LC-MS/MS method that provides a sensitive, reliable tool for regulatory monitoring of GC residues in diverse aquatic products, thereby supporting food safety assurance. Full article

In this study, the biocatalytic activity of four steroid-transforming strains isolated from the African frog Xenopus laevis and identified as Streptomyces rochei towards pregnane steroids has been investigated. All the isolated strains facilitated the reduction of the C20-carbonyl group and the structures of the metabolites were confirmed by mass spectrometric (MS) and ¹H NMR spectroscopic analyses. Hydrocortisone and progesterone were poorly transformed by the streptomycete strains, whereas cortexolone (Reichstein’s substance S) was effectively biotransformed, yielding more than 90% of 17α,20β,21α-trihydroxy-4-pregnen-3-one (20β-S). Primarily, 20α-reduction was detected when the microbial isolates were incubated with 17α-hydroxyprogesterone with the yield of 17α,20α-dihydroxy-4-pregnen-3-one (17,20α-P) reaching 70%. The biological activity of 20β-S was evaluated in Danio rerio. The results demonstrated that 20β-S modulated stress- and anxiety-related behavioral responses and activated Pgr-dependent transcriptional pathways in the brain and ovarian tissues. These observations support the potential relevance of the synthesized progestin as a functional regulator in teleost physiology. The findings enhance our understanding of the biodiversity of steroid-transforming actinomycetes inhabiting amphibians and can be successfully employed for the effective microbiological synthesis of biologically active 20-hydroxylated progestins that serve as bioregulators in teleosts. Full article

Background/Objectives: Topical application of isosorbide diesters (IDEAS) derived from coconut and sunflower seed oil improve atopic dermatitis (AD) and reduce topical steroid use in adults. This randomized, double-blind, vehicle-controlled trial evaluates topical IDEAS (isosorbide diesters) with colloidal oatmeal for pediatric AD. Methods: Subjects aged 2–17 with mild to moderate AD applied either colloidal oatmeal cream or colloidal oatmeal cream with IDEAS daily. Hydrocortisone 2.5% was used as needed. AD severity, itch, sleep, steroid use, and microbiome data were collected at baseline, week 4, and week 8. Results: More participants in the IDEAS group compared to the control group achieved EASI 50 (81.0% vs. 56.3%, p = 0.10) and EASI 75 (42.9% vs. 18.8%, p = 0.12) and achieved a 4-point reduction in subjective itch at week 4 (45.5% vs. 6.3%, p = 0.0085) and week 8 (42.9% vs. 12.5%, p = 0.045). Use of topical steroids was lower in the IDEAS group (3.4 g vs. 13.3 g, p = 0.012) and the relative abundance of Staphylococcus aureus was reduced after 8 weeks. Conclusions: The addition of IDEAS to colloidal lotion improved AD, improved itch, reduced the use of topical steroids, and reduced the relative abundance of S. aureus in the skin microbiome. Full article

Background: Acute respiratory distress syndrome (ARDS), recognized as an inflammatory and life-threatening lung injury, is typified by severe hypoxaemia, lack of heart-related pulmonary edema, and bilateral lung infiltrates. Glucocorticoids are anti-inflammatory and immunoregulatory agents that are considered a viable treatment for ARDS. This study sought to contrast the effects of methylprednisolone, hydrocortisone, and dexamethasone at equivalent doses in ARDS. Methods: About 195 ARDS patients were allocated at random to take methylprednisolone (1 mg/kg/day), hydrocortisone (350 mg/day), or dexamethasone (13 mg/day). The primary and secondary outcomes over 28 days following the initiation of glucocorticoid therapy involved mortality, ventilator-free days, duration of hospitalization, duration of intensive care unit (ICU), total number of patients requiring invasive mechanical ventilation, and changes in the means of arterial oxygen partial pressure to inspired oxygen fraction (PaO₂/FiO₂) and oxygen saturation percentage to inspired oxygen fraction (SpO₂/FiO₂) ratios. Results: Over the 28-day follow-up, regarding mortality, there was a significant difference between dexamethasone and hydrocortisone, as well as between methylprednisolone and hydrocortisone. However, methylprednisolone exhibited the lowest mortality. There were no significant differences among study groups in ventilator-free days, hospitalization duration, ICU duration, and requirement for invasive mechanical ventilation. On the other hand, methylprednisolone had the lowest means of both durations of hospitalization and ICU, and the lowest requirement for invasive mechanical ventilation. Each study group exhibited a significant increase in both PaO₂/FiO₂ and SpO₂/FiO₂ ratios at follow-up time. However, dexamethasone showed the highest means of both PaO₂/FiO₂ and SpO₂/FiO₂ ratios at follow-up time. There was a significant difference in PaO₂/FiO₂ and SpO₂/FiO₂ ratios at follow-up assessment between dexamethasone and hydrocortisone. Conclusions: At equivalent doses, treating ARDS with methylprednisolone may be more successful than using dexamethasone and hydrocortisone. Full article

Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic–pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ≥2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (−0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements. Full article

Background/Objectives: Persistent inflammation driven by cytokines/chemokines plays a crucial role in the pathogenesis of numerous chronic inflammatory and autoimmune conditions, including rheumatoid arthritis, atopic dermatitis, and ulcerative colitis. Current therapeutic agents often present limitations due to adverse effects. Thykamine™, a new plant-derived multi-target drug, has demonstrated promising anti-inflammatory effects and a favorable safety profile in clinical settings. This study aimed to compare the in vitro chemokine-inhibitory potency of Thykamine™, a novel plant-derived anti-inflammatory compound, with that of six marketed corticosteroid and non-steroidal agents. Methods: This study compared the in vitro potency of Thykamine™ against widely prescribed anti-inflammatory agents, including corticosteroids (betamethasone, clobetasol, hydrocortisone, prednisone) and non-steroidal therapies (crisaborole, pimecrolimus). Potency was assessed by measuring the inhibition of key pro-inflammatory chemokines: MCP-1, MIP-1α, MIP-1β, and RANTES in lipopolysaccharide-stimulated U937 cells. Results: Area-under-the-curve (AUC) analyses confirmed that Thykamine™ inhibited secretion of the chemokines MCP-1, MIP-1α, and MIP-1β with significantly greater potency than all other agents tested. Thykamine™ also suppressed secretion of RANTES similarly to prednisone and significantly more than betamethasone, clobetasol, hydrocortisone, and pimecrolimus but less than crisaborole due to crisaborole’s elevated potency when administered at high concentration. Conclusions: Overall, Thykamine™ showed significantly greater or comparable inhibitory potency, particularly at lower concentrations, without evidence of cytotoxicity. These findings underscore the potential of Thykamine™ as a potent, multi-target anti-inflammatory therapy, which could offer substantial clinical advantages by effectively controlling chemokine-mediated inflammation with potentially fewer adverse effects. The results of this study support the need for evaluation of the clinical therapeutic efficacy of Thykamine™ in a wide range of autoimmune conditions. Full article

Background/Objectives: Systemic hydrocortisone (HCS) in very low birth weight (VLBW) infants is commonly used to treat early hypotension or prevent bronchopulmonary dysplasia. This study evaluated the associations between postnatal HCS exposure and neurodevelopment in VLBW infants by comparing regional brain volume at term-equivalent age (TEA) with neurodevelopmental outcomes in early infancy. Methods: This retrospective cohort study included VLBW infants admitted to a neonatal intensive care unit (NICU) between 2013 and 2019. The cumulative HCS dose during hospitalization was recorded, and regional brain volumes were analyzed using magnetic resonance imaging at TEA. Neurodevelopmental outcomes were assessed at a corrected age for prematurity of 18–24 months. Results: Among 146 infants, 57 were classified in the high HCS group (>90 mg/kg) and 89 in the low HCS group (≤90 mg/kg HCS). Bronchopulmonary dysplasia, periventricular leukomalacia, and sepsis were more frequent in the high HCS group. Ninety-five infants underwent magnetic resonance imaging, which revealed reduced brain volumes in the high HCS group. At follow-up, cerebral palsy (35.9% vs. 9.1%, p = 0.003), neurodevelopmental impairment (54.0% vs. 23.6%, p = 0.002), and head circumference <10th percentile (64.3% vs. 19.5%, p < 0.001) were more common in the high HCS group. After adjustment, HCS > 90 mg/kg remained independently associated with cerebral palsy (adjusted odds ratio [aOR] 5.44, p = 0.016) and reduced head circumference (aOR 4.45, p = 0.016). Conclusions: High cumulative HC exposure correlated with reduced brain volume at TEA and adverse neurodevelopmental outcomes at 24 months of age. Careful monitoring of dose and treatment duration is essential to balance therapeutic benefits against potential risks. Full article

Intravenous medications are frequently administered through shared catheter lines in neonatal intensive care units (NICUs) due to the limited venous access in preterm infants, raising concerns about drug incompatibilities that may cause serious complications. Hydrocortisone sodium (HDC), ampicillin (ABPC), and cefotaxime (CTX) are commonly used in NICUs and are often co-administered with unfractionated heparin (UFH), which is routinely infused to prevent catheter occlusion. This study evaluated the physicochemical compatibility of HDC, ABPC, and CTX when mixed with UFH. Each drug was combined with UFH at equal volumes, and the mixtures were assessed immediately and after 3 h of storage by visual inspection, pH measurement, UV absorbance, and HPLC-UV analysis. No precipitation, turbidity, or color changes were observed in any mixture, and UV absorbance showed no relevant deviations compared with controls. Slight pH variations were detected but remained within acceptable limits. In semi-quantitative HPLC analysis, relative peak area changes were all below 10%, indicating no major degradation of the drugs. These findings suggest that HDC, ABPC, and CTX maintain acceptable physicochemical compatibility when co-administered with UFH, supporting their safe concomitant use in NICU practice. Full article

NR0B1 (DAX-1) is an orphan nuclear receptor essential for the development and regulation of the adrenal glands and gonads. Pathogenic variants in NR0B1 cause X-linked adrenal hypoplasia congenita (AHC), which typically presents with adrenal insufficiency and hypogonadotropic hypogonadism (HH) in boys. Delayed diagnosis during adolescence is uncommon but, when it occurs, can lead to preventable adrenal crisis, underscoring the need for early recognition of atypical presentations. We describe a 14-year-old boy who presented with adrenal insufficiency and delayed puberty. Genetic testing revealed a novel hemizygous in-frame duplication variant of NR0B1 (NM_000475.4:c.833_835dup p.(Leu278dup)). This variant has not been previously reported in association with X-linked AHC. The patient received hydrocortisone (10–12 mg/m²/day) and fludrocortisone (0.1 mg/day) as replacement therapy for adrenal insufficiency, along with testosterone supplementation (100–240 mg/day) to induce pubertal progression. Plasma ACTH levels gradually decreased from 10,175 pg/mL at diagnosis to 215 pg/mL during follow-up, accompanied by clinical improvement in skin pigmentation and pubertal development. This case underscores the importance of NR0B1 genetic testing in children with adrenal insufficiency and HH. Early recognition and genetic confirmation are critical for appropriate management and genetic counseling. Identification of novel variants expands the NR0B1 mutational spectrum and enhances our understanding of genotype–phenotype correlations in X-linked AHC. Full article

Background: Critical illness-related corticosteroid insufficiency (CIRCI) diagnosis remains controversial, largely due to the complex pathophysiology of sepsis, which challenges the reliability of conventional biochemical testing. Recent international guidelines have moved away from strict cortisol threshold-based diagnostic criteria for adrenal insufficiency, relying more on clinical evaluation. However, the applicability and diagnostic accuracy of these revised approaches in non-Western populations remain unexplored. Objective: This study aimed to assessthe diagnostic accuracy and clinical utility of baseline total cortisol levels for guiding corticosteroid therapy in a cohort of patients admitted to the intensive care unit (ICU) with septic shock in a tertiary care hospital in the United Arab Emirates. Methods: A ten-year retrospective observational study (2012–2022) of intensive care patients with septic shock was conducted. CIRCI was operationally defined by a documented clinical decision to administer hydrocortisone >24 h. Receiver Operating Characteristic (ROC) analysis assessed diagnostic performance; Decision Curve Analysis (DCA) evaluated clinical utility of performed cortisol levels. Results: Among 43 patients in the ICU with septic shock, 13 (30.2%) received hydrocortisone (CIRCI group). Mean cortisol was found to be paradoxically higher in the CIRCI group (1341.6 ± 1112.5 vs. 976.0 ± 798.7 nmol/L, p = 0.24). ROC analysis demonstrated poor diagnostic performance (AUC 0.61, 95% CI: 0.44–0.78). International guideline cutoff of <276 nmol/L showed 0% sensitivity in identifying CIRCI. Multiple thresholds yielded negative Youden indices, indicating performance of cortisol levels being worse than a random chance. DCA demonstrated zero net benefit for cortisol-guided therapy across all threshold probabilities when compared to clincial practice strategies. Only clinical factors predicted corticosteroid initiation: high vasopressor requirements (OR 3.2, 95% CI: 1.1–9.4, p = 0.03) and persistent shock >48 h (OR 2.8, 95% CI: 1.0–7.9, p = 0.05). Cortisol level had no predictive value (OR 1.0, 95% CI: 0.9–1.0, p = 0.89). Conclusions: In this cohort, baseline total cortisol demonstrated poor diagnostic accuracy and lacked clinical utility for guiding corticosteroid therapy in patients with sepsis. Our findings reinforce the importance of clinical judgement over biochemical testing in identifying patients with septic shock requiring corticosteroid therapy, in line with the recent international guidelines. Full article