Exosomes derived from M2 macrophages prevent steroid-induced osteonecrosis of the femoral head by modulating inflammation, promoting bone formation and inhibiting bone resorption.

Inflammatory reactions are involved in the development of steroid-induced osteonecrosis of the femoral head(ONFH). Studies have explored the therapeutic efficacy of inhibiting inflammatory reactions in steroid-induced ONFH and revealed that inhibiting inflammation may be a new strategy for preventing the development of steroid-induced ONFH. Exosomes derived from M2 macrophages(M2-Exos) display anti-inflammatory properties. This study aimed to examine the preventive effect of M2-Exos on early-stage steroid-induced ONFH and explore the underlying mechanisms involved. In vitro, we explored the effect of M2-Exos on the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells(BMMSCs). In vivo, we investigated the role of M2-Exos on inflammation, osteoclastogenesis, osteogenesis and angiogenesis in an early-stage rat model of steroid-induced ONFH. We found that M2-Exos promoted the proliferation and osteogenic differentiation of BMMSCs. Additionally, M2-Exos effectively attenuated the osteonecrotic changes, inhibited the expression of proinflammatory mediators, promoted osteogenesis and angiogenesis, reduced osteoclastogenesis, and regulated the polarization of M1/M2 macrophages in steroid-induced ONFH. Taken together, our data suggest that M2-Exos are effective at preventing steroid-induced ONFH. These findings may be helpful for providing a potential strategy to prevent the development of steroid-induced ONFH.

Non-traumatic osteonecrosis of the femoral head induced by steroid and alcohol exposure is associated with intestinal flora alterations and metabolomic profiles.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a severe disease that primarily affects the middle-aged population, imposing a significant economic and social burden. Recent research has linked the progression of non-traumatic osteonecrosis of the femoral head (NONFH) to the composition of the gut microbiota. Steroids and alcohol are considered major contributing factors. However, the relationship between NONFH caused by two etiologies and the microbiota remains unclear. In this study, we examined the gut microbiota and fecal metabolic phenotypes of two groups of patients, and analyzed potential differences in the pathogenic mechanisms from both the microbial and metabolic perspectives. METHODS: Utilizing fecal samples from 68 NONFH patients (32 steroid-induced, 36 alcohol-induced), high-throughput 16 S rDNA sequencing and liquid chromatography with tandem mass spectrometry (LC-MS/MS) metabolomics analyses were conducted. Univariate and multivariate analyses were applied to the omics data, employing linear discriminant analysis effect size to identify potential biomarkers. Additionally, functional annotation of differential metabolites and associated pathways was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Subsequently, Spearman correlation analysis was employed to assess the potential correlations between differential gut microbiota and metabolites. RESULTS: High-throughput 16 S rDNA sequencing revealed significant gut microbial differences. At the genus level, the alcohol group had higher Lactobacillus and Roseburia, while the steroid group had more Megasphaera and Akkermansia. LC-MS/MS metabolomic analysis indicates significant differences in fecal metabolites between steroid- and alcohol-induced ONFH patients. Alcohol-induced ONFH (AONFH) showed elevated levels of L-Lysine and Oxoglutaric acid, while steroid-induced ONFH(SONFH) had increased Gluconic acid and Phosphoric acid. KEGG annotation revealed 10 pathways with metabolite differences between AONFH and SONFH patients. Correlation analysis revealed the association between differential gut flora and differential metabolites. CONCLUSIONS: Our results suggest that hormones and alcohol can induce changes in the gut microbiota, leading to alterations in fecal metabolites. These changes, driven by different pathways, contribute to the progression of the disease. The study opens new research directions for understanding the pathogenic mechanisms of hormone- or alcohol-induced NONFH, suggesting that differentiated preventive and therapeutic approaches may be needed for NONFH caused by different triggers.

Anabolic-androgenic steroids are linked to depression and anxiety in male bodybuilders: the hidden psychogenic side of anabolic androgenic steroids.

BACKGROUND: The prevalence of anabolic-androgenic steroids (AAS) use is on the rise among athletes and bodybuilders worldwide. In addition to the well-documented adverse effects on hepatic, renal, and reproductive functions, there is an increasing recognition of psychiatric complications associated with AAS use. This study aimed to investigate psychiatric morbidity among male bodybuilders who are AAS users. METHODS: In this cross-sectional study, 25 male bodybuilders using AAS (mean age 31.2 ± 8.9 years) were compared with a control group of 25 healthy male bodybuilders matched in age (31.3 ± 5.5 years). The demographic, hormonal, and biochemical parameters of the participants were recorded. The impact of AAS use on psychiatric morbidity was assessed using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) in both groups. RESULTS: The BDI and BAI scores were significantly higher in male bodybuilders using anabolic-androgenic steroids (p < 0.0001). While the control group showed no instances of anxiety, seven individuals in the AAS user group reported mild anxiety. No participants in the control group exhibited depression, whereas seven AAS users displayed depressive symptoms (4 mild, 3 moderate). Correlations were observed between lactate dehydrogenase (LDH) levels and BAI scores, creatinine levels and both BAI and BDI scores, as well as between estradiol levels and BDI. CONCLUSION: The study concluded that AAS use among male bodybuilders is associated with elevated levels of depression and anxiety. Our findings suggest a potential correlation between anxiety and depression levels and the levels of creatinine, LDH, and estradiol in AAS users.

[Transcriptome data mining combined with clinical and animal experiments for identification of syndrome element marker genes during entire course of steroid-induced osteonecrosis of femoral head].

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.

Elucidating the role of the GC/GR/GLUT1 axis in steroid-induced osteonecrosis of the femoral head: A proteomic approach.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent and incapacitating condition that affects the hip joint. Unfortunately, early diagnostic and treatment measures are limited. METHODS: Our study employed Tandem Mass Tag (TMT) labeling mass spectrometry (MS)-based quantitative proteome to compare the proteins of femoral head tissues in patients with SONFH with those of patients who sustained femoral neck fracture (FNF). We investigated the level and effects of glucose transporter member 1 (GLUT1) in SONFH patients and MC3T3-E1 cells and examined the function and molecular mechanism of GLUT1 in the context of SONFH using in vivo and in vitro approaches. RESULTS: The SONFH group exhibited significant changes in protein expression levels compared to the fracture group. Specifically, we observed the up-regulation of 86 proteins and the down-regulation of 138 proteins in the SONFH group. Among the differentially expressed proteins, GLUT1 was down-regulated and associated with glucose metabolic processes in the SONFH group. Further analysis using Parallel Reaction Monitoring (PRM), WB, and PCR confirmed that the protein was significantly down-regulated in both femoral head tissue samples from SONFH patients and dexamethasone-treated MC3T3-E1 cells. Moreover, overexpression of GLUT1 effectively reduced glucocorticoid (GC)-induced apoptosis and the suppression of osteoblast proliferation and osteogenic differentiation in MC3T3-E1 cells, as well as GC-induced femoral head destruction in GC-induced ONFH rat models. Additionally, our research demonstrated that GC down-regulated GLUT1 transcription via glucocorticoid receptors in MC3T3-E1 cells. CONCLUSIONS: GLUT1 was down-regulated in patients with SONFH; furthermore, down-regulated GLUT1 promoted apoptosis and inhibited osteoblast ossification in dexamethasone-induced MC3T3-E1 cells and contributed to GC-induced femoral head destruction in a SONFH rat model. Glucocorticoids inhibited the transcriptional activity of GLUT1, leading to a reduction in the amount and activity of GLUT1 in the cells and ultimately promoting apoptosis and inhibiting osteoblast ossification via the GC/GR/GLUT1 axis in SONFH.

Relapse and side effects of steroid therapy beyond 3 years in autoimmune pancreatitis: A multicenter retrospective study.

BACKGROUND: The impact of extended steroid administration on patients with autoimmune pancreatitis after a 3-year maintenance period remains poorly understood. This study analyzed the advantage and disadvantage of continuing steroid therapy beyond 3 years. METHODS: In this retrospective multicenter study across 17 institutions, patients who successfully completed 3 years of maintenance therapy without experiencing relapse were categorized into two groups: the maintenance therapy discontinuation group, who discontinued steroid therapy after the initial 3-year period, and maintenance therapy continuation group, who continued steroid therapy beyond 3 years. The cumulative relapse rate after 3 years of maintenance therapy was the primary outcome. Relapse predictors were compared using the Gray test for cumulative relapse incidence by specific factor. RESULTS: Of 211 patients, 105 experienced no relapse during the 3-year maintenance therapy and were divided into two groups: 69 in the maintenance therapy discontinuation group and 36 in the maintenance therapy continuation group. The relapse rate was lower in the maintenance therapy continuation group than in the maintenance therapy discontinuation group (P = 0.035). Predictors of relapse after 3 years included cessation of maintenance therapy (hazard ratio [HR] = 3.76; 95 % confidence interval [CI] = 1.07-13.3, P = 0.040) and renal involvement (HR = 2.88; 95 % CI = 1.04-7.99, P = 0.042). The maintenance therapy continuation group showed a significantly higher prevalence of macrovascular complications, compared with the maintenance therapy discontinuation group (P = 0.005). CONCLUSIONS: Cessation of steroid maintenance therapy and renal involvement were predictors of relapse after 3 years of maintenance therapy. However, the long-term use of steroids may increase the risk of macrovascular complications.

Dexamethasone Induced Osteocyte Apoptosis in Steroid-Induced Femoral Head Osteonecrosis through ROS-Mediated Oxidative Stress.

OBJECTIVE: Glucocorticoid (GC) overuse is strongly associated with steroid-induced osteonecrosis of the femoral head (SINFH). However, the underlying mechanism of SINFH remains unclear. This study aims to investigate the effect of dexamethasone (Dex)-induced oxidative stress on osteocyte apoptosis and the underlying mechanisms. METHODS: Ten patients with SINFH and 10 patients with developmental dysplasia of the hips (DDH) were enrolled in our study. Sixty rats were randomly assigned to the Control, Dex, Dex + N-Acetyl-L-cysteine (NAC), Dex + Dibenziodolium chloride (DPI), NAC, and DPI groups. Magnetic resonance imaging (MRI) was used to examine edema in the femoral head of rats. Histopathological staining was performed to assess osteonecrosis. Immunofluorescence staining with TUNEL and 8-OHdG was conducted to evaluate osteocyte apoptosis and oxidative damage. Immunohistochemical staining was carried out to detect the expression of NOX1, NOX2, and NOX4. Viability and apoptosis of MLO-Y4 cells were measured using the CCK-8 assay and TUNEL staining. 8-OHdG staining was conducted to detect oxidative stress. 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining was performed to measure reactive oxygen species (ROS). The expression of NOX1, NOX2, and NOX4 in MLO-Y4 cells was analyzed by Western blotting. Multiple comparisons were performed using one-way analysis of variance (ANOVA). RESULTS: In patients and the rat model, hematoxylin-eosin (HE) staining revealed a significantly higher rate of empty lacunae in the SINFH group than in the DDH group. Immunofluorescence staining indicated a significant increase in TUNEL-positive cells and 8-OHdG-positive cells in the SINFH group compared to the DDH group. Immunohistochemical staining demonstrated a significant increase in the expression of NOX1, NOX2, and NOX4 proteins in SINFH patients compared to DDH patients. Moreover, immunohistochemical staining showed a significant increase in the proportion of NOX2-positive cells compared to the Control group in the femoral head of rats. In vitro, Dex significantly inhibited the viability of osteocyte cells and induced apoptosis. After Dex treatment, the intracellular ROS level increased. However, Dex treatment did not alter the expression of NOX proteins in vitro. Additionally, NAC and DPI inhibited the generation of intracellular ROS and partially alleviated osteocyte apoptosis in vivo and in vitro. CONCLUSION: This study demonstrates that GC promotes apoptosis of osteocyte cells through ROS-induced oxidative stress. Furthermore, we found that the increased expression of NOXs induced by GC serves as an important source of ROS generation.

Identification and analysis of mitochondria-related central genes in steroid-induced osteonecrosis of the femoral head, along with drug prediction.

Purpose: Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory orthopedic hip joint disease that primarily affects middle-aged and young individuals. SONFH may be caused by ischemia and hypoxia of the femoral head, where mitochondria play a crucial role in oxidative reactions. Currently, there is limited literature on whether mitochondria are involved in the progression of SONFH. Here, we aim to identify and validate key potential mitochondrial-related genes in SONFH through bioinformatics analysis. This study aims to provide initial evidence that mitochondria play a role in the progression of SONFH and further elucidate the mechanisms of mitochondria in SONFH. Methods: The GSE123568 mRNA expression profile dataset includes 10 non-SONFH (non-steroid-induced osteonecrosis of the femoral head) samples and 30 SONFH samples. The GSE74089 mRNA expression profile dataset includes 4 healthy samples and 4 samples with ischemic necrosis of the femoral head. Both datasets were downloaded from the Gene Expression Omnibus (GEO) database. The mitochondrial-related genes are derived from MitoCarta3.0, which includes data for all 1136 human genes with high confidence in mitochondrial localization based on integrated proteomics, computational, and microscopy approaches. By intersecting the GSE123568 and GSE74089 datasets with a set of mitochondrial-related genes, we screened for mitochondrial-related genes involved in SONFH. Subsequently, we used the good Samples Genes method in R language to remove outlier genes and samples in the GSE123568 dataset. We further used WGCNA to construct a scale-free co-expression network and selected the hub gene set with the highest connectivity. We then intersected this gene set with the previously identified mitochondrial-related genes to select the genes with the highest correlation. A total of 7 mitochondrial-related genes were selected. Next, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the selected mitochondrial-related genes using R software. Furthermore, we performed protein network analysis on the differentially expressed proteins encoded by the mitochondrial genes using STRING. We used the GSEA software to group the genes within the gene set in the GSE123568 dataset based on their coordinated changes and evaluate their impact on phenotype changes. Subsequently, we grouped the samples based on the 7 selected mitochondrial-related genes using R software and observed the differences in immune cell infiltration between the groups. Finally, we evaluated the prognostic significance of these features in the two datasets, consisting of a total of 48 samples, by integrating disease status and the 7 gene features using the cox method in the survival R package. We performed ROC analysis using the roc function in the pROC package and evaluated the AUC and confidence intervals using the ci function to obtain the final AUC results. Results: Identification and analysis of 7 intersecting DEGs (differentially expressed genes) were obtained among peripheral blood, cartilage samples, hub genes, and mitochondrial-related genes. These 7 DEGs include FTH1, LACTB, PDK3, RAB5IF, SOD2, and SQOR, all of which are upregulated genes with no intersection in the downregulated gene set. Subsequently, GO and KEGG pathway enrichment analysis revealed that the upregulated DEGs are primarily involved in processes such as oxidative stress, release of cytochrome C from mitochondria, negative regulation of intrinsic apoptotic signaling pathway, cell apoptosis, mitochondrial metabolism, p53 signaling pathway, and NK cell-mediated cytotoxicity. GSEA also revealed enriched pathways associated with hub genes. Finally, the diagnostic value of these key genes for hormone-related ischemic necrosis of the femoral head (SONFH) was confirmed using ROC curves. Conclusion: BID, FTH1, LACTB, PDK3, RAB5IF, SOD2, and SQOR may serve as potential diagnostic mitochondrial-related biomarkers for SONFH. Additionally, they hold research value in investigating the involvement of mitochondria in the pathogenesis of ischemic necrosis of the femoral head.

Pneumocystis jirovecii pneumonia mortality risk associated with preceding long-term steroid use for the underlying disease: A multicenter, retrospective cohort study.

OBJECTIVE: Long-term steroid use increases the risk of developing Pneumocystis pneumonia (PcP), but there are limited reports on the relation of long-term steroid and PcP mortality. METHODS: Retrospective multicenter study to identify risk factors for PcP mortality, including average steroid dose before the first visit for PcP in non-human immunodeficiency virus (HIV)-PcP patients. We generated receiver operating characteristic (ROC) curves for 90-day all-cause mortality and the mean daily steroid dose per unit body weight in the preceding 10 to 90 days in 10-day increments. Patients were dichotomized by 90-day mortality and propensity score-based stabilized inverse probability of treatment weighting (IPTW) adjusted covariates of age, sex, and underlying disease. Multivariate analysis with logistic regression assessed whether long-term corticosteroid use affected outcome. RESULTS: Of 133 patients with non-HIV-PcP, 37 died within 90 days of initial diagnosis. The area under the ROC curve for 1-40 days was highest, and the optimal cutoff point of median adjunctive corticosteroid dosage was 0.34 mg/kg/day. Past steroid dose, underlying interstitial lung disease and emphysema, lower serum albumin and lower lymphocyte count, higher lactate dehydrogenase, use of therapeutic pentamidine and therapeutic high-dose steroids were all significantly associated with mortality. Underlying autoimmune disease, past immunosuppressant use, and a longer time from onset to start of treatment, were associated lower mortality. Logistic regression analysis after adjusting for age, sex, and underlying disease with IPTW revealed that steroid dose 1-40 days before the first visit for PcP (per 0.1 mg/kg/day increment, odds ratio 1.36 [95% confidence interval = 1.16-1.66], P<0.001), low lymphocyte counts, and high lactate dehydrogenase revel were independent mortality risk factor, while respiratory failure, early steroid, and sulfamethoxazole/trimethoprim for PcP treatment did not. CONCLUSION: A steroid dose before PcP onset was strongly associated with 90-day mortality in non-HIV-PcP patients, emphasizing the importance of appropriate prophylaxis especially in this population.

Hemophagocytic lymphohistiocytosis induced by nivolumab/ipilimumab combination therapy: A case of lung adenocarcinoma that responded to early steroid pulse therapy.

BACKGROUND: Immune checkpoint inhibitors have been reported to have excellent therapeutic effects on various malignant tumors. However, immune-related adverse events can occur, targeting various organs. CASE PRESENTATION: A 49-year-old male with lung carcinoma was started on carboplatin + pemetrexed + nivolumab (every 3 weeks) + ipilimumab (every 6 weeks), and nivolumab/ipilimumab was administered in the 3rd course. Subsequently, fever and fatigue developed, and grade 3 liver damage was also noted, so he was admitted to Kindai University Hospital. A bone marrow aspirate examination was performed on the third day of illness, and a definitive diagnosis of hemophagocytic lymphohistiocytosis (HLH) was made. It was determined that immediate therapeutic intervention was necessary, and pulse therapy with methylprednisolone was started on the third day of illness. After 3 days of pulse treatment, a rapid recovery of platelet values, a decrease in ferritin levels, and a decrease in lactate dehydrogenase were observed. Subjective symptoms such as fever and fatigue also quickly improved. CONCLUSION: Early diagnosis and treatment for HLH resulted in a positive response. The number of HLH cases may increase in the future due to the expansion of immune checkpoint inhibitor indications.

Knowledge and attitudes toward the use of anabolic-androgenic steroids among physical education university students: a cross-sectional study from Palestine.

The use of androgenic-anabolic steroids (AASs) has increased in recent years, especially among athletes, due to their effect on body shape and performance. These agents could have serious side effects on this highly susceptible population, which tends to use these substances frequently to promote muscle growth and physical performance. Therefore, this study aimed to evaluate the knowledge and attitudes toward the use of anabolic androgenic steroids among physical education university students in Palestine. A cross-sectional study of physical education students from November 2020 to January 2021 was conducted using an electronic questionnaire. The main outcome was to measure the level of knowledge and use of the AAS. A total of 380 students were included. The mean age of the students was 21 years (SD = 4.2), and the study participants were distributed almost equally according to sex. Approximately a quarter of the students were smokers. Eighty percent (80%) of the study participants were from the West Bank, while the remaining 20% were from Jerusalem and 48 territories. Furthermore, most of the students lived with their families; half lived in cities, approximately 152 (40%) lived in villages, and only 29 (8%) lived in camps. The average level of knowledge of the AAS was 2.95 out of 8 (37/100), with a median of three. Furthermore, only 36 (10%) of the participants had satisfactory knowledge, scoring 80% or more. Regarding the use of AAS, 11 (2.9%) participants, all males, confirmed that they were currently using AAS. Additionally, approximately 28 (7%) had previously used them, while 30 (8%) planned to try them in the future. Overall, 221 (58%) patients were confirmed to use vitamins and minerals. Our study showed that most of the participants had a substantial lack of information on the potential side effects of AAS, while the level of use was comparable with that of other populations.

Adult survivors of childhood-onset steroid-dependent and steroid-resistant nephrotic syndrome treated with cyclosporine: a long-term single-center experience.

BACKGROUND: Although evidence has confirmed that cyclosporine (CS) is efficacious against childhood-onset steroid-dependent and steroid-resistant nephrotic syndrome (SD/SRNS), some patients may continue to relapse during adulthood. However, predictive factors for adult active disease and kidney complications, such as chronic kidney disease (CKD) and hypertension, in this cohort remain unknown. METHODS: We conducted a retrospective study on the long-term outcomes of 81 young adults with childhood-onset SD/SRNS treated with CS. The primary endpoint was the probability of active disease into adulthood. The secondary endpoint was the probability of developing kidney complications. RESULTS: At the last follow-up (median age, 23.2 years; median disease duration, 15.8 years), 44 adult patients (54%) continued to have active disease, whereas 16 patients developed CKD or hypertension, respectively. The proportion of patients developing kidney complications was similar between the active disease and long-term remission groups. Young age at NS onset and history of relapse during the initial CS (median, 31 months) were independent predictive factors for active disease. Acute kidney injury at NS onset, focal segmental glomerulosclerosis, and irreversible CS nephrotoxicity were identified as risk factors for the development of CKD, whereas older age was identified as a risk factor for the development of CKD and hypertension. CONCLUSIONS: More than 50% of adult survivors treated with CS continued to have active disease, and each 20% developed CKD or hypertension. A long-term follow-up is necessary for patients with SD/SRNS to identify the development of kidney complications later in adulthood that can be attributed to prior disease and CS treatment in childhood, irrespective of disease activity. A higher resolution version of the Graphical abstract is available as Supplementary information.

Feasibility of steroid-free tacrolimus-basiliximab immunosuppression in pediatric liver transplantation and predictors for steroid requirement.

Avoidance of steroids in pediatric liver transplantation may reduce toxicity and morbidity. The aim of this study was to analyze the feasibility of a steroid-free tacrolimus-basiliximab immunosuppression scheme, the risk factors associated with steroid requirement, and safety parameters. Patients who underwent liver transplantation for biliary atresia between 2011 and 2019 were included and followed for 6 months after transplantation. Immunosuppression consisted of tacrolimus-based treatment with basiliximab induction. Steroid-free survival was estimated, and risk factors for steroid requirement were evaluated using multivariate Cox regression analysis. A total of 76 patients were included, of whom 42 (55.3%) required steroids (>14 d) due to biopsy-proven acute rejection (47.6%, n = 20), instability in liver function tests (35.7%, n = 15), tacrolimus-related adverse drug reactions (14.3%, n = 6), or other reasons (bronchospasm episode, n = 1). Steroid-free survival was 45.9% (95% CI, 35.9-58.8). Independent factors associated with steroid requirement included tortuosity in tacrolimus trough levels (≥1.76 vs. <1.76: HR 5.8, 95% CI, 2.6-12.7; p < 0.001) and mean tacrolimus trough levels (≥ 6.4 ng/mL vs. < 6.4 ng/mL: HR 0.4, 95% CI, 0.2-0.7; p = 0.002). The rate of bacterial and viral infections was comparable between patients with and without steroids, although in the former group, cytomegalovirus infection developed earlier ( p = 0.03). Patients receiving steroids had higher total cholesterol, LDL, and HDL levels ( p < 0.05) during follow-up, but no changes in the height Z-score were observed 1 year after transplantation. Basiliximab induction in combination with tacrolimus-based treatment avoided steroid requirements in 45% of the patients. Tacrolimus variability and trough levels below 6.4 ng/mL independently increased the risk of steroid requirement. Further efforts should be focused on personalizing immunosuppressive treatment.

Steroid use in measles: A retrospective cohort study during the 2017 outbreak in tertiary referral center, Rome and Latina, Italy.

INTRODUCTION: Since early January 2017, a new measles outbreak in Italy has been observed. The aim of the study was to compare features between adults and children measles cases and evaluate the effect of steroid treatment on the above parameters. METHODS: A retrospective multicenter, descriptive study was performed. We analyzed all patients admitted to the Department of Public Health and Infectious Diseases, Sapienza University, Rome and Latina, from January 2017 to December 2017 and discharged with diagnosis of measles. RESULTS: We identified 113 patients discharged with the diagnosis of measles infection cases of which 59 adults and 54 children (≤16 years). In adult population 32 patients (54 %) were males, with a median age of 30.5 years old and all unvaccinated (100 %). Keratoconjunctivitis 30 (50 %) was the most frequent complication. In pediatric population 27 (50 %) patients were males, with a median age of 3 years old. Information on measles vaccination status was available for only 21 (38.8 %) of cases. Keratoconjunctivitis 40 (74 %) was the most frequent complication. Analyzing the differences between adult and pediatric patients we found that children were significantly more likely to have keratoconjunctivitis and diarrhea as complications than adults in which the rate of thrombocytopenia and hepatitis was highest. Thirty-nine adult subjects (66 %) have been treated with systemic corticosteroids. CONCLUSIONS: Pediatric patients differ from adults in complications and liver involvement. Regarding steroids use, although there is no clear indication of steroid use during measles, there is no evidence of a worse outcome in our cases series.

Characteristics of the Online Market for Anabolic-Androgenic Steroids in Central Asia: A Netnographic Analysis.

Background: With the online proliferation of illegal substances, the Internet offers a wide variety of information on the acquisition and intake of anabolic-androgenic steroids (AAS) and other performance and image enhancing drugs. This study focuses on investigating the characteristics of the online AAS market in Central Asia. OBJECTIVES: The primary objectives of this study were to investigate the accessibility and features of the online market for AAS in Central Asia. To achieve this, we employed a netnographic approach for a systematic exploration of websites advertising and selling AAS. The study aimed to conduct a comprehensive analysis of several key aspects, including the variety of AAS products offered, the quality of health advice provided the level of product availability, the procedures involved in making purchases, and the pricing structures within this market. RESULTS: Twenty-one websites supplying AAS in Central Asia met our inclusion criteria. Using content analysis, data were gathered on AAS offerings, quality of health advice provided, availability, purchase process, and prices. Data were synthesized using descriptive statistics. Results indicate that AAS are easily accessible for purchase without valid medical prescription in the Central Asia online market. Most websites advertised the aesthetic and ergogenic benefits of AAS use without indicating the potential complications and adverse effects. CONCLUSIONS: Public health efforts to mitigate AAS use in Central Asia should consider both the online accessibility of AAS and the lack of accompanying information on potential complications as well as adverse effects associated with their use. Efforts must be intensified to curtail the proliferation of AAS and related misleading information on the Central Asian online market.