Objective To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure. Methods Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described. ResultsThe age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences (P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group. Conclusion The incidence of ONFH after GC exposure in China’s SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.
Objective To determine if the therapeutic response to an inhaled corticosteroid is attenuated in individuals with asthma who smoke.Methods 38 outpatients with chronic stable asthma who visited during March 2008 and January 2009 were enrolled in the study. 23 cases were nonsmokers and 15 cases were smokers. All of them were treated by daily inhaled budesonide, and β2 agonist when necessary.They were required to record symptoms and peak expiratory flow every day on an asthmatic diary card. Thepatients were followed 28 days. ACT score, asthma-symptom score, Asthma Control Test ( ACT) score,pulmonary function, and peak expiratory flow were compared between the non-smoking and the smoking asthmatic patients. Results All of the patients had statistically significant increases in ACT score, mean morning and night PEF, mean forced expiratory volume in 1 second, and a significant decrease in asthmasymptom score after budesonide treatment compared with before. There were significantly greater changes inany of these parameters in the non-smokers than in the smokers. Conclusions Active cigarette smoking impairs the efficacy of short term inhaled corticosteroid treatment in asthma. This finding has important implications for the management of patients with asthma who smoke.
Objective To evaluate the efficacy of long-term inhaled salmeterol / fluticasone combined with low-dose oral erythromycin in patients with bronchiectasis. Methods Sixty-two patients with bronchiectasis after exacerbation and maintained stable were randomly divided into three groups. Group A was treated with low-dose oral erythromycin, group B inhaled salmeterol/fluticasone, and group C inhaled salmeterol/fluticasone plus low-dose oral erythromycin. The study duration lasted for 6 months. The clinical symptoms, dyspnea scale, exacerbation frequency, and pulmonary function parameters were measured and compared. Results Fifty-four patients completed the whole study and 8 cases withdrew. The results showed that 6 months of low-dose erythromycin therapy can improve the clinical symptoms, whille exacerbation frequency was also decreased. Inhaled salmeterol/fluticasone improved lung function, however, had no effect on cough, expectoration and exacerbation frequency. Inhaled salmeterol/fluticasone combined with erythromycin was more significantly effective in improving lung functions as well as symptoms. Conclusions Long-terminhaled salmeterol/fluticasone combined with low-dose oral erythromycin can improve the clinical symptoms and lung function, decrease the frequency of exacerbation in patients with bronchiectasis. It may be as an alternative to the maintenance treatment of bronchiectasis.
Objective To investigate the potential effect of glucocorticoids (referred to as 'hormones' here) on decreasing case fatality rate in patients with human immunodeficiency virus (HIV) negative Pneumocystis jirovecii pneumonia (PJP). Methods The clinical data of a cohort of 93 patients that were diagnosed with HIV-negative PJP at Jiangxi Provincial People's Hospital between April 2019 and April 2022 were retrospectively analyzed. These patients were classified into two groups based on the partial pressure of oxygen in arterial blood (PaO2), specifically PaO2 ≥70 mm Hg and PaO2 <70 mm Hg. The association between case fatality rate and various factors such as underlying diseases, hormone use, mechanical ventilation, and others was examined. Results Over a period of three years, 93 cases of HIV-negative PJP were identified. The most prevalent underlying diseases were solid organ transplantation (n=34, 36.6%), rheumatic system diseases (n=26, 28.0%), and malignant tumors (n=15, 16.1%). 51 cases had arterial PaO2 levels ≥70 mm Hg, while 42 cases had levels <70 mm Hg. Moreover, 19 patients required invasive ventilation, 39 patients were treated with non-invasive ventilation, while 50 patients received oxygenation using a nasal cannula. Out of the 93 patients, 31 died from the disease, resulting in an overall case fatality rate of 33.3%. Meanwhile, 62 patients survived. In patients with arterial PaO2 levels ≥70 mm Hg, the administration of hormones did not significantly affect the case fatality rate (P > 0.05); In patients with arterial PaO2 level <70 mm Hg, the administration of hormones did not significantly affect the case fatality rate (P > 0.05). Conclusion Hormone use did not contribute to improved survival rates in HIV-negative PJP patients, regardless of arterial PaO2 level.
ObjectiveTo evaluate the effects of icariin on autophagy induced by low-concentration of glucocorticoid and exosome production in bone microvascular endothelial cells (BMECs).MethodsBMECs were isolated from femoral heads resected in total hip arthroplasty and then intervened with hydrocortisone of low concentration (0, 0.03, 0.06, 0.10 mg/mL), which were set as groups A, B, C, and D, respectively. On the basis of hydrocortisone intervention, 5×10−5 mol/L of icariin was added to each group (set as groups A1, B1, C1 and D1, respectively). Western blot was used to detect the expressions of microtubule-associated protein 1 light chain 3B (LC3B) and dead bone slice 1 (p62) after 24 hours. Exosomes were extracted from BMECs treated with icariin (intervention group) and without icariin (non-intervention group), and the diameter and concentration of exosomes were evaluated by nanoparticle tracking analysis technique. The total protein content of exosomes was detected by BCA method, and the expressions of proteins carried by exosomes including CD9, CD81, transforming growth factor β1 (TGF-β1), and vascular endothelial growth factor A (VEGFA) were assessed by Western blot. The BMECs were further divided into three groups: BMECs in the experimental group and the control group were co-cultured with exosomes secreted by BMECs treated with or without icariin, respectively; the blank control group was BMECs without exosome intervention. The three groups were treated with hydrocortisone and Western blot was used to detect the expressions of LC3B and p62. The scratching assay was used to detect cell migration ability; angiogenic ability of BMECs was also assessed.ResultsWith the increase of hydrocortisone concentration, the protein expression of LC3B-Ⅱ increased gradually, and the protein expression of p62 decreased gradually (P<0.01). Compared with group with same concentration of hydrocortisone, the protein expression of LC3B-Ⅱ decreased and the protein expression of p62 increased after the administration of icariin (P<0.01). The concentration of exosomes in the intervention group was significantly higher than that in the non-intervention group (t=−10.191, P=0.001); and there was no significant difference in exosome diameter and total protein content between the two groups (P>0.05). CD9 and CD81 proteins were highly expressed in the non-intervention group and the intervention group, and the relative expression ratios of VEGFA/CD9 and TGF-β1/CD9 proteins in the intervention group were significantly higher than those in the non-intervention group (P<0.01). After co-culture of exosomes, the protein expression of p62 increased in blank control group, control group, and experimental group, while the protein expression of LC3B-Ⅱ decreased. There were significant differences among groups (P<0.05). When treated with hydrocortisone for 12 and 24 hours, the scratch closure rate of the control group and experimental group was significantly higher than that of the blank control group (P<0.05), and the scratch closure rate of the experimental group was significantly higher than that of the control group (P<0.05). When treated with hydrocortisone for 4 and 8 hours, the number of lumens, number of sprouting vessels, and length of tubule branches in the experimental group and the control group were significantly greater than those in the blank control group (P<0.05); the length of tubule branches and the number of lumens in the experimental group were significantly greater than those in the control group (P<0.05).ConclusionIcariin and BMECs-derived exosomes can improve the autophagy of BMECs induced by low concentration of glucocorticoid.
ObjectiveTo analyze the prognostic factors of vision of myelin oligodendrocyte glycoprotein (MOG) antibody positive associated optic neuritis (ON) after methylprednisolone pulse therapy. MethodsA clinical observational study. A total of 32 patients (47 eyes) with MOG antibody positive ON were observed and followed up in the ophthalmology department of Beijing Tongren Hospital Affiliated to Capital Medical University and Beijing Puren Hospital from March 2019 to January 2022. Clinical data including the best corrected visual acuity (BCVA) and orbital magnetic resonance imaging were recorded. The BCVA was examined by Snellen visual acuity chart, which was finally converted into the logarithm of the minimal angle of resolution (logMAR) for statistical analysis. There were 22 case (38 eyes) with complete image data. All patients were treated with intravenous methylprednisolone pulse (IVMP) for 3-5 days. According to the intervention time (from onset to glucocorticoid treatment), the patients were divided into three groups: ＜7 d group, 7-14 d and ＞14 d group, with 16, 13, 11 eyes, respectively. The median follow-up time was 28 months. After 1 week, 1, 3 and 6 months treatment, the same equipment and methods were used for relevant examinations to observe the changes of visual acuity and the factors influencing the prognosis of visual acuity after IVMP treatment. Logistic regression and linear regression were used to analyze the prognostic correlation factors. Receiver operating characteristic (ROC) curve was used to determine the critical cut-off point of intervention timing. ResultsAmong the patients, 16 were male and 16 were female. The median onset age was 26 years. The onset duration time was 5-60 days. There were 18 cases (56.3%, 18/32) with abnormal serum immune indexes. The initial symptom was decreased vision with unilateral or bilateral ON. Seventeen (53.1%, 17/32) cases had unilateral ON and 15 (46.9%, 15/32) cases with bilateral ON. Thirty-six eyes (76.6%, 36/47) got optic disc edema, 37 eyes (78.7%, 37/47) accompanied by pain of ocular movement. The nadir logMAR BCVA was mean 1.69±0.13. Long T2WI signals with segmental thickening in the orbital segment of the optic nerve were obtained in 27 eyes (71.1%, 27/38) and in 24 eyes (63.2%, 24/38) with optic nerve and sheath enhancement. During the follow-up period, there were 10 cases of relapse (31.3%, 10/32). The logMAR BCVA of attacked eyes were 0.52±0.09, 0.22±0.06, 0.12±0.06, 0.10±0.06 at 1 week and 1, 3 and 6 months after IVMP treatment, respectively. The rate of BCVA improvement was the fastest at 1 week after treatment, and BCVA returned to stability at 3 months. Logistic regression analysis showed that the timing of intervention was significantly correlated with the prognosis of vision in primary onset patients (odds ratio=12.17, P=0.006), with a negative linear regression relationship (r=－0.48, 95% confidence interval －0.71-－0.17, P=0.008). Comparing the logMAR BCVA between the intervention time ＞14 group with the ＜7 group and the 7-14 group, there were statistically significant difference (P=0.017, 0.037), respectively. The cut-off point of ROC curve to predict the optimal intervention time was 13.5 days. Other factors such as: gender, age, predisposing factor, pain of eye motion, edema of optic disc, bilateral ON, imaging changes, abnormal autoimmune indicators were not associated with the prognosis of visual acuity. ConclusionThe timing of hormone intervention in primary onset patients is an important factor affecting the prognosis of vision and the optimal intervention time window of IVMP is two weeks.
Glucocorticoids are the first-line therapy of many neurological disorders, with the treatment regimen varying across types and characteristics of neurological disorders. This article reviews the national and international guidelines and expert consensuses in the past decade on glucocorticoids treatment for neurological disorders, and summarizes recommendations from the latest Chinese guidelines and consensuses. In summary, the most frequently used pulse therapy of glucocorticoids in China is intravenous infusion of high-dose (usually 1000 mg/d) methylprednisolone in a short period (often <5 d), followed by gradual tapering, bridging with oral prednisone or direct discontinuation. The treatment regimen for children and juveniles is similar to that for adults but the dose is adjusted by body weight. Pharmacodynamics of glucocorticoids should be considered for the treatment of perinatal women. To provide appropriate glucocorticoids treatment for patients with neurological disorders, clinicians should fully understand features of each neurological disorder and clinical characteristics of individual patient.