Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8⁺T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.
Male ; Humans ; Adult ; Middle Aged ; Aged ; Immune Checkpoint Inhibitors/adverse effects* ; Retrospective Studies ; Antineoplastic Agents, Immunological/adverse effects* ; Liver ; Glucocorticoids/therapeutic use*

OBJECTIVES: To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG). METHODS: A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (n=29), mycophenolate mofetil (MMF) group (GC+MMF; n=33), methotrexate (MTX) group (GC+MTX; n=30), and tacrolimus (FK506) group (GC+FK506; n=38). Treatment outcomes and adverse reactions were compared among the groups. RESULTS: After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (P<0.05). After 3 months of treatment, the FK506 group had a significantly lower dose of prednisone than the GC group, and after 6 and 9 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower dose of prednisone than the GC group (P<0.05). After 12 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower incidence rate of GC-related adverse reactions than the GC group (P<0.05). CONCLUSIONS For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.
Humans ; Child ; Prednisone/adverse effects* ; Tacrolimus/adverse effects* ; Retrospective Studies ; Activities of Daily Living ; Immunosuppressive Agents/adverse effects* ; Myasthenia Gravis/drug therapy* ; Glucocorticoids/therapeutic use* ; Mycophenolic Acid/adverse effects*

Humans ; Child ; Glucocorticoids/therapeutic use* ; Airway Extubation ; Airway Obstruction/prevention & control* ; Intubation, Intratracheal/adverse effects*

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use* ; Glucocorticoids/therapeutic use* ; Hematopoietic Stem Cell Transplantation/methods* ; Humans ; Pneumonia/etiology* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

OBJECTIVES: To study the clinical effect and adverse drug reactions of different doses of glucocorticoid (GC) in the treatment of children with recurrence of steroid-sensitive nephrotic syndrome (SSNS). METHODS: A total of 67 children who were hospitalized and diagnosed with SSNS recurrence in the Department of Nephrology, Children's Hospital, Capital Institute of Pediatrics, from November 2017 to December 2019 were enrolled. They were randomly divided into a moderate-dose GC group (32 children) and a full-dose GC group (35 children). The two groups were compared in terms of urinary protein clearance, recurrence rate within 6 months, and incidence rate of GC-associated adverse reactions. RESULTS: There was no significant difference in the urinary protein clearance rate between the moderate-dose GC and full-dose GC groups (91% vs 94%, P>0.05). There was also no significant difference in the recurrence rate within 6 months between the two groups (41% vs 36%, P>0.05). At 6 months of follow-up, compared with the full-dose GC group, the moderate-dose GC group had a significantly lower cumulative dose of prednisone [(87±18) mg/kg vs (98±16) mg/kg, P=0.039] and a significantly lower proportion of children with an abnormal increase in body weight (6% vs 33%, P=0.045). The logistic regression analysis showed that prednisone dose ≥10 mg/alternate day at enrollment was a risk factor for recurrence within 6 months in children with SSNS (P=0.018). CONCLUSIONS For children with SSNS recurrence, moderate-dose GC has similar effects to full-dose GC in the remission induction rate and the recurrence rate within 6 months, with a lower cumulative dose and fewer GC-associated adverse reactions within 6 months than full-dose GC.
Child ; Glucocorticoids/therapeutic use* ; Humans ; Nephrotic Syndrome/drug therapy* ; Prednisone/adverse effects* ; Prospective Studies ; Remission Induction

BACKGROUND: At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. METHODS: The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. DISCUSSION: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019. TRIAL REGISTRATION ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.
Betacoronavirus ; drug effects ; Coronavirus Infections ; drug therapy ; Glucocorticoids ; adverse effects ; therapeutic use ; Humans ; Pandemics ; Pneumonia, Viral ; drug therapy ; Randomized Controlled Trials as Topic ; Severity of Illness Index

BACKGROUND: Glucocorticoids have been widely used to treat patients with chronic obstructive pulmonary disease (COPD). Nevertheless, corticosteroid insensitivity is a major barrier to the effective treatment of COPD and its mechanism remains unclear. This study aimed to evaluate the effect of cathelicidin LL-37 on corticosteroid insensitivity in COPD rat model, and to explore the involved mechanisms. METHODS: COPD model was established by exposing male Wistar rats to cigarette smoke combined with intratracheal instillation of lipopolysaccharide (LPS). Inhaled budesonide and LL-37 were consequently applied to COPD models separately or collectively to confirm the effects on inflammatory cytokines (tumor necrosis factor [TNF]-α and transforming growth factor [TGF]-β) by enzyme-linked immunosorbent assay (ELISA) and lung tissue histopathological morphology. Expression of histone deacetylase-2 (HDAC2) and phosphorylation of Akt (p-AKT) in lung were also measured. RESULTS: Briefly, COPD model rats showed an increased basal release of inflammatory cytokines (lung TNF-α: 45.7 ± 6.1 vs. 20.1 ± 3.8 pg/mL, P < 0.01; serum TNF-α: 8.9 ± 1.2 vs. 6.7 ± 0.5 pg/mL, P = 0.01; lung TGF-β: 122.4 ± 20.8 vs. 81.9 ± 10.8 pg/mL, P < 0.01; serum TGF-β: 38.9 ± 8.5 vs. 20.6 ± 2.3 pg/mL, P < 0.01) and COPD related lung tissue histopathological changes, as well as corticosteroid resistance molecular profile characterized by an increase in phosphoinositide 3-kinase (PI3K)/Akt (0.5 ± 0.1 fold of control vs. 0.2 ± 0.1 fold of control, P = 0.04) and a decrease in HDAC2 expression and activity (expression: 13.1 ± 0.4 μmol/μg vs. 17.4 ± 1.1 μmol/μg, P < 0.01; activity: 1.1 ± 0.1 unit vs. 1.4 ± 0.1 unit, P < 0.01), compared with control group. In addition, LL-37 enhanced the anti-inflammatory effect of budesonide in an additive manner. Treatment with combination of inhaled corticosteroids (ICS) and LL-37 led to a significant increase of HDAC2 expression and activity (expression: 15.7 ± 0.4 μmol/μg vs. 14.1 ± 0.9 μmol/μg, P < 0.01; activity: 1.3 ± 0.1 unit vs. 1.0 ± 0.1 unit, P < 0.01), along with decrease of p-AKT compared to budesonide monotherapy (0.1 ± 0.0 fold of control vs. 0.3 ± 0.1 fold of control, P < 0.01). CONCLUSIONS This study suggested that LL-37 could improve the anti-inflammatory activity of budesonide in cigarette smoke and LPS-induced COPD rat model by enhancing the expression and activity of HDAC2. The mechanism of this function of LL-37 might involve the inhibition of PI3K/Akt pathway.
Animals ; Antimicrobial Cationic Peptides ; pharmacology ; therapeutic use ; Glucocorticoids ; metabolism ; Histone Deacetylase 2 ; metabolism ; Humans ; Inflammation ; chemically induced ; drug therapy ; Lipopolysaccharides ; pharmacology ; Male ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; metabolism ; Rats ; Rats, Wistar ; Smoking ; adverse effects ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo study the clinical effect and safety of early postnatal application of glucocorticoids in the prevention of bronchopulmonary dysplasia (BPD) in preterm infants.

METHODSThe databases including PubMed, Cochrane Library, Embase, CNKI, Wanfang Data, and VIP were comprehensively searched for articles on early postnatal application of glucocorticoids in the prevention of BPD in preterm infants published up to June 2016. Review Manager 5.3 was used for the Meta analysis of 16 randomized controlled trials (RCTs) that met the inclusion criteria.

RESULTSA total of 2 962 participants were enrolled in the 16 RCTs, with 1 486 patients in the trial group and 1 476 in the control group. The Meta analysis showed that early postnatal application of glucocorticoids reduced the incidence rate of BPD at a corrected gestational age of 36 weeks (OR=0.73, 95%CI: 0.61-0.87, P=0.0004), but there was an increase in the risk of hyperglycemia (OR=1.61, 95%CI: 1.24-2.09, P=0.0003), hypertension (OR=1.63, 95%CI: 1.11-2.38, P=0.01), and intestinal perforation (OR=1.51, 95%CI: 1.12-2.04, P=0.007).

CONCLUSIONSAt present, it is not recommended to use glucocorticoids to prevent BPD in preterm infants. Its advantages and disadvantages need further studies, with special focuses on the adverse effects of hyperglycemia, hypertension, and intestinal perforation.

Bronchopulmonary Dysplasia ; prevention & control ; Glucocorticoids ; adverse effects ; therapeutic use ; Humans ; Hyperglycemia ; chemically induced ; Hypertension ; chemically induced ; Infant, Newborn ; Infant, Premature ; Intestinal Perforation ; chemically induced

Entecavir (Baraclude®) is an oral antiviral drug used for the treatment of HBV. Entecavir is a reverse transcriptase inhibitor which prevents the HBV from multiplying. Most common adverse reactions caused by entecavir are headache, fatigue, dizziness, and nausea. Until now, there has been no report of peripheral neuropathy as a side effect associated with entecavir treatment. Herein, we report a case of peripheral neuropathy which probably occurred after treatment with entecavir in a hepatitis B patient. The possibility of the occurrence of this side effect should be carefully taken into consideration when a patient takes a high dose of entecavir for a long period of time or has risk factors for neuropathy at the time of initiating entecavir therapy.
Administration, Oral ; Antiviral Agents/*adverse effects/therapeutic use ; Brain/diagnostic imaging ; Drug Therapy, Combination ; Duloxetine Hydrochloride/therapeutic use ; Glucocorticoids/therapeutic use ; Guanine/adverse effects/*analogs & derivatives/therapeutic use ; Hepatitis B, Chronic/drug therapy ; Humans ; Male ; Middle Aged ; Polyneuropathies/*diagnosis/drug therapy/etiology ; Prednisolone/therapeutic use ; Pregabalin/therapeutic use ; Tomography, X-Ray Computed

OBJECTIVETo investigate the role of perindopril for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) in rabbits.

METHODSA total of 45 male New Zealand white rabbits (10 months old, weight 3.0 to 3.5 kg) were randomly divided into 3 groups involving normal control group (muscle injection of saline solution, n = 15, group NC), model group (muscle injection of dexamethasone, n = 15, group GIOP), and treatment group (muscle injection of dexamethasone combined with oral perindopril, n = 15, group GIOP+ACEI). All rabbits put to death after 12 weeks' treatment. The changes of bone mass and strength were observed and analyzed by bone histomorphology, biomechanics, metabolic bone related serological indexes and mRNA expression.

RESULTSAt 12 weeks, the analysis of bone histomorphology and biomechanics results showed that the bone mass and bone strength of group GIOP were significantly lower than that of group NC (P < 0.05); after perindopril treatment, the bone mass and bone strength of group GIOP+ACEI were higher obviously than that of group GIOP (P < 0.05). Mineralizing surface,mineral apposition rate and serum osteocalcin in group GIOP decreased than group NC; however, osteoclast number, osteoclast surface, eroded surface, and urinary deoxypyridinoline in group GIOP increased than group NC (P < 0.05); these changes were inhibited after perindopril treatment (P < 0.05). Quantitative RT-PCR revealed that after dexamethasone treatment, the ratio of SOST mRNS expression and RANKL/OPG mRNA expression obviously increased than that of group NC (P < 0.05); and Runx2 expression decreased significantly (P < 0.05); while the changes of mRNA expression were improved by perindopril treatment.

CONCLUSIONPerindopril can promote bone formation and inhibit bone resorption to deduce glucocorticoid-induced osteoporosis. This study provides a new method for prevention and treatment of GIOP.

Animals ; Biomechanical Phenomena ; Glucocorticoids ; adverse effects ; Male ; Osteoporosis ; chemically induced ; prevention & control ; Perindopril ; therapeutic use ; Rabbits