BACKGROUND: The efficacy of rituximab in steroid-resistant nephrotic syndrome (SRNS) is controversial. We previously reported that rituximab in combination with methylprednisolone pulse therapy (MPT) and immunosuppressants was associated with favorable outcomes. We determined risk factors for poor response following rituximab treatment, which remains unknown.
METHODS: This retrospective study included 45 patients with childhood-onset SRNS treated with rituximab across four pediatric kidney facilities. Treatment effects were categorized as complete remission (CR), partial remission (PR), and no remission (NR) at one year after rituximab treatment. The primary outcome was the rate of CR, PR, and NR. Risk factors for non-CR were calculated with multivariate logistic regression. Adverse events and the relationship between disease status at one year and long-term prognosis were also evaluated.
RESULTS: The rates of CR, PR, and NR at one year were 69%, 24%, and 7%, respectively. The median time from rituximab administration to CR was 90 days. The median follow-up period after rituximab administration was 7.4 years. In multivariate analysis, significant risk factors for poor response were the pathologic finding of focal segmental glomerular sclerosis and a long interval between SRNS diagnosis and rituximab administration. The rates of CR were 90.3% and 21.4% in patients receiving rituximab within and after 6 months following SRNS diagnosis, respectively (p < 0.001). Five patients developed chronic kidney disease stage G5, including 2 of the 11 patients with PR and all 3 patients with NR, whereas none of the 31 patients with CR developed chronic kidney disease stage G5.
CONCLUSIONS: Early administration of rituximab in combination with MPT and immunosuppressants might achieve favorable outcomes in patients with SRNS.

UNASSIGNED: Inflammation was associated with the severity of severe cerebral venous thrombosis (CVT) on admission and poor prognosis at discharge. Hereditary protein C/S deficiency (hereditary PCD/PSD) not only promotes thrombosis but also activates the inflammatory response, further inducing venous thrombosis. However, conventional treatments such as standard anticoagulant/endovascular therapy (EVT) do not seem to improve prognosis. Anti-inflammatory therapy may be a new way to treat the disease.
UNASSIGNED: We enrolled five patients with acute/subacute severe CVT with hereditary PCD/PSD from January 2020 to July 2022. In addition to standard anticoagulant therapy, all of them were given short-term methylprednisolone pulse therapy. Neurological deficit, increased intracranial pressure, venous recanalization, serum and cerebrospinal fluid (CSF) inflammatory markers and adverse events were retrospectively described before and after treatment and at 6 months after discharge.
UNASSIGNED: Inflammatory indexes of all patients were significantly elevated on admission. After methylprednisolone pulse therapy, serum inflammatory indexes including neutrophil-to-lymphocyte ratio (P=0.043); platelet-to-lymphocyte ratio (P=0.043); systemic immune inflammatory index (P=0.043); interleukin-6 (P=0.043) and hypersensitive C-reactive protein (P=0.022) reduced dramatically compared with baseline. CSF inflammatory indexes had a decreasing trend compared with baseline (P>0.05). In terms of venous recanalization, one patient achieved complete recanalization, four patients obtained partial recanalization. Compared with baseline on admission, the NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS) and intracranial pressure were all considerably lower at discharge (P=0.029, P=0.041 and P=0.017). At 6-month follow-up, NIHSS and mRS further declined. During hospitalization and 6-month follow-up, none of the five patients experienced severe steroid-related adverse effects such as recurrence of venous thrombosis, spontaneous fracture or osteonecrosis, and gastroduodenal ulcer.
UNASSIGNED: Acute/subacute severe CVT with hereditary PCD/PSD has high levels of inflammation. In addition to conventional anticoagulant therapy, early anti-inflammatory therapy using steroids may be necessary. Nevertheless, substantial randomized controlled trials with larger sample sizes are required for further investigation.

Childhood primary angiitis of the central nervous system (cPACNS) is a vasculitis of unknown etiology that is confined to the central nervous system (CNS) and can lead to repeated cerebral infarctions if left untreated. Several cases of cPACNS after COVID-19 have been reported. Herein, we present a case of post-vaccination cPACNS. A 9-year-old healthy boy presented with persistent headache and fever after receiving the second COVID-19 vaccine (BNT162b2/Pfizer-BioNtech) dose. Brain magnetic resonance angiography (MRA) performed on the sixth day of symptom onset after vaccination revealed stenosis of the left middle cerebral artery; the patient was referred to our department on the 12th day of symptom onset. Blood tests indicated only minimal evidence of inflammation, whereas cerebrospinal fluid examination indicated pleocytosis. Brain magnetic resonance imaging (MRI) revealed vascular wall thickening and contrast enhancement of the artery with worsened stenosis. We diagnosed the patient as having cPACNS and treated him with three courses of methylprednisolone pulse therapy. The headaches and fever disappeared with improvement of vascular stenosis. The patient has been in remission for more than 1 year since cPACNS onset. This is the first report of a case of cPACNS after mRNA vaccination for COVID-19. Most previous cases of COVID-19-associated cPACNS presented with ischemic stroke. However, the present case could be treated for vasculitis prior to stroke and thus had a favorable prognosis. The mRNA vaccine for COVID-19 differs from other existing vaccines, and further accumulation of data of cases is required to determine adverse CNS reactions.

UNASSIGNED: Previous studies have identified the predictors of severe infections in ANCA-associated vasculitis. However, lymphopenia has not been fully evaluated as a predictor of subsequent severe infections in patients with microscopic polyangiitis (MPA). The aim of this study was to assess the association between lymphopenia and severe infections requiring hospitalization after receiving immunosuppressive therapy for MPA.
UNASSIGNED: This single-centre retrospective cohort study included 130 consecutive patients with newly diagnosed MPA from Aichi Medical University Hospital, Japan, who received immunosuppressive therapy between March 2004 and December 2020. The relationship between lymphopenia and subsequent severe infections was assessed using time-dependent multivariate Cox proportional hazard models adjusted for clinically relevant factors.
UNASSIGNED: During the follow-up period (median: 38 months; interquartile range: 15-63 months), 56 severe infectious episodes occurred in 51 patients (39.2%). Time-dependent multivariate Cox proportional hazard analyses identified older age [adjusted hazard ratio (HR) = 1.74 per 10 years, 95% CI: 1.13, 2.67], methylprednisolone pulse therapy (adjusted HR = 2.04, 95% CI: 1.03, 4.02), moderate lymphopenia (vs normal, adjusted HR = 7.17, 95% CI: 3.10, 16.6) and severe lymphopenia (vs normal, adjusted HR = 36.1, 95% CI: 11.8, 110.9) as significant predictors of severe infection.
UNASSIGNED: Lymphopenia is a predictor of subsequent severe infections in patients with MPA who receive immunosuppressive therapy. These results suggest the importance of sustained infection surveillance, particularly in older patients who develop lymphopenia during strong immunosuppressive therapy.

UNASSIGNED: Corticosteroids are common treatments in certain diseases that cause acute respiratory failure (ARF) and are sometimes administered empirically for patients with critical ARF. Associations between changes in clinical parameters following initiation of steroid pulse therapy and mortality in patients with ARF have not been previously investigated.
UNASSIGNED: This was a single-center and retrospective cohort study. Parameters on the day of methylprednisolone pulse therapy initiation (day 1) and the day following the end of methylprednisolone therapy (day 4) in patients who were admitted because of ARF and underwent methylprednisolone pulse therapy between October 2008 and July 2021 were reviewed.
UNASSIGNED: A total of 98 patients were included in our analysis, and 45 (46%) died at our hospital. Change in lactate dehydrogenase (LDH) from day 1 to day 4 (ΔLDH) was significantly higher in the in-hospital death group than in the survival group (-68 IU/L in the survival group versus 46 IU/L in the in-hospital death group, p < 0.01). Multivariate logistic analyses showed that age >75 years old (odds ratio (OR), 3.88; 95% confidence interval (CI), 1.38-10.9; p < 0.01), previously diagnosed interstitial lung disease (OR, 3.43; 95% CI, 1.10-10.7; p = 0.03), ΔLDH > 0 (OR, 6.47; 95% CI, 2.30-18.2; p < 0.01), and ΔSequential Organ Failure Assessment score > 0 (OR, 3.06; 95% CI, 1.10-8.51; p = 0.03) were significantly associated with in-hospital mortality.
UNASSIGNED: This study showed that elevation of serum LDH level during methylprednisolone pulse therapy was a predictive factor for high in-hospital mortality in patients with ARF.

BACKGROUND: In contrast to the adult population, limited information is currently available on risk factors for ventilator-associated pneumonia (VAP) in children. Therapeutic hypothermia has been identified as a risk factor for the early onset of VAP in adults; however, the relationship between VAP and normothermia remains unclear. The present study investigated risk factors for VAP in children, with a focus on the deleterious effects of therapeutic normothermia on VAP.
METHODS: We retrospectively investigated the clinical characteristics of children treated with mechanical ventilation for more than 48 h and analyzed risk factors for VAP. The endpoint was the onset of VAP by the seventh day after the initiation of mechanical ventilation.
RESULTS: Among the 288 patients enrolled, seven (2.4%) developed VAP. No significant differences were observed in clinical backgrounds between the VAP and non-VAP groups. A univariate analysis identified target temperature management (TTM) at 36°C (p < 0.0001) and methylprednisolone (mPSL) pulse therapy (p = 0.02) as risk factors for VAP. An analysis of the time to the onset of VAP by the Kaplan-Meier plot and log-rank test revealed a significantly higher incidence of VAP in the TTM group (p < 0.0001) and mPSL pulse group (p = 0.001).
CONCLUSIONS: TTM at 36°C and mPSL pulse therapy may be risk factors for VAP in the pediatric population.

The patient, a 58-year-old man, experienced weakness of the proximal muscles in both lower extremities, and Lambert-Eaton myasthenic syndrome and small cell carcinoma of unknown primary origin were diagnosed. He received symptomatic treatment for myasthenia and radiochemotherapy for small cell carcinoma; once this regimen, the myasthenic symptoms improved. However, acute myocardial infarction occurred, after which type II respiratory failure developed, and the patient required ventilator management with tracheal intubation. Acute-phase treatment, such as plasma exchange, intravenous immune globulin therapy, and methylprednisolone pulse therapy, and intensification of symptomatic treatment allowed for extubation, and eventually the patient was able to walk independently. According to electrophysiological examination, compound muscle action potentials were larger at discharge than at the time of exacerbation.

暂无摘要。

Immune-related cardiotoxicities are uncommon but potentially fatal. The study aims to evaluate the value of pacemakers and methylprednisolone pulse therapy (MPPT) to patients with immune-related myocarditis concomitant with complete heart block (CHB). We first reviewed medical records of three patients with immune-related myocarditis concomitant with CHB. For the pooled analysis, we searched related cases with immune-related myocarditis in the PubMed database and screened the patients. Clinical characteristics, management, and outcomes were summarized. Our three patients developed immune-related myocarditis concomitant with CHB about 2 weeks after receiving pembrolizumab, and were successfully treated with pacemaker implantation and high-dose steroids (two received MPPT). In the pooled analysis, 21 cases were eligible with an overall fatality rate of 52%. Patients with pacemakers had a fatality rate of 38%, significantly lower than patients without them (38% vs 100%; p = 0.035), particularly the MPPT subgroup (25% vs 100%; p = 0.019). All five patients without pacemakers expired. Among patients with pacemakers, MPPT patients tended to have an inferior rate compared with non-MPPT patients. Timely pacemaker implantation played a crucial role in improving the outcomes of patients with immune-related myocarditis concomitant with CHB. Patients receiving MPPT appeared to have a better prognosis. Additionally, multidisciplinary consultation should be recommended for better management.

To investigate the differentiation of regulatory T cells (Tregs) induced by methylprednisolone (MP) pulse therapy in patients with Systemic Lupus Erythematosus (SLE).
We enrolled 30 patients with SLE and analyzed peripheral blood mononuclear cells (PBMCs) before and after MP pulse therapy. Peripheral Tregs, apoptosis of PBMCs subsets, and TGFβ production by monocytes was quantified by flow cytometry. Proliferation and IFN-γ production of CD4+ T cells were measured. Furthermore, TGFβ1 production by human monocyte-derived macrophages (HMDM) stimulated with MP-treated CD4+ T cells were quantified by ELISA.
Peripheral Tregs was significantly increased after MP pulse therapy (6.76 ± 1.46% vs. 3.82 ± 1.02%, p < 0.01), with an expansion of Nrp1- induced Tregs (4.54 ± 0.46% vs. 1.75 ± 0.38%, p < 0.01). Proliferation and IFN-γ production of CD4+ T cells were significantly decreased after MP pulse therapy. MP pulse therapy induced CD4+ T cell apoptosis (early apoptosis, 26.34 ± 3.54% vs. 14.81 ± 2.89%, p < 0.01) and TGFβ expression on monocytes (6.02% vs. 2.45%, p < 0.01). Furthermore, MP induced CD4+ T cell apoptosis in vitro, which stimulated HMDM to produce TGFβ. Moreover, elevated TGFβ level in supernatant from HMDM stimulated with MP-treated CD4+ T cells promoted Tregs differentiation.
MP pulse therapy induces CD4+ T cell apoptosis, which promotes monocytes to produce TGFβ and further facilitates Tregs differentiation. Newly-differentiated Tregs suppress proliferation and IFN-γ production of CD4+ T cells and contribute to immunoregulatory milieu after MP pulse therapy.