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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. Conclusion: Early administration of rituximab in combination with MPT and immunosuppressants might achieve favorable outcomes in patients with SRNS. [ABSTRACT FROM AUTHOR]

Wensi Hao,1,2 Yaqin Gu,1,2 Shuyuan Hu,1,2 Xunming Ji,1,2 Yuping Wang,2 Jiangang Duan1,2 1Department of Emergency, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jiangang Duan, Department of Emergency, Xuanwu Hospital, Capital Medical University, No. 45, Changchun St, Xicheng District, Beijing, 100053, People’s Republic of China, Email duanjiangang@xwhosp.orgBackground: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: severe cerebral venous thrombosis, hereditary protein C deficiency, hereditary protein S deficiency, thrombosis, inflammation, methylprednisolone pulse therapy

Objective 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. Methods 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. Results 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. Conclusion 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. [ABSTRACT FROM AUTHOR]

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.

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.

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). Conclusion: TTM at 36°C and mPSL pulse therapy may be risk factors for VAP in the pediatric population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious conditions characterized by necrosis of the skin and mucus membranes, and are mainly caused by medication and infections. Although the exact pathomechanism of SJS/TEN remains unclear, keratinocyte death is thought to be triggered by immune reactions to these antigens. While there is no established therapy for SJS/TEN, corticosteroids and intravenous immunoglobulin (IVIG) have been utilized as immunomodulator. We previously conducted a study to evaluate the efficacy of IVIG therapy in Japanese patients with SJS/TEN. IVIG was administered at a dosage of 400 mg/kg/day for 5 consecutive days as an additional therapy with systemic steroids. Prompt amelioration was observed in seven of the eight patients. All patients survived without sequelae. Recently, we retrospectively analyzed 132 cases of SJS/TEN treated in our two hospitals. The mortality rates in the patients treated with methylprednisolone pulse were 0% (0/31) for SJS and 7.0% (3/43) for TEN, and 0% (0/10) in the TEN patients treated with methylprednisolone pulse in combination with IVIG. These results suggest that early treatment with high-dose steroids, including methylprednisolone pulse therapy, and IVIG together with corticosteroids are possible therapeutic options to improve the prognosis of SJS/TEN.

Introduction: Patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive amyopathic dermatomyositis (ADM) often develop rapidly progressive interstitial lung diseases (RP-ILD), with poor treatment success. Many studies have shown that this is the main cause of death in patients with anti-MDA5 antibody-positive ADM.Case Presentation: A 37-years-old woman developed a cough, shortness of breath, and a rash on both hands, which resembled Gottron's signs. Upon laboratory examination, the results were as follows: antinuclear antibody (ANA) positive; anti-Ro52 antibody positive; and anti-MDA5 antibody positive. Pulmonary high-resolution CT (HRCT) scan showed pulmonary interstitial inflammatory changes, and mediastinal and subcutaneous emphysema. She was finally diagnosed with anti-MDA5 antibody-positive ADM accompanied by RP-ILD. She was first given high-dose-steroid pulse therapy with methylprednisolone (500 mg per day for 3 days) followed by methylprednisolone (40 mg, daily), cyclosporine A (100 mg, twice per day), and hydroxychloroquine (200 mg, twice per day). Since her discharge from our hospital in March of 2018, she has maintained the methylprednisolone therapy (tapered to 10 mg daily), cyclosporine A (100 mg, twice per day), and hydroxychloroquine (200 mg, twice per day).Outcomes: Pulmonary HRCT scans taken on 4, 9, and 26 months after her discharge from our hospital showed that the interstitial pneumonitis had significantly improved and that mediastinal and subcutaneous emphysema had been gradually absorbed. The patient can now participate in regular work and activities of daily living.Conclusion: The treatment of methylprednisolone pulse therapy combined with cyclosporine A and hydroxychloroquine may be an option for the RP-ILD accompanied by anti-MDA-positive ADM. After the acute phase, this combination therapy strategy is helpful to the disease control of patients.

Methylprednisolone is an effective drug in the treatment of autoimmune disease, such as multiple sclerosis (MS), due to long‐acting anti‐inflammatory, antiallergic and immunosuppressant. Previous studies have noted the importance of myeloid‐derived suppressor cells (MDSC) in MS progression. However, it is still not known whether methylprednisolone could influence the ratio and function of MDSC during MS treatment. In the current study, we found an increased ratio of MDSC at the onset of EAE in mice model; but methylprednisolone pulse therapy (MPPT) did not alter the percentage and suppressive function of MDSC during disease attenuation. However, the percentage of G‐MDSC in PBMC significantly increased in patients with MS. Surprisingly, relapsing MS patients showed a significant increase in both M‐MDSC and G‐MDSC after MPPT. The disease remission positively correlated expansion of MDSC and expression of arginase‐1. Additionally, MPPT reduced the expression of inhibitory glucocorticoid (GCs) receptor β subunit on MDSC while elevating serum levels of immune regulatory S100A8/A9 heterodimer. Thus, MDSC dynamics and function in mouse EAE differ from those in human MS during MPPT. Our study suggested that GCs treatment may help relieve the acute phase of MS by expanding MDSC through up‐regulating of GR signalling and S100A8/A9 heterodimers. [ABSTRACT FROM AUTHOR]

The aim of the present study was to analyze the effects of methylprednisolone pulse therapy (MPPT) courses on bone metabolism in patients with Graves' ophthalmopathy (GO). A retrospective analysis of 45 patients with moderate-to-severe active GO who received 1 or 2 courses of MPPT was performed. Of these, 16 patients underwent 2 courses of treatment. Bone metabolic markers and the density of the lumbar spine (L1-4), femoral neck and total hip were measured using a dual-energy X-ray bone density instrument, and the differences in bone metabolism prior to and after treatment were determined for each group and compared. The results indicated that serum I collagen N-terminal peptide (P1NP) and serum β-collagen crosslinked C-terminal peptide (CTX) were markedly decreased after the first pulse of treatment. In those patients who received a second course of MPPT, CTX levels were significantly decreased, but P1NP was not significantly different from the baseline value. CTX and P1NP levels remained unchanged between the first and second course of MPPT; similarly, there were no changes from baseline in 25(OH) vitamin D3 and bone mineral density after the first and second course of MPPT. However, the level of 25(OH) vitamin D3 was significantly elevated after the second course compared with the first course. In conclusion, the side effects of MPPT on bone metabolism were marginal and a second course of MPPT did not worsen bone metabolism. These MPPT regimens may therefore be considered to be a safe and effective treatment option for patients with moderate-to-severe active GO. [ABSTRACT FROM AUTHOR]

Pulse corticosteroid therapy is effective for alopecia areata (AA) in the early stage. The risk and efficacy of this therapy for patients with several backgrounds, however, remains controversial. To explore the predictive factors of the response and risk factors of this therapy, data from 105 AA patients treated with methylprednisolone (500 mg) i.v. for 3 days consecutively in our facility were retrospectively analyzed. Among good responders, longer time from the onset to therapy was correlated with longer time required for hair regrowth (P = 0.037, n = 27). Multivariate models demonstrated that "severity", "relapse" and longer "duration from the latest onset" were significantly and independently associated with poorer outcome (P < 0.01). "History of atopic dermatitis (AD)" was also associated with poorer outcome, but this correlation could be explained by the effect that duration from the latest onset of AA was longer among participants with AD. We propose that earlier initiation of pulse corticosteroid therapy is preferable for better outcome of AA, particularly among patients with AD. Clinicians should be mindful of the occurrence of mild adverse effects in the elderly patients. [ABSTRACT FROM AUTHOR]

Tomoaki Higashiyama,1 Yasuhiro Nishida,2 Masahito Ohji1 1Department of Ophthalmology, 2Clinical Medical Education Center, Shiga University of Medical Science, Shiga, Japan Purpose: To characterize the relationship between inflammation and swelling of extraocular muscles in thyroid-associated ophthalmopathy before and after methylprednisolone pulse therapy.Methods: The signal intensities and volumes of the superior rectus (SR), inferior rectus (IR), lateral rectus (LR), medial rectus (MR), and superior oblique (SO) muscles were measured with magnetic resonance imaging in 25 eyes of 25 patients with thyroid-associated ophthalmopathy in the acute inflammatory phase before and after methylprednisolone pulse therapy. The signal intensity ratios (SIRs) of muscles and brain white matter were calculated.Result: The mean SIRs before treatment were 2.28±0.74 in SR, 2.66±0.57 in IR, 2.03±0.42 in LR, 2.45±0.49 in MR, and 1.98±0.48 in SO muscles. The mean SIRs after treatment were 1.82±0.62, 1.84±0.52, 1.70±0.35, 1.95±0.46, and 1.60±0.36, respectively. The mean volumes (cm3) before treatment were 1.35±0.67 in SR, 1.21±0.39 in IR, 0.66±0.13 in LR, 0.94±0.31 in MR, and 0.58±0.14 in SO muscles. Those after treatment were 1.12±0.45, 0.91±0.31, 0.61±0.12, 0.85±0.28, and 0.49±0.11, respectively. The SIRs showed significantly positive correlations with volumes both before and after treatment in SR muscles (before, r=0.77; after, r=0.69), IR muscles (before, r=0.65; after, r=0.60), MR muscles (before, r=0.69; after, r=0.73), and SO muscles (before, r=0.52; after, r=0.50) (P

Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

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.

A meta-analysis of published trials on the treatment of alopecia areata (AA) came to the conclusion that most have been reported poorly and so small that any important clinical benefits are inconclusive, and considering the possibility of spontaneous remission, especially for those in the early stages of the disease, the options of not being treated or depending on individual preference, and of wearing a wig may be alternative ways of dealing with the condition. And yet, from clinical practice, we know that depending on patient age, surface area, disease duration, and comorbidities an empiric treatment algorithm can be designed that is successful in a significant proportion of patients. More recently, it has been suggested that Janus kinase (JAK) inhibitors may represent the drug of choice for AA, based on robust scientific background and preliminary clinical study results. The fact is that a sophisticated treatment of AA cannot be reduced to one drug, while in many patients, depending on disease duration and surface area, either intravenous methylprednisolone pulse therapy, intralesional triamcinolone acetonide or subcutaneous methotrexate will achieve remission rates in the range of the efficacy of the JAK inhibitors. Moreover, at this time point, affordability of the JAK inhibitors for long-term treatment, sustainability of treatment result, and long-term safety are major issues with regard to the treatment of AA with JAK inhibitors. [ABSTRACT FROM AUTHOR]

A 76-year-old woman was diagnosed with thyroid-associated orbitopathy (TAO) associated with hypothyroidism at another clinic. Magnetic resonance imaging showed enlargements of the extraocular muscles. Because her best-corrected visual acuity (BCVA) was 0.01OD, she was referred to the Chiba University Hospital. She had an elevation of serum IgG4. She was diagnosed with possible IgG4-related ophthalmic disease (IgG4-ROD) accompanied by optic nerve compression with the mass. She underwent methylprednisolone pulse therapy, and, two months later, her BCVA and visual field defect were greatly improved. Our findings indicate that ophthalmologists should be aware that IgG4-ROD can be masked by lesions associated with TAO. [ABSTRACT FROM AUTHOR]

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.

Abstract Background Herpes simplex virus (HSV) infection carries one of the poorest outcomes of neonatal liver failure (NLF). Neonates with disseminated HSV infection can develop hemophagocytic lymphohistiocytosis (HLH), and occasionally need orthotopic liver transplantation. Early interventions may be critical for the cure of NLF. Case Report We describe herewith a 6-day-old neonate with fulminant hepatic failure due to disseminated HSV-1 infection, who successfully responded to high-dose corticosteroid therapy 72 hours after the onset of disease. Preceding acyclovir, gamma globulin, and exchange blood transfusion therapies failed to control the disease. Methylprednisolone pulse therapy led to a drastic improvement of liver function and cytokine storms, and prevented the disease progression to HLH. Sustained levels of plasma and cerebrospinal fluid HSV DNA declined after prolonged acyclovir therapy. Bilateral lesions of the periventricular white matter areas, assessed by magnetic resonance imaging, disappeared at 3 months of age. The infant showed normal growth and development at 4 years of age. Conclusion Early anti-hypercytokinemia therapy using corticosteroid, and prolonged antiviral therapy might only provide the transplantation-free cure of NLF with HSV dissemination.

Purpose: To characterize the relationship between inflammation and swelling of extraocular muscles in thyroid-associated ophthalmopathy before and after methylprednisolone pulse therapy. Methods: The signal intensities and volumes of the superior rectus (SR), inferior rectus (IR), lateral rectus (LR), medial rectus (MR), and superior oblique (SO) muscles were measured with magnetic resonance imaging in 25 eyes of 25 patients with thyroid-associated ophthalmopathy in the acute inflammatory phase before and after methylprednisolone pulse therapy. The signal intensity ratios (SIRs) of muscles and brain white matter were calculated. Result: The mean SIRs before treatment were 2.28±0.74 in SR, 2.66±0.57 in IR, 2.03±0.42 in LR, 2.45±0.49 in MR, and 1.98±0.48 in SO muscles. The mean SIRs after treatment were 1.82±0.62, 1.84±0.52, 1.70±0.35, 1.95±0.46, and 1.60±0.36, respectively. The mean volumes (cm3) before treatment were 1.35±0.67 in SR, 1.21±0.39 in IR, 0.66±0.13 in LR, 0.94±0.31 in MR, and 0.58±0.14 in SO muscles. Those after treatment were 1.12±0.45, 0.91±0.31, 0.61±0.12, 0.85±0.28, and 0.49±0.11, respectively. The SIRs showed significantly positive correlations with volumes both before and after treatment in SR muscles (before, r=0.77; after, r=0.69), IR muscles (before, r=0.65; after, r=0.60), MR muscles (before, r=0.69; after, r=0.73), and SO muscles (before, r=0.52; after, r=0.50) (P<0.01 for all correlations). Conclusion: Swelling reflected the inflammation in extraocular muscles of thyroid-associated ophthalmopathy both before and after treatment. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the changes of orbital tissue volumes and proptosis after methylprednisolone pulse therapy in thyroid-associated ophthalmopathy (TAO). Methods: The cross-sectional areas of orbital tissues and proptosis were measured with magnetic resonance imaging in 40 orbits of 20 patients with TAO before and after methylprednisolone pulse therapy. The volumes of the whole orbit, orbital fatty tissue, and extraocular muscles were calculated. The volumes and proptosis were compared before and after treatment using a paired t test. Results: Before treatment, the mean volumes were 33.0 ± 4.8 cm in the whole orbit, 19.9 ± 4.1 cm in the orbital fatty tissue, and 4.6 ± 1.2 cm in the total extraocular muscles. After treatment, the mean volumes were 32.5 ± 4.4 cm in the whole orbit, 19.9 ± 3.7 cm in the orbital fatty tissue, and 4.0 ± 1.0 cm in the total extraocular muscles. The mean volumes of the whole orbit ( P = 0.17) and orbital fatty tissue ( P = 0.82) were not significantly decreased after treatment, while the mean volume of total extraocular muscles was significantly decreased ( P < 0.001). The mean proptosis value was 18.9 ± 2.8 mm before treatment and 18.6 ± 3.4 mm after treatment. The mean proptosis value was not significantly decreased after treatment ( P = 0.30). Conclusions: The volume of orbital fatty tissue seemed to be unchanged after methylprednisolone pulse therapy while that of total extraocular muscles was decreased. The proptosis value seemed to be unchanged after treatment. [ABSTRACT FROM AUTHOR]

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. • MP pulse therapy promotes the apoptosis of CD4+ T cells in lupus patients. • Monocytes produce more TGFβ after MP pulse therapy. • The elevated level of TGFβ facilitates the differentiation of Tregs. [ABSTRACT FROM AUTHOR]

Aim C3 glomerulonephritis ( C3GN) is a recently described disease that is related to membranoproliferative glomerulonephritis ( MPGN). We retrospectively compared the frequencies, clinical characteristics, treatment modalities, and outcomes of C3GN and MPGN in a cohort of Japanese children. Methods Children who were pathologically diagnosed with MPGN (type I or III) in our hospital were divided into two groups based on immunofluorescence imaging of renal biopsies: children with MPGN induced by classical complement pathway activation (classical MPGN) and children with C3GN. Results Of 14 children with MPGN (five boys), four had classical MPGN, eight had C3GN, and two had unclassifiable glomerulonephritis. Four children with classical MPGN and seven with C3GN received methylprednisolone pulse therapy followed by oral prednisolone for 2 years ( MPT+ PSL therapy). Subsequently, six of seven children with C3GN received combined therapy (prednisolone, azathioprine, and anticoagulants) for 2 years because they responded poorly to MPT+ PSL therapy. At the last follow-up visit, two children with classical MPGN and seven with C3GN had not achieved remission. One child with classical MPGN and five with C3GN had hypocomplementaemia at the last follow-up. None of the children had renal impairment. Conclusion More than half of the patients previously diagnosed with MPGN fulfilled the criteria for C3GN in children. C3GN may be more refractory than classical MPGN to immunosuppressant therapy. [ABSTRACT FROM AUTHOR]

Purpose: To quantitatively evaluate the efficacy of methylprednisolone pulse therapy for extraocular muscle inflammation in thyroid-associated ophthalmopathy (TAO) using the short-tau inversion-recovery (STIR) technique of magnetic resonance imaging (MRI). Methods: The signal intensities of the superior rectus (SR), inferior rectus (IR), lateral rectus (LR), medial rectus (MR), and superior oblique (SO) muscles were measured using the STIR images from 34 eyes of 17 patients with TAO before and after methylprednisolone pulse therapy and 19 eyes of 19 controls. The signal intensity ratio (SIR) of the signal intensity in muscles to that in brain white matter was calculated. Results: The mean SIRs of the controls were 1.08 ± 0.26 in the SR, 1.32 ± 0.29 in the IR, 1.34 ± 0.19 in the LR, 1.47 ± 0.25 in the MR, and 1.28 ± 0.22 in the SO muscles. SIRs exceeding 2.0 were out of the normal range. The SIRs of the patients with TAO before treatment were 2.19 ± 0.64, 2.44 ± 0.58, 1.96 ± 0.43, 2.24 ± 0.47, and 1.91 ± 0.42, respectively, which was significantly ( P < 0.001) higher than those of the controls; after treatment, the mean SIRs were 1.82 ± 0.57, 1.81 ± 0.49, 1.64 ± 0.35, 1.88 ± 0.43, and 1.54 ± 0.33, respectively, significantly ( P < 0.001) lower in all muscles than those before treatment. However, the SIRs of some muscles remained over 2.0. Moreover, all cases that had deterioration of TAO had one or more muscles with a SIR exceeding 2.5 after treatment. Conclusion: Extraocular muscle inflammation in TAO improved with treatment. However, inflammation in some muscles persisted after treatment, and a high SIR in the muscle after treatment suggested the risk of deterioration of TAO. [ABSTRACT FROM AUTHOR]

Hyperosmolar nonketotic hyperglycemic coma (HNKHC) is a serious, rare complication induced by methylprednisolone (MP) pulse therapy for acute rejection after orthotopic liver transplantation (OLT). Herein, we report an unusual case of a 58-year-old woman who experienced acute rejection at 30 months after OLT, only one case in which HNKHC resulted in MP pulse therapy for acute rejection in all 913 recipients in our center. The general morbidity of HNKHC was 1.09% in this study. HNKHC is characterized by rapid onset, rapid progression, and a lack of specific clinical manifestations. High-dose MP management was a clear risk factor. The principle of treatment included rapid rehydration, low-dose insulin infusion, and correcting disorders of electrolytes and acidosis. In conclusion, clinicians considering MP pulse therapy after OLT should be alert to the occurrence of HNKHC. [ABSTRACT FROM AUTHOR]

A 35-year-old female patient was diagnosed with pulmonary arterial hypertension (PAH) by right heart catheterization (RHC) in the 3rd month of systemic lupus erythematosus (SLE) duration with high disease activity. Through methylprednisolone pulse therapy, she got total recovery from PAH proven by repeat catheterization and follow-ups. This is the first simultaneously diagnosed, totally recovered, gold standard-proved SLE-PAH case ever reported in the literature. We would like to share this successful case, and at the same time, we want to highlight the relationship between presentation of PAH and active disease manifestations of SLE patients, and to discuss how immune suppressive treatment could benefit this subset of patients. [ABSTRACT FROM PUBLISHER]

The article presents a case study of a 12-year-old boy was referred to the hospital for hematuria and proteinuria detected via school urine screening. Topics include the high-dose intravenous methylprednisolone pulse therapy has been commonly used to treat various inflammatory, autoimmune, and renal diseases, the dipyridamole (DIP) is used as an antiplatelet drug in combination therapy for pediatric IgA nephropathy, and the overdose of DIP is known to induce myocardial ischemia.

Background: Calcineurin inhibitors (CIs) with/without intravenous methylprednisolone pulse therapy (MPT) constitute the standard treatment for childhood-onset, steroid-resistant nephrotic syndrome (SRNS). However, some patients fail to achieve remission. We treated SRNS patients resistant to CIs and MPT with additional rituximab combined with MPT and immunosuppressive agents. Methods: Ten patients (aged 2-14 years) with CI- and MPT-resistant SRNS were enrolled. Patients were administered rituximab (1-4 doses; 375 mg/m) followed by MPT (30 mg/kg/day of methylprednisolone for 3 consecutive days) once every 2-4 weeks until complete remission (CR). We analyzed clinical outcome and safety. Results: Six patients received a single dose of rituximab, 2 received two doses, and 2 received four doses. Seven patients achieved CR, 1 achieved partial remission, and 2 showed no response. Although 2 patients with no response progressed to end-stage renal failure, 7 patients with CR preserved normal renal function without proteinuria at the last observation. There were two serious adverse events. Conclusions: Additional rituximab combined with conventional MPT and immunosuppressive agents is a promising option for overcoming refractory SRNS. Aggressive B cell suppression by rituximab may ameliorate resistance to conventional treatments and a cocktail of other immunosuppressive agents, such as CIs, MMF, mizoribine, may be beneficial. However, as intense immunosuppression may cause serious adverse events, further evaluation is necessary. [ABSTRACT FROM AUTHOR]