Metagenome-wide association study of gut microbiome revealed potential microbial marker set for diagnosis of pediatric myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is an acquired immune-mediated disorder of the neuromuscular junction that causes fluctuating skeletal muscle weakness and fatigue. Pediatric MG and adult MG have many different characteristics, and current MG diagnostic methods for children are not quite fit. Previous studies indicate that alterations in the gut microbiota may be associated with adult MG. However, it has not been determined whether the gut microbiota are altered in pediatric MG patients. METHODS: Our study recruited 53 pediatric MG patients and 46 age- and gender-matched healthy controls (HC). We sequenced the fecal samples of recruited individuals using whole-genome shotgun sequencing and analyzed the data with in-house bioinformatics pipeline. RESULTS: We built an MG disease classifier based on the abundance of five species, Fusobacterium mortiferum, Prevotella stercorea, Prevotella copri, Megamonas funiformis, and Megamonas hypermegale. The classifier obtained 94% area under the curve (AUC) in cross-validation and 84% AUC in the independent validation cohort. Gut microbiome analysis revealed the presence of human adenovirus F/D in 10 MG patients. Significantly different pathways and gene families between MG patients and HC belonged to P. copri, Clostridium bartlettii, and Bacteroides massiliensis. Based on functional annotation, we found that the gut microbiome affects the production of short-chain fatty acids (SCFAs), and we confirmed the decrease in SCFA levels in pediatric MG patients via serum tests. CONCLUSIONS: The study indicated that altered fecal microbiota might play vital roles in pediatric MG's pathogenesis by reducing SCFAs. The microbial markers might serve as novel diagnostic methods for pediatric MG.

Whole-exome sequencing reveals a rare interferon gamma receptor 1 mutation associated with myasthenia gravis.

Our study is aimed to explore the underlying genetic basis of myasthenia gravis. We collected a Chinese pedigree with myasthenia gravis, and whole-exome sequencing was performed on the two affected siblings and their parents. The candidate pathogenic gene was identified by bioinformatics filtering, which was further verified by Sanger sequencing. The homozygous mutation c.G40A (p.V14M) in interferon gamma receptor 1was identified. Moreover, the mutation was also detected in 3 cases of 44 sporadic myasthenia gravis patients. The p.V14M substitution in interferon gamma receptor 1 may affect the signal peptide function and the translocation on cell membrane, which could disrupt the binding of the ligand of interferon gamma and antibody production, contributing to myasthenia gravis susceptibility. We discovered that a rare variant c.G40A in interferon gamma receptor 1 potentially contributes to the myasthenia gravis pathogenesis. Further functional studies are needed to confirm the effect of the interferon gamma receptor 1 on the myasthenia gravis phenotype.

Metastatic Thymoma-Associated Myasthenia Gravis: Favorable Response to Steroid Pulse Therapy Plus Immunosuppressive Agent.

BACKGROUND Our study retrospectively reviewed the therapeutic effect of steroid pulse therapy in combination with an immunosuppressive agent in myasthenia gravis (MG) patients with metastatic thymoma. MATERIAL AND METHODS MG patients with metastatic thymoma that underwent methylprednisolone pulse therapy plus cyclophosphamide were retrospectively analyzed. Patients initially received methylprednisolone pulse therapy followed by oral methylprednisolone. Cyclophosphamide was prescribed simultaneously at the beginning of treatment. Clinical outcomes, including therapeutic efficacy and adverse effects of MG and thymoma, were assessed. RESULTS Twelve patients were recruited. According to histological classification, 4 cases were type B2 thymoma, 3 were type B3, 2 were type B1, and 1 was type AB. After combined treatment for 15 days, both the thymoma and MG responded dramatically to high-dose methylprednisolone plus cyclophosphamide. The symptoms of MG were improved in all patients, with marked improvement in 6 patients and basic remission in 4. Interestingly, complete remission of thymoma was achieved in 5 patients and partial remission in 7 patients. Myasthenic crisis was observed in 1 patient and was relieved after intubation and ventilation. Adverse reactions were observed in 7 patients (58.3%), most commonly infections, and all were resolved without discontinuation of therapy. During the follow-up, all patients were stabilized except for 1 with pleural metastasis who received further treatment and another 1 who died from myasthenic crisis. CONCLUSIONS The present study in a series of MG patients with metastatic thymoma indicated that steroid pulse therapy in combination with immunosuppressive agents was an effective and well-tolerated for treatment of both metastatic thymoma and MG. Glucocorticoid pulse therapy plus immunosuppressive agents should therefore be considered in MG patients with metastatic thymoma.

Therapeutic Potential of Docetaxel plus Cisplatin Chemotherapy for Myasthenia Gravis Patients with Metastatic Thymoma.

The prognosis of myasthenia gravis (MG) in association with invasive or metastatic thymoma is usually worse, and therapeutic options are quite limited. Here, we retrospectively reported the therapeutic effect of docetaxel plus cisplatin (docetaxel/cisplatin) chemotherapy in 7 MG patients with metastatic thymoma. Previously, all patients underwent thymectomy at the first onset of thymoma. After the metastasis of thymoma, none of the patients received thymectomy due to unresectable conditions after surgeon's evaluation for great risk of myasthenic crisis (n = 5) or patients' refusal (n = 2). All patients received docetaxel (75 mg/m2) and cisplatin (70 mg/m2) on day 1 (d1) every 21 days, with the cycle ranging from 1 to 4. After docetaxel/cisplatin chemotherapy, one patient achieved partial response, and 6 with stable disease of the tumors. The clinical symptoms of MG were alleviated in all patients, 2 with complete remission and the other 5 with marked improvement. Myelosuppression was the major adverse event, occurring in 2 patients (grade II and IV). MG relapse occurred in one patient during the follow-up. Our study presented a series of MG patients with metastatic thymoma who underwent docetaxel/cisplatin chemotherapy. Besides the improved/stabilized thymoma, markedly improvement of MG with the tolerable adverse events was achieved. Docetaxel/cisplatin chemotherapy appears to be an effective treatment for selected patients with MG in association with unresectable metastatic thymoma. Further follow-up of these patients and additional subjects will be needed to determine whether the therapeutic benefits are durable.

Developing and validating a nomogram to predict myasthenia gravis exacerbation in patients with postoperative thymoma recurrence.

Background: Myasthenia gravis (MG) is one of the most common accessory syndromes for thymoma patients. To reduce MG exacerbation and guide clinical practice, we developed a nomogram for predicting MG exacerbation in patients with postoperative thymoma recurrence. Methods: Retrospective study of 176 patients with recurrence following thymoma resection who were admitted to the People's Hospital of Shijiazhuang's Center of Treatment of Myasthenia Gravis between 2013 and 2021. Among them, 120 patients with recurrent thymoma from 2013 to 2020 were selected as the training cohort, and 56 patients in 2021 as the validation cohort. Univariate and multivariate logical regression was used to determine the risk factors and draw the nomogram, and the parameters in the nomogram were proportionally assigned from 0 to 100 points. Finally, the performance of the model is evaluated by internal inspection and external inspection. Results: Multivariate analysis revealed that postoperative treatment plan and the pathologic classification of the thymoma were independent predictors of MG exacerbation in the training cohort (n=120), so they were used to create the nomogram, which had a well-fit calibration curve and good concordance index of 0.77 [95% confidence interval (CI): 0.69-0.86] for the training cohort and 0.74 (95% CI: 0.58-0.91) for the validation cohort, respectively. Calculations were made to determine the nomogram's sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV). The training cohort were 75.7% (95% CI: 66.1-83.4%), 64.7% (95% CI: 38.6-84.7%), 92.9% (95% CI: 84.5-97.1%) and 30.6% (95% CI: 16.9-48.3%) respectively, while the corresponding validation cohort were 84.1% (95% CI: 69.3-92.8%), 66.7% (95% CI: 35.4-88.7%), 90.2% (95% CI: 75.9-96.8%) and 53.3% (95% CI: 27.4-77.7%) respectively. Conclusions: We identified the risk factors for MG exacerbation in patients with postoperative recurrence of thymoma and drew a nomogram, which can be used to calculate the probability of MG exacerbation and guide clinicians to choose post-operative treatment.

Effect of Jianpiyiqi granule on ocular myasthenia gravis in children prepared with a formula from Traditional Chinese Medicine.

OBJECTIVE: To investigate the effect of Jianpiyiqi granule, prepared according to a Traditional Chinese Medicine (TCM) formula, on the ocular type of myasthenia gravis (MG) caused by a defect in synaptic transmission at the neuromuscular junction. METHODS: A total of 155 children with ocular MG were recruited from January 2008 to January 2015. All individuals received ineffective glucocorticoid treatment prior to admission, and were given Jianpiyiqi granules (two doses per day) for 12 months. Plasma levels of acetylcholine receptor autoantibodies (AChR-Ab), cytokines, immune parameters and clinical score were analyzed. RESULTS: After intervention with Jianpiyiqi granule for 12 months, the levels of cytokines [including interleukin (IL)-6, IL-12, IL-17], immune parameters [including immunoglobulin G (IgG), IgM, free triiodothyronine, free thyroxine] and AChR-Ab were significantly decreased (P = 0.042, P = 0.049, P = 0.011, P = 0.02, P = 0.04, P = 0.03, P = 0.01; F = 21.60, P = 0.000). In contrast, IL-4 levels were significantly increased (P = 0.049). The absolute clinical score after treatment declined significantly compared with before treatment (F = 33.24, P = 0.000). The effective cure rate and the total effective rate gradually increased to a maximum of 149 (96.2%) and 151 (97.4%) in MG patients after 12 months of treatment, respectively. CONCLUSION: The Jianpiyiqi granule treatment lowered AChR-Ab levels and improved cytokine and other immune parameter levels, which suggests that the granule could be an ancillary treatment for ocular MG in children caused by a defect in synaptic transmission at the neuromuscular junction.

Docetaxel/cisplatin Therapy in Myasthenia Gravis with Hypertension/diabetes.

BACKGROUND: Therapeutic options for thymoma-associated myasthenia gravis (MG) patients complicated with hypertension and/or diabetes post thymectomy are often conventional steroids. As the prevalence of diabetes and hypertension globally increases, other therapeutic options for these patients are of great importance. MATERIAL/METHODS: 9 patients with thymoma-associated MG complicated with hypertension and/or diabetes after thymectomy were administered 75 mg/m2 of docetaxel and 70 mg/m2 of cisplatin on day 1. The treatment could be repeated at 3-week intervals, ranging from 1 to 4 cycles according to the status of the patients. Therapeutic efficacy and side effects were evaluated. RESULTS: 2 patients were complicated with type 2 diabetes, 6 with hypertension, and 1 with both diabetes and hypertension. After docetaxel/cisplain therapy, the MG symptoms were markedly improved in all patients (2, complete remission; 3, basic remission; 3, marked improvement; 1, improvement). Acetylcholine receptor (AchR) antibody levels were decreased in 8 patients. Minor adverse effects were observed in 2 patients, 1 with Grade II gastrointestinal reaction, and the other with pulmonary infection. CONCLUSION: Docetaxel plus cisplatin might be an effective therapeutic option for thymoma-associated MG patients complicated with hypertension /diabetes post thymectomy without worsening thymoma and hypertension / diabetes.

[Observation on therapeutic effect of chronic prostatitis treated mainly by warming needle moxibustion].

OBJECTIVE: To explore an effective method for increasing therapeutic effect on chronic prostatitis. METHODS: Eighty-two cases of chronic prostatitis were randomly divided into two groups. The western medicine group of 42 cases were treated with routine western medicine combined with retention enteroclysis of 30 g Danshen (Red Sage Root) decoction; the warming needle moxibustion plus western medicine group of 40 cases were treated with the western medicine of the western medicine group plus warming needle moxibustion at Guanyuan (CV 4), Qihai (CV 6) and Zhongji (CV 3), etc. RESULTS: In the warming needle moxibustion plus western medicine grbup, 20 cases were cured, 12 cases were markedly effective, 5 cases were effective and 3 cases were ineffective, the total effective rate being 92. 5%; and in the western medicine group, the corresponding figures were 13, 10, 7, 12 cases and 71.4%, with a significant difference between the two groups in the total effective rate (P < 0.05). CONCLUSION: Warming needle moxibustion can increase the therapeutic effect on chronic prostatitis.