Serum amyloid A facilitates expansion of CD4+ T cell and CD19+ B cell subsets implicated in the severity of myasthenia gravis patients.

Serum amyloid A (SAA) is a clinically useful inflammatory marker involved in the pathogenesis of autoimmune diseases. This study aimed to explore the SAA levels in a cohort of patients with myasthenia gravis (MG) in relation to disease-related clinical parameters and myasthenic crisis (MC) and elucidate the effects of SAA on immune response. A total of 82 MG patients including 50 new-onset MG patients and 32 MC patients were enrolled in this study. Baseline data and laboratory parameters of all enrolled MG patients were routinely recorded through electronic medical systems. SAA levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. CD4+ T and CD19+ B cell subsets were analyzed by flow cytometry. In vitro, human recombinant SAA (Apo-SAA) was applied to stimulate peripheral blood mononuclear cells (PBMCs) from MG patients to observe the effect on T and B cell differentiation. Our results indicated that SAA levels in new-onset MG patients were higher than those in controls and were positively correlated with QMG score, MGFA classification, plasmablast cells, IL-6, and IL-17 levels. Subgroup analysis revealed that SAA levels were increased in generalized MG (GMG) patients than in ocular MG (OMG), as well as elevated in late-onset MG (LOMG) than in early-onset MG (EOMG) and higher in MGFA III/IV compared with MGFA I/II. The ROC curve demonstrated that SAA showed good diagnostic value for MC, especially when combined with NLR. In vitro, Apo-SAA promoted the Th1 cells, Th17 cells, plasmablast cells, and plasma cells differentiation in MG PBMCs. The present findings suggested that SAA was increased in MG patients and promoted expansion of CD4+ T cell and CD19+ B cell subsets, which implicated in the severity of MG patients.

Exploring Potential Biomarkers of Early Thymoma based on Serum Proteomics.

BACKGROUND: Early diagnosis remains difficult because the early symptoms of thymoma are atypical. OBJECTIVES: This study aimed to analyze the changes of serum proteins in the early stage of thymoma (stage I/II) by proteomics method and to screen and validate candidate biomarkers. METHODS: Proteins were extracted from 8 sera patients with stage I/II thymoma and 9 healthy controls. The levels of serum proteins were detected by data-independent acquisition (DIA) quantitative proteomics techniques, and the differential proteins were identified. The proteomic results were verified by enzyme-linked immunosorbent assay. Additionally, differentially expressed proteins were analyzed using receiver operating characteristic curves (ROC). RESULTS: There were 80 differentially expressed proteins between the patients with thymoma and the healthy control group, among which 39 were up-regulated and 41 were down-regulated. Differential protein enrichment is involved in environmental information processing, signaling molecules and interactions, and in the body system and the immune system. The analysis of receptor working characteristic curves showed that the areas under the curve of CORO1A, SAA1 and LTA4H were all larger than 0.8, indicating that these proteins had good diagnostic value. CONCLUSION: CORO1A, SAA1 and LTA4H may be new biomarkers for early screening of thymoma.

POTEE mutation as a potential predictive biomarker for immune checkpoint inhibitors in lung adenocarcinoma.

Precise selection of patients who could benefit from immune checkpoint inhibitors (ICIs) is an important challenge for immunotherapy in lung cancer. POTEE (POTE Ankyrin Domain Family Member E) is a member of one primate-specific gene family which have been identified as cancer-related antigens and potential target for immunotherapy of cancer. Here, we investigated the correlation between POTEE mutation and the clinical outcome of ICIs treatment in non-small cell lung cancer (NSCLC). We merged three NSCLC cohorts (n = 165) to assess predictive value of POTEE mutation of immunotherapy efficacy in NSCLC. The prognostic analysis and the potential molecular mechanism exploration were conducted based on the data from The Cancer Genome Atlas (TCGA) database. In the merged cohort, patients with POTEE-mutation (POTEE-Mut) had a significantly higher objective response rate (ORR) (100% vs 27.7%; P < 0.001) and longer progression-free survival (PFS) (P = 0.001; HR 0.08; 95% CI 0.01 - 0.54) compared to patients with POTEE wild-type (POTEE-WT) in NSCLC. Also, patients with POTEE-Mut showed higher ORR (100% vs 27.2%; P < 0.001) and longer PFS (P = 0.001; HR 0.07; 95% CI 0.01 - 0.52) in lung adenocarcinoma (LUAD). POTEE mutation was significantly associated with higher tumor mutational burden (TMB) and higher neoantigen load (NAL), but not with PD-L1 expression in LUAD. Gene set enrichment analyses (GSEA) analysis revealed prominent enrichment of signatures related to DNA repair in POTEE-Mut group (P < 0.001) in LUAD. Our results indicate that POTEE mutation could serve as a potential predictive biomarker for ICIs in LUAD. However, prospective cohort studies are still needed for further validation.

Proteomics analysis of serum from thymoma patients.

Thymoma is the most common malignant tumor in thymic epithelial tumors (TETS). This study aimed to identify the changes in serum proteomics in patients with thymoma. Proteins were extracted from twenty patients with thymoma serum and nine healthy controls and prepared for mass spectrometry (MS) analysis. Data independent acquisition (DIA) quantitative proteomics technique was used to examine the serum proteome. Differential proteins of abundance changes in the serum were identified. Bioinformatics was used to examine the differential proteins. Functional tagging and enrichment analysis were conducted using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The string database was used to assess the interaction of different proteins. In all, 486 proteins were found in all samples. There were differences in 58 serum proteins between patients and healthy blood donors, 35 up-regulated and 23 down-regulated. These proteins are primarily exocrine and serum membrane proteins involved in controlling immunological responses and antigen binding, according to GO functional annotation. KEGG functional annotation showed that these proteins play a significant role in the complement and coagulation cascade and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signal pathway. Notably, the KEGG pathway (complement and coagulation cascade) is enriched, and three key activators were up-regulated: von willebrand factor (VWF), coagulation factor v (F5) and vitamin k-dependent protein c (PC). Protein-protein interaction (PPI) analysis showed that six proteins ((VWF, F5, thrombin reactive protein 1 (THBS1), mannose-binding lectin-associated serine protease 2 (MASP2), apolipoprotein B (APOB), and apolipoprotein (a) (LPA)) were up-regulated and two proteins (Metalloproteinase inhibitor 1(TIMP1), ferritin light chain (FTL)) were down-regulated. The results of this study showed that several proteins involved in complement and coagulation cascades were up-regulated in the serum of patients.

Identification of Potential Serum Protein Biomarkers in Thymoma with Myasthenia Gravis After Docetaxel Treatment.

INTRODUCTION: Myasthenia gravis (MG) is a devastating acquired autoimmune disease that can seriously affect the patient's quality of life. It is also a common complication of thymoma. Previous studies have shown that docetaxel alleviates myasthenic symptoms in thymoma with MG (TMG). However, little is known about the protein expression profiles and biomarkers for efficacy after docetaxel treatment. METHODS: We recruited 9 healthy controls and 30 patients with TMG for the serum proteomics study with data-independent acquisition (DIA) technology. We further recruited additional 30 patients for the key protein validation by enzyme-linked immunosorbent assay (ELISA). RESULTS: We identified 43 proteins by trend analysis and analyzed the interaction between these proteins and MG pathogenic proteins from the DisGNET database and the correlation analysis with clinical data of patients with TMG. Among these, KRAS and SELP were screened out and validated. KRAS and SELP increased in patients with TMG and decreased significantly after docetaxel treatment. CONCLUSIONS: Our study revealed that the serum proteins were differentially expressed after docetaxel treatment, suggesting their important role in patients with TMG, as well as the critical role of KRAS and SELP as biomarkers in evaluating the efficacy of docetaxel treatment.

Anxiety and depression in thymoma patients in China before surgery.

BACKGROUND: The study's goal was to investigate the percentage of anxiety and depression in Chinese thymoma patients before surgery, and also the factors that influence it. METHODS: The study included patients who had an anterior mediastinal mass discovered by chest CT and were scheduled for video-assisted thoracoscopic surgery. The mental health rating scales were completed by all patients before surgery. Patients were divided into two groups based on the Hospital Anxiety and Depression Scale (HADS): anxiety/depression and non-anxiety/depression. The association between thymoma clinical factors and the HADS score was studied statistically. RESULTS: The study comprised eighty patients with thymoma. Before the operation, 22.5% (18/80) of the patients had anxiety and/or depression. The resigned coping style characteristics, along with myasthenia gravis (MG), were associated with preoperative anxiety and depression. The greater the score of the resigned dimension, the greater the risk of anxiety and depression, based on the results of logical regression analysis. Thymoma patients with myasthenia gravis have a higher risk of anxiety and depression. CONCLUSION: Patients with myasthenia gravis and resigned coping style were found to have higher anxiety and depression before surgery for Chinese thymoma patients.

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.

Prognostic factors for overall survival after surgical resection in patients with thymic epithelial tumors: A systematic review and meta-analysis.

BACKGROUND: Thymic epithelial tumors (TETs) originate in the thymic epithelial cell, including thymoma and thymic carcinoma. Surgical resection is the first choice for most patients. However, some studies have shown that the factors affecting the prognosis of these patients are not consistent. To evaluate prognostic factors in patients with surgically resected thymic epithelial tumors, we performed a meta-analysis. METHODS: We searched the Chinese biomedical literature database, Pubmed, Embase, Cochrane Library and other electronic databases. Studies including postoperative overall survival (OS) and predictors of TETs were included. We made a comprehensive analysis the hazard ratios (HRs) through a single proportional combination. HRs were combined using single proportion combinations. RESULTS: The meta-analysis included 11,695 patients from 26 studies. The pooled OS was 84% at 5 years and 73% at 10 years after TETs operation. The age as continuous-year (HR 1.04, 95% confidence interval (CI) 1.02-1.04), incomplete resection (HR 4.41, 95% CI 3.32-5.85), WHO histologic classification (B2/B3 vs A/AB/B1 HR 2.76, 95% CI 1.25-6.21), Masaoka Stage (stage III/IV vs I/II HR 2.74, 95% CI 2.12-3.55,) were the poor prognostic factors. CONCLUSIONS: For patients with TETs after surgical resection, advanced age, incomplete resection, WHO classification B2/B3, and higher Masaoka stage are risk factors for poor prognosis.

Observation on the efficacy of different methylprednisolone regimens in the treatment of myasthenia gravis.

Objective: To investigate the efficacy of different methylprednisolone regimens in the treatment of myasthenia gravis (MG). Methods: A total of 98 patients with MG admitted to Shijiazhuang People's Hospital from December 2018 to November 2019 were randomly divided into two groups, with 49 cases in each group. Patients in the control group received high-dose methylprednisolone pulse therapy, while those in the experimental group received medium-dose periodic therapy of methylprednisolone. Anti-acetylcholine receptor antibodies (AChRab), clinical absolute scores, complement levels (C3, C4), T lymphocyte subsets (CD3+, CD4+, CD4+CD25+), cytokines [interferon-γ (INF-γ), transforming growth factor-ß1 (TGF-ß1), interleukin-6 (IL- 6), interleukin-18 (IL-18)], and changes in quality of life [15-item Myasthenia Gravis Quality of Life Scale (MGQOL-15) score] were compared between the two groups before treatment and one and three months after treatment. Moreover, the incidence of adverse drug reactions in the two groups during 3 months of treatment was compared. Results: After three months of treatment, ACHRAB, clinical absolute score, CD3+, CD4+, INF-γ, IL-6, IL-18 and MGQOL-15 scores in both groups were significantly decreased compared with those before treatment (p<0.05), and the scores of C3, C4, CD4+CD25+ and TGF-ß1 in both groups were significantly higher than those before treatment (p<0.05), and the experimental group had more significant changes than the control group (p<0.05). During three months of treatment, the total incidence of adverse drug reactions in the experimental group was significantly lower than that in the control group (p<0.05). Conclusions: The medium-dose periodic therapy of methylprednisolone is more prominent in the long-term efficacy performance. It can improve the immunity and quality of life of patients, and it is safer and has high clinical application value.

Analysis of clinical features of myasthenia gravis complicated with hyperthyroidism.

Objectives: To investigate the clinical features of patients with myasthenia gravis complicated with and without hyperthyroidism. Methods: A total of 2083 patients with myasthenia gravis (MG) admitted in Center of Treatment of Myasthenia Gravis Hebei Province between January 2013 and July 2020 were retrospectively analyzed and divided into two groups: Group-A and Group-B, with 108 MG patients complicated with hyperthyroidism in Group-A and 1975 MG patients without thyroid disease in Group-B. The age of onset, gender, Osserman classification, acetylcholine receptor antibody and thymus status of the two groups were analyzed in the two groups. Independent-sample t test was used for intra-group comparison, and χ2 test was utilized for comparison of enumeration data. P<0.05 indicates a statistically significant difference. Results: The age of onset in Group-A was significantly lower than that in Group-B (p=0.000), the number of female patients was significantly higher than that in Group-B (p=0.037), and the level of Achrabs titer was significantly lower than that in Group-B (p=0.000). The incidence of thymoma in Group-A was significantly lower than that in Group-B (p=0.012), while the incidence of thymic hyperplasia was significantly higher than that in Group-B (p=0.000). Conclusion: Patients with MG complicated with hyperthyroidism are mainly female, with a lower age of onset, a lower level of acetylcholine receptor antibody, a lower incidence of thymoma, and a higher incidence of thymic hyperplasia. The clinical features of such patients are remarkably different from those of MG without thyroid disease.

Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis.

Background: Myasthenia gravis (MG) is an acquired autoimmune disease of the neuromuscular junction. As immunosuppressive agents used to treat MG have a significant impact on the growth and development of children, treatment is extremely challenging. Jianpi Yiqi Bugan Yishen Decoction (JYBYD) has been developed to treat MG and has achieved satisfactory results in clinical practice. This study aimed to explore its action mechanism and evaluate its active ingredients and potential therapeutic targets. Methods: Single-cell transcriptome sequencing of peripheral blood immune cells of children with MG was performed to reveal the changes in immune cell profiles before and after JYBYD treatment. Lewis rats were included in the model, with classic MG induced by subcutaneous injection of the immunogen acetylcholine receptor (AChR). Twenty rats were divided into two groups and administered normal saline and JYBYD by gavage daily. Results: An increase in cell populations characterized by cortactin expression was observed, which has a potential effect on the recovery of lesions at the neuromuscular junction in patients with MG. Based on the differential expression of genes in various immune cells and the predicted targets of traditional Chinese medicine (TCM) compounds, the possible therapeutic targets of JYBYD in different cell subsets were identified, among which STAT1, MCL1, and FOS were the most frequent. Comprehensive network pharmacological analysis suggested quercetin, luteolin, and resveratrol as important active ingredients of JYBYD for the treatment of children with MG. JYBYD could relieve myasthenia symptoms and reduce the AChR-Ab titer in the rat model. Immunohistochemistry results of the muscle showed that JYBYD treatment decreased the expression of STAT1, MCL1, and c-FOS proteins in the muscles of MG rat models. Conclusions: The results of this study are of significance for the clinical application of JYBYD and drug development against MG in children.

Effect of Buzhong Yiqi decoction on anti-acetylcholine receptor antibody and clinical status in juvenile ocular myasthenia gravis.

ABSTRACT: Ocular myasthenia gravis (MG) is the mainly widespread type of MG among juveniles. Buzhong Yiqi decoction (BZ) is a well-known traditional Chinese medicine prescription for treating MG. It has rarely been discussed whether the concentration of anti-acetylcholine receptor (AChR) antibodies is related to the clinical status of juvenile ocular myasthenia gravis (JOMG) treated with BZ.The patients with JOMG who had more than once AChR-antibody (ab) test and treated with BZ were retrospectively identified from June 2013 to January 2020 in the first hospital in Shijiazhuang. The presence or absence of ocular symptoms was used to grade the effectiveness of treatment. Generalized estimating equations logistic regression analysis was used to evaluate the effect of AChR ab concentration on the clinical status of MG.A total of 549 AChR-ab tests were performed in 135 patients, and the corresponding clinical status was recorded. One hundred two patients received treatment with BZ only and 33 combined with immunosuppressive drugs. In the group receiving only BZ treatment, the anti-acetylcholine receptor ab concentration was positively correlated with the clinical score after treatment.The results suggest that BZ could affect the AChR-ab. Repeated AChR-ab assays can provide information about the clinical status. For JOMG patients who only receive Buzhong Yiqi Decoction treatment, this can support treatment decisions.

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.

Efficacy and safety of double-filtration plasmapheresis treatment of myasthenia gravis: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the efficacy of double-filtration plasmapheresis (DFPP) treatment of myasthenia gravis (MG) through a systematic review and meta-analysis. METHODS: PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) on DFPP for MG from database establishment to June 2019. Two researchers independently screened the articles, extracted the data, and cross checked the results. RevMan 5.3 was used for statistical analyses. RESULTS: Seven RCTs and 2 CCTs were found comprising 329 patients. The results showed that clinical MG remission rate after DFPP treatment was significantly higher (OR = 4.33; 95% confidence interval [CI], 1.97-9.53; P < .001) and the serum levels of antititin antibody was significantly decreased (standardized mean difference [SMD] = 9.30; 95% CI, 7.51-11.08; P < .001). In addition, the quantitative MG (QMG) score, hospital stay and time to remission of MG symptoms, and acetylcholine receptor antibody (AchRAb) decreased in the DFPP treatment group; however, these outcomes had high heterogeneity among the studies. Only one study has reported on the adverse effects, including hypotension and hematoma. CONCLUSION: This meta-analysis suggests that DFPP can be recommended for the short-term mitigation of MG. Because our review was limited by the quantity and quality of the included studies, the above conclusions should be verified by additional high-quality studies.

Assessment of the risks of a myasthenic crisis after thymectomy in patients with myasthenia gravis: a systematic review and meta-analysis of 25 studies.

BACKGROUND: Despite the burgeoning literature describing preoperative and postoperative risks of a myasthenic crisis after thymectomy (MCAT) in patients with myasthenia gravis, substantial differences exist in the risk factors identified by previous studies. We conducted a meta-analysis to assess the reported risk factors and MCAT risk. METHODS: We collected relevant studies on the risk factors for MCAT by searching the PubMed, Embase, The Cochrane Library, China Biology Medicine (CBM), WanFang Data, VIP and CNKI databases. The search period ranged from the establishment of the database to November 2019. RESULTS: Twenty-five of the 458 identified studies were eligible for the meta-analysis. Seven retrospective cohort studies and 18 case-control studies were included, and 14 risk factors for MCAT were extracted. Meta-analyses of the association between MCAT and risk factors related to the patient's preoperative condition included a preoperative history of MC, preoperative bulbar symptoms, IIa + IIb + III + VI, IIb + III + VI, VI + V, dosage of pyridostigmine bromide prior to the operation, a preoperative AchR-Ab level > 100 (nm/L), preoperative pulmonary function, preoperative complications, and preoperative disease course. Meta-analyses of the association between MCAT and surgery-related risk factors included intraoperative blood loss > 1000 mL and the mode of operation. Meta-analyses of the association between MCAT and postoperative risk factors included postoperative lung infection, thymoma and the WHO classification. The operation time was not an independent risk factor for MCAT. CONCLUSIONS: The independent risk factors for MCAT were a preoperative history of MC, preoperative bulbar symptoms, preoperative MG Osserman stage, preoperative dosage of pyridostigmine bromide, preoperative serum AchR-Ab level, lung function, major postoperative complications, disease duration before thymectomy, blood loss, thoracotomy, postoperative lung infection, thymoma, and WHO classification.

Meta-analysis of subxiphoid approach versus lateral approach for thoracoscopic Thymectomy.

BACKGROUND: Compared with traditional open surgery for thymectomy, video-assisted thoracoscopic surgery (VATS) reduces hospital stay, decreases postoperative pain, and recovers faster. VATS has become increasingly popular in the past decade. VATS techniques to perform a thymectomy include subxiphoid video-assisted thoracoscopic surgery (SVATS) or lateral video-assisted thoracoscopic surgery (LVATS). In this study, our objective was to systematically review on VATS thymectomy and draw a meta-analysis on the outcomes between the two approaches. METHODS: We searched online databases and identified studies from database inception to 2019 that compared SVATS to LVATS thymectomy. Study endpoints included operative time, operative blood loss, length of hospital stay, postoperative pleural drainage, postoperative complications, conversion to open, oncologic outcomes. RESULTS: Four hundred seventy-one patients were included in this study, for which 200 and 271 patients underwent SVATS and LVATS thymectomy, respectively. Patients in the SVATS group had significantly less operative time, operative blood loss, length of hospital stay, and postoperative complications were identified. There was no statistical difference in postoperative pleural drainage, conversion to open and oncologic outcomes. No hospital deaths were recorded for either procedure. CONCLUSIONS: While randomized controlled studies are required to make definitive conclusions, this meta-analysis suggests that SVATS thymectomy is safe and can achieve good and safe operative and perioperative outcomes similar or better to LVATS thymectomy.

Is chest tube drainage necessary after subxiphoid thoracoscopic thymectomy?

BACKGROUND: Subxiphoid thoracoscopic thymectomy has been increasingly performed in recent years. This study aimed to assess the differences in outcomes between subxiphoid thoracoscopic thymectomy with and without chest tube drainage. METHODS: Overall, 205 subxiphoid thoracoscopic thymectomy operations were performed for myasthenia gravis, including 90 cases without and 115 cases with chest tube drainage. The clinical characteristics and perioperative outcomes of the patients were compared. RESULTS: The patients included 112 women and 93 men, with a mean age of 41 years. Two patients in the group without and 5 patient in the group with chest tube drainage developed dyspnea. In the group without chest tube, 6 patients had residual pneumothorax or pleural effusion and had a thoracentesis after surgery (6/90). In the group with chest tube, 7 patients developed delayed pleural effusion and had a thoracentesis after chest tube removal (7/115). The patients in the group without chest tube drainage group yielded lower pain scores. CONCLUSIONS: The omission of chest tube drainage may be a feasible and safe choice for patients with myasthenia gravis undergoing subxiphoid thoracoscopic thymectomy, but further prospective studies are required.

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.

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.

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.