Batoclimab vs Placebo for Generalized Myasthenia Gravis: A Randomized Clinical Trial.

Importance: Myasthenia gravis (MG) is caused by autoantibodies that disrupt the neuromuscular junction. The neonatal fragment crystallizable receptor (FcRn) antagonists, efgartigimod and rozanolixizumab, reduce immunoglobulin G (IgG) level in the circulation and alleviate symptoms in patients with generalized MG. Objective: To examine the efficacy and safety profile of batoclimab, a monoclonal IgG1 antibody, in patients with generalized MG. Design, Setting, and Participants: This was a multicenter randomized clinical trial conducted from September 15, 2021, to June 29, 2022, at 27 centers in China. Adult patients 18 years or older with generalized MG were screened, and those who were antibody positive were enrolled. Intervention: Eligible patients received batoclimab or matching placebo in addition to standard of care. Each treatment cycle consisted of 6 weekly subcutaneous injections of batoclimab, 680 mg, or matching placebo followed by 4 weeks of observation. A second treatment cycle was conducted in patients who required continuing treatment. Main Outcome and Measure: The primary outcome was sustained improvement, as defined by a 3-point or greater reduction in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline for 4 or more consecutive weeks in the first cycle in individuals who were positive for acetylcholine receptor or muscle-specific kinase antibodies. Results: A total of 178 adult patients with generalized MG were screened, 132 were randomly assigned, 131 tested positive for antibodies, and 1 tested negative for antibodies. A total of 132 patients (mean [SE] age, 43.8 [13.6] years; 88 women [67.2%]) were enrolled. The rate of sustained MG-ADL improvement in the first cycle in antibody-positive patients was 31.3% (20 of 64) in the placebo group vs 58.2% (39 of 67) in the batoclimab group (odds ratio, 3.45; 95% CI, 1.62-7.35; P = .001). The MG-ADL score diverged between the 2 groups as early as week 2. The mean (SE) maximum difference in MG-ADL score reduction occurred 1 week after the last dose (day 43, 1.7 [0.3] in the placebo group vs 3.6 [0.3] in the batoclimab group; group difference, -1.9; 95% CI, -2.8 to -1.0; nominal P < .001). The rates of treatment-related and severe treatment-emergent adverse events in patients were 36.9% (24 of 65) and 7.7% (5 of 65) in the placebo group vs 70.1% (47 of 67) and 3.0% (2 of 67) in the batoclimab group, respectively. Conclusions and Relevance: Batoclimab increased the rate of sustained MG-ADL improvement and was well tolerated in adult patients with generalized MG. Clinical effects and the extent of IgG reduction were similar to those previously reported for efgartigimod and rozanolixizumab. Future studies of large sample size are needed to further understand the safety profile of batoclimab. Trial Registration: ClinicalTrials.gov Identifier: NCT05039190.

Case report: Mononeuropathy multiplex of extranodal natural killer/T-cell lymphoma misdiagnosed as systemic vasculitis.

Background: Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive non-Hodgkin lymphoma that typically develops in the upper aerodigestive tract. Case presentation: We encountered an ENKTL patient who presented with purpura-like rashes and foot drops as initial symptoms and later developed other peripheral nerve involvement. The nerve conduction study of both the motor nerve and the sensory nerve showed axonal damage resembling mononeuropathy multiplex. Although the initial response to steroids was encouraging, the patient's symptoms reappeared and aggravated. A biopsy of the abdominal subcutaneous fat tissue with additional immunohistochemistry revealed neoplastic NK/T lymphocytes. Conclusion: We reported the first case presented as mononeuropathy multiplex as the initial clinical manifestation in ENKTL patients. Lymphoma should be considered in the diagnosis of atypical mononeuropathy in multiplex patients.

Differentiation Between Amyotrophic Lateral Sclerosis and Mimics Using Quantitative Analysis of Fsciculation with Muscle Ultrasound.

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis (ALS). Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020. Healthy adults from a community were recruited as healthy controls. Muscle strength was assessed using the Medical Research Council (MRC) scale. At the first visit to the hospital, patients were assessed for maximal grade of fasciculations, total fasciculation score, and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography. The sensitivity and specificity of maximal grade of fasciculations, total fasciculation score, and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses. Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9% and 9.8%, respectively (χ2 = 172.436, P < 0.01). Of the 16 limb muscles detected, the total fasciculation score [median (interquartile range)] was 29 (15, 41) in ALS patients and 3 (0, 8) in neuropathy-radiculopathy patients (Z = 9.642, P < 0.001). Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4, followed by patients with MRC score 5, and then in those with MRC score 0 and 1. The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6% and 93.4%, respectively (cut-off value 14). In patients with ALS, for muscles with MRC score 4 and 5, the percentage of muscles with fasciculation grades ≥ 3 was 42.3% and 24.1% respectively, while in neuropathy-radiculopathy patients, the percentage for muscles with MRC score 4 and 5 was only 1.7% and 0, respectively. Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.

Treatment of insomnia in myasthenia gravis-A prospective study on non-benzodiazepine hypnotics in the treatment of myasthenia gravis patients with insomnia.

Objectives: This study aimed to evaluate the efficacy and safety of non-benzodiazepine hypnotics in the treatment of myasthenia gravis (MG) patients with insomnia. Methods: This is a prospective longitudinal study. Outpatients who met the criteria for stable MG and insomnia diagnosis according to the International Classification of Sleep Disorders (third edition) were included in the study. They took a regular dose of non-benzodiazepine hypnotics (zolpidem 10 mg per night or zopiclone 7.5 mg per night) based on their own preferences. Patients received psychotherapy (including sleep health education) and were followed up for 4-5 weeks. Cases with lung diseases, respiratory disorders, or inappropriate use of hypnotic medications were excluded. The primary outcome is the difference in total Pittsburgh Sleep Quality Index (PSQI) score between baseline and the end of follow-up period. Secondary outcomes include the difference in Myasthenia Gravis Activities of Daily Living (MG-ADL) score, 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9) between baseline and the end of follow-up period and the safety of medication. Results: A total of 75 MG patients with insomnia were included in this study. After 4-5 weeks of treatment, the total PSQI score and MG-ADL score were lower than baseline (p < 0.01). No patients had an increased MG-ADL score. The incidence rate of adverse events was 16.0% (12 cases), including dizziness (6 cases, 8.0%), drowsiness (3 cases, 4.0%), fatigue (2 cases, 2.7%), and nausea (1 case, 1.3%), all of which were mild. No patients had new onset breathing disorders. Conclusion: Non-benzodiazepine hypnotics are safe and effective for stable MG patients who need insomnia treatment.

The cross-sectional area of peripheral nerve in amyotrophic lateral sclerosis: A case-control study.

OBJECTIVE: A growing body of literature recognises the importance of peripheral nerve ultrasound in neuromuscular disorders. Several attempts have been made to differentiate amyotrophic lateral sclerosis (ALS) from multifocal motor neuropathy (MMN) using peripheral nerve ultrasound. A much-debated question is whether the cross-sectional area (CSA) of peripheral nerve in ALS patients is significantly smaller compared to healthy controls. This study aims to determine the CSA of peripheral nerves in patients with ALS. METHODS: One hundred and thirty-nine patients with ALS and 75 healthy controls were recruited. Ultrasound of the median, ulnar, and trunks of the brachial plexus and cervical nerve roots was undertaken in ALS patients and controls. RESULTS: Compared to controls, ALS patients had mild reductions of the median nerve, most sites of the ulnar nerve, trunks of the brachial plexus and cervical nerve roots. Another important finding of this study is that the median nerve tends to have a more significant reduction than the ulnar nerve in ALS patients, especially at the proximal. CONCLUSIONS: Ultrasound could be sensitive to nerve motor fibre loss in patients with ALS. CSA at the proximal Median nerve may be a promising biomarker in patients with ALS.

Iron metabolism in non-anemic myasthenia gravis patients: A cohort study.

BACKGROUND: The association of iron metabolism parameters with disease severity and outcome in myasthenia gravis (MG) patients has not been reported. This study was conducted to determined clinical factors including iron metabolism parameters correlated with disease severity and future outcome in non-anemic immunotherapy-naïve MG patients first receiving immunotherapy. MATERIAL AND METHODS: One hundred and ten patients were included at baseline to explore predictor variables associated with disease severity represented by variables derived from MG activities of daily living (MG-ADL) score using multivariate logistic regression, after which 103 and 98 patients were included respectively in multivariate survival analyses at 6-month and 12-month follow-up to identify predictors for minimal manifestation status (MMS) after starting immunotherapy. RESULTS: Higher ferritin level was independently associated with higher risk of severe generalized disease in non-anemic immunotherapy-naïve MG patients. Total iron binding capacity <250 µg/dL and the interval between onset and immunotherapy <1 year were independent predictors for MMS at 6-month and 12-month follow-up after initiating immunotherapy. Transferrin <2.00 g/L was an independent predictor for MMS at 12-month follow-up. CONCLUSION: Iron metabolism parameters might be promising biomarkers for evaluating disease severity and guiding therapeutic decision in MG patients.

Treatment of primary progressive aphasia by repetitive transcranial magnetic stimulation: a randomized, double-blind, placebo-controlled study.

To evaluate the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) in patients with primary progressive aphasia (PPA). In this randomized, double-blind trial in a single center, patients who were diagnosed with PPA were randomly assigned to receive either real rTMS or sham rTMS treatment. High-frequency rTMS was delivered to the dorsolateral prefrontal cortex (DLPFC). The primary outcome was the change in Boston Naming Test (BNT) score at each follow-up compared to the baseline. The secondary outcomes included change in CAL (Communicative Activity Log) and WAB (Western Aphasia Battery) compared to baseline and neuropsychological assessments. Forty patients (16 with nonfluent, 12 with semantic and 12 with logopenic variant PPA) were enrolled and randomly assigned to the rTMS or sham rTMS group, with 20 patients in each group. Thirty-five patients (87.5%) completed a 6-month follow-up. Compared to the sham rTMS group, the BNT improvement and WAB improvement in the real rTMS group were significantly higher. These significant improvements could be observed throughout the entire 6-month follow-up. At 1 month and 3 months after treatment, CAL improvements of real rTMS were significantly higher than sham rTMS. The improvements in BNT, CAL and WAB did not significantly differ among PPA variants. No significant improvement in neuropsychological assessments was observed. High-frequency rTMS delivered to DLPFC improved language functions in patients with different PPA variants. The efficacy was still observed after 6 months of treatment. Trial registration: NCT04431401 ( https://clinicaltrials.gov/ct2/show/NCT04431401 ).

Iron metabolism patterns in non-anemic patients with myasthenia gravis: A cross-sectional and follow-up study.

Background and purpose: Iron metabolism in myasthenia gravis (MG) and factors associated with it are explored by few published studies. Therefore, this study aimed to compare iron metabolism patterns between patients with MG and healthy individuals as well as between the same group of patients before and after immunotherapy, and to identify predictors of iron metabolism disorders in MG. Materials and methods: For this study, 105 patients and healthy individuals were included at baseline, after which paired parametric and non-parametric tests were adopted to compare their iron metabolism patterns, and multivariate binary logistic regression was used to identify predictors of iron metabolism disorders. Patients with MG were then followed up for 12 ± 3 months to explore alterations in their iron metabolism patterns after starting immunotherapy with the help of paired tests. Results: Non-anemic immunotherapy-naive patients with MG had significantly lower serum iron (SI) and transferrin saturation (TS) levels than healthy individuals. Premenopausal female was significantly associated with SI < 65 µg/dL and iron deficiency in these patients. However, iron metabolism parameters did not significantly alter after around 12 months of immunotherapy in patients with MG. Conclusion: Iron inadequacy was present in patients with MG, particularly premenopausal female patients, and it would hardly improve after immunotherapy. Given the significant role of iron in human body, it should be given more attention in patients with MG.

Successful Management of Generalized Myasthenia Gravis Induced by Atezolizumab in a Patient With Extensive-Stage SCLC: A Case Report.

Immune checkpoint inhibitors including atezolizumab and durvalumab have been approved as the first-line treatment in extensive-stage SCLC. However, immune checkpoint inhibitors can cause immune-related adverse events, which will lead to the shelving of follow-up treatment and the progression and deterioration of SCLC. Myasthenia gravis (MG) is a relatively rare and fatal presentation of immune-related adverse events, and experience with immune-related MG in patients with SCLC is limited. Herein we present a patient who developed generalized MG after receiving three cycles of treatment with etoposide, carboplatin, and atezolizumab. Immune-related MG was identified, with pyridostigmine bromide, intravenous immunoglobulin, and glucocorticoids given in time. Fortunately, the patient's MG was relieved, and treatment of SCLC was restarted subsequently.

Long-Term Efficacy of Non-steroid Immunosuppressive Agents in Anti-Muscle-Specific Kinase Positive Myasthenia Gravis Patients: A Prospective Study.

Background and Purpose: Anti-muscle-specific kinase (MuSK) positive myasthenia gravis (MG) is characterized by a high relapsing rate, thus, choosing the appropriate oral drug regimen is a challenge. This study aimed to evaluate the efficacy of oral immunosuppressants (IS) in preventing relapse in MuSK-MG. Methods: This prospective cohort observational study included patients with MuSK-MG at Peking Union Medical College Hospital between January 1, 2018, and November 15, 2021. The patients were divided into 2 groups: those with (IS+) or without (IS-) non-steroid immunosuppressive agents. The primary outcome was relapsed at follow-up, and the log-rank test was used to compare the proportion of maintenance-free relapse between the groups; hazard ratio (HR) was calculated using the Cox proportional hazards models. Results: Fifty-three of 59 patients with MuSK-MG were included in the cohort, 14 were in the IS+ group, and 39 were in the IS- group. Twenty-four cases in the cohort experienced relapse at least once; the relapse rate was 2/14 (14.3%) in the IS+ group and 22/39 (56.4%) in the IS- group. At the end of follow-up, the proportion of maintenance-free relapse was significantly different between the two groups (log-rank χ2 = 4.94, P = 0.02). Of all the potential confounders, only the use of IS was associated with a reduced risk of relapse. The HR for relapse among patients in the IS+ group was 0.21 (95%CI 0.05-0.58) and was 0.23 (95%CI 0.05-0.93) in a model adjusted for age, sex, relapse history, highest Myasthenia Gravis Foundation of America (MGFA), and accumulated time of steroid therapy. Conclusions: This study provides evidence that oral non-steroid immunosuppressive agents may be beneficial in reducing relapse in patients with MuSK-MG.

Association Between Clinical Factors and Result of Immune Checkpoint Inhibitor Related Myasthenia Gravis: A Single Center Experience and Systematic Review.

Background: Neurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase use of ICIs, incidence of nirAEs is growing, among which ICI related MG (irMG) is causing high fatality rate. Given the limited evidence, data from a large cohort of patients with irMG is needed to aid in recognition and management of this fatal complication. Objective: This study aimed to summarize clinical characteristics of irMG and explore predictors of irMG clinical outcome. Methods: We summarized our institution's patients who were diagnosed as irMG between Sep 2019 and Oct 2021. We systematically reviewed the literature through Oct 2021 to identify all similar reported patients who met inclusion criteria. As the control group, patients with idiopathic MG were used. We collected data on clinical features, management, and outcomes of both irMG and idioMG cases. Further statistical analysis was conducted. Results: Sixty three irMG patients and 380 idioMG patients were included in the final analysis. For irMG patients, six were from our institution while the rest 57 were from reported cases. The average age of irMG patients is 70.16 years old. Forty three were male. Average time from first ICI injection to symptom onset was 5.500 weeks. Eleven patients had a past history of MG. Higher MGFA classification and higher QMGS rates were observed in irMG patients compared to idioMG patients. For complication, more irMG patients had myositis or myocarditis overlapping compared to idioMG patients. The most commonly used treatment was corticosteroids for both idioMG and irMG. Twenty one patients (35%) with irMG had unfavorable disease outcome. Single variate and multivariate binary logistic regression proved that association with myocarditis, high MGFA classification or QMGS rates at first visit were negatively related to disease outcome in irMG patients. Conclusion: irMG is a life-threatening adverse event. irMG has unique clinical manifestations and clinical outcome compared to idioMG. When suspicious, early evaluation of MGFA classification, QMGS rates and myositis/myocarditis evaluation are recommended.

Nerve Ultrasound Performances in Differentiating POEMS Syndrome from CIDP.

Chronic inflammatory demyelinating polyneuropathy (CIDP) and polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome are both acquired demyelinating polyneuropathies. We aim to explore the different features of ultrasonographic changes between CIDP and POEMS syndrome. Nerve ultrasonographic studies were performed in 120 patients with CIDP and 34 patients with POEMS syndrome. Cross-sectional areas (CSAs) were measured on the bilateral median nerve, ulnar nerve, and brachial plexus. Nerve conduction studies were performed on median and ulnar nerves to detect motor conduction blocks (CBs). CSAs at all sites were larger in patients with CIDP and POEMS syndrome than in healthy controls. Maximal CSA (median (min to max)) was 14 (6-194) mm2 for median nerve, 9 (4-92) mm2 for ulnar nerve, and 14 (7-199) mm2 for brachial plexus in CIDP and 11 (8-16) mm2 for median nerve, 8.5 (6-13) mm2 for ulnar nerve, and 14 (10-20) mm2 for brachial plexus in POEMS syndrome. The ratio of maximum/minimum CSA of the median nerve was significantly larger in CIDP (2.8 ± 2.8) than in POEMS syndrome (1.7 ± 0.3). CBs or probable CBs were detected in 60 out of 120 CIDP patients but in none of the POEMS syndromes. For distinguishing CIDP and POEMS syndrome, a two-step protocol using CB and maximum/minimum CSA of the median nerve yields a sensitivity of 93% and a specificity of 79%. In conclusion, compared with CIDP, nerve CSA enlargement was more homogeneous along the same nerve in individual POEMS patients, as well as among different POEMS patients. The addition of nerve ultrasound to nerve conduction studies significantly improves the differential diagnosis between the two diseases.

Nerve ultrasound may help predicting response to immune treatment in chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUNDS: Nerve ultrasound has been proven to be an accurate tool in diagnosing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, its value in guiding treatment has not been well evaluated. The aim of this study was to explore whether nerve ultrasound and its changing trend could predict the response to immune treatment in CIDP. METHODS: Eighty-nine therapy-naive CIDP patients were recruited prospectively and treated with steroids and/or intravenous immunoglobulin (IVIG). Ultrasonographic and electrophysiological studies were performed on the median and ulnar nerves before treatment in all patients and followed up in 45 patients. The cross-sectional area (CSA) was measured at ten sites on both the median and ulnar nerves. RESULTS: The response rate to steroids (95%) was significantly higher than that to IVIG (70%) (P = 0.001) in patients with normal or moderately enlarged CSA, while there was no significant difference in the response rate between steroid therapy (84%) and IVIG (75%) (P = 0.653) in patients with markedly enlarged CSA. CSAs decreased in 15 patients during follow-up, most of whom had good IVIG and steroid responses (83%) and no need for immune suppressant treatment (82%). CONCLUSIONS: Nerve ultrasonography could help guide treatment strategies in patients with CIDP. Patients with normal or moderately enlarged CSA may respond better to steroids than to IVIG. The decrease in CSA after treatment may also indicate better prognosis.

Patients With Myasthenia Gravis With Acute Onset of Dyspnea: Predictors of Progression to Myasthenic Crisis and Prognosis.

Background: Life-threatening myasthenic crisis (MC) occurs in 10-20% of the patients with myasthenia gravis (MG). It is important to identify the predictors of progression to MC and prognosis in the patients with MG with acute exacerbations. Objective: This study aimed to explore the predictors of progression to MC in the patients with MG with acute onset of dyspnea and their short-term and long-term prognosis. Methods: This study is a retrospective cohort study. We collected and analyzed data on all the patients with MG with acute dyspnea over a 10-year period in a single center using the univariate and multivariate analysis. Results: Eighty-six patients with MG were included. In their first acute dyspnea episodes, 36 (41.9%) episodes eventually progressed to MC. A multivariate analysis showed that the early-onset MG (adjusted OR: 3.079, 95% CI 1.052-9.012) and respiratory infection as a trigger (adjusted OR: 3.926, 95% CI 1.141-13.510) were independent risk factors for the progression to MC, while intravenous immunoglobulin (IVIg) treatment prior to the mechanical ventilation (adjusted OR: 0.253, 95% CI 0.087-0.732) was a protective factor. The prognosis did not significantly differ between the patients with and without MC during the MG course, with a total of 45 (52.3%) patients reaching post-intervention status better than minimal manifestations at the last follow-up. Conclusion: When treating the patients with MG with acute dyspnea, the clinicians should be aware of the risk factors of progression to MC, such as early-onset MG and respiratory infection. IVIg is an effective treatment. With proper immunosuppressive therapy, this group of patients had an overall good long-term prognosis.

Fasciculation differences between ALS and non-ALS patients: an ultrasound study.

BACKGROUND: Fasciculation is an important sign for the diagnosis of amyotrophic lateral sclerosis (ALS). Our study aimed to analyze the difference in fasciculation detected with muscle ultrasonography (MUS) between ALS patients and non-ALS patients with symptoms resembling ALS. METHODS: Eighty-eight ALS patients and fifty-four non-ALS (eight multifocal motor neuropathy, 32 chronic inflammatory demyelinating polyneuropathy/Charcot-Marie-Tooth, and 14 cervical spondylopathy or lumbar spondylopathy) patients were recruited. MUS was performed on 19 muscle groups in cervical, lumbosacral, bulbar, and thoracic regions for each patient. The intensity of fasciculation was divided into five grades based on firing frequency and number in the involved muscle groups. RESULTS: The overall detection rates were 72.8% in ALS and 18% in non-ALS patients. The fasciculation grades (median [IQR]) were 2 (0-3) in ALS and 0 (0-0) in non-ALS patients (P < 0.001). Fasciculations were observed in four regions for ALS patients and primarily distributed in proximal limbs. Fasciculations in non-ALS patients were primarily low-grade and mostly distributed in distal limbs. DISCUSSION: The fasciculation grade was higher in ALS than non-ALS patients. The distribution pattern of fasciculation was different between ALS and non-ALS patients. CONCLUSIONS: The fasciculation grade and distribution pattern detected with MUS could help distinguish ALS from non-ALS patients.

Light-Chain Amyloidosis With Peripheral Neuropathy as an Initial Presentation.

Objective: This study aimed to better understand the clinical, electrophysiological, pathological features and prognosis of peripheral nerve involvements in primary immunoglobulin light-chain (AL) amyloidosis. Methods: We retrospectively reviewed the clinical data of eight AL amyloidosis patients with peripheral neuropathy as the initial presentation including clinical features, histopathological findings and treatment. Results: There were seven males and one female aged from 52 to 66 years. Initial symptoms included symmetrical lower extremity numbness, lower extremity pain and carpal tunnel syndrome. Seven patients suffered from severe pain and required pain management. Six patients had predominant autonomic dysfunction. Six patients had cardiac involvement, and one patient had renal involvement. Monoclonal proteins were found in all patients, with IgA λ in one, IgG λ in two, λ alone in three, κ alone in one and IgM κ in one. Sural nerve biopsies were performed in 7 cases, all of which showed amyloid deposition in the endoneurium (in the perivascular region in some cases), in addition to moderate to severe myelinated fiber loss with axonal degeneration. Six patients were treated with combined chemotherapy. In three patients who began chemotherapy earlier (6-10 months after onset), two achieved a hematological complete response, and one achieved a partial response. three patients who had delayed chemotherapy (36 months after onset) died between 5 and 12 months after diagnosis. Conclusion: Early recognition of AL amyloidosis with peripheral neuropathy as the initial symptom is very important. Nerve biopsy can help to make the diagnosis. Early diagnosis and chemotherapy are critical to achieve better outcomes.

Differential Expression of miRNA in the Peripheral Blood Mononuclear Cells in Myasthenia Gravis with Muscle-Specific Receptor Tyrosine Kinase Antibodies.

To determine if differential profile of miRNAs in peripheral blood mononuclear cells (PBMCs) could be identified in muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis (MuSK-MG) and linked to disease stage, a case-control method was used to compare the difference in miRNA expression profiles of PBMCs using next generation sequencing (NGS) in MuSK-MG patients and healthy controls (HCs). Six significant miRNAs from the discovery set were then validated using RT-qPCR in 11 MuSK-MG patients and 10 HCs. A unique miRNA prediction algorithm was used to predict the target genes of differentially expressed miRNAs and a network of miRNA gene pathways. Compared with HCs, 101 differentially expressed miRNAs were screened in MuSK-MG, of which 5 miRNAs were upregulated, and 96 miRNAs were downregulated. The top six differentially expressed molecules were selected for verification; four of them (miR-340-5p, miR-106b-5p, miR-27a-3p, and miR-15a-3p) were significantly different. The network analysis of miRNA gene pathways revealed that differentially expressed miRNAs were involved in a complex set of biological processes. Clinically, the four miRNAs that were validated are not correlated to MuSK antibody titers and quantitative myasthenia gravis score. Four miRNAs that were validated in this study have specificity to distinguish MuSK-MG from HCs.

[Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer].

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS: Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Clinical recommendations for perioperative immunotherapy-induced adverse events in patients with non-small cell lung cancer.

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.