Cell-based versus enzyme-linked immunosorbent assay for detection of anti-Tribbles homolog 2 autoantibodies in Chinese patients with narcolepsy.

STUDY OBJECTIVES: Narcolepsy type 1 (NT1) is attributed to a deficiency in cerebrospinal fluid orexin and is considered linked to autoimmunity. The levels of anti-Tribbles homolog 2 (TRIB2) autoantibodies are elevated in the sera of some patients with narcolepsy with cataplexy. Additionally, injecting mice with serum immunoglobulin from patients with narcolepsy with positive anti-TRIB2 antibodies can induce hypothalamic neuron loss and alterations in sleep patterns. Consequently, we hypothesized the existence of a potential association between anti-TRIB2 antibodies and narcolepsy. To test this possibility, we used cell-based assays (CBAs) and enzyme-linked immunosorbent assays (ELISAs) to detect the presence of anti-TRIB2 antibodies in Chinese patients with narcolepsy. METHODS: We included 68 patients with NT1; 39 patients with other central disorders of hypersomnolence; and 43 healthy controls (HCs). A CBA and a conventional ELISA were used to detect anti-TRIB2 antibody levels in patient sera. RESULTS: CBA was used to detect serum anti-TRIB2 antibodies in Chinese patients with narcolepsy, and the results were negative. However, when the ELISA was used, only two NT1 patients had TRIB2 antibody titers higher than the mean titer plus 2 SD of the HCs. CONCLUSIONS: In our study, ELISA identified TRIB2 autoantibodies in sera of narcolepsy patients where CBA failed to demonstrate them. Contrary to our hypothesis, this intriguing finding deserves further research to elucidate the potential association between TRIB2 and NT1. Exploring the implications of TRIB2 autoantibodies in narcolepsy and disparate outcomes between ELISA and CBA could provide crucial insights.

Association between cytokines and fatigue in patients with type 1 narcolepsy.

BACKGROUND: Fatigue is a frequent complaint among patients with narcolepsy. Studies have shown that inflammatory cytokines are associated with fatigue in neurological disorders; however, this association has not been identified in patients with type 1 narcolepsy. The purpose of this study was to investigate the potential relationship between cytokines and fatigue in patients with type 1 narcolepsy. METHODS: We investigated the association between 12 inflammatory cytokines and fatigue in 49 patients with type 1 narcolepsy. The Multidimensional Fatigue Inventory-20 was used to assess the fatigue severity. The associations of fatigue were identified using Spearman and Pearson correlation analyses. A linear regression analysis model was used to adjust the confounding factors and evaluate the associations of fatigue. RESULTS: Correlation analysis showed that the plasma interleukin (IL)-2 level (r = 0.409, p = 0.004) was positively correlated with fatigue in patients with narcolepsy type 1. After adjusting for confounding factors, the linear regression model revealed a positive association between the IL-2 level (ß = 1.148, p = 0.04) and fatigue in individuals diagnosed with type 1 narcolepsy. CONCLUSION: IL-2 levels show a positive correlation with fatigue in type 1 narcolepsy, suggesting its potential role in the pathophysiology of fatigue.

Serum metabolomics study of narcolepsy type 1 based on ultra-performance liquid chromatography-tandem mass spectrometry.

Narcolepsy is a chronic and underrecognized sleep disorder characterized by excessive daytime sleepiness and cataplexy. Furthermore, narcolepsy type 1 (NT1) has serious negative impacts on an individual's health, society, and the economy. Currently, many sleep centers lack the means to measure orexin levels in the cerebrospinal fluid. We aimed to analyze the characteristics of metabolite changes in patients with NT1, measured by ultra-performance liquid chromatography-tandem mass spectrometry. A principal component analysis (PCA), an orthogonal partial least square discriminant analysis (OPLS-DA), t tests, and volcano plots were used to construct a model of abnormal metabolic pathways in narcolepsy. We identified molecular changes in serum specimens from narcolepsy patients and compared them with control groups, including dehydroepiandrosterone, epinephrine, N-methyl-D-aspartic acid, and other metabolites, based on an OPLS-loading plot analysis. Nine metabolites yielded an area under the receiver operating curve > 0.75. Meanwhile, seven abnormal metabolic pathways were correlated with differential metabolites, such as metabolic pathways; neuroactive ligand‒receptor interaction; and glycine, serine, and threonine metabolism. To our knowledge, this is the first study to reveal the characteristic metabolite changes in sera from NT1 patients for the selection of potential blood biomarkers and the elucidation of NT1 pathogenesis.

Clinical characteristics and outcome correlates of Chinese patients with takotsubo syndrome: Results from the first Chinese takotsubo syndrome registry.

OBJECTIVE: To investigate clinical features and outcomes of Chinese patients with Takotsubo syndrome (TTS). METHODS: We established the first Chinese Registry of Takotsubo Syndrome (ChiTTS Registry) and analyzed demographic, clinical, therapeutical, and outcome data to characterize clinical and outcome features of Chinese TTS patients. RESULTS: In 112 enrolled patients in the ChiTTS registry from 02/01/2016 to 12/28/2021, the mean age was 59.4 ± 18.7 years old, and 27.7% were men. A total of 41.1% patients experienced respiratory and circulatory complications during hospitalization, and 17.3% patients developed cardiogenic shock. Physical triggers, dyspnea, tachycardia, and younger age (< 70 years old) predicted in-hospital complications. The MACCE rate during follow up was 13.9% per patient per year and the rate of all-cause death was 12.8% per patient per year. TTS patients with in-hospital complications developed more long-term MACCE (24.6% vs. 6.6% per patient-year, P < 0.001) and higher all-cause mortality (21.9% vs. 6.6% per patient-year, P = 0.001) than those without. The Kaplan-Meier survival analysis showed that more MACCE occurred in TTS patients with tachycardia during 3-year follow-up (HR 4.18; 95% CI 1.80-9.74; log-rank test P < 0.001). Among all medications at discharge, only beta-blocker was associated with reduced long-term MACCE (HR: 0.35; 95% CI: 0.12-0.996; P = 0.049). CONCLUSION: We investigated clinical and outcome features of patients in the first Chinese TTS Registry. Tachycardiac TTS patients developed more inpatient and long-term adverse cardiovascular events.

Impact of obstructive sleep apnea on outcomes of pulmonary embolism: A systematic review and meta­analysis.

The current review aimed to assess the effect of obstructive sleep apnea (OSA) on the severity and outcomes of pulmonary embolism (PE). PubMed, Embase, ScienceDirect, CENTRAL and Google Scholar were searched for studies assessing the impact of OSA on severity and outcomes of PE. A total of 12 studies were included. Meta-analysis revealed that simplified PE severity index of >1 and pulmonary artery obstruction index score was significantly higher in patients with OSA as compared with controls, but there was no difference in right ventricle to left ventricle short-axis diameter. The need for non-invasive ventilation was significantly higher in patients with OSA but there was no difference in the need for mechanical ventilation. Patients with OSA had a significantly higher incidence of recurrence of PE. Meta-analysis also showed a statistically significantly lower risk of in-hospital mortality in patients with OSA as compared with controls, but without any difference in the risk of late mortality. Adjusted data on mortality indicated a significantly lower risk of mortality in PE patients with comorbid OSA. Limited data shows that comorbid OSA increases the severity of PE but has no effect on right ventricular function. OSA may increase the risk of recurrent PE. Paradoxically, the presence of OSA may also reduce the risk of in-hospital mortality. Results must be interpreted with caution owing to high inter-study heterogeneity and lack of matching of baseline characteristics. Current evidence needs to be confirmed by high-quality prospective studies.

Endoscopic resection of bronchial mucoepidermoid carcinoma in a young adult man: A case report and review of literature.

BACKGROUND: Primary tracheobronchial mucoepidermoid carcinoma (MEC), derived from salivary mucus glands, is an uncommon neoplasm in adults. At present, surgery is still the preferred treatment for adult bronchial MEC, although it may cause significant trauma and loss of lung function. Here, we report a patient with endobronchial MEC who received the interventional bronchoscopic therapy to remove the neoplasm and no recurrence occurred during follow-up. CASE SUMMARY: A 28-year-old man was admitted to our unit with mild hemoptysis for 3 d. Physical examination did not show any abnormal signs, and the serological indexes were all in the normal range. Chest computed tomography (CT) indicated an intraluminal nodule in the bronchus intermedius with homogeneous density and a well-defined margin. Upon fiberoptic bronchoscopy, an endobronchial pedunculated polypoid was discovered without submucosal involvement. As the neoplasm was confined to the bronchus, interventional bronchoscopy was performed to remove the mass by high-frequency electric knife and laser resection. Tissue was sampled and histopathological examination confirmed the diagnosis of low-grade MEC. As the proliferation index was low, no further treatment was given. During 2 years of follow-up, the patient's condition was good and no relapse was discovered under fluorescence bronchoscopy or CT scan. CONCLUSION: Interventional bronchoscopy can be considered for treatment of low-grade bronchial MEC, with few complications and preserved lung function.

Comparison of postprocedural new-onset atrial fibrillation between transcatheter and surgical aortic valve replacement: A systematic review and meta-analysis based on 16 randomized controlled trials.

BACKGROUND: Presently, transcatheter aortic valve replacement (TAVR) as an effective and convenient intervention has been adopted extensively for patients with severe aortic disease. However, after surgical aortic valve replacement (SAVR) and TAVR, the incidence of new-onset atrial fibrillation (NOAF) is prevalently found. This meta-analysis was designed to comprehensively compare the incidence of NOAF at different times after TAVR and SAVR for patients with severe aortic disease. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science up to October 1, 2020 was conducted for relevant studies that comparing TAVR and SAVR in the treatment of severe aortic disease. The primary outcomes were the incidence of NOAF with early, midterm and long term follow-up. The secondary outcomes included permanent pacemaker (PM) implantation, myocardial infarction (MI), cardiogenic shock, as well as mortality and other complications. Two reviewers assessed trial quality and extracted the data independently. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2. RESULTS: A total of 16 studies including 13,310 patients were identified. The pooled results indicated that, compared with SAVR, TAVR experienced a significantly lower incidence of 30-day/in-hospital, 1-year, 2-year, and 5-year NOAF, with pooled risk ratios (RRs) of 0.31 (95% confidence interval [CI] 0.23-0.41; 5725 pts), 0.30 (95% CI 0.24-0.39; 6321 pts), 0.48 (95% CI 0.38-0.61; 3441 pts), and 0.45 (95% CI 0.37-0.55; 2268 pts) respectively. In addition, TAVR showed lower incidence of MI (RR 0.62; 95% CI 0.40-0.97) and cardiogenic shock (RR 0.34; 95% CI 0.19-0.59), but higher incidence of permanent PM (RR 3.16; 95% CI 1.61-6.21) and major vascular complications (RR 2.22; 95% CI 1.14-4.32) at 30-day/in-hospital. At 1- and 2-year after procedure, compared with SAVR, TAVR experienced a significantly higher incidence of neurological events, transient ischemic attacks (TIA), permanent PM, and major vascular complications, respectively. At 5-year after procedure, compared with SAVR, TAVR experienced a significantly higher incidence of TIA and re-intervention respectively. There was no difference in 30-day, 1-year, 2-year, and 5-year all-cause or cardiovascular mortality as well as stroke between TAVR and SAVR. CONCLUSIONS: Our analysis showed that TAVR was superior to SAVR in decreasing the both short and long term postprocedural NOAF. TAVR was equal to SAVR in early, midterm and long term mortality. In addition, TAVR showed lower incidence of 30-day/in-hospital MI and cardiogenic shock after procedure. However, pooled results showed that TAVR was inferior to SAVR in reducing permanent pacemaker implantation, neurological events, TIA, major vascular complications, and re-intervention.

MicroRNA-26a-2 maintains stress resiliency and antidepressant efficacy by targeting the serotonergic autoreceptor HTR1A.

The association between dysregulated serotonergic activity and major depressive disorder (MDD) is well known. However, the various mechanisms underlying serotonergic dysregulation in MDD remain unclear. Previous research on serotonergic (5-HT) neurons identified microRNA-26a (miR-26a) targeting of the serotonin autoreceptor, 5-HT receptor 1A (HTR1A). Reporter assays with the Htr1a 5'UTR sequence were performed in vitro. Adult transgenic mouse models altering miR-26a-2 and Htr1a expression were used for chronic social defeat, antidepressant treatment, and in vivo lentiviral experiments. Mice were tested for anxiety-like behavior using the elevated plus-maze, dark-light transfer, and open-field tests, and for depression-like behavior using the forced-swim test. We confirmed that miR-26a-2 downregulates Htr1a expression in 5-HT neurons in vitro. miR-26a-2 levels were significantly upregulated in the mouse dorsal raphe nucleus (DRN) following antidepressant therapy. The transgenic murine model overexpressing miR-26a-2 in serotonergic neurons displayed improved behavioral resiliency to social defeat. These effects were abrogated by the addition of Htr1a overexpression. In contrast, the transgenic murine model with miR-26a-2 knockdown in serotonergic neurons displayed increased anxious behavior and weakened antidepressant response. These effects were rescued by silencing Htr1a expression. Our findings suggest that miR-26a-2 functions as an endogenous antidepressant by targeting HTR1A in serotonergic neurons.

[Impact of obstructive sleep apnea-hypopnea syndrome on cerebral microbleeds in patients with cerebral infarction].

OBJECTIVE: To investigate the impact of obstructive sleep apnea-hypopnea syndrome (OSAHS) on cerebral microbleeds (CMBs) in patients with cerebral infarction. METHODS: Consecutive patients with acute cerebral infarction who had cerebral microbleeds shown by susceptibility-weighted imaging (SWI) were enrolled to undergo polysomnography (PSG). The patients were divided into two groups, namely non-OSAHS group with apnea-hypopnea index (AHI) less than 5 and OSAHS group with greater AHI, and the clinical and radiological features of cerebral microbleeds were compared between them. RESULTS: Forty-nine patients were enrolled in this study, including 27 (55.1%) with both cerebral infarction and OSAHS and 22 (44.9%) with cerebral infarction but not OSAHS. A comparison of the risk factors showed that hypertension, a smoking history, and a history of stroke were more prevalent in patients with OSAHS than in those without OSAHS (P<0.05). The incidences of subclinical stroke in OSAHS and non-OSAHS patients were 37.0% (10/27) and 9.0% (2/22) (P<0.05), respectively. Neurological imaging revealed a greater number of cerebral microbleeds in OSAHS group than in non-OSAHS group (P<0.05). In OSAHS patients, 77.8% of the microbleeds were distributed in cortical-subcortical areas, 55.6% in the basal ganglia area, and 25.9% in the infratentorial area, as compared to the percentages of 50.0%, 40.9% and 50.0% in non-OSAHS patients, respectively (P<0.05). In OSAHS patients, 40.7% also had leukoaraiosis, and 48.1% had two or more causes, as compared to the percentages of 13.6% and 18.2% in non-OSAHS patients, respectively (P<0.05). CONCLUSIONS: OSAHS can be a risk factor for cerebral microbleeds. Patients with both cerebral infarction and OSAHS tend to have greater and more extensive lesions of cerebral microbleeds, more complicated cause of the disease, and a grater likeliness of stroke recurrence.

[Macrostructure of sleep in patients with vascular cognitive impairment-no dementia].

OBJECTIVE: To investigate the sleep structure in patients with vascular cognitive impairment-no dementia (VCI-ND) and its differences from that of normal individuals. METHODS: The whole night sleep record of 20 patients with VCI-ND were monitored by 32-head video-taped polysomnographic system, and the results were compared with the data of 20 normal subjects. RESULTS: Compared with normal subjects, patients with VCI-ND showed significantly reduced total sleep duration, increased waking times, increased stage 1 sleep, decreased stage 2 sleep, decreased stage 3 sleep, decreased rapid eye movement stage (REM) and reduced sleep efficiency. CONCLUSION: Increased light sleep as well as decreased slow-wave stage 3-4 sleep and decreased REM stage may be a specific electroneurophysiologic marker for VCI-ND, but large-sampled multi-centered randomized controlled trial is necessary to test the validity of these features as specific markers for screening and early diagnostic purposes.

Polymyositis/dermatomyositis associated with acute myelocytic leukemia.

Polymyositis (PM) and dermatomyositis (DM) are inflammatory myopathic diseases that often accompany cancers. However, the relationship between PM/DM and acute myelocytic leukemia (AML) has not been elucidated. We present a case of PM that developed AML 12 months after initial diagnosis. We reviewed the cases in English literature and analyzed the association between PM/DM and AML. We conclude that PM/DM is a paraneoplastic syndrome of AML.