Rationale:Immune checkpoint inhibitors have led to the development of new approaches for cancer treatment with positive outcomes. However, checkpoint blockade is associated with a unique spectrum of immune-related adverse events (irAEs), which may cause irreversible neurological deficits and even death.Patient concerns:We presented a case of a 57-year-old man with non-small-cell lung cancer.who developed ptosis, dyspnea, and muscle weakness as initial symptoms with progression after the treatment with ipilimumab and nivolumab.Diagnoses:Myasthenia gravis was confirmed by serum acetylcholine receptor antibody and single fiber electromyography. Myositis was identified by high level of serum creatine phosphokinase and electromyography. Polyneuropathy was identified by nerve conduction study.Interventions:The patient underwent treatment with steroid and pyridostigmine. Respiratory rehabilitation was also performed.Outcomes:Dyspnea and muscle weakness improved gradually. Ipilimumab and nivolumab were permanently discontinued.Lessons:This case has increased the clinical awareness by indicating that the checkpoint inhibitors-related neurological irAEs could be complicated and simultaneously involve multiple neurological systems. Early recognition and complete evaluation are critical in clinical practice.
A series of new organic dyes exploiting coplanar indacenodithiophene as the central π-spacer of the classical donor-(π-spacer)-acceptor configuration were synthesized and characterized for dye-sensitized solar cells. The coplanarity of the indacenodithiophene core facilitates efficient donor to acceptor charge transfer, imparting the new organic dyes significant bathochromic shifts and remarkable power conversion efficiencies of up to 6.7% (DTInDT) under AM 1.5G radiation.
The contribution of circulatory tau and β‐amyloid in Parkinson's disease (PD), especially the cognitive function, remains inconclusive. Extracellular vesicles (EVs) cargo these proteins throughout the bloodstream after they are directly secreted from many cells, including neurons. The present study aims to investigate the role of the plasma EV‐borne tau and β‐amyloid as biomarkers for cognitive dysfunction in PD by investigating subjects with mild to moderate stage of PD (n = 116) and non‐PD controls (n = 46). Plasma EVs were isolated, and immunomagnetic reduction‐based immunoassay was used to assess the levels of α‐synuclein, tau, and β‐amyloid 1‐42 (Aβ1‐42) within the EVs. Artificial neural network (ANN) models were then applied to predict cognitive dysfunction. We observed no significant difference in plasma EV tau and Aβ1‐42 between PD patients and controls. Plasma EV tau was significantly associated with cognitive function. Moreover, plasma EV tau and Aβ1‐42 were significantly elevated in PD patients with cognitive impairment when compared to PD patients with optimal cognition. The ANN model used the plasma EV α‐synuclein, tau, and Aβ1‐42, as well as the patient's age and gender, as predicting factors. The model achieved an accuracy of 91.3% in identifying cognitive dysfunction in PD patients, and plasma EV tau and Aβ1‐42 are the most valuable factors. In conclusion, plasma EV tau and Aβ1‐42 are significant markers of cognitive function in PD patients. Combining with the plasma EV α‐synuclein, age, and sex, plasma EV tau and Aβ1‐42 can identify cognitive dysfunction in PD patients. This study corroborates the prognostic roles of plasma EV tau and Aβ1‐42 in PD.
Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin, responsible for neuronal development, function, and survival. Assessments of peripheral blood BDNF in patients with Parkinson’s disease (PD) previously yielded inconsistent results. Plasma exosomes can carry BDNF, so this study investigated the role of plasma exosomal BDNF level as a biomarker of PD. A total of 114 patients with mild to moderate PD and 42 non-PD controls were recruited, and their clinical presentations were evaluated. Plasma exosomes were isolated with exoEasy Maxi Kits, and enzyme-linked immunosorbent assay was used to assess plasma exosomal BDNF levels. Statistical analysis was performed using SPSS version 19.0, and findings were considered significant at p < 0.05. The analysis revealed no significant differences in plasma exosomal BDNF levels between patients with PD and controls. Patients with PD with low plasma exosomal BDNF levels (in the lowest quartile) exhibited a significant association with daily activity dysfunction but not with cognition/mood or overall motor symptoms as assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS). Investigation of UPDRS part III subitems revealed that low plasma exosomal BDNF level was significantly associated with increased motor severity of postural instability and gait disturbance (PIGD)-associated symptoms (rising from a chair, gait, and postural stability) after adjustment for age and sex. In conclusion, although plasma exosomal BDNF level could not distinguish patients with PD from controls, the association with PIGD symptoms in patients with PD may indicate its potential role as a biomarker. Follow-up studies should investigate the association between plasma exosomal BDNF levels and changes in clinical symptoms.
Background: Neurofilament light chain (NfL) is essential for axonal maintenance and reflects neuronal damage. Extracellular vesicles (EVs), especially exosomes, secreted by cells into the blood, are emerging as novel biomedical research platforms of physiological and pathological processes. The present study investigated the possible association between plasma EV NfL and Parkinson’s disease (PD). Methods: One hundred and sixteen patients with mild to moderate PD and 46 non-PD, neurological controls were recruited, and their clinical motor symptoms and cognitive function were evaluated. Plasma EVs were isolated using an exoEasy kit, and immunomagnetic reduction assay was used to assess EV NfL level. Statistical analysis was performed using SPSS 25.0, and p < 0.05 was considered significant. Results: The isolated plasma EVs were validated according to size and the presence of specific surface markers. Compared with the neurological control group, the levels of plasma EV NfL in patients with PD were not significantly different (PD: 9.42 ± 3.89, control: 9.53 ± 3.62 pg/mL plasma, p = 0.71). On the other hand, plasma EV NfL in patients with PD trendwise correlated with the severity of akinetic rigidity ( p = 0.05). PD patients with optimal EV NfL (lowest quartile) had 6.66 ± 2.08 lower Unified Parkinson’s Disease Rating Scale-III score after adjustment for age, sex, and disease duration. Conclusion: Plasma EV NfL levels did not distinguish patients with PD from the neurological control group. The possible correlation between plasma EV NfL with the severity of motor symptoms within the PD patients, especially with akinetic rigidity, was noted. Further clinical validation of the blood EV NfL by a longitudinal follow-up study of PD patients is warranted.
Gait disturbance and imbalance are the major symptoms of Parkinson disease (PD), with fall being the most undesirable consequence. However, few effective evidence-based treatments are available for alleviating these symptoms and preventing falls. Cholinesterase inhibitors (ChEIs) are a well-established treatment for PD dementia with possible impacts on gait, balance, and fall reduction. The present study involved a meta-analysis of randomized controlled trials (RCTs) to investigate the effects of ChEIs on gait, balance, and fall in patients with PD. We searched for studies using the PubMed, Embase, and Web of Science databases. The major outcomes were effects on gait parameters, balance, and fall. This study was registered with PROSPERO (CRD42021254733). Five RCTs were included in the present meta-analysis. ChEIs did not significantly increase gait speed in PD patients (mean difference [MD]: 0.03 m/s, 95% confidence interval [CI]: −0.02 to 0.07, p = 0.29). However, ChEI treatment significantly decreased step or stride variability during the single task (standard MD: −0.43, 95% CI = −0.79 to −0.06, p = 0.02). Regarding fall and balance, trending but nonsignificant beneficial effects were observed with ChEI treatment. In conclusion, although ChEI treatment did not significantly improve gait speed and reduce fall, it can significantly reduce step or stride variability. Considering that gait disorder is a challenging issue in patients with PD and that ChEIs are generally tolerable, the present meta-analysis may provide more evidence for the benefit of ChEIs on PD gait disturbance as an alternative treatment consideration.
Plasma extracellular vesicles (EVs) containing various molecules, including cytokines, can reflect the intracellular condition and participate in cell-to-cell signaling, thus emerging as biomarkers for Parkinson’s disease (PD). Inflammation may be a crucial risk factor for PD development and progression. The present study investigated the role of plasma EV cytokines as the biomarkers of PD. This cross-sectional study recruited 113 patients with PD, with mild to moderate stage disease, and 48 controls. Plasma EVs were isolated, and the levels of cytokines, including pro-interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1, were evaluated. Patients with PD had significantly increased plasma EV pro-IL-1β and TNF-α levels compared with controls after adjustment for age and sex. Despite the lack of a significant association between plasma EV cytokines and motor symptom severity in patients with PD, cognitive dysfunction severity, assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment, was significantly associated with plasma EV pro-IL-1β, IL-6, IL-10, and TNF-α levels. This association was PD specific and not found in controls. Furthermore, patients with PD cognitive deficit (MMSE < 26) exhibited a distinguished EV cytokine profile compared to those without cognitive deficit. The findings support the concept of inflammatory pathogenesis in the development and progression of PD and indicate that plasma EV cytokines may serve as PD biomarkers in future.
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