RESUMO
Gray matter (GM) atrophies were observed in multiple sclerosis, neuromyelitis optica spectrum disorders (both anti-aquaporin-4 antibody-positive [AQP4+], and -negative [AQP4-] subtypes NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Revealing the pathogenesis of brain atrophy in these disorders would help their differential diagnosis and guide therapeutic strategies. To determine the neurobiological underpinnings of GM atrophies in multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, and MOGAD, we conducted a virtual histology analysis that links T1-weighted image derived GM atrophy and gene expression using a multicenter cohort of 324 patients with multiple sclerosis, 197 patients with AQP4+ NMOSD, 75 patients with AQP4- NMOSD, 47 patients with MOGAD, and 2,169 healthy controls (HCs). First, interregional GM atrophy profiles across the cortical and subcortical regions were determined by Cohen's d between patients with multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, MOGAD and HCs. Then, the GM atrophy profiles were spatially correlated with the gene expressions extracted from the Allen Human Brain Atlas, respectively. Finally, we explored the virtual histology of clinical feature relevant GM atrophy by subgroup analysis that stratified by physical disability, disease duration, number of relapses, lesion burden, and cognitive function. Multiple sclerosis showed severe widespread GM atrophy pattern, mainly involving subcortical nuclei and brainstem. AQP4+ NMOSD showed obvious widespread GM atrophy pattern, predominately located in occipital cortex as well as cerebellum. AQP4- NMOSD showed mild widespread GM atrophy pattern, mainly located in frontal and parietal cortices. MOGAD showed GM atrophy mainly involving the frontal and temporal cortices. High expression of genes specific to microglia, astrocytes, oligodendrocytes, and endothelial cells in multiple sclerosis, S1 pyramidal cells in AQP4+ NMOSD, as well as S1 and CA1 pyramidal cells in MOGAD had spatial correlations with GM atrophy profiles were observed, while no atrophy profile related gene expression was found in AQP4- NMOSD. Virtual histology of clinical feature relevant GM atrophy mainly pointed to the shared neuronal and endothelial cells among the four neuroinflammatory diseases. The unique underlying virtual histology patterns were microglia, astrocytes, and oligodendrocytes for multiple sclerosis; astrocytes for AQP4+ NMOSD; and oligodendrocytes for MOGAD. Neuronal and endothelial cells were shared potential targets across these neuroinflammatory diseases. These findings might help their differential diagnosis and optimal therapeutic strategies.
RESUMO
Background: Malignant pleural mesothelioma (MPM) is an aggressive and rare malignant pleural tumor. Methods: MPM patients diagnosed in Beijing Chaoyang Hospital and Beijing Tongren Hospital were the focus of this study. We collected and analyzed the histological, radiological, and metabolic features of MPM patients. At the same time, Cox univariable and multivariable analyses were used to explore the laboratory risk factors affecting the prognosis of MPM patients. Results: A total of 129 MPM patients were included in this study. MPM includes three main histological subtypes: epithelioid, sarcomatoid and biphasic. Among them, epithelial subtypes accounted for the highest proportion. Calretinin, Wilms' tumor gene (WT1), cytokeratin 5/6 (CK5/6), and D2-40 were the most useful mesothelial markers to support a MPM diagnosis. The imaging features of MPM patients are pleural thickening and pleural effusion. In PET-CT, the affected pleura showed obvious high uptake of tracer, and the degree was related to the specific subtype. The median follow-up time was 55.0 (30.0, 94.0) months. A total of 92 (71.3%) patients died during follow-up. The median survival time of patients was 21.0 (9.0, 48.0) months. The Cox multivariable analysis showed that age [hazard ratio (HR), 1.824; 95% confidence interval (CI) 1.159-2.872; p = 0.009; uncorrected], ESR (HR, 2.197; 95% CI 1.318-3.664; p = 0.003; with Bonferroni correction), lymphocytes (HR, 0.436; 95% CI 0.258-0.737; p = 0.002; with Bonferroni correction), platelets (HR, 1.802; 95% CI 1.084-2.997; p = 0.023; uncorrected) and total protein (HR, 0.625; 95% CI 0.394-0.990; p = 0.045; uncorrected) were independent risk factors for prognosis, after adjusting for confounding factors. Conclusions: Age, ESR, lymphocytes, platelets and total protein may be related to the prognosis of MPM patients. Summarizing the histological, radiological, and metabolic features of MPM patients in the two centers can increase clinicians' understanding of this rare tumor.
