Structural neuroimaging studies on chronic smokers using voxel-based morphometry (VBM) had provided cumulative evidence of gray matter (GM) changes relative to nonsmokers. However, not all the studies reported entirely consistent findings. Here, we aimed at identifying consistent GM anomalies in chronic smokers by performing a meta-analysis, and a systematic search of VBM studies on chronic smokers and nonsmokers published in PubMed and Embase database from 2000 to April 2012. Meta-analysis was performed using a newly improved voxel-based meta-analytic tool, namely effect size signed differential mapping, to quantitatively explore the GM abnormalities between chronic smokers and nonsmokers. A total of 7 eligible VBM studies involving 213 chronic smokers and 205 nonsmokers met the inclusion criteria. A considerable regional GM volume decrease was detected in the anterior cingulate cortex (ACC) (BA 24) extending to BA32 in chronic smokers. The findings remain largely unchanged in the entire brain jackknife sensitivity analyses. The results of the present meta-analysis provide evidence of GM changes in ACC in chronic smokers which may be an important potential therapeutic neuro-target for nicotine dependence.

Since Binswanger's description of subcortical arteriosclerotic encephalopathy in 1894, numerous cases have been reported. Several authors doubt the validity of this malady, although the majority consider it to be a disease entity. We report seven cases with this type of pallor of myelin, only two of which are accompanied by a history of dementia. Among the seven cases, two had arteriosclerosis of penetrating arteries and arterioles in cerebral white matter. Electron microscopy showed splitting of myelin sheaths, probably the result of edema. In reviewing the blood supply of the cerebral white matter, we conclude that no pathological alterations of medullary branches of the cerebral arteries, the same vessels supplying the white matter, can give rise to such diffuse pallor of white matter and spare the arcuate fibres. This pallor can only be due to cerebral edema, most likely of hypoxic-ischemic, hypotensive, or acidotic origin. We also contend that arteriosclerosis can only cause dementia through multiple infarcts or lacunae, if it indeed leads to dementia. RESUME: La maladie de Binswanger: Une demence due a des infarctus multiples? Depuis la description de l'encephalopathie art^riosclerotique sous-corticale par Binswanger en 1894, plusieurs cas ont ete rapport^s. Plusieurs auteurs doutent la validity de cette maladie, bien que la majorite la considerent comme une entite medicale. Nous rapportons sept cas atteints de ce type de paleur de mydline, dont seulement deux sont accompagnes d'une histoire de d6mence. Parmi les sept cas, deux etaient l'arteYiosclerose des arteres et des arterioles p6netrantes dans la substance blanche c6rebrale. La microscopie 61ectronique montra l'6clatement des gaines de myeMine, probalement le resultat de l'oedeme. En examinant l'approvisionnement sanguin de la substance blanche c6r6brale, nous concluons qu'aucune alteration pathologique des rameaux m6dullaires des arteres ce>6brales, les memes vaisseaux qui fournissent la substance blanche, ne peuvent causer une telle paleur diffuse de la substance blanche et au meme temps dviter les fibres arciformes. Seulement cette paleur peuvent etre le resultat de l'oedeme cerebrale, vraisemblablement d'origine hypoxiqueisch6mique, hypotensive, ou acidotique. Nous constatons egalement que l'arteriosclerose peut causer la demence seulement par des infarctus multiples ou par des cavites, si en verite elle produit la d6mence.

This study quantified the differences in the efficacy and safety of different stimulation domains of anti-CD19 chimeric antigen receptor (CAR) T therapy for B-cell acute lymphoblastic leukemia (B-ALL). Clinical trials related to anti-CD19 CAR T-cell therapy for B-ALL were searched in public databases from database inception to 13 November 2021. The differences in overall survival (OS) and progression-free survival (PFS) of B-ALL patients treated with anti-CAR T-cell therapy containing 4-1BB and CD28 co-stimulatory domains were compared by establishing a parametric survival function. The overall remission rate (ORR), the proportion of people with minimal residual disease (MRD)-negative complete remission (CR), the incidence of cytokine release syndrome (CRS), and the neurotoxicity across different co-stimulatory domains was assessed using a random-effects model. The correlation between the ORR, MRD-negative CR, PFS, and OS was tested. The results showed that the median OS of anti-CAR T-cell treatment containing 4-1BB and CD28 co-stimulatory domains was 15.0 months (95% CI: 11.0–20.0) and 8.5 months (95% CI: 5.0–14.0), and the median PFS was 7.0 months (95% CI: 4.0–11.5) and 3.0 months (95% CI: 1.5–7.0), respectively. Anti-CD19 CAR T-cells in the 4-1BB co-stimulatory domain showed superior benefits in patients who achieved ORR. The incidence of neurotoxicity was significantly higher in the CD28 co-stimulatory domain of anti-CD19 CAR T-cells than in the 4-1BB co-stimulatory domain. In addition, the ORR and MRD-negative CR were strongly correlated with OS and PFS, and PFS and OS were strongly correlated. The 4-1BB co-stimulatory domain suggested a better benefit–risk ratio than the CD28 co-stimulatory domain in B-ALL.