The impact of smoking on tuberculosis treatment outcomes: a meta-analysis.

BACKGROUND: Cigarette smoking contributes to tuberculosis (TB) epidemiology. However, limited evidence exists on how smoking impacts TB treatment outcomes such as treatment loss to follow-up and culture conversion.METHODS: This meta-analysis assessed current evidence of the impact of active cigarette smoking on TB treatment outcomes. PubMed, Scopus, Embase, and the Cochrane Library were searched for English-language articles published from database inception through 2017. Articles addressing active pulmonary TB and cigarette smoking were identified and data abstracted. Smokers were defined as those who smoked every day or some days at the time of interview/diagnosis. Non-smokers did not smoke at the time of interview/diagnosis. Unfavorable outcomes included any outcome other than cure or completion of TB treatment. Three different data sets were examined: 8 articles addressing unfavorable treatment outcomes, 9 analyzing only treatment loss to follow-up, and 5 addressing delayed smear or culture conversion. Studies that had <20 subjects or that addressed only populations with comorbidities were excluded.RESULTS: We identified 1030 studies; 21 studies fulfilled the inclusion/exclusion criteria. Smokers had greater odds of unfavorable outcomes (pooled odds ratio [pOR] 1.23, 95%CI 1.14-1.33), delayed smear or culture conversion (pOR 1.55, 95%CI 1.04-2.07), and treatment loss to follow-up (pOR 1.35, 95%CI 1.21-1.50).CONCLUSION: Cigarette smoking is associated with negative treatment results and delayed conversion to negative smear or culture, suggesting smoking is an important factor for consideration in TB elimination efforts.

Trophic factors intervention regenerates the nestin-expressing cell population in a model of perinatal excitotoxicity: Implications for perinatal brain injury and prematurity.

We previously showed that TSC1 (a combination of transferrin and IGF-1) is a potent inductor of myelinogenesis in myelin deficient rats and in demyelinated adult mice. More recently, we demonstrated that regeneration of oligodendrocyte progenitors and myelin are possible with a single dose of TSC1 in a mouse model of Premature birth. Here, using the same mouse model of perinatal white matter damage due to glutamate excitotoxicity (GME), we tested the hypothesis that regeneration of endogenous nestin-expressing neural progenitors improves the outcome of prematurity. Treatments: N-methyl-D-aspartate (NMDA), saline, NMDA+TSC1 together or NMDA followed byTSC1 3 days later, were stereotaxically delivered into the corpus callosum of P4 mouse pups. Fluorescence analysis showed an intense enrichment of nestin-expressing cells in groups injected with NMDA+TSC1 from which many were generated by proliferation. Moreover, when TSC1 was injected three days after the primary insult it was still able to reduce ventricular enlargement and extensively rescue nestin-expressing progenitors. Cells co-expressing the proliferation marker Ki67, CNPase and faint nestin label were more abundant in groups injected with MNDA+TSC1 at 35 days after injection. Stereological analysis showed that the number of nestin-expressing cells in the sub-ventricular zone correlated inversely with the volume of the ventricle. A delayed administration of TSC1 after excitotoxicity reduced ventriculomegaly but not as much as, when NMDA and TSC1 were injected simultaneously. Thus, the earliest TSC1 was administered, the more tissue was rescued as shown by reduced ventriculomegaly. Astrocytes responded to GME by upregulating the expression of estrogen receptor and this expression was attenuated in the presence of TSC1 suggesting a decreased inflammation and a lesser need for estrogen-mediated central nervous system (CNS) neuroprotection.