Functionally relevant white matter degradation in multiple sclerosis: a tract-based spatial meta-analysis

Purpose To identify statistical consensus between published studies for distribution and functional relevance of tract white matter (WM) degradation in multiple sclerosis (MS). Materials and Methods By systematically searching online databases, tract-based spatial statistics studies were identified that compared fractional anisotropy (FA; a marker for WM integrity) in MS patients to healthy control subjects, correlated FA in MS patients with physical disability, or correlated FA in MS patients with cognitive performance. Voxelwise meta-analysis was performed by using the Signed Differential Mapping method for each comparison. Moderating effects of mean age, mean physical disability score, imager magnet strength, lesion load, and number of diffusion directions were assessed by means of meta-regression. Results Meta-analysis was performed on data from 495 patients and 253 control subjects across 12 studies. MS diagnosis was significantly associated with widespread lower tract FA (nine studies; largest cluster, 4379 voxels; z = 7.1; P < .001). Greater physical disability was significantly associated with lower FA in the right posterior cingulum, left callosal splenium, right inferior fronto-occipital fasciculus, and left fornix crus (six studies; 323 voxels; z = 1.7; P = .001). Impaired cognition was significantly associated with lower FA in the callosal genu, thalamus, right posterior cingulum, and fornix crus (seven studies; largest cluster, 980 voxels; z = 2.5; P < .001). Conclusion WM damage is widespread in MS with differential and only minimally overlapping distributions of low FA that relates to physical disability and cognitive impairment. The higher number of clusters of lower FA in relation to cognition and their higher z scores suggest that cerebral WM damage may have a greater relevance to cognitive dysfunction than physical disability in MS, and that low anterior callosal and thalamic FA have specific importance to cognitive status

Immunocytochemical assessment of bone marrow aspirates for monitoring response to chemotherapy in small-cell lung cancer patients

Recent reports have suggested that tumour cell immunodetection in bone marrow of small-cell lung cancer patients is by far more frequent than found cytohistologically and may have clinical relevance. This study evaluates primarily the efficacy of chemotherapy as method of in vivo purging, but also the relationship of marrow involvement with survival. A total of 112 bone marrow aspirates from 30 chemo-naïve patients were stained twice using anti-NCAM antibodies, first at diagnosis and then after chemotherapy (24 patients) or at disease progression (six patients). Marrow contamination was associated with lower survival (P = 0.002), and was also detected in 7/17 patients conventionally staged as having limited disease. At multivariate analysis, marrow involvement was an independent factor of unfavourable prognosis (P = 0.033). The amount of tumour contamination, before and after chemotherapy, remained unchanged also in responders and even in the subset of patients with apparent limited disease. Following chemotherapy, bone marrow became tumour negative only in 25% of initially positive responders and in none of non-responders. Our results indicate that (i) chemotherapy is not effective in purging bone marrow even in chemo-responsive patients and (ii) a subset of patients with limited disease and negative bone marrow aspirates might have a more favourable prognosis. © 1999 Cancer Research Campaig

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe

Metabolomic analysis shows differential hepatic effects of T-2 and T-3 in rats after short-term feeding with high fat diet

Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T2 and T3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible. Our results showed that both T2 and T3 strongly induced autophagy and intra-hepatic acylcarnitine flux but prevented the generation of sphingolipid/ceramides in animals fed HFD. Interestingly, although both T2 and T3 decreased hepatic fat content, only T2 was able to rescue the impairment in AKT and MAPK/ERK pathways caused by HFD. In summary, we have identified and characterized the effects of T2 and T3 on hepatic metabolism during short-term exposure to HFD. These findings illuminate the common and divergent metabolic pathways by T2 and T3 that also may be important in the prevention and treatment of NAFLD.Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T-2) and triiodothyronine (T-3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T-2 and T-3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible. Our results showed that both T-2 and T-3 strongly induced autophagy and intra-hepatic acylcarnitine flux but prevented the generation of sphingolipid/ceramides in animals fed HFD. Interestingly, although both T-2 and T-3 decreased hepatic fat content, only T-2 was able to rescue the impairment in AKT and MAPK/ERK pathways caused by HFD. In summary, we have identified and characterized the effects of T-2 and T-3 on hepatic metabolism during short-term exposure to HFD. These findings illuminate the common and divergent metabolic pathways by T-2 and T-3 that also may be important in the prevention and treatment of NAFLD