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Background: Cachexia, a syndrome of muscle atrophy, adipose loss, and anorexia, is associated with reduced survival in cancer patients. The colon adenocarcinoma C26c20 cell line secretes the cytokine leukemia inhibitory factor (LIF) which induces cachexia. We characterized how LIF promotes cachexia-associated weight loss and anorexia in mice through JAK-dependent changes in adipose and hypothalamic tissues., Methods: Cachexia was induced in vivo with the heterotopic allotransplanted administration of C26c20 colon adenocarcinoma cells or the intraperitoneal administration of recombinant LIF in the absence or presence of JAK inhibitors. Blood, adipose, and hypothalamic tissues were collected and processed for cyto/adipokine ELISAs, immunoblot analysis, and quantitative RT-PCR. Cachexia-associated lipolysis was induced in vitro by stimulating differentiated adipocytes with recombinant LIF or IL-6 in the absence or presence of lipase or JAK inhibitors. These adipocytes were processed for glycerol release into the media, immunoblot analysis, and RT-PCR., Results: Tumor-secreted LIF induced changes in adipose tissue expression and serum levels of IL-6 and leptin in a JAK-dependent manner influencing cachexia-associated adipose wasting and anorexia. We identified two JAK inhibitors that block IL-6 family-mediated adipocyte lipolysis and IL-6 induction using an in vitro cachexia lipolysis assay. JAK inhibitors administered to the in vivo C26c20 cancer cachexia mouse models led to 1) a decrease in STAT3 phosphorylation in hypothalamic and adipose tissues, 2) a reverse in the cachexia serum cyto/adipokine signature, 3) a delay in cancer cachexia-associated anorexia and adipose loss, and 4) an improvement in overall survival., Conclusions: JAK inhibitors suppress LIF-associated adipose loss and anorexia in both in vitro and in vivo models of cancer cachexia., Competing Interests: Conflict of Interest: The authors disclose no conflicts

The carbohydrate-binding molecule galectin-3 has garnered significant attention recently as a biomarker for various conditions ranging from cardiac disease to obesity. Although there have been several recent studies investigating its role in stroke and other cerebrovascular diseases, awareness of this emerging biomarker in the wider neurology community is limited. We performed a systematic search in PubMed, Embase, Scopus, CINAHL, Clinicaltrials.gov and the Cochrane library in November and December 2016 for articles related to galectin-3 and cerebrovascular disease. We included both human and pre-clinical studies in order to provide a comprehensive view of the state of the literature on this topic. The majority of the relevant literature focuses on stroke, cerebral ischemia and atherosclerosis, but some recent attention has also been devoted to intracranial and subarachnoid hemorrhage. Higher blood levels of galectin-3 correlate with worse outcomes in atherosclerotic disease as well as in intracranial and subarachnoid hemorrhage in human studies. However, experimental evidence supporting the role of galectin-3 in these phenotypes is not as robust. It is likely that the role of galectin-3 in the inflammatory cascade within the central nervous system following injury is responsible for many of its effects, but its varied physiological functions and multiple sites of expression mean that it may have different effects depending on the nature of the disease condition and the time since injury. In summary, experimental and human research raises the possibility that galectin-3, which is closely linked to the inflammatory cascade, could be of value as a prognostic marker and therapeutic target in cerebrovascular disease., (© 2017 EAN.)

There are limited data investigating the epidemiology and resource utilization associated with parenteral prostacyclin use in children. We sought to examine national trends in treatment practices and resource utilization during prostacyclin initiation for pulmonary arterial hypertension (PAH) at children's hospitals in the United States. Patients with PAH initiated on parenteral epoprostenol and treprostinil (2004-2014) were identified using a nationwide administrative database. Demographics, clinical characteristics, and resource utilization were compared between epoprostenol and treprostinil groups. Costs were indexed in 2014 US dollars. Among 1448 children admitted with a primary or secondary diagnosis of PAH, 280 (19%) were initiated on parenteral prostacyclins (epoprostenol n = 195 and treprostinil n = 85). Epoprostenol predominated early (97% of initiations in 2005); however, treprostinil predominated recently (52-67% of initiations/year). Children initiated on treprostinil had shorter ICU stays (1 [IQR = 0-4] vs. 4 [0-10] days, P < 0.001), shorter total lengths of stay (4 [2-9] vs. 8 [4-18] days, P = 0.001), and lower in-hospital mortality (1 vs. 12%, P = 0.001) with no difference in 30-day (13 vs. 19%, P = 0.19) or one-year readmission rates (56 vs. 61%, P = 0.41). Inpatient costs were lower for treprostinil initiation ($23,779 [11,830-39,535] vs. $32,976 [11,904-94,082], P = 0.03), with a greater difference in the recent era (2009-2013). Though significant variation exists regarding prostacyclin use for PAH across US centers, prostacyclins are common among children with PAH. Treprostinil initiation has been increasing and is associated with less resource utilization and lower cost compared to epoprostenol initiation. Post-discharge outcome data are needed to fully inform decision-making about the relative benefits of parental prostacyclin drug choice.