To provide evidence-based recommendations to oncologists and others for the treatment of patients with metastatic pancreatic cancer.
American Society of Clinical Oncology convened an Expert Panel of ...medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts to conduct a systematic review of the literature from April 2004 to June 2015. Outcomes were overall survival, disease-free survival, progression-free survival, and adverse events.
Twenty-four randomized controlled trials met the systematic review criteria.
A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. Goals of care, patient preferences, treatment response, psychological status, support systems, and symptom burden should guide decisions for treatments. A palliative care referral should occur at first visit. FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin; favorable comorbidity profile) or gemcitabine plus nanoparticle albumin-bound (NAB) -paclitaxel (adequate comorbidity profile) should be offered to patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1 based on patient preference and support system available. Gemcitabine alone is recommended for patients with ECOG PS 2 or with a comorbidity profile that precludes other regimens; the addition of capecitabine or erlotinib may be offered. Patients with an ECOG PS ≥ 3 and poorly controlled comorbid conditions should be offered cancer-directed therapy only on a case-by-case basis; supportive care should be emphasized. For second-line therapy, gemcitabine plus NAB-paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX, an ECOG PS 0 to 1, and a favorable comorbidity profile; fluorouracil plus oxaliplatin, irinotecan, or nanoliposomal irinotecan should be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, ECOG PS 0 to 1, and favorable comorbidity profile, and gemcitabine or fluorouracil should be offered to patients with either an ECOG PS 2 or a comorbidity profile that precludes other regimens. Additional information is available at www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki.
Lithium–sulfur (Li‐S) batteries have a high specific energy capacity and density of 1675 mAh g−1 and 2670 Wh kg−1, respectively, rendering them among the most promising successors for lithium‐ion ...batteries. However, there are myriads of obstacles in the practical application and commercialization of Li‐S batteries, including the low conductivity of sulfur and its discharge products (Li2S/Li2S2), volume expansion of sulfur electrode, and the polysulfide shuttle effect. Hence, immense attention has been devoted to rectifying these issues, of which the application of metal‐based compounds (i.e., transition metal, metal phosphides, sulfides, oxides, carbides, nitrides, phosphosulfides, MXenes, hydroxides, and metal‐organic frameworks) as sulfur hosts is profiled as a fascinating strategy to hinder the polysulfide shuttle effect stemming from the polar–polar interactions between the metal compounds and polysulfides. This review encompasses the fundamental electrochemical principles of Li‐S batteries and insights into the interactions between the metal‐based compounds and the polysulfides, with emphasis on the intimate structure–activity relationship corroborated with theoretical calculations. Additionally, the integration of conductive carbon‐based materials to ameliorate the existing adsorptive abilities of the metal‐based compound is systematically discussed. Lastly, the challenges and prospects toward the smart design of catalysts for the future development of practical Li‐S batteries are presented.
The lithium–sulfur battery is the frontrunner technology for potential large‐scale energy storage stemming from its high specific energy capacity and superior energy density. The transition metals, metal dichalcogenides, metal phosphides, metal oxides, metal carbides, metal nitrides, and others (e.g., metal phosphosulfides, metal hydroxides, metal–organic frameworks and hybrids), which can serve as robust cathodes for high‐performance Li–S batteries, are presented.
Hemophagocytic Lymphohistiocytosis (HLH) is a group of disorders culminating in systemic inflammation and multi-organ failure with high incidence of hepatic dysfunction. Overproduction of IFN-γ is ...the main immunopathological driver in this disorder. Monokine induced by IFN-γ (CXCL9) serves as a biomarker for disease activity and response to treatment in this disorder. However, very little is understood about the actual functional role of CXCL9 in pathogenesis in HLH. In the current study, we sought to determine the role of CXCL9 in pathogenesis in murine models of both Familial HLH (prf1
) and Toll Like Receptor (TLR) 9 repeated stimulation induced Macrophage Activation Syndrome (MAS), a form of secondary HLH. FHL and MAS were induced in both CXCL9 genetically deficient mice (cxcl9
) and controls as well as using AMG487, a pharmacological antagonist of the CXCL9 receptor, CXCR3. Results showed that CXCL9 genetic deficiency did not improve disease parameters or hepatitis in both models. Consistent with genetic ablation of CXCL9, inhibition of its receptor, CXCR3, by AMG487 did not show any significant effects in the FHL model. Taken together, inhibition of CXCL9-CXCR3 interaction does not ameliorate HLH physiology in general, or hepatitis as a classical target organ of disease.
Background
The present study compared the treatment changes in the upper airway, hyoid bone position and craniofacial morphology between two groups of children with skeletal class II malocclusion ...treated with the headgear activator (HGA) and Herbst appliance (Herbst).
Setting and sample population
Orthodontic population from the Faculty of Dentistry of the University of Hong Kong.
Methods
Thirty‐four skeletal class II patients treated with the HGA (17 patients, mean age 10.6 ± 1.5 years) and the Herbst (17 patients, mean age 11.0 ± 1.4 years) were matched for sex, age, overjet, skeletal class and mandibular divergence. The patients received lateral cephalometric radiographs (LCRs) at the beginning of treatment (T1), after treatment (T2) and at follow‐up (T3). In the HGA group, patients underwent LCRs 7 months before the beginning of treatment (T0), which were used as growth reference for intra‐group comparison. Paired Student's t tests were used for intra‐ and inter‐group comparisons (α = .05).
Results
Treatment changes (T2‐T1) did not differ significantly between the groups. However, at follow‐up (T3‐T1) the Herbst group showed a smaller increase than the HGA group in the vertical position of the hyoid bone relative to the Frankfort plane (P = .013) and mandibular plane (P = .013).
Conclusions
There were no significant differences in the upper airway, hyoid bone position and craniofacial morphology between the groups at the end of treatment. However, the Herbst may provide better long‐term control of the vertical position of the hyoid bone than the HGA in children with skeletal class II malocclusion.
OBJECTIVES/GOALS: Familial Hemophagocytic Lymphohistiocytosis (FHL) is a systemic inflammatory disease, causing acute liver failure (ALF). Elevated Interferon gamma (IFN-γ) results in increased ...hepatic transcription of the chemokines CXCL9 and CXCL10. Inhibition of their receptor CXCR3 may reduce leukocyte recruitment and ameliorate hepatitis. METHODS/STUDY POPULATION: To determine the functional role of the IFN-γ-induced ligands, CXCL9 and CXCL10, in hepatic leukocyte recruitment via CXCR3 we used a prf-/- mouse infected with Lymphocytic Choriomeningitis Virus (LCMV) in our well-established model mimicking human FHL. We used AMG487, a small molecule CXCR3 antagonist, while maintaining intact IFN-γ signaling. Mice were sacrificed 10 days after infection when mice developed features of FHL: cytopenias, organomegaly, elevated serum ferritin and sCD25, and hepatic inflammation. Hepatic inflammation was characterized using flow cytometry, liver histology and noninvasive markers of hepatitis (ALT, liver size). RESULTS/ANTICIPATED RESULTS: AMG487 did not ameliorate the overall disease phenotype with mice developing similar FHL characteristics compared to control, including weight loss, elevation of ALT and sIL-2r as well as degree of thrombocytopenia and anemia. There was significant reduction of recruitment of CXCR3+CD4+ T cells and B cells in mice treated with AMG487. This indicates the importance of CXCR3 receptor in humoral response in FHL hepatitis. In addition, treatment with AMG487 resulted in reduction of CXCR3 expression in hepatic inflammatory monocyte (iMonos) measured by mean fluorescence intensity (MFI). DISCUSSION/SIGNIFICANCE: This is the first pre-clinical experience using AMG487, a small molecule CXCR3 antagonist, to treat FHL hepatitis. AMG487 changed the hepatic inflammatory milieu, reducing CD4 T-cell and B-cell recruitment, as well as CXCR3 expression on iMonos. However, it did not ameliorate FHL hepatitis and other therapeutic approaches should be pursued.
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