On the Thermodynamics of Hot Hadronic Matter

The equation of state of hot hadronic matter is obtained, by taking into account the contribution of the massive states with the help of the resonance spectrum $\tau (m)\sim m^3$ justified by the authors in previous papers. This equation of state is in agreement with that provided by the low-temperature expansion for the pion intracting gas. It is shown that in this picture the deconfinement phase transition is absent, in agreement with lattice gauge calculations which show the only phase transition of chiral symmetry restoration. The latter is modelled with the help of the restriction of the number of the effective degrees of freedom in the hadron phase to that of the microscopic degrees of freedom in the quark-gluon phase, through the corresponding truncation of the hadronic resonance spectrum, and the decrease of the effective hadron masses with temperature, predicted by Brown and Rho. The results are in agreement with lattice gauge data and show a smooth crossover in the thermodynamic variables in a temperature range $\sim 50$ MeV.Comment: 21 pages, LaTeX, 3 postscript figure

Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in juvenile idiopathic arthritis: results of the phase 4 registry

Background This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs). Methods Children aged ≥2 to \u3c18 years with rheumatoid-factor–positive or –negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (≤6 months) an nsNSAID or celecoxib. Enrolled patients were followed to the end of the study, whether they remained on the original NSAID, switched, or discontinued therapy altogether. All adverse events (AEs) regardless of severity were captured in the database. Results A total of 274 patients (nsNSAID, n = 219; celecoxib, n = 55) were observed for 410 patient-years of observation. Naproxen, meloxicam, and nabumetone were the most frequently used nsNSAIDs. At baseline, the celecoxib group was older, had a numerically longer median time since diagnosis, and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance. AEs reported were those frequently observed with NSAID treatment and were similar across groups (nsNSAIDs: 52.0%; celecoxib: 52.9%). Twelve unique patients experienced a total of 18 serious AEs; the most frequent were infections, and none was attributed to NSAID use. Conclusions The safety profile of celecoxib and nsNSAIDs appears similar overall. The results from this registry, ongoing pharmacovigilance, and the phase 3 trial that led to the approval of celecoxib for children with JIA provide evidence that the benefit-risk for celecoxib treatment in JIA remains positive

Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in juvenile idiopathic arthritis: results of the phase 4 registry

BACKGROUND: This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs). METHODS: Children aged ≥2 to <18 years with rheumatoid-factor–positive or –negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (≤6 months) an nsNSAID or celecoxib. Enrolled patients were followed to the end of the study, whether they remained on the original NSAID, switched, or discontinued therapy altogether. All adverse events (AEs) regardless of severity were captured in the database. RESULTS: A total of 274 patients (nsNSAID, n = 219; celecoxib, n = 55) were observed for 410 patient-years of observation. Naproxen, meloxicam, and nabumetone were the most frequently used nsNSAIDs. At baseline, the celecoxib group was older, had a numerically longer median time since diagnosis, and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance. AEs reported were those frequently observed with NSAID treatment and were similar across groups (nsNSAIDs: 52.0%; celecoxib: 52.9%). Twelve unique patients experienced a total of 18 serious AEs; the most frequent were infections, and none was attributed to NSAID use. CONCLUSIONS: The safety profile of celecoxib and nsNSAIDs appears similar overall. The results from this registry, ongoing pharmacovigilance, and the phase 3 trial that led to the approval of celecoxib for children with JIA provide evidence that the benefit-risk for celecoxib treatment in JIA remains positive. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00688545

Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages.

Activated macrophages undergo metabolic reprogramming, which drives their pro-inflammatory phenotype, but the mechanistic basis for this remains obscure. Here, we demonstrate that upon lipopolysaccharide (LPS) stimulation, macrophages shift from producing ATP by oxidative phosphorylation to glycolysis while also increasing succinate levels. We show that increased mitochondrial oxidation of succinate via succinate dehydrogenase (SDH) and an elevation of mitochondrial membrane potential combine to drive mitochondrial reactive oxygen species (ROS) production. RNA sequencing reveals that this combination induces a pro-inflammatory gene expression profile, while an inhibitor of succinate oxidation, dimethyl malonate (DMM), promotes an anti-inflammatory outcome. Blocking ROS production with rotenone by uncoupling mitochondria or by expressing the alternative oxidase (AOX) inhibits this inflammatory phenotype, with AOX protecting mice from LPS lethality. The metabolic alterations that occur upon activation of macrophages therefore repurpose mitochondria from ATP synthesis to ROS production in order to promote a pro-inflammatory state

High Levels of DEK Autoantibodies in Sera of Patients With Polyarticular Juvenile Idiopathic Arthritis and With Early Disease Flares Following Cessation of Antiâ Tumor Necrosis Factor Therapy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142962/1/art40404_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142962/2/art40404-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142962/3/art40404.pd

Boganmeldelser

Intet resum

Measuring Process of Arthritis Care. A Proposed Set of Quality Measures for the Process of Care in Juvenile Idiopathic Arthritis

The ability to assess quality of care is a necessary component of continuous quality improvement. The assessment typically is accomplished by determination of compliance with a defined set of quality measures (QMs). The objective of this effort was to establish a set of QM for the assessment of the process of care in JIA

The effect on survival of continuing chemotherapy to near death

<p>Abstract</p> <p>Background</p> <p>Overuse of anti-cancer therapy is an important quality-of-care issue. An aggressive approach to treatment can have negative effects on quality of life and cost, but its effect on survival is not well-defined.</p> <p>Methods</p> <p>Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 7,879 Medicare-enrolled patients aged 65 or older who died after having survived at least 3 months after diagnosis of advanced non-small cell lung cancer (NSCLC) between 1991 and 1999. We used Cox proportional hazards regression analysis, propensity scores, and instrumental variable analysis (IVA) to compare survival among patients who never received chemotherapy (n = 4,345), those who received standard chemotherapy but not within two weeks prior to death (n = 3,235), and those who were still receiving chemotherapy within 14 days of death (n = 299). Geographic variation in the application of chemotherapy was used as the instrument for IVA.</p> <p>Results</p> <p>Receipt of chemotherapy was associated with a 2-month improvement in overall survival. However, based on three different statistical approaches, no additional survival benefit was evident from continuing chemotherapy within 14 days of death. Moreover, patients receiving chemotherapy near the end of life were much less likely to enter hospice (81% versus 51% with no chemotherapy and 52% with standard chemotherapy, P < 0.001), or were more likely to be admitted within only 3 days of death.</p> <p>Conclusions</p> <p>Continuing chemotherapy for advanced NSCLC until very near death is associated with a decreased likelihood of receiving hospice care but not prolonged survival. Oncologists should strive to discontinue chemotherapy as death approaches and encourage patients to enroll in hospice for better end-of-life palliative care.</p