Animal Models of Rheumatoid Arthritis

Autoimmunity is a condition in which the host organizes an immune response against its own antigens. Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, characterized by the presence of chronic inflammatory infiltrates, the development of destructive arthropathy, bone erosion, and degradation of the articular cartilage and subchondral bone. There is currently no treatment that resolves the disease, only the use of palliatives, and not all patients respond to pharmacologic therapy. According to RA multifactorial origin, several in vivo models have been used to evaluate its pathophysiology as well as to identify the usefulness of biomarkers to predict, to diagnose, or to evaluate the prognosis of the disease. This chapter focuses on the most common in vivo models used for the study of RA, including those related with genetic, immunological, hormonal, and environmental interactions. Similarly, the potential of these models to understand RA pathogenesis and to test preventive and therapeutic strategies of autoimmune disorder is also highlighted. In conclusion, of all the animal models discussed, the CIA model could be considered the most successful by generating arthritis using type II collagen and adjuvants and evaluating therapeutic compounds both intra-articularly and systemically

Pre-operative conditions seen in the universe of patients undergoing abdominal wall reconstruction for large subcostal hernias.

Pre-operative conditions seen in the universe of patients undergoing abdominal wall reconstruction for large subcostal hernias.</p

Fig 1 -

(Upper left): Right subcostal hernia measuring 26 x 23 cm in a patient with liver cirrhosis Child-Pugh A who had a right hepatectomy and a right colectomy one year before due to invasive hepatocellular carcinoma. (Upper right): A retromuscular plane behind the right transversus abdominis, the right rectus and the left rectus muscles has been developed, and closure between right posterior rectus sheath and right transversalis fascia has been achieved. (Lower left): A 30 x 30 cm large pore polypropylene mesh has been placed in the retromuscular plane. (Lower right): With the operating table flexed, horizontal closure of the right subcostal defect has been performed to provide restoration of the myofascial continuity of the abdominal wall.</p

Adrenalectomy for solid tumor metastases: Results of a multicenter European study

Background. We assessed the results of adienalectomy for solid tumor metastases in 317 patients recruited from 30 European Centers. Methods. Patients with histologically proven adrenal metastatic disease and undergoing complete removal(s) of the affected.gland(s) were eligible. Results. Non-small cell lung cancer (NSCLC) was the most frequent tumor type followed by colorectal and renal cell carcinoma. Adrenal metastases were synchronous 6 months) in 73 (23%) patients and isolated in 213 (67%). The median disease-free interval was 18.5 months. Laparoscopic resection was used in 46% of patients. Surgery was limited to the adrenal gland in 73% of patients and RO resection was achieved in 86% of cases. The median overall survival was 29 months (95 % confidence interval,. 24.69733.30). The survival rates at 1, 2, 3, and 5 years were 80%, 61%,. 42%, and 35%, respectively. Patients with renal" cancer showed a median survival of 84 months, patients with NSCLC 26 months, and patients with colorectal cancer 29 months (P =.017). Differences in survival between metachronous and synchronous lesions were also significant (30 vs 23 months; P =.038). Conclusion. Surgical removal of adrenal metastasis is associated with long-term survival in se

Adrenalectomy for solid tumor metastases: Results of a multicenter European study

BACKGROUND: We assessed the results of adrenalectomy for solid tumor metastases in 317 patients recruited from 30 European centers. METHODS: Patients with histologically proven adrenal metastatic disease and undergoing complete removal(s) of the affected gland(s) were eligible. RESULTS: Non-small cell lung cancer (NSCLC) was the most frequent tumor type followed by colorectal and renal cell carcinoma. Adrenal metastases were synchronous (???6 months) in 73 (23%) patients and isolated in 213 (67%). The median disease-free interval was 18.5 months. Laparoscopic resection was used in 46% of patients. Surgery was limited to the adrenal gland in 73% of patients and R0 resection was achieved in 86% of cases. The median overall survival was 29 months (95% confidence interval, 24.69-33.30). The survival rates at 1, 2, 3, and 5 years were 80%, 61%, 42%, and 35%, respectively. Patients with renal cancer showed a median survival of 84 months, patients with NSCLC 26 months, and patients with colorectal cancer 29 months (P = .017). Differences in survival between metachronous and synchronous lesions were also significant (30 vs. 23 months; P = .038). CONCLUSION: Surgical removal of adrenal metastasis is associated with long-term survival in selected patient

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. RESULTS: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. CONCLUSION: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk