Excessive cholecalciferol supplementation increases kidney dysfunction associated with intrarenal artery calcification in obese insulin-resistant mice.

Diabetes mellitus accelerates vascular calcification (VC) and increases the risk of end-stage renal disease (ESRD). Nevertheless, the impact of VC in renal disease progression in type 2 diabetes mellitus (T2DM) is poorly understood. We addressed the effect of VC and mechanisms involved in renal dysfunction in a murine model of insulin resistance and obesity (ob/ob), comparing with their healthy littermates (C57BL/6). We analyzed VC and renal function in both mouse strains after challenging them with Vitamin D3 (VitD3). Although VitD3 similarly increased serum calcium and induced bone disease in both strains, 24-hour urine volume and creatinine pronouncedly decreased only in ob/ob mice. Moreover, ob/ob increased urinary albumin/creatinine ratio (ACR), indicating kidney dysfunction. In parallel, ob/ob developed extensive intrarenal VC after VitD3. Coincidently with increased intrarenal vascular mineralization, our results demonstrated that Bone Morphogenetic Protein-2 (BMP-2) was highly expressed in these arteries exclusively in ob/ob. These data depict a greater susceptibility of ob/ob mice to develop renal disease after VitD3 in comparison to paired C57BL/6. In conclusion, this study unfolds novel mechanisms of progressive renal dysfunction in diabetes mellitus (DM) after VitD3 in vivo associated with increased intrarenal VC and highlights possible harmful effects of long-term supplementation of VitD3 in this population.

Intussusception reveals MUTYH-associated polyposis syndrome and colorectal cancer: a case report.

BACKGROUND: We are reporting a rare case of MUTYH-associated polyposis, a colorectal cancer hereditary syndrome, diagnosticated after an intussusception. Colorectal cancer is an important cause of cancer related mortality that can be manifested by an intussusception, a rare occurrence in adults and almost always related to tumors. Approximately 5% of colorectal cancers can be attributed to syndromes known to cause hereditary colorectal cancer, such as MUTYH-associated polyposis, autosomal genetic syndrome associated with this disease. CASE PRESENTATION: We present the case of a 44 years old male, that sought medical consultation with a complaint of abdominal discomfort, that after five days changed its characteristics. The patient was sent to the emergency department were a CT-scan revealed intestinal sub-occlusion by ileocolic invagination. Right colectomy was carried out. The anatomic-pathological examination revealed a moderately differentiated mucinous adenocarcinoma and multiples sessile polyps, which led to the suspicion of a genetic syndrome. In the genetics analysis two mutations were observed in the MUTYH gene, and MUTYH-associated polyposis was diagnosticated. CONCLUSION: This case demonstrates the importance of meticulous analysis of the patient examinations results to identify possible discrete alterations that can lead to improved understanding of disease.

Comparison of different laboratory tests in the evaluation of hemorrhagic risk of patients using rivaroxaban in the critical care setting: diagnostic accuracy study.

BACKGROUND: Rivaroxaban is a direct oral anticoagulant designed to dispense with the necessity of laboratory monitoring. However, monitoring rivaroxaban levels is necessary in certain clinical conditions, especially in the critical care setting. METHODS: This is a diagnostic accuracy study evaluating sensitivity and specificity of prothrombin time (PT), activated partial thromboplastin time (aPTT), and Dilute Russell viper venom time (dRVVT), to evaluate the hemorrhagic risk in patients taking rivaroxaban. The study used a convenience sample of 40 clinically stable patients using rivaroxaban to treat deep vein thrombosis or atrial fibrillation admitted in a private hospital in Brazil, compared to a group of 60 healthy controls. The samples from patients were collected two hours after the use of the medication (peak) and two hours before the next dose (trough). RESULTS: The correlation with the plasmatic concentration measured by anti-FXa assay was higher for PT and dRVVTS. The PT and aPTT tests presented higher specificity, while dRVVT was 100% sensible. CONCLUSIONS: There was a strong correlation between the tests and the plasma concentration of the drug. Additionally, our results demonstrated the potential use of dRVVT as a screening test in the emergency room and the need of a second test to improve specificity.