Deficiency of immunoregulatory indoleamine 2,3-dioxygenase 1in juvenile diabetes.

A defect in indoleamine 2,3-dioxygenase 1 (IDO1), which is responsible for immunoregulatory tryptophan catabolism, impairs development of immune tolerance to autoantigens in NOD mice, a model for human autoimmune type 1 diabetes (T1D). Whether IDO1 function is also defective in T1D is still unknown. We investigated IDO1 function in sera and peripheral blood mononuclear cells (PBMCs) from children with T1D and matched controls. These children were further included in a discovery study to identify SNPs in IDO1 that might modify the risk of T1D. T1D in children was characterized by a remarkable defect in IDO1 function. A common haplotype, associated with dysfunctional IDO1, increased the risk of developing T1D in the discovery and also confirmation studies. In T1D patients sharing such a common IDO1 haplotype, incubation of PBMCs in vitro with tocilizumab (TCZ) - an IL-6 receptor blocker - would, however, rescue IDO1 activity. In an experimental setting with diabetic NOD mice, TCZ was found to restore normoglycemia via IDO1-dependent mechanisms. Thus, functional SNPs of IDO1 are associated with defective tryptophan catabolism in human T1D, and maneuvers aimed at restoring IDO1 function would be therapeutically effective in at least a subgroup of T1D pediatric patients.

Cerebral Sinovenous Thrombosis in the Asphyxiated Cooled Infants: A Prospective Observational Study.

BACKGROUND: Cerebral sinovenous thrombosis is unusual in the asphyxiated cooled infants, but reliable data regarding the incidence of this comorbidity are lacking. We assessed the incidence of sinovenous thrombosis in a population of asphyxiated cooled infants by performing routine brain magnetic resonance venography. METHODS: All asphyxiated infants who underwent therapeutic cooling at our institution completed brain magnetic resonance venography after rewarming. Assessing the incidence of cerebral sinovenous thrombosis was the primary goal. Secondary analyses included group comparisons for laboratory tests and monitored parameters, relationship between variables, logistic regression models, and receiver operating characteristic curve for cerebral sinovenous thrombosis prediction. RESULTS: Cerebral sinovenous thrombosis was detected in 10 of 37 infants (27%), most commonly affecting the superior sagittal sinus (eight of ten). These infants manifested higher blanket (P < 0.001) and lower esophageal temperatures (P = 0.006), lower platelet counts (P = 0.045), and received more red blood cell transfusions (P = 0.038) than the cooled infants without thrombosis. Blanket temperature was independently associated with cerebral sinovenous thrombosis (P = 0.049), and 32°C/hour was the optimal cutoff value to predict the event (sensitivity, 90%; specificity, 88.5%). CONCLUSIONS: High incidence or cerebral sinovenous thrombosis in neonates treated with therapeutic hypothermia suggests that magnetic resonance venography may be reasonable in many of these children. High blanket temperature may be one variable that helps identify patients at higher risk.

Autonomic neuropathy in diabetes mellitus.

Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. The pathogenesis is still unclear and probably multifactorial. Once DAN becomes clinically evident, no form of therapy has been identified, which can effectively stop or reverse it. Prevention strategies are based on strict glycemic control with intensive insulin treatment, multifactorial intervention, and lifestyle modification including control of hypertension, dyslipidemia, stop smoking, weight loss, and adequate physical exercise. The present review summarizes the latest knowledge regarding clinical presentation, epidemiology, pathogenesis, and management of DAN, with some mention to childhood and adolescent population.

Childhood Crohn's disease presenting as chronic constipation.

Inflammatory bowel disease (IBD) include Crohn's disease (CD) and ulcerative colitis (UC). In children signs and symptoms of IBD are often non-specific, diagnosis is more difficult than in adults and systemic manifestation as growth failure and delayed puberty are common. While abdominal pain, rectal bleeding and diarrhoea are usual symptoms, constipation represents an unusual presentation of CD or UC. We report a 9-years-old girl with severe constipation, worsening abdominal pain, intermittent fever, diagnosed as CD. To our knowledge, this is a rare case of CD presenting as chronic constipation in children; we can find, in reviewed recent literature, only few report of similar condition.