A pediatric neurologic assessment score may drive the eculizumab-based treatment of Escherichia coli-related hemolytic uremic syndrome with neurological involvement.

BACKGROUND: Thrombotic microangiopathy (TMA) is a clinical syndrome encompassing a large group of rare but severe disorders including thrombotic thrombocytopenic purpura (TTP) and both typical and atypical forms of hemolytic uremic syndrome (HUS). The key role of the complement system is well known in TTP and atypical HUS, but recent reports describe its involvement in the pathogenesis of HUS secondary to gastrointestinal infections due to Shiga toxin-producing Escherichia coli (STEC). METHODS: TMA mainly affects the kidney, but extra-renal complications are frequently described. The involvement of the central nervous system (CNS) represents often a life-threatening condition and it can result in serious long-term disability in HUS patients who overcome the acute phase of illness. In the present study, we retrospectively analyzed a pediatric cohort of a single tertiary pediatric hospital in Southern Italy, in which this complication occurred in 12/54 children (22% of cases), of whom five with severe neurological involvement had been successfully treated with eculizumab. RESULTS: The great clinical variability of brain injury in our cohort has led us to retrospectively build a "neurological score" useful to assess the clinical severity of neurologic involvement. Subjects with higher neurologic score due to the most severe CNS involvement resulted in the group of patients early treated with eculizumab, obtaining a good clinical response (four out five patients). In conclusion, the early treatment with eculizumab in children with severe neurological involvement during STEC-HUS was associated with complete regression of both acute kidney injury (AKI) and neurological lesions observed at magnetic resonance imaging (MRI). CONCLUSIONS: A "neurological score" may be a useful tool to drive the early treatment of CNS complications in STEC-HUS with eculizumab, although future perspective controlled studies are urgently needed to validate this therapeutic approach.

Endovascular Treatment of Large and Giant Carotid Aneurysms with Flow-Diverter Stents Alone or in Combination with Coils: A Multicenter Experience and Long-Term Follow-up.

BACKGROUND: Although flow diverters (FDs) have been widely accepted by neurointerventionists, their safety has yet to be fully defined. Stratification by aneurysm size and location is essential for correct evaluation of treatment outcomes and risks of flow diversion. OBJECTIVE: To compare neurological and anatomic outcomes and evaluate the risk of complications after endovascular treatment of large or giant internal carotid artery (ICA) aneurysms with FD/FDs alone or together with coil embolization. METHODS: We reviewed all patients with large or giant, ruptured or unruptured ICA aneurysms who underwent endovascular treatment with flow diversion alone (group A) or with concomitant coiling (group B) in 4 international institutions between 2010 and 2015. Anatomic outcome was evaluated using the Byrne scale on digital subtraction angiography and/or angioMRI and/or angioCT scans 3, 6, 12, and 24 months postoperatively. RESULTS: We collected 44 patients with large or giant ICA aneurysms. Four patients (9%) presented with aneurysmal subarachnoid hemorrhage (SAH). FD/FDs were used alone in 26 patients and in combination with coil embolization in the 18 remaining patients. The mortality rate due to procedure-related and/or neurological complications was 2.2%. Twelve months after the procedure, 88.6% (n = 39) of patients had a favorable neurological outcome. One year after the procedure, the aneurysm was completely occluded in 72.7% of patients: 61.5% (16/18) in group A and 88.9% (16/26) in group B. CONCLUSION: Clinical outcomes and rates of intraoperative and postoperative complications did not differ significantly between the groups. Better anatomic results using FD/FDs combined with coils were documented 6 months after the procedure; this option seems to provide a higher aneurysm occlusion rate and reduce the need for retreatment.

Level of Internet use among Greek adolescents with type 1 diabetes.

Background Compulsive Internet use has emerged as a contemporary addictive behavior. Our aim was to investigate the reasons for Greek adolescents with type 1 diabetes mellitus (T1DM) and their families to use the Internet and additionally to investigate the level of Internet use and its associations to demographic, socio-economic parameters and glycemic control. Methods Patients with T1DM, aged >12 years and their parents were recruited during their regular visits to the Pediatric Diabetes Clinic. A similar group of healthy children, age- and sex-matched served as a control group. All participants were asked to fill out the Greek translated version of the Internet Addiction Test (IAT). Caregivers of patients with T1DM were asked to complete a second questionnaire consisting of questions regarding demographic and socio-economic data of the family and data concerning disease management. Results Thirty-five patients with T1DM (mean decimal age of 14.95 ± 1.90 years) and 35 controls participated in the study. Nine patients were on an insulin pump whereas the rest were on multiple daily injections. The mean total score of the patients' IAT questionnaires was significantly lower compared to the controls (26.26 ± 12.67 vs. 39.91 ± 18.55, p = 0.003). Controls were characterized as exhibiting moderate addictive behavior at a significantly higher percentage than patients (31.43% vs. 2.86%, p = 0.002). All patients on insulin pumps demonstrated normal Internet use. Mild addictive behavior was associated with a lower parental educational level. Finally, level of Internet use (IAT score) was positively associated to glycemic control (HbA1c value) with a correlation that was approaching significance (r = 0.315, p = 0.065). Conclusions Adolescents with T1DM and especially those on an insulin pump exhibit normal Internet use compared to their healthy peers. Time consumed on Internet correlates reversibly with glycemic control.

Dysregulated PI3K/Akt/PTEN pathway is a marker of a short disease-free survival in node-negative breast carcinoma.

The phosphoinositide 3-kinase/Akt pathway is involved in the pathogenesis of several human cancers. In this study, the biological and prognostic value of phosphoinositide 3-kinase/Akt pathway dysregulation was assessed by immunohistochemistry in a well-characterized series of 72 patients with node-negative breast cancer with a long-term follow-up. Phosphorylated Akt and PTEN expression was reduced in 32% and 12.5% of the tumors, respectively. Phosphorylated Akt or PTEN status was not associated with the main clinicopathologic and biological parameters, whereas their expression was tightly related to their downstream targets cyclin D1 and p27(Kip1) which are involved in cell proliferation. Survival analysis showed a strong association between a shorter disease-free survival and the dysregulated expression of phosphorylated Akt (P = .036), PTEN (P = .003), p27(Kip1) (P = .008), and Ki67 (P = .0007), or the distinct subtypes of breast tumors (luminal, HER2 overexpressing, and basal-like; P = .03). Moreover, multivariate analysis using the Cox proportional-hazards regression model showed that PTEN and Ki67 were independent predictive factors of disease recurrence and that their simultaneous dysregulation strongly increased the hazards ratio of the patients with node-negative breast cancer (hazards ratio, 38.30; P = .0014). In conclusion, our results show that the dysregulation of the phosphoinositide 3-kinase/Akt/PTEN pathway is relevant to the prognosis in node-negative breast carcinoma and that the evaluation of key components of this pathway might be a useful tool to identify the patients with node-negative breast cancer at high-risk of disease recurrence.

Markers of cell proliferation, apoptosis, and angiogenesis in thyroid adenomas: a comparative immunohistochemical and genetic investigation of functioning and nonfunctioning nodules.

OBJECTIVE: To perform (i) an immunohistochemical investigation of cell proliferation, apoptosis, angiogenesis, and malignancy markers in 15 functioning and 15 nonfunctioning thyroid adenomas, and in normal adjacent tissue, and (ii) a genetic analysis of thyroid-stimulating hormone receptor (TSH-r), Gsalpha, and RAS mutations in the same group of adenomas, in order to describe their expression within tissues and to correlate them with the hormonal functioning. DESIGN: Thirty patients who underwent surgery for a solitary thyroid nodule were included in the study. Adenomas and normal adjacent tissues were evaluated by immunohistochemistry using the following antibodies: MIB-1 for proliferative activity, bcl-2 and mutant p53 for apoptosis control, vascular endothelial growth factor-A (VEGF-A) for angiogenic activity, and galectin-3 as a marker for malignancy. To calculate microvascular density, "hot spots" were selected and defined by cells positive for CD34 staining. Genetic analysis for TSH-r, Gsalpha, and H-, K-, and N-RAS mutations was performed on adenoma specimens. MAIN OUTCOMES: Our results evidenced that a proportion of both functioning and nonfunctioning adenomas showed immunohistochemical phenotypes similar to normal adjacent tissue. No differences were found between functioning and nonfunctioning thyroid adenomas with regard to the expression of markers associated to angiogenesis (VEGF-A, microvascular density) and apoptosis control (mutant p53, bcl-2). All adenomas resulted negative for galectin-3 immunostaining. MIB-1 was the only marker showing a substantial difference of expression between the two groups of adenomas. TSH-r mutations were found in 12 out of 15 functioning adenomas, whereas the absence of Gsalpha and H-, K-, and N-RAS mutations was demonstrated in all adenomas. CONCLUSIONS: Our data suggest that the differences between functioning and nonfunctioning thyroid adenomas are restricted to the genetic mutations of the TSH-r, to the hormonal status of tumors, and to the proliferative activity, not involving markers of apoptosis control and angiogenesis.

Low utility of plasma Nociceptin/orphanin FQ in the diagnosis of hepatocellular carcinoma.

AIM: The utility of serum alpha-fetoprotein (alpha-FP) in the detection of hepatocellular carcinoma (HCC) is questionable. Very high circulating levels of nociceptin/orphanin FQ (N/OFQ), a ligand for a novel opioid receptor, have recently been reported in HCC. The aim of this study was to assess the role of plasma N/OFQ in the diagnosis of HCC arising in patients with liver cirrhosis. METHODS: Plasma N/OFQ levels were measured by ELISA in 58 patients (28 HCC and 30 liver cirrhosis) and in 25 healthy controls. The values were correlated with clinical and laboratory features including alpha-FP. Spearman index, biserial correlation coefficient, non parametric combination (NPC) test and discriminant stepwise analysis were used for statistical evaluation of data. RESULTS: The upper normal limit of nociceptin was 122 pg/mL. Plasma levels above this cut-off were found in 21.4% of patients with HCC, in 23.3% of those with cirrhosis and in 8% of healthy subjects. alpha-FP serum levels > 200 ng/mL were found in 46.4% of the patients with HCC and in none of those with cirrhosis. No correlation was found between N/OFQ levels and any of the clinical and laboratory features, including alpha-FP. By NPC test, HCC and cirrhotic patients were different with regard to alpha-FP (P = 0.000) but not in terms of nociceptin (P = 0.595). By point biserial correlation, HCC presence was positively correlated with alpha-FP (rpb = 0.52, P = 0.000) but not with N/OFQ (rpb = 0.16, P = 0.157). In a discriminant analysis, alpha-FP was significant in the Wilks test (Y = -0.709 + 0.03 alpha-FP) and properly classified 81% of all patients and 61% of HCC. N/OFQ had lower sensitivity, specificity and predictive values than alpha-FP. CONCLUSION: Nociceptin is increased in patients with chronic liver disease, independently of the presence of HCC, although the underlying mechanism has yet to be clarified. We conclude it is not a useful marker for HCC.

Postpartum ovarian vein thrombosis with simultaneous pyelocaliectasis: diagnosis and follow-up by MR imaging. Case report and literature review.

We describe the critical role of MR imaging in a case of postpartum ovarian vein thrombosis (OVT) with concomitant pyelocaliceal ectasia. MR imaging confirmed the diagnosis suspected on the basis of ultrasonography and computed tomography by demonstration of a subacute clot with high signal intensity within the right ovarian vein and its complete resolution after anticoagulant therapy. MR imaging is a useful noninvasive, accurate tool for the diagnosis and follow-up of this potentially life-threatening condition, providing information helpful for choosing a prompt medical treatment rather than a surgical therapy. To our knowledge, no previous case of OVT causing pyelocaliceal ectasia documented by MR imaging has been reported. However, even though our case is suggestive, a cause-effect relationship between OVT and hydronephrosis could not be demonstrated with certainty.

Serum thrombopoietin in chronic liver disease: relation to severity of the disease and spleen size.

BACKGROUND/AIMS: Thrombopoietin is a thrombopoietic factor mainly synthesized in the liver. Its production is regulated by the mass of megakaryocytes and platelets. Impaired production of thrombopoietin may be responsible for thrombocytopenia in chronic liver disease. METHODOLOGY: We studied thrombopoietin serum concentration in 68 patients with chronic liver disease of various degrees (39 with thrombocytopenia), in 5 patients with thrombocytopenia due to hematological disease, and in 27 healthy controls. RESULTS: Thrombopoietin concentration was higher in patients with liver disease than in controls. Patients with hematological disease had much higher thrombopoietin concentration than patients with liver disease. Among patients with liver disease and thrombocytopenia, thrombopoietin concentration was higher in cirrhosis than in chronic hepatitis. A negative correlation was found between platelet counts and spleen size and between thrombopoietin concentration and spleen size. No correlation was found between thrombopoietin concentration and liver disease severity. CONCLUSIONS: Patients with liver disease and thrombocytopenia have serum thrombopoietin concentration higher than normal controls. It seems therefore that the liver, even seriously diseased, maintains the ability to produce thrombopoietin. In the liver patients the number of circulating platelets and the serum levels of thrombopoietin are inversely correlated with the size of the spleen suggesting that thrombopoietin, although normally produced, might be turned over in platelets sequestrated in the spleen.