image guided ablations for thyroid tumours

Image guided ablations might be regarded as a promising effective and safe alternative for treatment of recurrent thyroid cancer in particular in patients with high surgical risk or refusing surgery. Furthermore, image guided ablations seems to represent a promising alternative to surgery or observation for micropapillary thyroid carcinoma, with the aim of providing an effective treatment with minimal invasiveness. Further studies are necessary to confirm the role in this settin

Biopsy of liver metastasis for women with breast cancer: Impact on survival

Abstract Background Biopsy of metastatic site of disease can influence treatment decisions, but its impact on survival remains uncertain. Patients and methods One-hundred patients with first metachronous liver metastases (LM) from breast cancer (BC) who underwent liver biopsy between 1999 and 2009 were identified. One-hundred matched control patients with LM from BC and no biopsy were selected. Results Liver biopsy had no statistically significant impact on survival when comparing biopsied patients to controls [HR 0.82 (95% CI 0.58–1.16)]. Patients with early metastasis (within 3 years) undergoing liver biopsy had a better survival [HR 0.60 (95% CI 0.38–0.97)] compared to those who did not. Liver biopsy had no statistically significant impact on survival in patients with late LM (after 3 years) [HR 1.09 (95% CI 0.69–1.74)]. We observed that 18 out of 100 biopsied patients (18.0%) had a conversion of predictive factors which allowed adjusting for therapy, specifically new expression of ER ( n = 5), overexpression of HER2 ( n = 12) or both ( n = 1). Fourteen out of 18 (77.8%) received anti-HER2 treatment for the first time at the time of metastasis and 3 others (16.7%) received hormone therapy. Those 18 patients showed a better survival compared to the other 82 biopsied patients [HR 0.55 (95% CI 0.28–1.10)] and compared to the 13 biopsied patients with disappearance of features which predicted responsiveness to a given treatment [HR 0.19 (95% CI 0.06–0.62)]. Conclusions Liver biopsy can impact survival of patients with early metastases from BC. Discordance between primary and distant lesions can offer the patients new treatment options

Image-guided thermal ablation of central renal tumors with retrograde cold pyeloperfusion technique: a monocentric experience

Purpose: To evaluate feasibility, safety and efficacy of image-guided thermal ablations associated with retrograde pyeloperfusion in patients with centrally located renal tumors. Materials and methods: 48 patients (15 women, 33 men, mean age 69.1 ± 11.8) were treated with image-guided thermal ablation associated with pyeloperfusion for 58 centrally located renal tumors (mean diameter 32.3 ± 7.32 mm). 7 patients had a single kidney. Microwave and radiofrequency ablation were used. All treatments were performed with ultrasound, CT, or fusion imaging guidance under general anesthesia and simultaneous retrograde cold pyeloperfusion technique. Results: Procedure was feasible in all cases. Technical success and primary technical efficacy were reached in 51/58 (88%) and 45/54 tumors (83%). With a second ablation performed in 5 tumors, secondary technical efficacy was achieved in 50/50 (100%) tumors. Minor and major complications occurred in 8/58 (13%) and 5/58 (8%) tumors. No significative change in renal function occurred after treatment. During follow-up, 5 recurrences occurred, that were retreated with a second ablation. At last follow up (mean 32.2 ± 22.0 months), 41/48 (85%) treated patients were free from disease. The median TTP and PFS were 27.0 (range, 2.3–80.0) and 26.5 months (range, 2.3–80.0), respectively. Conclusion: Image-guided thermal ablation associated with protective pyeloperfusion is a feasible, safe, and effective treatment option for patients with central renal tumors with a minimal impact on renal function and relevant potential to avoid nephrectomy

Insulin resistance, diabetic kidney disease, and all-cause mortality in individuals with type 2 diabetes. a prospective cohort study

BACKGROUND: It is unclear whether insulin resistance (IR) contributes to excess mortality in patients with type 2 diabetes independent of diabetic kidney disease (DKD), which is strongly associated with IR and is a major risk factor for cardiovascular disease (CVD), the main cause of death in these individuals. We tested this hypothesis in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian Multicentre Study.METHODS: This observational, prospective, cohort study enrolled 15,773 patients with type 2 diabetes attending 19 Italian Diabetes Clinics in 2006-2008. Insulin sensitivity was assessed as estimated glucose disposal rate (eGDR), which was validated against the euglycaemic-hyperinsulinemic clamp technique. Vital status on October 31, 2015, was retrieved for 15,656 patients (99.3%). Participants were stratified by eGDR tertiles from T1 (≥ 5.35mg/kg/min) to T3 (≤ 4.14mg/kg/min, highest IR).RESULTS: CVD risk profile was worse in T2 and T3 vs T1. eGDR tertiles were independently associated with micro- and macroalbuminuria and the albuminuric DKD phenotypes (albuminuria with preserved or reduced estimated glomerular filtration rate [eGFR]) as well as with eGFR categories or the nonalbuminuric DKD phenotype. Over a 7.4-year follow-up, unadjusted death rates and mortality risks increased progressively across eGDR tertiles, but remained significantly elevated after adjustment only in T3 vs T1 (age- and gender- adjusted death rate, 22.35 vs 16.74 per 1000 person-years, p<0.0001, and hazard ratio [HR] adjusted for multiple confounders including DKD, 1.140 [95% confidence interval [CI], 1.049-1.238], p=0.002). However, eGDR was independently associated with mortality in participants with no DKD (adjusted HR, 1.214 [95% CI, 1.072-1.375], p=0.002) and in those with nonalbuminuric DKD (1.276 [1.034-1.575], p=0.023), but not in those with the albuminuric DKD phenotypes. Moreover, the association was stronger in males and in younger individuals and was observed in those without but not with prior CVD, though interaction was significant only for age.CONCLUSIONS: The proxy of insulin sensitivity eGDR predicts all-cause mortality in type 2 diabetes, independent of confounders including DKD. However, the impact of IR in individuals with albuminuric DKD may be mediated by its relationship with albuminuria.TRIAL REGISTRATION: ClinicalTrials.gov , NCT00715481, retrospectively registered 15 July 2008

Independent association of atherogenic dyslipidaemia with all-cause mortality in individuals with type 2 diabetes and modifying effect of gender. a prospective cohort study

Atherogenic dyslipidaemia has been implicated in the residual risk for cardiovascular morbidity and mortality, which remains despite attainment of LDL cholesterol goals especially in individuals with type 2 diabetes. However, its relationship with all-cause death has not been sufficiently explored. This analysis evaluated the independent association of increased triglycerides and triglyceride:HDL cholesterol ratio (TG:HDL) and decreased HDL cholesterol with total mortality and the possible modifying effect of gender in a large cohort of patients with type 2 diabetes

Two novel C-terminus RUNX2 mutations in two cleidocranial dysplasia (CCD) patients impairing p53 expression

Cleidocranial dysplasia (CCD), a dominantly inherited skeletal disease, is characterized by a variable phenotype ranging from dental alterations to severe skeletal defects. Either de novo or inherited mutations in the RUNX2 gene have been identified in most CCD patients. Transcription factor RUNX2, the osteogenic master gene, plays a central role in the commitment of mesenchymal stem cells to osteoblast lineage. With the aim to analyse the effects of RUNX2 mutations in CCD patients, we investigated RUNX2 gene expression and the osteogenic potential of two CCD patients’ cells. In addition, with the aim to better understand how RUNX2 mutations interfere with osteogenic differentiation, we performed string analyses to identify proteins interacting with RUNX2 and analysed p53 expression levels. Our findings demonstrated for the first time that, in addition to the alteration of downstream gene expression, RUNX2 mutations impair p53 expression affecting osteogenic maturation. In conclusion, the present work provides new insights into the role of RUNX2 mutations in CCD patients and suggests that an in-depth analysis of the RUNX2-associated gene network may contribute to better understand the complex molecular and phenotypic alterations in mutant subjects

Distribution of cardiovascular disease and retinopathy in patients with type 2 diabetes according to different classification systems for chronic kidney disease: a cross-sectional analysis of the renal insufficiency and cardiovascular events (RIACE) Italian multicenter study

BACKGROUND: The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF's KDOQI) staging system for chronic kidney disease (CKD) is based primarily on estimated GFR (eGFR). This study aimed at assessing whether reclassification of subjects with type 2 diabetes using two recent classifications based on both eGFR and albuminuria, the Alberta Kidney Disease Network (AKDN) and the Kidney Disease: Improving Global Outcomes (KDIGO), provides a better definition of burden from cardiovascular disease (CVD) and diabetic retinopathy (DR) than the NKF's KDOQI classification. METHODS: This is a cross-sectional analysis of patients with type 2 diabetes (n = 15,773) from the Renal Insufficiency And Cardiovascular Events Italian Multicenter Study, consecutively visiting 19 Diabetes Clinics throughout Italy in years 2007-2008. Exclusion criteria were dialysis or renal transplantation. CKD was defined based on eGFR, as calculated from serum creatinine by the simplified Modification of Diet in Renal Disease Study equation, and albuminuria, as measured by immunonephelometry or immunoturbidimetry. DR was assessed by dilated fundoscopy. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events. RESULTS: Though prevalence of complications increased with increasing CKD severity with all three classifications, it differed significantly between NKF's KDOQI stages and AKDN or KDIGO risk categories. The AKDN and KDIGO systems resulted in appropriate reclassification of uncomplicated patients in the lowest risk categories and a more graded independent association with CVD and DR than the NKF's KDOQI classification. However, CVD, but not DR prevalence was higher in the lowest risk categories of the new classifications than in the lowest stages of the NKF's KDOQI, due to the inclusion of subjects with reduced eGFR without albuminuria. CVD prevalence differed also among eGFR and albuminuria categories grouped into AKDN and KDIGO risk category 1 and moderate, respectively, and to a lesser extent into higher risk categories. CONCLUSIONS: Though the new systems perform better than the NKF's KDOQI in grading complications and identifying diabetic subjects without complications, they might underestimate CVD burden in patients assigned to lower risk categories and should be tested in large prospective studies

Assessing a candidate IIA dual to metastable supersymmetry-breaking

We analyze the space of linearized non-supersymmetric deformations around a IIA solution found by Cvetic, Gibbons, Lu and Pope (CGLP) in hep-th/0101096. We impose boundary conditions aimed at singling out among those perturbations those describing the backreaction of anti-D2 branes on the CGLP background. The corresponding supergravity solution is a would-be dual to a metastable supersymmetry-breaking state. However, it turns out that this candidate bulk solution is inevitably riddled with IR divergences of its flux densities and action, whose physical meaning and implications for models of string cosmology call for further investigation.Comment: 33 pages. v2: reference added, clarifications in the introductio

Chemotherapy effects on brain glucose metabolism at rest

Background: A growing number of studies reports that chemotherapy may impair brain functions inducing cognitive changes which can persist in a subset of cancer survivors. Aims: To investigate the neural basis of the chemotherapy-induced neurobehavioral changes by means of metabolic imaging and voxel-based statistical parametric mapping analyses. Methods: We studied the resting brain [18]FDG-PET/CT images of 43 adult cancer patients with solid (n=12, 28%) or hematologic malignancies (n=31, 72%); 12 patients were studied prior to chemotherapy (No chemotherapy) while treated patients were divided into two matched subgroups: Early High (6 chemotherapy cycles, n=10), and Late Low (>9 months after chemotherapy, <6 chemotherapy cycles, n=21). Findings: Compared to No chemotherapy, the Early High subgroup showed a significant bilateral (p<0.05) lower regional cerebral metabolic rate of glucose metabolism in both the prefrontal cortices and white matter, cerebellum, posterior medial cortices and limbic regions. A similar pattern emerged in the Early High versus Low Late comparison, while no significant result was obtained in the Low Late versus No chemotherapy comparison. The number of cycles and the post-chemotherapy time were negatively and positively correlated, respectively, with a set of these same brain regions. Interpretation: The present study shows that chemotherapy induces significant transient changes in the glucose metabolism of multiple cerebral cortical and white matter regions with a prevailing involvement of the prefrontal cortex. The severity of these changes are significantly related with the number of chemotherapy cycles and a subset of brain regions seems to present longer lasting, but more subtle, metabolic changes

Expression of FBXW11 in normal and disease-associated osteogenic cells

The ubiquitin-proteasome system (UPS) plays an important role in maintaining cellular homeostasis by degrading a multitude of key regulatory proteins. FBXW11, also known as b-TrCP2, belongs to the F-box family, which targets the proteins to be degraded by UPS. Transcription factors or proteins associated with cell cycle can be modulated by FBXW11, which may stimulate or inhibit cellular proliferation. Although FBXW11 has been investigated in embryogenesis and cancer, its expression has not been evaluated in osteogenic cells. With the aim to explore FBXW11gene expression modulation in the osteogenic lineage we performed molecular investigations in mesenchymal stem cells (MSCs) and osteogenic cells in normal and pathological conditions. In vitro experiments as well as ex vivo investigations have been performed. In particular, we explored the FBXW11 expression in normal osteogenic cells as well as in cells of cleidocranial dysplasia (CCD) patients or osteosarcoma cells. Our data showed that FBXW11 expression is modulated during osteogenesis and overexpressed in circulating MSCs and in osteogenically stimulated cells of CCD patients. In addition, FBXW11 is post-transcriptionally regulated in osteosarcoma cells leading to increased levels of beta-catenin. In conclusion, our findings show the modulation of FBXW11 in osteogenic lineage and its dysregulation in impaired osteogenic cells