The multidimensional prognostic index (MPI) predicts long-term mortality in old type 2 diabetes mellitus patients: a 13-year follow-up study.

PURPOSE: The Multidimensional Prognostic Index (MPI) is a tool capable of holistically frame older patients in different settings and affected by different pathologies, establishing a risk of adverse events. Among them, type 2 diabetes mellitus (T2DM), a common metabolic disease in the elderly, is responsible for complications and deaths. Few previous works have focused specifically on MPI and DM, and none have followed up the patients for more than 3 years. The aim of the present study is to analyze MPI accuracy in predicting mortality in a cohort of T2DM patients followed-up for 13 years. METHODS: The enrolled subjects were evaluated with MPI, identifying three levels of risk: MPI1 (low risk, 0.0-0.33), MPI2 (moderate risk, 0.34-0.66), and MPI3 (severe risk, 0.67-1.0), and with glycated hemoglobin, and years since T2DM diagnosis. RESULTS: One hundred and seven patients met the inclusion criteria. MPI3 was excluded by further analysis since it was made up of only three patients. Overall, cognitive performances, autonomies in daily living, nutritional status, risk of pressure injuries, comorbidities, and taken drugs were better (p ≤ 0.0077) in MPI1 than MPI2; moreover, the story of T2DM was shorter (p = 0.0026). Cox model showed an overall 13-year survival of 51.9%, and survival rates were significantly smaller in MPI2 (HR: 4.71, p = 0.0007). Finally, increased age (HR: 1.15), poorer cognitive abilities (HR: 1.26), vascular (HR: 2.15), and kidney (HR: 2.17) diseases were independently associated with death. CONCLUSION: Our results prove that MPI predicts short-, mid-, and even long-term mortality in T2DM patients, whose death seems to be related to age and cognitive status, and even more to vascular and kidney diseases.

The single-point insulin sensitivity estimator (SPISE) index is a strong predictor of abnormal glucose metabolism in overweight/obese children: a long-term follow-up study.

PURPOSE: To investigate the relationship between the single-point insulin sensitivity estimator (SPISE) index, an insulin sensitivity indicator validated in adolescents and adults, and metabolic profile in overweight/obese children, and to evaluate whether basal SPISE is predictive of impaired glucose regulation (IGR) development later in life. METHODS: The SPISE index (= 600 × HDL0.185/Triglycerides0.2 × BMI1.338) was calculated in 909 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy, and in 99 normal-weight, age-, sex-comparable children, selected as a reference group, together with other insulin-derived indicators of insulin sensitivity/resistance. 200 overweight/obese children were followed-up for 6.5 [3.5-10] years, data were used for longitudinal retrospective investigations. RESULTS: At baseline, 96/909 (11%) overweight/obese children had IGR; in this subgroup, SPISE was significantly lower than in normo-glycaemic youths (6.3 ± 1.7 vs. 7 ± 1.6, p < 0.001). The SPISE index correlated positively with the insulin sensitivity index (ISI) and the disposition index (DI), negatively with age, blood pressure, HOMA-IR, basal and 120 min blood glucose and insulin (all p values < 0.001). A correlation between SPISE, HOMA-IR and ISI was also reported in normal-weight children. At the 6.5-year follow-up, lower basal SPISE-but not ISI or HOMA-IR-was an independent predictor of IGR development (OR = 3.89(1.65-9.13), p = 0.002; AUROC: 0.82(0.72-0.92), p < 0.001). CONCLUSION: In children, low SPISE index is significantly associated with metabolic abnormalities and predicts the development of IGR in life.

ANGPTL4 gene E40K variation protects against obesity-associated dyslipidemia in participants with obesity.

OBJECTIVE: ANGPTL4 inhibits lipoprotein lipase in adipose tissue, regulating plasma triglycerides levels. In persons with obesity plasma ANGPTL4 levels have been positively correlated with body fat mass, TG levels and low HDL. A loss-of-function E40K mutation in ANGPTL4 prevents LPL inhibition, resulting in lower TGs and higher HDLc in the general population. Since obesity determines metabolic alterations and consequently is a major risk factor for cardiovascular disease, the aim was to explore if obesity-related metabolic abnormalities are modified by the ANGPTL4-E40K mutation. METHODS: ANGPTL4-E40K was screened in 1206 Italian participants, of which 863 (71.5%) with obesity. All subjects without diabetes underwent OGTT with calculation of indices of insulin-sensitivity. RESULTS: Participants with obesity carrying the E40K variant had significantly lower TG (p = 0.001) and higher HDLc levels (p = 0.024). Also in the whole population low TGs and high HDLc were confirmed in E40K carriers. In the obese subpopulation it was observed that almost all E40K carriers were within the lowest quartile of TGs (p = 1.1 × 10-9). E40K had no substantial effect of on glucose metabolism. Finally, none of the obese E40K carriers had T2D, and together with the favourable lipid profile, they resemble a metabolically healthy obese (MHO) phenotype, compared to 38% of E40E wild-type obese that had diabetes and/or dyslipidaemia (p = 0.0106). CONCLUSIONS: In participants with obesity the ANGPTL4-E40K variant protects against dyslipidemia. The phenotype of obese E40K carriers is that of a patient with obesity without metabolic alterations, similar to the phenotype described as metabolic healthy obesity.

Presence of diabetes-specific autoimmunity in women with gestational diabetes mellitus (GDM) predicts impaired glucose regulation at follow-up.

PURPOSE: Gestational diabetes mellitus (GDM) is the most frequent complication of pregnancy; around 10% of GDM cases may be determined by autoimmunity, and our aims were to establish the role of autoimmunity in a population of Sardinian women affected by GDM, to find predictive factors for autoimmune GDM, and to determine type 1 diabetes (T1D) auto-antibodies (Aabs) together with glucose tolerance after a mean 21.2 months of follow-up. METHODS: We consecutively recruited 143 women affected by GDM and 60 without GDM; clinical data and pregnancy outcomes were obtained by outpatient visit or phone recall. T1D auto-antibodies GADA, IA2-A, IAA, ZnT8-A were measured in the whole population at baseline, and in the Aab-positive women at follow-up. RESULTS: The overall prevalence of autoimmunity was 6.4% (13/203). No significant difference was found in the prevalence of auto-antibodies between GDM (5.6%) and control (8.3%) women, neither in antibody titres. Highest titres for GADA and ZnT8-A were observed in the control group; no phenotypic factors were predictive for autoimmune GDM. Diabetes-related autoantibodies were still present in all the GDM women at follow-up, and their presence was associated with a 2.65 (p < 0.0016) relative risk (RR) of glucose impairment. CONCLUSION: We observed a low prevalence (5.6%) of diabetes-related autoimmunity in our GDM cohort, consistent with the prevalence reported in previous studies. It was not possible to uncover features predictive of autoimmune GDM. However, given the significant risk of a persistent impaired glycemic regulation at follow-up, it is advisable to control for glucose tolerance in GDM women with diabetes-related autoimmunity.

High prevalence of diabetes-specific autoimmunity in first-degree relatives of Sardinian patients with type 1 diabetes.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) in Sardinia is among the highest in the world (44.8 cases/100,000 person-years). Recommendations of the Immunology of Diabetes Society advise evaluating autoantibody positivity in first-degree relatives (FDRs) of patients with T1DM, for their higher risk to develop the disease. The aim of this study was to determine the prevalence of beta-cell autoimmunity in FDRs of T1DM patients in Sardinia. METHODS: A total of 188 Sardinian families were recruited in collaboration between diabetes and pediatric units of university and district hospitals in Sardinia. The recruitment involved 188 patients with diagnosed T1DM and all their available FDRs (n = 447). Autoantibodies (Aabs) against GAD, IA2, insulin, and ZnT8 were measured in all subjects. Human leukocyte antigen (HLA) risk genotypes (HLA-DR and DQ loci) were analyzed in 43 Aabs-positive FDR. RESULTS: The prevalence of Aabs (any type of autoantibody, single or multiple) in FDR was 11.9% (53/447). Of those with autoantibodies, 62.3% (33/53) were positive to only 1 autoantibody, 22.6% (12/53) had 2 autoantibodies, 7.55% (4/53) had 3 autoantibodies, and 7.55% (4/53) had all 4 autoantibodies. Typing of HLA-DR and DQ loci showed that 89% of FDR carried moderate- to high-risk genotypes, with only 5 FDR with low-risk genotypes. CONCLUSIONS: The prevalence of T1DM autoantibodies in FDRs of T1DM patients was very high (11.9%) in the Sardinian population, higher than in other populations from the United States and Europe, and similar to that observed in Finland. Autoantibody positivity strongly associated with HLA risk. This study provides evidence of the high risk of T1DM in FDR of T1DM patients in Sardinia and warrants longitudinal follow-up to estimate the risk of progression to T1DM in high-risk populations.

The vitamin D receptor (VDR) gene rs11568820 variant is associated with type 2 diabetes and impaired insulin secretion in Italian adult subjects, and associates with increased cardio-metabolic risk in children.

BACKGROUND AND AIMS: 1α,25-dihydroxyvitamin-D3, the biologically active vitamin D, plays a central role in several metabolic pathways through the binding to the vitamin D receptor (VDR). VDR has been shown to be involved in cardiovascular diseases, cancer, autoimmunity and type 2 diabetes mellitus (T2DM). Several polymorphisms in the VDR gene have been described. Among these, the rs11568820 G-to-A nucleotide substitution was found to be functional, modulating the transcription of the VDR gene. Objective of this study was to perform an association study between rs11568820 polymorphism and T2DM in a cohort of Italian adults with T2DM and in non-diabetic controls. To add further insight into the role of VDR gene we explored whether this association begins early in life in overweight/obese children, or becomes manifest only in adulthood. METHODS AND RESULTS: As many as 1788 adults and 878 children were genotyped for the rs11568820 polymorphism. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin-resistance and secretion were also calculated. The AA genotype was significantly more frequent in adults with T2DM compared to controls (7.5% vs. 4.6%, P = 0.037), and conferred a higher risk of T2DM (ORHom = 1.69C.I. = [1.13-2.53], P = 0.011). In the adult cohort, rs11568820 was also associated with reduced indices of ß-cell insulin secretion. In children, the AA genotype was associated with 2 h high-normal glucose, a marker of cardio-metabolic risk. CONCLUSIONS: Our study demonstrates for the first time that VDR gene AA carriers have higher risk of T2DM and impaired insulin secretion. In children, the association between AA homozygous and high-normal 2h glucose suggests that mild alterations associated with this genotype may appear early in life.

Anterior pituitary autoantibodies in patients with type 1 diabetes mellitus: methodological problems and clinical correlations.

BACKGROUND: Anti-pituitary antibodies (APA) were described in patients with Type 1 Diabetes (T1D) but their prevalence and relevance remain controversial. MATERIALS AND METHODS: We evaluated the APA prevalence in Sardinian sera from 100 T1D patients, 70 Type 2 Diabetes (T2D) patients and 62 healthy controls, using indirect immunofluorescence on bovine pituitary sections. To compare two different substrates, we tested using bovine sections, further T1D patient sera (n = 11, from Pisa) previously analysed for APA on monkey sections, while some T1D Sardinian patient sera (n = 22) were tested on monkey sections. According to preliminary experiments, positivity were considered ≥1:200 and ≥1:20 for bovine and monkey substrates, respectively. RESULTS AND DISCUSSION: Using bovine sections, APA were detected in 7/100 Sardinian T1D patients (at 1:200 titer) and in none of the other Sardinian sera tested. When the T1D sera from Pisa were tested on bovine and the T1D Sardinian sera were tested on monkey, none of these sera showed corresponding positivity for APA. Pituitary hormone dysfunctions were not found in the 7 APA-positive Sardinian T1D patients. The present study shows that the presence of APA at low-titer is highly related to T1D but not associated with any pituitary dysfunction while the animal species used as substrate appears crucial. CONCLUSION: Further studies are needed to ascertain whether APA detected by different animal species may have different pathological relevance in T1D and/or whether APA in the long run may predict future anterior pituitary dysfunction.

Breast MRI artefacts: evaluation and solutions in 630 consecutive patients.

AIM: To evaluate the problems that may arise in breast magnetic resonance imaging (MRI) related to the presence of artefacts and pitfalls, in order to improve its accuracy, sensitivity, and specificity. MATERIALS AND METHODS: Six hundred and thirty breast MRI examinations performed using a 1.5 T magnet were analysed retrospectively. Each type of artefact that may have affected the correct interpretation of the acquired images was considered and analysed. In particular, the presence of technical artefacts, which are related to patient-dependent factors or to the examination itself, and non-technical artefacts, which are the result of inadequate and incorrect image interpretation occurring in absence of technical issues, were examined. In every case of suspicious findings, doubtful lesions were subjected to histological characterization for appropriate therapeutic planning. In the remainder of cases, patients underwent follow-up for at least 18 months. RESULTS: Artefacts were found in 33% of all examinations, among those 48.6% were caused by movement, 33.6% were due to non-homogeneous or failed fat saturation, 8.7% to incorrect positioning of the patient, 7.2% to metallic artefacts, 1.4% to aliasing, and 0.5% were "zebra artefacts". When the artefact was identified in a sequence, the sequence was performed a second time after corrective measures. No artefacts affected diagnostic interpretation of the obtained images. CONCLUSION: The present study provides a specific and precise review of the most frequent artefacts with a discussion of possible and practical solutions. A highly qualified team is required to perform accurate diagnostic tests and to limit or remove the possibility of misinterpretation.

The role of second-look ultrasound of BIRADS-3 mammary lesions detected by breast MR imaging.

OBJECTIVE: To asses the value of second-look ultrasound (US) for identifying BIRADS 3 (Breast Imaging Reporting Data System) mammary lesions detected by breast Magnetic Resonance imaging (MRI). MATERIALS AND METHODS: From April 2008 to May 2009 330 breast MRI were performed of which 60 patients are classified as BIRADS 3. 84 lesions underwent second-look US and percutaneous vacuum biopsy Vacora system US-guided. STATISTICAL ANALYSIS: lesions were stratified into two groups: visible on US (Group 1) and not visible on US (Group 2). The clinical impact of second-look US was studied in terms of negative predictive value (NPV). RESULTS: The positive predictive value (PPV) of category 3 BIRADS MRI was found to be 89%. Second look-US results detected lesions in 51% of the MRI enhancing lesions. The second look-US showed a NPV of 97%. The NPV of second look-US was significantly greater than the NPV of MRI BIRADS 3 (97% vs 89%, p<0.05). The logistic regression analysis showed a higher number of malignant lesions in group 1 than in group 2 (7vs 2, OR 3.7, p<0.05). CONCLUSIONS: The second-look US permitted the correct management of subcentimetric MRI BIRADS 3 lesions not visible with conventional imaging tecniques.

Cost-effectiveness of two breast biopsy procedures: surgical biopsy versus vacuum-assisted biopsy.

PURPOSE: The aim of this study was to compare the cost-effectiveness of two breast biopsy procedures: surgical biopsy and vacuum-assisted biopsy (VAB). MATERIALS AND METHODS: Between November 2008 and September 2009, 200 patients with suspicious breast lesions underwent biopsy procedures at our radiology department: 100 underwent VAB and 100 underwent surgical biopsy. 66 lesions were sampled under sonographic guidance, 109 under mammographic guidance and 25 under magnetic resonance guidance. RESULTS: All procedures were successfully completed. No significant differences in diagnostic efficacy were found between the biopsy procedures. Surgical biopsy has a higher unit cost compared with VAB. CONCLUSIONS: Our analysis emphasises the benefits of VAB compared with surgical biopsy in terms of both cost-effectiveness, and less invasiveness from a psychological and aesthetic point of view.

Value of the correct diagnostic pathway through conventional imaging (mammography and ultrasound) in evaluating breast disease.

PURPOSE: This study evaluated the role of the correct diagnostic pathway through conventional imaging in evaluating breast disease. MATERIALS AND METHODS: Six hundred patients aged between 35 and 75 years were enrolled in the study. All patients underwent detailed history and clinical examination, ultrasound (US) and mammography. US scans were repeated after mammography. All suspicious lesions were studied by cytological and histological characterisation and magnetic resonance (MR) imaging. RESULTS: The first US scan showed 147 solid lesions, 67 lesions characterised by posterior acoustic shadowing and 193 areas of heterogeneous echostructure. The second US scan, performed after mammography, confirmed 123/147 solid nodular lesions, 53/67 lesions characterised by posterior acoustic shadowing and 183/193 areas of heterogeneous echostructure; it also showed 13 nodular lesions not seen on the first scan and two cases of nodular lesions with irregular calcifications. CONCLUSIONS: Our experience suggests that US not performed in conjunction with mammography gives rise to incorrect diagnostic interpretations (either false positive or false negative results). The detection rate of the US scan performed after mammography increases from 4.16% to 5.5%.

Cost-effectiveness analysis of two vacuum-assisted breast biopsy systems: Mammotome and Vacora.

PURPOSE: This study was undertaken to compare the cost effectiveness of two vacuum-assisted breast biopsy devices, the Mammotome and Vacora systems. MATERIALS AND METHODS: Between January and June 2006, 238 vacuum-assisted breast biopsies were performed at our radiology department. Five out of 238 lesions were excluded because of inadequate sampling. The Mammotome system was used in 108/233 lesions and the Vacora system in 125/233. Fifty-eight lesions underwent ultrasound-guided breast biopsy, and 50 lesions underwent mammography-guided biopsy with both Mammotome and Vacora devices. Magnetic-resonance-guided biopsy was possible with the Vacora system only (17/125 lesions). RESULTS: All procedures were successfully completed. No significant differences were found between the results of the Mammotome and Vacora biopsies in terms of effectiveness: sensitivity was 84.4% and 86.2%, respectively, and specificity 100%. In terms of cost, the Mammotome system has higher costs per procedure compared with the Vacora. CONCLUSIONS: Our clinical results confirm the diagnostic accuracy of both the Mammotome and Vacora systems, whereas our cost analysis shows that there is a considerable difference, mostly related to the initial investment.

Pathological classification of DCIS and planning of therapeutic management.

BACKGROUND: Ductal intraepitelial neoplasia (DIN) represents a spectrum of disease that may progress from usual hyperplasia to ductal carcinoma in situ (DCIS) grade 3. The aim of the study was to asses the correlation between the DIN classification and the surgical treatment including sentinel lymph node biopsy (SLNB). PATIENTS AND METHODS: In this retrospective study, 229 patients with DIN had undergone conservative or radical surgical treatment and SLNB in cases of DIN1C-DIN3. RESULTS: Breast conservative surgery was the definitive treatment in 80% of the cases. The H&E evaluation of excised sentinel nodes was negative for metastatic disease; nevertheless the immunohistochemical (IHC) evaluation revealed the presence of metastatic cells in 6 patients (3.7%). CONCLUSION: In cases of DIN lesions SLNB is not indicated. The only reason SLNB should be considered is when there is an evidence of invasive foci at definitive histology or when radical mastectomy is proposed.

Indications for breast magnetic resonance imaging. Consensus document "Attualità in senologia", Florence 2007.

The clinical use of breast magnetic resonance (MR) imaging is increasing, especially for applications requiring paramagnetic contrast-agent injection. This document presents a synthetic list of acceptable indications with potential advantages for women according to evidence from the literature and the expert opinion of the panel that developed this statement. We generally recommend that breast MR imaging be performed in centres with experience in conventional breast imaging [mammography and ultrasonography (US)] and needle-biopsy procedures (under stereotactic or US guidance) as well as in breast MR imaging and second-look US for findings not revealed by conventional imaging performed before MR imaging. In our opinion, there is no evidence in favour of breast MR imaging as a diagnostic tool to characterise equivocal findings at conventional imaging when needle-biopsy procedures can be performed, nor for the study of asymptomatic, non-high-risk women with negative conventional imaging. After a description of technical and methodological requirements, we define the indications and limitations of breast MR imaging for surveillance of high-risk women, local staging before surgery, evaluation of the effect of neoadjuvant chemotherapy, breast previously treated for carcinoma, carcinoma of unknown primary syndrome, nipple discharge and breast implants.

MR imaging-guided 10-gauge vacuum-assisted breast biopsy: histological characterisation.

PURPOSE: The aim of this study was to evaluate a handheld vacuum-assisted device for magnetic resonance imaging (MRI)-guided breast biopsy. MATERIALS AND METHODS: In 47 patients, a total of 47 suspicious breast lesions (mean maximum diameter 9 mm) seen with MRI (no suspicious changes on breast ultrasound or mammography) were sampled using a 10-gauge vacuum-assisted breast biopsy (VAB) device under MRI guidance. Histology of biopsy specimens was compared with final histology after surgery or with follow-up in benign lesions. RESULTS: Technical success was achieved in all biopsies. Histological results from VAB revealed malignancy in 15 lesions (32%), atypical ductal hyperplasia in four lesions (8%) and benign findings in 28 lesions (60%). One of four lesions with atypical ductal hyperplasia was upgraded to ductal carcinoma in situ after surgery. One of seven lesions showing ductal carcinoma was upgraded to invasive carcinoma after surgery. Two lesions diagnosed as infiltrating carcinoma by VAB were not validated at excisional biopsy due to complete removal of the lesion during the procedure. During the follow-up (mean 18 months) of histologically benign lesions, we observed no cases of breast cancer development. Because of morphological changes on follow-up MRI scans, two lesions underwent surgical excision, which confirmed their benign nature. Besides minor complications (massive bleeding, n = 1) requiring no further therapeutic intervention, no complications occurred. CONCLUSIONS: MRI-guided biopsy of breast lesions using a handheld vacuum-assisted device is a safe and effective method for the workup of suspicious lesions seen on breast MRI alone.

MR breast imaging: a comparative analysis of conventional and parallel imaging acquisition.

PURPOSE: The objective of this study was to compare conventional breast magnetic resonance imaging (MRI) with breast MRI acquired with the sensitivity-encoding (SENSE) technique on a 1.5-T MRI scanner in the same patient, on the basis of image quality and kinetics analysis. MATERIALS AND METHODS: Thirty-one patients with suspicious mammography and US findings were included in the study. Conventional breast MRI consisted of the following sequences: T1 (matrix, 288 x 512); T2 (matrix 225 x 512); short tau inversion recovery (STIR) (matrix 320 x 224) and dynamic T1 [2D fast-field echo (FFE)] (matrix 256 x 512; temporal resolution

FEM analysis of RF breast ablation: multiprobe versus cool-tip electrode.

BACKGROUND: Radio-frequency ablation (RFA) has recently received much attention as an effective minimally invasive strategy for the local treatment of tumors. The purpose of this study was to evaluate the efficacy of single-needle cool-tip RF breast ablation in terms of temperature distribution and duration of the procedure as compared to multiprobe RF breast ablation. MATERIALS AND METHODS: Two different commercially available radiofrequency ablation needle electrodes were compared. Finite-element method (FEM) models were developed to simulate the thermoablation procedures. A series of ex vivo radiofrequency thermal lesions were induced to check the response of the FEM calculations. RESULTS: Data obtained from FEM models and from ex vivo procedures showed that cool-tip RF breast ablation assures better performances than multiprobe RF breast ablation in terms of temperature distribution and duration of the procedure. Histopathological analysis of the cool-tip RF thermoablated specimens showed successful induction of coagulation necrosis in the thermoablated specimens. CONCLUSION: Data obtained from FEM models and from ex vivo procedures suggest that the proposed cool-tip RF breast ablation may kill more tumor cells in vivo with a single application than the multiprobe RF breast ablation.

[Intraoperative radiolocalization of intraductal breast carcinoma: sentinel lymph node evaluation]. / La radiolocalizzazione intraoperatoria nel carcinoma intraduttale della mammella: valutazione del linfonodo sentinella.

Sentinel lymph node biopsy and intraoperatory radiolocalization (RLI) are fast becoming the standard surgical treatment for invasive breast cancer. Actually, it seems, they have the same rule in "high risk" DCIS of the breast.