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Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3–10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8–11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3–15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.

Background:Aromatase inhibitor (AI) therapy in women with estrogen receptor-positive (ER+) breast cancer (BC) causes accelerated bone loss and increased risk of osteoporosis and fractures as side effects. Denosumab (i.e. 60 mg twice a year) is a viable therapy against bone resorption, but the short-term monitoring of bone mineral density (BMD) change with time is still an unmet clinical need, since the current techniques (including dual-energy X-ray absorptiometry, DXA) require 1-2 years between two consecutive measurements [1]. Radiofrequency Echographic Multi Spectrometry (REMS), with high performance in terms of precision and repeatability [2], might be used in this setting of patients for short-term monitoring of bone health-related parameters.Objectives:The objective is the short-term monitoring of the effect of AIs with/without denosumab on bone health in BC patients using REMS and DXA scans at lumbar spine.Methods:Post-menopausal ER+ BC patients treated with adjuvant AIs were recruited. Two subgroups were identified, whether receiving also 60 mg of denosumab therapy every 6 months or not (named Group A and Group B, respectively). All patients underwent baseline DXA and REMS lumbar spine scans at time T0, previous to the first AI therapy, and after 12 months (time T1). REMS scan only was repeated also at 18 months (T2), since a 6-month interval between two consecutive scans is not recommended for DXA. The bone mineral density (BMD) was measured with both techniques.Results:Overall, 254 ER+ BC patients were enrolled (127 per group). The effect of denosumab on BMD is reported in Table. The BMD values obtained by DXA and REMS were not significantly different at T0 and T1, whereas the difference between Group A and B at T1 was statistically significant (pConclusion:Several studies have shown the effect of denosumab on BMD over a period not less than 2 years from the start of treatment. This study showed the feasibility of short-term follow-up using REMS lumbar spine scans at 6-month time steps.References:[1]Diez-Perez A et al, Aging Clin Exp Res 2019;31(10):1375–89[2]Di Paola M et al, Osteoporos Int 2018;30:391–402Table 1.BMD values, expressed as g/cm2, measured by DXA and REMS for Group A (patients receiving AIs only) and Group B (patients receiving AIs and denosumab) at baseline (T0), 12 months (T1) and 18 months (T2) from the start of therapy. Results are presented as median values with 25thand 75thpercentiles. P-values are obtained with a Mann-Whitney test.DXAREMSScan timeGroup AGroup BpGroup AGroup BpT00.840 (0.719-0.959)0.867 (0.723-0.958)0.990.833 (0.708-0.949)0.855 (0.714-0.973)0.77T10.823 (0.702-0.944)0.889 (0.749-0.990)0.0030.819 (0.691-0.927)0.887 (0.740-1.018)T2---0.801 (0.679-0.909)0.899 (0.754-1.020)Note:The authorsD. Ciardo, M. Ciccarese, F. Conversano, M. Di Paola, R. Forcignanò, A. Grimaldi, F.A. Lombardi, M. Muratore and P. Pisaniare listed in alphabetical orderDisclosure of Interests:None declared

Background The Aromatase Inhibitors (AIs)-based therapy used in breast cancer patients to profoundly lower estrogen levels seems to enhance the loss of bone mineral density (BMD) and to increase the fragility fracture rate [1]. Several clinical studies demonstrated that, in breast cancer patients that received the adjuvant AIs, the subcutaneous administration of Denosumab-based therapy significantly increased BMD values and reduced the rate of clinical fractures. Objectives To monitor the short-term Denosumab and AIs therapeutic effects on BMD in breast cancer patients through an innovative echographic approach, the EchoSound technology [2]. Methods 154 breast cancer patients selected for receiving the adiuvant AIs therapy were recruited. All the patients underwent spinal and femoral dual X-ray absorptiometry (DXA) examinations before AIs therapy administration starting (time T0). After AIs treatment starting, enrolled patients were divided into 2 groups: 105 patients received only the AIs treatment (Group A), whereas the remaining 49 patients (Group B) received also an additional Denosumab treatment, in order to contrast the BMD reduction induced by AIs administration. Follow-up measurements were conducted at two different time points: 12 (T1) and 18 (T2) months from AIs treatment starting. At time T1, patients underwent both DXA examinations and EchoSound echographic scans, whereas at time T2 only the echographic scans were performed, since DXA cannot be used for short-term follow-ups. Results At time T1, the following results were obtained on lumbar spine: Group A showed a BMD decrement, which was equal to -2.07%±1.66% (p Conclusions By using the EchoSound technology the short-term follow-up of the positive Denosumab effects on BMD reduction in patients treated with adjuvant AIs was feasible and accurate. This approach can be also useful to monitor the therapy effectiveness in patients undergoing specific anti-osteoporotic treatments. References J Clin Endocrinol Metab.2011;96:308. Clin Cases Min Bone Metab 2015;12:142. Acknowledgements Work partially funded by FESR PO Apulia Region 2007–13; Action 1.2.4 (grant n. 3Q5AX31: ECHOLIGHT Project). Disclosure of Interest P. Pisani: None declared, M. Muratore: None declared, F. Conversano Shareholder of: Echolight spa, a National Research Council spin-off that may or may not benefit from results of this study, E. Casciaro Shareholder of: Echolight spa, a National Research Council spin-off that may or may not benefit from results of this study, M. Di Paola: None declared, R. Forcignano: None declared, M. Ciccarese: None declared, G. Surico: None declared, L. Quarta: None declared, E. Quarta: None declared, D. Costanza: None declared, R. Franchini: None declared, R. Tarparelli Employee of: Echolight Spa, S. Casciaro Shareholder of: Echolight spa, a National Research Council spin-off that may or may not benefit from results of this study

Background. In large-scale clinical trials, the proliferation signal inhibitor (PSI) everolimus (EVL) combined with cyclosporine (CsA) and steroids, has been shown to be efficacious among de novo renal transplant recipients. Development of proteinuria has been shown to be an important predictor of renal dysfunction after conversion from CsA to a PSI-based regimen, and a key marker of allograft disease progression. Whether EVL de novo treatment is associated with a similar proteinuric effect is still under investigation. Methods. We compared the development of proteinuria among a cohort of 24 renal transplant recipients who were prescribed EVL (3 mg/d; n = 12; high-dose group) or 1.5 mg/d (n = 12; standard-dose group), in association with CsA, versus third control cohort of 12 patients who received mycophenolate mofetil (control group). EVL doses were adjusted to achieve trough blood levels of 3-8 ng/mL and 8-12 ng/mL among the standard and high-dose groups, respectively. We assessed renal function and protein excretion over a 2-year observation. Results. The high-dose group showed a trend toward greater proteinuria than the standard-dose on control groups. They showed significantly greater proteinuria from 9 months until 2 years; 0.86 ± 0.5, 0.5 ± 0.3, 0.47 ± 0.2 g/24 h (P = .03 and P = .02, respectively, at 24 months). Mean proteinuria significantly correlated with mean EVL doses (n = .73; P = .0001). Concomitantly, the estimated glomerular filtration rate (eGFR) was significantly lower among patients treated with EVL 3.0 versus 1.5 mg/d (53.7 ± 24 vs 73.04 ± 17.6 mL/min; P = .037). Among patients in the standard-dose, the eGFR was consistently higher than the control group (62.6 ± 29 mL/min). Conclusion. EVL/CsA therapy is a safe alternative regimen for de novo renal transplant recipients. Higher EVL doses are correlated with greater increases in proteinuria. The standard EVL dose seems to be useful treatment strategy to prevent acute rejection episodes, with a better renal prognosis in the long term.

Background Experimental evidence indicates that statins might have direct vascular effects independently from low-density lipoprotein (LDL) cholesterol reduction and we reported that the reduction in urinary albumin excretion rate during Simvastatin treatment in type 2 diabetic patients was not correlated with LDL-cholesterol decrease. However in humans there are no data regarding possible additional effects of Simvastatin on blood pressure and urinary albumin excretion beyond its capacity to lower serum cholesterol. Patients and methods Twenty-six microalbuminuric hypertensive type 2 diabetic patients (diastolic blood pressure — after four months wash-out from the previous antihypertensive therapy — consistently > 90 and 3.9 and

In a large cohort (no. = 361) of NIDDM probands and their concordant/discordant siblings from no. = 132 families we studied: 1. the levels of plasma prorenin in non affected siblings of NIDDM probands as opposed to normal subjects without family history of diabetes, and 2. whether plasma prorenin raises in parallel to urinary protein loss in NIDDM patients. Prorenin (solid-phase trypsin) and micro-macroalbuminuria (radioimmunoassay) were evaluated. Plasma prorenin was higher in NIDDM probands and siblings than in non NIDDM siblings (37+/-31 vs. 25+/-15 ng/ml/h, p0.0005) who, in turn, showed higher plasma prorenin than non diabetic controls without family history of diabetes (25+/-15 vs. 17+/-8 ng/ml/h, p0.005). Plasma prorenin was higher in NIDDM siblings of micro-macroalbuminuric probands than in NIDDM siblings of non micro-macroalbuminuric probands (40+/-26 vs. 29+/-20 ng/ml/h, mean +/- SD, p = 0.0058) whereas no difference was found among non diabetic siblings (24+/-14 vs. 22+/-11 ng/ml/h, NS). Our data confirm that plasma prorenin is elevated in NIDDM patients, and show: 1. that the raise of plasma prorenin in non-NIDDM siblings of a diabetic patient does not depend entirely from the presence of diabetes, and 2. that plasma prorenin in NIDDM probands and their concordant siblings goes along with micro-macroalbuminuria.

OBJECTIVE To evaluate the possible association of three candidate gene polymorphisms with essential hypertension in the genetically homogeneous Sardinian population. SUBJECTS AND METHODS We studied 494 unrelated, nondiabetic subjects, 213 (43.2%) with essential hypertension. All subjects underwent a 75 g oral glucose tolerance test with determination of glycemia and insulinemia and serum lipids. The polymorphisms evaluated comprised Trp64Arg of the beta 3-adrenergic receptor, Gly40Ser of the glucagon receptor gene and the insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene. RESULTS Among the overall population studied, 48 (9.7%) were heterozygous carriers of the Trp64Arg polymorphism. The frequency of the Trp64Arg variant was significantly higher in hypertensives (13.6%) than normotensives (6.8%; chi 2 5.73, P = 0.017). The 48 subjects with the Trp64Arg variant had significantly higher (P < 0.049) serum triglyceride levels than the 446 with the Trp64Trp variant, while no significant differences were observed, either fasting or during the 75 g oral glucose tolerance test, in glycemia and insulinemia. No differences were found between hypertensive and normotensive subjects for ACE gene insertion/deletion polymorphism nor in the frequency of the Gly40Ser coding change in exon 2 of the glucagon receptor gene. CONCLUSIONS Our results are consistent with the thesis that the Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is associated more often with the condition of high blood pressure than with normal blood pressure.

Objective: The liver is the major site of apolipoprotein(a) synthesis, and an inverse correlation between the size of apolipoprotein(a) isoforms and its serum levels have been described. We evaluated the Apo(a) serum levels and its isoforms in patients with liver cirrhosis at different stages of the disease (Childe Turcotte classification), and during the characteristic phase of liver synthesis decline. Methods: We studied 84 patients with liver cirrhosis and 185 control subjects with normal liver function. Results: Apo(a) serum levels were significantly lower (p < 0.01) in cirrhotic patients and, after 24 months, six patients showing a change from class A to class B had a statistically significant decrease in Apo(a) concentrations (p = 0.0313). Moreover, our data showed an inversion of the small/large isoforms ratio in patient with cirrhosis in spite of the reduction in plasma concentration. Conclusion: We showed a reduction of Apo(a) serum concentrations in a large number of patients with cirrhosis and, for the first time, during the characteristic phase of liver synthesis decline, confirming the liver as the major site of Apoliprotein(a) synthesis. Moreover we showed in the cirrhotic patients that the normal correlation between Apo(a) isoforms and Apo(a) concentrations is not conserved and the low levels are not dependent upon a high prevalence of large isoforms.

The minimal model is widely used to evaluate insulin action on glucose disappearance from frequently sampled intravenous glucose tolerance tests (FSIGT). The common protocols are a regular (rFSIGT, single injection of 0.3 g/kg of glucose) and an insulin-modified test (mFSIGT, with an additional insulin administration at 20 min). This study compared the insulin sensitivity index (SI) and glucose effectiveness (SG) obtained in the same individual (16 normal subjects) with the two tests. SI was 7.11 ± 0.80 10−4 ⋅ min−1 ⋅ μU−1 ⋅ ml in rFSIGT and 6.96 ± 0.83 in mFSIGT ( P = 0.656), regression r = 0.92, P < 0.0001; SG was 0.0260 ± 0.0028 min−1 and 0.0357 ± 0.0052, respectively, statistically different ( P = 0.013) but still with a good regression ( r = 0.66, P = 0.0051). SG and insulin amount during the early period correlated ( r = 0.6, P = 0.015 in rFSIGT and r = 0.76, P = 0.0006 in mFSIGT). In summary, both FSIGTs with minimal model analysis provide the same SI, which is a very robust index. SG was different by 28% due probably to the relationship between SG and the amount of circulating insulin. In studies comparing groups, the simpler rFSIGT can still be used with the advantage of accounting for endogenous insulin, thus offering the possibility of direct inferences on the β-cell activity.

OBJECTIVE To study the long-term effects of simvastatin on urinary albumin excretion rate (AER) in normotensive microalbuminuric type 2 diabetic patients with hypercholesterolemia. RESEARCH DESIGN AND METHODS A total of 19 normotensive microalbuminuric hypercholesterolemic type 2 diabetic patients entered a double-blind crossover study for 2 years, receiving either simvastatin (20 mg/day) or placebo (each treatment for 1 year). RESULTS Simvastatin significantly decreased plasma cholesterol (total and LDL) after 52 weeks of treatment. A concomitant significant decrease of AER (25% from basal) with no significant changes in creatinine clearance was observed during the same period. CONCLUSIONS Our data are in keeping with the hypothesis that simvastatin might be used as an additional means to preserve renal function in microalbuminuric hypercholesterolemic type 2 diabetic patients.

A Gly40Ser amino acid substitution in the glucagon receptor gene has been associated with non-insulin-dependent diabetes mellitus (NIDDM), but the questions raised about its physiological implications have not been resolved. The aim of this study was to determine the frequency of the Gly40Ser mutation in different regions of Sardinia and to investigate the physiological implications of the mutation in glucose and insulin homeostasis. We studied a population of 691 subjects, selected on the basis of their Sardinian origin. Only heterozygous subjects were found, 21 of 574 (3.6 %) in NIDDM patients and 5 of 117 in non-diabetic subjects (4.2 %). In northern Sardinia 3.4 % of the NIDDM patients were carriers of the Gly40Ser substitution, 1.4 % in central Sardinia, while 7.6 % carried the substitution in the Southern part. No significant differences were found between hypertensive and normotensive subjects with respect to the presence of Gly40Ser. Ten subjects with Gly40Ser were carefully matched for diabetic state, BMI, age, sex, and geographical origin with 10 patients with Gly40, and a glucagon infusion test was performed using 1, 3, 9 and 27 ng glucagon kg–1· min–1 for 30 min. Blood for determination of glucose, glucagon, and insulin concentrations was drawn at 15-min intervals from the Controlateral arm. Plasma glucagon increased dose-dependently during the infusion with no significant difference between the two groups. Carriers of Gly40Ser had a significantly lower (p < 0.02) increase in plasma glucose concentration in response to glucagon infusion compared to Gly40 homozygous subjects at all times, while the plasma insulin increase was not significantly different at any time. In conclusion, our results indicate that the Gly40Ser variation is not associated with NIDDM in the Sardinian population, and that its frequency varies in different parts of Sardinia. Moreover in vivo Gly40Ser plays a physiological role in the glucose homeostasis under glucagon control both in NIDDM and non-diabetic subjects. This latter result suggests that this amino acid substitution in the glucagon receptor may lead to a decreased blood glucose concentration because of the reduced stimulation of liver glucose output via the glucagon receptor. [Diabetologia (1997) 40: 89–94]

Allograft rejection during the first year after renal transplantation can lead to persistent allograft dysfunction and reduced long-term graft survival. Thus, it is important to define early predictors of kidney damage, less invasive than allograft biopsy. Urinary glycosaminoglycan/proteoglycan concentration and distribution, N-acetyl-β-(d)-glucosaminidase (NAG), and monokine induced by IFN-γ (MIG) levels were evaluated in the immediate post-transplant and during a 1-year follow-up. We observed increased urinary levels of MIG, urinary trypsin inhibitor and its degradation products, the lack of urinary heparan sulfate excretion, and the decreased chondroitin sulfate relative content at day 1 post-transplant in most patients who developed complications in the postoperative period. Moreover, urinary MIG levels showed significant correlations with NAG, C-reactive protein, and GFR at day 1 post-transplant. The monitoring of glycosaminoglycan/proteoglycan urinary pattern and the levels of urine MIG could serve as useful markers for predicting possible complications of transplantation, unraveling an early inflammatory state, on whose basis the immunosuppressive therapy could be appropriately modified.

We describe cases of isolated functioning insulinoma occurring in two members of the same family (father and daughter). The father had a first encapsulated insulinoma diagnosed at 14 years of age and at the age of 33 years he was operated on for a second insulinoma infiltrating the exocrine pancreas with lymph node metastases. The daughter was operated on for an encapsulated insulinoma in the tail of the pancreas when she was 6 years old. No clinical and laboratory signs of other endocrine disturbances have so far been detected in either care or in any other members of the family. Our report suggests the possibility of multiple familial insulinoma, although this is an extremely rare condition. Our data also indicate that insulinomas, even if well controlled by medical treatment, should always be removed by surgery because malignancy cannot be excluded with certainty. Moreover, patients should be closely followed up, as recurrence may develop up to 15 years after surgery.

Experimental evidence indicates that statins might have direct vascular effects independently from low-density lipoprotein (LDL) cholesterol reduction and we reported that the reduction in urinary albumin excretion rate during Simvastatin treatment in type 2 diabetic patients was not correlated with LDL-cholesterol decrease. However in humans there are no data regarding possible additional effects of Simvastatin on blood pressure and urinary albumin excretion beyond its capacity to lower serum cholesterol.Twenty-six microalbuminuric hypertensive type 2 diabetic patients (diastolic blood pressure - after four months wash-out from the previous antihypertensive therapy - consistently90 and100 mmHg; plasma LDL-cholesterol3.9 and6.5 mmol L-1) were enrolled in the study. In random order, these patients received Simvastatin (20 mg day-1) or Cholestyramine (6 g three times a day) for a period of 10 months and after three months of wash-out (cross-over) the sequence was reversed for an additional 10 months. Blood pressure, lipid parameters, glycated haemoglobin and urinary albumin excretion were measured during the study. Additionally, in eight patients, urinary glycosaminoglycan excretion (GAG) was also measured during the study.Simvastatin and Cholestyramine were equally effective in reducing total and LDL cholesterol. Only during Simvastatin treatment a significant reduction in diastolic blood pressure and both 24 h urinary albumin and GAG excretion rates were observed, while no significant changes were seen with Cholestyramine treatment.Our results clearly show for the first time that the reduction of blood pressure, together with 24 h urinary albumin excretion rate - two established cardiovascular risk factors, obtained during Simvastatin therapy in hypertensive type 2 diabetic patients - is in large part independent from the reduction of LDL Cholesterol.

A significantly different prevalence in the Gly40Ser variant of the glucagon receptor gene in a small group of essential hypertensive patients compared with normotensive probands was described in a Caucasian population. It has been postulated that this variant may exacerbate the antinatriuretic effect of high plasma insulin levels commonly seen in hypertensive subjects, leading to volume expansion and rise in blood pressure level. The aim of this study was to evaluate the prevalence of the Gly40Ser variant in a population of 404 non-insulin-dependent diabetic patients of Sardinian origin. No association of the Gly40Ser variant with hypertension was seen in this large population.

Patients with homozygous β -thalassemia show an abnormal lipoprotein profile. In asymptomatic heterozygotes the lipid pattern is less markedly affected but interestingly related to a diminished cardiovascular risk. The extent and significance of these findings are still a matter of debate and no data are available on lipoprotein(a) plasma levels. Seventy patients with homozygous β -thalassemia (HT-P), 70 β -thalassemia trait carriers (TT-C) and 70 sex and age-matched controls were investigated and their plasma lipoprotein profile and apo(a) phenotypes determined. In a subgroup of these same subjects (12 HT-P, 12 TT-C and 24 controls) and in 12 bone marrow-transplanted homozygous β -thalassemic patients (BMT-P) plasma lipoprotein composition was assessed. HT-P disclosed significantly lower total-cholesterol, LDL-cholesterol, HDL-cholesterol, apo A-I, apo B plasma levels and higher triglyceride concentration than TT-C (−7, −11, −8, −8, −13 and +11%, respectively) or controls (−39, −50, −46, −32, −30 and +35%, respectively). All lipoprotein subclasses were triglyceride-enriched, while LDLs were also protein-enriched and HDLs protein-depleted. TT-C disclosed a small but significant reduction in apo A-I and apo B plasma levels but only minor lipoprotein abnormalities with respect to the controls. BMT-P lipoprotein composition was intermediate between HT-P and normal subjects. Apo(a) plasma levels did not differ among the groups. A higher prevalence of `small' apo(a) isoforms was present in HT-P. Within the same `isoform group', apo(a) plasma levels were significantly lower in HT-P than in TT-C or controls. Since liver cirrhosis is almost always present in HT-P, it is conceivable that an altered hepatic apo(a) synthesis or catabolism due perhaps to diminished apolipoprotein glycation may be involved. In TT-C a partially improved cardiovascular risk profile was apparent (low hematocrit, low LDL-cholesterol and apo B), thus justifying the claim for a low prevalence of ischemic heart disease, but no Lp(a) plasma level modification could be detected.

We report herein the effects of cyclical variations of endogenous sex steroids during the menstrual cycle on plasma lipids and apolipoproteins (apo) in normal women. We examined 16 normal women (age range 25-36 yr) with normal menstrual cycles of 28-31 days. The study covered the period from the 1st day of a menstrual phase (basal) until the 1st day of the following menstrual phase. During the study all women maintained a normolipidic diet (30% fat). Plasma total cholesterol and low-density-lipoprotein cholesterol were significantly higher than basal in the preovulatory phase until progesterone started to increase in the postovulatory phase [day +8 from luteinizing hormone (LH) surge]. High-density-lipoprotein cholesterol was significantly higher than basal from day -1 to the day after LH surge, whereas plasma apoAI levels were significantly higher from day -8 to day +8 (from LH surge). Plasma apo(a) increased significantly during the luteal phase in four women characterized by a single S4 band and lower basal plasma levels of apo(a). Our results indicate that endogenous female sex steroids have significant effects on the circulating levels of plasma lipids and apolipoproteins, including apo(a). More work needs to be done to elucidate the significance of the observed apo(a) changes, and the different phases of the menstrual cycle must be taken into account when evaluating the lipidic risk profile in premenopausal women.

Progressive capillary occlusion often leads to severe retinopathy within 15–20 years of the onset of Type 1 (insulin-dependent) diabetes mellitus. Lipoprotein (a), a complex formed by apolipoprotein (a), apo B-100 and lipids, is considered an independent, genetically determined, predictor of cardiovascular disease. It may have antifibrinolytic properties in view of its similarity to plasminogen. To test the hypothesis that circulating lipoprotein (a) is associated with the process that leads to clinically active diabetic retinopathy, we measured the circulating levels of apolipoprotein (a) (which are strictly correlated with those of lipoprotein (a)) in two groups of patients with Type 1 diabetes of at least 15 years duration: 25 with active retinopathy and 27 without clinically detectable retinal lesions. Thirty-eight healthy subjects of the same age and sex served as controls. Serum apolipoprotein (a) was higher in the patients with active retinopathy (36(2-193) U/dl, geometric mean and range) than in those without clinically detectable retinal lesion (17(1–160)) and the control subjects (14(0–115)), p < 0.01 in both cases. The distribution of apolipoprotein (a) levels was skewed to the left, as expected, in the patients without clinically evident retinal lesions and the control groups, but there was a bimodal trend of distribution among those with active retinopathy. The levels of glycated haemoglobin were similar in the two groups of diabetic patients, and no significant differences were found for total and HDL cholesterol, triglycerides or apolipoproteins A1 and B between them and the control subjects. These preliminary results suggest that serum apolipoprotein (a) is elevated in patients with active retinopathy. The role of this lipoprotein as a predictor or a pathogenic effector of diabetic retinopathy, or both deserves further investigation.

A significantly different prevalence in the Gly40Ser variant of the glucagon receptor gene in a small group of essential hypertensive patients compared with normotensive probands was described in a Caucasian population. It has been postulated that this variant may exacerbate the antinatriuretic effect of high plasma insulin levels commonly seen in hypertensive subjects, leading to volume expansion and rise in blood pressure level. The aim of this study was to evaluate the prevalence of the Gly40Ser variant in a population of 404 non-insulin-dependent diabetic patients of Sardinian origin. No association of the Gly40Ser variant with hypertension was seen in this large population.

Purpose: The VICTOR-1 study demonstrated that the all-oral metronomic combination of vinorelbine and capecitabine is highly active and well tolerated in hormone receptor-positive/HER2-negative patients. The VICTOR-2 study was designed to confirm these results. Methods: Patients received mVNR 40 mg three times a week and mCAPE 500 mg three times a day, continuously. The primary endpoint was the clinical benefit rate (CBR); secondary endpoints were toxicity, objective response rate (ORR), and progression-free survival (PFS). Results: Eighty patients were evaluable for the primary efficacy analysis. Median age was 65.3 years; most patients had HR-positive tumors (65 %). The CBR was 45.7 % (95 % CI 28.8–63.4) and 51.1 % (95 % CI 35.8–66.3) in first- and ≥ second-line therapy, respectively. The ORR was 35.5 % in first-line (95 % CI 19.2–54.6) and 25.6 % in ≥second-line (95 % CI 13.5–41.2). The median duration of response was 11.3 and 6.4 months and PFS rates at 1 year were 24.3 and 22.2 %, respectively. In triple-negative breast cancer patients (N = 28, 35 %) a lower, but clinically relevant CBR (35.7, 95 % CI 18.6–55.9) was observed. The main toxicities per cycle were non-febrile neutropenia (1.1 %), hand-foot syndrome (1.0 %), nausea and vomiting (1.0 %), leucopenia (0.8 %), fatigue (0.7 %), and diarrhea (0.4 %). Conclusion: The VICTOR-2 study confirms the clinical activity of mVNR and mCAPE in HER2-negative breast cancer patients, suggesting that the easy schedule of administration, which requires monthly blood tests and limits patients’ dependence on hospitals, and the low cost of the drugs are valuable elements, even for countries with limited access to innovative or expensive drugs.

The Barcelona Clinic Liver Cancer advanced stage (BCLC C) of hepatocellular carcinoma (HCC) includes a heterogeneous population, where sorafenib alone is the recommended treatment. In this study our aim was to assess treatment and overall survival (OS) of BCLC C patients sub-classified according to clinical features (Performance Status [PS], macro-vascular invasion [MVI], extra-hepatic spread [EHS] or MVI+EHS) determining their allocation to this stage. From the Italian Liver Cancer database, we analysed 835 consecutive BCLC C patients diagnosed between 2008 and 2014. Patients were sub-classified as: PS1 alone (n=385, 46.1%), PS2 alone (n=146, 17.5%), MVI (n=224, 26.8%), EHS (n=51, 6.1%) and MVI+EHS (n=29, 3.5%). MVI, EHS and MVI+EHS patients had larger and multifocal/massive HCCs and higher alpha-fetoprotein levels than PS1 and PS2 patients. Median OS significantly declined from PS1 (38.6 months) to PS2 (22.3 months), EHS (11.2 months), MVI (8.2 months) and MVI+EHS (3.1 months) (P