GH provocative tests stimulate the growth in children with idiopathic short stature.

CONTEXT: Growth hormone (GH) deficiency in a child with short stature is diagnosed by GH secretion provocative tests. When the test response is considered adequate, the short stature is considered idiopathic (ISS). OBJECTIVE: To determine the effect of GH provocative tests on the growth rate in children with idiopathic short stature. DESIGN: Children with short stature with a normal response to at least one GH provocative test were enrolled. Height and growth velocity were measured prior to and after stimulus tests during the follow-up. METHODS: Height, mid-parental height, body weight, and body mass index were measured. The height and growth rate were converted to percentiles and Standard Deviation Scores (SDS) using reference ranges standardized by age and sex. GH provocative tests employed arginine or clonidine as secretagogues. RESULTS: Fourty-six children of both genders were enrolled. In thirty-six children, height was measured at the time of testing and on an average time prior to and after the tests of 210 days and 180 days respectively. After testing the children displayed a 3.4-fold increase in their estimated 90-day growth rate. The median (inter-quartile range, IQR) 90 days growth of children pre-and post-tests were 0.7 (0.2-1.0) cm and 2.4 (1.7-3.1) cm respectively with a mean 3,4-fold increase (p < 0.0001). The median (IQR) 90 days growth of children pre- and post-tests calculated as standard deviation scores (SDS) were -4.0 (-5.4--2.1) SDS and 0.1 (-1.9-1.4) SDS respectively (p < 0.0001). Ten children with ISS were observed for about 5 months before the GH provocative tests. A small increase in the growth rate was seen only in 2 out of 10 children before testing while it increased in all of them after the tests. The difference in the median growth rate at the first and the second observation was not significant (p = 0.219). CONCLUSIONS: Two sequential somatotropic axis provocative tests increase the growth rate in children with idiopathic short stature. The duration of this effect is yet to be determined.

Bile duct injury after cholecystectomy: timing of surgical repair should be based on clinical presentation. The experience of a tertiary referral center with Hepp-Couinaud hepatico-jejunostomy.

Impact of timing of repair on outcomes of patients repaired with Hepp-Couinaud hepatico-jejunostomy (HC-HJ) after bile duct injury (BDI) during cholecystectomy remains debated. This is an observational retrospective study at a tertiary referral hepato-biliary center. HC-HJ was always performed in patients without sepsis or bile leak and with dilated bile ducts. Timing of repair was classified as: early (≤ 2 weeks), intermediate (> 2 weeks, ≤ 6 weeks), and delayed (> 6 weeks). 114 patients underwent HC-HJ between 1994 and 2022: 42.1% underwent previous attempts of repair at referring institutions (Group A) and 57.9% were referred without any attempt of repair before referral (Group B). Overall, a delayed HC-HJ was performed in 78% of patients; intermediate and early repair were performed in 17% and 6%, respectively. In Group B, 10.6% of patients underwent an early, 27.3% an intermediate, and 62.1% a delayed repair. Postoperative mortality was nil. Median follow-up was 106.7 months. Overall primary patency (PP) attainment rate was 94.7%, with a 5- and 10-year actuarial primary patency (APP) of 84.6% and 84%, respectively. Post-repair bile leak was associated with PP loss in the entire population (odds ratio [OR] 9.75, 95% confidence interval [CI] 1.64-57.87, p = 0.012); no correlation of PP loss with timing of repair was noted. Treatment of anastomotic stricture (occurred in 15.3% of patients) was performed with percutaneous treatment, achieving absence of biliary symptoms in 93% and 91% of cases at 5 and 10 years, respectively. BDI can be successfully repaired by HC-HJ regardless of timing when surgery is performed in stable patients with dilated bile ducts and without bile leak.

Bile duct injury following cholecystectomy: delayed referral to a tertiary care center is strongly associated with malpractice litigation.

BACKGROUND: Bile duct injury (BDI) following cholecystectomy is associated with malpractice litigation. Aim of this study was to evaluate risk factors for litigation in patients with BDI referred in a tertiary care center. METHODS: Patients treated for BDI between 1994 and 2016. Stabilized inverse probability therapy weighting was used and multivariable logistic regression analysis identified risk factors for malpractice litigation. RESULTS: Of the 211 treated patients, 98 met the inclusion criteria: early-referral group (<20 days; 51.0%), late-referral (≥20 days; 49.0%). 36 patients (36.7%) initiated malpractice litigation with verdict in favor of plaintiff in 86.7% of cases (median payment = €90 500, up to €600 000). Attempts at surgical and endoscopic repair before referral were significantly higher in late-referral group. Failed postoperative management (delayed referral, attempts at repair before referral) was one of the strongest predictors for litigation. Risk of litigation progressively increased from 23.8%, when referral time was within 19 days, to 54.5% (61-120 days), to 60.0% (121-210 days) and to 65.1% (211-365 days). DISCUSSION: Litigation rate after BDI was 37%. Delayed referral to tertiary care center was one of the strongest predictors for litigation. Prompt referral to tertiary experienced centers without any attempt at repair may reduce the risk of litigation.

The DiaCoVAb Study in South Italy: Immune Response to SARS-CoV-2 Vaccination in Dialysis Patients.

INTRODUCTION: Since the pandemic of COVID-19 started from December 2019, remarkable numbers of infections and deaths associated with COVID-19 have been recorded worldwide. End-stage kidney disease patients on dialysis are particularly at high risk of infections due to impairments in the innate and adaptive immune systems. Vaccination on dialysis patients (DP) still remains challenging because of the variable response and a low seroconversion rate compared with healthy participants (HP). Therefore, it is urgently necessary to establish a different vaccination strategy for DP, in terms of the dose and administration time. METHODS: Here, we report an observational prospective cohort study in which the immunogenic efficacies of SARS-CoV-2 vaccine BNT162b2 on DP and HP were evaluated by absolute quantification of IgG levels in the blood. RESULTS: DP showed a delayed seroconversion after two vaccine doses, with a low absolute IgG levels compared to HP. While HP reached complete seroconversion within 10 days from the administration of a second dose, only 76% of DP were seropositive. After the booster dose, DP had a strongly improved seroconversion rate as well as antibody levels, reaching 97% seropositivity and 50 times enhancement on antibody levels. DISCUSSION/CONCLUSION: These results prompt to suggest an additional vaccine dose in DP, reducing the interval of time from the second dose. Since limited data are available on immune response in DP overtime after three vaccine doses currently, our study is among the first reports demonstrating the improved seropositivity and IgG levels in DP after the booster vaccine dose.

Pancreatico-Jejunostomy On Isolated Loop After Pancreatico-Duodenectomy: Is It Worthwhile?

BACKGROUND: Postoperative morbidity remains a significant problem after pancreatico-duodenectomy. The management of pancreatic stump continues to be a challenge, and many technical solutions have been developed over the years. In this study, we report the results obtained with the use of an isolated loop for pancreatico-jejunostomy in patients with soft pancreas and small pancreatic duct diameter. METHODS: Clinical data of patients submitted to pancreatico-duodenectomy in a period of sixteen years (2005-2020) were extracted from a prospective database. Patients with soft pancreas, main duct diameter < 2 mm and reconstruction by pancreatico-jejunostomy on single loop or isolated loop were selected. Primary end-point was the incidence of clinically relevant fistulas in the two groups of patients. Secondary endpoint was the length of postoperative hospital stay. A propensity score matching analysis was used for the statistics. RESULTS: Two hundred and twenty-one patients with the above characteristics were found in the database. One hundred and twelve of these received a single-loop reconstruction and 109 an isolated loop reconstruction. Incidence of clinically relevant fistulas was higher in the first group (41% vs 27%; p = 0.023). Postoperative hospital stay was significantly shorter in the second group (21 days vs 15; p < 0.001). These results were confirmed at the propensity score matching. CONCLUSION: In patients with soft pancreatic texture and small main duct diameter, pancreatico-jejunostomy on isolated loop is associated with a lower incidence of clinically relevant fistulas than after classic reconstruction. The duration of postoperative hospital stay was significantly reduced, with consequent reduction of cost.

Outcomes comparison of Pancreato-Gastrostomy and Isolated Jejunal Loop Pancreato-Jejunostomy following Pancreato-Duodenectomy in patients with soft pancreas and at moderate-high risk for POPF: a retrospective multicenter experience-based analysis.

Following pancreatoduodenectomy (PD), the modality of pancreato-enteric continuity restoration may impact on postoperative pancreatic fistula (POPF) risk. The aim of this study is to compare, among patients with soft pancreas and at moderate/high risk for POPF, the outcomes of PD with Pancreato-Gastrostomy (PG), versus Isolated Jejunal Loop Pancreato-Jejunostomy (IJL-PJ). 193 patients with a Callery Fistula Risk Score (C-FRS) ≥ 3 operated at 3 HPB Units, two performing PG and one IJL-PJ as their preferred anastomotic technique following PD (2009-2019) were included in this study (PG = 123, IJL-PJ = 70). Primary outcomes were POPF, clinically relevant (cr-)postoperative pancreatic hemorrhage (cr-PPH), delayed gastric emptying (cr-DGE), and postoperative major complications and mortality. POPF, cr-PPH, and cr-DGE occurred in 21.8%, 17.6%, and 11.4% of patients, and did not differ significantly between PG (26%, 19.5%, and 10.6%, respectively) and IJL-PJ (17.1%, 14.3%, and 12.9%, respectively; all p > 0.05) patients. Major (Dindo ≥ 3) complication and mortality rates were 26.4% and 3.3%, respectively, and did not differ significantly between PG (29.3% and 3.8%) and IJL-PJ (21.4% and 2.9) patients (p > 0.05). A faster surgical drain and nasogastric tube removal matched a significantly shorter hospitalization among IJL-PJ patients (median LOS: 18 days versus 25 days among PG patients, p < 0.001). In conclusion, IJL-PJ and PG, when performed by surgeons specialized with the concerned anastomotic technique in patients with soft pancreas and moderate/high risk for POPF, have similar results in terms of perioperative mortality and postoperative complications both overall and specific for PD.

Effectiveness on major cardiovascular risk factors of an educational program to promote a Mediterranean type of diet among the employees of the company FCA Italia S.p.A.

AIMS: The educational program implemented at the Pratola Serra (Avellino, Italy) facility of the company FCA (Fiat Chrysler Automobiles), had as its goal to raise awareness among people to adopt behaviors inspired by the principles of a Mediterranean diet, physical activity and prevention of the main cardiovascular risk factors. METHODS: The educational program was implemented in two different ways in order to compare, according to an intervention-control scheme, the performance of the subgroups and the effect of the types of intervention. On both groups measurements of the vital parameters were carried out and compared by means of statistical probabilistic tests. RESULTS: The educational intervention was shown to be effective in: encouraging healthy food choices both in the workplace and at home (with a statistically significant reduction in caloric intake, animal protein, saturated fatty acids, cholesterol and glycemic load and an increase in vegetable proteins), significantly increasing physical activity and reducing body weight, body mass index, waist circumference, total cholesterol, LDL cholesterol and blood glucose in the participants. CONCLUSIONS: The educational campaign proved effective in increasing the well-being of the participants, confirming the effectiveness of a multifactorial intervention based on the promotion of a dietary model rather than individual foods.

Effects of a multifactorial ecosustainable isocaloric diet on liver fat in patients with type 2 diabetes: randomized clinical trial.

INTRODUCTION: Treatment options for non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2D) are still a matter of debate. We compared the effects of a diet including different components versus a proven beneficial diet rich in monounsaturated fatty acids (MUFAs) on liver fat in T2D. RESEARCH DESIGN AND METHODS: According to a parallel design, 49 individuals with T2D, overweight/obese, with high waist circumference, 35-75 years-old, in satisfactory blood glucose control with diet or drugs not affecting liver fat content, were randomly assigned to an 8-week isocaloric intervention with a MUFA diet (n=26) or a multifactorial diet rich in fiber, MUFA, n-6 and n-3 polyunsaturated fatty acids, polyphenols, and vitamins D, E, and C (n=23). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS complete data were available for n=21 (MUFA diet) and n=18 (multifactorial diet) participants. RESULTS: Adherence to dietary interventions was optimal. No significant differences between groups in body weight reduction, plasma glycated hemoglobin, insulin, glucose, lipids and liver enzymes were observed. Liver fat significantly decreased after both the multifactorial diet (9.18%±7.78% vs 5.22%±4.80%, p=0.003) and the MUFA diet (9.47%±8.89% vs 8.07%±8.52%, p=0.027) with a statistically significant difference between changes either in absolute terms (-4.0%±4.5% vs -1.4%±2.7%, p=0.035) or percent (-40%±33% vs -19%±25%, p=0.030). CONCLUSIONS: An isocaloric multifactorial diet including several beneficial dietary components induced a clinically relevant reduction of liver fat in patients with T2D, more pronounced than that induced by simply replacing saturated fat with MUFA. This suggests that the 'optimal diet' for NAFLD treatment in T2D should be based on synergic actions of different dietary components on multiple pathophysiological pathways. TRIAL REGISTRATION NUMBER: NCT03380416.

An integrated care pathway for cancer patients with diabetes: A proposal from the Italian experience.

Diabetes and cancer frequently coexist in the same subject, often with relevant clinical effects on the management and prognosis of the comorbid patient. The existing guidelines, however, do not appropriately address many clinical issues in this setting. Although collaboration between diabetologists and oncologists should play an important role in achieving appropriate levels of care, close coordination or agreement between these specialists is seldom offered. There is an urgent need for greater interdisciplinary integration between all specialists involved in this setting, for a shared approach ensuring that organisational silos are overcome. To this end, the Italian Associations of Medical Diabetologists (AMD) and the Italian Association of Medical Oncology (AIOM) recently established a dedicated Working Group on 'Diabetes and Cancer'. The working group outlined a diagnostic and therapeutic clinical pathway dedicated to hospitalised patients with diabetes and cancer. In this article, we describe the Italian proposal including some suggested measures to assess, monitor and improve blood glucose control in the hospital setting, to integrate different specialists from both areas, as well as to ensure discharge planning and continuity of care from the hospital to the territory.

Preferential MGMT methylation could predispose a subset of KIT/PDGFRA-WT GISTs, including SDH-deficient ones, to respond to alkylating agents.

BACKGROUND: Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GISTs) constitute a small KIT/PDGFRA-WT GIST subgroup featuring DNA methylation which, although pervasive, appears nevertheless not randomly distributed. Although often indolent, these tumors are mostly chemorefractory in aggressive cases. Promoter methylation-induced O6-methylguanine DNA methyltransferase (MGMT) inactivation improves the efficacy of alkylating agents in gliomas, colorectal cancer and diffuse large B cell lymphoma. MGMT methylation has been found in some GISTs, without determining SDH status. Thirty-six GISTs were enrolled in past sarcoma trials testing alkylating agents, with negative results. Nevertheless, a possible effect on MGMT-methylated GISTs could have escaped detection, since tested GISTs were neither selected by genotype nor investigated for SDH; MGMT was studied in two cases only, revealing baseline activity; these trials were performed prior to the adoption of Choi criteria, the most sensitive for detecting GIST responses to therapy. Under these circumstances, we investigated whether MGMT methylation is preferentially found in SDH-deficient cases (identified by SDHB immunohistochemistry) by analyzing 48 pathogenetically heterogeneous GISTs by methylation-specific PCR, as a premise for possible investigations on the use of alkylating drugs in these tumors. RESULTS: Nine GISTs of our series were SDH-deficient, revealing significantly enriched in MGMT-methylated cases (6/9-67%-, vs. 6/39-15%- of SDH-proficient GISTs; p = 0.004). The pathogenetically heterogeneous KIT/PDGFRA-WT GISTs were also significantly MGMT-methylated (11/24-46%-, vs. 1/24-4%- of KIT/PDGFRA-mutant cases, p = 0.002). CONCLUSIONS: A subset of KIT/PDGFRA-WT GISTs, including their largest pathogenetically characterized subgroup (i.e., SDH-deficient ones), is preferentially MGMT-methylated. This finding could foster a reappraisal of alkylating agents for treating malignant cases occurring among these overall chemorefractory tumors.

Pasta Consumption and Connected Dietary Habits: Associations with Glucose Control, Adiposity Measures, and Cardiovascular Risk Factors in People with Type 2 Diabetes-TOSCA.IT Study.

BACKGROUND: Pasta is a refined carbohydrate with a low glycemic index. Whether pasta shares the metabolic advantages of other low glycemic index foods has not really been investigated. The aim of this study is to document, in people with type-2 diabetes, the consumption of pasta, the connected dietary habits, and the association with glucose control, measures of adiposity, and major cardiovascular risk factors. METHODS: We studied 2562 participants. The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. Sex-specific quartiles of pasta consumption were created in order to explore the study aims. RESULTS: A higher pasta consumption was associated with a lower intake of proteins, total and saturated fat, cholesterol, added sugar, and fiber. Glucose control, body mass index, prevalence of obesity, and visceral obesity were not significantly different across the quartiles of pasta intake. No relation was found with LDL cholesterol and triglycerides, but there was an inverse relation with HDL-cholesterol. Systolic blood pressure increased with pasta consumption; but this relation was not confirmed after correction for confounders. CONCLUSIONS: In people with type-2 diabetes, the consumption of pasta, within the limits recommended for total carbohydrates intake, is not associated with worsening of glucose control, measures of adiposity, and major cardiovascular risk factors.

Gastrointestinal effects of extra-virgin olive oil associated with lower postprandial glycemia in type 1 diabetes.

OBJECTIVE: To explore the possible mechanisms behind the lower glycemic response observed when extra-virgin olive oil (EVOO) is added to a high-glycemic index meal in patients with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: According to a randomized cross-over design, eleven T1D patients (6 women, 5 men) on insulin pump consumed in the metabolic ward, one week apart, three high-glycemic index meals differing only for amount and quality of fat: high-monounsaturated fat (EVOO), high-saturated fat (Butter), and low-fat (LF). Before and after the meals, blood glucose (continuous glucose monitoring), gastric emptying rate (ultrasound technique), and plasma concentrations of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide GIP (ELISA), glucagon (RIA), and lipids (colorimetric assays) were evaluated. RESULTS: Blood glucose iAUC (mmol/lx360 min) was lower after the EVOO (690 ± 431) than after the Butter (1320 ± 600) and LF meals (1007 ± 990) (M ± SD, p = 0.041 by repeated measures ANOVA). Gastric antrum volume was significantly larger in the early (60-90 min) postprandial phase (106 ± 21 vs. 90 ± 16 ml, p = 0.048) and significantly smaller in the late phase (330-360 min) (46 ± 10 vs. 57 ± 22 ml, p = 0.045) after the EVOO than after Butter meal. EVOO significantly increased postprandial GLP-1 iAUC (261 ± 311) compared to Butter (189 ± 349) (pmol/Lx180 min, p = 0.009). Postprandial GIP and glucagon responses were not significantly different between EVOO and Butter. Postprandial triglyceride iAUC was significantly higher after EVOO (100 ± 53) than after Butter (65 ± 60) (mmol/l × 360 min, p = 0.048). CONCLUSIONS: Changes in gastric emptying and GLP-1 secretion and reduced glucose absorption through glucose-lipid competition may contribute to lower glycemia after a high-glycemic index meal with EVOO in T1D patients. CLINICAL TRIALS NUMBER: NCT02330939.

Impact of a Mediterranean Dietary Pattern and Its Components on Cardiovascular Risk Factors, Glucose Control, and Body Weight in People with Type 2 Diabetes: A Real-Life Study.

This study evaluates the relation of a Mediterranean dietary pattern and its individual components with the cardiovascular risk factors profile, plasma glucose and body mass index (BMI) in people with type 2 diabetes. We studied 2568 participants at 57 diabetes clinics. Diet was assessed with the EPIC (European Prospective Investigation into Cancer and Nutrition) questionnaire, adherence to the Mediterranean diet was evaluated with the relative Mediterranean diet score (rMED). A high compared to a low score was associated with a better quality of diet and a greater adherence to the nutritional recommendations for diabetes. However, even in the group achieving a high score, only a small proportion of participants met the recommendations for fiber and saturated fat (respectively 17% and 30%). Nonetheless, a high score was associated with lower values of plasma lipids, blood pressure, glycated hemoglobin, and BMI. The relationship of the single food items components of the rMED score with the achievement of treatment targets for plasma lipids, blood pressure, glucose, and BMI were also explored. The study findings support the Mediterranean dietary model as a suitable model for type 2 diabetes and the concept that the beneficial health effects of the Mediterranean diet lie primarily in its synergy among various nutrients and foods rather than on any individual component.

Mirizzi Syndrome: Diagnosis and Management of a Challenging Biliary Disease.

Background: Mirizzi syndrome is a condition difficult to diagnose and treat, representing a particular "challenge" for the biliary surgeon. The disease can mimic cancer of the gallbladder, causing considerable diagnostic difficulties. Furthermore, it increases the risk of intraoperative biliary injury during cholecystectomy. The aim of this study is to point out some particular aspects of diagnosis and treatment of this condition. Methods: The clinical records of patients with Mirizzi syndrome, treated in the last five years, were reviewed. Clinical data, cholangiograms, preoperative diagnosis, operative procedures, and early and late results were examined. Results: Eighteen consecutive patients were treated in the last five years. Presenting symptoms were jaundice, pain, and cholangitis. Preoperative diagnosis of Mirizzi syndrome was achieved in 11 patients, while 6 had a diagnosis of gallbladder cancer and 1 of Klatskin tumor. Seventeen patients underwent surgery, including cholecystectomy in 8 cases, bile duct repair over T-tube in 3 cases, and hepaticojejunostomy in 4 cases. Two cases (11.1%) of gallbladder cancer associated with the Mirizzi syndrome were incidentally found: a patient underwent right hepatectomy and another patient was unresectable. The overall morbidity rate was 16.6%. There was no postoperative mortality. An ERCP with stent insertion was required in three cases after surgery. Sixteen patients were asymptomatic at a mean distance of 24 months (range: 6-48) after surgery. Conclusions: Mirizzi syndrome requires being treated by an experienced biliary surgeon after a careful assessment of the local situation and anatomy. The preoperative placement of a stent via ERCP can simplify the surgical procedure.

Diabetologists and Oncologists attitudes towards treating diabetes in the oncologic patient: Insights from an exploratory survey.

AIMS: Diabetes and cancer frequently coexist in the same subject, often having relevant effects on the management and prognosis of the oncologic patient. However, existing guidelines do not deal with many clinical issues in this setting appropriately. In evaluating the opinions of Diabetologists and Oncologists dealing with diabetes care in people with cancer, the Italian Association of Diabetologists (AMD) promoted a dedicated exploratory survey. METHODS: The survey was carried out through the web or handily delivered printed copies between October 2014 and April 2015, in Italy. It was composed of 27 questions intended to gather information on the characteristics of participants and to examine their clinical habits in this context, and participation was totally free and anonymous. RESULTS: A total of 252 physicians participated in the survey. Diabetologists accounted for 51.1% of respondents. According to survey results, in spite of the presence of diabetes (or diabetic complications) worsening the outcome of cancer treatments, the counseling or intervention of a Diabetologist was only required for less than two-thirds of hospitalized patients. For subjects with a life expectancy of months, 80% of specialists considered a glycemic target of 120-250 mg/dL optimal whereas Oncologists were more likely to consider a range of 180-360 mg/dL for patients with a shorter life expectancy. Furthermore, 1 participant out of 3 indicated 1-4 measurements/day as the most appropriate frequency for blood glucose monitoring including in the palliative setting. Insulin was the therapy of choice for the majority of respondents albeit with different routes of administration. CONCLUSIONS: This survey provides interesting preliminary data that could help facilitate and optimize the management of patients with cancer and diabetes, promoting the delivery of an organic answer to fragmented assistance, to potentially inappropriate behaviors, and to a tailored therapy in a context of particular clinical fragility.

Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial.

BACKGROUND: The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. METHODS: TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50-75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2-3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15-45 mg) or a sulfonylurea (5-15 mg glibenclamide, 2-6 mg glimepiride, or 30-120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. FINDINGS: Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 per 100 person-years) who were given sulfonylureas (hazard ratio 0·96, 95% CI 0·74-1·26, p=0·79). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p<0·0001). Moderate weight gain (less than 2 kg, on average) occurred in both groups. Rates of heart failure, bladder cancer, and fractures were not significantly different between treatment groups. INTERPRETATION: In this long-term, pragmatic trial, incidence of cardiovascular events was similar with sulfonylureas (mostly glimepiride and gliclazide) and pioglitazone as add-on treatments to metformin. Both of these widely available and affordable treatments are suitable options with respect to efficacy and adverse events, although pioglitazone was associated with fewer hypoglycaemia events. FUNDING: Italian Medicines Agency, Diabete Ricerca, and Italian Diabetes Society.

The Mucocele of the Gallbladder.

The gallbladder polyps are a common finding during ultrasonography but only in rare cases they may be a cancer. When a polyp is greater than 1 cm, the cholecystectomy is usually performed. In these images, a polyp of 4 cm corresponding to a collection of mucus (mucocele) is reported. This unusual polyp of the gallbladder was caused by heterotopic intestinal mucosa.

Polyphenol intake and cardiovascular risk factors in a population with type 2 diabetes: The TOSCA.IT study.

BACKGROUND: The role of polyphenol intake on cardiovascular risk factors is little explored, particularly in people with diabetes. AIM: To evaluate the association between the intake of total polyphenols and polyphenol classes with the major cardiovascular risk factors in a population with type 2 diabetes. METHODS: Dietary habits were investigated in 2573 males and females participants of the TOSCA.IT study. The European Prospective Investigation on Cancer and Nutrition (EPIC) questionnaire was used to assess dietary habits. In all participants, among others, we assessed anthropometry, plasma lipids, blood pressure, C-reactive protein and HbA1c following a standard protocol. The USDA and Phenol-Explorer databases were used to estimate the polyphenol content of the habitual diet. RESULTS: Average intake of polyphenols was 683.3 ± 5.8 mg/day. Flavonoids and phenolic acids were the predominant classes (47.5% and 47.4%, respectively). After adjusting for potential confounders, people with the highest intake of energy-adjusted polyphenols (upper tertile) had a more favorable cardiovascular risk factors profile as compared to people with the lowest intake (lower tertile) (BMI was 30.7 vs 29.9 kg/m2, HDL-cholesterol was 45.1 vs 46.9 mg/dl, LDL-cholesterol was 103.2 vs 102.1 mg/dl, triglycerides were 153.4 vs 148.0 mg/dl, systolic and diastolic blood pressure were respectively 135.3 vs 134.3 and 80.5 vs 79.6 mm/Hg, HbA1c was 7.70 vs 7.67%, and C-reactive Protein was 1.29 vs 1.25 mg/dl, p < .001 for all). The findings were very similar when the analysis was conducted separately for flavonoids or phenolic acids, the two main classes of polyphenols consumed in this population. CONCLUSIONS: Polyphenol intake is associated with a more favorable cardiovascular risk factors profile, independent of major confounders. These findings support the consumption of foods and beverages rich in different classes of polyphenols particularly in people with diabetes. CLINICAL TRIAL: http://www.clinicaltrials.gov; Study ID number: NCT00700856.

Unexpected gallbladder cancer: Surgical strategies and prognostic factors.

Gallbladder cancer is the most common tumor of the biliary tract and it is associated with a poor prognosis. Unexpected gallbladder cancer is a cancer incidentally discovered, as a surprise, at the histological examination after cholecystectomy for gallstones or other indications. It is a potentially curable disease, with an intermediate or good prognosis in most cases. An adequate surgical strategy is mandatory to improve the prognosis and an adjunctive radical resection may be required depending on the depth of invasion. If the cancer discovered after cholecystectomy is a pTis or a pT1a, a second surgical procedure is not mandatory. In the other cases (pT1b, pT2 and pT3 cancer) a re-resection (4b + 5 liver segmentectomy, lymphadenectomy and port-sites excision in some cases) is required to obtain a radical excision of the tumor and an accurate disease staging. The operative specimens of re-resection should be examined by the pathologist to find any "residual" tumor. The "residual disease" is the most important prognostic factor, significantly reducing median disease-free survival and disease-specific survival. The other factors include depth of parietal invasion, metastatic nodal disease, surgical margin status, cholecystectomy for acute cholecystitis, histological differentiation, lymphatic, vascular and peri-neural invasion and overall TNM-stage.

Diabetology and oncology meet in a network model: union is strength.

Diabetes and cancer are increasingly common conditions, and the management of cancer patients with diabetes is often challenging. Diabetes in cancer patients poses several complex clinical issues, including which treatment is suitable to control hyperglycemia, how to better counteract glucocorticoid-induced hyperglycemia, and how to manage nutritional problems of cachectic patients and glucose variability linked to artificial nutrition. A key aspect to consider is the patients' position on the trajectory of the oncologic disease, both to establish which level of glycemic control should be pursued and to decide the most suitable antidiabetic treatment to recommend. Endocrinologists are rarely involved in the management of patients with advanced cancer. Furthermore, lack of guidelines results in a "trial-and-error" approach, often with suboptimal disease management. Lastly, cancer survivors represent a frequently underestimated category of patients at higher cardiometabolic risk. A practical solution for these challenges lies in the implementation of care networks based on a close partnership and ongoing communication between oncologists, endocrinologists, and nutritionists, placing the patient at the center of the care process. At the same time, universities and scientific societies should play a key role in promoting research into areas of intersection of oncology and endocrinology, in raising awareness of common possibilities of primary and secondary prevention of metabolic and oncologic diseases, as well as specific challenges of managing diabetes and cancer, and proper training of health workers, while also supporting the shared implementation of effective management strategies.