Search

Abstract Background A Chronic Kidney Disease (CKD) Epidemiology Collaboration (EPI) formula not including a Black race coefficient has been recently developed and is now recommended in the US. The new (2021) equation was shown to yield higher estimated glomerular filtration rate (eGFR) values than the old (2009) one in a non-Black general population sample, thus reclassifying a significant number of individuals to a better eGFR category. However, reclassified individuals were previously shown to have a lower risk of progression to end-stage kidney disease, but higher adjusted risks for all-cause death and morbidity and mortality from cardiovascular disease than those not reclassified. This study evaluated the prognostic impact of switching from the 2009 to the 2021 CKD-EPI equation in non-Black individuals with type 2 diabetes. Methods The Renal Insufficiency And Cardiovascular Events (RIACE) was a prospective cohort study enrolling 15,773 Caucasian patients in 19 Italian centers in 2006–2008. Cardiometabolic risk profile, treatments, complications, and comorbidities were assessed at baseline and eGFR was calculated with the two equations. Vital status was retrieved on 31 October 2015 for 15,656 participants (99.3%). Results With the 2021 equation, the eGFR value increased in all patients, except for 293 individuals with a 2009 eGFR ≥ 105 ml·min− 1·1.73 m− 2. The median difference was 4.10 ml·min− 1·1.73 m− 2 and was higher in males, older individuals and those in the G2 category. Reclassification decreased the percentage of patients with reduced eGFR from 17.28 to 13.96% and with any CKD from 36.23 to 34.03%. Reclassified individuals had better cardiometabolic risk profile and lower prevalence of complications and use of medications than non-reclassified individuals. Risk of death versus the 2009 G1 category was lower for reclassified than non-reclassified participants in all eGFR categories and, particularly, in each 2009 eGFR category, though difference was significant only in the G4-G5 category. The Receiver Operator Characteristic curves were statistically, but not clinically different with the two equations. Conclusion Changing from the 2009 to the 2021 CKD-EPI equation results in higher eGFR and lower CKD prevalence, with a lower risk of death in reclassified patients with an eGFR

Abstract Background Heart failure and type 2 diabetes are prevalent public health issues in Europe. These complex chronic conditions require extensive pharmacological management, ongoing self-care, and behavioral changes. Despite the known benefits of lifestyle changes, such as regular exercise and better control of blood sugar levels, patients may need help implementing the recommended changes. This study aims to assess the effectiveness of a telemedicine program for managing heart failure and type 2 diabetes at home. The program focuses on promoting lifestyle changes. Methods and analysis During scheduled outpatient cardiology evaluations, eligible patients are recruited and randomly assigned to either an intervention or control group in a 1:1 ratio. The intervention group receives support from a nursing case manager through a structured home-based teleassistance program and a trainer for daily physical activity stimulation. They also have access to teleconsultations with cardiologists and diabetes specialists as needed, telemonitoring of vital signs, and daily step tracking. An app records and monitors daily drug treatment, glycemia, blood pressure, heart rate, and other clinical parameters. Patients can also self-report symptoms and communicate via a chat and videoconference system with a Nurse Case Manager. The control group receives routine care. Data collection occurs before intervention and 6 months after baseline during a new outpatient cardiology evaluation. The primary outcome is to measure the difference in the distance walked during a 6-min walk test between baseline and after 6 months. The key secondary outcomes include improving the disease status and physical activity profile. Data will be analyzed according to the intention-to-treat principles. Discussion This study will provide evidence on the efficacy of a telemedicine home-based management model to maintain correct lifestyles in patients with both heart failure and type 2 diabetes, improving self-management, their empowerment on the diseases, and increasing their knowledge and ability to recognize symptoms early. Trial registration ClinicalTrials.gov NCT05633784. Registered on November 30, 2022.

Abstract Background Foot ulcers and/or infections are common long-term complications of diabetes and are associated with increased mortality, especially from cardiovascular disease, though only a few studies have investigated the independent contribution of these events to risk of death. This study aimed at assessing the association of history of diabetic foot with all-cause mortality in individuals with type 2 diabetes, independent of cardiovascular risk factors, other complications, and comorbidities. Methods This prospective cohort study enrolled 15,773 Caucasian patients in 19 Italian centers in the years 2006–2008. Prior lower extremity, coronary, and cerebrovascular events and major comorbidities were ascertained by medical records, diabetic retinopathy by fundoscopy, diabetic kidney disease by albuminuria and estimated glomerular filtration rate, cardiovascular risk factors by standard methods. All-cause mortality was retrieved for 15,656 patients on 31 October 2015. Results At baseline, 892 patients (5.7%) had a history of diabetic foot, including ulcer/gangrene and/or amputation (n = 565; 3.58%), with (n = 126; 0.80%) or without (n = 439; 2.78%) lower limb revascularization, and revascularization alone (n = 330; 2.09%). History of diabetic foot was associated with all-cause death over a 7.42-year follow-up (adjusted hazard ratio, 1.502 [95% confidence interval, 1.346–1.676], p

Abstract Background We assessed whether hepatic steatosis with or without significant fibrosis (determined by validated non-invasive biomarkers) is associated with an increased 10-year estimated risk for cardiovascular disease (CVD) in people with type 1 diabetes mellitus (T1DM). Methods We conducted a retrospective, multicenter, cross-sectional study involving 1,254 adults with established T1DM without pre-existing CVD. We used the hepatic steatosis index (HSI) and fibrosis (FIB)-4 index for non-invasively detecting hepatic steatosis (defined as HSI > 36), with or without coexisting significant fibrosis (defined as FIB-4 index ≥ 1.3 or

IntroductionDenosumab is a monoclonal antibody blocking the receptor activator of nuclear factor kappa-B/receptor activator of nuclear factor kappa-B ligand (RANK/RANKL) pathway, thus inhibiting osteoclastogenesis. Since RANK and RANKL are also involved in the immune system activation, denosumab might interfere with the response against infections. Our study aimed to explore the relationship between denosumab treatment and coronavirus disease 2019 (COVID-19).Design and methodsThe occurrence and severity of COVID-19 were recorded in consecutive patients referred to the Endocrinology Department of Papa Giovanni XXIII Hospital, Bergamo, from 1 January 2020 to 1 January 2021. Patients treated with denosumab were compared to outpatient controls. Patients’ features were summarized by descriptive statistics. Multivariate logistic regression assessed the relationship between denosumab and COVID-19, adjusting for potential confounders. Subgroup analyses according to age, sex, body mass index (BMI), smoking status, and vitamin D levels were performed.ResultsThe final population included 331 patients treated with denosumab and 357 controls. COVID-19 incidence was lower in the denosumab group (7.6% vs. 14.6%, p = 0.004). COVID-19 severity was similar in both groups. Multiple logistic regression confirmed an association between denosumab and a reduced occurrence of symptomatic COVID-19 [odds ratio (OR) 0.46, 95% CI 0.21–0.98, p = 0.049]. Subgroup analyses suggested a potential protective effect of denosumab in patients over 75 years (OR 0.12, 95% CI 0.02–0.6, p = 0.011), with a significant interaction between denosumab and age categories (p = 0.047).ConclusionOur study confirms that denosumab may be safely continued in COVID-19 patients. RANK/RANKL inhibition seems associated with a reduced incidence of symptomatic COVID-19, particularly among the elderly.

Abstract Background An “obesity paradox” for mortality has been shown in chronic disorders such as diabetes, and attributed to methodological bias, including the use of body mass index (BMI) for obesity definition. This analysis investigated the independent association of BMI versus surrogate measures of central adiposity with all-cause mortality in individuals with type 2 diabetes. Methods The Renal Insufficiency And Cardiovascular Events Italian Multicentre Study is a prospective cohort study that enrolled 15,773 patients in 19 Italian centres in 2006–2008. Exposures were BMI and the surrogate measures of central adiposity waist circumference (WC), waist-to-height ratio (WHtR), and A Body Shape Index (ABSI). Vital status was retrieved on 31 October 2015 for 15,656 patients (99.3%), Results Age- and sex-adjusted hazard ratios and 95% confidence intervals were significantly higher in BMI-based underweight (1.729 [1.193–2.505), P = 0.004), moderately obese (1.214 [1.058–1.392), P = 0.006) and severely obese (1.703 [1.402–2.068), P

IntroductionThyroid dysfunctions associated with SARS-CoV-2 acute infection have been extensively described since the beginning of COVID-19 pandemics. Conversely, few data are available on the occurrence of thyroid autoimmunity after COVID-19 resolution. We assessed the prevalence of autoimmune thyroid disease (ATD) and thyroid dysfunctions in COVID-19 survivors three months after hospital admission.Design and methodsSingle-center, prospective, observational, cohort study performed at ASST Papa Giovanni XXIII Hospital, Bergamo, Italy. 599 COVID-19 survivors were prospectively evaluated for thyroid function and autoimmunity thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb). When a positive antibody concentration was detected, thyroid ultrasound was performed. Multiple logistic regression model was used to estimate the association between autoimmunity and demographic characteristics, respiratory support, and comorbidities. Autoimmunity results were compared to a cohort of 498 controls referred to our Institution for non-thyroid diseases before the pandemic onset. A sensitivity analysis comparing 330 COVID-19 patients with 330 age and sex-matched controls was performed.ResultsUnivariate and multivariate analysis found that female sex was positively associated (OR 2.01, SE 0.48, p = 0.003), and type 2 diabetes (T2DM) was negatively associated (OR 0.36, SE 0.16, p = 0.025) with thyroid autoimmunity; hospitalization, ICU admission, respiratory support, or COVID-19 treatment were not associated with thyroid autoimmunity (p > 0.05). TPOAb prevalence was greater in COVID-19 survivors than in controls: 15.7% vs 7.7%, p = 0.002. Ultrasonographic features of thyroiditis were present in 94.9% of the evaluated patients with positive antibodies. TSH was within the normal range in 95% of patients.ConclusionsAutoimmune thyroid disease prevalence in COVID-19 survivors was doubled as compared to age and sex-matched controls, suggesting a role of SARS-CoV-2 in eliciting thyroid autoimmunity.

Abstract Background It is unclear whether insulin resistance (IR) contributes to excess mortality in patients with type 2 diabetes independent of diabetic kidney disease (DKD), which is strongly associated with IR and is a major risk factor for cardiovascular disease (CVD), the main cause of death in these individuals. We tested this hypothesis in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian Multicentre Study. Methods This observational, prospective, cohort study enrolled 15,773 patients with type 2 diabetes attending 19 Italian Diabetes Clinics in 2006–2008. Insulin sensitivity was assessed as estimated glucose disposal rate (eGDR), which was validated against the euglycaemic-hyperinsulinemic clamp technique. Vital status on October 31, 2015, was retrieved for 15,656 patients (99.3%). Participants were stratified by eGDR tertiles from T1 (≥ 5.35 mg/kg/min) to T3 (≤ 4.14 mg/kg/min, highest IR). Results CVD risk profile was worse in T2 and T3 vs T1. eGDR tertiles were independently associated with micro- and macroalbuminuria and the albuminuric DKD phenotypes (albuminuria with preserved or reduced estimated glomerular filtration rate [eGFR]) as well as with eGFR categories or the nonalbuminuric DKD phenotype. Over a 7.4-year follow-up, unadjusted death rates and mortality risks increased progressively across eGDR tertiles, but remained significantly elevated after adjustment only in T3 vs T1 (age- and gender- adjusted death rate, 22.35 vs 16.74 per 1000 person-years, p

Abstract Background Atherogenic dyslipidaemia has been implicated in the residual risk for cardiovascular morbidity and mortality, which remains despite attainment of LDL cholesterol goals especially in individuals with type 2 diabetes. However, its relationship with all-cause death has not been sufficiently explored. This analysis evaluated the independent association of increased triglycerides and triglyceride:HDL cholesterol ratio (TG:HDL) and decreased HDL cholesterol with total mortality and the possible modifying effect of gender in a large cohort of patients with type 2 diabetes. Methods This observational, prospective study enrolled 15,773 patients in 19 Diabetes Clinics throughout Italy in the years 2006–2008. Triglycerides and total and HDL cholesterol were measured by colorimetric enzymatic methods. Vital status was retrieved on 31 October 2015 for 15,656 patients (99.3%). Participants were stratified by quartiles of triglycerides, HDL cholesterol, and TG:HDL. Results There were 3,602 deaths over a follow-up 7.42 ± 2.05 years (31.0 × 1000 person-years). In the unadjusted analyses, the highest TG:HDL (but not triglyceride) and the lowest HDL cholesterol quartile were associated with increased death rate and mortality risk. When sequentially adjusting for confounders, including total, LDL, or non-HDL cholesterol and lipid-lowering treatment, mortality risk was significantly higher in the highest triglyceride (hazard ratio 1.167 [95% confidence interval 1.055–1.291], p = 0.003) and TG:HDL (1.192 [1.082–1.314], p

Abstract Background Resistant hypertension is independently associated with an increased risk of death in the general hypertensive population. We assessed whether resistant hypertension is an independent predictor of all-cause mortality in individuals with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study. Methods On 31 October 2015, vital status information was retrieved for 15,656 of the 15,773 participants enrolled in 2006–2008. Based on baseline blood pressure (BP) values and treatment, participants were categorized as normotensive, untreated hypertensive, controlled hypertensive (i.e., on-target with 3 drugs or controlled with > 4 drugs). Kaplan–Meier and Cox proportional hazards regression analyses were used to assess the association with all-cause mortality. Results Using the 130/80 mmHg targets for categorization, crude mortality rates and Kaplan–Meier estimates were highest among resistant hypertension participants, especially those with controlled resistant hypertension. As compared with resistant hypertension, risk for all-cause mortality was significantly lower for all the other groups, including individuals with controlled hypertension (hazard ratio 0.81 [95% confidence interval 0.74–0.89], P

BackgroundAngiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monotherapy.Methods and findingsVARIETY was a prospective, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether, at similar blood pressure (BP) control, combined therapy with benazepril (10 mg/day) and valsartan (160 mg/day) would prevent microalbuminuria more effectively than benazepril (20 mg/day) or valsartan (320 mg/day) monotherapy in 612 type 2 diabetic patients with high-normal albuminuria included between July 2007 and April 2013 by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS and 8 diabetology or nephrology units in Italy. Time to progression to microalbuminuria was the primary outcome. Analyses were intention to treat. Baseline characteristics were similar among groups. During a median [interquartile range, IQR] follow-up of 66 [42 to 83] months, 53 patients (27.0%) on combination therapy, 57 (28.1%) on benazepril, and 64 (31.8%) on valsartan reached microalbuminuria. Using an accelerated failure time model, the estimated acceleration factors were 1.410 (95% CI: 0.806 to 2.467, P = 0.229) for benazepril compared to combination therapy, 0.799 (95% CI: 0.422 to 1.514, P = 0.492) for benazepril compared to valsartan, and 1.665 (95% CI: 1.007 to 2.746, P = 0.047) for valsartan compared to combination therapy. Between-group differences in estimated acceleration factors were nonsignificant after adjustment for predefined confounders. BP control was similar across groups. All treatments were safe and tolerated well, with a slight excess of hyperkalemia and hypotension in the combination therapy group. The main study limitation was the lower than expected albuminuria at inclusion.ConclusionsRisk/benefit profile of study treatments was similar. Dual renin-angiotensin system (RAS) blockade is not recommended as compared to benazepril or valsartan monotherapy for prevention of microalbuminuria in normoalbuminuric type 2 diabetic patients.Trial registrationEudraCT 2006-005954-62; ClinicalTrials.gov NCT00503152.

Introduction In addition to favoring renal disease progression, renal ‘hyperfiltration’ has been associated with an increased risk of death, though it is unclear whether and how excess mortality is related to increased renal function. We investigated whether renal hyperfiltration is an independent predictor of death in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian multicenter study.Research design and methods This observational, prospective cohort study enrolled 15 773 patients with type 2 diabetes consecutively attending 19 Italian diabetes clinics in 2006–2008. Serum creatinine, albuminuria, cardiovascular risk factors, and complications/comorbidities were assessed at baseline. Vital status on 31 October 2015 was retrieved for 15 656 patients (99.26%). Patients were stratified (A) by absolute estimated glomerular filtration rate (eGFR) values in eGFR deciles or Kidney Disease: Improving Global Outcomes (KDIGO) categories and (B) based on age-corrected thresholds or age and gender-specific 95th and 5th percentiles in hyperfiltration, hypofiltration, and normofiltration groups.Results The highest eGFR decile/category and the hyperfiltration group included (partly) different individuals with similar clinical features. Age and gender-adjusted death rates were significantly higher in deciles 1, 9, and 10 (≥103.9, 50.9–62.7, and

This study evaluated the activity of the ethanolic extract of pequi peel (EEPP) and immunostaining with matrix metalloproteinases 2 and 9 (MMP2 and MMP9), and tissue inhibitor of metalloproteinases 1 and 2 (TIMP1 and TIMP2) in the myocardium of rats subjected to acute cardiotoxicity using doxorubicin (DOX). Thirty Wistar rats (six groups of five animals) were used as follows: sham group (SG), water and saline; group G1, 16 mg/kg of DOX and 300 mg/kg of EEPP for 17 days; group G2, 16 mg/kg of DOX and 600 mg/kg of EEPP for 17 days; group G3, 16 mg/kg of DOX and 300 mg/kg of EEPP for 10 days; group G4, 16 mg/kg of DOX and 600 mg/kg of EEPP for 10 days; and control group (CG), 16 mg/kg of DOX. Three days after administering DOX (day 17), euthanasia was performed, and samples were collected for anatomopathological analysis. Myocyte vacuolar degeneration, cardiomyocyte disorganization and myofibrillar fragmentation, necrosis, mononuclear inflammatory infiltrate, Anitschkow cells, fibrosis, congestion, and edema were observed in the hearts of DOX recipients. In G1 and G2, EEPP attenuated myocyte vacuolar degeneration whereas in G4, EEPP attenuated cardiomyocyte disorganization. The percentage of cells immunoreactive for TIMP1 was higher in G1. It was concluded that EEPP minimizes the deleterious effects of DOX on rat myocardium. Doses of 300 and 600 mg/kg for 17 days attenuate the vacuolar degeneration of myocytes. The dose of 600 mg/kg for 10 days reduced cardiomyocyte disorganization, and the dose of 300 mg/kg for 17 days increased TIMP1 expression in the myocardium of DOX-treated rats.

An association between liver stiffness, a surrogate measure of liver fibrosis, and chronic kidney disease (CKD) in patients with nonalcoholic fatty liver disease (NAFLD) has been proposed. However, most studies were small and had low statistical power. We systematically searched PubMed-MEDLINE and Scopus from inception to August 2021 for cross-sectional or cohort studies reporting the association between liver stiffness diagnosed by vibration controlled transient elastography (VCTE) and renal dysfunction. The primary outcome was CKD, defined as a composite of urinary albumin to creatinine ratio (UACR) ≥ 30 mg/g and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Measures of association from individual studies were meta-analyzed using random effects models. Of the 526 titles initially scrutinized, 7 cross-sectional studies fulfilled the criteria and were included. For CKD, risk was higher in patients with liver fibrosis assessed by VCTE, compared with patients without (n = 5 studies: OR 2.49, 95% CI 1.89–3.29; test for overall effect z = 6.475, p < 0.001). When increased UACR was considered as an outcome, elevated liver stiffness was associated with a significantly increased risk as well (n = 3 studies: OR 1. 98 95% CI 1.29–3.05; test for overall effect z = 3.113, p = 0.002). Neither analysis showed significant heterogeneity (I2 = 0% and I2 = 46.5%, respectively for the two outcomes). This meta-analysis indicates that elevated liver stiffness is associated with increased odds of kidney outcomes among patients with NAFLD. Wider use of VCTE to screen for advanced fibrosis might help identify patients at risk of end-stage renal disease.

Background. Aromatase inhibitors in women with breast cancer have been associated with cancer treatment-induced bone loss (CTIBL), increased fracture risk, and impairment of glucose metabolism. Denosumab (Dmab), a monoclonal antibody against RANKL, which is a key regulator of the osteoclast activity, is effective as an antiresorptive agent in the treatment of CTIBL. Since RANKL/RANK pathway may contribute to the pathogenesis of glucometabolic disorders, it has been suggested that Dmab may improve glucose homeostasis. Our pilot study evaluated the effect of a single administration of 60 mg Dmab on glucose metabolism in a cohort of women with breast cancer treated with aromatase inhibitors. Methods. Fifteen postmenopausal nondiabetic women were prospectively enrolled. Oral glucose tolerance test (OGTT) and metabolic parameters, including FGF21, were assessed at baseline and one month after Dmab injection. Midterm glucose control was evaluated by measuring glycated haemoglobin (HbA1c) levels 5 months after Dmab. Results. Parameters of glucose metabolism were not different one month after Dmab but circulating FGF21 levels significantly decreased (128.5 ± 46.8 versus 100.2 ± 48.8 pg/mL; p=0.016). Considering patients with insulin resistance at baseline (HOMA-IR > 2.5 and Matsuda Index

Complement activation has been increasingly implicated in the pathogenesis of type 2 diabetes and its chronic complications. It is unknown whether complement factor H (CFH) genetic variants, which have been previously associated with complement-mediated organ damage likely due to inefficient complement modulation, influence the risk of renal and cardiovascular events and response to therapy with angiotensin-converting enzyme inhibitors (ACEi) in type 2 diabetic patients. Here, we have analyzed the c.2808G>T, (p.Glu936Asp) CFH polymorphism, which tags the H3 CFH haplotype associated to low plasma factor H levels and predisposing to atypical hemolytic uremic syndrome, in 1,158 type 2 diabetics prospectively followed in the Bergamo nephrologic complications of type 2 diabetes randomized, controlled clinical trial (BENEDICT) that evaluated the effect of the ACEi trandolapril on new onset microalbuminuria. At multivariable Cox analysis, the p.Glu936Asp polymorphism (Asp/Asp homozygotes, recessive model) was associated with increased risk of microalbuminuria [adjusted hazard ratio (HR) 3.25 (95% CI 1.46–7.24), P = 0.0038] and cardiovascular events [adjusted HR 2.68 (95% CI 1.23–5.87), P = 0.013]. The p.Glu936Asp genotype significantly interacted with ACEi therapy in predicting microalbuminuria. ACEi therapy was not nephroprotective in Asp/Asp homozygotes [adjusted HR 1.54 (0.18–13.07), P = 0.691 vs. non-ACEi-treated Asp/Asp patients], whereas it significantly reduced microalbuminuria events in Glu/Asp or Glu/Glu patients [adjusted HR 0.38 (0.24–0.60), P < 0.0001 vs. non-ACEi-treated Glu/Asp or Glu/Glu patients]. Among ACEi-treated patients, the risk of developing cardiovascular events was higher in Asp/Asp homozygotes than in Glu/Asp or Glu/Glu patients [adjusted HR 3.26 (1.29–8.28), P = 0.013]. Our results indicate that type 2 diabetic patients Asp/Asp homozygotes in the p.Glu936Asp CFH polymorphism are at increased risk of microalbuminuria and cardiovascular complications and may be less likely to benefit from ACEi therapy. Further studies are required to confirm our findings.

Cushing’s syndrome is associated with increased morbidity and mortality. Although surgery is the first-line treatment, drugs can still play a role as an ancillary treatment to be employed while waiting for surgery, after unsuccessful operation or in patients unsuitable for surgery. We were asked to evaluate a 32-year-old male waiting for cardiac transplantation. Idiopathic hypokinetic cardiomyopathy had been diagnosed since 6 years. He was on treatment with multiple drugs, had a pacemaker, an implantable cardioverter and an external device for the support of systolic function. Physical examination showed severely impaired general status, signs of hypercortisolism and multiple vertebral compression fractures. We administered teriparatide, and the few evaluable parameters supported the diagnosis of ACTH-dependent hypercortisolism: serum cortisol was 24.2 μg/dL in the morning and 20.3 μg/dL after overnight 1 mg dexamethasone, urinary free cortisol (UFC) was 258 μg/24 h and ACTH 125 pg/mL. Pituitary CT was negative. Pasireotide 300 μg bid was administered and uptitrated to 600 μg bid. Treatment was well tolerated, achieving dramatic improvement of clinical picture with progressive normalization of serum cortisol and ACTH levels as well as UFC. After 4 months, the patient underwent successful heart transplantation. Many complications ensued and were overcome. Pituitary MRI was negative. On pasireotide 300 μg bid and prednisone 2.5 mg/day (as part of immunosuppressive therapy), morning serum cortisol and ACTH were 15.6 μg/dL and 54 pg/mL respectively, UFC was 37 μg/24 h, fasting glucose: 107 mg/dL and HbA1c: 6.5%. In conclusion, primary treatment with pasireotide achieved remission of hypercortisolism, thus allowing the patient to undergo heart transplantation.

The presence of severe renal insufficiency in type 2 diabetes patients often challenges the diabetologist to prescribe a drug therapy, leading to a satisfactory glycemic balance with the minimal risk of hypoglycaemia. Diabetics with renal dysfunction present an increased risk of hypoglycemic episodes, and oral drugs are often ìcontraindications in these patients , especially if they are eliminated by the kidney. This last class of drugs requires a reduction in dosages to avoid the risk of prolonged hypoglycaemic episodes. In particular, in patients with severe renal insufficiency, metformin must be suspended in order to avoid the risk of lactic acidosis. Here we report the case of a young woman with type 2 diabetes, who quickly developed severe renal failure, unfortunately without remission. This case emphasizes the efficacy and safety of insulin-associated linagliptin for good glycemic control in patients with severe renal impairment, with marked reduction in hypoglycaemic episodes (Diabetology).

Avaliou-se a ação do extrato etanólico da casca do pequi (EECP) e a imunomarcação de metaloproteinases de matriz 2 e 9 (MMP2 e MMP9), e inibidores teciduais das metaloproteinases de matriz 1 e 2 (TIMP1 e TIMP2), no miocárdio de ratos submetidos à cardiotoxicidade aguda pela doxorrubicina (DOX). Utilizaram-se 30 ratos Wistar, em seis grupos de cinco animais, sendo Grupo Sham (GS) água e salina; (G1) 16 mg/kg de DOX e 300 mg/kg de EECP por 17 dias; (G2) 16 mg/kg de DOX e 600 mg/kg de EECP por 17 dias; (G3) 16 mg/kg de DOX e 300 mg/kg de EECP por 10 dias; (G4) 16 mg/kg de DOX e 600 mg/kg de EECP por 10 dias; e grupo controle (GC) 16 mg/kg de DOX. Três dias após a aplicação da DOX, no dia 17, realizaram-se a eutanásia e colheita de amostras para análises antomopatológicas. No coração dos ratos que receberam DOX observaram-se degeneração vacuolar miocítica, desorganização dos cardiomiócitos e fragmentação das miofibrilas, necrose, infiltrado inflamatório mononuclear, células de Anitschkow, fibrose, congestão e edema. Nos grupos G1 e G2 o EECP atenuou a degeneração vacuolar miocítica e no G4 atenuou a desorganização dos cardiomiócitos. TIMP1 foi constatada em maior porcentagem de células marcadas no grupo de ratos que recebeu 300 mg/kg do EECP por 17 dias. Conclui-se que o EECP minimiza os efeitos deletérios da DOX no miocárdio de ratos. Nas doses de 300 e 600 mg/kg por 17 dias atenua a degeneração vacuolar miocítica, a 600 mg/kg por 10 dias reduz a desorganização dos cardiomiócitos e a 300 mg/kg por 17 dias aumenta a expressão de TIMP1 no miocárdio de ratos tratados com DOX.

Hyperglycaemic patients admitted to hospital have worse clinical outcomes with higher operational costs than normoglycaemic patients. Identifying, defining and treating hyperglycaemia promptly and appropriately is essential during hospitalization; adequate “continuity of care” must be assured after discharge. This requires a multidisciplinary clinical collaboration between the internist and the diabetes team, which plays a central role in the treatment course and should be involved soon after patient admission to the hospital. This document aims to establish guidelines and recommendations for good clinical practice in managing hyperglycaemic Internal Medicine patients, with or without previous diagnosis of diabetes. The Associazione Medici Diabetologi (AMD), Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti (FADOI) and Società Italiana di Diabetologia (SID) have decided to publish a document useful for internists in the management of hospitalised patients with hyperglycaemia. The Trialogue project, coordinated by the Board of Scientific experts from the three Scientific Societies, was initiated for this purpose. A questionnaire consisting of 16 multiple choice questions on the management of hyperglycaemia in hospital was answered by 660 physicians from over 250 internal medicine units distributed throughout Italy. Analysis of responses has yielded an overview of routine clinical practice and provided a wealth of ideas to better identify critical points in the treatment of hospitalized patients with hyperglycaemia. These recommendations were developed with the aim of providing mutually agreed practical guidance (instructions for use) that can be readily applied by healthcare professionals in routine clinical practice.

O objetivo deste estudo foi avaliar o efeito antioxidante do extrato hidroalcoolico da casca do pequi (EHCP) em ratos após a administração de doxorrubicina (DOX). Foram utilizados ratos da raça Wistar, distribuídos em quatro grupos, sendo que os animais do G1 (n=6) receberam água e solução salina (grupo controle), G2 (n=7) EHCP e solução salina, G3 (n=7) água e DOX e G4 (n=6) EHCP e DOX. O EHCP foi administrado por gavagem durante 10 dias aos ratos dos grupos G2 e G4 e água aos dos G1 e G3. DOX na dose de 10mg kg-1 e solução salina 0,9% foram administradas por via intravenosa no dia sete após o início do experimento aos animais de G3 e G4 e aos de G1 e G2, respectivamente. Foram avaliados peso e taxa de mortalidade. Dez dias após o início do experimento, foi avaliada a concentração sérica de creatina quinase MB (CK-MB), troponina e mioglobina, e os ratos foram submetidos à eutanásia e à avaliação anatomopatológica. Não houve diferença entre os tratamentos quanto ao peso dos animais (PThe objective of this study was to evaluate the antioxidant effect of the hydroalcoholic extract of pequi peel (HEPP) in rats after administration of doxorubicin (DOX). Were used 26 Wistar rats divided into four groups, which G1 (n=6) received water and saline solution (control group), G2 (n=7) HEPP and saline solution, G3 (n=7) water and DOX, and G4 (n=6) HEPP and DOX. The HEPP was administered by gavage for 10 days to G2 and G4 and water to G1 and G3. DOX and saline solution were administered intravenously on day seven after the start of the experiment, with the DOX (10mg kg-1) applied in G3 and G4, and saline solution 0.9% in G1 and G2. Were evaluated weight and mortality rate. Ten days after the start of the experiment were evaluated creatina kinase MB (CK-MB), troponin and myoglobin, and the rats were euthanized and evaluated morphologically. There was no difference between treatments in weight of animals (P>0.05). About the mortality rate an increase in group 2 was showed (P

During the collared peccaries’ (Tayassu tajacu) management, raised in captivity at Rio Grande do Norte’s Semi-arid, is common, in the hottest hours of the day, the animals’ death after clinical manifestations of myophaty by capture. The objective of this work was to study the stress syndrome in collared peccary, submitted to capture and containment in different hours of the morning. Thirty-five collared peccaries were used and divided in seven groups with five animals, they were evaluated to each one hour, to 6 a.m up to 1 p.m, generating seven intervals (treatments). For 35 days, in week intervals, clinical, hematologic, anatomopathologic exams, and physico-chemical of the meat were realized. There was significant increase (P

Atherogenic dyslipidemia seems to play a major role in microvascular complications and in residual microvascular risk after statin therapy, which reduces triglycerides up to 40%. We assessed whether raised TG levels are associated with an increased burden from microvascular complications in patients with type 2 diabetes.Subjects from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study (n=15,773) were divided in 4 groups depending on whether they had plasma triglycerides below (NTG, 67.8%) or above (HTG, 32.2%) 1.7 mmol/L and were (42.4%) or not on (57.6%) statin therapy. Estimated GFR (eGFR) was calculated from serum creatinine, albuminuria was measured by immunonephelometry or immunoturbidimetry, and retinopathy was evaluated by fundus examination.HTG subjects, either with or without statin, had higher prevalence of albuminuria, reduced eGFR and chronic kidney disease (CKD), especially the albuminuric forms, but not of retinopathy, than NTG subjects. In contrast, cardiovascular disease and advanced DR were more prevalent in subjects on statin than in those not, independently of triglyceride levels. Logistic regression analysis confirmed that HTG, without or with statin, was independently associated with micro and macroalbuminuria, mildly to severely reduced eGFR, and all CKD phenotypes, but not with retinopathy. The adjusted odd ratios for CKD increased linearly for every 0.26 mmol/L increase (approximately one decile) in triglyceride levels. The increase was higher with increasing severity of albuminuria, eGFR loss and CKD phenotype as well as in subjects receiving than in those not receiving statin treatment.Triglycerides are associated with CKD, but not retinopathy in subjects with type 2 diabetes, independently of statin treatment. These data point to a possible role of hypertriglyceridemia in the development of CKD, though it remains to be demonstrated that diabetic individuals might benefit from triglyceride reduction with statins and eventually with combination therapy with fibrates.www.ClinicalTrials.gov NCT00715481.

The scientific documentation supporting the potential clinical and economic benefits of a growing use of off-patent generic drugs in clinical practice seems to be limited in Italy as yet.We compared differences in outcomes between off-patent generic drugs and off-patent brand drugs in real clinical practice. The outcomes were: persistence and compliance with therapy, mortality, and other health resources consumption (hospitalizations, specialist examinations, other drugs) and total costs. Retrospective analysis was carried out by using the administrative databases of five Local Healthcare Units (ASLs - Aziende Sanitarie Locali) in the Lombardy Region of Italy. Data from the five ASLs were aggregated through a meta-analysis, which produced an estimate indicator of the mean or percentage difference between the two groups (branded vs. generic) and their respective significance tests. The therapeutic areas and studied drugs were: diabetes: metformin - A10BA02; hypertension: amlodipine - C08CA01; dyslipidemia: simvastatin - C10AA01; psychiatry: sertraline - N06AB06; cardiology: propafenone - C01BC03; osteoporosis: alendronate - M05BA04.The 5 Local Healthcare Units (ASL) represent a population of 3,847,004 inhabitants. The selected sample included 347,073 patients, or 9.02% of the total ASL population; 67% of the patients were treated with off-patent brand drugs. The average age was 68 years, with no difference between the two groups. After 34 months of observation, compliance and persistence were in favor to generic drugs in all therapeutic areas and statistically significant in the metformin, amlodipine, simvastatin, and sertraline groups. The clinical outcomes (hospitalizations, mortality, and other health costs) show no statistically significant differences between off-patent generic vs. off-patent brand medicines.Off-patent generic drugs appear to be a therapy option of choice in Italy as well, based on clinical outcomes and economic consequences, both for the National Health Service and patients, considering that the price difference between brand and generic drugs is completely charged on patients.