Paget Disease of Bone Harboring Bone Metastatic Neuroendocrine Cancer: A Case Report.

In this case report, we describe an uncommon case of neuroendocrine cancer of unknown origin began with cauda equina syndrome in a patient affected by Paget disease of bone (PDB). A 76-year-old man with diagnosis of PDB, without history of pain or bone deformity, developed sudden severe low back pain. Bone alkaline phosphatase was increased and MRI and whole-body scintigraphy confirmed the localization of the disease at the third vertebra of the lumbar spine. Treatment with Neridronic Acid was started, but after only 2 weeks of therapy anuria and bowel occlusion occurred together with lower limb weakness and walking impairment. Cauda equina syndrome consequent to spinal stenosis at the level of L2-L3 was diagnosed after admission to Emergency Department and the patient underwent neurosurgery for spinal medulla decompression. The histologic results showed a complete subversion of bone structure in neoplastic tissue, consistent with metastatic neuroendocrine carcinoma of unknown origin. In conclusion, low back pain in the elderly may require deep investigation to individuate rare diseases. In asymptomatic patients with apparently stable PDB, the sudden appearance of pain or neurologic symptoms may alert the clinician for the possibility of other superimposing diseases, like bone metastases.

Microbiota and Glucidic Metabolism: A Link with Multiple Aspects and Perspectives.

The global prevalence of overweight and obesity has dramatically increased in the last few decades, with a significant socioeconomic burden. In this narrative review, we include clinical studies aiming to provide the necessary knowledge on the role of the gut microbiota in the development of diabetic pathology and glucose-metabolism-related disorders. In particular, the role of a certain microbial composition of the fermentative type seems to emerge without a specific link to the development in certain subjects of obesity and the chronic inflammation of the adipose tissues, which underlies the pathological development of all the diseases related to glucose metabolism and metabolic syndrome. The gut microbiota plays an important role in glucose tolerance. Conclusion. New knowledge and new information is presented on the development of individualized therapies for patients affected by all the conditions related to reduced glucose tolerance and insulin resistance.

Lack of Association between Serum Chitotriosidase Activity and Arterial Stiffness in Type 2 Diabetes without Cardiovascular Complications.

Chitotriosidase (CHIT), a mammalian chitinase secreted by neutrophils and activated macrophages, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. The aim of this study is to evaluate CHIT activity as an early biomarker of arterial stiffness in people with T2D free from overt vascular complications. In this cross-sectional study, arterial stiffness as measured using standard pulse wave velocity (PWV) was evaluated in 174 people with T2D without overt vascular disease. Then, we measured CHIT serum activity with an electrochemiluminescence assay in two subgroups of participants: 35 with the highest (high-PWV) and 40 with the lowest (low-PWV) PWV values. CHIT activity was no different between the low-PVW and high-PWV groups (12.7 [9.6-17.9] vs. 11.4 [8.8-15.0] nmol/mL/h, respectively). Compared with the low-PWV group, the high-PWV participants were older (p < 0.001); had a longer duration of diabetes (p = 0.03); higher ankle-brachial index ABI (p = 0.04), systolic blood pressure (p = 0.002), diastolic blood pressure (p = 0.005), fasting blood glucose (p = 0.008), and HbA1c (p = 0.005); and lower eGFR (p = 0.03) and body mass index (BMI) (p = 0.01). No association was present with sex, duration of diabetes, age, BMI, peripheral blood pressure, laboratory parameters, and glucose-lowering medications or ongoing antihypertensive therapy. Although no association was found, this study provides novel data about the association of CHIT activity with CVD, focusing on a specific outcome (arterial stiffness) in a well-defined population of subjects with T2D without established CVD.

Development of a clinical risk score to predict death in patients with COVID-19.

OBJECTIVE: To build a clinical risk score to aid risk stratification among hospitalised COVID-19 patients. METHODS: The score was built using data of 417 consecutive COVID-19 in patients from Kuwait. Risk factors for COVID-19 mortality were identified by multivariate logistic regressions and assigned weighted points proportional to their beta coefficient values. A final score was obtained for each patient and tested against death to calculate an Receiver-operating characteristic curve. Youden's index was used to determine the cut-off value for death prediction risk. The score was internally validated using another COVID-19 Kuwaiti-patient cohort of 923 patients. External validation was carried out using 178 patients from the Italian CoViDiab cohort. RESULTS: Deceased COVID-19 patients more likely showed glucose levels of 7.0-11.1 mmol/L (34.4%, p < 0.0001) or >11.1 mmol/L (44.3%, p < 0.0001), and comorbidities such as diabetes and hypertension compared to those who survived (39.3% vs. 20.4% [p = 0.0027] and 45.9% vs. 26.6% [p = 0.0036], respectively). The risk factors for in-hospital mortality in the final model were gender, nationality, asthma, and glucose categories (<5.0, 5.5-6.9, 7.0-11.1, or 11.1 > mmol/L). A score of ≥5.5 points predicted death with 75% sensitivity and 86.3% specificity (area under the curve (AUC) 0.901). Internal validation resulted in an AUC of 0.826, and external validation showed an AUC of 0.687. CONCLUSION: This clinical risk score was built with easy-to-collect data and had good probability of predicting in-hospital death among COVID-19 patients.

Influence of Gender in Diabetes Mellitus and Its Complication.

In medicine, there is growing evidence that gender differences are important and lead to variations in the pathophysiology and treatment of many diseases with traits that appear to be particularly relevant in influencing the outcomes of many morbid forms. Today, the inclusion of gender in biomedical research, to improve the scientific quality and scientific relevance of knowledge, of technology is an increasingly present element precisely due to the practical implications that derive from it. Gender differences describe the biological variability between women and men, which is, in turn, related to differences in the information contained in sex chromosomes, the specific gene expression of autosomes linked to sex, the different number and quality of sex hormones, and their different effects on systems and organs, without neglecting the fact that each of the sexes has different target organs on which these hormones act. Additionally, both genders undergo metabolic changes throughout their lives, and this is especially true for women who show more dramatic changes due to their role in reproduction. Gender differences are not only the result of our genetic makeup but are also mixed with socio-cultural habits, behaviors, and lifestyles, differences between women and men, exposure to specific environmental influences, different food and lifestyle styles or stress, or different attitude in compliance with treatments and disease prevention campaigns. Gender differences also affect behavior throughout life, and physical changes can have implications for lifestyle, social roles, and mental health. Therefore, determinism and therapeutic outcome in chronic diseases are influenced by a complex combination of biological and environmental factors, not forgetting that there are many interactions of social and biological factors in women and men. This review will address the role of gender differences in the management of various forms of diabetes and its complications considering the different biological functions of hormones, the difference in body composition, physiological differences in glucose and fat metabolism, also considering the role of the microbiota. intestinal, as well as the description of gestational diabetes linked to possible pathophysiological events typical of reproduction.

Effects of the COVID-19 lockdown on glycaemic control in subjects with type 2 diabetes: the glycalock study.

AIM: To assess the effect of the coronavirus disease 2019 (COVID-19) lockdown on glycaemic control in subjects with type 2 diabetes (T2D). MATERIALS AND METHODS: In this observational, multicentre, retrospective study conducted in the Lazio region, Italy, we compared the differences in the HbA1c levels of 141 subjects with T2D exposed to lockdown with 123 matched controls with T2D who attended the study centres 1 year before. Basal data were collected from 9 December to 9 March and follow-up data from 3 June to 10 July in 2020 for the lockdown group, and during the same timeframes in 2019 for the control groups. Changes in HbA1c (ΔHbA1c) and body mass index (ΔBMI) during lockdown were compared among patients with different psychological well-being, as evaluated by tertiles of the Psychological General Well-Being Index (PGWBS). RESULTS: No difference in ΔHbA1c was found between the lockdown and control groups (lockdown group -0.1% [-0.5%-0.3%] vs. control group -0.1% [-0.4%-0.2%]; p = .482). Also, no difference was found in ΔBMI (p = .316) or ΔGlucose (p = .538). In the lockdown group, subjects with worse PGWBS showed a worsening of HbA1c (p = .041 for the trend among PGWBS tertiles) and BMI (p = .022). CONCLUSIONS: The COVID-19 lockdown did not significantly impact glycaemic control in people with T2D. People with poor psychological well-being may experience a worsening a glycaemic control because of restrictions resulting from lockdown. These findings may aid healthcare providers in diabetes management once the second wave of COVID-19 has ended.

Cardiometabolic multimorbidity is associated with a worse Covid-19 prognosis than individual cardiometabolic risk factors: a multicentre retrospective study (CoViDiab II).

BACKGROUND: Cardiometabolic disorders may worsen Covid-19 outcomes. We investigated features and Covid-19 outcomes for patients with or without diabetes, and with or without cardiometabolic multimorbidity. METHODS: We collected and compared data retrospectively from patients hospitalized for Covid-19 with and without diabetes, and with and without cardiometabolic multimorbidity (defined as ≥ two of three risk factors of diabetes, hypertension or dyslipidaemia). Multivariate logistic regression was used to assess the risk of the primary composite outcome (any of mechanical ventilation, admission to an intensive care unit [ICU] or death) in patients with diabetes and in those with cardiometabolic multimorbidity, adjusting for confounders. RESULTS: Of 354 patients enrolled, those with diabetes (n = 81), compared with those without diabetes (n = 273), had characteristics associated with the primary composite outcome that included older age, higher prevalence of hypertension and chronic obstructive pulmonary disease (COPD), higher levels of inflammatory markers and a lower PaO2/FIO2 ratio. The risk of the primary composite outcome in the 277 patients who completed the study as of May 15th, 2020, was higher in those with diabetes (Adjusted Odds Ratio (adjOR) 2.04, 95%CI 1.12-3.73, p = 0.020), hypertension (adjOR 2.31, 95%CI: 1.37-3.92, p = 0.002) and COPD (adjOR 2.67, 95%CI 1.23-5.80, p = 0.013). Patients with cardiometabolic multimorbidity were at higher risk compared to patients with no cardiometabolic conditions (adjOR 3.19 95%CI 1.61-6.34, p = 0.001). The risk for patients with a single cardiometabolic risk factor did not differ with that for patients with no cardiometabolic risk factors (adjOR 1.66, 0.90-3.06, adjp = 0.10). CONCLUSIONS: Patients with diabetes hospitalized for Covid-19 present with high-risk features. They are at increased risk of adverse outcomes, likely because diabetes clusters with other cardiometabolic conditions.

Sclerostin is expressed in the atherosclerotic plaques of patients who undergoing carotid endarterectomy.

BACKGROUND: Sclerostin (SC) is a monomeric glycoprotein expressed by osteocytes that affects bone formation. Recent studies have suggested a potential role for this protein in the pathophysiology of vascular diseases. The aim of the present study was to investigate SC expression in atherosclerotic plaques of patients affected by severe atherosclerotic disease who underwent carotid endarterectomy. We also evaluated possible differences in SC expression between patients with and without type 2 diabetes (T2D). METHODS: This was a cross-sectional study involving 46 patients aged 55 to 80 years (mean, 71.1 ± 6.7 years, 36 men, 15 patients with T2D) who underwent carotid endarterectomy. Immunohistochemical levels of SC were evaluated in the atherosclerotic plaques by double-staining immunochemistry, and serum SC levels were evaluated by enzyme-linked immunosorbent assay. RESULTS: Sclerostin was present in the atherosclerotic plaques of all subjects investigated and increased significantly in the media compared with the intima (P < 0.0001) as well as in vascular smooth muscle cells (VSMCs) compared with the infiltrating macrophages (P < 0.0001). However, no significant difference in SC expression was observed between patients with and without T2D. No correlation was found between serum and immunohistochemical levels of SC; significantly increased SC serum levels were detected in males compared with females (P = 0.049). CONCLUSIONS: We have demonstrated, for the first time, the expression of SC in VSMCs of atherosclerotic plaques, suggesting a potential role for this protein in the development of atherosclerosis. Further studies are needed to understand if the role played by SC is detrimental or protective in the atherosclerotic disease process.

Current status and future directions in the treatment of bone metastases from breast cancer.

The clinical treatment of bone metastasis from breast cancer is currently based on the systemic administration of antiresorptive agents, radiopharmaceuticals, and/or local treatments such as radiation therapy, radiofrequency ablation and surgery. However, these therapeutic options are merely palliative and do not show to have a significant positive impact on patients' survival. In addition, the systemic administration of antiresorptive drugs and/or antitumour agents and/or radiopharmaceuticals may negatively affect normal bone metabolism with detrimental consequences for cancer patients. Hence, the need to identify alternative therapeutic strategies that, based on the hallmarks of bone metastasis, can effectively thwart tumour cell growth while, at the same time, overcoming antitumour drug-induced bone loss and preserving bone health. To this aim, current studies are directed toward the development of new molecules with low toxicity and/or novel drug delivery systems, which may efficiently hinder the growth of metastatic cells, while other studies are focussed on the design of new clinical treatments that, by acting on early stages of breast cancer, may prevent the homing and the subsequent growth of cancer cells in the bone. These treatments might also target occult micro-metastases before their development into clinically evident bone lesions, ultimately hindering bone relapse and disease progression. However, this therapeutic approach implies the identification of early stage breast cancer patients being at high risk of developing bone metastases. The discovery of novel specific biomarkers as predictor of metastatic bone disease may help clinicians in selecting these patients.

Evidence of diabetes-specific autoimmunity in obese subjects with normal glucose tolerance.

BACKGROUND: Recently, significant attention has been paid to the possible activation of an autoimmune response in the presence of obesity. The aim of this study was to evaluate and compare the frequencies of autoantibodies typical of autoimmune diabetes in obese patients with normal glucose tolerance (NGT), obese patients with type 2 diabetes (T2D) and controls. We also evaluated the presence of immunoreactivity to Hashimoto's thyroiditis and autoimmune gastritis. MATERIALS AND METHODS: Consecutive sera from obese patients, 444 with NGT, 322 with T2D, and 212 controls were analysed by radioimmunoassay or enzyme-linked immunosorbent assay for glutamic acid decarboxylase, protein tyrosine phosphatase islet antigen-2 (IA-2)IC and IA-2(256-760) , islet beta-cell zinc cation transporter (ZnT8), thyroid peroxidase, and anti-parietal cell autoantibodies. RESULTS: Altogether the presence of organ-specific autoantibodies was significantly more frequent in obese patients with NGT (128/444, 28.5%) and obese with T2D (79/322, 24.5%) than in controls (36/212, 17%; P = 0.002). Thyroid peroxidase immunoreactivity was prevalent in all groups of subjects investigated. The frequencies of diabetes-specific autoantibodies were slightly higher in obese patients with NGT (20/444, 4.5%) than in obese with T2D (12/322, 3.7%) and controls (4/212, 1.9%). The anti IA-2(256-760) was the most frequent islet autoantibody in obese subjects with NGT (14/20, 70%). CONCLUSIONS: We observed significant evidence of immunoreactivity specific to diabetes, thyroid, and gastric-parietal cells in obese patients with NGT. The relatively higher frequency of the diabetes-related IA-2(256-760) autoantibodies in obese patients with NGT may suggest that this autoantibody could be associated with obesity the presence of obesity itself.

Clinical Impact of Cystatin C/Cathepsin L and Follistatin/Activin A Systems in Breast Cancer Progression: A Preliminary Report.

This study was directed to assess the clinical impact of the circulating cathepsin L, cystatin C, activin A, and follistatin in breast cancer patients. The serum concentrations of these molecules were determined by immunoenzymatic assays, and their association with some clinico-pathological parameters of breast cancer progression was evaluated. Our results identified cystatin C and activin A as predictive markers for the presence of breast cancer and bone metastasis, respectively. Therefore, these proteins may have a clinical role as circulating biomarkers in the diagnosis and therapeutic monitoring of breast cancer patients.

Exercise at lunchtime: effect on glycemic control and oxidative stress in middle-aged men with type 2 diabetes.

PURPOSE: Postprandial hyperglycemia and glycemic oscillations have been associated with increased oxidative stress. We sought to investigate the effect of two walking exercise protocols performed during lunchtime on glycemic control and oxidative stress in type 2 diabetic (T2D) patients. METHODS: Nine T2D patients participated in three randomized crossover trials; a control trial (Con), with participants having a standard lunch followed by their normal daily activities and two exercise trials (ContEx and Splitex). In ContEx, subjects performed 40 min of brisk walking 40 min after lunch, whereas in SplitEx the walking exercise was divided in two 20-min isoenergetic bouts, before and 40 min after meal. 24-h glycemic control was monitored by continuous glucose monitoring. 24-h urinary levels of 8-iso PGF2ɑ were measured as a marker of oxidative stress. RESULTS: SplitEx resulted in less time spent in moderate hyperglycemia after lunch vs ContEx (42.4 ± 38.7% vs 68.2 ± 32.7%, P = 0.04). ContEx reduced hyperglycemic time after breakfast consumed the morning after the exercise session (58.3 ± 29.6 Con vs 40.2 ± 33.4% ContEx, P = 0.02). Compared with Con, 24-h urinary isoprostanes were decreased both in ContEx (-68%, P = 0.02) and SplitEx (-63%, P = 0.04). CONCLUSIONS: Splitting an exercise session into two bouts, pre- and post-lunch, affects mainly the glycemic response to lunch, while a single-continuous isoenergetic session exerts its effect later in the 24-h period. Both exercise modalities effectively attenuate systemic oxidative stress with similar overall benefits.

Vitamin D in cancer chemoprevention.

CONTEXT: There is increasing evidence that Vitamin D (Vit D) and its metabolites, besides their well-known calcium-related functions, may also exert antiproliferative, pro-differentiating, and immune modulatory effects on tumor cells in vitro and may also delay tumor growth in vivo. OBJECTIVE: The aim of this review is to provide fresh insight into the most recent advances on the role of Vit D and its analogues as chemopreventive drugs in cancer therapy. METHODS: A systematic review of experimental and clinical studies on Vit D and cancer was undertaken by using the major electronic health database including ISI Web of Science, Medline, PubMed, Scopus and Google Scholar. RESULTS AND CONCLUSION: Experimental and clinical observations suggest that Vit D and its analogues may be effective in preventing the malignant transformation and/or the progression of various types of human tumors including breast cancer, prostate cancer, colorectal cancer, and some hematological malignances. These findings suggest the possibility of the clinical use of these molecules as novel potential chemopreventive and anticancer agents.

Flavonols and flavan-3-ols as modulators of xanthine oxidase and manganese superoxide dismutase activity.

Experiments were performed to assess the dose-dependent effects of quercetin, kaempferol, (+) catechin, and (-) epicatechin on superoxide radical production through the modulation of manganese superoxide dismutase and xanthine oxidase activities. The experiments were carried out at flavanoid concentrations ranging from 1 µM to 100 µM. This investigation highlighted that flavonols induced opposite effects on superoxide radical production at different doses, i.e. pro-oxidant at the highest concentration (100 µM) and anti-oxidant at the lowest concentration (1 µM). Similar behaviors were observed for xanthine oxidase with flavan-3ols. The diastereoisomer (the catechin) acted as a stronger radical scavenger than the epicatechin. However, flavan-3ols were less pro-oxidant than flavonols: in fact, the addition of the superoxide dismutase enzyme was able to cancel the flavan-3ols' pro-oxidant effect. This study also shows that the absence of the 4-carbonyl group conjugated with the 2-3 double bonds in the heterocyclic ring cancelled the pro-oxidant effect of flavan-3ols. The opposite dose-dependent effects of flavonols suggest that they may be used as either a pro-oxidant or antioxidant.

Wrist circumference is a clinical marker of insulin resistance in overweight and obese children and adolescents.

BACKGROUND: Excess fat is one of the main determinants of insulin resistance, representing the metabolic basis for developing future cardiovascular disease. The aim of the current study was to find an easy-to-detect clinical marker of insulin resistance which can be used to identify young subjects at increased risk of cardiovascular disease. METHODS AND RESULTS: Four-hundred and seventy-seven overweight/obese children and adolescents (mean age 10.31±2.80 years) were consecutively enrolled. Standard deviation score body mass index, fasting biochemical parameters, and homeostasis model assessment of insulin resistance were evaluated. Statistical differences were investigated using multiple linear regression analysis. Manual measure of wrist circumference was evaluated in all children and adolescents. Fifty-one subjects, randomly selected, underwent nuclear magnetic resonance imaging of the wrist to evaluate transversal wrist area at the Lister tubercle level. A statistically significant association was found between manual measure of wrist circumference and insulin levels or homeostasis model assessment of insulin resistance (ß=0.34 and 0.35, respectively; P<10(-5) for both comparisons). These associations were more significant than those between SD score body mass index and insulin levels or homeostasis model assessment of insulin resistance (ß=0.12 and 0.10, respectively; P≤0.02 for both comparisons). Nuclear magnetic resonance imaging acquisition clarified that the association between wrist circumference and insulin levels or homeostasis model assessment of insulin resistance reflected the association with bone tissue-related areas (P≤0.01 for both) but not with the adipose tissue ones (P>0.05), explaining 20% and 17% of the variances of the 2 parameters. CONCLUSIONS: Our findings suggest a close relationship among wrist circumference, its bone component, and insulin resistance in overweight/obese children and adolescents, opening new perspectives in the prediction of cardiovascular disease.

[Childhhood obesity, insulin resistance and increased cardiovascular risk]. / Obesità infantile, insulino-resistenza ed aumentato rischio cardiovascolare.

Excess fat is one of the major risk factors for insulin resistance predisposing to the development of cardiovascular diseases in western countries. We know that obese patients are strongly at risk of cardiovascular diseases, like myocardial infarction or stroke. These diseases are the most frequent cause of death in the adult population, representing a social and economic problem. Today there are not available and useful markers for screening and diagnosis of insulin- resistance in young people. "Easy-to-detect" clinical markers must be found to identify young subjects at risk of cardiovascular diseases. Very interesting the relationship between wrist circumference, its bone composition and insulin resistance.

Effects of oleuropein on tumor cell growth and bone remodelling: Potential clinical implications for the prevention and treatment of malignant bone diseases.

Oleuropein (Ole) is the main bioactive phenolic compound present in olive leaves, fruits and olive oil. This molecule has been shown to exert beneficial effects on several human pathological conditions. In particular, recent preclinical and observational studies have provided evidence that Ole exhibits chemo-preventive effects on different types of human tumors. Studies undertaken to elucidate the specific mechanisms underlying these effects have shown that this molecule may thwart several key steps of malignant progression, including tumor cell proliferation, survival, angiogenesis, invasion and metastasis, by modulating the expression and activity of several growth factors, cytokines, adhesion molecules and enzymes involved in these processes. Interestingly, experimental observations have highlighted the fact that most of these signalling molecules also appear to be actively involved in the homing and growth of disseminating cancer cells in bones and, ultimately, in the development of metastatic bone diseases. These findings, and the experimental and clinical data reporting the preventive activity of Ole on various pathological conditions associated with a bone loss, are indicative of a potential therapeutic role of this molecule in the prevention and treatment of cancer-related bone diseases. This paper provides a current overview regarding the molecular mechanisms and the experimental findings underpinning a possible clinical role of Ole in the prevention and development of cancer-related bone diseases.

Decrease of coronary heart disease risk with GLP1-receptor agonists or SGLT2 inhibitors therapy in patients with type 2 diabetes in primary cardiovascular prevention: A 24 months follow-up study.

AIMS: The aim of this real-world study is to evaluate the effect of glucagon-like peptide1 receptor-agonist (GLP1 RA) and sodium-glucose co-transporter2 inhibitor (SGLT2i) on coronary heart disease (CHD) risk, in patients with type 2 diabetes (T2D) in primary cardiovascular prevention. METHODS: Data from 312 patients with T2D, without CHD history, starting treatment with GLP1 RA (n = 174) or SGLT2i (n = 138), were retrospectively collected. UKPDS-RE score was used to estimate 10-years risk for CHD before and 6, 12 and 24 months after prescription. RESULTS: The 10-year CHD risk significantly decreased over 24 months in both GLP1 RA and SGLT2i groups (p = 0.037 and p < 0.001, respectively), with 3% and 7% CHD risk reduction already obtained after the first 6 months of GLP1 RA and SGLT2i therapy respectively (p < 0.001 in both groups. Analyses by categories of baseline CHD risk showed significant reductions of CHD risk in the severe risk categories of both groups (p < 0.001). CHD risk reduction obtained with SGLT2i was higher than with GLP1 RA at 6 and 12 months but not at 24 months. CONCLUSION: This real-world study shows that both GLP1 RA and SGLT2i reduce the 10-year risk for cardiovascular disease in patients with T2D in primary cardiovascular prevention.

Identification of the Inappropriate Clinical Actions (DON'T) to Improve the Management of Patients with Type 2 Diabetes Failing Basal Insulin Supported Oral Treatment: Results of Survey for a Panel of Diabetes Specialists in Italy.

INTRODUCTION: Despite the development of several recommendations, glycemic control in a large proportion of patients with type 2 diabetes, including those treated with insulin, remains suboptimal. This study is aimed to identify a set of actions to promote the reduction of inappropriate clinical practices in type 2 diabetes failing basal insulin supported oral therapy (BOT). METHODS: A panel of diabetes specialists was assembled to identify a list of ten corrective actions, "things not to do," for the management of type 2 diabetes: five concerning treatments, procedures and diagnostic tests and five about relationship, communication and information. The Choosing Wisely methodology and approach were the inspiration. RESULTS: A total of 73/73 (100%) panelists responded to the survey. Twenty-four actions were proposed. The final list of inappropriate actions deemed most important to improve the management of patients with type 2 diabetes failing BOT were: (1) do not use secretagogues-do not neglect the use of innovative glucose-lowering agents; (2) do not underestimate the risk of lack of hypoglycemia awareness; (3) do not underestimate the benefit of personalization of therapy; (4) do not delay insulin intensification; (5) do not delay modification of the therapeutic regimen. In the area of patient communication, the following actions were identified: (1) do not fail to train in the management of hypoglycemia; (2) do not underestimate whether the patient has understood the modification of therapy; (3) do not prescribe injection therapy without adequately instructing the patient to titrate it; (4) do not ignore the patient's adherence; (5) do not stop listening to the patient and verify learning. CONCLUSION: A set of corrective experience-based actions to enact in a timely manner, which can assist physicians in improving clinical outcomes and patients' needs in terms of communications and interaction, is proposed. The list is intended to promote discussions among diabetes specialists to provide high-value diabetes care.

Activin A and bone metastasis.

Activin A, is a multifunctional cytokine of the transforming growth factor-beta superfamily of growth factors. This molecule has been shown to be implicated in the regulation of a broad range of important biological functions including bone remodelling. Therefore, a deregulation in the activin signalling pathway may result in disturbances of normal bone metabolism and, eventually, in the onset of severe pathological conditions associated with an altered bone resorption. These observations support the concept that Act A might also be implicated in the pathogenesis of bone metastasis. This review provides insight into the most recent advances in understanding the role of this growth factor in the pathogenesis of bone metastasis, and discusses the implications related to the biomedical applications of these findings.