Validation in type 2 diabetes of a metabolomic signature of all-cause mortality.

CONTEXT: Mortality in type 2 diabetes is twice that of the normoglycemic population. Unravelling biomarkers that identify high-risk patients for referral to the most aggressive and costly prevention strategies is needed. OBJECTIVE: To validate in type 2 diabetes the association with all-cause mortality of a 14-metabolite score (14-MS) previously reported in the general population and whether this score can be used to improve well-established mortality prediction models. METHODS: This is a sub-study consisting of 600 patients from the "Sapienza University Mortality and Morbidity Event Rate" (SUMMER) study in diabetes, a prospective multicentre investigation on all-cause mortality in patients with type 2 diabetes. Metabolic biomarkers were quantified from serum samples using high-throughput proton nuclear magnetic resonance metabolomics. RESULTS: In type 2 diabetes, the 14-MS showed a significant (p < 0.0001) association with mortality, which was lower (p < 0.0001) than that reported in the general population. This difference was mainly due to two metabolites (histidine and ratio of polyunsaturated fatty acids to total fatty acids) with an effect size that was significantly (p = 0.01) lower in diabetes than in the general population. A parsimonious 12-MS (i.e. lacking the 2 metabolites mentioned above) improved patient discrimination and classification of two well-established mortality prediction models (p < 0.0001 for all measures). CONCLUSIONS: The metabolomic signature of mortality in the general population is only partially effective in type 2 diabetes. Prediction markers developed and validated in the general population must be revalidated if they are to be used in patients with diabetes.

Circadian Genes Expression Patterns in Disorders Due to Enzyme Deficiencies in the Heme Biosynthetic Pathway.

Heme is a member of the porphyrins family of cyclic tetrapyrroles and influences various cell processes and signalling pathways. Enzyme deficiencies in the heme biosynthetic pathway provoke rare human inherited metabolic diseases called porphyrias. Protein levels and activity of enzymes involved in the heme biosynthetic pathway and especially 5'-Aminolevulinate Synthase 1 are featured by 24-h rhythmic oscillations driven by the biological clock. Heme biosynthesis and circadian pathways intermingle with mutual modulatory roles. Notably, heme is a ligand of important cogs of the molecular clockwork, which upon heme binding recruit co-repressors and inhibit the transcription of numerous genes enriching metabolic pathways and encoding functional proteins bringing on crucial cell processes. Herein, we assessed mRNA levels of circadian genes in patients suffering from porphyrias and found several modifications of core clock genes and clock-controlled genes expression, associated with metabolic and electrolytic changes. Overall, our results show an altered expression of circadian genes accompanying heme biosynthesis disorders and confirm the need to deepen the knowledge of the mechanisms through which the alteration of the circadian clock circuitry could take part in determining signs and symptoms of porphyria patients and then again could represent a target for innovative therapeutic strategies.

[Percutaneous intervention therapy for vascular erectile dysfunction]. / Il trattamento interventistico percutaneo può risolvere la disfunzione erettile vasculogenica.

Erectile dysfunction (ED) is defined as the inability to get and maintain a sufficient erection to ensure an acceptable sexual activity for the subject and the partner. Although ED does not represent per se a serious disease, it carries a notable and severe influence on quality of life, with significant implications on familiar and social relationship; DE may cause depression, shame, impairment of personal esteem and relational problems. Among many possible etiologies of ED, atherosclerotic disease of penile arteries represents one of the most frequent causes, so it should always be looked for in patients with multiple risk factors for cardiovascular disease or an established coronary or peripheral artery disease. Up to 75% of patients with ED have a stenosis of the iliac-pudendus-penile artery system, deputy to perfusion of male genital organ. Recently the potential treatment of this pathologic condition by percutaneous approach has emerged with valid angiographic results and with a significant improvement in symptoms and quality of life. This review focuses on the normal anatomy and physiology of erection, the pathophysiology of ED, the common points between ED and ischemic cardiomyopathy and, lastly, the new chance of endovascular intervention for ED, to give our cardiologist colleagues the opportunity to screen and adequately treat patients with vascular ED.

[PLFT and TUMT long-term clinical results in Italy]. / Risultati a lungo termine del trattamento dell'adenoma prostatico mediante TUMT-PLFT.

Microwaves are electromagnetic radiations with wavelengths ranging from 300 MHz (0.3 GHz) and 300 GHz. Microwaves treatment reduces prostate tissue using the heat produced by microwaves. When the tissue absorbs the energy from the microwaves it coagulates and tissue necrosis occours. During hyperthermia the intraprostatic temperatures reached 40-45 °C with symptomatic improvement due to destruction of the alpha-adrenergic nerve fibers around the prostate. The term 'thermotherapy' was therefore coined to describe treatment temperatures above 45°C and hyperthermia for those below this level. Unlike thermotherapy, high-energy (thermotherapy) can achieve temperatures greater than 70°C (158°F), causing thermoablation of prostatic tissue. The authors report their experience with PLFT over a period of 8 years. They describe the technique of the treatment, the goal and its results. Many of these patients, however, were older, had a larger prostate volume, and had more surgical comorbidities, making this subset more likely to benefit from a minimally invasive option. With PLFT-TUMT, patients have a less-invasive therapy, with a catheter-free rate of 82-91% in selected patients, although the majority must also continue medical therapy.