Profiles of sulfonylurea use in Diabetes Mellitus type 2: An analysis of clinical practice over the last 10 years.

AIMS: Describing the evolution over time in the use of sulfonylureas (SUs) and the characteristics of patients at first prescription and at interruption of treatment with SUs. METHODS: Retrospective evaluation of data from the Italian Association of Diabetologists (AMD) Annals registry (2010-2020), about T2D patients who started treatment with SUs. The longitudinal probability of remaining on SUs was estimated by Kaplan Meier survival curves. RESULTS: SU prescription decreased from 30.7 % (2010) to 12.9 % (2020). Patients started on SU were 68.2 ±â€¯11.2 years old, mostly males (55.5 %), with diabetes duration = 10.1 ±â€¯8.3 years, BMI = 29.7 ±â€¯5.5 kg/m2, and HbA1c = 8.3 ±â€¯1.7 % [67 mmol/mol]. After one year, the probability of staying on SU was 85.4 %, 75.9 % after two years, 68.2 % after 3 years, 56.6 % after 5 years. Patients who discontinued SUs had higher BMI and HbA1c, were younger, more often males and treated with insulin. Over time, the percentage of subjects switched to metformin, DPP4i, SGLT2i, and GLP1RA increased, whereas use of glinides, glitazones, acarbose and insulin declined. CONCLUSIONS: These data suggest a consensus, slowly, but increasingly aligning with the current National indications of dismissing SUs for the treatment of T2D. The new drugs for diabetes should represent a preferable choice in all patients who do not have specific contraindications.

Raman amplification for trapped radiation in crystalline single Si nanoparticle.

In a single crystalline Si particle, we observed a huge amplification of the Raman peak at 521 cm-1. With an AFM microscope, coupled with a Micro-Raman spectrometer, we investigate a single Si particle at wavelengths of 532 nm, 633 nm, and 785 nm. As observed by transmission electron microscopy, it has an octahedral shape of 150 nm in size. Thermal effects were detected on the Raman peak when the laser radiation, trapped inside, determines the heating of the particle up to its fusion. In these cases, the Raman peak splits into two components, the first at the crystal position and the other shifted at a lower value. The data permit the identification of the amplification mechanism of the Raman peak as trapped radiation moving forward and backwards into the particle. The thermal effects are attributed to phonon confinement and reduced thermal exchange with the surrounding. The present results are discussed in light of local order, the uncertainty principle, and phonon dispersion curves, and corroborated by shape-dependent simulation of absorption, scattering, and extinction behaviour.

Pharmacogenetics of oral antidiabetes drugs: evidence for diverse signals at the IRS1 locus.

To investigate the role of IRS1 locus on failure to oral antidiabetes drugs (OADs) we genotyped single-nucleotide polymorphisms (SNPs), rs2943641, rs7578326 (tagging all SNPs genome-wide associated with type 2 diabetes (T2D) and related traits at this locus) and rs1801278 (that is, the loss-of-function IRS1 G972R amino acid substitution) in 2662 patients with T2D. Although no association with OAD failure was observed for rs2943641 and rs7578326 SNPs (odds ratio (OR): 1.04, 95% confidence interval (CI): 0.93-1.16 and OR: 0.97, 95% CI: 0.87-1.09 respectively), a significant association was observed for rs1801278 (OR: 1.34, 95% CI: 1.08-1.66). When meta-analyzed with previous published data, an allelic OR of 1.41 (1.15-1.72; P=0.001) was obtained, so that homozygous R972R individuals have >80% higher risk of failing to OADs as compared with their G972G counterparts. In all, though further studies are needed for confirming this finding, our present data point to IRS1 rs1801278 as a potential biomarker for pursuing the goal of stratified medicine in the field of antihyperglycemic treatment in T2D.

Hemorheological alterations in adults with prediabetes identified by hemoglobin A1c levels.

BACKGROUND AND AIMS: A link between increased blood viscosity and type 2 diabetes has been previously reported. Herein, we investigated the association of blood viscosity with prediabetes, identified by glycated hemoglobin A1c (HbA1c) according to the new American Diabetes Association criteria, and subclinical atherosclerosis. METHODS AND RESULTS: The study cohort includes 1136 non-diabetic adults submitted to anthropometrical evaluation, an oral glucose tolerance test and ultrasound measurement of carotid intima-media thickness (IMT). Whole blood viscosity was estimated using a validated formula based on hematocrit and total plasma proteins. After adjusting for age, and gender, individuals with HbA1c-defined prediabetes (HbA1c 5.7-6.4% [39-47 mmol/mol]) exhibited significantly higher values of hematocrit, and predicted blood viscosity as compared with controls. Increased levels of IMT were observed in subjects with HbA1c-defined prediabetes in comparison to controls. Predicted blood viscosity was positively correlated with age, waist circumference, blood pressure, cholesterol, triglycerides, fibrinogen, white blood cell, HbA1c, fasting and 2-h post-load glucose levels, fasting insulin, IMT and inversely correlated with HDL and Matsuda index of insulin sensitivity. Of the three glycemic parameters, i.e. HbA1c, fasting and 2-h post-load glucose, only HbA1c showed a significant correlation with predicted blood viscosity (ß = 0.054, P = 0.04) in a multivariate regression analysis model including multiple atherosclerosis risk factors. CONCLUSION: The study shows that individuals with HbA1c-defined prediabetes have increased predicted blood viscosity and IMT. The HbA1c criterion may be helpful to capture individuals with an increased risk of diabetes and cardiovascular disease who may benefit from an intensive lifestyle intervention.

Nanofat 2.0: experimental evidence for a fat grafting rich in mesenchymal stem cells.

Different strategies have been developed in the last decade to obtain fat grafts as rich as possible of mesenchymal stem cells, so exploiting their regenerative potential. Recently, a new kind of fat grafting, called "nanofat", has been obtained after several steps of fat emulsification and filtration. The final liquid suspension, virtually devoid of mature adipocytes, would improve tissue repair because of the presence of adipose mesenchymal stem cells (ASCs). However, since it is probable that many ASCs may be lost in the numerous phases of this procedure, we describe here a novel version of fat grafting, which we call "nanofat 2.0", likely richer in ASCs, obtained avoiding the final phases of the nanofat protocol. The viability, the density and proliferation rate of ASCs in nanofat 2.0 sample were compared with samples of nanofat and simple lipoaspirate. Although the density of ASCs was initially higher in lipoaspirate sample, the higher proliferation rate of cells in nanofat 2.0 virtually filled the gap within 8 days. By contrast, the density of ASCs in nanofat sample was the poorest at any time. Results show that nanofat 2.0 emulsion is considerably rich in stem cells, featuring a marked proliferation capability.

Strong infrared photoluminescence in highly porous layers of large faceted Si crystalline nanoparticles.

Almost all physical processes in solids are influenced by phonons, but their effect is frequently overlooked. In this paper, we investigate the photoluminescence of large silicon nanoparticles (approximately 100 nm size, synthesized by chemical vapor deposition) in the visible to the infrared detection range. We find that upon increasing laser irradiance, an enormous photoluminescence emission band appears in the infrared. Its intensity exhibits a superlinear power dependence, increasing over four orders of magnitude in the investigated pump power range. Particles of different sizes as well as different shapes in porous layers are investigated. The results are discussed taking into account the efficient generation of phonons under high-power pumping, and the reduced capability, porosity dependent, of the silicon nanoparticles to exchange energy with each other and with the substrate. Our findings are relevant for heat management strategies in silicon.

Intravitreal bevacizumab in the successful management of choroidal metastases secondary to lung and breast cancer unresponsive to systemic therapy: a case series.

PURPOSE: Management of choroidal metastases is commonly with systemic chemotherapy; however, if tumours are refractory to treatment and vision is endangered, local therapy modalities are feasible. A novel option is the use of intravitreal bevacizumab. This report presents three cases of choroidal metastatic tumours secondary to lung and breast cancer treated with intravitreal bevazizumab. PATIENTS AND METHODS: Three patients with choroidal metastases secondary to lung and breast tumours were treated at the Ophthalmology Unit, University of Rome 'Sapienza', S.Andrea Hospital from January 2009 to August 2012. All patients developed vision loss with diagnosis of chorioidal metastasis during systemic chemotherapy. Off label intravitreal bevacizumab treatment was performed with two 1.25 mg injections in two patients and four injections in one patient at 30-day intervals. RESULTS: Vision improved, subretinal fluid resolved, and choroidal tumour regression was obtained in all cases. Follow-up was 6, 9, and 12 months and there were no complications related to treatment. CONCLUSIONS: Intravitreal bevacizumab administration represented an efficacious therapeutic option with rapid effect in the treatment of choroidal metastatic tumours unresponsive to systemic therapy. It can have a role in the management of these tumours by preventing vision loss and improving the quality of life of patients.

High circulating irisin levels are associated with insulin resistance and vascular atherosclerosis in a cohort of nondiabetic adult subjects.

Irisin, a novel myokine, was proposed to be able to regulate glucose homeostasis and obesity in mice. Whether irisin levels are associated with cardio-metabolic variables, insulin sensitivity, and vascular atherosclerosis in humans remain unsettled. To determine the associations between circulating irisin levels, cardio-metabolic variables, insulin sensitivity, and common carotid intima-media thickness (IMT), an indicator of vascular atherosclerosis, a cross-sectional evaluation of circulating irisin levels and cardio-metabolic variables in 192 White adults was conducted. Insulin sensitivity and insulin clearance were assessed by euglycemic-hyperinsulinemic clamp. Common carotid IMT was measured by ultrasound. After adjusting for age and gender, irisin levels were positively correlated with body fat mass (r = 0.12, P < 0.05), fasting (r = 0.17, P < 0.01), 2 h post-load insulin (r = 0.15, P < 0.02) levels, and IMT (r = 0.29, P < 0.0001) and were negatively correlated with insulin-stimulated glucose disposal (r = -0.18, P = 0.007), Matsuda index (r = -0.13, P < 0.04), disposition index (r = -0.278, P < 0.0001), and insulin clearance (r = -0.26, P < 0.0001). After adjusting for age, gender, and BMI, individuals in the highest tertile of irisin levels exhibited higher body fat mass (P < 0.01), fasting (P < 0.05), 2 h post-load (P < 0.01) insulin levels, carotid IMT (P < 0.001), lower insulin-stimulated glucose disposal (P < 0.001), Matsuda index (P < 0.01), disposition index (P < 0.01), and insulin clearance (P < 0.001) as compared with subjects in the lowest tertile of circulating irisin levels. Irisin is inversely associated with insulin sensitivity and positively associated with carotid IMT in humans, suggesting either increased release by adipose/muscle tissue in response to deterioration of insulin sensitivity or a compensatory increase in irisin to overcome an underlying irisin resistance.

Increased carotid intima-media thickness in the physiologic range is associated with impaired postprandial glucose metabolism, insulin resistance and beta cell dysfunction.

BACKGROUND: Carotid Intima-Media Thickness (C-IMT) is a reliable predictor of cardiovascular events. We examined if increased C-IMT was associated with defects in glucose metabolism in non-diabetic subjects independently of age. METHODS: In 366 Caucasian non-diabetic subjects of the CARAMERIS study, we measured glucose response during a 75 g-Oral Glucose Tolerance Test (OGTT), insulin sensitivity index (ISI, by Matsuda Index), Liver Insulin Resistance Index (Liver-IR), insulin secretion by ΔAUC Ins0-120/Glu0-120 (ΔI/ΔG) and beta cell function (Disposition Index, DI). RESULTS: Subjects were divided in two groups according to the median age (AGE1 ≤ 45 y; AGE2 > 45 y). Only 5 subjects in AGE1 and 32 in AGE2 had C-IMT > 0.9 mm. Compared to AGE1, AGE2 had a worse cardio-metabolic profile, increased cholesterol, glucose and insulin concentrations, blood pressure and C-IMT. Both ΔI/ΔG ratio and DI were significantly reduced in AGE2. By considering tertiles of C-IMT in each AGE group (G1-G3, where G3 comprised the highest C-IMT), we found that G3 showed increased OGTT glucose profiles and Liver IR, decreased ISI and DI, compared to G1 in each AGE group. CONCLUSIONS: Increased C-IMT, but within normal ranges, is associated independently of age with altered postprandial glucose profile, increased peripheral and hepatic insulin resistance, decreased b-cell function. C-IMT measurement should become a routine analysis even in younger subjects to predict the risk of cardio-metabolic disease.

Increased levels of the Akt-specific phosphatase PH domain leucine-rich repeat protein phosphatase (PHLPP)-1 in obese participants are associated with insulin resistance.

AIMS/HYPOTHESIS: We determined the contribution to insulin resistance of the PH domain leucine-rich repeat protein phosphatase (PHLPP), which dephosphorylates Akt at Ser473, inhibiting its activity. We measured the abundance of PHLPP in fat and skeletal muscle from obese participants. To study the effect of PHLPP on insulin signalling, PHLPP (also known as PHLPP1) was overexpressed in HepG2 and L6 cells. METHODS: Subcutaneous fat samples were obtained from 82 morbidly obese and ten non-obese participants. Skeletal muscle samples were obtained from 12 obese and eight non-obese participants. Quantification of PHLPP-1 in human tissues was performed by immunoblotting. The functional consequences of recombinant PHLPP1 overexpression in hepatoma HepG2 cells and L6 myoblasts were investigated. RESULTS: Of the 82 obese participants, 31 had normal fasting glucose, 33 impaired fasting glucose and 18 type 2 diabetes. PHLPP-1 abundance was twofold higher in the three obese groups than in non-obese participants (p = 0.004). No differences were observed between obese participants with normal fasting glucose, impaired fasting glucose or type 2 diabetes. PHLPP-1 abundance was correlated with basal Akt Ser473 phosphorylation (r = -0.48; p = 0.001), BMI (r = 0.44; p < 0.0001), insulin (r = 0.35; p < 0.0001) and HOMA (r = 0.38; p < 0.0001). PHLPP-1 abundance was twofold higher in the skeletal muscle of 12 obese participants than in that of eight non-obese participants (p < 0.0001). Insulin treatment of HepG2 cells resulted in a dose- and time-dependent upregulation of PHLPP-1. Overexpression of PHLPP1 in HepG2 cells and L6 myoblasts resulted in impaired insulin signalling involving Akt/glycogen synthase kinase 3, glycogen synthesis and glucose transport. CONCLUSIONS/INTERPRETATION: Increased abundance of PHLPP-1, production of which is regulated by insulin, may represent a new molecular defect in insulin-resistant states such as obesity.

Ultrabiomicroscopy (UBM) in flap dislocation following LASIK: a case report.

PURPOSE: To describe postoperative laser-assisted in situ keratomileusis (LASIK) flap dislocation occurred after trauma METHODS: Ultrabiomicroscopy (UBM) is used to obtain a high-resolution imaging of the cornea. RESULTS: The UBM results are presented and compared with histologic and confoscan findings CONCLUSIONS: The technique is useful and easy to perform, offering more opportunities to study the anatomical changes in LASK flap dislocation occurred after trauma.

Ring keratopathy in a patient with psoriatic arthritis and ulcerative rectocolitis.

PURPOSE: To describe a bilateral ring-shaped corneal opacity associated to immunological bowel and skin diseases. METHODS: Ophthalmic examination, tear film evaluation, ultrasound biomicroscopy (UBM), rheumatologic examination, and haematological screening. RESULTS: A 30-year-old man with psoriatic arthritis and ulcerative rectocolitis showed an unusual bilateral ring keratopathy not responding to topical and oral anti-inflammatory treatment. UBM examination revealed the high reflectivity of lesions distributed in the anterior stroma. CONCLUSION: Although association with systemic autoimmune diseases together with the ring aspect could suggest the immunological origin of corneal lesions, degenerative keratopathy cannot be excluded because the poor response to therapy alongside the UBM findings.

[Radiation protection issues in brachytherapic treatment of prostatic cancer]. / Problematiche radioprotezionistiche nel trattamento brachiterapico del cancro della prostata.

Brachytherapy is an effective radiotherapeutic treatment for localized prostatic cancer. The permanent brachytherapy is a particular kind of radiotherapy which, US guided, uses permanently implanted seeds containing radioactive sources (Pd103 or I 125). The procedure is minimally invasive and allows to obtain high percentage of success which is comparable to surgery. The possibility to confine permanent radioactive implants in a well delimitated area doesn't exclude the exposition of both the medical staff and family's members of implanted patients. The radiation exposure involves the medical physicists, the radiotherapists, the Medical Radiology Technician, the anaesthetists, the surgeons, the professional nurses but also, after the brachytherapy treatment, public and family members, comforters and cares. It's necessary to consider radiation safety aspects of brachytherapy in order to reduce the risks of exposition. At the end, several studies showed that cremation of bodies could be a possible radiation source that remains in the patient's ashes, potentially inhaled by crematorium staff or members of the public.

Mitotropic compounds for the treatment of age-related macular degeneration. The metabolic approach and a pilot study.

Recent histopathologic studies have shown that mitochondria and peroxisomes of the retinal pigment epithelium may play a central role in the pathophysiology of age-related macular degeneration (AMD). We supposed that compounds which improve mitochondrial functions (mitotropic compounds) may show beneficial effects in preventing AMD. Fourteen patients affected by early AMD were treated with a mixture containing acetyl-L-carnitine (ALC), polyunsaturated fatty acids (PUFAs), coenzyme Q10 (CoQ10) and vitamin E, while an equal number of age- and sex-matched patients affected by early AMD were treated with vitamin E only. Recovery time after macular photostress, foveal sensitivity and mean defect in the visual field as well as blood lipid levels were recorded at the beginning and after 3, 6, 9, 12 and 24 months of follow-up. In the treated group, all the visual functions showed slight improvement which was evident after 3 months of treatment and remained nearly stationary by the end of 24 months. The same tests in the control group showed slow worsening. The divergence between treated and control groups became more marked with time, but the difference was not significant at any time of the follow-up. These findings suggest that the blend of ALC, PUFA, CoQ10 and vitamin E may improve retinal functions in early AMD.

Ultrasound biomicroscopy of the peripheral retina and the ciliary body in degenerative retinoschisis associated with pars plana cysts.

AIM: To evaluate the ciliary body and peripheral retina in degenerative retinoschisis associated with pars plana cysts using ultrasound biomicroscopy (UBM). METHODS: 18 eyes of 12 patients with degenerative retinoschisis associated with pars plana cysts were selected through binocular indirect ophthalmoscopy and Goldmann three mirror lens examination, both with scleral depression. These patients were studied in detail with UBM. RESULTS: Study of the ciliary body with UBM showed pars plana cysts of different size and uneven shape. In cross sections the morphology of pars plana cysts in detail and the close relation of the cysts with the oral region and the peripheral retina, where areas of cystoid degeneration and retinoschisis were present, were observed. In transverse sections three main morphological aspects of pars plana cysts could be differentiated ("isolated," "confluent," and "clustered" cysts). Furthermore, ultrabiomicroscopy allowed differential diagnosis between retinoschisis and associated retinal detachment in six eyes. CONCLUSIONS: The study of peripheral degenerative retinoschisis and pars plana cysts is possible in vivo by means of UBM, showing the detailed morphology of the lesions (not otherwise evident through ophthalmoscopic examination) and the close relation between pars plana cysts, cystoid degeneration, and peripheral retinoschisis.

Use of Erbium:YAG laser in the treatment of palpebral xanthelasmas.

OBJECTIVE: In light of the research and the use of lasers in the therapy of xanthelasmas, the authors report their experience in the treatment of this pathology with Erbium:YAG laser. MATERIALS AND METHODS: In 30 patients, all female, 70 xanthelasmas were treated with Erbium:YAG laser, 65 (93%) of which were on the upper eyelid and 5 (7%) on the lower eyelid, varying from 1 x 1.5 mm to 11 X 20 mm in size. Spots with a diameter of 1.6 mm, energy of 300 mJ, frequency of 1-5 Hz and in a number varying were used in relation to the extent of the pathology. RESULTS: In all cases, the appearance and functional results were good, without leaving scars and/or dyschromia. CONCLUSIONS: Erbium:YAG laser, in the treatment of xanthelasmas, is a parasurgical method that is simple to perform and because of the successful aesthetic and functional results, is a valid alternative to the more traditional treatment methods.

Ultrasound biomicroscopy in the clinical evaluation of ab externo holmium:YAG laser sclerostomies.

High-frequency ultrasound biomicroscopy (UBM) has extensive powers of resolution. This makes it possible to explore and study some areas of the anterior segment with a clarity close to that of histologic preparations. High-frequency UBM was used in the clinical evaluation of 10 glaucomatous eyes subjected to ab externo holmium:yttrium-aluminum-garnet (Ho:YAG) laser sclerostomy. The anatomic characteristics of the fistular paths were viewed and compared with echographic images. The authors demonstrated that in the 5 cases where the filtering bleb, fistular path, and internal ostium were present, there was a reduction of intraocular pressure. UBM is a high-definition diagnostic instrument in the follow-up of fistular paths and filtering blebs after Ho:YAG laser sclerostomy, making it possible to reoperate at an early stage before the onset of clinical manifestations.

[Efficacy and tolerance of azithromycin in respiratory tract infections in children]. / Efficacia e tollerabilità dell'azitromicina nelle infezioni respiratorie del bambino.

This study was carried out to determine the clinical efficacy and the clinical safety of azithromycin in a group of children with acute respiratory tract infections. The study involved 82 children treated with a single daily 10 mg/kg dose of azithromycin for three consecutive days. 7 days later, the overall clinical response was 100% (cure and improvement): bacteriological cure was achieved in 97.5% of the patients treated. Recurrences were never observed. Side effects not requiring interruption of therapy were observed in 3 patients (3.6%). The side effects were gastrointestinal disturbances. In conclusion azithromycin showed a remarkably clinical efficacy for treatment of acute respiratory infections in children. Tolerability and therapeutic compliance were excellent.

Visual disturbances associated with primary empty sella syndrome in patients with chronic renal failure.

After describing the main clinical features of primary empty sella syndrome and the main hormonal alterations in chronic renal failure, the authors report the results obtained in a group of 33 patients undergoing dialysis three times a week. Each patient had a complete ophthalmologic examination, with electroretinography and visual-evoked potentials, a complete radiologic examination, including skull stratigraphy (particularly of the sellar and parasellar bony structures), and a computed tomographic scan. In the whole group, visual acuity, ocular and lid motility, and visual fields were normal. In two patients, a slight bilateral papilledema, associated with a P100 latency increase and normal morphology and visual-evoked potentials, was reported. Two patients had initial unilateral papillary pallor associated with P100 amplitude alterations. In all four of these patients, radiologic examination showed a markedly pathologic sellar widening with thickening and double contour image of the floor. The report of a primary empty sella was confirmed by computed tomography in all four cases. The authors discuss the possible etiopathogenic mechanisms of the neuroophthalmologic symptoms associated with this syndrome.