Publications by authors named "Silvia Bini"

33 Publications

Outcome of cataract surgery in children affected by malignancies other than retinoblastoma with eye-lens radiation exposure.

Eur J Ophthalmol 2021 Apr 10:11206721211009445. Epub 2021 Apr 10.

San Paolo Ophthalmic Center, San Antonio Hospital - University Hospital, Padova, Italy.

Purpose: To describe, retrospectively, the visual outcome, feasibility, and safety of cataract surgery in a pediatric population affected by iatrogenic cataract, secondary to systemic oncological treatment for malignancies other than retinoblastoma.

Methods: Young patients, affected by radiation-induced cataract, who were referred to the San Paolo Ophthalmic Center in Padova between 2010 and 2017, were included in the study. All patients had previously received radiotherapy and/or chemotherapy treatment for malignancies, between 2004 and 2013. All medical records of infants who underwent cataract surgery were accurately reviewed.

Results: Eighteen eyes out of 11 patients included in the study underwent cataract surgery. The age at surgery was 9.7 ± 3.6 years. The interval between tumor diagnosis and cataract development was around 3 years. Mean follow-up after surgery was 15.4 ± 6.3 months. All eyes underwent posterior chamber intraocular lens implantation, posterior capsulotomy, and anterior vitrectomy in one time surgery. No intraoperative complications were shown. Post-operatively, only one eye received laser capsulotomy due to posterior capsule opacification. At the end of follow up, best-corrected visual acuity was 20/20 (LogMAR 0) in all eyes and significantly improved ( < 0.01) compared to baseline.

Conclusions: Iatrogenic-cataract surgery in pediatric oncological patients is a safe and effective way to improve visual acuity. Posterior capsulotomy and anterior vitrectomy at the time of surgery reduce the rate of posterior lens opacification and guarantee an excellent visual acuity in these patients.
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http://dx.doi.org/10.1177/11206721211009445DOI Listing
April 2021

Severe retinopathy of prematurity is associated with early post-natal low platelet count.

Sci Rep 2021 Jan 13;11(1):891. Epub 2021 Jan 13.

Department of Ophthalmology, University of Padova, Padova, Italy.

Pathophysiology of retinopathy of prematurity (ROP) still presents a gap. Lately blood tests parameters of premature infants have been measured at different times of ROP, attempting to detect correlations with ROP development and progression. So far, very early post-natal biomarkers, predictive of ROP outcome, have not been detected. Our purpose is to evaluate, in the earliest post birth blood sample, the correlation between routinely dosed blood parameters and ROP outcome. 563 preterm babies, screened according to ROP guidelines, were included and classified in conformity with ET-ROP study in "Group 1" (ROP needing treatment), "Group 2" (ROP spontaneously regressed) and "noROP" group (never developed ROP). The earliest (within an hour after delivery) blood test parameters routinely dosed in each preterm infant were collected. Platelet count was decreased in Group 1 versus noROP group (p = 0.0416) and in Group 2 versus noROP group (p = 0.1093). The difference of thrombocytopenic infants among groups was statistically significant (p = 0.0071). CRP was higher in noROP versus all ROPs (p = 0.0331). First post-natal blood sample revealed a significant thrombocytopenia in ROP needing treatment, suggesting a role of platelets in the pathophysiology and progression of ROP, possibly considering it as a predictive parameter of ROP evolution.
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http://dx.doi.org/10.1038/s41598-020-79535-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807000PMC
January 2021

Corneal side effects induced by EGFR-inhibitor antibody-drug conjugate ABT-414 in patients with recurrent glioblastoma: a prospective clinical and confocal microscopy study.

Ther Adv Med Oncol 2020 27;12:1758835920907543. Epub 2020 May 27.

IRCCS - Fondazione Bietti, Rome, Italy.

Background: The aim of this study was to prospectively analyse, for the first time worldwide by clinical confocal microscopy (CCM), corneal side effects secondary to the use of epidermal growth factor receptor (EGFR) inhibitor depatuxizumab mafodotin (ABT-414) in a cohort of patients affected by EGFR-amplified recurrent glioblastoma.

Methods: Each enrolled patient underwent full ophthalmologic examination including CCM of the cornea. Each patient was examined at baseline and every 2 weeks during treatment as long as patient conditions allowed it.

Results: A total of 10 patients were consecutively enrolled. Median follow-up was 5 months. No Common Terminology Criteria for Adverse Events Version 4.0 grade 4 toxicity was documented. Two (20%) grade 3 toxicities were documented at week 8. CCM examination detected in all eyes multiple and diffuse hyperreflective white round spots in the corneal basal epithelial layers (100%), progressive subbasal nerve plexus layer fibres fragmentation followed by full disappearance (100%) and appearance of round cystic structures in the corneal epithelium (100%). All CCM documented side effects reached the peak of prevalence and severity after a median of 3 infusions. After treatment discontinuation, the reversibility of corneal side effects was documented at CCM after a median of 4 weeks.

Conclusion: ABT-414 toxicity is not only directed to the corneal epithelium, but also to corneal nerves. Side effects are detectable in all treated patients and CCM documents early corneal epithelium and subbasal nerve plexus toxicity, with subsequent progressive restoration after treatment discontinuation. Ocular side effects due to ABT-414 can be manageable.
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http://dx.doi.org/10.1177/1758835920907543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278095PMC
May 2020

Uveal Melanoma Biopsy: A Review.

Cancers (Basel) 2019 Jul 30;11(8). Epub 2019 Jul 30.

Department of Ophthalmology, University of Padova, 35128 Padova, Italy.

Intraocular tumor diagnosis is based on clinical findings supported by additional imaging tools, such as ultrasound, optical coherence tomography and angiographic techniques, usually without the need for invasive procedures or tissue sampling. Despite improvements in the local treatment of uveal melanoma (UM), the prevention and treatment of the metastatic disease remain unsolved, and nearly 50% of patients develop liver metastasis. The current model suggests that tumor cells have already spread by the time of diagnosis, remaining dormant until there are favorable conditions. Tumor sampling procedures at the time of primary tumor diagnosis/treatment are therefore now commonly performed, usually not to confirm the diagnosis of UM, but to obtain a tissue sample for prognostication, to assess patient's specific metastatic risk. Moreover, several studies are ongoing to identify genes specific to UM tumorigenesis, leading to several potential targeted therapeutic strategies. Genetic information can also influence the surveillance timing and metastatic screening type of patients affected by UM. In spite of the widespread use of biopsies in general surgical practice, in ophthalmic oncology the indications and contraindications for tumor biopsy continue to be under debate. The purpose of this review paper is to critically evaluate the role of uveal melanoma biopsy in ophthalmic oncology.
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http://dx.doi.org/10.3390/cancers11081075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721328PMC
July 2019

Sub-threshold micropulse laser treatment reduces inflammatory biomarkers in aqueous humour of diabetic patients with macular edema.

Sci Rep 2019 07 11;9(1):10034. Epub 2019 Jul 11.

IRCCS - Fondazione Bietti, Rome, Italy.

Subthreshold micropulse laser (SMPL) is a tissue-sparing technique whose efficacy is demonstrated for diabetic macular edema (DME) treatment. However, its mechanism of action is poorly known. A prospective observational study was performed on naïve DME patients treated with SMPL, to evaluate the changes of aqueous humor (AH) inflammatory and vaso-active biomarkers after treatments. AH samples of eighteen DME eyes were collected before and after SMPL. Ten non-diabetic AH samples served as controls. Full ophthalmic evaluation, spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography were performed in DME group. Glass chip protein array was used to quantify 58 inflammatory molecules. Central retinal thickness (CRT) and visual acuity were also monitored. Several molecules showed different concentrations in DME eyes versus controls (p value < 0.05). Fas Ligand (FasL), Macrophage Inflammatory Proteins (MIP)-1α, Regulated on Activation Normal T Cell Expressed and Secreted (RANTES) and Vascular Endothelial Growth Factor (VEGF) were increased in DME at baseline versus controls and decreased after SMPL treatments (p < 0.05). CRT reduction and visual acuity improvement were also found. Inflammatory cytokines, mainly produced by the retinal microglia, were significantly reduced after treatments, suggesting that SMPL may act by de-activating microglial cells, and reducing local inflammatory diabetes-related response.
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http://dx.doi.org/10.1038/s41598-019-46515-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624368PMC
July 2019

Final versus referral diagnosis of childhood visual impairment in an Italian tertiary low vision rehabilitation centre.

Eur J Ophthalmol 2020 Sep 12;30(5):1156-1161. Epub 2019 Jun 12.

IRCCS-Fondazione Bietti, Rome, Italy.

Purpose: To compare the final diagnosis of the causes of low vision in children attending a tertiary rehabilitation centre for visually impaired children versus referral diagnosis.

Methods: Retrospective review of clinical charts of all children referred to the Robert Hollman Foundation, a tertiary centre for visually impaired children, between January 2010 and June 2011. The following clinical data were analysed: entry diagnosis made by the referral ophthalmologist and final diagnosis made at Robert Hollman Foundation based on a complete ophthalmic evaluation.

Results: Ninety-two consecutive children (mean age = 2.37 ± 1.98 years, range = 0-9) were included. A referral diagnosis was retrieved in 76 cases (82.6%), including cerebral visual impairment (14.1%), retinopathy of prematurity (14.1%), hereditary retinal diseases (10.9%), nystagmus (8.7%) and other rarer diseases (34.8%). In the remaining 16 children (17.4%), a precise referral diagnosis was unavailable. Final clinical diagnosis made at Robert Hollman Foundation was normal visual function in 8.7%, cerebral visual impairment in 30.4%, retinopathy of prematurity in 10.9%, hereditary retinal disease in 9.8% and other in 40.2%. In 17 cases (18.5%), the diagnosis made at the Robert Hollman Foundation did not confirm the entry diagnosis. Among patients where measurement of visual acuity was possible (84), 66.7% were blind or seriously visual impaired, and the main causes were cerebral visual impairment (32.1%) and retinopathy of prematurity (16.1%).

Conclusion: The most frequent diseases were cerebral visual impairment, retinopathy of prematurity and hereditary retinal diseases. Approximately one-third of referred children had not a correct diagnosis at baseline. The activity of an ophthalmic tertiary centre is essential to offer a precise diagnosis to visually impaired (sometimes with other deficits) children.
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http://dx.doi.org/10.1177/1120672119854251DOI Listing
September 2020

Aqueous humour concentrations of PEDF and Erythropoietin are not influenced by subthreshold micropulse laser treatment of diabetic macular edema.

Biosci Rep 2019 06 18;39(6). Epub 2019 Jun 18.

IRCCS - Fondazione Bietti, Rome, Italy.

To determine if aqueous humour (AH) concentrations of Retinal Pigment Epithelium (RPE)'s biomarkers are modified after subthreshold micropulse laser (SMPL) treatment of diabetic macular edema (DME). Naïve DME and healthy subjects were enrolled. All DME patients received SMPL treatments (577-nm yellow light, 5% duty cycle of 0.2 s, power 250 mW), according to study protocol. AH of DME eyes was sampled at baseline and periodically after first SMPL treatment. Control eyes were sampled before cataract surgery. Pigment Epithelium Derived Factor (PEDF) and Erythropoietin (EPO) were quantified with glass-chip protein array. Eighteen DME patients (central retinal thickness ≤ 400 μm on Spectral Domain Optical Coherence Tomography (SD-OCT)) and ten controls were enrolled. The main exclusion criteria were high refractive error, proliferative diabetic retinopathy, glaucoma and neurodegenerative disorders. PEDF concentration was decreased in DME patients at baseline versus controls (=0.012), while EPO was increased (=0.029). Both molecules' concentrations remained stable during follow-up after treatments, compared with DME-baseline.: The AH concentrations of RPE biomarkers were significantly different in DME treatment-naïve eyes versus controls. The expression of PEDF and EPO remained unchanged after treatments with SMPL in DME eyes. These data are relevant for future research and applications of SMPL.
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http://dx.doi.org/10.1042/BSR20190328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579974PMC
June 2019

Single Retinal Layer Changes After Subthreshold Micropulse Yellow Laser in Diabetic Macular Edema.

Ophthalmic Surg Lasers Imaging Retina 2018 11;49(11):e218-e225

A pilot prospective, interventional study has been conducted on 10 patients with diabetic macular edema (DME) treated with subthreshold micropulse laser (SMPL) to evaluate changes of individual retinal layers and to correlate with functional changes. All patients underwent complete ophthalmologic evaluation including spectral-domain optical coherence tomography (OCT) and microperimetry at baseline, 3 months, 6 months, 9 months, and 12 months. Compared with baseline, a significant decrease was found in inner nuclear layer (INL) and outer retinal layer (ORL) thickness in the central 1 mm (P < .05). Increase in best-corrected visual acuity was significantly and inversely correlated to central retinal thickness (CRT) (P = .0027), INL (P = .0167), and outer nuclear layer (ONL) thickness (P = .0107). Increase in retinal sensitivity was significantly and inversely correlated to CRT and ONL thickness (P < .01). Therefore, SMPL showed to improve firstly functional parameters and then morphologic parameters. Functional parameters were inversely correlated to CRT, INL, and ONL thickness. The exact mechanism of reduction of INL thickness induced by SMPL remains to be further evaluated. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e218-e225.].
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http://dx.doi.org/10.3928/23258160-20181101-22DOI Listing
November 2018

Hyperreflective Intraretinal Foci as an OCT Biomarker of Retinal Inflammation in Diabetic Macular Edema.

Invest Ophthalmol Vis Sci 2018 11;59(13):5366

Department of Ophthalmology, University of Padova, Padova, Italy.

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http://dx.doi.org/10.1167/iovs.18-25611DOI Listing
November 2018

CHANGES OF AQUEOUS HUMOR MÜLLER CELLS' BIOMARKERS IN HUMAN PATIENTS AFFECTED BY DIABETIC MACULAR EDEMA AFTER SUBTHRESHOLD MICROPULSE LASER TREATMENT.

Retina 2020 Jan;40(1):126-134

Department of Ophthalmology, University Hospital Maggiore della Carità, Novara, Italy.

Purpose: To evaluate the changes in activity of biomarkers of Mu[Combining Diaeresis]ller cells (MC) in aqueous humor of patients with diabetic macular edema after subthreshold micropulse laser, over 1 year.

Methods: Patients with untreated diabetic macular edema and central retinal thickness ≤ 400 μm were enrolled. Best-corrected visual acuity, full ophthalmic examination, and optical coherence tomography were performed. Subthreshold micropulse laser was applied every 3 months. Glial fibrillary acidic protein and inwardly rectifying potassium channel (Kir 4.1), MC activity markers, and vascular endothelial growth factor were quantified in the aqueous humor collected at baseline and at 1, 3, and 12 months after laser. Changes in the macular thickness and inner nuclear layer thickness, where MC bodies are located, were measured.

Results: Ten eyes of 10 patients were included. Best-corrected visual acuity improved at 3 months (P = 0.047) and remained stable. Inner nuclear layer thickness significantly reduced at 12 months (P = 0.012). Glial fibrillary acidic protein, Kir 4.1, and vascular endothelial growth factor decreased at 1 and/or 3 and/or 12 months compared with baseline (P < 0.05).

Conclusion: Subthreshold micropulse laser improves visual function in diabetic macular edema. Kir 4.1 and glial fibrillary acidic protein decrease and inner nuclear layer thickness reduction demonstrate that subthreshold micropulse laser may restore MC function. Subthreshold micropulse laser also reduces vascular endothelial growth factor concentration. The effect of subthreshold micropulse laser in diabetic macular edema may in part be due to changes of MC metabolic activity.
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http://dx.doi.org/10.1097/IAE.0000000000002356DOI Listing
January 2020

Diabetic Macular Edema With and Without Subfoveal Neuroretinal Detachment: Two Different Morphologic and Functional Entities.

Am J Ophthalmol 2017 Sep 4;181:149-155. Epub 2017 Jul 4.

Department of Ophthalmology, University of Padova, Padova, Italy; Fondazione G. B. Bietti, IRCCS, Rome, Italy. Electronic address:

Purpose: To assess specific morphologic and functional characteristics in eyes with diabetic macular edema (DME) with subfoveal neuroretinal detachment (SND+) vs DME without SND (SND-).

Design: Cross-sectional, prospective, comparative case series.

Methods: Seventy-two patients (72 eyes: 22 eyes SND+ and 50 eyes SND-) with treatment-naïve, center-involving DME were evaluated. Data gathering included fundus color photographs, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), best-corrected visual acuity (BCVA), and microperimetry. The following parameters were evaluated with SD-OCT: central macular thickness (CMT [including SND]); central retinal thickness (CRT [excluding SND]); choroidal thickness (CT); nasal and temporal retinal thickness (RT) at 500 μm and 1500 μm from the fovea; the number of hyperreflective retinal spots (HRS) in the central 3000 μm; and the presence of SND and integrity of the external limiting membrane (ELM). Retinal sensitivity (RS) was evaluated within 4 degrees and 12 degrees of the fovea. Correlation among CT, RS, and HRS in patients with and without SND was determined.

Results: CMT (P = .032), temporal RT at 1500 μm (P = .03), mean CT (P = .009), and mean number of HRS (P = .0001) were all higher in SND+ vs SND- eyes. CRT, BCVA, HbA1c, and prevalence of systemic arterial hypertension were not different between the 2 groups. RS within 4 degrees (P = .002) and 12 degrees (P = .015) was lower in SND+ vs SND- eyes. SND correlated significantly with disruption of the ELM (54.55% vs 24%, P = .01) and lower RS. A direct correlation was found between the number of HRS, presence of SND, CT, and RS within 12 degrees in SND- eyes, and an inverse correlation was found between CT and RS within 12degrees in SND+ eyes.

Conclusions: These data may improve characterization of DME in eyes with SND. DME with SND correlates with greater CT, more HRS, disruption of the ELM, and significant macular functional impairment (RS decrease) vs SND-.
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http://dx.doi.org/10.1016/j.ajo.2017.06.026DOI Listing
September 2017

Psychotropic drugs prescription in undocumented migrants and indigent natives in Italy.

Int Clin Psychopharmacol 2017 09;32(5):294-297

aDepartment of Medicine and Surgery, University of Milano-Bicocca bDepartment of Clinical Sciences and Community Health, University of Milan cIRCCS - Istituto Auxologico Italiano, Experimental Laboratory for Auxo-endocrinological Research, Milan, Italy.

To evaluate psychotropic drug use in undocumented migrants and natives in the same conditions of poverty. We studied drug dispensation by a nongovernmental organization during the year 2014. Drugs were identified according to the Anatomical Chemical Therapeutic classification and their quantity was measured in defined daily doses (DDD). We determined the percentage of patients taking at least one medicine with psychotropic activity in relation to the total number of patients receiving medicines of any class. We also calculated the individual DDD for psychoactive drugs. The percentage of natives receiving this type of medicine is significantly higher than that of undocumented migrants. Individual DDDs for each class of psychotropic drug are comparable in Italians and undocumented migrants and, among the latter, no difference was found in relation to ethnicity. Our findings describe for the first time the use of psychotropic medicines by undocumented migrants. On this basis, we hypothesize that poverty is more important than migration and ethnicity in generating the need for this type of pharmacological treatment. Both natives and undocumented migrants show poor adherence to treatment. This situation should be considered when programming health interventions in this field for the very poor and undocumented migrants.
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http://dx.doi.org/10.1097/YIC.0000000000000184DOI Listing
September 2017

A decade-long telemedicine screening program for diabetic retinopathy in the north-east of Italy.

J Diabetes Complications 2017 Aug 13;31(8):1348-1353. Epub 2017 Apr 13.

Department of Ophthalmology, University of Padova, Italy; Fondazione G. B. Bietti, IRCCS, Roma, Italy. Electronic address:

Aim: To describe a decade long telemedicine screening for diabetic retinopathy (DR) in the metropolitan area of Padova (North-East Italy) and to report about prevalence/incidence of DR and maculopathy, rate of progression to STDR and optimal screening interval in patients with no DR at first examination.

Methods: Observational, longitudinal, cohort study; 9347 patients with Type 1 and Type 2 diabetes mellitus (DM) underwent 17,344 fundus exams (three-45° color photos per eye) in two diabetes clinics and were graded in the Reading Centre, by certified personnel. The incidence of STDR, progression of maculopathy and risk factors were evaluated by log Rank test (Kaplan-Meier method). A receiver operating curve was used to determine the optimal screening interval in patients who at the first examination had no DR.

Results: The overall prevalence of DR was 27.6%:12.5% mild non proliferative (NPDR), 11.3% moderate NPDR, 2.9% severe NPDR and 0.9% proliferative (PDR). The overall prevalence of maculopathy was 5.7%: 2.8% mild, 2.2% moderate, and 0.7% severe maculopathy. The 10-year incidence of STDR was: 0.6% in no DR, 5.5% in mild NPDR and 21.1% in moderate NPDR at first examination. The 10-year incidence of maculopathy was: 2.1% mild, 1.7% moderate and 0.2% severe. The incidence of STDR in patients with type 1 and type 2 DM and duration>10years was 8.21% and 8.15%;in type 1 DM with duration <10years was 5.5% and in type 2 DM and duration <10years was 1.91%.In patients with no DR at first screening, the best (sensitivity-specificity) follow-up interval is 2.5years.

Conclusions: Screening every 2.5-year in patients without DR at the first examination seems to be adequate. Duration of disease is a relevant risk factor for progression to STDR, however patients with type 1 DM and duration <10years have greater incidence of STDR than patients with type 2 DM and similar disease duration. Epidemiologic data from this decade-long screening program in the North East of Italy may serve for implementing a national screening program.
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http://dx.doi.org/10.1016/j.jdiacomp.2017.04.010DOI Listing
August 2017

Imaging retinal inflammatory biomarkers after intravitreal steroid and anti-VEGF treatment in diabetic macular oedema.

Acta Ophthalmol 2017 Aug 24;95(5):464-471. Epub 2016 Oct 24.

Department of Ophthalmology, University of Padova, Padova, Italy.

Purpose: To evaluate changes of specific retinal imaging biomarkers [intraretinal hyper-reflective retinal spots: HRS ; subfoveal neuroretinal detachment: SND; and increased foveal autofluorescence: IFAF after intravitreal steroid or anti-vascular endothelial growth factor treatment in diabetic macular oedema (DME)] as possible indicators of retinal inflammatory condition.

Methods: Retrospective analysis of images and clinical charts of 49 eyes (49 patients) with DME treated with intravitreal dexamethasone (dexamethasone, 23 eyes) or intravitreal ranibizumab (ranibizumab, 26 eyes). All patients had fundus colour photograph, spectral domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF), best-corrected visual acuity (BCVA) and microperimetry recorded before and 1 month after the end of treatment. Central macular thickness (CMT), number of HRS and presence of SND were evaluated by SD OCT. Fundus autofluorescence images were evaluated for area of (IFAF). Retinal sensitivity within 4° and 12° from fovea was quantified by microperimetry. Changes in morphologic and functional parameters were assessed, and correlation was performed by Pearson's correlation.

Results: Best-corrected visual acuity and CMT improved in all patients, (p < 0.05, for both groups). Mean number of HRS decreased after both treatments (p < 0.0001). Subfoveal neuroretinal detachment resolved in 85.7% dexamethasone-treated eyes (p = 0.014) and in 50% ranibizumab-treated eyes (p = 0.025). Mean IFAF area decreased in both groups, (p < 0.0001, for both). A significantly higher decrease in CMT was observed in dexamethasone- versus ranibizumab-treated eyes, (p = 0.032). In dexamethasone group, higher number of HRS at baseline and larger IFAF were correlated with higher increase in retinal sensitivity; eyes with SND at baseline had major decrease in CMT versus those without SND, (p = 0.003).

Conclusion: Higher number of HRS, larger area of IFAF and presence of SND may indicate a prevalent inflammatory condition in DME with specific response to targeted treatment.
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http://dx.doi.org/10.1111/aos.13294DOI Listing
August 2017

Pharmacoepidemiological Data from Drug Dispensing Charities as a Measure of Health Patterns in a Population not Assisted by the Italian National Health Service.

J Public Health Res 2016 Aug 19;5(2):623. Epub 2016 Aug 19.

Departmet of Clinical Sciences and Community Health, University of Milano.

We analysed drug dispensation by charitable organisations in a year time. Drugs were grouped according to the Anatomic Therapeutic Chemical classification and the amount dispensed was calculated with the system of the Daily Defined Dose (DDD) and expressed as DDD/1000 subjects/day. A number of 87,550 subjects were studied (13,308 Italians; 74,242 Immigrants). Though we noticed a great sesonal variability, the drugs most frequently dispensed were those for the respiratory, cardiovascular and gastrointestinal system and antibiotics, which is different from the rest of the Italian population and the immigrant population assisted by our National Health Service (NHS). We also found that chronic diseases are increasing in these subjects. We conclude that the subjects not receiving NHS assitance have, at least in part, different health patterns and requirements. This should be considered when planning tailored interventions.
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http://dx.doi.org/10.4081/jphr.2016.623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062753PMC
August 2016

HYPERREFLECTIVE RETINAL SPOTS IN NORMAL AND DIABETIC EYES: B-Scan and En Face Spectral Domain Optical Coherence Tomography Evaluation.

Retina 2017 Jun;37(6):1092-1103

*Department of Ophthalmology, University of Padova, Padova, Italy; †University Campus Biomedico, Roma, Italy; and ‡Fondazione G. B. Bietti, IRCCS, Roma, Italy.

Purpose: To evaluate hyperreflective retinal spots (HRS), in normal subjects and diabetic patients without and with macular edema (diabetic macular edema, DME), on linear B-scans and corresponding en face image of spectral-domain optical coherence tomography.

Methods: Retrospective evaluation of images of 54 eyes/subjects (16 normal subjects, 19 diabetic patients without DME, and 19 with DME). On horizontal B-scan spectral-domain optical coherence tomography, passing through the center of the fovea, the following characteristics of HRS were evaluated: location (inner retina or outer retina), size (≤30 or >30 μm), reflectivity (similar to nerve fiber layer or to retinal pigment epithelium-Bruch complex), and presence or absence of back shadowing. On en face spectral-domain optical coherence tomography, the following patterns were evaluated: 1) isolated HRS (not corresponding to any visible lesion); 2) HRS corresponding to a segment of retinal capillary or microaneurysm wall; and 3) HRS corresponding to hard exudate. All gradings were performed twice by two graders in a masked fashion.

Results: Size ≤30 μm, reflectivity similar to nerve fiber layer, and absence of back shadowing were associated with absence of vessels or any other lesion on en face image (P = 0.0001 for all). Size >30 μm, reflectivity similar to retinal pigment epithelium-Bruch complex, presence of back shadowing, and location in the outer retina were all associated with presence of hard exudate on en face imaging (P < 0.0001 for all). Multiple logistic regression analysis showed that HRS present in the inner retina (P < 0.0001), size >30 μm (P = 0.0029), and presence of back shadowing (P < 0.0001) are directly associated with presence of microaneurysms on en face image. Intragrader and intergrader repeatability were excellent for all evaluations.

Conclusion: Hyperreflective retinal spots ≤30 μm, reflectivity similar to nerve fiber layer, and absence of back shadowing may represent activated microglial cells; HRS >30 μm, reflectivity similar to retinal pigment epithelium-Bruch complex, presence of back shadowing, and location in the outer retina may represent hard exudate; HRS >30 μm, presence of back shadowing, and location in the inner retina may represent microaneurysms. These hypotheses may be tested in further studies.
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http://dx.doi.org/10.1097/IAE.0000000000001304DOI Listing
June 2017

Long-term longitudinal modifications in mesopic microperimetry in early and intermediate age-related macular degeneration.

Graefes Arch Clin Exp Ophthalmol 2017 Feb 31;255(2):301-309. Epub 2016 Aug 31.

Department of Ophthalmology University of Padova, Via Giustiniani 2, 35128, Padova, Italy.

Purpose: To evaluate functional changes (retinal sensitivity and fixation characteristics) determined by microperimetry in patients with early and intermediate AMD over 6 years.

Methods: Prospective, longitudinal follow-up (FU) study of 16 patients (29 eyes) with early and intermediate AMD (AREDS 2 and AREDS 3 classification). All eyes underwent: complete ophthalmic examination with best corrected visual acuity (BCVA) determination, color fundus photo (CFP), optical coherence tomography and microperimetry. All CFP were evaluated by two retinal specialists masked to functional data for changes in severity of clinical features over the course of FU.

Results: Of 17 eyes graded as AREDS 2 at baseline, 14 (82.35 %) remained stable, and 3 (18.75 %) progressed to AREDS 3. Of 12 eyes graded as AREDS 3 at baseline, 10 remained stable (83.33 %), and 2 (16.67 %) progressed to AREDS 4. Mean BCVA significantly deteriorated in both AREDS 2 (p = 0.006) and AREDS 3 (p = 0.016), with greater decrease in AREDS 3 (p = 0.01)6. Mean retinal sensitivity (RS) significantly decreased over time in both AREDS 2 (p < 0.0001) and AREDS 3 group (p = 0.002), with greater decrease in AREDS 3 (p = 0.006). The mean number of dense scotomas did not change in AREDS 2 (p = 0.3), but significantly increased in the AREDS 3 group (p = 0.035). Points with decreased RS were located in all but the central point (p < 0.0001 for all), without significant differences in number among rings. In the AREDS 2 group, fixation stability remained unchanged. In the AREDS 3 group, four eyes deteriorated from stable to unstable fixation at FU (p = 0.045).

Conclusion: A significant deterioration in RS is reported in early and intermediate AMD eyes, whereas fixation stability changed only in intermediate AMD (AREDS 3) over long-term follow-up. Microperimetry examination can become a new functional biomarker in early and intermediate AMD patients.
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http://dx.doi.org/10.1007/s00417-016-3466-zDOI Listing
February 2017

Predictive algorithms for early detection of retinopathy of prematurity.

Acta Ophthalmol 2017 Mar 20;95(2):158-164. Epub 2016 Jun 20.

Department of Woman's and Child's Health, University of Padova, Padova, Italy.

Purpose: To evaluate sensitivity, specificity and the safest cut-offs of three predictive algorithms (WINROP, ROPScore and CHOP ROP) for retinopathy of prematurity (ROP).

Methods: A retrospective study was conducted in three centres from 2012 to 2014; 445 preterms with gestational age (GA) ≤ 30 weeks and/or birthweight (BW) ≤ 1500 g, and additional unstable cases, were included. No-ROP, mild and type 1 ROP were categorized. The algorithms were analysed for infants with all parameters (GA, BW, weight gain, oxygen therapy, blood transfusion) needed for calculation (399 babies).

Results: Retinopathy of prematurity (ROP) was identified in both eyes in 116 patients (26.1%), and 44 (9.9%) had type 1 ROP. Gestational age and BW were significantly lower in ROP group compared with no-ROP subjects (GA: 26.7 ± 2.2 and 30.2 ± 1.9, respectively, p < 0.0001; BW: 839.8 ± 287.0 and 1288.1 ± 321.5 g, respectively, p = 0.0016). Customized alarms of ROPScore and CHOP ROP correctly identified all infants having any ROP or type 1 ROP. WINROP missed 19 cases of ROP, including three type 1 ROP. ROPScore and CHOP ROP provided the best performances with an area under the receiver operating characteristic curve for the detection of severe ROP of 0.93 (95% CI, 0.90-0.96, and 95% CI, 0.89-0.96, respectively), and WINROP obtained 0.83 (95% CI, 0.77-0.87). Median time from alarm to treatment was 11.1, 5.1 and 9.1 weeks, for WINROP, ROPScore and CHOP ROP, respectively.

Conclusion: ROPScore and CHOP ROP showed 100% sensitivity to identify sight-threatening ROP. Predictive algorithms are a reliable tool for early identification of infants requiring referral to an ophthalmologist, for reorganizing resources and reducing stressful procedures to preterm babies.
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http://dx.doi.org/10.1111/aos.13117DOI Listing
March 2017

Multimodal retinal imaging of diabetic macular edema: toward new paradigms of pathophysiology.

Graefes Arch Clin Exp Ophthalmol 2016 Sep 7;254(9):1661-8. Epub 2016 May 7.

Department of Ophthalmology, University of Padova, Via Giustiniani 2, 35128, Padova, Italy.

The pathophysiology of diabetic macular edema (DME) is multifactorial and partly still unknown. An increasing body of evidence suggests that neurodegeneration and retinal glial cells activation occur even before the earliest clinical manifestation of diabetic retinal vasculopathy. Nowadays, new non-invasive techniques are available to assess and characterize DME, not only in a quantitative perspective, but also making it possible to understand and quantify the pathogenic processes sustaining fluid accumulation. Optical coherence tomography (OCT) allows documenting not only parameters such as macular volume, central and sectorial retinal thickness, fluid localization, and integrity of retinal layers, but also new still poorly investigated reflectivity aspects. Hyperreflective intraretinal spots (HRS) have been detected on OCT scans through the retinal layers, with a presumptive migration pattern towards the external layers during the occurrence of diabetic retinopathy and DME. These HRS have been hypothesised to represent an in-vivo marker of microglial activation. Autofluorescence of the fundus (FAF) also offers a non-invasive imaging technique of DME. The area of increased FAF correlates with the presence of intraretinal fluid and probably retinal glial activation. Microperimetry allows the measurement of retinal sensitivity by testing specific selected retinal areas. Some studies have shown that increased macular FAF in DME correlates better with visual function assessed with microperimetry than with visual acuity, showing that new imaging and functional techniques may help to elucidate DME pathogenesis and to target therapeutical strategies.
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http://dx.doi.org/10.1007/s00417-016-3361-7DOI Listing
September 2016

Post-prandial anorexigenic gut peptide, appetite and glucometabolic responses at different eating rates in obese patients undergoing laparoscopic sleeve gastrectomy.

Endocrine 2017 Jan 29;55(1):113-123. Epub 2016 Mar 29.

Division of Internal Medicine, San Gerardo Hospital, University of Milan Bicocca, Monza, Italy.

Although different hypotheses have been proposed, the underlying mechanism(s) of the weight loss induced by laparoscopic sleeve gastrectomy (LSG) is still unknown. The aim of this study was to determine whether eating the same meal at different rates (fast vs. slow feeding) evokes different post-prandial anorexigenic gut peptide responses in ten obese patients undergoing LSG. Circulating levels of GLP-1, PYY, glucose, insulin and triglycerides were measured before and 3 months after LSG. Visual analogue scales were used to evaluate the subjective feelings of hunger and satiety. Irrespective of the operative state, either fast or slow feeding did not stimulate GLP-1 release (vs. 0 min); plasma levels of PYY were increased (vs. 0 min) by fast and slow feeding only after LSG. There were no differences in post-prandial levels of GLP-1 when comparing fast to slow feeding or pre-to-post-operative state. Plasma levels of PYY after fast or slow feeding were higher in post, rather than pre-operative state, with no differences when comparing PYY release after fast and slow feeding. Hunger and satiety were decreased and increased, respectively, (vs. 0 min) by food intake. Fast feeding evoked a higher satiety than slow feeding in both pre- and post-operative states, with no differences in hunger. In both pre- and post-operative states, there were similar responses for hunger and satiety after food intake. Finally, LSG improved insulin resistance after either fast or slow feeding. These (negative) findings would suggest a negligible contribution of the anorexigenic gut peptide responses in LSG-induced weight loss.
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http://dx.doi.org/10.1007/s12020-016-0933-6DOI Listing
January 2017

HYPERREFLECTIVE RETINAL SPOTS AND VISUAL FUNCTION AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN CENTER-INVOLVING DIABETIC MACULAR EDEMA.

Retina 2016 Jul;36(7):1298-308

*Department of Ophthalmology, University of Padova, Padova, Italy; and †Fondazione G.B. Bietti, IRCCS, Rome, Italy.

Background: To assess and correlate early modifications in hyperreflective retinal spots (HRS), retinal sensitivity (RS), fixation stability, and best-corrected visual acuity (BCVA) after anti-vascular endothelial growth factor treatment in naive center-involving diabetic macular edema.

Methods: Cross-sectional comparative case-control series. Twenty diabetic patients underwent 3 consecutive intravitreal anti-vascular endothelial growth factor injections in the study eye (20 fellow eyes served as control), full ophthalmologic examination including spectral domain optical coherence tomography (Retinascan RS-3000; Nidek, Gamagori, Japan), and microperimetry (MP1; Nidek) at baseline (Visit-V1), 1 month after each injection (V2, V3, V4), and at 6 months (V5). Central retinal thickness, inner and outer retinal thickness, number of HRS, BCVA, RS, and bivariate contour ellipse area were evaluated by analysis of variance test with Bonferroni post hoc test. Correlation analyses were performed by Spearman correlation.

Results: In treated eyes, central retinal thickness and inner retinal thickness significantly decreased at V2, V3, V4 versus V1 (P < 0.03 at least for all); the mean number of HRS significantly decreased in both inner and outer retina at all follow-up visits versus V1 (P < 0.008 at least for all); mean RS and bivariate contour ellipse area remained statistically unchanged during the follow-up; BCVA significantly improved at V3, V4, and V5 versus V1 (P = 0.009 at least for all). In fellow eyes, central retinal thickness, HRS, RS, and BCVA did not change at any follow-up. The number of HRS correlated inversely with RS, directly with bivariate contour ellipse area, and not significantly with BCVA.

Conclusion: A significant decrease in HRS in the retina after anti-vascular endothelial growth factor treatment is documented. A decrease in HRS correlates with functional parameters, specifically RS. New parameters may be used for treatment evaluation in center-involving diabetic macular edema.
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http://dx.doi.org/10.1097/IAE.0000000000000912DOI Listing
July 2016

Anticipatory and consummatory effects of (hedonic) chocolate intake are associated with increased circulating levels of the orexigenic peptide ghrelin and endocannabinoids in obese adults.

Food Nutr Res 2015 4;59:29678. Epub 2015 Nov 4.

Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-endocrinological Research, Milan and Verbania, Italy.

Background: Hedonic hunger refers to consumption of food just for pleasure and not to maintain energy homeostasis. Recently, consumption of food for pleasure was reported to be associated with increased circulating levels of both the orexigenic peptide ghrelin and the endocannabinoid 2-arachidonoyl-glycerol (2-AG) in normal-weight subjects. To date, the effects of hedonic hunger, and in particular of chocolate craving, on these mediators in obese subjects are still unknown.

Methods: To explore the role of some gastrointestinal orexigenic and anorexigenic peptides and endocannabinoids (and some related congeners) in chocolate consumption, we measured changes in circulating levels of ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), anandamide (AEA), 2-AG, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) in 10 satiated severely obese subjects after consumption of chocolate and, on a separate day, of a non-palatable isocaloric food with the same bromatologic composition. Evaluation of hunger and satiety was also performed by visual analogic scale.

Results: The anticipatory phase and the consumption of food for pleasure were associated with increased circulating levels of ghrelin, AEA, 2-AG, and OEA. In contrast, the levels of GLP-1, PYY, and PEA did not differ before and after the exposure/ingestion of either chocolate or non-palatable foods. Hunger and satiety were higher and lower, respectively, in the hedonic session than in the non-palatable one.

Conclusions: When motivation to eat is generated by exposure to, and consumption of, chocolate a peripheral activation of specific endogenous rewarding chemical signals, including ghrelin, AEA, and 2-AG, is observed in obese subjects. Although preliminary, these findings predict the effectiveness of ghrelin and endocannabinoid antagonists in the treatment of obesity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636866PMC
http://dx.doi.org/10.3402/fnr.v59.29678DOI Listing
November 2015

Proteome analysis of retinal glia cells-related inflammatory cytokines in the aqueous humour of diabetic patients.

Acta Ophthalmol 2016 Feb 13;94(1):56-64. Epub 2015 Aug 13.

Department of Ophthalmology, University of Padova, Padova, Italy.

Purpose: Retinal glia cells (RGC) activation and release of inflammatory cytokines have been associated with development of diabetic retinopathy (DR). In this study, we evaluated by protein array the presence of aqueous humour (AH) cytokines secreted by RGC in patients with diabetes without DR and with mild DR.

Methods: This is a cross-sectional, case-control study. Thirty-five subjects (diabetics and controls) underwent full ophthalmic examination and AH samples collection before cataract surgery at the Department of Ophthalmology University of Padova. AH samples were analysed for total protein concentration (Bradford method) and RGC-related inflammatory cytokines using glass chip protein arrays.

Results: Twelve diabetic patients without DR, 11 diabetic patients with mild DR and 12 non-diabetic controls were included. There was no significant difference in total protein concentration among the 3 groups. Interleukin IL-1β, IL-3, interferon gamma (IFN-ɣ), (IFN-ɣ)-induced protein (IP)-10 and monocyte chemotactic protein (MCP)-2 were significantly increased in diabetics versus controls. IFN-ɣ, IL-1α, IL-3 and MCP-2 were significantly increased in diabetics without DR versus controls, whereas granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-ɣ, IL-10, IP-10, regulated and normal T cell expressed and secreted (RANTES), and soluble tumour necrosis factor receptor (sTNF-R)II were significantly increased in diabetics with mild DR versus controls. Macrophage inflammatory protein (MIP-1β), GMCSF, RANTES and sTNF-RII were significantly increased in diabetics with mild DR versus diabetics without DR (p < 0.05 at least for all).

Conclusions: Differences in expression profile of AH cytokines between diabetics, without and with mild DR, and controls have been documented. Retinal neuroinflammatory biomarkers of RGC activation evaluated in AH by protein array analysis could guide in detecting specific phenotypes with potential for personalized management.
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http://dx.doi.org/10.1111/aos.12812DOI Listing
February 2016

Aqueous Humor Biomarkers of Müller Cell Activation in Diabetic Eyes.

Invest Ophthalmol Vis Sci 2015 Jun;56(6):3913-8

Department of Ophthalmology University of Padova, Padova, Italy 2Fondazione G. B. Bietti, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Roma, Italy.

Purpose: To identify early biomarkers of retinal Müller cell activation in diabetic eyes with or without clinically detectable signs of diabetic retinopathy (DR).

Methods: This study was a cross-sectional comparative case series. The aqueous humor (AH) of 34 eyes was collected in 12 healthy controls, 11 diabetic patients without DR, and 11 diabetic patients with nonproliferative DR. Full ophthalmic examination and spectral-domain optical coherence tomography were performed in all eyes. Glial fibrillary acidic protein (GFAP), aquaporin 1 (AQP1), and aquaporin 4 (AQP4) were quantified in AH samples as biomarkers of Müller cell activity by ELISA. Statistical analysis was performed with ANOVA followed by Tukey-Kramer post hoc test.

Results: There was no significant difference in the age among the three groups. Mean concentration of GFAP, AQP1, and AQP4 significantly increased in diabetic eyes versus controls (P < 0.05, for each comparison). Glial fibrillary acidic protein and AQP1 showed an approximate 2-fold increase, whereas AQP4 showed an approximate 25-fold increase in diabetics with DR versus controls. In diabetics without DR, AQP4 showed an approximate 6-fold increase versus controls.

Conclusions: Glial fibrillary acidic protein, AQP1, and AQP4-biomarkers of Müller cell activity-are significantly increased in human eyes with diabetes, confirming that Müller cells are precociously affected by diabetes mellitus.
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http://dx.doi.org/10.1167/iovs.15-16554DOI Listing
June 2015

Different effects of cholestyramine on postprandial secretions of cholecystokinin and peptide YY in women with bulimia nervosa.

Neuropsychobiology 2014 20;70(4):228-34. Epub 2014 Dec 20.

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Objective: Patients with bulimia nervosa (BN) are reported to have decreased postprandial levels of cholecystokinin (CCK) and peptide YY (PYY). Fatty nutrients are the most powerful stimulus for releasing these peptides. Cholestyramine is an anion exchanger which adsorbs bile salts and reduces the digestion of lipids, affecting the secretion of both CCK and PYY. To further characterise the physiology of these peptides in BN, we aimed to investigate the effects of cholestyramine (12 g, per os) or placebo administered with a high-fat meal on CCK and PYY secretions in bulimic versus healthy women.

Results: Postprandial CCK levels significantly increased in both healthy and bulimic women after placebo + the high-fat meal, without any significant difference between the two groups. Cholestyramine administration significantly increased postprandial CCK responses in both healthy and bulimic women; however, significantly lower CCK levels were observed in BN. Postprandial PYY levels significantly increased after placebo administration in healthy women after the high-fat meal, whereas no significant changes were found in bulimic women. Cholestyramine, administered with the high-fat meal, significantly reduced postprandial PYY response in healthy women, but not in bulimic women. Finally, there was a negative correlation of the area under the curve with respect to the increase of PYY (after placebo administration) with binge frequency in the bulimic women.

Conclusion: In BN an altered postprandial secretion of CCK may be evidenced when cholestyramine is combined with a high-fat meal. Instead, the postprandial secretion of PYY is significantly blunted and not affected by cholestyramine administration.
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http://dx.doi.org/10.1159/000368160DOI Listing
February 2016

Severely obese adolescents and adults exhibit a different association of circulating levels of adipokines and leukocyte expression of the related receptors with insulin resistance.

Int J Endocrinol 2013 21;2013:565967. Epub 2013 Dec 21.

Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-Endocrinological Research, Via Ariosto 13, 20145 Milan, Italy ; Istituto Auxologico Italiano, IRCCS, Division of Metabolic Diseases, Corso Mameli, 199, 28921 Verbania, Italy.

Obese adults frequently exhibit a low-grade inflammation and insulin resistance, which have been hypothesized to be established early in childhood. Aim of this study was to evaluate the age-dependent relationships between inflammatory state and insulin resistance in obese adolescents and adults. Clinical and metabolic parameters, circulating adipokines (TNF- α , adiponectin, and leptin), ghrelin, their leukocyte receptors (TNFR1, ADIPOR2, OBRL and GHSR1a), and acute phase reactants (CRP and white blood cells) were assessed in lean and obese adolescents compared with the adult counterparts. Only obese adults had higher HOMA-IR, insulin, and triglycerides compared to the lean group. An inflammatory state was present in obese adolescents and adults, as demonstrated by the higher values of CRP and neutrophils. There were no group differences in circulating levels of TNF- α and leukocyte expression of TNFR1. Adiponectin concentrations and leukocyte expression of ADIPOR2 were higher in the lean groups than in the corresponding obese counterparts. For leptin and leukocyte expression of OBRL, the results were opposed. Circulating levels of ghrelin were higher in lean adolescents and adults than the related lean groups, while there was a higher leukocyte expression of GHSR1a in (only) lean adults than obese adults. When the analysis was performed in (lean or obese) adults, TNF- α , neutrophils, leptin, and GHSR1a were predictors of HOMA-IR. None of the considered independent variables accounted for the degree of insulin resistance in the adolescent group. In conclusion, a dissociation between the low-grade inflammation and insulin resistance is supposed to exist in the early phases of obesity.
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http://dx.doi.org/10.1155/2013/565967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880700PMC
January 2014

Hyperreflective intraretinal spots in diabetics without and with nonproliferative diabetic retinopathy: an in vivo study using spectral domain OCT.

J Diabetes Res 2013 9;2013:491835. Epub 2013 Dec 9.

Department of Ophthalmology, University of Padova, Via Giustiniani 2, 35128 Padova, Italy ; Fondazione G.B. Bietti, Via Livenza 3, 00198 Roma, Italy.

Purpose: To evaluate the presence of hyperreflective spots (HRS) in diabetic patients without clinically detectable retinopathy (no DR) or with nonproliferative mild to moderate retinopathy (DR) without macular edema, and compare the results to controls.

Methods: 36 subjects were enrolled: 12 with no DR, 12 with DR, and 12 normal subjects who served as controls. All studied subjects underwent full ophthalmologic examination and spectral domain optical coherence tomography (SD-OCT). SD-OCT images were analyzed to measure and localize HRS. Each image was analyzed by two independent, masked examiners.

Results: The number of HRS was significantly higher in both diabetics without and with retinopathy versus controls (P < 0.05) and in diabetics with retinopathy versus diabetics without retinopathy (P < 0.05). The HRS were mainly located in the inner retina layers (inner limiting membrane, ganglion cell layer, and inner nuclear layer). The intraobserver and interobserver agreement was almost perfect (κ > 0.9).

Conclusions: SD-OCT hyperreflective spots are present in diabetic eyes even when clinical retinopathy is undetectable. Their number increases with progressing retinopathy. Initially, HRS are mainly located in the inner retina, where the resident microglia is present. With progressing retinopathy, HRS reach the outer retinal layer. HRS may represent a surrogate of microglial activation in diabetic retina.
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http://dx.doi.org/10.1155/2013/491835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3872101PMC
June 2014

Repolarization alternans heterogeneity in healthy subjects and acute myocardial infarction patients.

Med Eng Phys 2012 Apr 10;34(3):305-12. Epub 2011 Aug 10.

Department of Information Engineering, Polytechnic University of Marche, Ancona, Italy.

An association between heterogeneity of repolarization alternans (RA) and cardiac electrical instability has been reported. Characterization of RA in health and identification of physiological RA heterogeneity may help discrimination of abnormal RA cases more likely associated to arrhythmic events. Thus, aim of the present study was the identification of a physiological RA region in terms of mean temporal location (MRAD) with respect to the T apex, and mean amplitude (MRAA), by application of our heart-rate adaptive match filter method to clinical ECG recordings from 51 control healthy (CH) subjects and 43 acute myocardial infarction (AMI) patients. Results indicate that RA occurring within the first half of the T wave is dominant in both CH and AMI populations (74.5% and 53.5% of cases, respectively; P<0.05). Definition of physiological RA region in the MRAD vs. MRAA plane (-83 ms ≤ MRAD ≤ 23 ms, 0≤ MRAA ≤ 30 μV) provided 0% and 32.6% abnormal RA cases among the CH subjects and AMI patients, respectively. We conclude that myocardial infarction may associate with an RA occurring early (MRAD<-83 ms) or late (MRAD >23 ms) along the JT segment, in addition or in alternative to an abnormally high RA amplitude (MRAA >30 μV).
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http://dx.doi.org/10.1016/j.medengphy.2011.07.019DOI Listing
April 2012

Physiological interpretation of inductance and low-resistance terms in four-element windkessel models: assessment by generalized sensitivity function analysis.

Med Eng Phys 2011 Jul 4;33(6):739-54. Epub 2011 Mar 4.

Department of Biomedical, Electronics and Telecommunication Engineering, Polytechnic University of Marche, Ancona, Italy.

Physiological relevance of parameters of three arterial models, denominated W4P, W4S and IVW, was assessed by computation of parameter-related generalized sensitivity functions (GSFs), which allow the definition of heart-cycle time intervals where the information content of experimental data, useful for estimation of each model parameter, is concentrated. The W4P and W4S are derived from the three-element windkessel by connecting an inductance, L, in parallel or in series, respectively, with aortic characteristic impedance, R(c). In the IVW, L is placed in series at the input of a viscoelastic windkessel, incorporating a Voigt cell (a resistor, R(d), in series with a capacitor, C). Pressure and flow measured in the ascending aorta of five ferrets and five dogs were used to estimate all model parameters, by fitting to pressure. For each model structure, parameter-related GSFs were generated. Focusing on controversial L, R(c) and R(d) physical meaning, our GSF analysis yielded the conclusion that, in both the W4S and the IVW, but not in the W4P, the L-term is suitable to represent the inertial properties of blood motion. Moreover, the meaning of aortic characteristic impedance ascribed to R(c) is questionable; while R(d) is likely to account for viscous losses of arterial wall motion.
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http://dx.doi.org/10.1016/j.medengphy.2011.01.012DOI Listing
July 2011