Novel Technique of Transepithelial Corneal Cross-Linking Using Iontophoresis in Progressive Keratoconus

In this work, the authors presented the techniques and the preliminary results at 6 months of a randomized controlled trial (NCT02117999) comparing a novel transepithelial corneal cross-linking protocol using iontophoresis with the Dresden protocol for the treatment of progressive keratoconus. At 6months, there was a significant average improvement with an average flattening of themaximum simulated keratometry reading of 0.72\ub11.20D(P = 0.01); in addition, corrected distance visual acuity improved significantly (P = 0.08) and spherical equivalent refraction was significantly lessmyopic (P = 0.02) 6months a\u17fter transepithelial corneal cross-linkingwith iontophoresis. The novel protocol using iontophoresis showed comparable resultswith standard corneal cross-linking to halt progression of keratoconus during 6-month follow-up. Investigation of the long-term RCT outcomes are ongoing to verify the efficacy of this transepithelial corneal cross-linking protocol and to determine if it may be comparable with standard corneal cross-linking in themanagement of progressive keratoconus

Investigation of adaptive optics imaging biomarkers for detecting pathological changes of the cone mosaic in patients with type 1 diabetes mellitus

Purpose To investigate a set of adaptive optics (AO) imaging biomarkers for the assessment of changes of the cone mosaic spatial arrangement in patients with type 1 diabetes mellitus (DM1). Methods 16 patients with 20/20 visual acuity and a diagnosis of DM1 in the past 8 years to 37 years and 20 age-matched healthy volunteers were recruited in this study. Cone density, cone spacing and Voronoi diagrams were calculated on 160x160 μm images of the cone mosaic acquired with an AO flood illumination retinal camera at 1.5 degrees eccentricity from the fovea along all retinal meridians. From the cone spacing measures and Voronoi diagrams, the linear dispersion index (LDi) and the heterogeneity packing index (HPi) were computed respectively. Logistic regression analysis was conducted to discriminate DM1 patients without diabetic retinopathy from controls using the cone metrics as predictors. Results Of the 16 DM1 patients, eight had no signs of diabetic retinopathy (noDR) and eight had mild nonproliferative diabetic retinopathy (NPDR) on fundoscopy. On average, cone density, LDi and HPi values were significantly different (P<0.05) between noDR or NPDR eyes and controls, with these differences increasing with duration of diabetes. However, each cone metric alone was not sufficiently sensitive to discriminate entirely between membership of noDR cases and controls. The complementary use of all the three cone metrics in the logistic regression model gained 100% accuracy to identify noDR cases with respect to controls. PLOS ONE | DOI:10.1371/journal.pone.0151380 March 10, 2016 1 / 14 OPEN ACCESS Citation: Lombardo M, Parravano M, Serrao S, Ziccardi L, Giannini D, Lombardo G (2016) Investigation of Adaptive Optics Imaging Biomarkers for Detecting Pathological Changes of the Cone Mosaic in Patients with Type 1 Diabetes Mellitus. PLoS ONE 11(3): e0151380. doi:10.1371/journal. pone.0151380 Editor: Knut Stieger, Justus-Liebig-University Giessen, GERMANY Received: December 17, 2015 Accepted: February 27, 2016 Published: March 10, 2016 Copyright: © 2016 Lombardo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: Research for this work was supported by the Italian Ministry of Health (5x1000 funding), by the National Framework Program for Research and Innovation PON (grant n. 01_00110) and by Fondazione Roma. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Vision Engineering Italy srl funder provided support in the form of salaries for author GL, but did not have any Conclusion The present set of AO imaging biomarkers identified reliably abnormalities in the spatial arrangement of the parafoveal cones in DM1 patients, even when no signs of diabetic retinopathy were seen on fundoscopy

All-Optical Method to Assess Stromal Concentration of Riboflavin in Conventional and Accelerated UV-A Irradiation of the Human Cornea.

PURPOSE. We investigated the concentration of riboflavin in human donor corneas during corneal cross-linking using two-photon optical microscopy and spectrophotometry. METHODS. Eight corneal tissues were de-epithelialized and soaked with 20% dextran-enriched 0.1% riboflavin solution for 30 minutes. After stromal soaking, three tissues were irradiated using a 3 mW/cm(2) UV-A device for 30 minutes and three tissues irradiated using a 10 mW/cm2 device for 9 minutes. Two additional tissues were used as positive controls. A Ti:sapphire laser at 810 nm was used to perform two-photon emission fluorescence (TPEF) and second harmonic generation axial scanning measurements in all specimens before and after stromal soaking and after UV-A irradiation. In addition, spectrophotometry was used to collect the absorbance spectra of each tissue at the same time intervals. Analysis of the absorbance spectra and TPEF signals provided measures of the concentration depth profile of riboflavin in corneal stroma. RESULTS. After stromal soaking, the average peak concentration of riboflavin (0.020% +-0.001%) was found between a stromal depth of 100 and 250 lm; the concentration of riboflavin was almost constant up to 320 6 53 lm depth, then decreased toward the endothelium, though riboflavin was still enriched in the posterior stroma (0.016%% 6 0.001%). After conventional and accelerated UV-A irradiation, the concentration of riboflavin decreased uniformly 87% 6 2% and 67% 6 3% (P < 0.001), respectively. CONCLUSIONS. The combined use of two-photon optical microscopy and spectrophotometry provides relevant information for investigating the concentration of riboflavin in corneal stroma. The method can assist with the assessment of novel riboflavin formulations and different UV-A irradiation protocols

Sensitisation of spinal cord pain processing in medication overuse headache involves supraspinal pain control.

Medication overuse could interfere with the activity of critical brain regions involved in the supraspinal control of pain signals at the trigeminal and spinal level, leading to a sensitisation phenomenon responsible for chronic pain. We hypothesised that medication-overuse headache ( MOH) patients might display abnormal processing of pain stimuli at the spinal level and defective functioning of the diffuse noxious inhibitory controls. We tested 31 MOH patients before (bWT) and after (aWT) standard inpatient withdrawal treatment, 28 episodic migraine ( EM) patients and 23 healthy control subjects. We measured the threshold, the area and the temporal summation threshold (TST) of the nociceptive withdrawal reflex before, during and after activation of the diffuse noxious inhibitory controls by means of the cold pressor test. A significantly lower TST was found in both the MOH (bWT and aWT) and the EM patients compared with the controls, and in the MOH patients bWT compared with both the MOH patients aWT and the EM patients. In the MOH bWT patients the cold pressor test induced a TST increase significantly lower than that found in the MOH aWT, EM and control groups. Abnormal spinal cord pain processing and a decrease of the antinociceptive activity of the supraspinal structures in MOH patients can be hypothesised. These abnormalities could, in part, be related to the medication overuse, given that the withdrawal treatment was related to an improvement in the neurophysiological findings

Metastatic renal cell carcinoma invading liver, duodenum and ivc, surgical treatment and literature review. A case report

Renal Cell Carcinoma has a biologic predisposition for direct vascular invasion: intravascular tumor thrombus is found in 5% to 20% of the cases inside the renal vein or the inferior vena cava. Despite new and effective conservative therapy such as targeted therapy and immunotherapy, cytoreductive nephrectomy and palliative nephrectomy continues to have an important role in T4 patient. The patient selection for cytoreductive nephrectomy should be done carefully. This report present an unique case of metastatic RCC with invasion of the duodenum, liver and retrohepatic IVC, the adopted surgical approach and a review of the literature. Complete surgical extirpation is possible in cases of RCC invading other organs such as pancreas, duodenum, liver, retroperitoneum and IVC. In this scenario, to narrow the possible intraoperative complication, a multidisciplinary approach and equipe is recommended

Low in‑hospital mortality rate in patients with COVID‑19 receiving thromboprophylaxis: data from the multicentre observational START‑COVID Register

Abstract COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease,and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years

Technical factors influencing cone packing density estimates in adaptive optics flood illuminated retinal images.

PURPOSE: To investigate the influence of various technical factors on the variation of cone packing density estimates in adaptive optics flood illuminated retinal images. METHODS: Adaptive optics images of the photoreceptor mosaic were obtained in fifteen healthy subjects. The cone density and Voronoi diagrams were assessed in sampling windows of 320×320 µm, 160×160 µm and 64×64 µm at 1.5 degree temporal and superior eccentricity from the preferred locus of fixation (PRL). The technical factors that have been analyzed included the sampling window size, the corrected retinal magnification factor (RMFcorr), the conversion from radial to linear distance from the PRL, the displacement between the PRL and foveal center and the manual checking of cone identification algorithm. Bland-Altman analysis was used to assess the agreement between cone density estimated within the different sampling window conditions. RESULTS: The cone density declined with decreasing sampling area and data between areas of different size showed low agreement. A high agreement was found between sampling areas of the same size when comparing density calculated with or without using individual RMFcorr. The agreement between cone density measured at radial and linear distances from the PRL and between data referred to the PRL or the foveal center was moderate. The percentage of Voronoi tiles with hexagonal packing arrangement was comparable between sampling areas of different size. The boundary effect, presence of any retinal vessels, and the manual selection of cones missed by the automated identification algorithm were identified as the factors influencing variation of cone packing arrangements in Voronoi diagrams. CONCLUSIONS: The sampling window size is the main technical factor that influences variation of cone density. Clear identification of each cone in the image and the use of a large buffer zone are necessary to minimize factors influencing variation of Voronoi diagrams of the cone mosaic

Il ruolo degli incubatori. Creazione e sviluppo di nuove imprese

Le maggiori difficoltà che un imprenditore si trova ad affrontare nella creazione di una nuova impresa sono quelle di reperire i finanziamenti necessari e gli strumenti indispensabili per il suo funzionamento: i locali, gli uffici, i laboratori, il management, il personale e la consulenza tecnica e fiscale. Occorre conoscere il mercato nel quale l’impresa si colloca ed assicurarsi una rete esterna per la commercializzazione dei suoi prodotti. La preparazione delle strutture aziendali richiede denaro e tempo e quindi, invece di impegnarsi per mesi in ricerche di locali, attrezzature, personale e servizi può potersi rivolgere ad una struttura che, a prezzi competitivi, offra al suo interno i servizi basilari per avviare un’impresa. Gli incubatori sono nati proprio per offrire strumenti per favorire la crescita e il successo delle imprese, attraverso una rete di risorse e di servizi di supporto alle attività imprenditoriali; mettono a disposizione i locali, i servizi logistici di base e la rete di conoscenze personali che si forma durante la comune convivenza in un’unica struttura ospitante. Gli incubatori più attrezzati offrono anche servizi manageriali e consulenza tecnica, legale e fiscale. Si tratta, tuttavia, di una soluzione provvisoria poiché usualmente la prosecuzione dell’attività di un’impresa in un incubatore è autorizzata di anno in anno ed è comunque limitata ad un massimo di 3-5 anni. Dopo la fase di avviamento l’impresa, se il business ha avuto successo, si trasferisce fuori dall’incubatore in una struttura indipendente, completando così un processo di creazione di nuova imprenditoria, di posti di lavoro e di stimolo all’economia regionale e nazionale. Il capitolo illustra i principali tipi e modelli di incubatori diffusi nei diversi paesi