A self-sustaining endocytic-based loop promotes breast cancer plasticity leading to aggressiveness and pro-metastatic behavior

The subversion of endocytic routes leads to malignant transformation and has been implicated in human cancers. However, there is scarce evidence for genetic alterations of endocytic proteins as causative in high incidence human cancers. Here, we report that Epsin 3 (EPN3) is an oncogene with prognostic and therapeutic relevance in breast cancer. Mechanistically, EPN3 drives breast tumorigenesis by increasing E-cadherin endocytosis, followed by the activation of a \u3b2-catenin/TCF4-dependent partial epithelial-to-mesenchymal transition (EMT), followed by the establishment of a TGF\u3b2-dependent autocrine loop that sustains EMT. EPN3-induced partial EMT is instrumental for the transition from in situ to invasive breast carcinoma, and, accordingly, high EPN3 levels are detected at the invasive front of human breast cancers and independently predict metastatic rather than loco-regional recurrence. Thus, we uncover an endocytic-based mechanism able to generate TGF\u3b2-dependent regulatory loops conferring cellular plasticity and invasive behavior

One week of levofloxacin plus dexamethasone eye drops for cataract surgery: an innovative and rational therapeutic strategy

Background: Cataract surgery is the most common operation performed worldwide. A fixed topical corticosteroid-antibiotic combination is usually prescribed in clinical practice for 2 or more weeks to treat post surgical inflammation and prevent infection. However, this protracted schedule may increase the incidence of corticosteroid-related adverse events and notably promote antibiotic resistance. Methods: This International, multicentre, randomized, blinded-assessor, parallel-group clinical study evaluated the non-inferiority of 1-week levofloxacin/dexamethasone eye drops, followed by 1-week dexamethasone alone, vs. 2-week gold-standard tobramycin/dexamethasone (one drop QID for all schedules) to prevent and treat ocular inflammation and prevent infection after uncomplicated cataract surgery. Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) around a treatment difference >\u201310%. The study randomized 808 patients enrolled in 53 centres (Italy, Germany, Spain and Russia). The primary endpoint was the proportion of patients without anterior chamber inflammation on day 15 defined as the end of treatment. Endophthalmitis was the key secondary endpoint. This study is registered with EudraCT code: 2018-000286-36. Results: After the end of treatment, 95.2% of the patients in the test arm vs. 94.9% of the control arm had no signs of inflammation in the anterior chamber (difference between proportions of patients = 0.028; 95% CI: 120.0275/0.0331). No case of endophthalmitis was reported. No statistically significant difference was evident in any of the other secondary endpoints. Both treatments were well tolerated. Conclusions: Non-inferiority of the new short pharmacological strategy was proven. One week of levofloxacin/dexamethasone prevents infection, ensures complete control of inflammation in almost all patients and may contain antibiotic resistance

Cancer therapy and cardiotoxicity: The need of serial Doppler echocardiography

Cancer therapy has shown terrific progress leading to important reduction of morbidity and mortality of several kinds of cancer. The therapeutic management of oncologic patients includes combinations of drugs, radiation therapy and surgery. Many of these therapies produce adverse cardiovascular complications which may negatively affect both the quality of life and the prognosis. For several years the most common noninvasive method of monitoring cardiotoxicity has been represented by radionuclide ventriculography while other tests as effort EKG and stress myocardial perfusion imaging may detect ischemic complications, and 24-hour Holter monitoring unmask suspected arrhythmias. Also biomarkers such as troponine I and T and B-type natriuretic peptide may be useful for early detection of cardiotoxicity. Today, the widely used non-invasive method of monitoring cardiotoxicity of cancer therapy is, however, represented by Doppler-echocardiography which allows to identify the main forms of cardiac complications of cancer therapy: left ventricular (systolic and diastolic) dysfunction, valve heart disease, pericarditis and pericardial effusion, carotid artery lesions. Advanced ultrasound tools, as Integrated Backscatter and Tissue Doppler, but also simple ultrasound detection of "lung comet" on the anterior and lateral chest can be helpful for early, subclinical diagnosis of cardiac involvement. Serial Doppler echocardiographic evaluation has to be encouraged in the oncologic patients, before, during and even late after therapy completion. This is crucial when using anthracyclines, which have early but, most importantly, late, cumulative cardiac toxicity. The echocardiographic monitoring appears even indispensable after radiation therapy, whose detrimental effects may appear several years after the end of irradiation

Rotational stability and refractive outcomes of a single-piece aspheric toric intraocular lens with 4 fenestrated haptics

To assess the outcomes of implantation of a single-piece toric intraocular lens (IOL) with 4 fenestrated haptics

Evaluation of corneal optical properties in subjects wearing hydrogel etafilcon A contact lenses and the effect of administering mannitol-enriched sodium hyaluronate ophthalmic solution

Marco Lombardo,1,2 Marianna Rosati,1 Marco Pileri,3 Domenico Schiano-Lomoriello,1 Sebastiano Serrao11Fondazione G.B. Bietti IRCCS, 2Vision Engineering Italy Srl, 3Azienda Ospedaliera San Giovanni-Addolorata, Rome, ItalyBackground: The purpose of this study was to evaluate the effect of daily administration of mannitol-enriched sodium hyaluronate ophthalmic solution on the corneal optical properties of subjects wearing low Dk hydrogel (etafilcon A) contact lenses (CLs).Methods: Forty-five subjects wearing etafilcon A CLs daily for more than 6 months were recruited into this pilot study. Fifteen of the subjects administered a 10% mannitol-enriched 0.05% sodium hyaluronate solution (study group) once daily and 30 subjects did not administer any ophthalmic solution (control group). The subjects were examined at baseline and one month after recruitment. Changes in central corneal thickness (CCT) and corneal light backscatter were evaluated by Scheimpflug imaging (Pentacam HR). Changes in corneal total high-order aberration, corneal spherical aberration, coma, and trefoil were evaluated using the OPD scan II.Results: At one month, corneal light backscatter decreased significantly in the study group (≤18.30 arbitrary units; P<0.05) and this was highly correlated with a decrease in CCT (R=0.81; P=0.04). The decrease in corneal total high-order aberration, spherical aberration, and coma was significantly higher in the study group than in the control group (P<0.05). No changes in corneal light backscatter or CCT were found in the control group during follow-up.Conclusion: Once-daily administration of a mannitol-enriched lubricant ophthalmic solution was effective for improving the corneal optical quality and reducing corneal swelling in subjects wearing low Dk hydrogel (etafilcon A) CLs during one month follow-up.Keywords: corneal optical quality, corneal high-order aberrations, Scheimpflug imaging, corneal backscattering, contact lens, hypertonic lubricant solutio

Early alterations of corneal subbasal plexus in uncomplicated type 1 diabetes patients

Purpose. The purpose of our study is to describe the in vivo corneal confocal microscopy characteristics of subbasal nerve plexus in a highly selected population of patients affected by type 1 diabetes mellitus (T1DM) without any microvascular diabetes complications. Methods. We included 19 T1DM patients without diabetic peripheral neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, and microalbuminuria. All patients underwent in vivo corneal confocal microscopy and blood analysis to determine subbasal nerve plexus parameters and their correlation with clinical data. We compared the results with 19 healthy controls. Results. The T1DM group showed a significant decrease of the nerve fiber length (P=0.032), the nerve fiber length density (P=0.034), the number of fibers (P=0.005), and the number of branchings (P=0.028), compared to healthy subjects. The nerve fiber length, nerve fiber length density, and number of fibers were directly related to the age at onset of diabetes and inversely to the duration of DM. BMI (body mass index) was highly related to the nerve fiber length (r=-0.6, P=0.007), to the nerve fiber length density (r=-0.6, P=0.007), and to the number of fibers (r=-0.587, P=0.008). No significant correlations were found between the corneal parameters and HbA1c. Conclusions. Early subclinical fiber corneal variation could be easily detected using in vivo corneal confocal microscopy, even in type 1 diabetes without any microvascular diabetes complications, including diabetic peripheral neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, and microalbuminuria