A Case of Neurotrophic Keratopathy Concomitant to Brain Metastasis

We report a case of a 63-year-old Caucasian female referred to the cornea service of Clinica Oculistica with a neurotrophic corneal ulcer, decreased corneal sensitivity, absent corneal reflex, and decreased lacrimation. The medical record review was relevant for mastectomy and adjuvant therapy for breast cancer complicated by pontocerebellar angle metastasis. Eye patching and application of antibiotic and vitamin ointments were prescribed at first, without a significant improvement. Thus, treatment with autologous serum was started. In about two weeks, the cornea recovered and visual acuity improved with a residual corneal scarring. Finally, we should mention that, in our case, the main cause of the neurotrophic corneal ulcer could be identified in the previous trigeminal damage at the pontocerebellar angle and trigeminal ganglion. Sensory nerves play an important regulatory role via neuro-mediators on corneal wound healing, as denervation may interfere with cellular metabolism and inhibit mitosis, leading to an epithelial defect even with no direct damage

QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

BACKGROUND: Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc) exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. METHOD: We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine) and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine) with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine) or lithium. An Electrocardiogram (ECG) was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. RESULTS: Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms) however this was not the case in Group 1 (-1 ± 30 ms) (Repeated measures ANOVA p < 0,01). Furthermore we found a significant difference in the number of patients who exceeded the threshold of borderline QTc interval value (450 ms) between the two groups, with seven patients in Group 2 (38%) compared to one patient in Group 1 (7%) (Fisher Exact Text, p < 0,05). CONCLUSIONS: No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a combined treatment of antipsychotic and antidepressant agents

Comparison of local recurrence among early breast cancer patients treated with electron intraoperative radiotherapy vs hypofractionated photon radiotherapy an observational study

Purpose: To evaluate local recurrence (LR) in women with early breast cancer (BC) who underwent intraoperative radiation therapy with electrons particles (IORT-E) or adjuvant hypofractionated external radiotherapy (HYPOFX). Materials and methods: We retrospectively analyzed 470 patients with early BC treated at our center from September 2009 to December 2012. 235 women were treated with breast-conserving surgery and immediate IORT-E (21 Gy/1 fraction) while 235 patients underwent wide excision followed by hypofractionated whole-breast irradiation. Radiotherapy modality was chosen according to an individualized decision based on tumor features, stage, technical feasibility, age, and acceptance to be enrolled in the IORT-E group. Results: After a median follow-up of 6 years, we observed 8 (3.4%) and 1 (0.42%) LR in the IORT-E and in the HYPOFX group (p = 0.02), respectively. The two groups differed in the prevalence of clinical characteristics (p &lt; 0.05): age, tumor size, surgical margins, receptors, ki67, and histology. 4 and 1 woman in the IORT-E and HYPOFX group died of BC, respectively (p = 0.167). OS and DFS hazard ratio [HR] were 2.14 (95% IC, 1.10-4.15) and 2.09 (95% IC, 1.17-3.73), respectively. Conclusion: Our comparison showed that IORT-E and HYPOFX are two effective radiotherapy modalities after conservative surgery in early BC. However, at 6 years a significant higher rate of LR occurred in patients submitted to IORT-E with respect to HYPOFX. This finding may be correlated to some subsets of patients who, depending on the biological characteristics of the BC, may be less suitable to IORT-E

Brain activity pattern changes after adaptative working memory training in multiple sclerosis

Cognitive impairment and related abnormal brain activity are common in people with multiple sclerosis (PwMS). Adaptive training based on working memory (WM) has been shown to ameliorate cognitive symptoms, although the effects at a neural level are unclear. The aim of this study was to expand the existing research on the effects of an adaptive WM rehabilitative intervention on brain functional activity in PwMS. A sample of eighteen PwMS performed an 8-week home-based cognitive rehabilitation treatment based on adaptive WM training. PwMS were assessed before and after treatment using a validated neuropsychological battery and undergoing an fMRI session while carrying out a cognitive task (i.e., Paced Visual Serial Addition Test - PVSAT). fMRI activations were compared to the activation pattern elicited by eighteen matched healthy subjects performing the same task. At baseline, we found abnormal brain activity during PVSAT in PwMS when compared to healthy subjects, with a pattern including several bilateral activation clusters. Following rehabilitation, PwMS improved cognitive performance, as evaluated by the neuropsychological battery, and showed a different activation map with clusters mainly located in the right cerebellum and in the left hemisphere. The only significant cluster in the right hemisphere was located in the inferior parietal lobule, and the BOLD signal extracted in this area significantly correlated with cognitive performance both before and after the treatment. We suggest that WM training can improve the cognitive performance and reduce the abnormal activation of PwMS by partially maintaining or even restoring brain cognitive function

Introducing EDEN ISS - A European project on advancing plant cultivation technologies and operations

Plant cultivation in large-scale closed environments is challenging and several key technologies necessary for space-based plant production are not yet space-qualified or remain in early stages of development. The EDEN ISS project foresees development and demonstration of higher plant cultivation technologies, suitable for future deployment on the International Space Station and from a long-term perspective, within Moon and Mars habitats. The EDEN ISS consortium will design and test essential plant cultivation technologies using an International Standard Payload Rack form factor cultivation system for potential testing on-board the International Space Station. Furthermore, a Future Exploration Greenhouse will be designed with respect to future planetary bio-regenerative life support system deployments. The technologies will be tested in a laboratory environment as well as at the highly-isolated German Antarctic Neumayer Station III. A small and mobile container-sized test facility will be built in order to provide realistic mass flow relationships. In addition to technology development and validation, food safety and plant handling procedures will be developed. This paper describes the goals and objectives of EDEN ISS and the different project phases and milestones. Furthermore, the project consortium will be introduced and the role of each partner within the project is explained

The Use of Topical Corticosteroids for Treatment of Dry Eye Syndrome

Dry eye disease (DED) is a multifactorial disease that results in symptoms of discomfort, visual disturbance, and damage to the ocular surface. Because chronic inflammation plays an important role in DED, treatment with topical corticosteroids has been demonstrated to ameliorate the signs and symptoms of the disease. Although these agents have proven short-term efficacy, their long-term use may cause intraocular pressure elevation and cataract progression. A carefully review of the different studies shows that differences between corticosteroids may exist regarding the incidence of side effects and evidence of efficacy in DED patients

Recombinant Human Nerve Growth Factor (Cenegermin)-Driven Corneal Wound Healing Process: An Evidence-Based Analysis

: Purpose: To evaluate anterior segment optical coherence tomography (AS-OCT) to detect the wound healing process as per monitoring the effectiveness of cenegermin to treat moderate to severe neurotrophic keratoplasty. Methods: A retrospective chart review was realized to identify patients treated with cenegermin at the Clinica Oculistica, University of Genoa, Italy. All patients underwent careful examinations at baseline and follow-up visits. AS-OCT scans centered on the minimum corneal thickness (CT) area were always performed. We compared findings of AS-OCT with the findings from the slit-lamp examination. A linear regression analysis was used to evaluate factors associated with corneal healing. A further analysis, including a control group treated with 50% autologous serum (AS), was done to investigate and compare the efficacy of cenegermin. Results: Data from 16 eyes were studied. The average patients' age was 60.9 \ub1 21.1&nbsp;years; five (31.2%) eyes experienced persistent epithelial defect and 11 (68.8%) eyes had neurotrophic corneal ulcer. The average reepithelialization time was 3.9 \ub1 0.5 weeks in the cenegermin group versus 5.9 \ub1 1.9&nbsp;weeks in the AS group (p &lt; 0.01). The AS-OCT scans revealed an average CT at the thinnest point of 276.3 \ub1 74.1&nbsp;\u3bcm before treatment with an average increase of 176.5 \ub1 60.3&nbsp;\u3bcm at the end of the cenegermin treatment (B = -0.15; p = 0.035). The AS-OCT percentage increase in corneal thickness between the two groups was statistically significant (p &lt; 0.02). Conclusion: Understanding the cascade of events involved in the nerve growth factor-driven corneal wound healing process is clinically meaningful for the clinician. AS-OCT is an effective tool for systematic anterior segment imaging, allowing the detailed detection of the front-to-back layered corneal structure for quantitative analysis and monitoring of the healing process

CFSE: A New Method for Identifying Human Limbal Stem Cells and Following Their Migration in Human Cornea

Aim: To develop a method capable of identifying human corneal limbal stem cells (LSCs) and follow their proliferation and migration in the epithelium. Materials and methods: Ten fresh matched pairs of cadaveric normal human corneas were obtained from donors. Carboxyfluorescein diacetate succinimidyl ester (CFSE) was used to target LSCs. The distribution of CFSE-positive cell clusters was analyzed by fluorescence microscopy by counterstaining with 4',6-diamidino-2-phenylindole (DAPI). Fluorescence was digitally recorded for seven days, and the rate of cell movement was determined. Results: CFSE-labeled cells were tracked in corneas. Analysis of time sequences revealed that they moved centripetally. Daily average CFSE-labeled LSC movement was 0.073\ub10.01 cm (\ub1SD). Conclusion: CFSE allowed us to identify LSCs and to track their centripetal migration from the limbal basal layer to the anterior ocular surface. This experimental system appears to be a valuable tool for further studies on corneal epithelial cell migration and proliferation

Prospective evaluation of CO2 laser-assisted sclerectomy surgery (CLASS) with Mitomycin C

Purpose: Our purpose was to evaluate the clinical safety and efficacy of CO2 laser-assisted sclerectomy surgery (CLASS) with Mitomycin C (MMC) in open angle glaucoma (OAG).Methods: This was a prospective, uncontrolled, interventional case series. All subjects underwent CLASS procedure by a single surgeon. After the dissection of a partial thickness scleral flap, topical MMC 0.2 mg/ml was applied to the sclera and the conjunctiva for 3 min. The CO2 laser with a beam-manipulating system was used to ablate the scleral tissue and expose the Schlemm\u2019s canal area. Primary outcomes: intraocular pressure (IOP) change, number of IOP-lowering medicaments change. Adverse events were evaluated as secondary outcomes. Results: Twenty-one eyes of 21 patients underwent the CLASS procedure. Thirteen were primary OAG (62%), two normal pressure glaucoma (10%), three exfoliative glaucoma (14%) and three others secondary OAG. With a mean (SD) follow-up of 15.3 (5.9) months, the IOP changed from 25.4 (6.7) mmHg at baseline to 10.9 (3.4) mmHg al the last visit. Mean reduction of IOP was 1214.5 mmHg (95% CI, 1217.7 to 1211.2, P\u2009&lt;\u20090.001). The median (IQR) number of IOP-lowering medication decreased from 3 (3\u20133) at baseline to 1 (0\u20131) at the last visit (P\u2009&lt;\u20090.001). Visual acuity did not change significantly. Adverse events: five eyes (24%) developed iris adhesion to the filtration area that was successfully managed with office-based procedures. In one case (5%), CLASS was converted to trabeculectomy due to intraoperative perforation of the ablated area. There was one case of hypotony maculopathy successfully treated with placement of additional transconjunctival scleral flap sutures. Conclusions: The CLASS procedure with MMC is clinically safe and effective maintaining a large reduction in IOP and in the number of IOP-lowering medications with a mean follow-up of 15 months. Iris adhesion at the filtrating area warrants further evaluation and possibly reflects the surgeon\u2019s learning curve