Analysis of Retinal Layers in Fibromyalgia Patients with Premium Protocol in Optical Tomography Coherence and Quality of Life.

PURPOSE: To evaluate the inner retinal layers in fibromyalgia (FM) patients compared to control subjects using posterior pole protocol (PPole) analysis in optical coherence tomography (OCT) and to correlate structural retinal changes with subjective quality of life. METHODS: Seventy-four eyes of healthy subjects and 55 eyes of those with FM were analyzed. All subjects underwent retinal evaluation using the PPole protocol for Spectralis OCT (Heidelberg Engineering) to obtain measurements of the retinal nerve fiber layer (RNFL) and the ganglion cell layer (GCL) in the macular area. The EuroQol (EQ-5D) questionnaire and Fibromyalgia Impact Questionnaire (FIQ) were performed to analyze health-related quality of life. Additionally, the FM group was divided into three groups depending on the disease phenotype (atypical, depressive, and biological). RESULTS: Patients with FM presented with a reduction of the RNFL thickness compared to controls in 17/64 cells of the PPole area, and a reduction of the GCL thickness in 47/64 cells. Depressive FM phenotype showed the greatest number of cells with significant reduction compared with the control group in both RNFL and GCL layers. A correlation between temporal-inferior cells of the GCL and the EuroQol 5D questionnaire results was observed. CONCLUSIONS: Patients with FM present with a reduction of the inner retinal layers in the macular area. This degeneration correlates with disease severity/reduced quality of life in these patients. The PPole protocol for OCT is a non-invasive and fast tool that might help clinicians diagnose and monitor neurodegeneration in FM patients.

Brimonidine-LAPONITE® intravitreal formulation has an ocular hypotensive and neuroprotective effect throughout 6 months of follow-up in a glaucoma animal model.

Intravitreal administration is widely used in ophthalmological practice to maintain therapeutic drug levels near the neuroretina and because drug delivery systems are necessary to avoid reinjections and sight-threatening side effects. However, currently there is no intravitreal treatment for glaucoma. The brimonidine-LAPONITE® formulation was created with the aim of treating glaucoma for extended periods with a single intravitreal injection. Glaucoma was induced by producing ocular hypertension in two rat cohorts: [BRI-LAP] and [non-bri], with and without treatment, respectively. Eyes treated with brimonidine-LAPONITE® showed lower ocular pressure levels up to week 8 (p < 0.001), functional neuroprotection explored by scotopic and photopic negative response electroretinography (p = 0.042), and structural protection of the retina, retinal nerve fibre layer and ganglion cell layer (p = 0.038), especially on the superior-inferior axis explored by optical coherence tomography, which was corroborated by a higher retinal ganglion cell count (p = 0.040) using immunohistochemistry (Brn3a antibody) up to the end of the study (week 24). Furthermore, delayed neuroprotection was detected in the contralateral eye. Brimonidine was detected in treated rat eyes for up to 6 months. Brimonidine-LAPONITE® seems to be a potential sustained-delivery intravitreal drug for glaucoma treatment.

Redefiniendo la cirugía de glaucoma mínimamente invasiva. Cirugía mínimamente penetrante / Redefining minimally invasive glaucoma surgery. Minimally penetrating glaucoma surgery

No disponible

Understanding the reaction mechanism of the oxidative addition of ammonia by (PXP)Ir(i) complexes: the role of the X group.

An analysis of the electronic rearrangements for the oxidative addition of ammonia to a set of five representative (PXP)Ir pincer complexes (X = B, CH, O, N, SiH) is performed. We aim to understand the factors controlling the activation and reaction energies of this process by combining different theoretical strategies based on DFT calculations. Interestingly, complexes featuring higher activation barriers yield more exothermic reactions. The analysis of the reaction path using the bonding evolution theory shows that the main chemical events, N-H bond cleavage and Ir-H bond formation, take place before the transition structure is reached. Metal oxidation implies an electron density transfer from non-shared Ir pairs to the Ir-N bond. This decrement in the atomic charge of the metal provokes different effects in the ionic contribution of the Ir-X bonding depending on the nature of the X atom as shown by the interacting quantum atoms methodology.

Paneth and intestinal stem cells preserve their functional integrity during worsening of acute cellular rejection in small bowel transplantation.

Graft survival after small bowel transplantation remains impaired due to acute cellular rejection (ACR), the leading cause of graft loss. Although it was shown that the number of enteroendocrine progenitor cells in intestinal crypts was reduced during mild ACR, no results of Paneth and intestinal stem cells localized at the crypt bottom have been shown so far. Therefore, we wanted to elucidate integrity and functionality of the Paneth and stem cells during different degrees of ACR, and to assess whether these cells are the primary targets of the rejection process. We compared biopsies from ITx patients with no, mild, or moderate ACR by immunohistochemistry and quantitative PCR. Our results show that numbers of Paneth and stem cells remain constant in all study groups, whereas the transit-amplifying zone is the most impaired zone during ACR. We detected an unchanged level of antimicrobial peptides in Paneth cells and similar numbers of Ki-67+ IL-22R+ stem cells revealing cell functionality in moderate ACR samples. We conclude that Paneth and stem cells are not primary target cells during ACR. IL-22R+ Ki-67+ stem cells might be an interesting target cell population for protection and regeneration of the epithelial monolayer during/after a severe ACR in ITx patients.

Visual dysfunction and its correlation with retinal changes in patients with Alzheimer's disease.

AimTo evaluate visual dysfunction and its correlation with structural changes in the retina in patients with Alzheimer's disease (AD).MethodsPatients with AD (n=24) and controls (n=24) underwent evaluation of visual acuity (VA), color vision (using the Farnsworth and L'Anthony desaturated (D) 15 color tests), and contrast sensitivity vision (CSV; using the Pelli-Robson chart and CSV-1000E test) to measure visual dysfunction. Structural measurements of the retinal nerve fiber layer (RNFL) and macular thickness were obtained using spectral domain-optical coherence tomography (SD-OCT).ResultsCSV at three of the four spatial frequencies was significantly worse in AD patients than in controls. Color vision was significantly affected in AD patients based on the Farnsworth color test. Compared with controls, macular thinning was detected in all sectors except the fovea, and the RNFL exhibited significant thinning in the superior quadrant and lower average thickness (P<0.05). CSV was the functional parameter most strongly correlated with structural measurements in patients with AD. Color vision was strongly associated with macular volume (r>0.70, P<0.05). VA at different levels of contrast was associated with macular and RNFL thickness.ConclusionsPatients with AD had visual dysfunction that correlated with structural changes evaluated by SD-OCT. Macular measurements may be reliable indicators of visual impairment in AD patients.

The Latin American experience of allografting patients with severe aplastic anaemia: real-world data on the impact of stem cell source and ATG administration in HLA-identical sibling transplants.

We studied 298 patients with severe aplastic anaemia (SAA) allografted in four Latin American countries. The source of cells was bone marrow (BM) in 94 patients and PBSCs in 204 patients. Engraftment failed in 8.1% of recipients with no difference between BM and PBSCs (P=0.08). Incidence of acute GvHD (aGvHD) for BM and PBSCs was 30% vs 32% (P=0.18), and for grades III-IV was 2.6% vs 11.6% (P=0.01). Chronic GvHD (cGvHD) between BM and PBSCs was 37% vs 59% (P=0.002) and extensive 5% vs 23.6% (P=0.01). OS was 74% vs 76% for BM vs PBSCs (P=0.95). Event-free survival was superior in patients conditioned with anti-thymocyte globulin (ATG)-based regimens compared with other regimens (79% vs 61%, P=0.001) as excessive secondary graft failure was seen with other regimens (10% vs 26%, P=0.005) respectively. In multivariate analysis, aGvHD II-IV (hazard ratio (HR) 2.50, confidence interval (CI) 1.1-5.6, P=0.02) and aGvHD III-IV (HR 8.3 CI 3.4-20.2, P<0.001) proved to be independent negative predictors of survival. In conclusion, BM as a source of cells and ATG-based regimens should be standard because of higher GvHD incidence with PBSCs, although the latter combining with ATG in the conditioning regimen could be an option in selected high-risk patients.

Visual dysfunction and its correlation with retinal changes in patients with Parkinson's disease: an observational cross-sectional study.

OBJECTIVES: To evaluate visual dysfunction and its correlation with structural changes in the retina in patients with Parkinson's disease (PD). METHODS: Patients with PD (n=37) and controls (n=37) were included in an observational cross-sectional study, and underwent visual acuity (VA), colour vision (using the Farnsworth and Lanthony desaturated D15 colour tests) and contrast sensitivity vision (CSV; using the Pelli-Robson chart and CSV 1000E test) evaluation to measure visual dysfunction. Structural measurements of the retinal nerve fibre layer (RNFL), and macular and ganglion cell layer (GCL) thicknesses, were obtained using spectral domain optical coherence tomography (SD-OCT). Comparison of obtained data, and correlation analysis between functional and structural results were performed. RESULTS: VA (in all different contrast levels) and all CSV spatial frequencies were significantly worse in patients with PD than in controls. Colour vision was significantly affected based on the Lanthony colour test. Significant GCL loss was observed in the minimum GCL+inner plexiform layer. A clear tendency towards a reduction in several macular sectors (central, outer inferior, outer temporal and superior (inner and outer)) and in the temporal quadrant of the RNFL thickness was observed, although the difference was not significant. CSV was the functional parameter most strongly correlated with structural measurements in PD. Colour vision was associated with most GCL measurements. Macular thickness was strongly correlated with macular volume and functional parameters (r>0.70, p<0.05). CONCLUSIONS: Patients with PD had visual dysfunction that correlated with structural changes evaluated by SD-OCT. GCL measurements may be reliable indicators of visual impairment in patients with PD.

Sexual and natural selection in the evolution of extended phenotypes: the use of green nesting material in starlings.

Although sexual selection is typically considered the predominant force driving the evolution of ritualized sexual behaviours, natural selection may also play an important and often underappreciated role. The use of green aromatic plants among nesting birds has been interpreted as a component of extended phenotype that evolved either via natural selection due to potential sanitary functions or via sexual selection as a signal of male attractiveness. Here, we compared both hypotheses using comparative methods in starlings, a group where this behaviour is widespread. We found that the use of green plants was positively related to male-biased size dimorphism and that it was most likely to occur among cavity-nesting species. These results suggest that this behaviour is likely favoured by sexual selection, but also related to its sanitary use in response to higher parasite loads in cavities. We speculate that the use of green plants in starlings may be facilitated by cavity nesting and was subsequently co-opted as a sexual signal by males. Our results represent an example of how an extended phenotypic component of males becomes sexually selected by females. Thus, both natural selection and sexual selection are necessary to fully understand the evolution of ritualized behaviours involved in courtship.

Study of perfusion changes in the optic disc of patients with fibromyalgia syndrome using new colorimetric analysis software.

PURPOSE: We measured the amount of hemoglobin at the optic nerve head of fibromyalgia (FM) patients using new colorimetric analysis software. We also investigated whether perfusion defects of the optic nerve head in patients with FM lead to tissue atrophy and corresponding retinal nerve fiber layer (RNFL) thinning measured by optical coherence tomography (OCT). METHODS: We recruited for this cross-sectional study 118 FM patients and 76 sex- and age-matched healthy controls. All subjects underwent a complete neuro-ophthalmologic examination, which also included visual field testing using the Spark strategy in an Easyfield perimeter, and OCT examinations using the Spectralis. One photograph of the optic disc was obtained using a Cirrus™ Photo 800 multi-modality imager. We analyzed fundus photographs using Laguna ONhE software, a new method that allows hemoglobin levels to be measured at the optic nerve head. We compared hemoglobin percentages in different sectors of the nerve head and RNFL thicknesses between the two groups. RESULTS: Mean hemoglobin percentages and hemoglobin content in all optic nerve head sectors calculated by the Laguna ONhE program were significantly lower in FM patients than in healthy controls, and the main differences were detected in the outer ring, which corresponds with the neuroretinal rim. However, only the differences in the superotemporal RNFL were statistically significant. Correlations between the RNFL thickness and the percentage of hemoglobin in the different sectors were weak. CONCLUSION: Optic disc perfusion was decreased in patients with FM, especially within the neuroretinal rim, without clear involvement in the RNFL.

Evaluación de la perfusión del nervio óptico en las neuropatías ópticas y las enfermedades neurodegenerativas / Evaluation of optic nerve perfusion in optic neuropathies and neurodegenerative diseases

No disponible

Hallazgo de hipertrofia de la capa de fibras nerviosas de la retina en pacientes con ataxia de Charlevoix-Saguenay / Finding of retinal nerve fiber layer hypertrophy in ataxia of Charlevoix-Saguenay patients

OBJETIVO/MÉTODO: Se presenta la evaluación neurooftalmológica de cinco pacientes con ataxia espástica de Charlevoix-Saguenay (ARSACS). RESULTADOS/CONCLUSIONES: Los pacientes mostraron alteración en el campo visual, aumento de la visualización de la CFNR en las estereofotografías, nervio óptico de morfología normal en la evaluación con Heidelberg Retina Tomograph e incremento marcado del espesor de la CFNR en la tomografía de coherencia óptica (119-220 μm). Encontramos evidencia de que la hipertrofia de CFNR puede ser un hallazgo funduscópico alternativo a la persistencia de fibras de mielina descrita en la bibliografía previa. Se aconseja realizar una revisión de los criterios diagnósticos de la ARSACS

PURPOSE/METHODS: To present the neuro-ophthalmology examination in 5 spastic ataxia of Charlevoix-Saguenay (ARSACS) patients showing significant increases in retinal nerve fiber layer (RNFL) thickness. RESULTS/CONCLUSIONS: All patients showed abnormal visual fields, normal optic discs with increased visibility of RNFL in color stereo-photographs, normal examination with Heidelberg Retina Tomography instrument, and moderate to markedly increased RNFL thickness in Cirrus Optical Coherence Tomography evaluation (average thickness: 119 to 220 microns). We found evidence that RNFL hypertrophy may be an alternative funduscopic finding to the hypermyelinated retinal fibers in previous reports. A revision of ARSACS diagnostic criteria, particularly with regard to retinal alterations, is necessary

Reliability and validity of Cirrus and Spectralis optical coherence tomography for detecting retinal atrophy in Alzheimer's disease.

BACKGROUND: To evaluate and compare the ability of two Fourier-domain optical coherence tomography (OCT) devices to detect retinal and retinal nerve fibre layer (RNFL) atrophy in patients with Alzheimer's disease (AD) compared with healthy subjects; to test the intra-session reliability of two OCT devices in AD patients and healthy subjects. METHODS: AD patients (n=75) and age-matched healthy subjects (n=75) underwent three Macular Cube 200 × 200 protocols using the Cirrus and Spectralis OCT devices and three 360° circular scans centred on the optic disc using the Cirrus OCT device, the classic glaucoma application, and the new Nsite Axonal Analytics application of the Spectralis OCT instrument. Differences between healthy and AD eyes were compared, and measurements provided by each OCT protocol were compared. Reliability was measured using intraclass correlation coefficients and coefficients of variation. Correlations between OCT measurements and disease duration and severity were also analysed. RESULTS: Retinal thinning was observed in AD eyes in all areas except the fovea using both OCT devices. RNFL atrophy was detected in AD eyes with all three protocols, but the Nsite Axonal application was the most sensitive. Measurements by the two OCT devices were correlated, but differed significantly. Reliability was good using all protocols, but better with the glaucoma application of Spectralis. Mean RNFL thickness provided by the Nsite Axonal application correlated with disease duration. CONCLUSIONS: Fourier-domain OCT is a valid and reliable technique for detecting subclinical RNFL and retinal atrophy in AD, especially using the Nsite Axonal application. RNFL thickness decreased with disease duration.

Does KRAS mutational status predict chemoresistance in advanced non-small cell lung cancer (NSCLC)?

BACKGROUND: Clinical implications of KRAS mutational status in advanced non-small cell lung cancer (NSCLC) remain unclear. To clarify this point, we retrospectively explored whether KRAS mutations could impact tumor response, and disease control rate (DCR) to first-line platinum-based chemotherapy (CT) as well as progression-free survival (PFS) or overall survival (OS). METHODS: Between June 2009 and June 2012, 340 patients with advanced (stage IIIB/IV) NSCLC were reviewed in a single institution (Institut Gustave Roussy). Two hundred and one patients had a biomolecular profile and received a platinum-based first-line CT. Patients with an unknown mutational status or with actionable alterations were excluded. We retained two groups: patients with KRAS mutated tumor (MUT) and patients with wild-type KRAS/EGFR (WT). Multivariate analyses with Cox model were used. Survival curves were calculated with Kaplan-Meier method. RESULTS: One hundred and eight patients were included in the analysis: 39 in the MUT group and 69 in the WT group. Baseline radiological assessment demonstrated more brain (P=0.01) and liver (P=0.04) metastases in MUT patients. DCR was 76% for MUT vs. 91% for WT group (P=0.03), regardless of the type of platinum-based CT (use of pemetrexed or not). Although no statistically significant differences were found, shorter PFS (4.9 vs. 6.0 months; P=0.79) and OS (10.3 vs. 13.2 months; P=0.40) were observed for patients with KRAS mutated tumors in univariate analysis. CONCLUSIONS: KRAS mutant tumors had a lower DCR after the first-line platinum-based CT, but this difference did not translate in PFS or OS. The presence of KRAS mutations may confer a more aggressive disease, with greater baseline incidence of hepatic and cerebral metastases.

[Finding of retinal nerve fiber layer hypertrophy in ataxia of Charlevoix-Saguenay patients]. / Hallazgo de hipertrofia de la capa de fibras nerviosas de la retina en pacientes con ataxia de Charlevoix-Saguenay.

PURPOSE/METHODS: To present the neuro-ophthalmology examination in 5 spastic ataxia of Charlevoix-Saguenay (ARSACS) patients showing significant increases in retinal nerve fiber layer (RNFL) thickness. RESULTS/CONCLUSIONS: All patients showed abnormal visual fields, normal optic discs with increased visibility of RNFL in color stereo-photographs, normal examination with Heidelberg Retina Tomography instrument, and moderate to markedly increased RNFL thickness in Cirrus Optical Coherence Tomography evaluation (average thickness: 119 to 220 microns). We found evidence that RNFL hypertrophy may be an alternative funduscopic finding to the hypermyelinated retinal fibers in previous reports. A revision of ARSACS diagnostic criteria, particularly with regard to retinal alterations, is necessary.

Maintenance strategies in stage IV non-small-cell lung cancer (NSCLC): in which patients, with which drugs?

Four to six cycles of platinum-based chemotherapy are currently recommended for the first-line treatment of advanced non-small-cell lung cancer (NSCLC). Several studies have assessed the benefit of maintenance therapy following platinum-based first-line therapy, to improve disease control, and thus, progression-free and overall survival with minimal toxicity and maintenance or improvement of quality of life of patients. We review here clinical trials evaluating continuation maintenance therapy or switch maintenance therapy in locally advanced or metastatic NSCLC, to highlight the achievements made and critical issues faced. Based on the available results and limitations of these trials, maintenance therapy should be considered a good treatment strategy for a limited subgroup of patients. Maintenance therapy should be personalised according to the characteristics of patients and their disease, taking into account the data available for the agents used in this setting.