Ocular Risk Factors for Exudative AMD: A Novel Semiautomated Grading System

Purpose. To evaluate the contribution of the ocular risk factors in the conversion of the fellow eye of patients with unilateral exudative AMD, using a novel semiautomated grading system. Materials and Methods. Single-center, retrospective study including 89 consecutive patients with unilateral exudative AMD and ≥3 years of followup. Baseline color fundus photographs were graded using an innovative grading software, RetmarkerAMD (Critical Health SA). Results. The follow-up period was 60.9 ± 31.3 months. The occurrence of CNV was confirmed in 42 eyes (47.2%). The cumulative incidence of CNV was 23.6% at 2 years, 33.7% at 3 years, 39.3% at 5 years, and 47.2% at 10 years, with a mean annual incidence of 12.0% (95% CI = 0.088-0.162). The absolute number of drusen in the central 1000 and 3000  μ m (P < 0.05) and the absolute number of drusen ≥125 µm in the central 3000 and 6000 µm (P < 0.05) proved to be significant risk factors for CNV. Conclusion. The use of quantitative variables in the determination of the OR of developing CNV allowed the establishment of significant risk factors for neovascularization. The long follow-up period and the innovative methodology reinforce the value of our results. This trial is registered with ClinicalTrials.gov NCT00801541.

Ocular Risk Factors for Exudative AMD: A Novel Semiautomated Grading System

Purpose. To evaluate the contribution of the ocular risk factors in the conversion of the fellow eye of patients with unilateral exudative AMD, using a novel semiautomated grading system. Materials and Methods. Single-center, retrospective study including 89 consecutive patients with unilateral exudative AMD and ≥3 years of followup. Baseline color fundus photographs were graded using an innovative grading software, RetmarkerAMD (Critical Health SA). Results. The follow-up period was 60.9 ± 31.3 months. The occurrence of CNV was confirmed in 42 eyes (47.2%). The cumulative incidence of CNV was 23.6% at 2 years, 33.7% at 3 years, 39.3% at 5 years, and 47.2% at 10 years, with a mean annual incidence of 12.0% (95% CI = 0.088-0.162). The absolute number of drusen in the central 1000 and 3000  μ m (P < 0.05) and the absolute number of drusen ≥125 µm in the central 3000 and 6000 µm (P < 0.05) proved to be significant risk factors for CNV. Conclusion. The use of quantitative variables in the determination of the OR of developing CNV allowed the establishment of significant risk factors for neovascularization. The long follow-up period and the innovative methodology reinforce the value of our results. This trial is registered with ClinicalTrials.gov NCT00801541.

Abordagens estereológica e imunohistoquímica no câncer de próstata: uma reavaliação diagnóstica e possível terapêutica

Os esforços para melhorar o diagnóstico, o prognóstico e a vigilância do câncer de próstata (CaP) são relevantes. A superestimação do Escore de Gleason (GSC) pode submeter os indivíduos a um tratamento agressivo desnecessário. Foi tido como objetivo utilizar a estereologia em avaliações do CaP e investigar se o volume nuclear médio (VNM) correlaciona-se com o padrão primário de Gleason (Gpp), a fim de buscar um método alternativo devido à subjetividade do Escore de Gleason, que seja aquele, um método confiável e objetivo, sem discordância interobservador. Para isso, identificamos 74 amostras de prostatectomia radical, que foram divididos em seis grupos com base no Gpp, de 3 a 5. Controles (C) foram adquiridos em regiões não tumorais pareadas das mesmas amostras. O VNM foi estimado utilizando o método de "intersecção dos pontos amostrados". Diferenças estatísticas do VNM entre os grupos C e os grupos Gpp foram testadas utilizando o teste de Kruskall-Wallis e pós- teste de Dunn. As diferenças entre cada grupo Gpp e seus homólogos foram testados com o teste de Wilcoxon. As correlações foram avaliadas com a correlação de Spearman (R [Spearman]). As correlações entre o antígeno prostático específico (PSA) e o GSC (R [Spearman] de 0,76) e entre o PSA e o VNM (R [Spearman] de 0,78) foram moderadamente forte e altamente significativa, e a correlação entre o VNM e o Gpp (R [Spearman] de 0,53) foi moderada e altamente significativa. O VNM foi significativamente maior em regiões cancerígenas em comparação as regiões de controle-pareado. O planejamento adequado de um estudo, bem como a disponibilidade de equipamentos e softwares para a quantificação morfológica, pode proporcionar incentivo para rapidez e precisão para estimar o VNM como parâmetro auxiliar na avaliação do câncer de próstata. A reprodutibilidade falha interobservador do GSC tem mostrado possíveis conduções equivocadas dos pacientes portadores de CaP. O VNM representa um método reprodutível de classificação objetiva para o câncer de próstata. Portanto, os dados atuais favorecem o uso de VNM associado com GSC e o PSA na avaliação do câncer de próstata.

An automated machine vision system for the histological grading of cervical intraepithelial neoplasia (CIN)

The histological grading of cervical intraepithelial neoplasia (CIN) remains subjective, resulting in inter- and intra-observer variation and poor reproducibility in the grading of cervical lesions. This study has attempted to develop an objective grading system using automated machine vision. The architectural features of cervical squamous epithelium are quantitatively analysed using a combination of computerized digital image processing and Delaunay triangulation analysis; 230 images digitally captured from cases previously classified by a gynaecological pathologist included normal cervical squamous epithelium (n = 30), koilocytosis (n = 46), CIN 1 (n = 52), CIN 2 (n = 56), and CIN 3 (n=46). Intra- and inter-observer variation had kappa values of 0.502 and 0.415, respectively. A machine vision system was developed in KS400 macro programming language to segment and mark the centres of all nuclei within the epithelium. By object-oriented analysis of image components, the positional information of nuclei was used to construct a Delaunay triangulation mesh. Each mesh was analysed to compute triangle dimensions including the mean triangle area, the mean triangle edge length, and the number of triangles per unit area, giving an individual quantitative profile of measurements for each case. Discriminant analysis of the geometric data revealed the significant discriminatory variables from which a classification score was derived. The scoring system distinguished between normal and CIN 3 in 98.7% of cases and between koilocytosis and CIN 1 in 76.5% of cases, but only 62.3% of the CIN cases were classified into the correct group, with the CIN 2 group showing the highest rate of misclassification. Graphical plots of triangulation data demonstrated the continuum of morphological change from normal squamous epithelium to the highest grade of CIN, with overlapping of the groups originally defined by the pathologists. This study shows that automated location of nuclei in cervical biopsies using computerized image analysis is possible. Analysis of positional information enables quantitative evaluation of architectural features in CIN using Delaunay triangulation meshes, which is effective in the objective classification of CIN. This demonstrates the future potential of automated machine vision systems in diagnostic histopathology. Copyright (C) 2000 John Wiley and Sons, Ltd.

Tumor Regression Grading of Gastrointestinal Carcinomas after Neoadjuvant Treatment

Multimodal therapy concepts have been successfully implemented in the treatment of locally advanced gastrointestinal malignancies. The effects of neoadjuvant chemo- or radiochemotherapy such as scarry fibrosis or resorptive changes and inflammation can be determined by histopathological investigation of the subsequent resection specimen. Tumor regression grading (TRG) systems which aim to categorize the amount of regressive changes after cytotoxic treatment mostly refer onto the amount of therapy induced fibrosis in relation to residual tumor or the estimated percentage of residual tumor in relation to the previous tumor site. Commonly used TRGs for upper gastrointestinal carcinomas are the Mandard grading and the Becker grading system, e.g., and for rectal cancer the Dworak or the Rödel grading system, or other systems which follow similar definitions. Namely for gastro-esophageal carcinomas these TRGs provide important prognostic information since complete or subtotal tumor regression has shown to be associated with better patient's outcome. The prognostic value of TRG may even exceed those of currently used staging systems (e.g., TNM staging) for tumors treated by neoadjuvant therapy. There have been some limitations described regarding interobserver variability especially in borderline cases, which may be improved by standardization of work up of resection specimen and better training of histopathologic determination of regressive changes. It is highly recommended that TRG should be implemented in every histopathological report of neoadjuvant treated gastrointestinal carcinomas. The aim of this review is to disclose the relevance of histomorphological TRG to accomplish an optimal therapy for patients with gastrointestinal carcinomas.

Reconsidering the logic of World Federation of Neurosurgical Societies grading in patients with severe subarachnoid hemorrhage.

OBJECT Current data show a favorable outcome in up to 50% of patients with World Federation of Neurosurgical Societies (WFNS) Grade V subarachnoid hemorrhage (SAH) and a rather poor prediction of worst cases. Thus, the usefulness of the current WFNS grading system for identifying the worst scenarios for clinical studies and for making treatment decisions is limited. One reason for this lack of differentiation is the use of "negative" or "silent" diagnostic signs as part of the WFNS Grade V definition. The authors therefore reevaluated the WFNS scale by using "positive" clinical signs and the logic of the Glasgow Coma Scale as a progressive herniation score. METHODS The authors performed a retrospective analysis of 182 patients with SAH who had poor grades on the WFNS scale. Patients were graded according to the original WFNS scale and additionally according to a modified classification, the WFNS herniation (hWFNS) scale (Grade IV, no clinical signs of herniation; Grade V, clinical signs of herniation). The prediction of poor outcome was compared between these two grading systems. RESULTS The positive predictive values of Grade V for poor outcome were 74.3% (OR 3.79, 95% CI 1.94-7.54) for WFNS Grade V and 85.7% (OR 8.27, 95% CI 3.78-19.47) for hWFNS Grade V. With respect to mortality, the positive predictive values were 68.3% (OR 3.9, 95% CI 2.01-7.69) for WFNS Grade V and 77.9% (OR 6.22, 95% CI 3.07-13.14) for hWFNS Grade V. CONCLUSIONS Limiting WFNS Grade V to the positive clinical signs of the Glasgow Coma Scale such as flexion, extension, and pupillary abnormalities instead of including "no motor response" increases the prediction of mortality and poor outcome in patients with severe SAH.

6 versus 12 month performance of polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in an ovine thoracic interbody fusion model

Introduction Well-designed biodegradable scaffolds in combination with bone growth factors offer a valuable alternative to the current gold standard autograft in spinal fusion surgery Yong et al. (2013). Here we report on 6- vs 12- month data set evaluating the longitudinal performance of a CaP coated polycaprolactone (PCL) scaffold loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within a large preclinical animal model. Methods Twelve sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels; (i) calcium phosphate (CaP) coated polycaprolactone based scaffold plus 0.54µg rhBMP-2, (ii) CaP coated PCL- based scaffold alone or (iii) autograft (mulched rib head). Fusion assessments were performed via high resolution clinical computed tomography and histological evaluation were undertaken at six (n=6) and twelve (n=6) months post-surgery using the Sucato grading system (Sucato et al. 2004). Results The computed tomography fusion grades of the 6- and 12- months in the rhBMP-2 plus PCL- based scaffold group were 1.9 and 2.1 respectively, in the autograft group 1.9 and 1.3 respectively, and in the scaffold alone group 0.9 and 1.17 respectively. There were no statistically significant differences in the fusion scores between 6- and 12- month for the rhBMP plus PCL- based scaffold or PCL – based scaffold alone group however there was a significant reduction in scores in the autograft group. These scores were seen to correlate with histological evaluations of the respective groups. Conclusions The results of this study demonstrate the efficacy of scaffold-based delivery of rhBMP-2 in promoting higher fusion grades at 6- and 12- months in comparison to the scaffold alone or autograft group within the same time frame. Fusion grades achieved at six months using PCL+rhBMP-2 are not significantly increased at twelve months post-surgery.

Evaluation framework to assess orthopaedic procedures

Introduction & aims The demand for evidence of efficacy of treatments in general and orthopaedic surgical procedures in particular is ever increasing in Australia and worldwide. The aim of this study is to share the key elements of an evaluation framework recently implemented in Australia to determine the efficacy of bone-anchored prostheses. Method The proposed evaluation framework to determine the benefit and harms of bone-anchored prostheses for individuals with limb loss was extracted from a systematic review of the literature including seminal studies focusing on clinical benefits and safety of procedures involving screw-type implant (e.g., OPRA) and press-fit fixations (e.g., EEFT, ILP, OPL). [1-64] Results The literature review highlighted that a standard and replicable evaluation framework should focus on: • The clinical benefits with a systematic recording of health-related quality of life (e.g., SF-26, Q-TFA), mobility predictor (e.g., AMPRO), ambulation abilities (e.g., TUG, 6MWT), walking abilities (e.g., characteristic spatio-temporal) and actual activity level at baseline and follow-up post Stage 2 surgery, • The potential harms with systematic recording of residuum care, infection, implant stability, implant integrity, injuries (e.g., falls) after Stage 1 surgery. There was a general consensus around the instruments to monitor most of the benefits and harms. The benefits could be assessed using a wide spectrum of complementary assessments ranging from subjective patient self-reporting to objective measurements of physical activity. However, this latter was assessed using a broad range of measurements (e.g., pedometer, load cell, energy consumption). More importantly, the lack of consistent grading of infections was sufficiently noticeable to impede cross-fixation comparisons. Clearly, a more universal grading system is needed. Conclusions Investigators are encouraged to implement an evaluation framework featuring the domains and instruments proposed above using a single database to facilitate robust prospective studies about potential benefits and harms of their procedure. This work is also a milestone in the development of national and international clinical outcome registries.

A 16-Gene Signature Distinguishes Anaplastic Astrocytoma from Glioblastoma

Anaplastic astrocytoma (AA; Grade III) and glioblastoma (GBM; Grade IV) are diffusely infiltrating tumors and are called malignant astrocytomas. The treatment regimen and prognosis are distinctly different between anaplastic astrocytoma and glioblastoma patients. Although histopathology based current grading system is well accepted and largely reproducible, intratumoral histologic variations often lead to difficulties in classification of malignant astrocytoma samples. In order to obtain a more robust molecular classifier, we analysed RT-qPCR expression data of 175 differentially regulated genes across astrocytoma using Prediction Analysis of Microarrays (PAM) and found the most discriminatory 16-gene expression signature for the classification of anaplastic astrocytoma and glioblastoma. The 16-gene signature obtained in the training set was validated in the test set with diagnostic accuracy of 89%. Additionally, validation of the 16-gene signature in multiple independent cohorts revealed that the signature predicted anaplastic astrocytoma and glioblastoma samples with accuracy rates of 99%, 88%, and 92% in TCGA, GSE1993 and GSE4422 datasets, respectively. The protein-protein interaction network and pathway analysis suggested that the 16-genes of the signature identified epithelial-mesenchymal transition (EMT) pathway as the most differentially regulated pathway in glioblastoma compared to anaplastic astrocytoma. In addition to identifying 16 gene classification signature, we also demonstrated that genes involved in epithelial-mesenchymal transition may play an important role in distinguishing glioblastoma from anaplastic astrocytoma.

Subcutaneous fat composition of youthful and mature Canadian beef: emphasis on individual conjugated linoleic acid and trans-18:1 isomers

[EN]A comprehensive evaluation of the fatty acid composition of subcutaneous adipose tissue from beef cattle produced in western Canada was undertaken to determine if the current Canadian grading system is able to distinguish classes of animals with value added potential due to their fatty acid composition. Grades included youthful Canadian Yield Grade 1 A/AA beef, under (YUTM) and over (YOTM) 30 mo of age and the four mature grades (D1, D2, D2 and D4). Subcutaneous fat between the 12th and 13th ribs over the longissimus muscle was obtained from 18_21 animals per grade. Fatty acids were analyzed using a combination of silver-ion HPLC and GC with a highly polar 100 m column. There were no differences in total trans-18:1 content amongst grades, but adipose tissue from grade D1, D2 and D4 had more 11t-18:1 than YUTM (PB0.05), whereas adipose tissue from YUTM carcasses had more 10t-18:1 than all other grades (PB0.05). Adipose tissue from YUTM carcasses also had less total CLA (PB0.05) than the D grades, mainly due to a lower level of 9c,11t-CLA, but they had slightly more 7t,9c-CLA and 10t,12c-CLA (PB0.05). Adipose tissue from YOTM and D grades contained more n-3 fatty acids relative to YUTM (0.56% vs. 0.29%; PB0.05) and lower n-6:n-3 ratios (PB0.05). Overall, older animals (YOTM and D grades) had adipose tissue compositions with higher levels of fatty acids with reported health benefits. Taken together, these higher levels may provide opportunities for value added marketing if regulatory authorities allow claims for their enrichment based on demonstrated health benefits. Higher concentrations of beneficial fatty acids, however, need to be considered within the context of the complete fatty acid profile and it would be important to demonstrate their advantages in the presence of relatively high levels of saturated fatty acids.

Estudio de la trabeculectomía experimental mediante implante de PLGA como dispositivo de liberación controlada de fármacos

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Central area redd project [Ribble, Hodder and Lune catchments]

Redd counting is an integral part of most Fishery Officers duties. The number and distribution of salmonid redds throughout salmonid catchments provides invaluable information on the range and extent of spawning by both salmon and sea trout. A project was initiated by the Fisheries Science and Management Team of Central Area, North West Region in England in liaison with the Flood Defence function. The main objective of this project was to assess redd count data for Central Area and attempt to quantify these data in order to produce a grading system that would highlight key salmonid spawning areas. By showing which were the main areas for salmon and sea trout spawning, better informed decisions could be made on whether or not in-stream Flood Defence works should be given the go-ahead. The main salmonid catchments in Central Area were broken into individual reaches, approximately 1 km in length. The number of redds in these individual reaches were then calculated and a density per lkm value was obtained for each reach. A grading system was devised which involved looking at the range of density per km values and dividing this by five to produce 5 classes, A - E. A sixth class (F) was used where the density per Ion value was 0.00. This grading system was calculated at two levels of detail. Grades for salmon and sea trout were produced for each individual catchment and also on an Area-wide level. Maps were produced using a range of colours to represent the grade for each reach. These maps provide a highly useful overview of the status of salmonid spawning for each catchment over individual years and highlight the key salmon and sea trout spawning areas in each catchment. These maps and the associated summary data should now provide Flood Defence and Fisheries staff with a fairly detailed overview of the status of spawning in any location within the. main salmonid catchments in Central Area. Although these maps are very useful they should only be used as a guide. The current practice of consulting with the local Fishery Officer should be continued to ensure that expert local knowledge is taken into account.