An Innovative Neural Network Framework for Glomerulus Classification Based on Morphological and Texture Features Evaluated in Histological Images of Kidney Biopsy

Medical Imaging Computer Aided Diagnosis (CAD) systems could support physicians in several fields and recently are also applied in histopathology. The goal of this work is to design and test a novel CAD system module for the discrimination between glomeruli with a sclerotic and non-sclerotic condition, through the elaboration of histological images. The dataset was constituted by 26 kidney biopsies coming from 19 donors with Periodic Acid Schiff (PAS) staining. Preparation, digital acquisition and glomeruli annotations have been conducted by experts from the Department of Emergency and Organ Transplantation (DETO) of the University of Bari Aldo Moro (Italy). Starting from the annotated Regions Of Interest (ROIs), several feature extraction techniques were evaluated. Feature reduction and shallow artificial neural network were used for discriminating between the glomeruli classes. The mean and the best performances of the best ANN architecture were evaluated on an independent dataset. Metric comparison and analysis were performed to face the unbalanced dataset problem. Results on the test set asses that the proposed workflow, from the feature extraction to the supervised ANN approach, is consistent and reveals good performance in discriminating sclerotic and non-sclerotic glomeruli

A neural network for glomerulus classification based on histological images of kidney biopsy

Background: Computer-aided diagnosis (CAD) systems based on medical images could support physicians in the decision-making process. During the last decades, researchers have proposed CAD systems in several medical domains achieving promising results. CAD systems play an important role in digital pathology supporting pathologists in analyzing biopsy slides by means of standardized and objective workflows. In the proposed work, we designed and tested a novel CAD system module based on image processing techniques and machine learning, whose objective was to classify the condition affecting renal corpuscles (glomeruli) between sclerotic and non-sclerotic. Such discrimination is useful for the biopsy slides evaluation performed by pathologists. Results: We collected 26 digital slides taken from the kidneys of 19 donors with Periodic Acid-Schiff staining. Expert pathologists have conducted the slides preparation, digital acquisition and glomeruli annotations. Before setting the classifiers, we evaluated several feature extraction techniques from the annotated regions. Then, a feature reduction procedure followed by a shallow artificial neural network allowed discriminating between the glomeruli classes. We evaluated the workflow considering an independent dataset (i.e., processing images not used in the training procedure). Ten independent runs of the training algorithm, and evaluation, allowed achieving MCC and Accuracy of 0.95 (± 0.01) and 0.99 (standard deviation < 0.00), respectively. We also obtained good precision (0.9844 ± 0.0111) and recall (0.9310 ± 0.0153). Conclusions: Results on the test set confirm that the proposed workflow is consistent and reliable for the investigated domain, and it can support the clinical practice of discriminating the two classes of glomeruli. Analyses on misclassifications show that the involved images are usually affected by staining artefacts or present partial sections due to slice preparation and staining processes. In clinical practice, however, pathologists discard images showing such artefacts

Polymyxin B Hemoperfusion in Clinical Practice: The Picture from an Unbound Collaborative Registry

After the publication of the EUPHAS trial, the clinical use of polymyxin B hemoperfusion (Toraymyxin®) increased significantly in Italy. Nevertheless, no structured data collections have been carried out to underline the characteristics of treated patients. Therefore, a collaborative registry of clinical data was promoted among users in order to better define the structure of the prospective data collection named the EUPHAS2 project. Neither inclusion criteria nor therapeutic constraints were imposed, highlighting adherence to clinical evidence provided by previous randomized controlled trials, and also unusual or borderline practice in the selection of patients for polymyxin B-based cartridges (PMX-DHP). This first retrospective phase of data collection included patients with severe sepsis and septic shock treated with Toraymyxin over the last 3 years, up to July 2013. Thirty-one hospitals participated in the EUPHAS2 study, collecting data on 306 patients. Enrolled patients were grouped according to the main source of sepsis: abdominal (41.8%) and nonabdominal (58.2%). The abdominal patients had characteristics well matching those selected for the EUPHAS randomized controlled trial in terms of time-to-enrolment, severity of the illness, 28-day mortality and in-hospital mortality. Their 28-day mortality rate was 35% with a significant reduction of the Sequential Organ Failure Assessment Score (SOFA) score after 72 h of treatment (p < 0.001). Patients with nonabdominal sepsis were heterogeneous and only a few of them had their endotoxin activity tested in a manner not allowing a reliable evaluation of the real efficacy of the treatment and organ dysfunction control. Their 28-day mortality rate was 49% and the SOFA score did not significantly change before and after treatment. In conclusion, clinical experience confirms the results of the original EUPHAS randomized trial in terms of outcome for patients with abdominal severe sepsis. Specific studies focused on a population of patients with Gram-negative infections of nonabdominal origin are needed before recommending treatment with Toraymyxin as an effective therapy

Polymyxin-B hemoperfusion in septic patients: analysis of a multicenter registry

Background: In 2010, the EUPHAS 2 collaborative group created a registry with the purpose of recording data from critically ill patients suffering from severe sepsis and septic shock treated with polymyxin-B hemoperfusion (PMX-HP) for endotoxin removal. The aim of the registry was to verify the application of PMX-HP in the daily clinical practice. Methods: The EUPHAS 2 registry involved 57 centers between January 2010 and December 2014, collecting retrospective data of 357 patients (297 in Europe and 60 in Asia) suffering from severe sepsis and septic shock caused by proved or suspected infection related to Gram negative bacteria. All patients received atleast one cycle of extracorporeal endotoxin removal by PMX-HP. Results: Septic shock was diagnosed in 305 (85.4\ua0%) patients. The most common source of infection was abdominal (44.0\ua0%) followed by pulmonary (17.6\ua0%). Gram negative bacteria represented 60.6\ua0% of the pathogens responsible of infection. After 72\ua0h from the first cycle of PMX-HP, some of the SOFA score components significantly improved with respect to baseline: cardiovascular (2.16\ua0\ub1\ua01.77 from 3.32\ua0\ub1\ua01.29, p\ua0<\ua00.0001), respiratory (1.95\ua0\ub1\ua00.95 from 2.40\ua0\ub1\ua01.06, p\ua0<\ua00.001) and renal (1.84\ua0\ub1\ua01.77 from 2.23\ua0\ub1\ua01.62, p\ua0=\ua00.013). Overall 28-day survival rate was 54.5\ua0% (60.4\ua0% in abdominal and 47.5\ua0% in pulmonary infection). Patients with abdominal infection treated with PMX-HP within 24\ua0h from the diagnosis of septic shock had a 28-day survival rate of 64.5\ua0%. Patients showing a significantly cardiovascular improvement after PMX-HP had a 28-survival rate of 75\ua0% in comparison to the 39\ua0% of patients who did not (p\ua0<\ua00.001). Cox regression analysis found the variation of cardiovascular, respiratory and coagulation SOFA to be independent covariates for 28-day survival. In European patients were observed a higher 28-day (58.8 vs. 34.5\ua0%, p\ua0=\ua00.003), ICU (59 vs. 36.7\ua0%, p\ua0=\ua00.006) and hospital survival rate (53.2 vs. 35\ua0%, p\ua0=\ua00.02) than in Asian patients. However, the two populations were highly heterogeneous in terms of source of infection and severity scores at admission. Conclusion: The EUPHAS 2 is the largest registry conducted outside Japan on the clinical use of PMX-HP in septic patients. Data analysis confirmed the feasibility of PMX-HP to treat septic patients in daily clinical practice, showing clinical benefits associated with endotoxin removal without significant adverse events related to the extracorporeal technique. \ua9 2016, The Author(s)

Polymyxin-B hemoperfusion in septic patients: analysis of a multicenter registry

Background: In 2010, the EUPHAS 2 collaborative group created a registry with the purpose of recording data from critically ill patients suffering from severe sepsis and septic shock treated with polymyxin-B hemoperfusion (PMX-HP) for endotoxin removal. The aim of the registry was to verify the application of PMX-HP in the daily clinical practice. Methods: The EUPHAS 2 registry involved 57 centers between January 2010 and December 2014, collecting retrospective data of 357 patients (297 in Europe and 60 in Asia) suffering from severe sepsis and septic shock caused by proved or suspected infection related to Gram negative bacteria. All patients received atleast one cycle of extracorporeal endotoxin removal by PMX-HP. Results: Septic shock was diagnosed in 305 (85.4&nbsp;%) patients. The most common source of infection was abdominal (44.0&nbsp;%) followed by pulmonary (17.6&nbsp;%). Gram negative bacteria represented 60.6&nbsp;% of the pathogens responsible of infection. After 72&nbsp;h from the first cycle of PMX-HP, some of the SOFA score components significantly improved with respect to baseline: cardiovascular (2.16&nbsp;\ub1&nbsp;1.77 from 3.32&nbsp;\ub1&nbsp;1.29, p&nbsp;&lt;&nbsp;0.0001), respiratory (1.95&nbsp;\ub1&nbsp;0.95 from 2.40&nbsp;\ub1&nbsp;1.06, p&nbsp;&lt;&nbsp;0.001) and renal (1.84&nbsp;\ub1&nbsp;1.77 from 2.23&nbsp;\ub1&nbsp;1.62, p&nbsp;=&nbsp;0.013). Overall 28-day survival rate was 54.5&nbsp;% (60.4&nbsp;% in abdominal and 47.5&nbsp;% in pulmonary infection). Patients with abdominal infection treated with PMX-HP within 24&nbsp;h from the diagnosis of septic shock had a 28-day survival rate of 64.5&nbsp;%. Patients showing a significantly cardiovascular improvement after PMX-HP had a 28-survival rate of 75&nbsp;% in comparison to the 39&nbsp;% of patients who did not (p&nbsp;&lt;&nbsp;0.001). Cox regression analysis found the variation of cardiovascular, respiratory and coagulation SOFA to be independent covariates for 28-day survival. In European patients were observed a higher 28-day (58.8 vs. 34.5&nbsp;%, p&nbsp;=&nbsp;0.003), ICU (59 vs. 36.7&nbsp;%, p&nbsp;=&nbsp;0.006) and hospital survival rate (53.2 vs. 35&nbsp;%, p&nbsp;=&nbsp;0.02) than in Asian patients. However, the two populations were highly heterogeneous in terms of source of infection and severity scores at admission. Conclusion: The EUPHAS 2 is the largest registry conducted outside Japan on the clinical use of PMX-HP in septic patients. Data analysis confirmed the feasibility of PMX-HP to treat septic patients in daily clinical practice, showing clinical benefits associated with endotoxin removal without significant adverse events related to the extracorporeal technique