Evaluation of A Computer-Aided Detection Software for Prostate Cancer Prediction: Excellent Diagnostic Accuracy Independent of Preanalytical Factors.

Prostate cancer (PCa) is the most common noncutaneous cancer in men in the Western world. In addition to accurate diagnosis, Gleason grading and tumor volume estimates are critical for patient management. Computer-aided detection (CADe) software can be used to facilitate the diagnosis and improve the diagnostic accuracy and reporting consistency. However, preanalytical factors such as fixation and staining of prostate biopsy specimens and whole slide images (WSI) on scanners can vary significantly between pathology laboratories and may, therefore, impact the quality of WSI and utility of CADe algorithms. We evaluated the performance of a CADe software in predicting PCa on WSIs of prostate biopsy specimens and focused on whether there were any significant differences in image quality between WSIs obtained on different scanners and specimens from different histopathology laboratories. Thirty prostate biopsy specimens from 2 histopathology laboratories in the United States were included in this study. The hematoxylin and eosin slides of the biopsy specimens were scanned on 3 scanners, generating 90 WSIs. These WSIs were then analyzed using a CADe software (INIFY Prostate, Algorithm), which identified and annotated all areas suspicious for PCa and calculated the tumor volume (percentage area of the biopsy core involved). Study pathologists then reviewed the Algorithm's annotations and tumor volume calculation to confirm the diagnosis and identify benign glands that were misclassified as cancer (false positive) and cancer glands that were misclassified as benign (false negative). The CADe software worked equally well on WSIs from all 3 scanners and from both laboratories, with similar sensitivity and specificity. The overall sensitivity was 99.4%, and specificity was 97%. The percentage of suspicious cancer areas calculated by the Algorithm was similar for all 3 scanners. For WSIs with small foci of cancer (<1 mm), the Algorithm identified all cancer glands (sensitivity, 100%). Preanalytical factors had no significant impact on whole slide imaging and subsequent application of a CADe software. Prediction accuracy could potentially be further improved by processing biopsy specimens in a centralized histology laboratory and training the Algorithm on WSIs from the same laboratory in order to minimize variations in preanalytical factors and optimize the diagnostic performance of the Algorithm.

Blood compatibility of widely used central venous catheters; an experimental study.

An inserted central venous catheter (CVC) is considered foreign material by the inert host defence systems and induce inflammation and thrombus formation. The objective of this study was to evaluate blood compatibility of six commonly used CVCs. Three coated and three uncoated CVC materials were tested in a modified Chandler loop model. Each catheter material circulated in blood from ten different healthy volunteers for 1 h. Blood cell counts and measurements of the inert host defence systems were performed on blood samples from the loop. All the tested catheters demonstrated impact on blood cells, contact coagulation, the complement system, or inflammatory markers, although the impact varied significantly. Of the catheters we evaluated, the most unfavourable blood compatibility profile was found for the polyurethane CVC coated with chlorohexidine and silver sulfadiazine. The greatest variation in blood compatibility between test runs was noted for the silicone dialysis catheter. Poor blood compatibility should be taken seriously but given the experimental design of the current study the clinical significance remains to be evaluated.

Long-term use of noble metal alloy coated urinary catheters reduces recurrent CAUTI and decreases proinflammatory markers.

BACKGROUND: The objective of this study was to investigate a case of a permanently (suprapubic) catheterized woman with neurogenic bladder dysfunction. The patient had suffered from recurrent catheter-associated urinary tract infections (CAUTIs) since 2009, despite several prevention approaches and attempts. In 2013, the patient's catheter was substituted for the BIP Foley Catheter, coated with a noble metal alloy (NMA) of gold, silver, and palladium. METHOD: This is a retrospective-prospective clinical case study covering 4 years history for the control catheters and up to 2.5 years for the anti-infective BIP Foley Catheter. CAUTI incidences, symptoms, antibiotics, catheter performance, and comfort were evaluated. Levels of proinflammatory cytokines were measured pre- and post-substitution to BIP Foley Catheter in urine of the case and of four other permanently catheterized patients. In addition, the levels of noble metals were assessed in urine of the case subject during use of the BIP Foley Catheter. RESULTS: While using control catheters, the patient experienced symptomatic CAUTIs requiring antibiotics almost every month for 4 years. After 1 month with the BIP Foley Catheter, the symptoms disappeared, and the patient remained free of symptomatic CAUTIs and antibiotic treatment for the following 2.5 years, despite bacteriuria. The patient was satisfied with the comfort during insertion, use, and removal of the BIP Foley Catheter. Urinary levels of the proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNFα) decreased towards normal levels post catheter type substitution. Traces of noble metals detected in a few urine samples were ⩽4% of the permitted daily exposure. The levels of the noble metals gold, silver, and palladium remaining on the BIP Foley Catheter after use were the same as for unused catheters. CONCLUSION: Long-term use of a NMA-coated catheter was associated with cessation of frequent CAUTIs. The catheter was experienced as comfortable and inflammatory markers were reduced with time. The coating was stable, with no significant metal release into urine and is therefore safe for patient use.

Evaluation of central venous catheters coated with a noble metal alloy-A randomized clinical pilot study of coating durability, performance and tolerability.

The use of Central Venous Catheters (CVCs) commonly results in complications. Coatings with silver or metal alloys can reduce the risk associated with the use of CVC. We have evaluated the durability of a noble metal coated CVC (the Bactiguard Infectious Protection, BIP CVC) and compared with an uncoated CVC for clinical tolerability (Adverse Events, AEs) and performance, in order to create a baseline for a large future study. Patients undergoing major surgery, randomised at a 2:1 ratio to BIP CVC (n = 22) or standard CVC (n = 12), were catheterized 9 - 12 days, respectively. Adverse events, microbial colonization and metal release were measured. FINDINGS: There were no AEs in the BIP CVC-group, but 5 AEs occurred in 4 patients (1 patient had 2 AEs) in the standard CVC-group, p = 0.011 (whereof 3 were catheter related). The BIP CVC showed an initial release of coating metals in blood (gold, silver and palladium), which rapidly decreased and were far below Permitted Paily Exposure (PDE) for chronical use. The levels of silver concentration were far below those needed to develop microbial resistance. The performance was equal, and there was no difference concerning microbial colonization, for the two CVCs. CONCLUSION: In this pilot study the BIP CVC had significantly lower AEs and showed a comparable performance to the standard CVC. The coating was durable throughout the study length (up to 16 days) and toxicological evaluation showed good safety margins. Larger studies are needed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2337-2344, 2018.

Improved ex vivo blood compatibility of central venous catheter with noble metal alloy coating.

Central line associated bloodstream infections (CLABSIs) are a serious cause of morbidity and mortality induced by the use of central venous catheters (CVCs). Nobel metal alloy (NMA) coating is an advanced surface modification that prevents microbial adhesion and growth on catheters and thereby reduces the risk of infection. In vitro microbiological analyses have shown up to 90% reduction in microbial adhesion on coated CVC compared to uncoated ones. This study aimed to assess the blood compatibility of NMA-coated CVC according to ISO 10993-4. Hemolysis, thrombin-antithrombin (TAT) complex, platelet counts, fibrin deposition, and C3a and SC5b-9 complement activation were analyzed in human blood exposed to the NMA-coated and control CVCs using a Chandler-loop model. NMA-coated CVC did not induce hemolysis and fell in the "nonhemolytic" category according to ASTM F756-00. Significantly lower amounts of TAT were generated and less fibrin was deposited on NMA-coated CVC than on uncoated ones. Slightly higher platelet counts and lower complement markers were observed for NMA-coated CVC compared to uncoated ones. These data suggest that the NMA-coated CVC has better ex vivo blood compatibility compared to uncoated CVC. © 2015 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1359-1365, 2016.

Tolerability and performance of BIP endotracheal tubes with noble metal alloy coating--a randomized clinical evaluation study.

BACKGROUND: Hospital acquired infections worsen the outcome of patients treated in intensive care units and are costly. Coatings with silver or metal alloys may reduce or alter the formation of biofilm on invasive medical devices. An endotracheal tube (ETT) is used to connect the patient to a ventilator and coated tubes have been tested in relation to bacterial colonization and respiratory infection. In the present study, we aimed to evaluate and compare a coated and uncoated ETT for patient symptoms and local tracheal tolerability during short term clinical use. Degree of bacterial colonization was also described. METHODS: A silver-palladium-gold alloy coating ('Bactiguard®'Infection Protection, BIP) has been extensively used on urinary tract catheters and lately also on central venous catheters. We performed a randomised, single-blinded, controlled, first in man, post Conformité Européenne (EC) certification and CE marking study, focused on Bactiguard® coated ETTs (BIP ETT). Thirty patients at a tertiary university hospital scheduled for upper abdominal elective surgery with an expected duration of anaesthesia of at least 3 h were randomised; BIP ETT (n = 20) or standard ETT (n = 10). The tolerability was assessed with a modified version of Quality of Life Head and Neck Module, QLQ-H&N35 and by inspection of the tracheal mucosa with a fibre-optic bronchoscope before intubation and at extubation. Adverse Events (AE) and bacterial adherence were also studied. Statistical evaluations were carried out with the Fisher's Exact Test, the Clopper-Pearson method, as well as a Proportional Odds Model. RESULTS: Differences between groups were identified in 2 of 8 patient related symptoms with regard to tolerability by QLQ-H&N35 (cough, p = 0.022 and dry mouth, p = 0.014 in the treatment group.). No mucosal damage was identified with bronchoscopy. A low level of bacterial colonization with normal flora, equal between groups, was seen after short-term of intubation (median 5 h). No serious Adverse Events related to the use of an ETT were observed. The results should be treated with caution due to statistical confounders, a small study size and large inter-individual variability in bacterial adhesion. CONCLUSIONS: The new device BIP ETT is well tolerated and has good clinical performance during short-term intubation. Studies with larger sample sizes and longer intubation periods (>24 h) in the ICU-setting are needed and can now be planned in order to identify possible differences in clinical outcomes. TRIAL REGISTRATION: Registered in ClinicalTrials.gov, REGISTRATION NUMBER: NCT01682486 , Date of Registration: August, 30, 2012.