An AI based, open access screening tool for early diagnosis of Burkitt lymphoma

Burkitt Lymphoma (BL) is a highly treatable cancer. However, delayed diagnosis of BL contributes to high mortality in BL endemic regions of Africa. Lack of enough pathologists in the region is a major reason for delayed diagnosis. The work described in this paper is a proof-of-concept study to develop a targeted, open access AI tool for screening of histopathology slides in suspected BL cases. Slides were obtained from a total of 90 BL patients. 70 Tonsillectomy samples were used as controls. We fine-tuned 6 pre-trained models and evaluated the performance of all 6 models across different configurations. An ensemble-based consensus approach ensured a balanced and robust classification. The tool applies novel features to BL diagnosis including use of multiple image magnifications, thus enabling use of different magnifications of images based on the microscope/scanner available in remote clinics, composite scoring of multiple models and utilizing MIL with weak labeling and image augmentation, enabling use of relatively low sample size to achieve good performance on the inference set. The open access model allows free access to the AI tool from anywhere with an internet connection. The ultimate aim of this work is making pathology services accessible, efficient and timely in remote clinics in regions where BL is endemic. New generation of low-cost slide scanners/microscopes is expected to make slide images available immediately for the AI tool for screening and thus accelerate diagnosis by pathologists available locally or online

Imaging Long-Term Fate of Intramyocardially Implanted Mesenchymal Stem Cells in a Porcine Myocardial Infarction Model

The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [18F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [18F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33–35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC–associated [18F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [18F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI

Abstract B30: Establishment and maintenance of a PDX Core Facility

Abstract Patient Derived Xenografts (PDX) are a powerful technology with the potential to unlock key mechanisms of disease for a variety of difficult to treat cancers and cancers with no applicable laboratory models. These models have a wealth of potential applications in tumor genetics, biomarker discovery, progression of metastasis, fate of circulating tumor cells, and in drug development of novel therapies for advanced and drug-resistant tumors. While several individual laboratories can excel at establishing such models, there are challenges, both procedural and technical, which present serious obstacles for established investigators as well as new investigators without prior experience with PDX models. Therefore, for some Institutions it is preferable to designate a centralized “PDX Core” to streamline the workflow that is required for the success of such program. Here we describe and analyze the key components of a successful Academic PDX program. The PDX coordination branch carries out administrative duties to guarantee that the multiple components involved in generating PDXs are seamlessly integrated. In particular, it deals with logistical tasks including regulatory requirements (IRB, patient consent forms, IACUC), and sample accrual (patient selection, coordination with surgery schedules, specimen collection). In addition, it takes care of database maintenance and interface with clinical applications. The PDX laboratory branch meanwhile devises and implements standard operating procedures for sample processing, storage and implantation, and model maintenance, PDX characterization and distribution, and takes care of training of specialized personnel. The establishment of such centralized PDX core at MSKCC resulted in a tenfold increase in the Institution's ability to generate PDX models within a year of inception of the program. In particular, for ongoing projects, we observed an increase not just in sample accrual but also in tumor take rate. In addition, the number of different tumor types implanted expanded substantially, from six to over twenty. PDXs have the potential to be invaluable tools in understanding cancer and developing novel treatments. In our experience, the establishment of a centralized PDX core is both the most cost effective and efficient way for academic investigators to generate and gain access to novel, well characterized, and clinically annotated PDX models. Citation Format: Marissa Mattar, Rajesh K. Uthamanthil, Elisa de Stanchina. Establishment and maintenance of a PDX Core Facility. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr B30.</jats:p

Novel Antiseptic Urinary Catheters for Prevention of Urinary Tract Infections: Correlation of In Vivo and In Vitro Test Results▿

Urinary catheters are widely used for hospitalized patients and are often associated with high rates of urinary tract infection. We evaluated in vitro the antiadherence activity of a novel antiseptic Gendine-coated urinary catheter against several multidrug-resistant bacteria. Gendine-coated urinary catheters were compared to silver hydrogel-coated Foley catheters and uncoated catheters. Bacterial biofilm formation was assessed by quantitative culture and scanning electron microscopy. These data were further correlated to an in vivo rabbit model. We challenged 31 rabbits daily for 4 days by inoculating the urethral meatus with 1.0 × 109 CFU streptomycin-resistant Escherichia coli per day. In vitro, Gendine-coated urinary catheters reduced the CFU of all organisms tested for biofilm adherence compared with uncoated and silver hydrogel-coated catheters (P < 0.004). Scanning electron microscopy analysis showed that a thick biofilm overlaid the control catheter and the silver hydrogel-coated catheters but not the Gendine-coated urinary catheter. Similar results were found with the rabbit model. Bacteriuria was present in 60% of rabbits with uncoated catheters and 71% of those with silver hydrogel-coated catheters (P < 0.01) but not in those with Gendine-coated urinary catheters. No rabbits with Gendine-coated urinary catheters had invasive bladder infections. Histopathologic assessment revealed no differences in toxicity or staining. Gendine-coated urinary catheters were more efficacious in preventing catheter-associated colonization and urinary tract infections than were silver hydrogel-coated Foley catheters and uncoated catheters