Augmented Features Synergize Radiomics in Post-Operative Survival Prediction and Adjuvant Therapy Recommendation for Non-Small Cell Lung Cancer.

BACKGROUND: Owing to the cytotoxic effect, it is challenging for clinicians to decide whether post-operative adjuvant therapy is appropriate for a non-small cell lung cancer (NSCLC) patient. Radiomics has proven its promising ability in predicting survival but research on its actionable model, particularly for supporting the decision of adjuvant therapy, is limited. METHODS: Pre-operative contrast-enhanced CT images of 123 NSCLC cases were collected, including 76, 13, 16, and 18 cases from R01 and AMC cohorts of The Cancer Imaging Archive (TCIA), Jiangxi Cancer Hospital and Guangdong Provincial People's Hospital respectively. From each tumor region, 851 radiomic features were extracted and two augmented features were derived therewith to estimate the likelihood of adjuvant therapy. Both Cox regression and machine learning models with the selected main and interaction effects of 853 features were trained using 76 cases from R01 cohort, and their test performances on survival prediction were compared using 47 cases from the AMC cohort and two hospitals. For those cases where adjuvant therapy was unnecessary, recommendations on adjuvant therapy were made again by the outperforming model and compared with those by IBM Watson for Oncology (WFO). RESULTS: The Cox model outperformed the machine learning model in predicting survival on the test set (C-Index: 0.765 vs. 0.675). The Cox model consists of 5 predictors, interestingly 4 of which are interactions with augmented features facilitating the modulation of adjuvant therapy option. While WFO recommended no adjuvant therapy for only 13.6% of cases that received unnecessary adjuvant therapy, the same recommendations by the identified Cox model were extended to 54.5% of cases (McNemar's test p = 0.0003). CONCLUSIONS: A Cox model with radiomic and augmented features could predict survival accurately and support the decision of adjuvant therapy for bettering the benefit of NSCLC patients.

Developing optimized automated rule sets for reporting hemolysis, icterus and lipemia based on a priori outcomes analysis.

BACKGROUND: There is limited information about the effects of instituting CLSI Document C56A recommended workflows for the automated detection of hemolysis, lipemia and icterus (HIL) in different clinical laboratories and patient populations. We describe a process to develop and tailor automated reporting rules that are appropriate for the local laboratory population. METHODS: Automated decision algorithms were generated and applied to 2 high volume labs serving community and hospital populations. Proposed rules were applied to the datasets offline to predict the outcomes, and then were further optimized prior to implementation. RESULTS: Introduction of automated serum indices decreased HIL flagging compared to manual flagging. Hemolysis flagging was the greatest in all 3 patient populations, and was successfully reduced for LD, CK and AST by optimized rules that incorporated both the H-index result and the analyte result. Changes in flagging rates were also patient population specific, particularly for icterus which was a problem in hospitalized populations but not in the community. Overall, concordance between manual and automated flagging methods was very low in both laboratories. CONCLUSIONS: We demonstrate that flagging algorithms may not be universally transferable due to lab specific and population specific factors and demonstrate the benefits of local, a priori testing of algorithms prior to implementation.

Generation of lung adenocarcinoma DNA aptamers for cancer studies.

Lung cancer is the most lethal malignancy in the world, and each year thousands of people die from this disease. Early detection has proven to increase the 5-year survival for this cancer in general, independent of the origination site in the lung. To address this challenge, we have used cell-based SELEX (Systematic Evolution of Ligands by Exponential Enrichment) to select a panel of aptamers capable of distinguishing lung adenocarcinoma cells from normal lung epithelial cells. These aptamers bind at physiological and formalin-fixed conditions and display affinity for their targets with apparent K(d')s in the nanomolar range. Our findings suggest that the selected aptamers have the potential to be used in clinical settings, as well as to improve classification of nonsurgical specimens, another current challenge in lung cancer.

Fistula between right coronary artery vein graft and right atrium as an immediate complication of percutaneous coronary intervention.

Fistula between saphenous vein graft (SVG) and a cardiac chamber or structure is a rare complication after coronary artery bypass grafting (CABG). We report the first case of a fistula between SVG and the right atrium (RA) as an immediate complication after a percutaneous coronary intervention (PCI) in an 86-year-old female. She presented with inferior ST-elevation myocardial infarction (STEMI) and was treated with thrombolytic therapy in a peripheral hospital, which was unsuccessful. PCI to SVG to the right coronary (RCA) was complicated by a fistula to RA. Cardiac magnetic resonance (CMR) confirmed the site of the fistula and also presence of a significant arteriovenous (AV) shunt. Reversal of anticoagulation had no effect on fistula closure. Therefore, a covered stent was deployed for closure of the fistula to avoid long-term complications of the significant AV shunt. In summary, the diagnosis and appropriate management of this rare complication is challenging, but excellent result can be achieved by the use of appropriate percutaneous techniques.

Retrograde recanalization of chronic total occlusions from the transradial approach; early Canadian experience.

BACKGROUND: Retrograde approach for chronic total occlusions (CTO) improves recanalization success rates. Eight French (Fr) catheters and the femoral approach are advocated. OBJECTIVES: Evaluate whether transradial operators can achieve similar success rates using smaller catheters. METHODS: This is a single-operator series of 42 consecutive cases performed between January and December 2010, including 13 while demonstrating CTO recanalization. Patients were referred because of complexity of the CTO or after failed attempt. RESULTS: Most frequent indications for recanalization were CCS 3-4 angina (52%) and CCS 1-2 in 21%. Eighteen (43%) patients underwent previous failed attempts. CTO was in the right coronary in 74%, left anterior descending in 24%, and a left main in 1. Most lesions (88%) were ≥20 mm long and 52% were calcified. We used septal collateral channels (CC) in 33 (79%), epicardial CC in 8 (20%), and a saphenous vein graft in one case. Radial access was used in all patients and was bilateral in 37 (88%). Five cases required one radial and one femoral access. Six French guides were used in 91% for the retrograde side and 71% for the antegrade side. Otherwise, 7 Fr guides were used. The Corsair(®) was used in 38 (90%). Procedural success was achieved in 37 (88%), mostly using reverse controlled antegrade-retrograde tracking (60%) or retrograde crossing (29%). The average <24-h Hb drop was 0.75 ± 0.84 g/dl. No in-hospital major cardiac events occurred. CONCLUSION: Transradial retrograde CTO recanalization is feasible, safe, and still associated with high success rates despite the use of smaller guide catheters.

A rare and late angiographic presentation of DES fracture.

The drug-eluting stent (DES) era has seen an increasing number of stent fractures, which is considered one of the mechanisms of restenosis in DES. This increase in recognition could be due to various factors such as increased diagnosis compared to the bare-metal stent era, platform design and strut thickness, higher inflation pressures for DES deployment, and use of DES in more complex lesions (e.g., angulated, diffuse, calcified, bifurcated). The angiographic presentation of DES fracture has been reported as in-stent restenosis (either symptomatic or asymptomatic) in all published cases. We discuss a case of DES fracture presented as an ST-elevation myocardial infarction that was associated with a large coronary artery aneurysm.

Molecular recognition of small-cell lung cancer cells using aptamers.

Early diagnosis is the way to improve the rate of lung cancer survival, but is almost impossible today due to the lack of molecular probes that recognize lung cancer cells sensitively and selectively. We developed a new aptamer approach for the recognition of specific small-cell lung cancer (SCLC) cell-surface molecular markers. Our approach relies on cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX) to evolve aptamers for whole live cells that express a variety of surface markers representing molecular differences among cancer cells. When applied to different lung cancer cells including those from patient samples, these aptamers bind to SCLC cells with high affinity and specificity in various assay formats. When conjugated with magnetic and fluorescent nanoparticles, the aptamer nanoconjugates could effectively extract SCLC cells from mixed cell media for isolation, enrichment, and sensitive detection. These studies demonstrate the potential of the aptamer approach for early lung cancer detection.

Successful treatment of trifurcation and quadrifurcation lesions using a minimal protrusion balloon crush technique.

Percutaneous treatment of coronary bifurcation lesions remains a challenging aspect of interventional cardiology, but the approach to trifurcation and quadrifurcation lesions can be considered "double jeopardy." We describe two cases of trifurcation and one case of quadrifurcation that were treated percutaneously using a "minimal protrusion balloon crush technique." Immediate and long-term results were favorable with this approach.

Selection of aptamers for molecular recognition and characterization of cancer cells.

In this paper, we describe a new way to generate molecular probes for specific recognition of cancer cells. Molecular medicine will require a large number of probes for molecular recognition and characterization of a variety of diseased cells. Aptamers, single-stranded DNA/RNA probes, are poised to become a chemist's antibody and have the potential to serve as molecular probes for a variety of biomedical applications. By applying newly developed cell-SELEX (cell-based systematic evolution of ligands by exponential enrichment) against whole living cells, panels of aptamers have been evolved from an initial DNA library to characterize target cells at the molecular level. Ramos cells, a B-cell lymphoma cell line, were used as target cells for the generation of effective molecular probes. By taking advantages of the repetitive and broad enrichment strategy, the selected aptamers could bind to target cells and other closely related cell lines in variant patterns with an equilibrium dissociation constant (Kd) in the nanomolar range. Some aptamers could also specifically recognize the target lymphoma cells mixed with normal human bone marrow aspirates. The cell-based SELEX is simple, fast, and robust. The strategies used here will be highly useful for aptamer selection against complex target samples in order to generate a large number of aptamers in a variety of biomedical and biotechnological applications, paving the way for molecular diagnosis, therapy, and biomarker discovery.

Aptamers evolved from live cells as effective molecular probes for cancer study.

Using cell-based aptamer selection, we have developed a strategy to use the differences at the molecular level between any two types of cells for the identification of molecular signatures on the surface of targeted cells. A group of aptamers have been generated for the specific recognition of leukemia cells. The selected aptamers can bind to target cells with an equilibrium dissociation constant (K(d)) in the nanomolar-to-picomolar range. The cell-based selection process is simple, fast, straightforward, and reproducible, and, most importantly, can be done without prior knowledge of target molecules. The selected aptamers can specifically recognize target leukemia cells mixed with normal human bone marrow aspirates and can also identify cancer cells closely related to the target cell line in real clinical specimens. The cell-based aptamer selection holds a great promise in developing specific molecular probes for cancer diagnosis and cancer biomarker discovery.