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Incidental findings in CT imaging of coronary artery bypass grafts: results from a Canadian multicenter prospective cohort

To assess the prevalence and clinical significance of incidental findings identified during computed tomography imaging of coronary artery bypass grafts.

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Identification of membrane-associated proteins with pathogenic potential expressed by Corynebacterium pseudotuberculosis grown in animal serum

Previous works defining antigens that might be used as vaccine targets against Corynebacterium pseudotuberculosis, which is the causative agent of sheep and goat caseous lymphadenitis, have focused on secreted pr...

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NK/T Cell Lymphoma: Updates in Therapy

Abstract

Purpose of Review

Extranodal NK/T cell lymphoma (ENKL), nasal type, is a highly aggressive lymphoma which used to show a poor clinical outcome. Expression of P-glycoprotein on lymphoma cells of ENKL is a major reason for the refractoriness to conventional chemotherapy containing anthracycline. However, recent innovative approaches have improved the outcome and prognosis of ENKL. The purpose of this review is to summarize the proceedings of treatment.

Recent Findings

Concurrent chemoradiotherapy containing platinum and several drugs including L-asparaginase, methotrexate, and alkylators shows excellent outcomes for the limited-stage ENKL. SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) or other L-asparaginase-containing therapy is promising for advanced-stage ENKL, followed by either autologous or allogeneic hematopoietic stem cell transplantation. Anti-PD-1 or other immunological checkpoint inhibitors are recently reported to be effective for relapsed/refractory ENKL thought to be due to EBV-driven upregulation of PD-L1 expression.

Summary

The prognosis of ENKL is therefore improving by the introduction of these strategies. The 5-year overall survival (OS) rate of limited stage was 63.2% [95% confidence interval (CI), 55.3 to 70.0%] before 2010, but was 79.4% (95% CI, 66.9 to 87.6%) in 2010 or after. However, there still exists a room for improvement, particularly for advanced-stage patients. The 2-year OS of advanced ENKL was 30.3% (95% CI, 19.5 to 41.7%) before 2010, but was 40.5% (95% CI, 24.8 to 55.8%) in 2010 or after. Optimal treatment scheme should further be explored.

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Cancers, Vol. 10, Pages 31: Cell-Penetrating CaCO3 Nanocrystals for Improved Transport of NVP-BEZ235 across Membrane Barrier in T-Cell Lymphoma

Cancers, Vol. 10, Pages 31: Cell-Penetrating CaCO3 Nanocrystals for Improved Transport of NVP-BEZ235 across Membrane Barrier in T-Cell Lymphoma

Cancers doi: 10.3390/cancers10020031

Authors: Viviana Vergaro Monica Civallero Cinzia Citti Maria Cosenza Francesca Baldassarre Giuseppe Cannazza Samantha Pozzi Stefano Sacchi Francesco Fanizzi Giuseppe Ciccarella

Owing to their nano-sized porous structure, CaCO3 nanocrystals (CaCO3NCs) hold the promise to be utilized as desired materials for encapsulating molecules which demonstrate wide promise in drug delivery. We evaluate the possibility to encapsulate and release NVP-BEZ235, a novel and potent dual PI3K/mTOR inhibitor that is currently in phase I/II clinical trials for advanced solid tumors, from the CaCO3NCs. Its chemical nature shows some intrinsic limitations which induce to administer high doses leading to toxicity; to overcome these problems, here we proposed a strategy to enhance its intracellular penetration and its biological activity. Pristine CaCO3 NCs biocompatibility, cell interactions and internalization in in vitro experiments on T-cell lymphoma line, were studied. Confocal microscopy was used to monitor NCs-cell interactions and cellular uptake. We have further investigated the interaction nature and release mechanism of drug loaded/released within/from the NCs using an alternative approach based on liquid chromatography coupled to mass spectrometry. Our approach provides a good loading efficiency, therefore this drug delivery system was validated for biological activity in T-cell lymphoma: the anti-proliferative test and western blot results are very interesting because the proposed nano-formulation has an efficiency higher than free drug at the same nominal concentration.

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Development and External Validation of an Automated Computer-Aided Risk Score for Predicting Sepsis in Emergency Medical Admissions Using the Patient’s First Electronically Recorded Vital Signs and Blood Test Results

Objectives: To develop a logistic regression model to predict the risk of sepsis following emergency medical admission using the patient's first, routinely collected, electronically recorded vital signs and blood test results and to validate this novel computer-aided risk of sepsis model, using data from another hospital. Design: Cross-sectional model development and external validation study reporting the C-statistic based on a validated optimized algorithm to identify sepsis and severe sepsis (including septic shock) from administrative hospital databases using International Classification of Diseases, 10th Edition, codes. Setting: Two acute hospitals (York Hospital - development data; Northern Lincolnshire and Goole Hospital - external validation data). Patients: Adult emergency medical admissions discharged over a 24-month period with vital signs and blood test results recorded at admission. Interventions: None. Main Results: The prevalence of sepsis and severe sepsis was lower in York Hospital (18.5% = 4,861/2,6247; 5.3% = 1,387/2,6247) than Northern Lincolnshire and Goole Hospital (25.1% = 7,773/30,996; 9.2% = 2,864/30,996). The mortality for sepsis (York Hospital: 14.5% = 704/4,861; Northern Lincolnshire and Goole Hospital: 11.6% = 899/7,773) was lower than the mortality for severe sepsis (York Hospital: 29.0% = 402/1,387; Northern Lincolnshire and Goole Hospital: 21.4% = 612/2,864). The C-statistic for computer-aided risk of sepsis in York Hospital (all sepsis 0.78; sepsis: 0.73; severe sepsis: 0.80) was similar in an external hospital setting (Northern Lincolnshire and Goole Hospital: all sepsis 0.79; sepsis: 0.70; severe sepsis: 0.81). A cutoff value of 0.2 gives reasonable performance. Conclusions: We have developed a novel, externally validated computer-aided risk of sepsis, with reasonably good performance for estimating the risk of sepsis for emergency medical admissions using the patient's first, electronically recorded, vital signs and blood tests results. Since computer-aided risk of sepsis places no additional data collection burden on clinicians and is automated, it may now be carefully introduced and evaluated in hospitals with sufficient informatics infrastructure. Drs. Richardson and Mohammed had the original idea for this work. Dr. Faisal, Mr. Scally, and Dr. Mohammed undertook the statistical analyses. Mr. Beatson and Howes extracted the necessary data frames. Dr. Richardson gave a clinical perspective. Drs. Faisal and Mohammed wrote the first draft of this article, and all authors subsequently assisted in redrafting and have approved the final version. Dr. Mohammed will act as guarantor. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). Supported, in part, funded by the Health Foundation. The Health Foundation is an independent charity working to improve the quality of healthcare in the United Kingdom. This research was supported by the National Institute for Health Research (NIHR) Yorkshire and Humber Patient Safety Translational Research Centre (NIHR Yorkshire and Humber PSTRC). The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. All authors' institutions received funding from the Health Foundation. Mr. Scally and Speed received support for article research from the Health Foundation. For information regarding this article, E-mail: M.A.Mohammed5@Bradford.ac.uk Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Amplification of FRS2 in atypical lipomatous tumour/well -differentiated liposarcoma and dedifferentiated liposarcoma: a clinicopathological and genetic study of 146 cases

Abstract

Aims

Fibroblast growth factor receptor substrate 2 (FRS2) is located within the 12q13-15 band. The aim of this study was to evaluate the frequency of FRS2 amplification and its relationship with the clinicopathological features of atypical lipomatous tumour (ALT)/well-differentiated liposarcoma (WDL)/dedifferentiated liposarcoma (DDL).

Methods and results

FRS2 and MDM2 fluorescence in situ hybridization (FISH) was performed on 146 tumours (70 ALT/WDLs and 76 DDLs). One hundred and eight control samples were included for FRS2 analysis. FRS2 amplification was detected in 136 of 146 (93.2%) ALT/WDL/DDLs, including 63 ALT/WDLs and 73 DDLs. A higher FRS2/CEP12 ratio was observed in DDLs than in ALT/WDLs (p=0.0005). The FRS2/CEP12 ratio of peripheral tumours was lower than that of central tumours (p=0.00004). All of the ALT/WDL/DDLs showed MDM2 amplification (100%). The MDM2+/FRS2- series included 7 ALT/WDLs and 3 DDLs. Four of 7 (57.1%) MDM2+/FRS2- ALT/WDLs occurred in peripheral sites, slightly higher than the percentage of MDM2+/FRS2+ ALT/WDLs (28/63, 44.4%). All of the 3 MDM2+/FRS2- DDLs (100%) were peripheral tumours, a much higher proportion than that of MDM2+/FRS2+ DDLs (10/73, 13.7%). A high percentage of homologous pleomorphic liposarcoma-like DDLs (2/3) were observed in the MDM2+/FRS2- group. In the control group, all of the parosteal osteosarcomas (5/5, 100%) were FRS2-amplified, whereas the remaining 103 samples were FRS2-nonamplified.

Conclusions

These findings suggest that FRS2 is consistently amplified in ALT/WDL/DDLs and offer another avenue for the investigation of the biology of this tumour group. MDM2+/FRS2- cases seem to be associated with certain clinicopathological features, and further investigation is needed.

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