Patients undergoing recurrent CT exams: assessment of patients with non-malignant diseases,reasons for imaging and imaging appropriateness

To determine percent of patients without malignancy and ≤ 40 years of age with high cumulative radiation doses through recurrent CT exams and assess imaging appropriateness. From the cohort of patients who received cumulative effective dose (CED) of ≥ 100 mSv over a 5-year period, a sub-set was identified with non-malignant disease. The top 50 clinical indications leading to multiple CTs were determined. Clinical decision support (CDS) system scores were analyzed using a widely adopted standard of 1–3 (red) as “not usually appropriate,” 4–6 (yellow) “may or may not be appropriate,” and 7–9 (green) “usually appropriate.” Clinicians reviewed patient records to assess compliance with appropriate use criteria (AUC). 9.6% of patients in our series were with non-malignant conditions and 1.4% with age ≤ 40 years. CDS scores (rounded) were 2% red, 38% yellow, 27% green, and 33% unscored CTs. Clinical society guidelines for CT exams, wherever available, were followed in 87.5 to 100% of cases. AUCs were not available for several clinical indications as also referral guidelines for serial CT imaging. More than half of CT exams were unrelated to follow-up of a primary chronic disease. We are faced with a situation wherein patients in age ≤ 40 years require or are thought to require many CT exams over the course of a few years but the radiation risk creates concern. There is a fair number of conditions for which AUC are not available. Suggested solutions include development of CT scanners with lesser radiation dose and further development of appropriateness criteria.     

Development of immunofiltration assay by light addressable potentiometric sensor with genetically biotinylated recombinant antibody for rapid identification of Venezuelan equine encephalitis virus

A genetically biotinylated single chain fragment variable antibody (scFv) against Venezuelan equine encephalitis virus (VEE) was applied in a system consisting of an immunofiltration enzyme assay (IFA) with a light addressable potentiometric sensor (LAPS) for the rapid identification of VEE. The IFA involved formation of an immunocomplex sandwich consisting of VEE, biotinylated antibody, fluoresceinated antibody and streptavidin, capture of the sandwich by filtration on biotinylated membrane, and labeling of the sandwich by anti-fluorescein urease conjugate. The concentration ratio of biotinylated to fluoresceinated antibodies was investigated and optimized. By the IFA/LAPS assay, the limit of detection (LOD) of VEE was approximately 30 ng/ml, similar to that achieved when chemically biotinylated monoclonal antibody (mAb) was applied. Total assay variance of the IFA/LAPS assay for both intra- and inter-assay precision was less than 20%. Assay accuracy was measured by comparing VEE concentrations estimated by IFA/LAPS standard curve to those obtained by conventional protein assay. VEE concentrations were found to differ by no more than 10%. The IFA/LAPS assay sensitivity was approximately equal to that of a conventional enzyme-linked immunosorbent assay (ELISA) utilizing polystyrene plates and a chromogenic substrate; however, less time and effort were required for performance of the IFA/LAPS assay. More importantly, use of genetically biotinylated scFv in the IFA/LAPS assay obviates the need for chemical biotinylation of antibody with resultant possible impairment of the antigen-binding site. Furthermore, the potential for batch-to-batch variability resulting from inequality in the number of biotin molecules labeled per antibody molecule is eliminated.     

Mutation screening analysis of the retinoblastoma related gene RB2/p130 in sporadic ovarian cancer and head and neck squamous cell cancer.

AIMS: To investigate the involvement of the RB2/p130 gene in the pathogenesis of sporadic ovarian cancer in addition to head and neck squamous cell carcinoma (HNSCC). METHODS: Paired tumour and patient matched normal DNA samples from 43 sporadic ovarian tumours and 39 normal/tumour HNSCC DNA samples were screened. The mutation screen used polymerase chain reaction (PCR) amplification followed by single strand conformation polymorphism analysis and direct sequencing of the PCR products. Exons 19 and 20 (B domain) and exons 21 and 22 (C-terminus) were analysed for mutations. These exons were chosen because most of the point mutations in RB2/p130 are located in the C-terminal region and mutations in these exons have been identified previously in nasopharyngeal carcinomas and primary lung tumours. RESULTS: No abnormal band shifts were seen in the samples analysed, and no bands directly sequenced revealed the presence of mutations. CONCLUSIONS: Genetic alterations in the RB2/p130 gene (exons 19-22) are unlikely to be involved directly in the pathogenesis of sporadic ovarian cancer or HNSCC.     

Isolation and 1H/13C-NMR Studies on 19,20-Dihydrocondylocarpine: An Alkaloid from the Leaves of Ervatamia coronaria and Alstonia scholaris

Studies on the alkaloidal constituents of the leaves of ERVATAMIA CORONARIA Stapf and ALSTONIA SCHOLARIS have resulted in the isolation of (20 S)-19,20-dihydrocondylocarpine which has not been previously reported from these plants. The stereochemistry at C-20 was established with the help of n. O. e. difference measurements. (13)C-NMR assignments have been made by polarisation transfer techniques.     

Optic nerve elongation: does it exist?

The length of the optic nerves is a reflection of normal postnatal cranio-orbital development. Unilateral elongation of an optic nerve has been observed in two patients with orbital and skull base neoplasms. In the first case as compared to the patient's opposite, normal optic nerve, an elongated length of the involved optic nerve of 45 mm was present. The involved optic nerve in the second patient was 10 mm longer than the normal opposite optic nerve. The visual and extraocular function was preserved in the second patient. The first patient had only light perception in the affected eye. In this paper, the embryology, anatomy, and physiology of the optic nerve and its mechanisms of stretch and repair are discussed.     

Histamine reduces gap junctional communication of human tonsil high endothelial cells in culture

The regulation of gap junctional communication by histamine was studied in primary cultures of human tonsil high endothelial cells (HUTECs). We evaluated intercellular communication, levels, state of phosphorylation, and cellular distribution of gap junction protein subunits, mainly connexin (Cx)43. Histamine induced a time-dependent reduction in dye coupling (Lucifer yellow) associated with reduction in connexin43 localized at cell-cell appositions (immunofluorescence), without changes in levels and phosphorylation state of connexin43 (immunoblots). These effects were prevented with chlorpheniramine, an H1 receptor blocker; indomethacin, a cyclooxygenase blocker; or GF109203X, a protein kinase C inhibitor. Treatment with phorbol myristate acetate, a protein kinase C activator, and 4bromo (4Br)-A23187, a calcium ionophore, mimicked the histamine-induced effects on dye coupling. 8Bromo-cAMP doubled the dye coupling extent and prevented the histamine-induced reduction in incidence of dye coupling. After 24-h histamine treatment, known to desensitize H1 receptors, reapplication of histamine increased cell coupling in a way prevented by ranitidine, an H2 receptor blocker. Thus, activation of H1 and H2 receptors, which increase intracellular levels of free Ca2+ and cAMP, respectively, may affect gap junctional communication in opposite ways. Stabilization of actin filaments with phalloidine diminished but did not totally prevent histamine-induced cell shape changes and reduction in dye coupling. Hence, the histamine-induced reduction in gap junctional communication between HUTEC is mediated by cytoskeleton-dependent and -independent mechanisms and might contribute to modulate endothelial function in lymphoid tissue.     

Mapping Canadian Data Assets to Generate Real-World Evidence: Lessons Learned from Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration’s RWE Data Working Group

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8–11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration’s Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada.     

The role of multidisciplinary decision making in oropharyngeal cancer: do we follow guidelines and are treatment decisions being implemented?

European Archives of Oto-Rhino-Laryngology - A multidisciplinary team (MDT) approach to cancer management is gold-standard. With an increasing disease incidence and growing research into human...