The potential of optical proteomic technologies to individualize prognosis and guide rational treatment for cancer patients

Genomics and proteomics will improve outcome prediction in cancer and have great potential to help in the discovery of unknown mechanisms of metastasis, ripe for therapeutic exploitation. Current methods of prognosis estimation rely on clinical data, anatomical staging and histopathological features. It is hoped that translational genomic and proteomic research will discriminate more accurately than is possible at present between patients with a good prognosis and those who carry a high risk of recurrence. Rational treatments, targeted to the specific molecular pathways of an individual’s high-risk tumor, are at the core of tailored therapy. The aim of targeted oncology is to select the right patient for the right drug at precisely the right point in their cancer journey. Optical proteomics uses advanced optical imaging technologies to quantify the activity states of and associations between signaling proteins by measuring energy transfer between fluorophores attached to specific proteins. Förster resonance energy transfer (FRET) and fluorescence lifetime imaging microscopy (FLIM) assays are suitable for use in cell line models of cancer, fresh human tissues and formalin-fixed paraffin-embedded tissue (FFPE). In animal models, dynamic deep tissue FLIM/FRET imaging of cancer cells in vivo is now also feasible. Analysis of protein expression and post-translational modifications such as phosphorylation and ubiquitination can be performed in cell lines and are remarkably efficiently in cancer tissue samples using tissue microarrays (TMAs). FRET assays can be performed to quantify protein-protein interactions within FFPE tissue, far beyond the spatial resolution conventionally associated with light or confocal laser microscopy. Multivariate optical parameters can be correlated with disease relapse for individual patients. FRET-FLIM assays allow rapid screening of target modifiers using high content drug screens. Specific protein-protein interactions conferring a poor prognosis identified by high content tissue screening will be perturbed with targeted therapeutics. Future targeted drugs will be identified using high content/throughput drug screens that are based on multivariate proteomic assays. Response to therapy at a molecular level can be monitored using these assays while the patient receives treatment: utilizing re-biopsy tumor tissue samples in the neoadjuvant setting or by examining surrogate tissues. These technologies will prove to be both prognostic of risk for individuals when applied to tumor tissue at first diagnosis and predictive of response to specifically selected targeted anticancer drugs. Advanced optical assays have great potential to be translated into real-life benefit for cancer patients

Subcutaneous emphysema in patients undergoing root canal treatment: a systematic review of the factors affecting its development and management

Background: Subcutaneous emphysema is an infrequent mishap during root canal treatment which, in rare cases, can lead to severe complications. Aim: To systematically review the literature on the factors affecting the development of subcutaneous emphysema during root canal treatment, and on its management. Data sources: An electronic search was conducted in EMBASE (1947–2018), LILACS (1982–2018), PubMed (1950–2018), SciELO (1997–2018), Scopus (1970–2018), Web of Science (1900–2018) and two grey literature databases. Moreover, all issues of nine journals and four endodontic textbooks were hand-searched. Study eligibility criteria, participants, interventions: The retrieved studies were screened by two reviewers to select clinical studies, case reports or case series describing subcutaneous emphysema that developed during or immediately after root canal treatment in adult patients. Study appraisal and synthesis methods: Included studies were critically appraised according to a custom list of quality requirements. The extracted data were arranged in tables, and combined through a narrative synthesis. Results: The search retrieved 99 unique articles. Thirty six case reports and 15 case series describing a total of 65 cases of subcutaneous emphysema were included in this review. The methodological quality was medium. Reported cases of emphysema more often involved females and maxillary teeth. Drying of the root canal system with air under pressure, inadvertent extrusion of hydrogen peroxide through the apical foramen, the air-water spray produced by handpieces or laser devices, and the use of ozone gas were the most commonly suspected causes. Its management involved prescription of antibiotics and NSAIDs/analgesics, local application of ice packs or compresses and hospitalization. The signs and symptoms resolved completely within 1-17 days. Limitations: Case reports and case series are a low level of evidence. Conclusions and implications of key findings: Subcutaneous emphysema can develop during both nonsurgical and surgical root canal treatment. Pressurized air streams or air-water sprays should not be directed towards the root canals or areas with mucosal discontinuity. None of the management approaches were clearly related to expedited recovery. Guidelines should be developed in order to avoid unnecessary or potentially harmful interventions