RET Fusion Testing in Patients With NSCLC: The RETING Study.

Introduction: RET inhibitors with impressive overall response rates are now available for patients with NSCLC, yet the identification of RET fusions remains a difficult challenge. Most guidelines encourage the upfront use of next-generation sequencing (NGS), or alternatively, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) when NGS is not possible or available. Taken together, the suboptimal performance of single-analyte assays to detect RET fusions, although consistent with the notion of encouraging universal NGS, is currently widening some of the clinical practice gaps in the implementation of predictive biomarkers in patients with advanced NSCLC. Methods: This situation prompted us to evaluate several RET assays in a large multicenter cohort of RET fusion-positive NSCLC (n = 38) to obtain real-world data. In addition to RNA-based NGS (the criterion standard method), all positive specimens underwent break-apart RET FISH with two different assays and were also tested by an RT-PCR assay. Results: The most common RET partners were KIF5B (78.9%), followed by CCDC6 (15.8%). The two RET NGS-positive but FISH-negative samples contained a KIF5B(15)-RET(12) fusion. The three RET fusions not identified with RT-PCR were AKAP13(35)-RET(12), KIF5B(24)-RET(9) and KIF5B(24)-RET(11). All three false-negative RT-PCR cases were FISH-positive, exhibited a typical break-apart pattern, and contained a very high number of positive tumor cells with both FISH assays. Signet ring cells, psammoma bodies, and pleomorphic features were frequently observed (in 34.2%, 39.5%, and 39.5% of tumors, respectively). Conclusions: In-depth knowledge of the advantages and disadvantages of the different RET testing methodologies could help clinical and molecular tumor boards implement and maintain sensible algorithms for the rapid and effective detection of RET fusions in patients with NSCLC. The likelihood of RET false-negative results with both FISH and RT-PCR reinforces the need for upfront NGS in patients with NSCLC.

Oral Rehabilitation as Part of a Multidisciplinary Treatment in a Case Study of Pigmentary Incontinence.

We present the clinical course of a 9-year-old female patient with Bloch-Sulzberger syndrome and severe neurological deficit that met the major (classic cutaneous signs) and minor (dental anomalies and retinal pathology) diagnostic criteria of Landy and Donnai. Longitudinal multidisciplinary follow-up was carried out from birth to adulthood. Neurological involvement was assessed with electroencephalographic (EEG) and neuroimaging tests at different times during the patient's life. Cranio-maxillofacial involvement was evaluated using lateral skeletal facial and cephalometric analyses. The right and left facial widths were measured through frontal face analysis and using the vertical zygomatic-midline distance. Oral rehabilitation was performed through orthodontic treatment and major dental reconstruction using composite resins. This treatment aimed to improve the occlusion and masticatory function, relieve the transversal compression of the maxilla, and reconstruct the fractured teeth. We believe that, due to significant neurological and cognitive impairment, orthognathic surgery was not the best option for restoring function and improving oral health-related quality of life.

Managing patients taking edoxaban in dentistry.

BACKGROUND: Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. A new group of oral anticoagulants with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. The Food and Drug Administration has approved edoxaban, dabigatran, rivaroxaban and apixaban. Their advantages include: predictable pharmacokinetics, drug interactions and limited food, rapid onset of action and short half-life. However, they lack a specific reversal agent. MATERIAL AND METHODS: This paper examines the available evidence regarding rivaroxaban and sets out proposals for clinical guidance of dental practitioners treating these patients in primary dental care. A literature search was conducted through July 2016 for publications in PubMed and Cochrane Library using the keywords "edoxaban", "dabigatran", "rivaroxaban", "apixaban", "new oral anticoagulants", "novel oral anticoagulants", "bleeding" and "dental treatment" with the "and" boolean operator in the last 10 years. RESULTS: The number of patients taking edoxaban is increasing. There is no need for regular coagulation monitoring of patients on edoxaban therapy. For patients requiring minor oral surgery procedures, interruption of edoxaban is not generally necessary. Management of patients on anticoagulation therapy requires that dentists can accurately assess the patient prior to dental treatments. CONCLUSIONS: Their increased use means that oral care clinicians should have a sound understanding of the mechanism of action, pharmacology, reversal strategies and management of bleeding in patients taking edoxaban. There is a need for further clinical studies in order to establish more evidence-based guidelines for dental patients requiring edoxaban. Key words:Edoxaban, dabigatran, rivaroxaban, apixaban, novel oral anticoagulants, bleeding.