A new method for oral cancer biomarkers detection with a non-invasive cyto-salivary sampling and rapid-highly sensitive ELISA immunoassay: a pilot study in humans.

Introduction: Oral squamous cell carcinoma (OSCC) accounts for approximately 90% of oral malignancies and has a 5-year mortality rate close to 50%. A consistent part (70%) of all oral cancers is diagnosed at an advanced stage since available screening techniques are ineffective. Therefore, it would be urgent to improve them. The diagnostic gold standard is tissue biopsy with histological and immunohistochemical assessment. This method presents some limitations. Biopsy is invasive and the histopathological evaluation is semi-quantitative, and the absolute abundance of the target cannot be reliably determined. In addition, tissue is highly processed and may lead to loss of information of the natural state. The search for classical and new clinical biomarkers on fragments of tissue/cells collected with a cytobrush is a highly hopeful technique for early detection and diagnosis of OSCC, because of its non-invasive sampling and easy collection method. Methods: Here we analyzed cytobrush biopsies samples collected from the oral cavity of 15 patients with already diagnosed OSCC by applying an innovative high-sensitivity ELISA technique, in order to verify if this approach may provide useful information for detection, diagnosis, and prognosis of OSCC. To this end, we selected six biomarkers, already used in clinical practice for the diagnosis of OSCC (EGFR, Ki67, p53) or selected based on recent scientific and clinical data which indicate their presence or over-expression in cells undergoing transformation and their role as possible molecular targets in immunecheckpoints blockade therapies (PD-L1, HLA-E, B7-H6). Results: The selected tumor biomarkers were highly expressed in the tumor core, while were virtually negative in healthy tissue collected from the same patients. These differences were highly statistically significant and consistent with those obtained using the gold standard test clearly indicating that the proposed approach, i.e. analysis of biomarkers by a custom ELISA technique, is strongly reliable. Discussion: These preliminary data suggest that this non-invasive rapid phenotyping technique could be useful as a screening tool for phenotyping oral lesions and support clinical practice by precise indications on the characteristics of the lesion, also with a view to the application of new anti-tumor treatments, such as immunotherapy, aimed at OSCC patients.

Identification of a novel cord blood NK cell subpopulation expressing functional programmed death receptor-1.

Background: Natural Killer cells (NKs) represent the innate counterpart of TCRαß lymphocytes and are characterized by a high anti-tumor and an anti-viral cytotoxic activity. Recently, it has been demonstrated that NKs can express PD-1 as an additional inhibitory receptor. Specifically, PD-1 was identified on a subpopulation of terminally differentiated NKs from healthy adults with previous HCMV infection. So far it is unknown whether PD-1 appears during NK-cell development and whether this process is directly or indirectly related to HCMV infection. Methods: In this study, we analyzed the expression and function of PD-1 on Cord Blood derived NKs (CB-NKs) on a large cohort of newborns through multiparametric cytofluorimetric analysis. Results: We identified PD-1 on CB-NKs in more than of half the newborns analyzed. PD-1 was present on CD56dim NKs, and particularly abundant on CD56neg NKs, but only rarely present on CD56bright NKs. Importantly, unlike in adult healthy donors, in CB-NKs PD-1 is co-expressed not only with KIR, but also with NKG2A. PD-1 expression was independent of HCMV mother seropositivity and occurs in the absence of HCMV infection/reactivation during pregnancy. Notably, PD-1 expressed on CB-NKs was functional and mediated negative signals when triggered. Conclusion: To our understanding, this study is the first to report PD-1 expression on CB derived NKs and its features in perinatal conditions. These data may prove important in selecting the most suitable CB derived NK cell population for the development of different immunotherapeutic treatments.

Emerging potential of phototherapy in management of symptomatic oral lichen planus: A systematic review of randomised controlled clinical trials.

Phototherapy incorporating photobiomodulation therapy and antimicrobial photodynamic therapy has been utilised as antioxidants in symptomatic oral lichen planus (OLP) management; however, its role of intervention remains controversial. The aim of this systematic review of CRD42021227788 PROSPERO (an international prospective register of systematic reviews in health and social care) registration number was to oversee and determine phototherapy efficacy in patients with symptomatic OLP, identifying and bridging the literature gaps by proposing recommendations for future studies. A search strategy was developed in consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Various electronic databases were exercised to search for randomised controlled clinical trials (RCTs). Several search engines were employed to analyse a total of 177 studies of which nine included. A wide range of utilised laser and light-emitted diode wavelengths between 630 and 808 nm and irradiance ranged between 10 and 13 mW/cm2 were noted. 67% of studies reported a high risk of bias and a high heterogeneity obtained from numerical data for quantitative analysis, therefore meta-analysis was impossible to conduct. Despite inconsistency and diversity in phototherapy parameters, treatment protocols, photosensitiser (type, concentration and method of application) and outcome assessment tools, the majority of the studies showed positive results compared with standard care treatments. Hence, a necessity to perform well-designed RCTs with robust methodology is warranted, after acknowledging the current drawbacks and addressing the suggested recommendations highlighted in our review. Moreover, advanced knowledge in understanding further phototherapy-antioxidants molecular mechanistic in symptomatic OLP is required.

Clinical osseointegration of bone level implants with conical shape and textured surface with low primary stability.

BACKGROUND: Evidence shows lower chance for osseointegration of implants without sufficient primary stability. The present retrospective study observed bone level conical screw implants with textured surface without primary stability. METHODS: Twenty-six Stark conical screw implants, with V-Blast (Vanish Blast) surface treatment were placed with low primary stability, (insertion torque lower than 10 N/cm and visible mobility at lateral load of 250 g). A soft diet was prescribed. osseointegration was assessed applying 30 Ncm of reverse torque 6 months after placement. RESULTS: The 26 implants that did not achieve primary stability still had a survival rate of 96% after the observation period and were classified as successful according with ICOI Pisa consensus conference success, survival, failure classification .96% of the implants showed clinical osteointegration and were successfully restored. After 12 months, all implants remained functional. CONCLUSIONS: It can be concluded that bone-level implants with V-Blast surface in absence of functional loading are able to achieve osteointegration, even with low primary stability.

Presurgical implant-supported prosthesis: technique for cementation of a definitive prosthesis immediately after surgery.

A fixed prosthesis, supported by implants, was fabricated prior to surgery and cemented with passive fit immediately after placement of 14 implants in the mandible. The prosthesis was constructed before implant surgery on a plaster cast that precisely reproduced the patient's hard and soft tissues. The cast was built using a method that allowed the transfer of hard and soft tissue anatomy from computerized tomograms. A rigid surgical stent, cast in gold, was used to place the implants into prosthetically ideal positions under three-dimensional control. The prosthesis was placed immediately after implant placement, using an occlusion-driven method, which avoided the need for occlusal adjustments to the prosthesis.