PD-L1 in oral squamous cell carcinoma: A key biomarker from the laboratory to the bedside

Objectives and background: Oral squamous cell carcinoma (OSCC) is a highly malignant disease with an increasing incidence. The need to improve therapeutic strategies for patients affected by OSCC is an urgent challenge. Currently, the advent of immunotherapy represents an important step toward this aim. Programmed cell death-ligand 1 (PD-L1), a membrane protein that can be expressed on tumor and inflammatory cells is a key biomarker whose expression is determined by means of immunohistochemistry and is necessary for selecting patients for immunotherapy. Methods: In this study, we review the methods of PD-L1 assessment and outcomes achieved with immunotherapy in the treatment of OSCC patients. Results: Based on a meta-analysis we demonstrate a lack of prognostic significance of PD-L1 in OSCC. Conclusions: We also highlight unresolved issues including difficulties in standardizing PD-L1 evaluation and discuss future opportunities such as leveraging digital pathology

Long-Lasting Efficacy of Radio Electric Asymmetric Conveyer Neuromodulation Treatment on Functional Dysmetria, an Adaptive Motor Behavior

BackgroundFluctuating asymmetry (FA) is widely defined as the deviation from perfect bilateral symmetry and is considered an epigenetic measure of environmental stress. Rinaldi and Fontani hypothesized that the FA morpho-functional changes originate from an adaptive motor behavior determined by functional alterations in the cerebellum and neural circuits, not caused by a lesion, but induced by environmental stress. They called this phenomenon functional dysmetria (FD). On this premise, they developed the radio electric asymmetric conveyer (REAC) technology, a neuromodulation technology aimed at optimizing the best neuro-psycho-motor strategies in relation to environmental interaction.AimsPrevious studies showed that specific REAC neuro postural optimization (NPO) treatment can induce stable FD recovery. This study aimed to verify the duration of the NPO effect in inducing the stable FD recovery over timeMaterials and methodsData were retrospectively collected from a population of 29,794 subjects who underwent a specific semiological FD assessment and received the NPO treatment, regardless of the pathology referred.ResultsThe analysis of the data collected by the various participants in the study led us to ascertain the disappearance of FD in 100% of the cases treated, with a stability of the result detected up to 18 years after the single administration of the REAC NPO treatment.ConclusionsThe REAC NPO neurobiological modulation treatment consisting of a single administration surprisingly maintains a very long efficacy in the correction of FD. This effect can be explained as the long-lasting capacity of the NPO treatment to induce greater functional efficiency of the brain dynamics as proven in previous studies

Is the Da Vinci Xi system a real improvement for oncologic transoral robotic surgery? A systematic review of the literature

In this paper, we reviewed the current literature about TORS procedures performed with Xi system and we discussed the pros and cons of this robotic system comparing it to the previous Si model. A systematic literature review was conducted using the PubMed, Scopus, Web of Science and Cochrane databases for adequate published studies about TORS procedure performed with da Vinci Si and Xi models. Five papers on the TORS-Xi procedures met our inclusion and exclusion criteria. These papers showed results based on 74 subjects (mean age 60.51 ± 4.55 years old). The most common TORS procedure was performed to address the oropharynx (65 procedures). One case (1.35%) of a tongue base tumor was converted into a transmandibular approach. One subject (1.35%) had a positive margin, while two subjects (2.7%) had close/uncertain margins at final histology. Nine papers on the TORS-Si procedures met our inclusion and exclusion criteria. These papers showed results based on 128 subjects (mean age 59.79 ± 5.93 years old). The most common TORS procedure was performed to address the oropharynx (90 procedures). Three procedures (2.34%) were aborted due to inadequate exposure of the tumor. None of the subject had positive margins, while three subjects (2.34%) had close/uncertain margins at final histology. Despite its improved vision, easier docking and narrower robotic arms, the da Vinci Xi system has structural peculiarities that limit its applications for certain TORS procedures

Displacement of protein-bound aptamers with small molecules screened by fluorescence polarization

Small molecule inhibitors of proteins are invaluable tools in research and as starting points for drug development. However, their screening can be tedious, as most screening methods have to be tailored to the corresponding drug target. Here, we describe a detailed protocol for a modular and generally applicable assay for the identification of small organic compounds that displace an aptamer complexed to its target protein. The method relies on fluorescence-labeled aptamers and the increase of fluorescence polarization upon their binding to the target protein. The assay has high Z'-factors, making it compatible with high-throughput screening. It allows easy automation, making fluorescence readout the time-limiting step. As aptamers can be generated for virtually any protein target, the assay allows identification of small molecule inhibitors for targets or individual protein domains for which no functional screen is available. We provide the step-by-step protocol to screen for antagonists of the cytohesin class of small guanosine exchange factors

Functional and aesthetic outcomes of pedicled temporalis muscle flap for mesostructure reconstruction

The purpose of this work is to analyse the soundness of the Temporalis Muscle Flap as a safe and reliable flap to restore the aesthetic and functions of the facial mesostructure after its partial resection. Subjects were selected retrospectively and were invited to come to our outpatient clinic. Here, subjects completed a clinical evaluation in which the medical examiners evaluated the aesthetic outcome, the phonation, the ocular motility and the swallowing. Twenty-two subjects were enrolled in this study and completed the clinical evaluation. The mean value of the score obtained for the aesthetic outcome was 2.91 ± 0.92, slightly less than good. The VHI-30 questionnaire for voice evaluation obtained a mean score of 22.5 ± 11.5, pointing out minor voice problems. The mean value of the P-score evaluated during Fiberoptic Endoscopic Evaluation of Swallowing was 4.64 ± 0.95, highlighting the near absence of endoscopic signs of dysphagia. On the evaluation of ocular function, only one subject showed an inferior displacement of his right eyeball without vertical diplopia. The Temporalis Muscle Flap is a safe and reliable flap that can be used to reconstruct numerous surgical defects of the maxilla, giving an excellent recovery of physical aspect, phonation, and swallowing

Reactions of Diazo Compounds with Alkenes Catalysed by [RuCl(cod)(Cp)]: Effect of the Substituents in the Formation of Cyclopropanation or Metathesis Products

The reaction of diazo compounds with alkenes catalysed by complex [RuCl(cod)(Cp)] (cod= 1,5-cyclo-octadiene, Cp=cyclopentadienyl) has been studied. The catalytic cycle involves in the first step the decomposition of the diazo derivative to afford the reactive [RuCl(Cp){=C(R(1))R(2)}] intermediate and a mechanism is proposed for this step based on a kinetic study of the simple coupling reaction of ethyl diazoacetate. The evolution of the Ru-carbene intermediate in the presence of alkenes depends on the nature of the substituents at both the diazo N(2)=C(R(1))R(2) (R(1), R(2) = Ph, H; Ph, CO(2)Me; Ph, Ph; C(R(1))R(2) = fluorene) and the olefin substrates R(3)(H)C=C(H)R(4) (R(3), R(4) = CO(2)Et, CO(2)Et; Ph, Ph; Ph, Me; Ph, H; Me, Br; Me, CN; Ph, CN; H, CN; CN, CN). A remarkable reactivity of the complex was recorded, especially towards unstable aryldiazo compounds and electron-poor olefins. The results obtained indicate that either cyclopropanation or metathesis products can be formed: the first products are favoured by the presence of a cyano substituent at the double bond and the second ones by a phenyl