Adhesive dentistry is based on the development of materials which establish an effective bond with the tooth tissues. In this context, adhesive systems have attracted considerable research interest in recent years. Successful adhesive bonding depends on the chemistry of the adhesive, on appropriate clinical handling of the material as well as on the knowledge of the morphological changes caused on dental tissue by different bonding procedures. This paper outlines the status of contemporary adhesive systems, with particular emphasis on chemical characteristics and mode of interaction of the adhesives with enamel and dentinal tissues. Dental adhesives are used for several clinical applications and they can be classified based on the clinical regimen in "etch-and-rinse adhesives" and "self-etch adhesives". Other important considerations concern the different anatomical characteristics of enamel and dentine which are involved in the bonding procedures that have also implications for the technique used as well as for the quality of the bond. Etch-and-rinse adhesive systems generally perform better on enamel than self-etching systems which may be more suitable for bonding to dentine. In order to avoid a possible loss of the restoration, secondary caries or pulp damage due to bacteria penetration or due to cytotoxicity effects of eluted adhesive components, careful consideration of several factors is essential in selecting the suitable bonding procedure and adhesive system for the individual patient situation.
Background:
We investigated whether early dynamic changes of circulating free (cfDNA)
levels as well as the neutrophil to lymphocyte ratio (NLR) could predict
nivolumab effectiveness in pretreated patients with advanced non-small cell
lung cancer (NSCLC).
Methods:
A total of 45 patients receiving nivolumab 3 mg/kg every 2 weeks were
enrolled. Patients underwent a computed tomography scan and responses were
evaluated by the response evaluation criteria in solid tumors. Peripheral
blood samples were obtained from the patients and the cfDNA level as well as
the NLR were assessed. Time to progression (TTP) and overall survival (OS)
were determined.
Results:
Patients with increased cfDNA >20% at the sixth week reported
significantly worse survival outcomes (median OS: 5.7
versus
14.2 months,
p
< 0.001;
median TTP: 3.3
versus
10.2 months,
p
<
0.001), as well as patients with increased NLR >20% (median OS: 8.7
versus
14.6 months,
p
= 0.035; median
TTP: 5.2
versus
10.3 months,
p
= 0.039).
The combined increase of cfDNA and NLR >20% was associated with
significantly worse survival outcomes as compared with the remained
population (median OS: 5.8
versus
15.5 months,
p
= 0.012; median TTP: 3.2
versus
11.9 months,
p
= 0.028). Multivariable analysis identified
three significant factors associated with worse OS: combined cfDNA/NLR
increase >20% [hazard ratio (HR): 5.16; 95% confidence interval (CI),
1.09–24.29;
p
= 0.038], liver metastasis (HR: 0.44; 95% CI,
0.20–0.96;
p
= 0.038), and extra-thoracic disease (HR:
0.33; 95% CI, 0.12–0.89;
p
= 0.029).
Conclusion:
An early combined increase of both cfDNA and NLR over the course of the first
6 weeks of nivolumab therapy predicted worse survival in pretreated patients
with advanced NSCLC, suggesting a potential role in the real-time monitoring
of immunotherapy resistance.
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