Cancer is associated with higher morbidity and mortality and is the second leading cause of death in the US. Further, in some nations, cancer has overtaken heart disease as the leading cause of mortality. Identification of molecular mechanisms by which cancerous cells evade T cell-mediated cytotoxic damage has led to the modern era of immunotherapy in cancer treatment. Agents that release these immune brakes have shown activity to recover dysfunctional T cells and regress various cancer. Both cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death-1 (PD-1) play their role as physiologic brakes on unrestrained cytotoxic T effector function. CTLA-4 (CD 152) is a B7/CD28 family; it mediates immunosuppression by indirectly diminishing signaling through the co-stimulatory receptor CD28. Ipilimumab is the first and only FDA-approved CTLA-4 inhibitor; PD-1 is an inhibitory transmembrane protein expressed on T cells, B cells, Natural Killer cells (NKs), and Myeloid-Derived Suppressor Cells (MDSCs). Programmed Death-Ligand 1 (PD-L1) is expressed on the surface of multiple tissue types, including many tumor cells and hematopoietic cells. PD-L2 is more restricted to hematopoietic cells. Blockade of the PD-1 /PDL-1 pathway can enhance anti-tumor T cell reactivity and promotes immune control over the cancerous cells. Since the FDA approval of ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody) in 2011, six more immune checkpoint inhibitors (ICIs) have been approved for cancer therapy. PD-1 inhibitors nivolumab, pembrolizumab, cemiplimab and PD-L1 inhibitors atezolizumab, avelumab, and durvalumab are in the current list of the approved agents in addition to ipilimumab. In this review paper, we discuss the role of each immune checkpoint inhibitor (ICI), the landmark trials which led to their FDA approval, and the strength of the evidence per National Comprehensive Cancer Network (NCCN), which is broadly utilized by medical oncologists and hematologists in their daily practice.
Platelet-rich fibrin might serve as a potentially ideal scaffold in revascularization of immature permanent teeth with necrotic pulps as it is rich in growth factors, enhances cellular proliferation and differentiation, and acts as a matrix for tissue ingrowth.
Objective: The purpose of this study was to evaluate and compare the efficacy and safety of intranasal (IN)administration of midazolam (M), ketamine (K) and their combination (MK) to produce moderate sedation in young, uncooperative pediatric dental patients. Study design: In this three stage crossover trial forty five uncooperative ASA type-1 children, who required dental treatment, were randomly assigned to receive one of the three drugs/combination by IN route during three subsequent visits. The efficacy and safety of the agents were assessed by overall success rate and by monitoring of vital signs, respectively. Results: The onset of sedation was rapid with K as compared to M and MK. The difference was statistically significant(P<0.01) between K and M. The overall success rate was 89% with K, MK was 84% and 69% with M. The difference between the overall success rates of K and M was statistically significant (P<0.01). Vital signs were within physiological limits and there were no significant adverse effects with any medication.Conclusions: M, K and MK are safe and effective by IN route to produce moderate sedation for providing dental care to pediatric dental patients who have been otherwise indicated for treatment under general anesthesia.
BACKGROUND. The available evidence implicating the involvement of oxidative stress in the caries process suggests that local antioxidant status may be of importance in determining the susceptibility to the caries process. AIM. The aim of this study was to estimate the total antioxidant capacity (TAC) in unstimulated saliva of healthy children with and without severe early childhood caries (S-ECC) and to correlate the individual TAC level with dmft (d = decayed, m = missing, f = filled, t = teeth) score and age. MATERIAL AND METHODS. The TAC of saliva was investigated in 100 healthy children in the age range of 3-5 years divided in two groups, control and study group based on the absence or presence of caries, respectively. The antioxidant capacity of saliva was estimated by an adaptation of ABTS [2, 2'-Azino-di-(3-ethylbenzthiazoline sulphonate)] assay. RESULTS. The mean TAC level in the saliva of the children in study group was found to be significantly increased (P < 0.001), and a significantly linear regression was seen between the TAC and dmft score (P < 0.001) whereas it was insignificant between the TAC and age (P = 0.078). CONCLUSION. The results indicated that TAC of saliva increased significantly in children with S-ECC and increasing prevalence of dental caries predisposes to the increase in TAC of saliva.
The objective of this study was to compare and evaluate the efficacy and safety of drops and atomized administration of intranasal ketamine (INK) in terms of behavioral response for agent acceptance during administration and for agent efficacy and safety for the sedation of young uncooperative pediatric dental patients. Study design: Thirty Four uncooperative ASA grade-1 children, requiring dental treatment were randomly assigned to receive INK as drops and atomized spray in one of the subsequent visit. This was a two stage cross-over trial and each child received INK by both modes of administration. The vital signs were monitored continuously during each visit. Results: A statistically significant difference in patients acceptance (P<0.0001) was observed in the atomized administration when compared to drops administration for the procedural event of drug administration. Moreover, there were also significant differences (P<0.05) between onset of sedation and recovery time between two groups. All the vital signs were within normal physiological limits and there were no significant adverse effects in either group. Conclusions: INK is safe and effective by either mode of intranasal (IN) drug administration for moderate sedation in facilitating dental care for anxious and uncooperative pediatric dental patients. Moreover, INK when administered with the mucosal atomization device, the acceptance of the drug was associated with less aversive reaction, rapid onset and recovery of sedation, as compared to the drop administration of the same agent.
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