Combination or sequencing strategies to improve the outcome of metastatic renal cell carcinoma patients: a critical review

The introduction of novel anti-angiogenic therapies has greatly improved the outcome of patients with metastatic renal cell carcinoma (mRCC). The use of these therapies in combination or sequentially is proposed to provide greater efficacy. We have reviewed completed and ongoing clinical trials in mRCC that have reported efficacy and/or safety data of novel therapies used in combination or sequentially. Bevacizumab appears to be a useful partner when combined with interferon (IFN), while controversial results have been reported when combined with temsirolimus and everolimus. Other combinations appear to have unacceptable tolerability or require dose or schedule optimization. Sequencing data provide a clear indication that multiple lines of treatment may extend survival. The 'ideal' sequence, however, is still unknown. In conclusion, novel therapies used in combination or sequentially have potential to provide optimised treatment and patient outcomes in mRCC. The results from ongoing/planned trials are expected to help shape future therapy.     

Multimodal imaging for a theranostic approach in a murine model of B-cell lymphoma with engineered nanoparticles

Nanoparticles (NPs) are a promising tool for in vivo multimodality imaging and theranostic applications. Hyaluronic acid (HA)-based NPs have numerous active groups that make them ideal as tumor-targeted carriers. The B-lymphoma neoplastic cells express on their surfaces a clone-specific immunoglobulin receptor (Ig-BCR). The peptide A20-36 (pA20-36) selectively binds to the Ig-BCR of A20 lymphoma cells. In this work, we demonstrated the ability of core-shell chitosan-HA-NPs decorated with pA20-36 to specifically target A20 cells and reduce the tumor burden in a murine xenograft model. We monitored tumor growth using high-frequency ultrasonography and demonstrated targeting specificity and kinetics of the NPs via in vivo fluorescent reflectance imaging. This result was also confirmed by ex vivo magnetic resonance imaging and confocal microscopy. In conclusion, we demonstrated the ability of NPs loaded with fluorescent and paramagnetic tracers to act as multimodal imaging contrast agents and hence as a non-toxic, highly specific theranostic system.     

Comparative analysis of low-level laser therapy (660 nm) on inflammatory biomarker expression during the skin wound-repair process in young and aged rats

The wound-healing process plays an essential role in the protective response to epidermal injury by tissue regeneration. In the elderly, skin functions deteriorate as a consequence of morphological and structural changes. This study aimed to evaluate and compare the effect of low-level laser therapy (LLLT) in cutaneous wound healing in young and aged rats. A total of 60 male rats comprising 30 young (±30 days) and 30 aged (±500 days) was used. The animals were divided into four experimental groups and underwent skin wound and/or treatment with LLLT (660 nm, 30 mW, 1.07 W/cm², 0.028 cm², 72 J/cm², and 2 J). Analyses were conducted to verify the effects of LLLT in the tissue repair process, in the gene expression, and protein expression of TNF-α, IL-1β, and IL-10, obtained in skin wound model. Results showed that there were significant differences between the young control group and the aged control group and their respective treated groups (LLLT young and LLLT aged). We conclude that LLLT has shown to be effective in the treatment of skin wounds in young and aged animals at different stages of the tissue repair process, which suggests that different LLLT dosimetry should be considered in treatment of subjects of different ages. Further clinical trials are needed to confirm these findings in clinical settings.     

Effect of low-level laser therapy on types I and III collagen and inflammatory cells in rats with induced third-degree burns

Low-level laser therapy (LLLT) has been increasingly used to accelerate wound healing in third-degree burns. This study investigated the effects of lasers on the tissue repair process of third-degree burns. Burns were produced on the backs of male Wistar rats. The animals were divided into four groups (n?=?12): control, injury, LLLT 3 J/cm², and LLLT 4 J/cm². Each group was further divided into two subgroups; the rats in one subgroup were killed on day 8 and those in the other, on day 16 after injury. The animals in LLLT 3 J/cm² and LLLT 4 J/cm² were irradiated 1 h after injury, and irradiation was repeated every 48 h. Laser (660 nm, 35 mW) treatment at fluences of 3 and 4 J/cm² were used. After killing the rats, tissue fragments from the burnt area were removed for histological analysis. The LLLT-treated groups showed a significant decrease (p <0.05) in the number of inflammatory cells and increased collagen deposition compared to the injury group. Laser irradiation (both 3 and 4 J/cm²) resulted in reduction in the inflammatory process and improved collagen deposition, thereby ameliorating the healing of third-degree burns.     

Comparison of acute haemodynamic effects of nifedipine and isosorbide dinitrate in patients with heart failure following acute myocardial infarction

The acute haemodynamic effects of nifedipine (10 mg sublingually) and isosorbide dinitrate (5 mg sublingually) were compared in 13 patients with heart failure due to acute myocardial infarction. Nifedipine induced a significant reduction in systolic (from 122 ± 5 to 107 ± 3 mm Hg: mean ± SEM; P < 0.002) and diastolic blood pressure (from 85 ± 3 to 75 ± 2 mm Hg; P < 0.01). Heart rate did not change significantly, nor did mean right atrial pressure. The mean pulmonary arterial pressure was lowered from 31 ± 2 to 27 ± 2 mm Hg (P < 0.005). The left ventricular filling pressure decreased from 24 ± 1 to 19 ± 1 mm Hg (P < 0.0001). A significant increase in cardiac index (from 2.33 ± 0.13 to 2.69 ± 0.15 l/min per m²; P < 0.001) and in stroke volume index (from 24 ± 2 to 28 ± 2 ml/beats per m²; P < 0.005) was registered. Systemic vascular resistance fell from 1742 ± 145 to 1308 ± 85 dynes/sec per cm⁻⁵ (P < 0.00005). After isosorbide dinitrate was administered a significant reduction in mean right atrial pressure (from 9.5 ± 1.6 to 5.1 ± 1.2 mm Hg; P < 0.0001), in mean pulmonary arterial pressure (from 32 ± 1 to 23 ± 1 mm Hg; P < 0.00001) and in left ventricular filling pressure (from 23 ± 1 to 16 ± 1 mm Hg; P < 0.0001) was seen. No significant change in systolic and diastolic blood pressure, heart rate, cardiac index, stroke volume index and systemic vascular resistance was registered. No side-effects were seen after nifedipine and isosorbide dinitrate were administered.     

Five-year retrospective clinical study of indirect composite restorations luted with a light-cured composite in posterior teeth

Objectives

The purpose of this study was to evaluate the clinical performance of indirect composite onlays–overlays bonded with a light-cured composite on vital molars.

Materials and methods

Forty-one patients were restored with 79 indirect composite restorations. The restorations were studied for an observation time of 5 years. Marginal adaptation, marginal discolouration, secondary caries, colour match and anatomic form were clinically examined following modified United States Public Health Service criteria. Each restoration was also examined for fractures and debonding. Endodontic complications were registered. Survival rate, based just on failures that required a replacement, and success rate that included also failures that required a repair intervention were statistically determined using a restoration and a patient-related analysis.

Results

After 5 years, using each restoration as a statistical unit, the survival rate was 91.1 % and the success rate 84.8 %, with a high Kaplan–Meier estimated success probability of 0.852. Using the patient as the statistical unit, the survival rate was 90.2 % and the success rate 85.4 %, corresponding to a Kaplan–Meier estimated success probability of 0.857. On the basis of the criteria used, most of the restorations rated Alpha. Regarding marginal adaptation and marginal discolouration, 5 and 10.1 % of the restorations, respectively, revealed Bravo ratings

Conclusions

Indirect composite restorations offer a predictable and successful treatment modality giving an optimal preservation of sound tooth tissue.

Clinical relevance

The preparation, cementation and finishing procedures are considered key factors for the long-term success of the indirect composite restorations.     

Thrombotic Thrombocytopenic Purpura and Relapes: Why do case series differ?

We examined the retrospective case series of the Itallan Cooperative Group to determine the incidence of relapes in TTP patients. Of 60 patients who have crossed the 10-year threshold from the first episode, Only 9 (15%) relapsed during that period, a figure far lower than that reported recently. Such difference is hardly explainable on the basis of our current knowledge of the biological behaviour of TTP. Furthermore, we unsuccessfully analyzed the treatment performed in each of our relapsed patients, in search of some element that could retrospectively predict the subsequent relapse