Vasoactive Intestinal Peptide Maintains the Nonpathogenic Profile of Human Th17-Polarized Cells

The cytokine microenvironment modulates CD4 T cell differentiation causing the shift of naïve CD4 T cells into different cell subsets. This process is also regulated by modulators such as vasoactive intestinal peptide (VIP), a neuropeptide with known immunomodulatory properties on CD4 T cells that exert this action through specific receptors, vasoactive intestinal peptide receptor (VPAC)₁ and VPAC₂. Our results show that the pattern of VIP receptors expression ratio is modified during Th17 differentiation. In this report, we evaluate the capacity of VIP to modulate naïve human cells into Th17 cells in vitro by analyzing their functional phenotype. The presence of VIP maintains the nonpathogenic profile of Th17-polarized cells, increases the proliferation rate, and decreases their Th1 potential. VIP induces the upregulation of the STAT3 gene interaction with the VPAC₁ receptor during the onset of Th17 differentiation. Moreover, RAR-related orphan receptor C (RORC), RAR-related orphan receptor A (RORA), and interleukin (IL)-17A genes are upregulated in the presence of VIP through interaction with VPAC₁ and VPAC₂ receptors. Interestingly, VIP induces the expression of the IL-23R gene through interaction with the VPAC₂ receptor during the expansion phase. This is the first report that describes the differentiation of naïve human T cells to Th17-polarized cells in the presence of VIP and demonstrates how this differentiation regulates the expression of the VIP receptors.     

Age affects pegylated liposomal doxorubicin elimination and tolerability in patients over 70 years old

Purpose

Pegylated liposomal doxorubicin (PLD) is often used in elderly people, due to its improved tolerability. However, clinical and pharmacological data in the subset of patients over 70 are scanty.

Methods

PLD safety was evaluated in 35 patients (aged ≥70 years) who were treated with PLD as a single agent for 165 cycles. Doxorubicin plasma levels, leukocyte DNA breaks and monocyte count variations were measured as markers of drug exposure, DNA repair capability and reticuloendothelial system activation, respectively. A correlation between these markers and age was sought.

Results

Treatment was generally well tolerated. Skin erythrodysesthesia was the most frequent side effect, and no severe (G4) toxicity occurred. PLD plasma half-life generally correlated with age (P < 0.001) and was particularly prolonged in octogenarians (P = 0.005). Doxorubicin clearance significantly declined up to 70 % at cycle 7. DNA breaks increased over the first two cycles (P = 0.007) and were inversely correlated with age (P = 0.007) and directly with clearance (P = 0.006). Pre-treatment monocyte counts increased over cycles (P < 0.001) and were associated with an increase in clearance at cycle 3 (P = 0.015). The hand–foot–skin syndrome was significantly more severe in patients of advanced age or longer PLD half-life.

Conclusions

This study showed (1) increased systemic drug exposure over subsequent cycles; (2) association of age with increased drug exposure, reduced DNA repair capability and worse skin toxicity; (3) a relation between monocyte count and drug clearance.     

Impressive efficacy of sorafenib in a patient with an hepatocellular carcinoma and a portal vein thrombosis associated with a metastatic ENT cancer

Sorafenib, a new antiangiogenic and antiproliferative agent, is currently used for hepatocellular and renal cell carcinoma. We report here the case of a patient with two cancers, a locally advanced cancer of the piriform sinus and a hepatocellular carcinoma, who was given sorafenib. Tumor response of both cancers might suggest that sorafenib could be effective against head and neck cancer.     

Schwannome présacré: à propos d’un cas

Introduction

Presacral schwannomas are rare benign tumors, representing 1% to 5% of all schwannomas. We report a case diagnosed by imaging modalities (CT-MRI) and treated by complete surgical resection.

Case report

A 55-year-old female has had a history of abdominal pain since one year without compressive signs. A pelvic retrorectal mass has been discovered clinically. CT and MRI were very suggestive of a presacral schwannoma. Histological examination after complete surgical removal of the mass confirmed the diagnosis of a benign schwannoma.

Discussion

Giant presacral schwannomas are rare pelvic tumors. Often asymptomatic, they are diagnosed lately. CT and MRI are very useful in assessing the diagnosis and evaluating the extent of the tumor. Surgery is the therapeutic modality of first choice. Prognosis is good if the tumor is benign but recurrence is frequent.

Conclusion

Presacral schwannoma can cause pelvic pain. Imaging modalities (MRI++) often guide surgical resection.     

Effect Morphology and Surface Treatment of the Abutments of Dental Implants on the Dimension and Health of Peri-Implant Biological Space

Statement of the problem: The gingival configuration around implant abutments is of paramount importance for preserving the underlying marginal bone, and hence for the long-term success of dental implants. Objective: The objective was to study, clinically and histologically, the effects of the change in the morphology of abutments connected to the endosseous implant, and of their surface treatment. In particular, the objective was to ascertain the effect of changing the shape of the transepithelial pillar and the treatment of its surface on the dimensions, quality and health of the components of the peri-implant biological space, such as the dimensions of the epithelial and connective tissues of the biological space, the concentration of inflammatory cells and the density of collagen fibers. Methods: A clinical trial of 10 patients with a totally edentulous maxilla, who had four implants (IPX4010_GALIMPLANT^®, Sarria, Spain) inserted in the area of the first and second molars on both sides with computer-guided implant surgery, was conducted with the final purpose of assessing the quality of the peri-implant soft tissue attachment around the transepithelial abutments which were employed (aesthetic machined (RM), aesthetic anodized (RA), slim machined (SM) and slim anodized (SA)). At 8 weeks and following the collection of the samples (removal of the implant-abutment assembly with its surrounding hard and soft tissue) and their processing for subsequent histological and histomorphometric analysis in order to study the dimensions, quality and health of the peri-implant soft tissue area, the variables previously mentioned were determined according to the aims of the study. By using appropriate diameter trephine in order to obtain a useful fringe of soft tissue around the transepithelial pillars, ANOVA and chi-square tests were performed. Results: The SPSS statistical analysis ANOVA results revealed that the machined slim abutments have a better performance considering the variables analyzed with epithelial and connective attachment heights of 1.52 mm and 2.3 mm, respectively, and that connective density (density of collagen fibers) was high at 85.7% of the sample size affected by the design for the slim abutments and 92.9% of the high-density sample size affected by the surface treatment for the machined surface. Conclusions: All variables studied, despite the small sample size, showed the superiority of the slim machined abutment among the four groups.     

Estimating the cost of home dialysis in Tunisia: Application of theActivity-based costing methodology

Introduction: In Tunisia, in-centre haemodialysis (ICHD) is the most common type of dialysis. Despite the increasing demand, the number of haemodialysis machines per 100,000 inhabitants is still low. Home Haemodialysis (HHD) is a candidate solution to this problem. Despite its confirmed benefits over ICHD, HHD has not taken place in Tunisia. Aim: To describe the processes of home dialysis modalities, especially HHD, evaluate their costs, analyse them, in the context of medical practice in public health structures in Tunisia. Method: The Activity-Based Costing technique was applied: the processes of home dialysis modalities were modelled, the main activity and resource cost drivers identified, and cost equations developed. Based on data from the nephrology department of Sahloul hospital, the cost per session and annual costs for each home dialysis modality were calculated and analyzed. Results: Home Peritoneal Dialysis, already implemented in Tunisia; presented the lowest annual cost per patient 25344 TND versus 29232 TND for Conventional HHD and 54144 TND for Short-Daily HHD. The cost per session of the Short-Daily HHD (188,8 TND) was comparable to ICHD (180 TND). Consumables presented the most expensive resource for these modalities. Finally, the cost structure of HHD was comparable in Tunisia and France as well as in previous costing studies. Conclusion The cost of one session of HHD is estimated to 188,8 TND. The Tunisian ministry of health could adopt a flexible policy to start HHD program by implementing Conventional HHD first.