Synthetic blocks for bone regeneration : A systematic review and meta-analysis

This systematic review is aimed at evaluating the effectiveness of synthetic block materials for bone augmentation in preclinical in vivo studies. An electronic search was performed on Pubmed, Scopus, EMBASE. Articles selected underwent risk-of-bias assessment. The outcomes were: new bone formation and residual graft with histomorphometry, radiographic bone density, soft tissue parameters, complications. Meta-analysis was performed to compare new bone formation in test (synthetic blocks) vs. control group (autogenous blocks or spontaneous healing). The search yielded 214 articles. After screening, 39 studies were included, all performed on animal models: rabbits (n = 18 studies), dogs (n = 4), rats (n = 7), minipigs (n = 4), goats (n = 4), and sheep (n = 2). The meta-analysis on rabbit studies showed significantly higher new bone formation for synthetic blocks with respect to autogenous blocks both at four-week (mean difference (MD): 5.91%, 95% confidence intervals (CI): 1.04, 10.79%, p = 0.02) and at eight-week healing (MD: 4.44%, 95% CI: 0.71, 8.17%, p = 0.02). Other animal models evidenced a trend for better outcomes with synthetic blocks, though only based on qualitative analysis. Synthetic blocks may represent a viable resource in bone regenerative surgery for achieving new bone formation. Differences in the animal models, the design of included studies, and the bone defects treated should be considered when generalizing the results. Clinical studies are needed to confirm the effectiveness of synthetic blocks in bone augmentation procedures

Dental-derived stem cells and biowaste biomaterials: What's next in bone regenerative medicine applications

The human teeth and oral cavity harbor various populations of mesenchymal stem cells (MSCs), so called dental-derived stem cells (D-dSCs) with self-renewing and multilineage differentiation capabilities. D-dSCs properties involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment. Altogether, this viewpoint develops a general picture of current innovative strategies to employ D-dSCs combined with biomaterials and bioactive factors for regenerative medicine purposes, and offers information regarding the available scientific data and possible applications

Dental-derived stem cells and biowaste biomaterials: What’s next in bone regenerative medicine applications

The human teeth and oral cavity harbor various populations of mesenchymal stem cells (MSCs), so called dental-derived stem cells (D-dSCs) with self-renewing and multilineage differentiation capabilities. D-dSCs properties involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment. Altogether, this viewpoint develops a general picture of current innovative strategies to employ D-dSCs combined with biomaterials and bioactive factors for regenerative medicine purposes, and offers information regarding the available scientific data and possible applications

The impact of progesterone receptor expression on prognosis of patients with rapidly proliferating, hormone receptor-positive early breast cancer: a post hoc analysis of the IBIS 3 trial

Background:In the Italian Breast Cancer Intergroup Studies (IBIS) 3 phase III trial, we compared cyclophosphamide, methotrexate, 5-fluorouracil (CMF) alone to sequential epirubicin/CMF regimens in patients with rapidly proliferating early breast cancer (RPEBC). We performed a post hoc analysis in the subgroup of patients with hormone-receptor-positive RPEBC on the prognostic role of progesterone receptor (PgR) status.Methods:RPEBC was defined by thymidine labeling index (TLI) >3% or grade 3 or S-phase >10% or Ki67 >20%. We analyzed 466 patients with hormone-receptor-positive RPEBC receiving sequential epirubicin/CMF regimens followed by tamoxifen, and for whom the status of ER and PgR was available.Results:Considering both cut-off values of 10% and 20%, PgR expression was significantly associated with age, menopausal status, and ER expression; HER2 status was associated with PgR status only at a cutoff value of 20% PgR. Upon univariate analysis, tumor size, nodal status, and PgR were significantly associated with disease-free survival (DFS) and overall survival (OS), while age class and local treatment type were associated only with DFS. Patients with PgR 20%. Upon multivariate analysis, only tumor size, nodal status, and PgR were independent prognostic factors.Conclusions:Our results highlight the independent prognostic relevance of PgR expression in patients with hormone-receptor-positive RPEBC treated with adjuvant chemotherapy and endocrine therapy, where the definition of prognostic subgroups is still a major need

Phase II Study of Dehydroepiandrosterone in Androgen Receptor-Positive Metastatic Breast Cancer.

LESSONS LEARNED: The androgen receptor (AR) is present in most breast cancers (BC), but its exploitation as a therapeutic target has been limited.This study explored the activity of dehydroepiandrosterone (DHEA), a precursor being transformed into androgens within BC cells, in combination with an aromatase inhibitor (to block DHEA conversion into estrogens), in a two-stage phase II study in patients with AR-positive/estrogen receptor-positive/human epidermal growth receptor 2-negative metastatic BC.Although well tolerated, only 1 of 12 patients obtained a prolonged clinical benefit, and the study was closed after its first stage for poor activity. BACKGROUND: Androgen receptors (AR) are expressed in most breast cancers, and AR-agonists have some activity in these neoplasms. We investigated the safety and activity of the androgen precursor dehydroepiandrosterone (DHEA) in combination with an aromatase inhibitor (AI) in patients with AR-positive metastatic breast cancer (MBC). METHODS: A two-stage phase II study was conducted in two patient cohorts, one with estrogen receptor (ER)-positive (resistant to AIs) and the other with triple-negative MBC. DHEA 100 mg/day was administered orally. The combination with an AI aimed to prevent the conversion of DHEA into estrogens. The main endpoint was the clinical benefit rate. The triple-negative cohort was closed early. RESULTS: Twelve patients with ER-positive MBC were enrolled. DHEA-related adverse events, reported in four patients, included grade 2 fatigue, erythema, and transaminitis, and grade 1 drowsiness and musculoskeletal pain. Clinical benefit was observed in one patient with ER-positive disease whose tumor had AR gene amplification. There was wide inter- and intra-patient variation in serum levels of DHEA and its metabolites. CONCLUSION: DHEA showed excellent safety but poor activity in MBC. Although dose and patient selection could be improved, high serum level variability may hamper further DHEA development in this setting

Modellazione numerica 2DV a supporto di una progettazione ecocompatibile delle difese costiere.

Al fine di una gestione sostenibile, un tema di recente interesse scientifico \ue8 la messa a punto di nuove metodologie per una progettazione interdisciplinare delle difese della costa. In questo contributo si considera in particolare il problema della progettazione e/o ottimizzazione delle sezioni trasversali di barriere a protezione del litorale che rendano minimo l\u2019impatto sull\u2019ambiente e favoriscano aspetti quali la biodiversit\ue0 e la colonizzazione della struttura stessa. Lo scopo di questo lavoro \ue8 proporre un metodo combinato basato sulla simulazione numerica 2DV, e il raccoglimento di dati ecologici sul campo per capire la relazione tra gli effetti idrodinamici indotti dalle barriere e gli organismi colonizzatori. Questo metodo \ue8 stato applicato utilizzando il codice COBRAS-UC al sito di studio di Elmer, grazie alla cooperazione con l\u2019Universit\ue0 di Cantabria e Plymouth

Immediate oral rehabilitation with quad zygomatic implants : ultrasonic technique vs conventional drilling

The insertion of zygomatic implants is a challenging surgery and requires special care and great precision. Piezoelectric surgery offers several advantages, since it provides a more precise bone cutting with an improved intraoperative visibility and a low temperature increase.The aim of this case-control study was to evaluate if the use of ultrasonic instruments for zygomatic implant surgery can be as effective as standard drilling instruments in terms of clinical outcomes. Ninety-two patients with atrophic maxilla were included in the study. Implant sites were prepared either with ultrasonic technique (Test group- 47 patients) or with traditional drilling (Control group- 45 patients). In total, 368 zygomatic implants were inserted (202 with "extrasinus technique", 77 with "sinus slot technique" and 89 with "Br\ue5nemark technique"). Complete arch provisional prostheses were delivered 3 to 5 hours after the surgical operations. The mean follow-up after surgery was 24 months (range 12-32 months). The primary outcome evaluations based on implant survival rates and postoperative complications. The operative time and surgeon's stress were evaluated as secondary outcomes. According to the results, implant survival rate was 100% in Test, and 98.89% in Control group. The postoperative complications were seen in 9 patients (4 in Test,  5 in Control group), and the difference was not statistically significant. The operative time was longer in the Test group, however surgeons were more comfortable while using ultrasonic instruments. Within the limitations of this preliminary study, ultrasonic technique can be considered as a feasible alternative to traditional drilling for zygomatic implant surgery

Implant primary stability with an osteocondensation drilling protocol in different density polyurethane blocks

The implant primary stability is a fundamental condition for avoiding implant micro-motions that might result in fibrous encapsulation; its achievement is facilitated by macro- and micro-geometry of the implant, and by the bone density and architecture at the intended implant site. The aim was to evaluate an osteocondensing drilling protocol for dental implant positioning compared to standard protocol on polyurethane block. A total of 40 implants, 20 for each osteocondensing group (Test) and 20 for standard drilling group (Control), were positioned. Insertion torque (IT), removal torque (RT), and Periotest were measured. A IT, RT, and Periotest significant difference was present in favor of the implant osteocondensing protocol. The results suggested that osteocondensing protocol represents a useful technique for implant placement in poor density bone

The Expression of Programmed Death Ligand 1 and Vimentin in Resected Non-Metastatic Non-Small-Cell Lung Cancer: Interplay and Prognostic Effects

Programmed death ligand 1 (PD-L1) is an immune checkpoint with a role in cancer-related immune evasion. It is a target for cancer immunotherapy and its expression is detected for the use of some immune checkpoint inhibitors in advanced non-small cell lung cancer patients (NSCLC). Vimentin is a key component of the epithelial-to-mesenchymal transition phenotype. Its expression has negative prognostic effects in NSCLC. In this study, we retrospectively evaluated PD-L1 and vimentin expression in tumor cells, immune infiltrate and PD-L1 positive immune infiltrate via immunohistochemistry in tissue samples from resected non-metastatic NSCLC patients. We explored the interplay between PD-L1 and vimentin expression through Spearman’s correlation test. We performed univariate analysis through the Cox models for demographic and clinico-pathological variables, and also for dichotomized biomarkers, i.e., PD-L1 and vimentin in tumor cells, both with 1 and 50% cutoffs. We used Kaplan-Meier method to estimate the overall survival, comparing both vimentin and PD-L1 positive patients with all the others. We found a weak positive correlation between PD-L1 and vimentin expressions in tumor cells (r = 0.25; p = 0.001). We also observed a statistically not significant trend towards a shorter overall survival in patients with both PD-L1 and vimentin expression >1% (HR = 1.36; 95% CI: 0.96–1.93, p = 0.087). In conclusion, these findings suggest that interplay between PD-L1 and vimentin may exist in non-metastatic NSCLC patients and the positivity of both markers in tumor tissue is associated with a trend towards a worse prognosis