Ozone Treatment for the Management of Caries in Primary Dentition: A Systematic Review of Clinical Studies

Dental caries in children is a frequent and debilitating condition, whose management is often challenging. The aim of this systematic review was to investigate the effectiveness of ozone applications for the treatment of caries in primary dentition. According to PRISMA guidelines, a systematic literature search was performed up to 6 January 2024. Clinical studies using ozone to treat caries of deciduous teeth were considered for inclusion. Out of the 215 records retrieved, seven studies were eventually included in the review, all of which used gaseous ozone. Four studies were judged at high risk of bias, two at low risk, and one of some concerns. The great heterogeneity of designs, outcomes, and protocols made it impossible to conduct a meta-analysis. Despite some limitations, the evidence yielded by the included studies suggests that ozone application, regardless of the protocol applied, is comparable to other interventions in terms of clinical outcomes and anti-bacterial activity, with no reported adverse effects and good patient acceptance. Therefore, ozone application may be a non-invasive approach to treat caries in primary dentition, especially in very young and poorly cooperative patients. Further standardized and rigorous studies are, however, needed to identify the best clinical protocols for this specific field

Early fluoride intake and Molar Incisor Hypomineralisation (MIH) defects: A systematic review and dose-response meta-analysis

Background: Excessive intake of fluoride has been implicated in the complex multifactorial etiology of hypomineralisation (MIH) defects. Objective: To study the possible effect of early exposure to fluoride on the risk of molar incisor hypomineralisation, also through a dose-response approach. Methods: Observational and clinical studies investigating the relation between fluoride exposure from any source or evaluating exposure biomarkers and MIH defects. PubMed MEDLINE, Embase and Web of Science databases were con-sulted up to December 1, 2023, using terms related to “fluoride”, “enamel defects” and “demarcated opacities”. We performed a meta-analysis comparing the highest versus lowest fluoride exposure using a random-effects model, and we quantitively assessed this relation using piece-wise linear meta-regression. Results: Thirteen studies were included in the meta-analysis, 12 of which were eligible for the dose-response analysis, all regarding exposure from fluoride in drinking water. Three of them specifically addressed MIH, while the remaining concerned “demarcated opacities”, yet with features attributable to MIH. Comparing the highest versus lowest water fluoride exposure categories, virtually no evidence of a fluoride effect was identified, with an overall odds ratio of 0.93 [95% confidence interval 0.60; 1.45]. The dose-response meta-regression showed a decreasing risk for MIH defects exposure up to 1 mg/L, whereas an increase in risk emerged at higher exposure levels. Conclusions: This meta-analysis suggests that early systemic exposure to fluoride may affect the occurrence of MIH defects differently depending on fluoride concentration. However, these results need to be evaluated with caution due to potential methodological limitations of the studies included. (www.actabiomedica.it)

Neoadjuvant eribulin mesylate following anthracycline and taxane in triple negative breast cancer: Results from the HOPE study

Background Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy. Methods Patients with primary triple negative breast cancer 2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study. Results In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2–5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR. Conclusions Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial–mesenchymal transition, claims for further investigation. Trial registration EU Clinical Trial Register, EudraCT number 2012-004956-12

Nanoparticle albumin-bound paclitaxel: a big nano for the treatment of gastric cancer

Gastric cancer (GC) is the third cause of cancer-related death worldwide. Patients with unresectable GC can be treated with chemotherapy such as paclitaxel, which is a microtubule stabilizer. The use of nanoparticle albumin-bound paclitaxel (nab-ptx) avoids hypersensitivity reactions due to the absence of solvent needed to dissolve paclitaxel and it can be administered at higher doses. The ABSOLUTE randomized phase-3 clinical trial showed the non-inferiority of the nab-ptx used every week compared to the solvent-based paclitaxel used every week. This review describes the current advancements of the use of nab-ptx in GC in preclinical and clinical study investigations. The possibility of combining nab-ptx with other medications to improve response of patients to their specific molecular needs will also be debated

Colorectal cancer-screening program improves both short- and long-term outcomes: a single-center experience in Trieste

Screening programs (SC) have been proven to reduce both incidence and mortality of CRC. We retrospectively analyzed patients who underwent surgical treatment for CRC between 01/2011 and 01/2017. The current screening program in our region collects patients aged from 50 to 69. For this reason, out of a total of 600 patients, we compared 125 patients with CRC founded during the SC to 162 patients who presented with symptoms and were diagnosed between\ua050\u201369\ua0years old (NO-SC). 45% patients in the SC group were diagnosed as AJCC stage I vs 27% patients in the NO-SC group; 14% vs 20% were stage II, 14% vs 26% were stage III, and 3% vs 14% were stage IV (p 0.002). We found a significant difference in surgical approach: 89% SC vs 56% NO-SC patients had laparoscopic surgery (p 0.002). In the NO-SC group, 16% patients underwent resection in an emergency setting. Only 5% patients in the SC group had postoperative complications vs 14% patients in the NO-SC group (p 0.03). We had a 2-year OS of 86%, being 95% in the SC group and 80% in the NO-SC group (p 0.002). Likewise, the whole 2-year DFS was 77%, whereas it was 90% in the SC group and 66% in the NO-SC group (p 0.002). Screening significantly improves early diagnosis and accelerated surgical treatment. We obtained earlier stages at diagnosis, a less invasive surgical approach, and lower rates of complications and emergency surgery, all this leading to an improvement in both OS and DFS

Lenvatinib for the treatment of renal cell carcinoma

Introduction: Renal cell carcinoma (RCC) accounts for 2\u20133% of all solid tumors. Expression of the receptor for the vascular endothelial growth factor (VEGF) is one of the most common features of RCC. Areas covered: Lenvatinib is a novel multi-kinase inhibitor that has been studied in several solid tumors. It has shown promising results in the treatment of RCC, especially when combined with everolimus, In this review, we summarize the available data of lenvatinib for the treatment of advanced/metastatic renal cell carcinoma. Expert opinion: Lenvatinib in combination with everolimus has provided encouraging results in both clinical and laboratory investigations showing that blocking angiogenesis and the mTOR signalling pathway could be a remarkable approach for treating RCC. As an additive to this type of approach it would be interesting in future clinical settings testing also the combination of lenvatinib and everolimus with immune-therapy

Management of the axilla in breast cancer:\ua0outcome analysis in a series of ductal versus lobular invasive cancers

Introduction: Axillary lymph node dissection (ALND) has been considered essential for the staging of breast cancer (BC). As the impact of tumor biology on clinical outcomes is recognized, a surgical de-escalation approach is being implemented. We performed a retrospective study focused on surgical management of the axilla in invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). Materials and methods: 1151 newly diagnosed BCs, IDCs (79.6%) or ILCs (20.4%), were selected among patients treated at our Breast Cancer Unit from 2012 to 2018. Tumor characteristics and clinical information were collected and predictors of further metastasis after positive sentinel lymph node biopsy (SLNB) analyzed in relation to disease-free survival (DFS) and overall survival (OS). Results: 27.5% of patients with ILC had 65 3 metastatic lymph nodes at ALND after positive SLNB versus 11.48% of IDCs (p = 0.04). Risk predictors of further metastasis at ALND were the presence of > 2 positive lymph nodes at SLNB (OR = 4.72, 95% CI 1.15\u201319.5 p = 0.03), T3\u2013T4 tumors (OR = 4.93, 95% CI 1.10\u201322.2, p = 0.03) and Non-Luminal BC (OR = 2.74, 95% CI 1.16\u20136.50, p = 0.02). The lobular histotype was not associated with the risk of further metastasis at ALND (OR = 1.62, 95% CI 0.77\u20133.41, p = 0.20). Conclusions: ILC histology is not associated with higher risk of further metastasis at ALND in our analysis. However, surgical management decisions should be taken considering tumor histotype, biology and expected sensitivity to adjuvant therapies

Updates on the CDK4/6 inhibitory strategy and combinations in breast cancer

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in recent decades, improving the life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the Cyclin dependent kinase inhibitors family INK4 that specifically inhibit CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years, the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in other BC subtypes. In HER2-positive BC, a combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, the efficacy of CDK4/6 inhibitors has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions for ongoing clinical trials and predictive biomarkers will be further debated

Intracerebral Transplantation and In Vivo Bioluminescence Tracking of Human Neural Progenitor Cells in the Mouse Brain

Cell therapy has long been an emerging treatment paradigm in experimental neurobiology. However, cell transplantation studies often rely on end-point measurements and can therefore only evaluate longitudinal changes of cell migration and survival to a limited extent. This paper provides a reliable, minimally invasive protocol to transplant and longitudinally track neural progenitor cells (NPCs) in the adult mouse brain. Before transplantation, cells are transduced with a lentiviral vector comprising a bioluminescent (firefly-luciferase) and fluorescent (green fluorescent protein [GFP]) reporter. The NPCs are transplanted into the right cortical hemisphere using stereotaxic injections in the sensorimotor cortex. Following transplantation, grafted cells were detected through the intact skull for up to five weeks (at days 0, 3, 14, 21, 35) with a resolution limit of 6,000 cells using in vivo bioluminescence imaging. Subsequently, the transplanted cells are identified in histological brain sections and further characterized with immunofluorescence. Thus, this protocol provides a valuable tool to transplant, track, quantify, and characterize cells in the mouse brain