Evaluation of two different remineralising toothpastes in children with drug-controlled asthma and allergic rhinitis: a randomised clinical trial.

AIM: To compare the efficacy of two remineralising toothpastes in children suffering from asthma and allergic rhinitis after a 6-month study. METHODS: 40 patients aged between 6-14 years with enamel demineralisations were enrolled for the study at the Unit of Dental Hygiene of the University of Pavia (Italy). The following indices were collected: Schiff air index (SAI), plaque index (PI), bleeding on probing (BoP), salivary pH, Basic Erosive Wear Examination (BEWE), susceptibility index (SI) for hard and soft tissues' pathologies, and decayed missing filled teeth (DMFT). After mechanical debridement with piezoelectric instrumentation and glycine powder, patients were equally divided into two groups: Group 1 using a toothpaste with zinc hydroxyapatite, and Group 2 using a toothpaste containing calcium sodium phosphosilicate. The toothpaste had to be used twice a day. The time frames of the study were: baseline (T0), after 1 month (T1), after 3 months (T2), after 6 months (T3). CONCLUSION: The tested toothpastes can be proposed for home use in children with asthma and allergic rhinitis as they significantly reduced dental sensitivity and periodontal indices.

Final results of the real-life observational VICTOR-6 study on metronomic chemotherapy in elderly metastatic breast cancer (MBC) patients.

Nowadays, treatment of metastatic breast cancer (MBC) has been enriched with novel therapeutical strategies. Metronomic chemotherapy (mCHT) is a continuous and frequent administration of chemotherapy at a lower dose and so whit less toxicity. Thus, this strategy could be attractive for elderly MBC patients. Aim of this analysis is to provide insights into mCHT's activity in a real-life setting of elderly MBC patients. Data of patients ≥ 75 years old included in VICTOR-6 study were analyzed. VICTOR-6 is a multicentre, Italian, retrospective study, which collected data on mCHT in MBC patients treated between 2011 and 2016. A total of 112 patients were included. At the beginning of mCHT, median age was 81 years (75-98) and in 33% of the patients mCHT was the first line choice. Overall Response Rate (ORR) and Disease Control Rate (DCR) were 27.9% and 79.3%, respectively. Median PFS ranged between 7.6 and 9.1 months, OS between 14.1 and 18.5 months. The most relevant toxicity was the hematological one (24.1%); severe toxicity (grade 3-4) ranged from 0.9% for skin toxicity up to 8% for hematologic one. This is a large study about mCHT in elderly MBC patients, providing insights to be further investigated in this subgroup of frail patients.

Metronomic chemotherapy (mCHT) in metastatic triple-negative breast cancer (TNBC) patients: results of the VICTOR-6 study.

PURPOSE: Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting. METHODS: We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%). RESULTS: Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9-7.2) and 12.1 months (95% CI: 9.6-16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0-18.4), 6.1 months (95% CI: 4.0-8.9) for CTX-based and 5.3 months (95% CI: 4.1-9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3-16.7 and CTX-based ones (95%CI: 8.7-52.8). Tumour response, PFS and OS decreased proportionally in later lines. CONCLUSION: This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.

Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.

LL37 exerts a dual pathogenic role in psoriasis. Bound to self-DNA/RNA, LL37 licenses autoreactivity by stimulating plasmacytoid dendritic cells-(pDCs)-Type I interferon (IFN-I) and acts as autoantigen for pathogenic Th17-cells. In systemic lupus erythematosus (SLE), LL37 also triggers IFN-I in pDCs and is target of pathogenic autoantibodies. However, whether LL37 activates T-cells in SLE and how the latter differ from psoriasis LL37-specific T-cells is unknown. Here we found that 45% SLE patients had circulating T-cells strongly responding to LL37, which correlate with anti-LL37 antibodies/disease activity. In contrast to psoriatic Th17-cells, these LL37-specific SLE T-cells displayed a T-follicular helper-(TFH)-like phenotype, with CXCR5/Bcl-6 and IL-21 expression, implicating a role in stimulation of pathogenic autoantibodies. Accordingly, SLE LL37-specific T-cells promoted B-cell secretion of pathogenic anti-LL37 antibodies in vitro. Importantly, we identified abundant citrullinated LL37 (cit-LL37) in SLE tissues (skin and kidney) and observed very pronounced reactivity of LL37-specific SLE T-cells to cit-LL37, compared to native-LL37, which was much more occasional in psoriasis. Thus, in SLE, we identified LL37-specific T-cells with a distinct functional specialization and antigenic specificity. This suggests that autoantigenic specificity is independent from the nature of the autoantigen, but rather relies on the disease-specific milieu driving T-cell subset polarization and autoantigen modifications.

Metronomic chemotherapy for advanced breast cancer patients in the real world practice: Final results of the VICTOR-6 study.

Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3-10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8-11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3-15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.

Nod2 Deficiency in mice is Associated with Microbiota Variation Favouring the Expansion of mucosal CD4+ LAP+ Regulatory Cells.

Nucleotide-binding Oligomerization Domain-2 (NOD2) mutations are associated with an increased risk to develop Crohn's Disease. In previous studies, we have shown that Nod2-/- mice manifest increased proportion of Lamina Propria (LP) CD4+ LAP+ Foxp3- regulatory cells, when compared with Nod2+/+ mice, while CD4+ Foxp3 + regulatory cells were not affected. Here, we investigated the Nod2 gut microbiota, by 16S rRNA pyrosequencing, at steady state and after TNBS-colitis induction in mice reared separately or in cohousing, correlating the microbial profiles with LP regulatory T cells proportion and tissue cytokines content. We found that enrichment of Rikenella and Alistipes (Rikenellaceae) in Nod2-/- mice at 8 weeks of age reared separately was associated with increased proportion of CD4+ LAP+ Foxp3- cells and less severe TNBS-colitis. In co-housed mice the acquisition of Rickenellaceae by Nod2+/+ mice was associated with increased CD4+ LAP+ Foxp3- proportion and less severe colitis. Severe colitis was associated with enrichment of gram-negative pathobionts (Escherichia and Enterococcus), while less severe colitis with protective bacteria (Barnesiella, Odoribacter and Clostridium IV). Environmental factors acting on genetic background with different outcomes according to their impact on microbiota, predispose in different ways to inflammation. These results open a new scenario for therapeutic attempt to re-establish eubiosis in Inflammatory Bowel Disease patients with NOD2 polymorphisms.

Air-abrasive debridement with glycine powder versus manual debridement and chlorhexidine administration for the maintenance of peri-implant health status: a six-month randomized clinical trial.

STUDY DESIGN: This single-masked, randomized and six-month clinical intervention trial including two study groups was planned to evaluate the efficacy of maintenance treatment with glycine powder on the periodontal health of peri-implant tissues. METHODS: A total of 46 patients with partial or total edentulism, carrying a total of 88 implants, were assigned either to an air abrasive with the glycine powder treatment group (AAD) or to a manual debridement and clorexidine administration treatment group (MDA). Clinical data were collected before treatment and at 3 and 6 months after the treatment. Plaque index (PI), bleeding index (BOP), probing depth (PD), clinical attachment level (CAL) and bleeding score (BS) were analysed. RESULTS: After 3 months, AAD treatment statistically significantly improved BS (P < 0.05); at 6 months, AAD treatment statistically significantly improved indexes PD, PI, BOP and BS (P < 0.05). In addition, the AAD treatment proved to be more effective than MDA in maintaining the peri-implant health of PD at three and 6 months, and of PI at 6 months (P < 0.05). There were no significant changes of CAL in both groups, and all the indexes remained within the physiological levels. CONCLUSIONS: Within the limits of the study, treatment with glycine seems appropriate in the maintenance of peri-implant health and more effective than the traditional treatment with plastic curette and chlorhexidine.

Comparison to the scanning electron microscope of professional dental hygiene methods on metal-free layered structures and metal-free monolithic structures processed by different polymerization cycles.

AIM: Aim of the study was to find effective instrumental methodologies and procedures for scaling and deplaquing without compromising the structure of metal-free, monolithic lithium disilicate and layered zirconia prosthetics. METHODS: Of 14 decontaminated, extracted teeth in good anatomical condition, 7 veneers lithium disilicate monolithic and 7 layered zirconia crowns were prepared for testing and divided into 6 treatment groups. Each group was composed of a veneer and a crown. The division of the groups was carried out according to the type of treatment performed- instrumental carbon fiber and steel tips, prophylaxis paste with high and low RDA (Relative dentin abrasion), bicarbonate powder. Samples were examined and observed through a scanning electron microscope (SEM). Afterwards a detailed comparison of the images of treated and untreated samples was performed. The images were at the same magnification, thus showing the differences in the treated samples. RESULTS: The monolithic lithium disilicate presents minor damage to the surface but no excessive changes to the structure in general post treatment. The layered zirconia resulted in notable damage with evident abrasions on the layered ceramic structure after the use of ultrasound with a steel tip and air flow with bicarbonate. Carbon fibre tips and prophylaxis paste containing perlite and low RDA did not create notable changes to the properties of the materials in question. CONCLUSION: The results of the disilicate monolithic appear to show it to be a much more resistant material compared to layered zirconia in ceramic. Its resistance is demonstrated by the lack of notable damage in all the treatment groups.

Effect of a structured, active, home-based cancer-treatment program for the management of patients on oral chemotherapy.

INTRODUCTION: The advent of oral chemotherapy agents has had a strong impact on several aspects of the management of cancer patients, including survival rates, health-care expenditure, and health-related quality of life. However, access to care and adherence to oral chemotherapy are central to optimal outcomes. PATIENTS AND METHODS: In this multicenter observational study, we assessed the effect of the "Active Home Care" initiative - a structured, active, home-based cancer-treatment program - on quality of life, health-care utilization, and patient adherence and satisfaction using self-administered questionnaires. Sixty-two patients treated with oral chemotherapy (capecitabine, vinorelbine, imatinib, sunitinib, sorafenib, temozolomide, ibandronate) were enrolled in the program. Weekly home visits were scheduled, each one with a trained nurse who delivered the home-based chemotherapy and reviewed patients' compliance and treatment toxicity. An oncologist evaluated patients and modified the dosage of oral chemotherapy based on toxicity reported during the previous cycle at bi-weekly visits. RESULTS: A total of 460 home visits were performed between April 2012 and February 2013. The Active Home Care initiative was associated with significant improvements in physical functioning and symptoms, and reductions in the access to cancer facilities. Satisfaction with oral chemotherapy and care received was high. All patients reported having taken their medications according to their prescription, and no patient reported difficulties in managing the oral chemotherapy regimen. CONCLUSION: The Active Home Care program was associated with improvements in the quality of life of patients and caregivers, better adherence to treatment, and the effective management of therapy and cancer-related symptoms. Home-based cancer treatment may also optimize the utilization of health-care resources.

Nod2 deficiency is associated with an increased mucosal immunoregulatory response to commensal microorganisms.

On the basis of previous studies demonstrating that a breach of the colonic epithelial barrier is associated with a microbiota-dependent increase in lamina propria (LP) regulatory cells, we investigated if the lack of spontaneous intestinal inflammation observed in nucleotide-binding oligomerization domain 2 (Nod2)-/- mice was due to enhanced intestinal regulatory function. We found that the LP CD4+ T-cell population of Nod2-/- mice contains an increased percentage of CD4+ regulatory T cells bearing transforming growth factor -ß/latency peptide (LP CD4+LAP (latency-associated peptide) + T cells) both under baseline conditions and following an intentional breach of the colonic barrier induced by ethanol administration. In addition, we found that Nod2-/- mice manifest decreased severity of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis and that TNBS-colitis in Nod2-/- or Nod2+/+ mice is ameliorated by adoptive transfer of LP cells from ethanol-treated mice before, but not after, depletion of LAP+ T cells. This increased regulatory T-cell response in Nod2-/- mice could explain why NOD2 polymorphisms in humans are not in themselves sufficient to establish inflammatory lesions.

Scientific activity and needs among medical oncology units in sicily: a survey of the italian association of medical oncology.

In the era of targeted therapies and combined modalities of treatment, scientific research plays a role of paramount importance in improving knowledge of cancer treatment. The aim of this survey was to review the scientific activity of medical oncology units in Sicily and to analyze their needs and possible pitfalls in order to improve future scientific cooperation.The regional section of the Italian Association of medical Oncology (AIOM) approved this survey in November, 2007. A systematic review of scientific activity produced by medical oncology units in Sicily during the last 5 years has been reviewed. papers dealing with solid tumors reported in the pubmed web site have been included in the analysis. Data were reported as absolute number of published papers and impact factor per medical oncology unit and also as a ratio between global impact factor and the number of personnel working in each single unit to analyze scientific production according to the workforce of each institution.We identified a total of 283 papers reported in pubmed between 2004 and march, 2009. The mean number of publications/unit was 10.9 with a range of 0-50. The mean number of publications/year was 11.7 with a range of 0.2-10. The 15 units included in the impact factor evaluation published 252 papers with a total impact factor of 1014.6 points in 5 years with a mean of 63.4 points per institution and a mean of 4.02 points/paper. However only four medical oncology units reported a cumulative 5-year impact factor >100 points.This survey has shown that a minority of medical oncology units in Sicily is constantly involved in clinical research although at different levels of activity. Overall the percentage of patients enrolled in clinical trials is very low. The main reasons for lack of participation in clinical trials include insufficient medical personnel, the absence of a specifically dedicated research unit inside the medical oncology structures and in some cases lack of research experience and of specific interests in this field.

Intestinal microflora and immunoregulation.

Immune homeostasis at mucosal level results from controlled response to intestinal luminal antigens. Recent insights into the nature of inflammatory bowel diseases, derived mainly from studies of experimental models of colonic inflammation, strongly suggest that they can result from a loss of immune tolerance to antigens in the bacterial microflora. Investigations of the regulatory mechanisms operating at the mucosal level suggest that regulatory cells reactive to the intestinal microflora might play a role in cross-reactive protection toward different antigens. Expansion of microflora-reactive regulatory cells by probiotic administration is able to protect from experimental colitis. Characterization of regulatory cells in response to normal commensal flora, the basis of their development and the role of innate immunity in this process might contribute to the understanding of the development of inflammatory bowel diseases.

Olanzapine overdose in an 18-month-old child.

Olanzapine is an atypical antipsychotic medication that was approved for use in the United States in 1996. While it is a widely used medication in adults, there has been minimal investigation into its effect on children. We present the case of an 18-month-old boy who ingested 30-40 mg of olanzapine, which resulted in significant symptoms, including respiratory distress and mental status changes. Previously reported pediatric cases of olanzapine ingestion have described similar symptoms. Therefore, the pediatric population should be monitored closely when ingestions of olanzapine occur.

[Old myocardial infarct: echocardiographic study]. / L'infarto miocardico di vecchia data: studio ecocardiografico.

UNLABELLED: A large number of patients survives many years after an acute myocardial infarction (AMI). Echocardiographic study in patients with a very old myocardial infarction (VOMI) can certainly contribute to a better understanding of anatomical and functional damage of the heart. AIM OF THE STUDY: To describe the echocardiographic pattern and to analyze differences between patients with anterior (ant.) and inferior (inf.) VOMI and subjects treated or not with a thrombolytic agent (T+ and T-). METHODS, DESIGN OBSERVATIONAL STUDY: We performed an M-B mode and color-doppler echocardiographic examination of 136 patients (M/F: 130/6), mean age 64.4 +/- 9 years, with an isolated VOMI that is least 5 years old (mean 9.5 +/- 3.1; range 5-16 years), with a good visualization of left ventricular (lv) endocardial profile and without left bundle branch block or valvulopathy is related to myocardial infarction. We established electrocardiographic site and thrombolytic treatment on a documental basis dating from AMI. End diastolic volume index (EDVi), end systolic volume index (ESVi), ejection fraction (EF), wall motion score index (WMSI), left atrial antero-posterior diameter (AD) and presence of any lv aneurysm, scar, thrombus, mitral regurgitation (MR) were assessed. Data were compared with those of 100 normal subjects (controls) with sex, age and physical settlement similar to those of the patients. RESULTS: EDVi appeared much more enlarged in patients than in controls (p < 0.0001). There was a large difference between ant. VOMI and inf. VOMI (p < 0.0001); where as a smaller increase was noticed in T+ versus (vs) T- patients (p = 0.04). In comparison with controls, a smaller difference was observed in inf. VOMI (p = 0.002). ESVi presented a similar behaviour in patients vs controls and ant. vs inf. VOMI (p < 0.0001), but there was no statistical difference between T+ and T- while a large difference was detected between inf. VOMI and controls (p < 0.0001). EF was lower in patients than in controls (p < 0.0001) and in ant. VOMI rather than in inf. VOMI (p < 0.0001); no statistically relevant difference was seen between T+ and T-, while a large difference was observed between inf. VOMI and controls (p < 0.0001). WMSI appeared to be significantly worse in patients vs controls (p < 0.0001), but there was also a great difference between ant. and inf. VOMI (p < 0.0001). T+ had a better index in comparison with T- (p = 0.02). There was also large difference between inf. VOMI and controls (p < 0.0001). AD was larger in patients than in controls (p < 0.0001), but there was no statistical difference between ant. and inf. VOMI and T+ and T-; in comparison with controls, smaller difference was seen in inf. VOMI (p = 0.04). Aneurysm was seen in 16% of patients, more prevalently in ant. (27%) than in inf. VOMI (5%) (p < or = 0.001). Scarring was seen in 45% of patients and, like aneurysms, more in ant. (69%) than in inf. VOMI (22%) (p < or = 0.001). Thrombus was rarely detected (5%) and only in ant. VOMI (12%) with aneurism (p < or = 0.01 vs inf.). MR was seen in a large number of patients (48%) and in 27% of controls (p < or = 0.001). No significant difference was pointed out between ant. and inf. VOMI. Aneurysm, thrombus and MR (21.8 and 55% respectively) were more prevalent in T- than in T+ (9.3 and 48% respectively), with no statistical significance. Scarring prevailed in T+ (48%) rather than in T- (43%), without any statistical difference. CONCLUSIONS: Patients with VOMI show increased lv volumes, decreased EF and persistence of regional wall motion abnormalities. Volumetric and kinetic modifications mainly involve ant. VOMI, but inf. VOMI also presents similar but smaller modifications. Left atrial dimensions also increase in VOMI. Aneurysms, scars, MR occur frequently; while the presence of thrombus is infrequent. Thrombolytic therapy appears to be a long-term protection from anatomical and functional damage. Echocardiography seems to be the ideal tech

[The observation by echocardiographic monitoring of the behavior of the main morphofunctional parameters of the left ventricle after an acute myocardial infarct]. / Osservazione mediante monitoraggio ecocardiografico del comportamento dei principali parametri morfofunzionali del ventricolo sinistro dopo infarto miocardico acuto.

In acute myocardial infarction (AMI) echocardiography is a means for revealing anatomical and functional damage. Up to date utilization of this method to monitor cardiac function during the in-hospital phase of AMI is rarely adopted. We performed serial echocardiographic examinations during the in-hospital phase of AMI to study the behaviour of left ventricular function at day 1, day 4-6 and at pre-discharge (after 11 +/- 3 days from admission). End diastolic volume (EDV), end systolic volume (ESV), ejection fraction (EF), wall motion score index (WMSI) were assessed. The study involved 108 patients with first AMI and with adequate echocardiographic resolution, selected from a population of 194 subjects consecutively admitted to the coronary care unit for suspected AMI. The population features were: mean age 60 +/- 13 years, 89 males and 19 females, 61 with anterior AMI and 47 with inferior AMI, 77 treated and 31 not treated by thrombolysis. Echocardiography was performed on day 1 (always after thrombolysis in treated patients), day 4-6, and at pre-discharge (11 +/- 3 days after admission) EDV, ESV and EF were calculated by single plane area-length method from the apical 4-chamber view; WMSI was calculated on a left ventricular 16-segment model, using the following scale: 1: normal or hyperkinetic; 2: hypokinetic; 3: akinetic, 4: dyskinetic, 5: aneurysm, and dividing the sum by the number of visualized segments. A modification in EDV and ESV was considered if there was a +/- 10% change in comparison with the initial or previous examination; EF was also considered to be modified for changes +/- 10%; WMSI was considered to be improved or worsened either in case of score variations of previously altered segments or in case of detection of new abnormally contracting segments. In order to improve reproducibility and adequate comparison of serial measurements we used a cine-loop technology with dual or quad-screen imaging. EDV, ESV EF and WMSI presented heterogeneous variations from day 1 to pre-discharge. For each observed parameter, we identified three main groups and six subgroups. Main groups identify stability (Group I), improvement (Group II) and worsening (Group III); subgroups, concerning only Group II and III and named a, b and c, identify the characteristics of improvement or worsening: a: continuous or persistent, b: late and c: discontinuous. No significant differences were found in each parameter between thrombolysed and non thrombolysed patients. As to the concomitance of belonging to the same main group, EF and WMSI presented the greatest agreement: 76% of patients; ESV, EF and WMSI agreed in 71% of patients; EDV, ESV, EF and WMSI agreed only in 59% of patients.