Community water fluoridation and caries prevention: a critical review

The aim of this paper was to critically review the current role of community water fluoridation in preventing dental caries. Original articles and reviews published in English language from January 2001 to June 2006 were selected through MEDLINE database. Other sources were taken from the references of the selected papers. For the past 50 years community water fluoridation has been considered the milestone of caries prevention and as one of the major public health measures of the 20th century. However, it is now accepted that the primary cariostatic action of fluoride occurs after tooth eruption. Moreover, the caries reduction directly attributable to water fluoridation have declined in the last decades as the use of topical fluoride had become more widespread, whereas enamel fluorosis has been reported as an emerging problem in fluoridated areas. Several studies conducted in fluoridated and nonfluoridated communities suggested that this method of delivering fluoride may be unnecessary for caries prevention, particularly in the industrialized countries where the caries level has became low. Although water fluoridation may still be a relevant public health measure in poor and disadvantaged populations, the use of topical fluoride offers an optimal opportunity to prevent caries among people living in both industrialized and developing countries.     

Influence of Surgical Margins on the Outcome of Breast Cancer Patients: A Retrospective Analysis

Objective

Breast-conserving surgery has become the preferred treatment for early breast cancer. Yet the question of what constitutes a ‘safe margin’, in terms of impact on patient outcome, remains unanswered. Our aim was to address this knowledge gap by determining the prevalence of positive and narrow margins after breast-conserving surgery, and evaluating how margin status impacted local recurrence and overall survival.

Materials and Methods

We collected data about all women who underwent breast-conserving cancer surgery in our department between 2002 and 2011, focusing on patient and tumor characteristics, the distance from the tumor to the surgical margin, therapies administered, and outcome (measured in terms of local recurrence and overall survival). Data were analyzed by R (version 3.0.1), considering p < 0.05 as significant. Multivariate analyses were also performed.

Results

Of 1,192 women who received breast-conserving surgery, 264 were considered for widening; 111 of these patients had positive margins and 153 narrow (where narrow was defined as less than 5 mm). Widening was performed for 38 % of these patients (99/264) and mastectomy for 27 % (70/264), while 36 % (95/264) had no further surgery and were simply followed-up. Our multivariate analysis confirmed that local tumor recurrence and overall survival were not significantly influenced by margin status, either at initial surgery, or (for those patients with initially positive margins) at secondary margin-widening surgery. However, the following were found to be significantly correlated with local recurrence: tumor multifocality, high expression of Ki-67/Mib-1, comedo-like necrosis, and non-axillary lymph node positivity (p < 0.05).

Conclusions

We found the status of resection margins and the management of infiltrated or narrow margins to have no significant influence on local tumor recurrence rates or on overall patient survival. Instead, biological factors connected with tumor aggressiveness seem to play the most important role in breast cancer prognosis, independent of surgical radicality.     

The importance of being "not transplantable": an interesting patient

MitraClip therapy for Mitral Regurgitation(MR) in advanced-endstage heart failure(HF),could open a final bridge to improve symptoms and quality of life in \"not transplantable\" patients. We describe a homeless patient with NYHA class III HF, not elegible to heart transplantation for poor socio-economic status,and severe functional MR,treated with MitraClip. The patient was not suitable for conventional mitral valve repair because of high surgical risk and advanced HF (The STS mortality morbidity score=76%; EUROSCORE II=9,7%). Severe MR was confirmed at TEE preoperative evaluation of patient in which severe LV systolic dysfunction, diastolic dysfunction, severe right ventricle dysfunction, moderate tricuspid regurgitation and post-capillary pulmonary hypertension were detected. After 2 MitraClips implantation, TEE documented effective device position in relation to the main regurgitant jet, a MR grade reduction to 2 , with uneventful recovery. A gradual hemodynamic and general improvement was observed at three-month follow-up echocardiography documenting PAPs reduction and LVEF improvement. Beside, the patient showed HF symptoms reduction in NYHA class I-II. Management of functional MR in end-stage HF is an hard challenge, in addiction to the limited patient group feasibility and long-waiting list of heart transplantation. In the setting of this difficult current real-world experience, percutaneous tecnique was able to improve general conditions, quality of life and survival of our referred patient.     

In vivo selection of genetically modified erythroblastic progenitors leads to long-term correction of beta-thalassemia

Gene therapy for β-thalassemia requires stable transfer of a β-globin gene into hematopoietic stem cells (HSCs) and high and regulated hemoglobin expression in the erythroblastic progeny. We developed an erythroid-specific lentiviral vector driving the expression of the human β-globin gene from a minimal promoter/enhancer element containing two hypersensitive sites from the β-globin locus control region. Transplantation of transduced HSCs into thalassemic mice leads to stable and long-term correction of anemia with all red blood cells expressing the transgene. A frequency of 30–50% of transduced HSCs, harboring an average vector copy number per cell of 1, was sufficient to fully correct the thalassemic phenotype. In the mouse model of Cooley's anemia transplantation of transduced cells rescues lethality, leading to either a normal or a thalassemia intermedia phenotype. We show that genetically corrected erythroblasts undergo in vivo selection with preferential survival of progenitors harboring proviral integrations in genome sites more favorable to high levels of vector-derived expression. These data provide a rationale for a gene therapy approach to β-thalassemia based on partially myeloablative transplantation protocols.     

A novel type of familial transthyretin amyloidosis, ATTR Asn124Ser, with co-localization of kappa light chains.

A 68-year-old Italian woman who had a clinical history of thyroidectomy in 2002 presented with slowly progressing renal insufficiency and non-nephrotic proteinurea in 2004. A renal biopsy showed the occurrence of amyloid; the thyroid biopsy previously taken also revealed amyloid infiltration. Other amyloid-containing tissues included bone marrow and heart. The plasma cell level in the bone marrow was found to be less than 5% and both serum and urine samples were positive for a monoclonal kappa light chain band. DNA analysis unexpectedly revealed the presence of a novel transthyretin (TTR) mutation, ATTR Asn124Ser. Histologically, amyloid deposits in the thyroid had a homogeneous appearance with moderate Congophilia. In immunohistochemistry, a kappa light chain antiserum showed positive immunoreactivity with amyloid deposits in the thyroid. Furthermore, a TTR antiserum, anti-TTR50-127, also recognized a number of amyloid deposits stained positive with the kappa light chain antiserum. Overall, the kappa light chain antiserum reacted with most of the amyloid deposits in the thyroid, whereas TTR immunoreactivity was scarcer, with a scattered appearance. In contrast, only the anti-TTR50-127 antiserum labeled amyloid in the kidney, albeit not all deposits. In this study, we report a patient having a novel TTR variant, ATTR Asn124Ser, with co-localization of kappa light chains in the amyloid deposits in the thyroid tissue.     

A comprehensive management system for heart failure improves clinical outcomes and reduces medical resource utilization]

BACKGROUND: Hospital admissions for heart failure are common and readmission rates are high. Many admissions and readmissions may be avoidable, so that alternative strategies are needed to improve long-term management. METHODS: We conducted a randomized trial of the effect of a guideline-based intervention on rates of readmission within 90 days of hospital discharge and costs of care for patients who were hospitalized due to decompensated heart failure. The intervention consisted of comprehensive education of the patient and family, a prescribed diet and intensive application of guidelines' recommendations on pharmacological therapy. The intervention started before discharge and continued thereafter with follow-up visits for up to 3 months. Two hundred and nine guideline-managed patients were compared to 209 concurrent normally-discharged patients. RESULTS: Patients in the study group were more prescribed beta-blockers, ACE-inhibitors, angiotensin receptor blockers, and spironolactone. Sixteen patients (8%) in the intervention group and 31 (15%) among controls were readmitted for DRG 127, within 3 months of discharge (Fisher's exact test, p < 0.01), while the 6-month mortality rate was similar between groups (9 and 11.5% respectively). Quality of life significantly improved from 5.6 +/- 1.0 to 6.1 +/- 1.9 (Mann-Whitney U-test, p < 0.05). The overall costs of care were lower for guideline-managed patients (110 vs 150 Euro per patient per month), due to the lower readmission rates. CONCLUSIONS: Our study showed that a guideline-based management program for patients with heart failure at discharge improves quality of life and reduces readmission for DRG 127 and total bed days, allowing relevant cost savings.