Breast cancer early diagnosis experience in Florence: can a self referral policy achieve the results of service screening?

STUDY OBJECTIVE--To assess the impact of a breast clinic on a specific target population and evaluate early diagnosis performance indicators for breast cancer in the presence of a self referral policy. DESIGN--Women living in Florence between 1980 and 1989 who had undergone mammography at a self referral breast clinic were studied. Main outcome measures were the use of mammography in relation to age, symptoms, and the interval between two subsequent tests, and early diagnosis performance indicators were the detection rate (DR), the prevalence/incidence ratio, and the proportion of early detected cancers. Performance indicators were compared with those from formal screening programmes. SETTING--Florence, Italy. PATIENTS--All mammograms performed at the clinic from 1980-89 in 40-69 year old women living in Florence were examined (n = 42,226). Records included the date of birth and of the examination, the reason for testing (asymptomatic/presence of pain/presence of symptoms other than pain), and the TNM classification for breast cancer cases. MAIN RESULTS--The total number of mammograms performed per annum increased by 70% over the decade, but much of this was routine repeat mammography (54.1% in 1989). Rates of first examinations in asymptomatic women increased in the second half of the decade from 17 per 1000 in 1985 to 31 per 1000 in 1989. Mammographic coverage decreased with increasing age from 12.6% in 40-49 year olds to 6.0% in 60-69 years old. Performance indicators of the activity in asymptomatic women were comparable with those expected in service screening. The proportion of not advanced cancers detected in asymptomatic women was 62.3% with a DR of 5.3 per 1000, and the average prevalence/incidence ratio was 2.9. CONCLUSIONS--High quality mammography performed in a breast clinic in self referred asymptomatic women can achieve as good results as a formal invitation screening service. Only a few of these women will benefit, but those who do are likely to be younger (40-49 year old women).     

Role of nitric oxide in the biology, physiology and pathophysiology of reproduction

Following its benchmark discovery, nitric oxide (NO) is nowknown to play important functional roles in a variety of physiologicalsystems. Within the vasculature, NO induces vasodilation, inhibitsplatelet aggregation, prevents neutrophil/platelet adhesionto endothelial cells, inhibits smooth muscle cell proliferationand migration, regulates programmed cell death (apoptosis) andmaintains endothelial cell barrier function. NO generated byneurons acts as a neurotransmitter, whereas NO generated bymacrophages in response to invading microbes acts as an antimicrobialagent. Because neurons, blood vessels and cells of the immunesystem are integral parts of the reproductive organs, and inview of the important functional role that NO plays in thosesystems, it is likely that NO is an important regulator of thebiology and physiology of the reproductive system. Indeed, inthe past 10 years, NO has established itself as a polyvalentmolecule which plays a decisive role in regulating multiplefunctions within the female as well as the male reproductivesystem. This review provides an overview of the role of NO invarious reproductive organs under physiological and pathologicalconditions.     

DNA cross-link-dependent RAD50/MRE11/NBS1 subnuclear assembly requires the Fanconi anemia C protein

Fanconi anemia (FA) is a cancer-predisposition syndrome characterized by hypersensitivity to interstrand-cross-link (ICL) inducers. FA hypersensitivity to ICL has been correlated with alterations in homologous recombination, non-homologous end-joining, telomere maintenance, DNA-damage assessment and checkpoint regulation, processes in which the components of the RAD50/MRE11/NBS1 (RMN) complex are involved. To better characterize the mechanisms by which ICL are processed in human cells and to gain insight into their toxicity in FA, we examined (i). the RMN complex assembling in response to the ICL inducers mitomycin C (MMC) and photoactivated 8-methoxypsoralen and (ii). the proficiency of FA cells to perform RMN activation in response to ICL inducers. We show here that ICL activates the assembly of the RMN proteins into subnuclear foci, and that their formation proceeds independently of ICL incision, a step mainly dependent on XP-F/ERCC1 heterodimer activity. Interestingly, FA cells were unable to form RMN foci in response to either ICL inducer. Analysis by pulsed-field gel electrophoresis and single-cell gel electrophoresis of MMC-treated cells showed that FA cells from complementation group C (FA-C cells, defective in the FANCC gene) form double-strand breaks and unhook MMC-induced ICL similarly to FANCC wild-type cells. These observations imply that the absence of RMN assembly in FA-C cells is not simply due to the absence of DNA ends produced as intermediates of ICL processing, and indicates a direct role for FANCC in RMN focus assembly in response to ICL inducers. Moreover, we show that the formation of foci, including BRCA1 and/or RAD51 proteins, is significantly delayed in FA cells. These alterations in the assembly of DNA-repair proteins in FA provide an interpretation for the DNA-damage processing anomalies observed in FA cells and for the genetic instability and the cancer predisposition of the syndrome.     

Benign breast disease and breast cancer: a case-control study in a cohort in Italy

Sixty-two cases of invasive breast cancer were identified in a large cohort of women previously treated for biopsy-proven benign breast disease (BBD) at the Breast Unit of CSPO, in Florence, along with a group of 315 controls, strictly matched by age and year of diagnosis. A pathologist reviewed and reclassified all the original BBD slides according to recently proposed criteria (no evidence of epithelial proliferation, epithelial proliferation without or with atypia). Information about potential confounding factors was collected during personal interviews. In comparison to the women with "non-proliferative" BBD, women classified as having "proliferative disease without atypia" showed a weak and non-significant increase in risk (OR 1.3; 95% CI: 0.5-3.5). In contrast, women with "atypical hyperplasia" were at very high risk of developing breast cancer (OR 13.0; 95% CI: 4.1-41.7). When planning mammography screening or other large-scale early-diagnosis programmes for breast cancer in the general female population, follow-up of high-risk subgroups of BBD patients should be considered.     

How do I manage a patient with enterococcal bacteraemia?

BackgroundEnterococcal bacteraemia (EB) is common, particularly in the nosocomial setting, and its management poses a challenge for clinicians and microbiologists.ObjectivesThe aim was to summarize the more relevant features of EB and to provide a practical state-of-the-art on the topics that more directly affect its management.SourcesPubmed articles from inception to 31 May 2020.ContentThe following topics are covered: epidemiological, clinical and microbiological characteristics and factors associated with prognosis of EB; diagnosis and work-up, including the use of echocardiography to rule out endocarditis; antibiotic management with special focus on antimicrobial resistance and complicated EB; and the role of infectious disease consultation and the use of bundles in EB. In addition, three clinical vignettes are presented to illustrate the practical application of the guidance provided, and major gaps in the current evidence supporting EB management are discussed.ImplicationsEB is associated with large burdens of morbidity and mortality, particularly among fragile and immunosuppressed patients presenting complicated bacteraemia due to multidrug-resistant enterococci. Most cases of EB are caused by Enterococcus faecalis, followed by E. faecium. EB often presents as polymicrobial bacteraemia. Rapidly identifying patients at risk of EB is crucial for timely application of diagnostic techniques and empiric therapy. Early alert systems and rapid diagnostic techniques, such as matrix-assisted desorption ionization–time of flight mass spectrometry, especially if used together with infectious disease consultation within bundles, appear to improve management and prognosis of EB. Echocardiography is also key in the work-up of EB and should probably be more extensively used, although its exact indications in EB are still debated. Multidisciplinary approaches are warranted due to the complexity and severity of EB.     

Streptococcus pneumoniae serotype 19A in Latin America and the Caribbean: a systematic review and meta-analysis, 1990-2010

ABSTRACT: BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are in the process of implementation in Latin America. Experience in developed countries has shown that they reduce the incidence of invasive and non-invasive disease. However, there is evidence that the introduction of PCVs in universal mass vaccination programs, combined with inappropriate and extensive use of antibiotics, could be associated to changes in non-PCV serotypes, including serotype 19A. We conducted a systematic review to determine the distribution of serotype 19A, burden of pneumococcal disease and antibiotic resistance in the region. METHODS: We performed a systematic review of serotype 19A data from observational and randomized clinical studies in the region, conducted between 1990 and 2010, for children under 6 years. Pooled prevalence estimates from surveillance activities with confidence intervals were calculated. RESULTS: We included 100 studies in 22 countries and extracted data from 63. These data reported 19733 serotyped invasive pneumococcal isolates, 3.8% of which were serotype 19A. Serotype 19A isolates were responsible for 2.4% acute otitis media episodes, and accounted for 4.1% and 4.4% of 4,380 nasopharyngeal isolates from healthy children and in hospitalbased/ sick children, respectively. This serotype was stable over the twenty years of surveillance in the region. A total of 53.7% Spn19A isolates from meningitis cases and only 14% from non meningitis were resistant to penicillin. CONCLUSIONS: Before widespread PCV implementation in this region, serotype 19A was responsible for a relatively small number of pneumococcal disease cases. With increased use of PCVs and a greater number of serotypes included, monitoring S. pneumoniae serotype distribution will be essential for understanding the epidemiology of pneumococcal disease.     

Culture,Ethnicity, and Level of Education in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most frequent cause of dementia, where the abnormal accumulation of beta-amyloid (Aβ) and tau lead to neurodegeneration as well as loss of cognitive, behavioral, and functional abilities. The present review analyzes AD from a cross-cultural neuropsychological perspective, looking at differences in culture-associated variables, neuropsychological test performance and biomarkers across ethnic and racial groups. Studies have found significant effects of culture, preferred language, country of origin, race, and ethnicity on cognitive test performance, although the definition of those grouping terms varies across studies. Together, with the substantial underrepresentation of minority groups in research, the inconsistent classification might conduce to an inaccuratte diagnosis that often results from biases in testing procedures that favor the group to which test developers belong. These biases persist even after adjusting for variables related to disadvantageous societal conditions, such as low level of education, unfavorable socioeconomic status, health care access, or psychological stressors. All too frequently, educational level is confounded with culture. Minorities often have lower educational attainment and lower quality of education, causing differences in test results that are then attributed to culture. Higher levels of education are also associated with increased cognitive reserve, a protective factor against cognitive decline in the presence of neurodegeneration. Biomarker research suggests there might be significant differences in specific biomarker profiles for each ethnicity/race in need of accurate cultural definitions to adequately predict risk and disease progression across ethnic/racial groups. Overall, this review highlights the need for diversity in all domains of AD research that lack inclusion and the collection of relevant information from these groups.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01193-z.