Germline investigation in male breast cancer of DNA repair genes by next-generation sequencing.

PURPOSE: In order to better define the breast cancer (BC) genetic risk factors in men, a germline investigation was carried out on 81 Male BC cases by screening the 24 genes involved in BC predisposition, genome stability maintenance and DNA repair mechanisms by next-generation sequencing. METHODS: Germline DNAs were tested in a custom multi-gene panel focused on all coding exons and exon-intron boundaries of 24 selected genes using two amplicon-based assays on PGM-Ion Torrent (ThermoFisher Scientific) and MiSeq (Illumina) platforms. All variants were recorded and classified by using a custom pipeline. RESULTS: Clinical pathological data and the family history of 81 Male BC cases were gathered and analysed, revealing the average age of onset to be 61.3 years old and that in 35 cases there was a family history of BC. Our genetic screening allowed us to identify a germline mutation in 22 patients (23%) in 4 genes: BRCA2, BRIP1, MUTYH and PMS2. Moreover, 12 variants of unknown clinical significance (VUS) in 9 genes (BARD1, BRCA1, BRIP1, CHEK2, ERCC1, NBN, PALB2, PMS1, RAD50) were predicted as potentially pathogenic by in silico analysis bringing the mutation detection rate up to 40%. CONCLUSION: As expected, a positive family history is a strong predictor of germline BRCA2 mutations in male BC. Understanding the potential pathogenicity of VUS represents an extremely urgent need for the management of BC risk in Male BC cases and their own families.

Quality of life and satisfaction of patients after oncoplastic or traditional breast-conserving surgery using the BREAST-Q (BCT module): a prospective study.

INTRODUCTION: The oncoplastic conservative surgery was developed as a natural evolution of traditional surgery, attempting to improve the therapeutic and aesthetic outcomes where tumor resection could be followed by not-adequate results. Our primary aim is to evaluate how patient satisfaction and quality-of-life after conservative oncoplastic surgery, using BREAST-Q (BCT Module), change pre- and post-operatively. The secondary aim is to compare patient-reported outcome after oncoplastic or traditional conservative surgery. PATIENTS AND METHODS: We enrolled 647 patients who underwent traditional conservative surgery or oncoplastic surgery from January 2020 to December 2022. Only 232 women (35.9%) completed the BREAST-Q questionnaire on a web-based platform, at the preoperative phase and 3 months after treatment. RESULTS: The average score of "Psychosocial well-being" and "Satisfaction with Breasts" 3 months after surgery showed a statistically significant improvement, while the average score for "Physical well-being: Chest" at 3 months showed a worsening compared to the baseline. "Sexual well-being" did not show statistically significant change. A significant difference between the post-operative outcome of oncoplastic surgery and traditional surgery was observed only for Physical well-being (better for traditional surgery). CONCLUSIONS: The study showed significant improvement in patient-reported outcomes 3 months after the surgery, except for physical discomfort that increases especially after oncoplastic surgery. Furthermore, our data, as well as many others, point to the appropriateness of using OCS where there is an effective indication, while the perspective of patients cannot find significant superiority over TCS in any of the areas analyzed.

Norovirus contamination in different shellfish species harvested in the same production areas.

AIMS: To investigate Norovirus (NoV) contamination of mussels, clams and oysters harvested in two class B harvesting areas of the delta of the Po river, to choose a species as an indicator. METHODS AND RESULTS: Environmental parameters (temperature and salinity) and hydrometric levels of the tributary river were measured. Seventy shellfish samples (35 samples per area) were examined for Escherichia coli and NoV (GI and GII). NoV contamination was found in 51.4% of samples, of which, 2.9% contained only NoV GI, 14.3% only NoV GII, while the majority of the samples (34.3%) contained both genogroups. Most of the positive results (90.0%) were obtained in the period between November 2008 and April 2009. CONCLUSIONS: No significant differences were found between the results from the two harvesting areas and the three shellfish species. However, on the basis of the average C(t) values, the recovery rate (from 0.46 to 1.15%) and the distribution of positive results in the samplings, mussels seem to be a suitable indicator species to monitor viral contamination in these areas. SIGNIFICANCE AND IMPACT OF THE STUDY: The data allow the optimization of monitoring plans to improve the prevention strategies in terms of money and time, by the intensification of controls in the cold season and the use of one species as indicator.

Effect of high hydrostatic pressure on murine norovirus in Manila clams.

AIMS: Eating raw or insufficiently cooked bivalve molluscs contaminated with human noroviruses (NVs) can result in acute cases of gastroenteritis in humans. Manila clams (Ruditapes philippinarum) are particularly prone to exposure to NVs due to the brackish environment in which they are farmed which is known to be susceptible to human faecal contamination. High hydrostatic pressure processing (HHP) is a food treatment technique that has been shown to inactivate NV. METHODS AND RESULTS: In this study we investigated the ability of HHP to inactivate murine norovirus (MNV-1), a recognised surrogate for NV, in experimentally contaminated manila clams. Pools of contaminated live clams were subjected to hydrostatic pressure ranging from 300 to 500 MPa for different time intervals of between one and 10 min. The trial was repeated three times, at monthly intervals. CONCLUSIONS: Virus vitality post-treatment was assessed and the data obtained indicates that the use of high hydrostatic pressures of at least 500 MPa for 1 min was effective in inactivating MNV-1. SIGNIFICANCE AND IMPACT OF THE STUDY: HHP results to be an effective technique that could be applied to industrial process to obtain safe Manila clams ready to eat.

Occurrence of enteric viruses in shellfish and relation to climatic-environmental factors.

AIMS: To investigate the presence of enteric viruses [hepatitis A (HAV) and norovirus (NoV)] in shellfish harvested from the deltaic area of the Po river in relation to environmental factors. METHODS AND RESULTS: Fortnightly sampling of shellfish was carried out in two lagoon areas (category B production areas) and one sea area (category A). Environmental parameters in the lagoon and hydrometric level of the tributary river were monitored throughout the sampling period. Samples (n = 120) were analysed for bacterial (E. coli and Salmonella) and viral (HAV and NoV) contamination; samples from category B areas were analysed before and after purification treatment. All the samples were negative for HAV whereas 10 samples (8.3%), all harvested in the lagoon areas, were positive for NoV. Sequencing identified the strains as genotypes II.4 and II.b. None of the samples was found to be contaminated after depuration. CONCLUSIONS: The monitoring showed a low frequency of NoV presence; viral contamination, detected exclusively in shellfish collected from the deltaic area (category B), could be influenced by the flow of the tributary river. The data collected are useful for the design of targeted prevention strategies and for the modulation of control plans after meteorological events.

[The pattern of use of emergency department in the local unit of Como]. / La valutazione dell'appropriatezza di utilizzo dei servizi di urgenza/emergenza ospedaliera nella ASL della città di Como.

The pattern of use of emergency department of hospitals is on the agenda of policy makers at national, regional and local level. It is still difficult to achieve a balance between the claim for improving the accessibility in order to allow people in need to receive this level of care and the possible its inappropriate use. The triage procedure offers the possibility to assess priorities because the "white codex" identifies those whose access to emergency department could potentially be diverted to an other level of care. The use of the Emergency Department is studied in an affluent area of Northern Italy using an "ad hoc" tool and data linkage in order to describe the process and its possible failures. The results are aimed to give decision makers the opportunity to start addressing these issues on sounder bases particularly as far as triage based assessment is concerned.

[Pre-adolescents and sport: results of a health survey in some secondary schools of Brianza]. / I preadolescenti e lo sport: risultati di un'indagine in alcune scuole medie dell'area brianzola.

This study is aimed at assessing time dedicated to, motivation and involvement in physical activity on behalf of pre-adolescents. 802 students (49.3% boys and 50.7% girls; mean age: 12.6) attending 43 classes of 11 Brianza's post-elementary schools. A questionnaire was prepared and administered to the involved sample. Classes took part in this study through randomized selection and data were analyzed using program Epi Info 6. Most of the respondents (60.1%) stay involved in sport because "it makes me feel good" and 32.4% because sport is "enjoyable and entertaining". Pre-adolescents chose the sport in which they become engaged on the basis of personal inclination (40%), in order to share experiences and their free time with friends (15.4%); 13.7% declare to prefer sport to be practiced in team. (13.7%). The most practiced sport are: football (51.3% boys, 4.5% girls), volley (3.9%-36.4%), dance (0.8%-25.2%) e swimming (9.4%-14%). 80.8% in the sample practice physical activity in settings outside schools and, among these, 51.7% dedicate three or more hours weekly to extra-school activities. There are significant differences (p < 0.05) between males' and females' engagement in physical activity (mean value: 4.1 hours; males: 4.6 h, females: 3.5 h). Among pre-teens, 18% declare to be physically inactive at all; 15.7% do not take part in sport activities because afraid to be bullied or shamed by peers. Research show that males are significantly more involved in physical activity than females.

Transdermal nitroglycerin reduces the frequency of anginal attacks but fails to prevent silent ischemia.

OBJECTIVES: The aim of this study was to objectively evaluate the effects of intermittent administration of transdermal nitroglycerin on effort tolerance, frequency of anginal attacks and presence of silent ischemic events that occur during normal daily activities. BACKGROUND: Previous studies have shown that transdermal nitroglycerin patches reduce the incidence of anginal attacks and improve exercise capacity when given intermittently. However, no carefully controlled studies are available on the effects of these preparations (and their dosing schedule) on the occurrence of "silent" ischemic events during unrestricted daily activities. METHODS: Twelve men with chronic stable angina, a positive exercise test result and significant coronary artery disease completed a randomized, double-blind, placebo-controlled trial in which patches were worn either continuously or with overnight (8 h) removal. The effects of treatment were objectively assessed by both treadmill exercise testing and 24-h ambulatory electrocardiographic monitoring. RESULTS: Only the intermittent dosing schedule afforded a small but significant improvement in exercise tolerance and prolonged exercise duration and time to ST segment depression. The frequency of anginal attacks was also reduced by both the continuous and intermittent treatment, but the effects on symptoms were not paralleled by a concomitant reduction in ischemic episodes recorded during ambulatory monitoring. CONCLUSIONS: The results indicate that when used as monotherapy, intermittent transdermal nitroglycerin preparations lessen symptoms but are ineffective for the long-term prophylaxis of silent myocardial ischemia.

Symptom-limited exercise testing causes sustained diastolic dysfunction in patients with coronary disease and low effort tolerance.

Exercise stress testing is routinely used for the noninvasive assessment of coronary artery disease and is considered a safe procedure. However, the provocation of severe ischemia might potentially cause delayed recovery of myocardial function. To investigate the possibility that maximal exercise testing could induce prolonged impairment of left ventricular function, 15 patients with angiographically proved coronary disease and 9 age-matched control subjects with atypical chest pain and normal coronary arteries were studied. Radionuclide ventriculography was performed at rest, at peak exercise, during recovery and 2 and 7 days after exercise. Ejection fraction, peak filling and peak emptying rates and left ventricular wall motion were analyzed. All control subjects had a normal exercise test at maximal work loads and improved left ventricular function on exercise. Patients developed 1 mm ST depression at 217 +/- 161 s at a work load of 70 +/- 30 W and a rate-pressure product of 18,530 +/- 4,465 mm Hg x beats/min. Although exercise was discontinued when angina or equivalent symptoms occurred, in all patients diagnostic ST depression (greater than or equal to 1 mm) developed much earlier than symptoms. Predictably, at peak exercise patients showed a decrease in ejection fraction and peak emptying and filling rates. Ejection fraction and peak emptying rate normalized within the recovery period, whereas peak filling rate remained depressed throughout recovery (p less than 0.002) and was still reduced 2 days after exercise (p less than 0.02). In conclusion, in patients with severe impairement of coronary flow reserve, maximal exercise may cause sustained impairement of diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired left ventricular filling dynamics in patients with angina and angiographically normal coronary arteries: effect of beta adrenergic blockade.

OBJECTIVE: To assess exercise performance and resting left ventricular filling dynamics in patients with syndrome X (SX) in basal conditions and after 10 days treatment with oral atenolol. DESIGN AND PATIENTS: Exercise performance was studied and left ventricular filling assessed by Doppler-derived transmitral flow pattern analysis in 22 patients (16 female, mean (SD) age 53 (4) years) with angina, a positive exercise test, and angiographically smooth coronary arteries. Patients were studied after two 10 day treatment periods with either atenolol or placebo in a single-blind, randomised, crossover trial. The same protocol was followed in 10 patients with documented coronary artery disease (CAD) and in 13 controls (C). RESULTS: Unlike the controls, patients with SX and those with CAD consistently showed exercise-induced ST segment abnormalities and impaired resting left ventricular filling while on placebo. Atenolol significantly reduced episodes of angina, completely prevented exercise-induced ST segment changes in 18 SX patients, and delayed their onset in all patients with CAD: in both groups the agent significantly improved Doppler-derived indices (mean (SD)) of ventricular filling (E/A 0.97 (0.27) v 1.22 (0.32) and 0.84 (0.21) v 1.19 (0.37), respectively). CONCLUSIONS: The objective documentation of left ventricular filling abnormalities may be useful in confirming the clinical diagnosis of SX and in providing objective evidence of therapeutic benefit. The similarity of the symptoms and electrocardiographic and ventricular filling abnormalities found in patients with SX and in those with CAD suggests that ischaemia is involved in both groups.

Particulate matter from tobacco versus diesel car exhaust: an educational perspective.

BACKGROUND: Air pollution is a common alibi used by adolescents taking up smoking and by smokers uncertain about quitting. However, environmental tobacco smoke (ETS) causes fine particulate matter (PM) indoor pollution exceeding outdoor limits, while new engines and fuels have reduced particulate emissions by cars. Data comparing PM emission from ETS and a recently released diesel car are presented. METHODS: A 60 m3 garage was chosen to assess PM emission from three smouldering cigarettes (lit sequentially for 30 minutes) and from a TDCi 2000cc, idling for 30 minutes. RESULTS: Particulate was measured with a portable analyser with readings every two minutes. Background PM10, PM2.5, and PM1 levels (mean (SD)) were 15 (1), 13 (0.7), and 7 (0.6) microg/m3 in the car experiment and 36 (2), 28 (1), and 14 (0.8) microg/m3 in the ETS experiment, respectively. Mean (SD) PM recorded in the first hour after starting the engine were 44 (9), 31 (5), and 13 (1) microg/m3, while mean PM in the first hour after lighting cigarettes were 343 (192), 319 (178), and 168 (92) microg/m3 for PM(10), PM2.5, and PM1, respectively (p < 0.001, background corrected). CONCLUSIONS: ETS is a major source of PM pollution, contributing to indoor PM concentrations up to 10-fold those emitted from an idling ecodiesel engine. Besides its educational usefulness, this knowledge should also be considered from an ecological perspective.

Myocardial viability assessed with fluorodeoxyglucose and PET in patients with Q wave myocardial infarction receiving thrombolysis: relationship to coronary anatomy and ventricular function.

In previously thrombolysed patients, we analysed residual myocardial viability using the PET-FDG technique and correlated its presence and extent to the angiographic appearance of the infarct-related vessel and left ventricular function. Thirty-six patients who had undergone intravenous thromboloysis for acute myocardial infarction 4.8 +/- 7.2 months previously were studied. Coronary angiography, left ventriculography, and assessment of myocardial perfusion and metabolism were all performed within 1 week. All patients exhibited perfusion defects consistent with the clinically identified myocardial infarction site. Residual viability, as assessed by the PET-FDG technique, was present in 53% of cases. The infarct-related coronary artery was patent in 19 (53%) patients (TIMI grade 3, 79%); of the remaining 17 with occluded infarct-related arteries, 11 had collaterals to the infarct area. Significant FDG uptake was observed in 63% of patients with a patent infarct-related artery and in 41% of those with an occluded infarct-related artery. The same study protocol was adopted in a control group of 30 patients with myocardial infarction who did not receive thrombolysis. The number of infarct-related patent vessels was significantly lower in these patients (30 vs 53%) (TIMI grade 3, 56%), but the overall percentage of PET viability was again 53%. Qualitative analysis of the regional perfusion pattern showed that the magnitude and severity of the perfusion defect was similar in the two groups, regardless of the presence or absence of FDG uptake. Global left ventricular function was also similar in the two groups. However, regional wall motion was significantly better in the thrombolysed patients with a patent infarct-related artery than in those who had not received thrombolysis and whose culprit vessel was also patent. In conclusion, the results of our study support the notion that early recanalization of the infarct-related artery is critical for preserving left ventricular function. Although the number of patent infarct-related coronary arteries is greater and left ventricular function is better in successfully thrombolysed patients, the regional metabolic pattern does not apparently correlate with the patency of the infarct-related artery. This suggests that, in "chronic' myocardial infarction, residual tissue viability as assessed by fluorodeoxyglucose uptake does not necessarily correlate with coronary recanalization.

Regional glucose utilization in infarcted and remote myocardium: its relation to coronary anatomy and perfusion.

We studied the relationship between coronary anatomy, perfusion and metabolism in myocardial segments exhibiting transient and persistent perfusion defects on stress/rest 99Tcm-MIBI single photon emission tomography in 35 patients (31 males, 4 females, mean age 56 +/- 7 years) with a previous myocardial infarction. Quantitative coronary angiography and assessment of myocardial perfusion reserve and glucose metabolism were performed within 1 week of one another. Perfusion was assessed by SPET after the intravenous injection of 740 MBq of 99Tcm-MIBI at rest and after exercise. Regional myocardial glucose metabolism was assessed by position emission tomography at rest (200 MBq of 18F-2-deoxyglucose, FDG) after an overnight fast with no glucose loading. All 35 patients exhibited persistent perfusion defects consistent with the clinically identified infarct site, and 27 (77%) also showed various degrees of within-infarct FDG uptake; 11 patients developed exercise-induced transient perfusion defects within, or in the vicinity of, 15 infarct segments and resting FDG uptake was present in 10 of these segments (67%). Five patients also showed exercise-induced transient perfusion defects in nine segments remote from the site of infarct: resting FDG uptake was present in six of these regions (67%). Finally, nine patients had increased glucose uptake in non-infarcted regions not showing transient perfusion defects upon exercise testing and perfused by coronary arteries with only minor irregularities. Our results confirm the presence of viable tissue in a large proportion of infarct sites. Moreover, FDG uptake can be seen in regions perfused by coronary arteries showing minor irregularities, not necessarily resulting in detectable transient perfusion defects on a MIBI stress scan. Since the clinical significance of such findings is not clear, further studies should be conducted to assess the long-term evolution of perfusion, function and metabolism in non-revascularized patients of those remote areas which are apparently normally perfused, but show abnormal fasting FDG uptake after myocardial infarction. Such studies may have important implications for the management of post-infarct patients, as the preservation of coronary vasodilator reserve and myocardial metabolism in remote myocardium may be seen as an additional goal in the treatment of such patients.

Untractable diarrhea due to late onset celiac disease of the adult following pancreatoduodenectomy.

This case describes a rare cause of severe diarrhea that may occasionally plague the postoperative course of pancreatic resections. Although exceedingly rare this complication has already been described in another two patients undergoing pancreatoduodenectomy with diagnosis of duodenojejunal adenocarcinoma. Surgeons dedicated to pancreatic resections as well as pancreatologists caring for these patients should retain this possibility in their cultural background. Diarrhea, due to either exocrine insufficiency or interruption of sympathetic nerves to the small intestine, is a common complaint after pancreatoduodenectomy. A 54-year-old white female after a pancreatoduodenectomy with standard lymphatic clearance developed intractable diarrhea leading to severe cachexia. Recognition of the underlying occult celiac disease and institution of the appropriate dietary regimen allowed quick and expeditious recovery.

Occurrence of Acanthocephalus clavula (Acanthocephala) in Echinogammarus pungens (Amphipoda) from the River Adige.

Cystacanths of Acanthocephalus clavula Dujardin 1845 (Acanthocephala) were found in the hemocoels of naturally infected Echinogrammarus pungens M. Edwards 1840 (Amphipoda). Crustaceans were collected in Porto Frossone, an estuarine locality of the River Adige. Only 3 out of 562 E. pungens specimens were infected by A. clavula cystacanths; the larvae were enclosed in a thin acellular envelope. Infected amphipods were all females, and their total length was greater than that of uninfected females. Moreover, adult specimens of this acanthocephalan were found in the alimentary tract of Anguilla anguilla (L.) eels sampled in the crustacean collecting site. A description of cystacanths and their stages of development is reported here.