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We evaluated the impact of COVID-19 vaccination on disease outcome in hospitalized patients with SARS-CoV-2 infection with a prospective study. 745 vaccinated and 451 unvaccinated patients consecutively admitted to a COVID-19 Hospital from 1st September 2021 to 1st September 2022 were included. Compared with unvaccinated cases, vaccinated patients were older, had more comorbidities, but had a lower risk of O2 need (odds ratio, OR, 0.46; 95 % CI 0.32–0.65) by logistic regression analysis adjusted for age, sex, comorbidity and WHO COVID-19 Clinical Progression Scale at admission. The ORs for O2 need were 0.38 (0.24–0.61), 0.50 (0.30–0.83) and 0.57 (0.34–0.96) in patients vaccinated 14–120, 121–180 and > 180 days prior to hospitalization, respectively. An anti-spike Ig titer higher than 5000 U/ml was associated with a reduced risk of O2 need (OR 0.52; 95 % CI 0.30–0.92). This study shows that COVID-19 vaccination has a significant impact on COVID-19 outcomes in hospitalized patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Microinvasive breast carcinoma is an infiltrating carcinoma that measures ≤1 mm. The prognostic factors associated with this disease have not been extensively investigated. In this study, we aimed to perform a systematic review and meta-analysis to examine the prognostic factors of microinvasive breast carcinoma. From 618 screened records, 5 were selected. The meta-analyses found a significant association between lymph node status and prognosis. No significant prognostic impacts were found for the following factors: estrogen receptor, progesterone receptor, HER2 status, multifocality or grade of microinvasion, or patient's age. Therefore, the data obtained demonstrate that lymph node status is a main prognostic factor of microinvasive breast carcinoma. (1) Background: The prognostic factors of microinvasive (≤1 mm) breast carcinoma are not completely clear. The aim of this study was to perform a systematic review and meta-analysis to clarify these factors. (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. Two databases were interrogated, PubMed and Embase, and papers in English were included to address this question. The selected studies were those that reported on female patients affected by microinvasive carcinoma, and on prognostic factors with a hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS). (3) Results: In total, 618 records were identified. After removing duplicates (166), identification, and screening (336 by title and abstract alone, 116 by full text and eventual supplementary material), 5 papers were selected. Seven different meta-analyses were conducted in this study, all referring to DFS, analyzing the following prognostic factors: estrogen receptor, progesterone receptor, HER2 status, multifocality and grade of microinvasion, patient's age, and lymph node status. Only lymph node status was associated with prognosis and DFS (total number of cases: 1528; Z = 1.94; p = 0.05). The other factors examined did not significantly affect prognosis (p > 0.05). (4) Conclusions: Positive lymph node status significantly worsens prognosis in patients with microinvasive breast carcinoma. [ABSTRACT FROM AUTHOR]

Background The aim of the present study was to compare the cross-sectional association between smoking and depressive symptoms among adolescents between Sweden and Italy, two countries historically characterized by different norms about tobacco use and different tobacco control efforts. Methods A cross-sectional study including 3283 adolescents 15–16 years of age participating in the Swedish KUPOL study and 1947 same-age adolescents from the Italian BE-TEEN study. Current smoking was defined as any smoking in the past 30 days. Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale for Children (CES-DC) and the internalizing score of the Strengths and Difficulties Questionnaire (SDQ). Country differences were explored in stratified and interaction analyses. Results Current smoking was associated with a 2- to 3-fold increased odds of depressive symptoms among Swedish adolescents using both CES-DC and SDQ internalizing scale. Among Italian adolescents, slightly lower increased odds of 1.5–2.5 for depressive symptoms with smoking were found using the CES-DC but not the SDQ scale. Both multiplicative and additive interactions for country were significant. The association between smoking and depressive symptoms was weaker among Italian compared with Swedish adolescents for both scores. Conclusions Countries with different tobacco norms and control show different associations between smoking and depressive symptoms in adolescence, probably due to different psychosocial profiles of smokers. These findings need to be considered when planning tobacco prevention programmes, e.g. by focusing on early detection of mental health distress among adolescents in settings with declining smoking prevalence and restrictive tobacco control environments. [ABSTRACT FROM AUTHOR]

Aim: The study aimed to show if transanal reinforcement of the suture line can prevent anastomotic leakage (AL) after rectal cancer surgery, thus avoiding the need for a covering ileostomy. Methods: This is a prospective, multicentre, parallel‐arm randomized controlled equivalence trial. After standard total mesorectal excision, patients with anastomotic line at 1–3 cm from the dentate line were randomized to have transanal suture reinforcement (TAR group) or protective ileostomy (PI group). Results: Twenty‐nine patients had PI, 25 had TAR. The two groups were comparable both for baseline characteristics and intra‐operative aspects. Clinically evident AL occurred in four (16%) and five (17.24%) patients of the TAR and PI group, respectively, resulting in a difference of −1.20% (90% CI −17.93, 15.45), while subclinical AL at proctography was absent in 15 (65.22%) and 13 (50%) patients of the TAR and PI groups, respectively, resulting in a difference of 15% (90% CI −7.74 to 38.17). Conclusion: Preliminary data suggest that transanal reinforcement of the suture line performed in rectal cancer patients with suture line at 1–3 cm from the dentate line carries a similar (even if not equivalent) AL rate to covering ileostomy, suggesting that a covering ileostomy could be avoided in this selected group of patients. This indication needs to be addressed with future larger trials (clinicaltrials.gov ID number NCT02279771). [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) are human carcinogens, based on sufficient evidence for melanoma and limited evidence for non-Hodgkin lymphoma and breast cancer. Few data are available for liver cancer, although PCBs cause it in rats and determined liver damage in poisoned people. We investigated the association between PCB serum levels and hepatocellular carcinoma (HCC) with a case–control study in a PCB-polluted area in North Italy. We enrolled prospectively 102 HCC incident cases and 102 age and gender-matched hospital controls. Serum concentrations of 33 PCB congeners were determined by a gas chromatograph coupled to mass spectrometry. Of 102 HCC cases, 62 who had lost < 3 kg of body weight in past 3 years were included in the analysis (67.7% males, mean age 68 years). The odds ratio (OR) for HCC for 3rd compared to 1st tertile of PCB distribution was 1.76 (95% confidence interval 0.62–5.03) for total PCB, adjusting for socio-demographic variables and risk factors for HCC by logistic regression. For most PCB congeners, ORs > 1.5 or 2 were found, although the 95% CIs included the null value for almost all of them. This preliminary study suggests that PCBs might play a role in HCC development. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCB) have been classified by the International Agency for Research on Cancer (IARC) in Group 1 as carcinogenic to human, based on sufficient evidence in humans of an increased risk of cutaneous malignant melanoma and limited evidence for non-Hodgkin lymphoma (NHL). However present findings on the association of PCB exposure and NHL are still controversial. This study examined the relationship between PCB serum levels and risk of NHL in a Northern Italy area (Brescia province), where a chemical factory produced PCBs from 1938 to 1984, causing human contamination. A case–control study of 215 NHL patients and 215 control subjects was conducted. Cases and controls were assayed for serum levels of 33 PCB congeners. No associations were found between risk of NHL and serum levels of total PCBs (OR = 0.51; 95% CI: 0.25–1.04 for highest vs lowest quartile) or specific PCB congeners. The study confirmed a strong association of NHL with HCV infection (OR = 3.60; 95% CI: 1.30–10.02). This case-control study does not support the hypothesis of an association between current serum levels of PCBs and NHL development in the general population. • No association between current serum levels of PCBs and NHL development in the general population. • Association of NHL with HCV was confirmed. • The present is one of the largest study to examine the relationship between individual PCB levels and risk of NHL. [ABSTRACT FROM AUTHOR]

Tobacco use in adolescence has been linked to the onset of depressive symptoms, but results of previous studies are inconsistent. The aim of this study was to clarify if tobacco use during early adolescence may affect the short-term onset of depressive symptoms. The study is based on Swedish Kupol study (3959 students). Current cigarette smoking, snus use, and tobacco dependence were assessed using questionnaires at baseline and 1-year follow-up. Outcome was the onset of depressive symptoms measured with the CES-DC scale, using a cut-off ≥ 30 as threshold. Adjusted linear and logistic regression models were employed to calculate odds ratios (OR) and corresponding 95% confidence intervals (CI). CES-DC mean score at baseline was 14.3, higher in females than males (17.5 vs 10.9). The incidence of depressive symptoms at follow-up was 8.3%, greater in current than never smokers at baseline (13.7% vs 3.1%). Current cigarette smoking at the age of 13 years was strongly associated with the onset of depressive symptoms 1 year later, particularly in males (OR 12.7, 95% CI: 2.5–63.9), with a significant interaction between tobacco use and sex; feeling dependent on tobacco was also associated with depressive symptoms in males but not in females. Snus and overall tobacco use were not associated with the onset of depressive symptoms. Tobacco use during adolescence appears to influence the onset of depressive symptoms, with a stronger association in males than females. Pubertal maturation and sex-specific response patterns to the scale instrument may explain the moderating effect of sex. [ABSTRACT FROM AUTHOR]

The impact on time to results (TTR) and clinical decisions was evaluated for mono-microbial positive blood cultures (BC) processed using the BD Kiestra Work Cell Automation (WCA) system. Positive BC were processed by the WCA system by full-automatic subculture on solid media and digital imaging after 8 h of incubation (8-h method) followed by identification (ID) and antimicrobial susceptibility testing (AST). To evaluate the accuracy of the 8-h method, ID and AST from 8-h and overnight incubated colonies were compared for the same organisms. To evaluate its clinical impact, results from 102 BC processed by the 8-h method (cases) were compared with those from 100 BC processed by overnight incubation method (controls) in a comparable period. Identification after 8-h and overnight incubation gave concordant results in 101/102 (99.0%) isolates. Among a total of 1379 microorganism-antimicrobial combinations, categorical agreement was 99.4% (1371/1379); no very major error, 7 major errors, and one minor error were observed. TTR in cases (32.8 h ± 8.3 h) was significantly (p < 0.001) shorter than in controls (55.4 h ± 13.3 h). A significant reduction was observed for duration of empirical therapy (cases 54.8 h ± 23.3 h vs controls 86.9 h ± 34.1 h, p < 0.001) and 30-day crude mortality rate (cases 16.7% vs controls 29.0%, p < 0.037). Automation and 8-h digital reading of plates from positive BC, followed by ID and AST, greatly reduce TTR and shorten the duration of antimicrobial empiric therapy, possibly improving outcome in patients with mono-microbial bloodstream infections. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Exposure to polychlorinated biphenyls (PCBs) has been linked to the onset of cardiovascular, endocrine, and metabolic diseases, but no conclusive evidence has been provided so far. A chemical factory produced PCBs from 1938 to 1984 in Brescia (North Italy) resulting in environmental contamination and human exposure. We aimed to evaluate the association between PCB serum levels and subsequent incidence of chronic diseases through a prospective cohort study design. Methods Based on surveys conducted in Brescia province between 2001 and 2013, a cohort of 1331 subjects with at least one measure of PCB serum levels during the period was selected and followed longitudinally. Serum concentration of total PCBs was computed summing up the levels of 24 PCB congeners determined by gas chromatography. The data on incidence of hypertension, cardiovascular diseases, and endocrine and metabolic chronic diseases were retrieved from the Brescia Health Protection Agency database. Poisson regression models adjusted for age, level of education, BMI, cholesterol level, tobacco smoking and alcohol drinking were employed to calculate rate ratios (RRs). Results 1331 subjects were enrolled (45.7% males, mean age 50.6 years) contributing to 10,006 person-years of follow-up. A dose-response relationship was observed between PCB serum levels and the onset of hypertension (RR for 2nd and 3rd tertiles of serum PCB distribution: 2.07, 95% CI 1.18–3.63, and 2.41, 1.30–4.47, respectively). A possible, though not statistically significant, increase of the risk of cardiovascular disease was also found (RR for 2nd and 3rd tertiles of serum PCB distribution: 1.61, 0.72–3.64, and 1.96, 0.86–4.48, respectively). The results based on lipid-standardized PCBs were slightly attenuated. No association was found between PCB serum levels and occurrence of diabetes and endocrine disorders. Stratified analysis by body mass index showed an increased risk of hypertension in subjects at 2nd and 3rd tertile of serum PCB distribution in overweight/obese subjects only. Conclusions These results suggest that PCBs might play a role in the development of hypertension and possibly cardiovascular disease, though alternative explanations are to be considered too. Highlights • PCB serum levels at enrollment were associated with an increased risk of hypertension over time • Also incidence of cardiovascular disease may be related with PCB exposure • Risk of hypertension and cardiovascular disease was attenuated with models based on lipid-standardized PCB serum levels • PCB serum levels were not associated with incidence of diabetes, endocrine and thyroid diseases [ABSTRACT FROM AUTHOR]

Background: Two biomarkers, the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), have been shown to be indicative of systemic inflammation and predictive of mortality in general population. We aimed to assess the association of NLR and PLR, with risk of death in HIV-infected subjects when also taking account of HIV-related factors.Methods: We conducted a multicenter Italian cohort study from 2000 to 2012 including HIV-infected subjects naïve at antiretroviral treatment. The associations of NLR and PLR with all-cause mortality were tested by univariate and multivariate analyses using both time independent and dependent Cox proportional hazard models. We also fitted models with a cubic-spline for PLR and NLR to evaluate the possible non-linear relationship between biomarkers values and risk of death.Results: Eight-thousand and two hundred thirty patients (73.1% males) with a mean age of 38.4 years (SD 10.1) were enrolled. During a median follow-up of 3.9 years, 539 patients died. PLR < 100 and ≥ 200, as compared to PLR of 100-200, and NLR ≥ 2, as compared to < 2, were associated with risk of death at both univariate and multivariate analyses. Using multivariate models with restricted cubic-splines, we found a linear relationship of increasing risk of death with increasing values for NRL over 1.1, and an U-shape curve for PLR, with higher mortality risk for values higher or lower than 120.Conclusions: Our data suggest that NLR and PLR can reflect the severity of the underlying systemic disturbance of the inflammatory process and coagulation leading to augmented mortality in HIV positive subjects. [ABSTRACT FROM AUTHOR]

Background Delta-9-tetrahydrocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex®) has been recently approved for the management of treatment-resistant multiple sclerosis (MS) spasticity. Although the symptomatic relief of Sativex® on MS-spasticity has been consistently demonstrated, the pathogenetic implications remain unclear and the few electrophysiological studies performed to address this topic yielded controversial results. We therefore aimed to investigate the mechanisms underpinning the modulation of spastic hypertonia by Sativex®, at both central and spinal levels, through an extensive neurophysiological battery in patients with MS. Methods Nineteen MS patients with treatment-resistant spasticity were recruited. Before and after 4 weeks of treatment with Sativex® patients were clinically assessed with the Modified Ashworth Scale (MAS) and underwent a large neurophysiological protocol targeting measures of excitability and inhibition at both cortical [e.g., intracortical facilitation (ICF), short (SICI) and long (LICI) intracortical inhibition, cortical silent period (CSP)] and spinal level [e.g., H-reflex, H/M ratio and recovery curve of the H-reflex (HRC)]. A group of 19 healthy subjects served as controls. Results A significant reduction of the MAS score after 4 weeks of Sativex® treatment was detected. Before treatment, an increase in the late facilitatory phase of HRC was recorded in patients compared to the control group, that normalised post treatment. At central level, SICI and LICI were significantly higher in patients compared to healthy subjects. After therapy, a significant strengthening of inhibition (e.g. reduced LICI) and a non-significant facilitation (e.g. marginally increased ICF) occurred, suggesting a modulatory effect of Sativex® on different pathways, predominantly of inhibitory type. Sativex® treatment was well tolerated, with only 3 patients complaining about dizziness and bitter taste in their mouth. Discussion Our results confirm the clinical benefit of Sativex® on spastic hypertonia and demonstrate that it might modulate both cortical and spinal circuits, arguably in terms of both excitation and inhibition. We suggest that the clinical benefit was likely related to a net increase of inhibition at cortical level that, in turn, might have influenced spinal excitability. [ABSTRACT FROM AUTHOR]

Introduction Polychlorinated biphenyls (PCBs) are persistent pollutants classified among endocrine disruptors and human carcinogens. In an urban area in Northern Italy (Brescia), a chemical factory producing PCBs from 1938 to 1984 caused soil and food pollution. Since the discovering of the environmental pollution in the area in 2001, various public health interventions have been implemented to avoid human contamination. Methods Two independent surveys were carried out in 2003 and 2013 using the same study design and methods. A random sample of the adult general population living in four areas of the town with different soil contamination level was enrolled in both surveys. Investigation included serum levels of 24 PCB congeners and of other common clinical-chemical parameters and questions about residential and occupational history as well as current and past diet and consumption of locally produced food. 537 subjects were tested in the 2003 and 488 in the 2013 survey. Results Total PCB serum levels showed a strong correlation with age (Spearman r = 0.71 in 2003 and r = 0.80 in 2013), but not with gender. Consumers of food produced in the most polluted area had higher total PCB serum levels (median 15.6 and 4.7 ng/ml in 2003 and 2013, respectively) than non-consumers (4.1 and 2.3 ng/ml) and consumers of food produced in non-polluted areas (6.5 and 1.9 ng/ml), with increasing trend of PCB serum levels with cumulative local food intake. PCB serum levels from 2003 to 2013 survey declined by around half in all age groups, especially among the youngest people. The total PCB reduction was found to be due to a combination of a birth cohort effect (− 41% every 10 years) and survey period effect (− 18% in 2013 versus 2003), with medium chlorinated CB congeners showing the most relevant reduction (− 30%) between the two surveys. High chlorinated CBs were more strongly associated with birth cohort (− 46% every 10 years): in the 2013 survey they represented 58% of total PCBs in 60–79 years old while they were 37% among the under 40s with a median value 20 times higher in the oldest than in the youngest (3.1 versus 0.16 ng/ml). Conclusions PCBs serum levels declined from the 2003 to 2013 survey though they are still high in the elderly mainly because of past intake of locally produced contaminated food. Present findings suggest that PCBs food chain contamination and human absorption have been interrupted successfully in the area since discovery of the pollution in 2001. [ABSTRACT FROM AUTHOR]

Background: The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), two low cost, routinely available inflammatory indices, have been found to be associated with risk of death in patients with solid cancer, in both general population and HIV-positive subjects. However, no study investigated the role of NLR and PLR as predictive of cancer incidence so far. Methods: The aim of our study was to assess the association of PLR and NLR with risk of developing solid non-AIDS defining cancer (NADC) in HIV-infected subjects. We conducted a multicenter Italian cohort study from 2000 to 2012 including HIV-infected subjects naïve at antiretroviral treatment at enrollment. The associations of NLR and PLR with NADC incidence were evaluated by univariate and multivariate analyses using both time independent and time dependent Cox proportional hazard models. Results: Thirteen thousand five hundred fifty-nine patients (73.3 % males) with a mean age of 36.0 years (SD 10.0) were included. The median (inter-quartile range) of NLR and PLR at baseline were 1.47 (1.03-2.17) and 109.9 (79.6-155.3), respectively. During a median follow-up of 3.9 years, 337 subjects had a first diagnosis of solid NADC. The crude and age- and gender-standardized incidence rates were 3.57 and 3.91 per 1000 person-years, respectively. No statistically significant association was found between NLR and PLR and NADC incidence, using multivariate models, including also time-dependent Cox models with a cubic-spline for NLR and PLR. Conclusion: This study does not sustain the hypothesis that NRL and PLR may be useful for predicting the risk of cancer in HIV positive subjects. [ABSTRACT FROM AUTHOR]

Background: The systemic inflammatory response has been postulated as having prognostic significance in a wide range of different cancer types. We aimed to assess the prognostic role of inflammatory markers on survival in HIVinfected patients with Non-Hodgkin Lymphoma (NHL), and to compute a prognostic score based on inflammatory biomarkers. Methods: We evaluated data on HIV patients with NLH diagnosis between 1998 and 2012 in a HIV Italian Cohort. Using Cox proportional regression model, we assessed the prognostic role of Neutrophil-Lymphocyte Ratio (NLR), Platelet-Lymphocyte Ratio (PLR), Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI), and Prognostic Nutritional Index (PNI). We also computed a risk score equation, assigning patients to a derivation and a validation sample. The area under the curve (AUC) was use to evaluate the predictive ability of this score. Results: 215 non-Hodgkin lymphoma cases (80.0% males) with a mean age of 43.2 years were included. Deaths were observed in 98 (45.6%) patients during a median follow up of 5 years. GPS, mGPS, PI and PNI were independently associated with risk of death. We also computed a mortality risk score which included PNI and occurrence of an AIDS event within six months from NHL diagnosis. The AUCs were 0.69 (95% CI 0.58 to 0.81) and 0.69 (95% CI 0.57 to 0.81) at 3 and 5 years of the follow-up, respectively. Conclusions: GPS, mGPS, PI and PNI are independent prognostic factors for survival of HIV patients with NHL. [ABSTRACT FROM AUTHOR]

Background. Polychlorinated biphenyls (PCBs) have been found to be associated with diabetes in some, but not all, studies performed so far. The aim of this study was to assess the association between PCB serum levels and glycaemia and diabetes in people living in Brescia, a highly industrialised PCB-polluted town in Northern Italy. Design and Methods. 527 subjects were enrolled in a cross-sectional population-based study: they were interviewed face-to-face in 2003 and also provided a blood sample under fasting conditions. The concentration of 24 PCB congeners was determined using gas-chromatography (GC/MS). Subsequently, all subjects were included in a follow-up (cohort) study. According to the Local Health Authority health-care database, subjects were considered to be diabetic if they had diabetes at interview time (prevalent cases) or during a 7-year follow-up (incident cases). Results. A total of 53 subjects (10.0%) were diabetics: 28 had dia- betes at enrolment and other 25 developed the disease subsequently. Diabetes frequency increased according to the serum concentrations of total PCBs and single PCB congeners, but no association was found when estimates were adjusted for education, body mass index, age and gender by logistic regression analysis. Accordingly, glycaemia increased with PCB serum levels, but no association was observed when multiple regression analysis, including confounding factors, was performed. Conclusions. This study does not support the hypothesis that PCB environmental exposure is strictly associated with diabetes or glycaemia. [ABSTRACT FROM AUTHOR]

Abstract: Background: Polychlorinated biphenyls (PCBs) have been hypothesized to increase the risk of non-Hodgkin lymphoma (NHL), although conclusive evidence is still lacking. High levels of PCBs were found in soil in some areas close to a PCB-producing factory in Brescia, North Italy. We conducted a population-based case-control study among residents of the town to investigate the possible association between PCB pollution and NHL in this area. Methods: We included both incident and deceased NHL cases, and a random sample of the town residents as controls, frequency matched to cases as regards age and gender. Exposure to PCBs was estimated on the basis of the lifetime residential history of cases and controls in four different areas of the town—A, B and C (polluted areas) and D (control area). Results: A total of 495 cases (287 incident cases) and 1467 controls were enrolled. Positive associations were found between NHL and having resided for at least 10 years in the area A, the most polluted area (odds ratio, OR=1.8; p=0.02) and for having resided in any of the polluted areas considered together (A+B+C) (OR=1.4; p=0.08). However, no associations were evident for having resided 20 years or longer in the polluted areas or when analyzing the association with each subject''s main residence in his/her lifetime. Conclusion: This study provides some evidence for an association between PCB exposure and NHL, though results should be considered with caution in the absence of individual biological measures of exposure. [Copyright &y& Elsevier]

Abstract: Background: Polychlorinated biphenyls (PCBs) may interact with several thyroid functions. Severe environmental pollution by PCBs has been observed in Brescia, Italy, due to the presence of a factory that produced these compounds until 1984. Objectives: We aimed to investigate the correlation between serum levels of total PCBs and PCB 153 and thyroid hormone serum levels in adults in a cross-sectional population-based study. Methods: A total of 527 subjects were enrolled; they were face-to-face interviewed about their history of thyroid disease and provided a blood sample under fasting conditions. The serum levels of free and total triiodothyronine (FT3 and TT3), thyroxine (FT4 and TT4) and thyroid-stimulating hormone (TSH), anti-thyroperoxidase (anti-TPO) and anti-thyroglobulin (anti-TGA), and lipid-adjusted total PCBs and PCB 153 were determined. Results: There was no statistically significant difference in total PCB and PCB 153 concentrations in subjects with and without thyroid disease. Inverse, weak, statistically significant correlations were found between total PCBs and FT3 (Spearman''s r=−0.09) and between total PCBs and PCB 153 and TSH (Spearman''s r=−0.16 and −0.12, respectively). However, multiple regression analysis with FT3 and TSH serum levels as dependent variables and total PCBs and PCB 153 serum levels as predictors, including age, gender and BMI, showed a positive, rather than negative, association of PCBs and PCB 153 with FT3 and no association with TSH. Conclusions: This study does not support the hypothesis that relatively high PCB environmental exposure can determine substantial alterations in thyroid function among adult people. [Copyright &y& Elsevier]

Abstract: It is rarely possible to identify reverse faults that bring portions of substratum solid rock to lie above decomposed rock. Only where the differences between the fresh rock and weathered rock are very clear is it possible to recognise such faults. A “reverse profile” is defined as a slope profile in which fresh rock (granitoids) overlaps rocks which have been greatly altered by mature weathering (saprolite of granitoids). Such a profile occurs along the slopes of Molini Valley to the south of the village of Fabrizia (Calabria, southern Italy) and we interpret the morphological, mechanical and structural evidence as typical of a reverse fault. The mineral-petrographic analysis of the grus on the bed of the fault and of the cover of relatively fresh rock (Schmidt hammer 18–35) confirms that the granular framework can be attributed to subaerial alteration and not to mechanical deformation. The study area is located at the centre of the largest kinematic body of southern Calabria (the Serre massif-exclusively granitoids) until now considered to be only affected by extensional tectonics, creating high angle normal faults. In this area the tectonic processes, the thickness and spread of granitoid weathering mantles and the depth of the valleys, give rise to several landslides. These are generally translational slides with ample cut surfaces between the weathered body and the underlying fresh rock; as a consequence, very large deposits in the valleys can be found, mostly produced by debris flow processes. At the foot of the slopes around Fabrizia, coarse debris avalanches (with cobbles having a volume of over 0.3–0.4 m3) are occasionally observed, unless there is widespread development of a “reverse weathering profile” on the slopes above. [Copyright &y& Elsevier]

The prevalence of atopy and asthma, and their association with familial and environmental factors were investigated among 13- to 14-yr-old children living in Brescia, an industrialized town in North Italy. All the 1450 children attending primary school in the town were invited to participate, and 967 of them (66.7%, 493 males) provided a valid questionnaire filled in by their parents at home. We used a modified version of the questionnaire adopted in the Italian Study of Respiratory Disorders in Childhood and Environment, which is an extended version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Six hundred and twenty-eight subjects underwent skin prick test (SPT), and 308 of them (49%) were positive for at least one of the 12 allergen extracts commonly employed. Ninety-nine children (10.2%) had a physician's diagnosis of asthma – 12.4% of the males and 8.0% of the females (p = 0.03). The prevalence of wheezing in the past 12 months was 6.2%. Atopy was found in 76.8% of the subjects with, and in 45.6% of those without physician's diagnosis of asthma (p < 0.001). Analysis by multiple logistic regression showed an inverse association between physician-diagnosed asthma and female sex (odds ratio, OR = 0.5); presence of relatives in the bedroom in initial years of life (OR = 0.6); attending day care (OR = 0.4) and infant school (OR = 0.4); a positive association with parental history of wheezing (OR = 2.5) and asthma (OR = 3.8); and the child's history of asthmatic bronchitis (OR = 31.9) and atopic eczema (OR = 3.8) in the first 2 yr of life. The strength of the associations did not change when restricting the analysis to atopic asthma. In conclusion, atopy and clinical asthma among 13- to 14-yr-old adolescents are significantly associated with some familial and environmental factors, providing further support for the hygiene hypothesis. Prevalence of atopy, but not of asthma, is high in this industrialized area. The strong association found between atopy and clinical asthma suggests that atopy may play a role in causing asthma in genetically predisposed children only. [ABSTRACT FROM AUTHOR]

Objective: Fatty acid synthase (FAS) is a multienzyme protein required for the conversion of acetyl coenzyme A and malonyl coenzyme A to palpitate. High levels of FAS expression have been found in many human cancers, including breast, prostate and colon. In this study, we evaluated FAS activity levels and the expression of its mRNA in normal colorectal mucosa and cancer tissue from patients operated for colorectal carcinoma. In addition, the hypothesis of a relation between FAS activity and p53 mutation status of patients was tested. Methods: Forty-two patients were enrolled in the study. FAS activity was measured by using a radiometric assay. FAS gene expression was determined using quantitative reverse-transcription polymerase chain reaction and p53 mutations by polymerase chain reaction single-strand conformation polymorphism. Results: FAS activity levels were significantly higher in cancer than in the corresponding normal mucosa. Tumors located on the left side of the colon showed higher levels of FAS activity and tumors from male patients showed higher FAS activity than tumors from females. No difference was detected in mRNA FAS levels according to tumor side and gender. Moreover, lower levels of FAS activity were detected in patients carrying the p53 mutation. Conclusions: This study suggests that biological factors including sex and gene mutation status, as well as stratification of patients with colorectal cancer into right- and left-sided subsets, may be important in patient selection for targeted therapies and for the subsequent assessment of objective therapeutic responses. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: High levels of PCBs were recently found in soil, food and some farmers living close to a chemical factory which until the 1980s had produced polychlorinated biphenyls (PCBs) in Brescia, North Italy. We performed a survey on a random sample of subjects aged 20–79 years living in various areas of the town with different levels of soil pollution to investigate factors associated with increased levels of PCB in serum (24 congeners were tested). Total PCB values were closely related to age (Spearman r =0.68; p <0.0001). The 166 consumers of locally produced food had higher PCB levels than non-consumers (median=1143 versus 719; 95th centile=9301 versus 2635ng/g lipid) with the highest levels among consumers of food produced in the most contaminated area close to the factory (median=2551; 95th centile=33464ng/g lipid). A dose-effect relationship between consumption of food produced in this area and PCB blood levels was observed (Spearman r =0.52, p =0.0014). Consumers of only plant food produced in this area had higher levels of PCB than non-consumers (median=1100; 95th centile=10800ng/g lipid). Three subjects who had worked at the factory in the past showed high PCB levels. Distribution of PCB congeners did not differ between consumers of locally produced food and non-consumers, apart from PCB 209 which was found at high levels in former factory workers and was more common among consumers of food produced in the polluted area. In conclusion, we found high serum PCB levels in humans living in a highly polluted area in an industrialized town in Italy, due mainly to consumption of food produced in polluted areas. [Copyright &y& Elsevier]

: ObjectivesWe investigated the relation between hepatocellular carcinoma (HCC) etiology and biological and clinical parameters indicative of severity of liver disease and/or tumor characteristics and patient survival.: MethodsWe prospectively recruited 384 patients (82.3% male) with first diagnosis of HCC from 1995 to 1998 in Brescia, Italy. Etiology was assessed by interviewing patients regarding their history of alcohol intake and by testing sera for hepatitis B surface antigen and anti-hepatitis C virus (HCV) antibodies and HCV RNA.: ResultsHeavy alcohol intake (>60 g of ethanol per day for at least 1 decade) was found in 33.1% of cases, hepatitis B virus (HBV) infection in 9.4%, HCV in 19.8%, hemochromatosis in 1.3%, alcohol and HBV in 12.0%, alcohol and HCV in 16.1%, HBV and HCV in 3.1%, and no factor in 5.2%. Patients with HBV infection with or without heavy alcohol intake were significantly younger than the others (61.7 vs 64.7 yr, p < 0.001). The proportion of males was significantly higher in patients with heavy alcohol intake alone than in the other patient groups (93.7% vs 77.3%, p < 0.001). Among patients with HCV infection with or without heavy alcohol intake, fewer patients had maximum tumor diameter > 5 cm than the others (12% vs 29.1%, p < 0.001). Eighty patients (20.8%) were alive at the end of follow-up (median survival, 17.7 months), and no differences were observed in survival rates by HCC risk factor.: ConclusionsAlthough some differences were observed in severity of liver disease or tumor characteristics according to etiology, patient survival was not influenced by HCC etiology. [Copyright &y& Elsevier]

Serum polychlorinated biphenyls (PCBs) have been associated with some chronic diseases, but little evidence exists on their possible relationship with neurodegenerative diseases. We aimed to assess the relationship between PCB exposure and the occurrence of dementia and Parkinson disease in a prospective cohort study in a highly polluted area (Brescia-Caffaro). PCB exposure was assessed by measuring serum levels of 24 congeners. Data on the onset of dementia and Parkinson disease were retrieved by the Brescia Health Protection Agency Database. We used Poisson regression models adjusted for possible confounders to calculate rate ratios (RRs). A mediation analysis was performed to evaluate the mediatory role of cardiovascular diseases. 699 subjects without neurologic diseases at baseline were enrolled (48.1% males, 63.2 years of mean age) in 2001–2013 and followed up to 2018. During a mean follow-up of 8.8 years, 36 and 20 subjects developed dementia and Parkinson disease. Subjects in the 2nd and 3rd tertiles of the total PCBs distribution, compared with those in the 1st tertile, had a higher risk of dementia (RR = 2.30 and RR = 4.35). The estimates for Parkinson disease included the null value with wide confidence intervals. In the mediation analysis, the association between PCB exposure and dementia was dominated by the direct pathway and not by the hypertension-mediated pathway. We observed a positive association between total PCBs serum levels and the onset of dementia not mediated by hypertension. For Parkinson, the unstable risk estimates did not allow to draw a conclusion on a possible association. • PCB exposure was associated with higher risk of dementia independently of other risk factors. • These finding were confirmed using a dose-response analyses and controlling for lipids. • No conclusion can be made about the association between PCB exposure and Parkinson disease due to very few cases. [ABSTRACT FROM AUTHOR]

A letter to the editor on the role of steroid receptor pattern in the tamoxifen therapy of inoperable intra-abdominal desmoid tumors is presented.

This study aimed to assess the longitudinal association between PCB exposure and the subsequent occurrence of hypertension in a highly polluted area. The study subjects had at least one PCB serum measurement between 2003 and 2014 and were followed up to the end of 2017. Hypertension cases were obtained from the Brescia Health Protection Agency database. Risk ratios of hypertension for total PCBs, high-, middle- and low-chlorinated groups and some common congeners were estimated using Poisson regression models. 1031 subjects were included (43.4% males, mean age 45.3 years). 229 subjects developed hypertension during the follow-up. Total PCBs, middle- and high-chlorinated PCBs, and particularly PCB congeners 138, 153 and 180 were associated with an about 2-fold increased risk of hypertension comparing the third with first tertile of distribution. After lipid-standardization of PCB serum values, the excess risk showed only a slight attenuation. A dose-response linear relationship of the risk of hypertension by PCB serum concentrations as continuous variables was also observed. The PCBs-hypertension association was stronger in overweight/obese subjects than those with normal body mass index. In this prospective cohort study the serum levels of total and middle to high chlorinated (≥6 Cl) PCBs were associated with an increased risk of hypertension, particularly among overweight/obese subjects. Unlabelled Image • The aim was to assess the PCB-hypertension association in a highly PCB polluted area. • A prospective cohort study (n = 1031, mean follow-up = 6.8 years) was carried out. • An increased risk of hypertension was found for middle and high chlorinated PCBs. • Non-dioxin like PCBs 138, 153 and 180 were associated with higher risk of hypertension. • The risk of hypertension did not vary controlling for serum lipids and other major risk factors. [ABSTRACT FROM AUTHOR]

A structural weakness of the mucus barrier (MB) is thought to be a cause of ulcerative colitis (UC). This study aims to investigate the mucin (MUC) composition of MB in normal mucosa and UC. Ileocolonic biopsies were taken at disease onset and after treatment in 40 patients, including 20 with relapsing and 20 with remitting UC. Ileocolonic biopsies from 10 non-IBD patients were included as controls. Gut-specific MUC1, MUC2, MUC4, MUC5B, MUC12, MUC13, MUC15, and MUC17 were evaluated immunohistochemically. The promoters of mucin genes were also examined. Normal mucosa showed MUC2, MUC5B, and MUC13 in terminal ileum and colon, MUC17 in ileum, and MUC1, MUC4, MUC12, and MUC15 in colon. Membranous, cytoplasmic and vacuolar expressions were highlighted. Overall, the mucin expression was abnormal in UC. Derangements in MUC1, MUC4, and MUC5B were detected both at onset and after treatment. MUC2 and MUC13 were unaffected. Sequence analysis revealed glucocorticoid-responsive elements in the MUC1 promoter, retinoic-acid-responsive elements in the MUC4 promoter, and butyrate-responsive elements in the MUC5B promoter. In conclusion, MUCs exhibited distinct expression patterns in the gut. Their expression was disrupted in UC, regardless of the treatment protocols. Abnormal MUC1, MUC4, and MUC5B expression marked the barrier dysfunction in UC. [ABSTRACT FROM AUTHOR]

Aim: Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF. Method: Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis. Results: A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between‐treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow‐up visit. There were no other significant differences between the two groups for any of the other outcomes. Conclusion: While there was no difference in healing rates between the two treatments, PeG was more cost‐effective and associated with fewer adverse events. [ABSTRACT FROM AUTHOR]

Abstract Adverse health effects of cement plant exposure have been found in occupational contexts but are less defined for the general population living near plants. We aimed to summarize the evidence on the health effects of people exposed to ambient air pollution by cement plants. A systematic review using Embase, PubMed and Web of Science was performed. We included only non-occupational studies with a comparison group that focused on adverse health outcomes and biomarkers of internal dose or subclinical effect associated with cement plant exposure. Selection of articles was performed by two authors independently. Of 1491 articles identified by the initial search, 24 were included: 17 of them were included in the analysis of adverse health outcomes and 9 in the analysis of biomarkers of internal dose or subclinical effects. The studies were very heterogeneous in study design, measure of cement plant exposure, outcome detection, measure of association and adjustment for confounding. Almost all the studies found positive associations between cement plant exposure and respiratory diseases and symptoms. An excess risk of cancer incidence and mortality in both children and adults mainly concerning respiratory tract cancers was also reported in some studies. Higher values of heavy metals and of a biomarker of renal toxicity were found in the exposed compared to unexposed populations. In conclusion, there is some evidence for a possible role of cement plant exposure on health adverse effects, although many studies had serious or critical risk of bias and overall level of certainty was low. Highlights • Cement plant exposure was associated with higher risk of respiratory symptoms and lung function decline. • An excess risk of cancer incidence and mortality, mainly respiratory tract cancers was found in both children and adults. • Inconsistent results were described for cardiovascular diseases. • Exposed compared to unexposed subjects had higher blood or urinary concentration of heavy metals and of a marker of renal damage. [ABSTRACT FROM AUTHOR]

Background: The systemic inflammatory response has been postulated as having prognostic significance in a wide range of different cancer types. We aimed to assess the prognostic role of inflammatory markers on survival in HIV-infected patients with Non-Hodgkin Lymphoma (NHL), and to compute a prognostic score based on inflammatory biomarkers.Methods: We evaluated data on HIV patients with NLH diagnosis between 1998 and 2012 in a HIV Italian Cohort. Using Cox proportional regression model, we assessed the prognostic role of Neutrophil-Lymphocyte Ratio (NLR), Platelet-Lymphocyte Ratio (PLR), Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI), and Prognostic Nutritional Index (PNI). We also computed a risk score equation, assigning patients to a derivation and a validation sample. The area under the curve (AUC) was use to evaluate the predictive ability of this score.Results: 215 non-Hodgkin lymphoma cases (80.0% males) with a mean age of 43.2 years were included. Deaths were observed in 98 (45.6%) patients during a median follow up of 5 years. GPS, mGPS, PI and PNI were independently associated with risk of death. We also computed a mortality risk score which included PNI and occurrence of an AIDS event within six months from NHL diagnosis. The AUCs were 0.69 (95% CI 0.58 to 0.81) and 0.69 (95% CI 0.57 to 0.81) at 3 and 5 years of the follow-up, respectively.Conclusions: GPS, mGPS, PI and PNI are independent prognostic factors for survival of HIV patients with NHL. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCB) have been classified by the International Agency for Research on Cancer (IARC) in Group 1 as carcinogenic to human, based on sufficient evidence in humans of an increased risk of cutaneous malignant melanoma (CMM), however few studies have been done in the general population. This study examined the relationship between PCB plasma levels and risk of CMM adjusting for sun sensitivity and sun exposure in a province of Northern Italy (Brescia), where a chemical factory produced PCBs from 1938 to 1984 causing human contamination. A case–control study of 205 CMM patients and 205 control subjects was conducted. Cases and controls were assayed for plasma levels of 33 PCB congeners. No associations was found between risk of CMM and plasma levels of total PCB (OR = 0.81; 95% CI: 0.34–1.96 for highest vs lowest quartile) or specific congeners. The study confirmed the association with light skin colour (OR = 3.00; 95% CI: 1.91–4.73), cumulative lifetime UV exposure (OR = 2.56; 95% CI: 1.35–4.85) and high level of education (OR = 1.45; 95% CI: 1.03–2.05). This case-control study does not support the hypothesis of an association between current plasma levels of PCBs and CMM development in the general population. [ABSTRACT FROM AUTHOR]

Aim of the current study was to evaluate the inter‐observer agreement between pathologists in the diagnosis of celiac disease (CD), in the qualified context of a multicenter study. Biopsies from the “PreventCD” study, a multinational‐ prospective‐ randomized study in children with at least one‐first‐degree relative with CD and positive for HLA‐DQ2/HLA‐DQ8. Ninety‐eight biopsies were evaluated. Considering diagnostic samples with villous atrophy (VA), the agreement was satisfactory (κ = 0.84), but much less when assessing the severity of these lesions. The use of the recently proposed Corazza‐Villanacci classification showed a moderately higher level of agreement (κ = 0.39) than using the Marsh‐Oberhuber system (κ = 0.31). 57.1% of cases were considered correctly oriented. A number of >4 samples per patient was statistically associated to a better agreement; orientation did not impact on κ values. Agreement results in this study appear more satisfactory than in previous papers and this is justified by the involvement of centers with experience in CD diagnosis and by the well‐controlled setting. Despite this, the reproducibility was far from optimal with a poor agreement in grading the severity of VA. Our results stress the need of a minimum of four samples to be assessed by the pathologist. [ABSTRACT FROM AUTHOR]

Introduction: A chemical factory located in Brescia, an industrialized town in North Italy, produced polychlorinated biphenyls (PCBs) since the 1930s to the 1980s, determining a relevant pollution of soil, food and people. Since 2001, following a survey carried out in the general population living in the town, the individuals with PCB serum levels higher than the reference entered a follow-up study.Methods: We performed a prospective cohort study including subjects with at least three PCB measures during the period 2003-2015. We evaluated the temporal trends of total PCB serum levels, the most common PCB congeners (PCB 138,153, 170, 180, 194 and 209), and toxic equivalency of dioxin-like PCBs using univariate and multivariate mixed models with and without a cubic-spline term for time.Results: A total of 128 subjects were enrolled (46.1% males, mean age at enrolment 57.7 years). The geometric mean of PCBs decreased from 35.4ng/ml at 0-3 years to 29.3ng/ml at 4-8 years and to 23.0ng/ml at 9-12 years. A 3.8% reduction of total PCB serum levels per year was estimated using both univariate and multivariate mixed models adjusted for age; a similar reduction was found for the most common PCB congeners and for toxic equivalency. Total PCB serum levels decreased over time for each age group: -3.9%, -4.0% and -3.4% for subjects aged ≤55 years, 56-65 and ≥66 years, respectively.Conclusion: A significant decrease of serum concentrations of PCBs was observed in subjects with high serum levels of these chemicals at enrolment over a twelve year period. The decrease was evident for each PCB congener and age group. [ABSTRACT FROM AUTHOR]

Purpose: The analysis of daily physical activity characteristics is an important starting point to favor the promotion of proper physical activity against obesity. The aim of our study was to characterize physical activity organization, among the different intensities and across age and ponderal status, to verify whether the normal-weight condition has the same physical activity characteristics across ages. Methods: We recruited 381 female participants; 100 were between 6 and 10 years old; 134 were between 35 and 54 years, and 147 were between 55 and 69 years. The body mass index of participants ranged from normal weight to obese. Daily physical activity was objectively recorded in the period between 15 June and 15 July, from 2011 to 2014. The effects of age, ponderal status, and their interaction on daily physical activity were studied. Results: Normal-weight children (NW-C) have higher daily METs and more vigorous physical activity than other sub-samples, while overweight and obese children (OW-C, O-C) have the same daily physical activity characteristics as normal-weight adults and older adults (NW-A, NW-OA). Conclusions: In female population, the intensity of daily physical activity is a distinctive characteristic of NW-C, while time engaged in moderate physical activity is a distinctive characteristic for NW-A and NW-OA. As OW-C and O-C have the same physical activity characteristics as NW-A and NW-OA, it is suggested that an age-related approach in the field of physical activity promotion should be developed. [ABSTRACT FROM AUTHOR]

Background:Early detection of undiagnosed HIV infected patients is of paramount importance. The attitude of Italian hospital-based Internal Medicine physicians to prescribe HIV testing following the detection of HIV-associated signs, symptoms and behaviours (triggers) has been reported to be poor. The aim of the study is to quantify the extent of the missed opportunities for early HIV diagnosis in Internal Medicine Departments (IMD). Methods:Patients admitted to IMD of a General University Hospital in Italy in March–June 2013 were interviewed using a structured questionnaire investigating the presence of triggers for HIV testing, including patient’s characteristics, symptoms and conditions associated with HIV infection. HIV tests performed during hospitalisation were recorded. Results:HIV testing was performed in 73 (6.6%) out of 1113 hospitalisations (1072 patients), providing positive results in three cases (4.1%). All of them presented ≥1 triggers. Conversely, 853 triggers were identified in 528 hospitalisations with at least one trigger (47.4%). The proportion of hospitalisations where an HIV testing was prescribed was 3.1%, 9.5% and 16.0% in the presence of zero, one-to-two or more triggers, respectively. Age <70 years, female gender, length of hospital stay, haematological disease, HBV infection, multiple sexual partners and lymphadenopathy were predictors of HIV testing by logistic regression analysis. Conclusions:Although chances of an HIV test being performed in patients hospitalised in IMD increases along with the number of triggers, the number of tests being performed in people presenting with triggers is unacceptably low and requires educational interventions in order to obtain individual and public health advantages. [ABSTRACT FROM AUTHOR]

Background & aims In the natural history of hepatitis B virus ( HBV) chronic infection, the hepatocellular carcinoma ( HCC) risk is unclear. We assessed incidence and predictors of HCC by a systematic review and meta-analysis. Methods We included longitudinal studies and randomized controlled trials assessing HCC incidence in untreated patients with HBV chronic infection. Incidence rates and their 95% confidence intervals were extracted by each study and pooled together in random effects models. Results Sixty-six studies were included with a total of 347 859 patients. According to liver disease status, the summary incidence rates were in Europe, North America and East Asia, respectively: (a) asymptomatic carriers: 0.07 (95% confidence interval: 0.05-0.09), 0.19 (0.07-0.31) and 0.42 (0.21-0.63) per 100 person-years, respectively; (b) inactive carriers: 0.03 (0.0-0.10), 0.17 (0.02-0.62) and 0.06 (0.02-0.10), respectively; (c) chronic hepatitis: 0.12 (0.0-0.27), 0.48 (0.22-0.91) and 0.49 (0.32-0.66), respectively; (d) compensated cirrhosis (Child-Pugh A): 2.03 (1.30-2.77), 2.89 (1.23-4.55) and 3.37 (2.48-4.26) respectively. Multivariate meta-regression showed a significant increase in incidence rates for age, and for status of a symptomatic carrier, chronic hepatitis and compensated cirrhosis compared to inactive carrier, but not for geographical area after adjusting for age. An increase in the incidence rates was also observed for alcohol intake ≥60 g/dl, HBV genotype C with respect to B and HBV- DNA serum levels >2000 IU/ml, in Asian studies. Conclusions Hepatocellular carcinoma risk in untreated subjects with HBV chronic infection is strongly related with age and liver disease status. [ABSTRACT FROM AUTHOR]

Aim: The optimal surgical treatment for anatomical anal stenosis (AS) remains to be determined. The aim of this study was to determine the rates of complications and recurrence after anoplasty for anatomical AS and, wherever feasible, compare the outcomes for the various techniques. Method: A PROSPERO‐registered systematic review was reported following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Medline, PubMed, Embase, Cochrane Library of Systematic Review, Scopus and Web of Science were searched for articles published up to May 2021. Studies that assessed the outcomes of anoplasty in adult patients with anatomical AS were selected. The primary outcomes were complications and recurrence. The methodological quality of studies was appraised using the Joanna Briggs Institute critical appraisal tools. Results: From the total of 2705 unique screened records, 151 were assessed for eligibility. Only 29 studies (two prospective) met the inclusion criteria, reporting data on 556 patients [mean age 53 (18–83) years, 46% female]. Previous history of surgery for haemorrhoidal disease accounted for three quarters of cases. A total of 14 types of anoplasty were found, with the Y–V flap being the most performed technique [27% of cases (n = 149)]. Complications frequently occurred, with a pooled prevalence of 10.2% (95% CI 3.9%–24.1%) after Y–V flap and 11.5% (5.3%–23.0%) after rhomboid/diamond flap. Patients undergoing house flap achieved better results in terms of clinical improvement, satisfaction and quality of life compared with Y–V flap and rhomboid/diamond flap. When considering only studies with at least 12 months of follow‐up, the pooled prevalence of recurrence was 4.7% (2.2%–9.8%), with significantly higher rates observed in the prospective versus retrospective series [pooled prevalence 18.9% (11.5%–29.5%) vs. 3.6% (1.7–7.8%), respectively; p < 0.001]. Conclusion: Both complications and recurrence were significantly lower after house flap compared with rhomboid/diamond and Y–V flap. Better designed multicentre studies with longer follow‐up are needed to confirm these findings. PROSPERO registration number: CRD42021239493. [ABSTRACT FROM AUTHOR]

Neutrophil to lymphocyte ratio (NLR) has been shown to predict occurrence of cardiovascular events in the general population. The aim of our study was to evaluate the role of NLR to predict major cardiovascular disease (CVD) events in HIV-infected subjects. We performed a retrospective cohort study of HIV-infected patients residing in the Local Health Authority (LHA) of Brescia, northern Italy, from 2000 to 2012. The incidence of CVD events in HIV-positive patients was compared with that expected in the general population living in the same area, computing standardized incidence ratios (SIRs). To evaluate the predictive role of NLR, univariate and multivariate Cox regression models were applied, computing hazard ratios (HRs). A total of 3766 HIV-infected patients (mean age 38.1 years, 71.3% males) were included (person-years 28768.6). A total of 134 CVD events occurred in 119 HIV-infected patients. A 2-fold increased risk (SIR 2.02) of CVD was found in HIV-infected patients compared to the general population. NLR levels measured at baseline and during follow-up were independently associated with CVD incidence, when also adjusting for both traditional CVD risk factors and HIV-related factors (HR 3.05 for NLR≥ 1.2). The area under the receiver operating characteristics (ROC) curve showed a modest, not statistically significant, increase, from 0.81 to 0.83, with addition of NLR to Framingham risk score model covariates. In conclusion an elevated NLR is a predictor of risk CVD in HIV-infected patients, independently from the traditional CVD risk factors. [ABSTRACT FROM AUTHOR]

Background The management of bloating is unclear and its relationship with patients' well-being and treatment satisfaction independent of other abdominal symptoms is uncharacterized. We evaluated the association of bloating with patient-reported outcomes. Methods Thirty-nine centers for functional gastrointestinal disorders joined the laxative inadequate relief survey. We enrolled 2203 consecutive outpatients with functional constipation ( FC) or constipation-predominant irritable bowel syndrome ( IBS-C) in two cross-sectional waves. Both wave 1 and 2 included the SF-12, the patient assessment of constipation-symptoms ( PAC- SYM), and the treatment satisfaction questionnaire for medication ( TSQM-2). Wave 2 only included a global rating of change ( GRC) scale to assess patients' assessment of efficacy concerning treatment switches occurred in the 3 months prior to the interview. Bloating in the abdomen was defined on the basis of PAC- SYM item 3. Key Results The average age was 50.1 years ( SD, 16.7) and 82.1% of patients were women. The prevalence of bloating was 91.6% ( n = 1970). Bloating was associated with SF-12 Physical Composite Score ( p < 0.01), SF-12 Mental Composite Score ( p < 0.01), GRC ( p < 0.01), Satisfaction with treatment effectiveness ( p < 0.01), convenience of administration ( p < 0.01), and side effects ( p < 0.01) after adjustment for possible confounders. Conclusions & Inferences Our data suggest that patients regard bloating as a key element in assessing clinical changes and treatments' efficacy as this symptom exerts a strong influence on patient-reported outcomes independent of possible confounders and other symptoms of constipation. Our data provide the rationale to investigate the efficacy and tolerability of new treatments specifically addressing this important, yet disregarded, patients' complain. [ABSTRACT FROM AUTHOR]

Neoplasms with plasma cell differentiation may occasionally involve the skin. Cutaneous lesions may represent the first sign of an underlying systemic plasma cell malignancy, such as multiple myeloma, or the skin itself may be the primary site of occurrence of a hematological tumor with plasma cell differentiation. Starting from examples encountered in our daily practice, we discussed the diagnostic approach pathologists and clinicians should use when faced with cutaneous lesions with plasma cell differentiation. Cases of primary cutaneous marginal zone lymphoma, localized primary amyloidosis/amyloidoma, and cutaneous manifestations (secondary either to multiple myeloma or to plasmablastic lymphoma) are discussed, focusing on the importance of the adequate patient's work-up and precise clinicopathological correlation to get to the correct diagnosis and appropriate treatment. The pertinent literature has been reviewed, and the clinical presentation, pathological findings, main differential diagnoses, treatment, and outcome of neoplasms with plasma cell differentiation involving the skin are discussed. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: Distal sensory neuropathy is the most common form of diabetic neuropathy. We developed a novel antidromic technique for assessment of distal nerve function for early diagnosis of diabetic neuropathy. Methods: Diabetic and control groups underwent standard and more distal sensory nerve conduction studies (NCS); sensory nerve action potentials (SNAPs) of the proper digital branches of the medial plantar nerve were recorded with our method after stimulation at the sole and recording from digits I and II. Results: Comparison between controls and diabetics showed a statistically significant difference in mean SNAP amplitudes for all nerves tested. A higher percentage of abnormal SNAPs was obtained with our technique than with either conventional or more distal NCS in all patients. Conclusions: As compared with clinical evaluation and other NCS, our antidromic stimulation was the most sensitive method to detect abnormal sensory nerve conduction in symptomatic and asymptomatic diabetic patients. Muscle Nerve 50:193-199, 2014 [ABSTRACT FROM AUTHOR]

To estimate prevalence and incidence of thrombotic Primary Antiphospholipid Syndrome (PAPS) in the general population aged 18–49 years. The study was carried out in Valtrompia, a valley in northern Italy, in 2011–2015. The identification of PAPS cases leveraged three integrated sources: 1) Rheumatology Unit at the University Hospital; 2) General Practitioners; 3) hospital discharge codes of patients admitted for thrombotic events. Prevalence and incidence were estimated as 22.9 (95% C.I. 11.4–41.0) and 5.0 (2.6–8.7) cases per 100,000 individuals, respectively. The estimates were 28.3 and 4.8, and 17.2 and 5.1 in males and females, respectively. The type of disease onset was mainly of arterial type in men and venous in women. Thrombotic PAPS was found to be a rare disease in this population-based study. Prevalence and incidence were not significantly different between males and females aged 18–49 years, but a different type of onset was observed. [ABSTRACT FROM AUTHOR]

Abstract: Brescia (North Italy) is located in a highly industrialized area with diffuse environmental pollution by polychlorinated biphenyls (PCBs) and with a high incidence of hepatocellular carcinoma (HCC). We aimed to investigate the concentration of PCBs congeners in serum, liver and adipose tissue of patients with HCC living in this area. We enrolled prospectively 101 HCC incident cases. Lipid-adjusted PCBs concentration of single congeners and total PCBs concentration, computed as the sum of 24 PCBs congeners, were measured in the serum of all subjects and in the liver and abdominal fat of 59 HCC cases undergoing surgery. A high correlation was found between PCBs serum and liver (Spearman r =0.79), serum and fat (r =0.91), and liver and fat (r =0.75) concentrations. Serum PCBs concentration in HCC patients did not vary according to demographical, clinical or epidemiological variables, apart from age, as PCBs concentration increased linearly with the subject’s age. This study confirms that serum lipid-adjusted PCBs concentration is a valid measure of PCBs body storage and is highly correlated with PCBs concentration detected in other biological samples. [Copyright &y& Elsevier]

Abstract: Background: Hepatitis C virus (HCV) infection is a global health problem. In Western countries, illicit drug users (IDUs) constitute the largest proportion of HCV patients. International guidelines no longer regard ongoing illicit drug use as a contraindication to antiviral therapy for chronic hepatitis C (CHC). Nonetheless, in clinical practice, few IDUs have access to HCV treatment, likely because many physicians believe these patients will have poor adherence or a lack of treatment efficacy. Objective: The aim of this study was to assess effectiveness and tolerability of combination treatment with ribavirin plus recombinant or pegylated interferon-α in the treatment of CHC in IDUs. Methods: MEDLINE, EMBASE, and the Cochrane Library were searched for relevant studies published in English between 2000 and December 2008. The following terms were searched: chronic hepatitis C, interferons, antiviral agents, methadone, and substance-related disorders. Full-text articles and abstracts were searched using predefined criteria. A manual search of abstracts from 8 international meetings of hepatologists was also conducted. Only prospective studies with a sample size >15 and a homogeneous treatment schedule were included. Articles were extracted independently by 2 of the authors using an electronic standardized form including study quality indicators. Results: Sixteen prospective studies were included, and data from a cohort of 953 IDUs were analyzed. The estimated overall sustained virologic response (SVR) and dropout (DO) rates in IDUs were 52% (95% CI, 44%–60%) and 26% (18%–35%, 95% CI), respectively. The rate of psychiatric severe adverse events (SAEs) that led to treatment discontinuation was 2% (95% CI, 1%–3%). These prevalences were not significantly different from those reported in registration trials of treatment of CHC that excluded IDUs from the study population (SVR, 50% [95% CI, 39%–61%]; DO, 26% [95% CI, 12%–41%]; and psychiatric SAEs, 2% [95% CI, 0%–6%]). By subgroup analysis, active ongoing drug use negatively affected the rate of treatment success (39% [95% CI, 30%–49%] vs 55% [95% CI, 45%–64%]; P = 0.02). Conclusion: Based on data from 16 prospective clinical studies of CHC treatment in IDUs published in the past 10 years, findings on effectiveness and tolerability are comparable to those in the general population. [Copyright &y& Elsevier]

Objective: Spontaneous non-enzymatic reaction of protein amino groups with glucose and other reducing sugars, known as glycation or Maillard reaction, has long been considered irreversible and inevitably followed by slow conversion of fructosamines and advanced glycation end products. Instead, recent identification of fructosamine 3 kinase (FN3K) has unveiled that fructosamines can be physiologically repaired, so that the FN3K enzyme could be considered a new form of protein repair. Methods: Thirty-one consecutive patients with colorectal cancer were enrolled in the study. FN3K gene expression was determined using quantitative RT-PCR. Results: The mean level of FN3K gene expression was significantly lower in cancer tissue than in the corresponding normal colorectal mucosa, and FN3K gene was under-expressed most particularly in the tumours located on the left side of the colon. Conclusions: Low mRNA levels of this enzyme in colon cancer tissue with respect to normal surrounding mucosa suggests that neoplastic cells have lost a protective enzymatic system. Reduced FN3K gene expression may be important in the pathogenesis and progression of colorectal cancer. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

• Current smoking was not related to salivary cortisol concentration in adolescents. • Salivary cortisol concentration was not associated with depressive symptom scales. • No evidence of a role of HPA axis in smoking-depressive symptoms association. Several studies have shown that smoking increases the risk of depressive symptoms, and suggested a possible role of the hypothalamic-pituitary-adrenal axis in the smoking-depression pathway. This study aimed to assess if smokers have higher cortisol levels than non-smokers, and if higher cortisol levels are associated with depressive symptoms. Saliva samples were collected from a subgroup of 409 participants at enrolment (13-14 years old) and two years later (15-16 years old). First, we examined the association between smoking phenotypes and cortisol concentration. Second, we evaluated whether these associations differed between adolescents with and without depressive symptoms. The mean difference between smokers and non-smokers in cortisol concentrations was close to zero at both time points. For instance, the adjusted mean difference for morning cortisol concentration between current and non-current smokers was 0.000 µg/dl [95% CI -0.055, 0.056]. In addition, there were no differences in cortisol concentration at the second time-point between those who had smoked and those who did not during the two previous years. Moreover, cortisol levels were not associated with depressive symptoms. The hypothesis that dysregulation of the hypothalamic-pituitary-adrenal axis might be involved in the association between smoking behavior and depressive symptoms during adolescence was not supported by this data. [ABSTRACT FROM AUTHOR]

Background: Preschool children with clinically-diagnosed asthma have a higher rate of emergency department visits and consume more resources for management than older children. However, no clinical trials have yet been performed measuring the impact of a combined diagnostic, therapeutic and educational pathway regimen for evaluation of wheezing control in children aged less than 6 years. The purpose of the present study was to assess the impact of a pediatric program developed in Italy, the Diagnostic Therapeutic Educational Pathway (DTEP), for asthma management in children less than 6 years old attending an asthma referral center. Methods: This is a retrospective population-based cohort study performed in children with asthma aged 0–5 years, attending at "Io e l'Asma center", Brescia, Italy between September 2007 and December 2014. The incidence rates (IRs) of hospitalization, emergency room visits, use of outpatient services and drug usage for dyspnea, wheezing, or respiratory symptoms were evaluated for time periods prior to and after DTEP intervention. Results: A total of 741 patients, aged 0–5 years completed the DTEP, including 391 and 350 children aged 0–2 and 3–5 years, respectively. The percentage of children aged 0–2 and 3–5 years showing improved control of wheezing symptoms during the 1st to 3rd visit interval as a result of the DTEP intervention increased from 39.5 to 60.9% and from 25.5 to 75.5%, respectively. During these periods, the IRs showed a significant decrease for all outcomes, from-8.6% to − 80.4%. Although specific IRs for drug prescriptions declined, particularly for LABA plus corticosteroids, antibiotics, and systemic corticosteroids, they increased for SABA, inhaled corticosteroid and leukotriene receptor antagonist usage. Conclusions: The results suggest that a real-world assessment of the integrated DTEP program for preschool children provides evidence for improved wheezing control and reduction of adverse therapeutic related outcomes. [ABSTRACT FROM AUTHOR]