The prevalence and incidence of thrombotic primary antiphospholipid syndrome in adults aged 18-49 years: A population-based study in a mountain community in northern Italy.

OBJECTIVE: To estimate prevalence and incidence of thrombotic Primary Antiphospholipid Syndrome (PAPS) in the general population aged 18-49 years. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Mediterranean-Oriented Dietary Intervention Is Effective to Reduce Liver Steatosis in Patients with Nonalcoholic Fatty Liver Disease: Results from an Italian Clinical Trial.

Results: One hundred and fifty five subjects aged 20-59 years underwent (i) liver ultrasound (US), (ii) clinical and anthropometric evaluations, (iii) blood tests, and (iv) assessment of dietary habits. According to US evaluation, 73 of them had severe, moderate, or mild liver steatosis (NAFLD patients) and 82 had no liver steatosis (healthy controls). Fifty-eight NAFLD patients and 73 controls completed the study. Among NAFLD patients, 26 (45%) downgraded steatosis severity, 12 of which achieved complete steatosis regression (21%). Three of the healthy controls developed NAFLD. The NAFLD patients improved their dietary habits and reduced BMI and waist circumference, during the study period, more than healthy controls. Liver steatosis remission/regression was independent of changes in BMI or liver enzymes and was more frequent among patients with mild steatosis at baseline. Conclusions: Mediterranean dietary advices, without a personalised meal planning, were efficient in reducing/remitting NAFLD, especially among patients with mild disease, which argues in favour of early identification and lifestyle intervention. This trial is registered with NCT03300661.

Mucin Expression Profiles in Ulcerative Colitis: New Insights on the Histological Mucosal Healing.

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.

Why are rare diseases underdiagnosed? A clinical management study on detection of primary biliary cholangitis in primary care.

Background: There are about 7,000 rare diseases that affect 10% of the world population. Primary biliary cholangitis, an autoimmune chronic liver disease of the interlobular bile ducts, is one of the most common causes of chronic cholestasis. However, it is a rare, often underdiagnosed and undertreated, disease which can lead to cirrhosis and liver failure. We aimed to assess the proportion of undetected primary biliary cholangitis patients in primary care through a clinical management process. Methods: We made two extractions of the clinical data concerning liver diseases, risk factors and laboratory tests from the databases of a sample of general practitioners, with a check and correction of mistakes. The clinical data of the patients without liver disease and major risk factors, and with serum Alkaline Phosphatase above the laboratory reference values, were re-evaluated by each general practitioner with an expert gastroenterologist. The patients with elevated Alkaline Phosphatase values and without evidence of intrahepatic or extrahepatic causes of cholestasis were considered suspected for primary biliary cholangitis and assessed for antimitochondrial antibodies test and specialist' s evaluation, according to present guidelines. Results: A total of 20,480 adults attending 14 general practitioners in the province of Brescia, Northern Italy, were included in the study. Nine patients had a prior primary biliary cholangitis diagnosis, with a prevalence of 43.9/100000. After excluding 2094 (10.2%) patient with liver diseases or other causes of cholestasis, 121 subjects with Alkaline Phosphatase above the reference values were re-evaluated by the general practitioners and gastroenterologist, and 27 patients without symptoms or signs of cholestasis were considered suspected for primary biliary cholangitis: 9 of them were tested for antimitochondrial antibodies, and three new primary biliary cholangitis cases were detected (+33%). Discussion and Conclusions: This study shows that there is a not negligible burden of undetected cases of adult rare diseases that can be diagnosed in primary care, through a disease management procedure, without modifying the routine clinical practice.

Is weight gain preventable in women with early breast cancer undergoing chemotherapy? A real-world study on dietary pattern, physical activity, and body weight before and after chemotherapy.

PURPOSE: We aimed to investigate the role of a lifestyle intervention and clinical and therapeutic factors for preventing weight gain in early breast cancer (BC) patients from one week before to 12 months after chemotherapy. METHODS: Dietary assessments were conducted by a trained dietician using a food-frequency questionnaire at each clinical assessment. Total energy, macronutrients intakes, and physical activity were estimated and the Mediterranean Diet Score (MDS) for adherence to Mediterranean diet was calculated. At each follow-up visit, patients were provided with dietary advices according to Mediterranean and Italian guidelines by a registered dietician, after evaluation of their food records. The associations of clinical characteristics, dietary pattern, and physical activity with weight gain were evaluated by multiple logistic regression, with weight gain ≥5% from baseline value as a dichotomous dependent variable. RESULTS: 169 early BC patients who met all follow-up visits and provided complete data were included in the analysis. From baseline to last assessment, weight loss (≥5% decrease from baseline value), stable weight, and weight gain were observed in 23.1%, 58%, and 18.9% women, respectively. Overall, a 0.68 kg mean decrease in women's weight (-1.1% from baseline) was observed. The risk of gaining weight increased for having normal weight/underweight at baseline, receiving hormone therapy, MDS worsening, and physical activity decreasing from baseline to last assessment. CONCLUSION: Providing simple suggestions on Mediterranean diet principles was effective for preventing weight gain in normal weight women and favoring weight loss in overweight and obese women.

Efficacy and safety of Propionibacterium extract gel versus glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized controlled trial.

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.

CIC-rearranged sarcoma presenting with superior vena cava syndrome: case report.

CIC-rearranged sarcomas are rare mesenchymal neoplasms belonging to the family of undifferentiated small round cell sarcomas. This report details the case of a 45-year-old man presenting with symptoms of mediastinal compression, radiological diagnosis of a mediastinal mass and rapid evolution to full-blown superior vena cava syndrome. The emergency was successfully managed with a pharmacological approach. Formulation of a pathological diagnosis of CIC-rearranged sarcoma was initially supported by fluorescence in situ hybridisation findings and later validated by next-generation sequencing, which showed CIC-DUX4 gene fusion. A chemotherapy regimen was started with immediate benefits for the patient. The spectrum of pathological entities able to cause superior vena cava syndrome is wide, and recognition of rare causes is important to tailor the therapeutic approach to the specific disease. This is, to the best of our knowledge, the first report of CIC-rearranged sarcoma presenting with superior vena cava syndrome.

Anoplasty for anatomical anal stenosis: systematic review of complications and recurrences.

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.

The effect of known and unknown confounders on the relationship between air pollution and Covid-19 mortality in Italy: A sensitivity analysis of an ecological study based on the E-value.

Back in December 2019, the novel coronavirus disease 2019 (Covid-19) started rapidly spreading worldwide, especially in Italy that was among the most affected countries. The geographical distribution of air pollution and Covid-19 mortality in Italy suggested atmospheric pollution as a worsening factor of severe Covid-19 health outcomes. The present nationwide ecological study focused on all 107 Italian territorial areas, aiming to assess the potential association between Particulate Matter concentration, less than 2.5 µm in diameter (exposure), and Covid-19 mortality rate (outcome) throughout 2020, by looking at 28 potential confounders. A potential positive association between exposure and outcome was observed when performing a multivariate regression analysis with a Negative Binomial model, suggesting that an increase of 1 µg/m3 in the exposure is associated with an increase of 9.0% (95% CI: 6.5%-11.6%) in the average Covid-19 mortality rate, conditional on all 28 potential confounders. A sensitivity analysis, based on the E-value, shows that a hypothetical unmeasured confounder would have to be associated with both PM2.5 concentration and Covid-19 mortality rate by a rate ratio of at least 1.40-fold each to explain away the exposure-outcome association, conditional on all 28 covariates included in the main analysis model. Moreover, the Observed Covariate E-value (OCE) was reported to provide a contextualization of the E-value on the observed covariates included in the study. The OCE sensitivity analysis shows that a set of unknown confounders similar in size and magnitude to the set of the considered climatic factors could potentially explain away the estimated exposure-outcome association. Consequently, the role of climatic factors in the Covid-19 pandemic is worth of further investigation.

Country differences in the cross-sectional associations between smoking and depressive symptoms in adolescence.

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.

[Effects on mortality and morbidity among the population living close to the Valmadrera (Lombardy Region, Northern Italy) incinerator]. / Effetti sulla mortalità e morbilità nella popolazione residente nei pressi dell'inceneritore di Valmadrera (LC).

OBJECTIVES: assessment of the health effects on the resident population around the incinerator for municipal solid waste in Valmadrera (Lombardy Region, Northern Italy) in relation to the exposure level to the pollutants produced by the plant. DESIGN: historical cohort study, based on the resident population from 2003 to 2016 in the study area. With a dispersion model, based on PM10 emitted by the plant, three areas of exposure (high, medium, low) were defined and, on the basis of the residence of the cohort, different exposure levels were attributed to the subjects. The association between level of exposure and health effects were estimated by comparing the high and medium exposure levels with the low exposure level, using a Cox model, adjusted for age and socioeconomic deprivation index. MAIN OUTCOME MEASURES: mortality rates, hospitalization rates, cancer incidence rates, and perinatal outcomes were analysed for the main causes potentially associated with exposure to incineration plants. RESULTS: the subjects enrolled in the cohort were 106,056 (1,000,242 person-years). There were no statistically significant excesses of risk for almost all the outcomes investigated. Excessive mortality and hospitalization were found for liver/biliary cancers (HR women: 2.57; 95%CI 1.15-2.79; HR men: 2.22; 95%CI 1.10-4, 84). In the municipality where the plant is located, an excess prevalence (OR 1.78; 95%CI 1.43-2.21) of hepatitis C was found. CONCLUSIONS: the results suggest the absence of a relationship between residence in areas with different levels of pollutants emitted by the plant and the onset of almost all diseases. The associated causes do not have aetiological plausibility with exposure to pollutants from waste incineration. In particular, for liver/liver and biliary cancer, the association with infectious causes rather than exposure to environmental pollutants is more plausible.

Transanal reinforcement of low rectal anastomosis versus protective ileostomy after total mesorectal excision for rectal cancer. Preliminary results of a randomized clinical trial.

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).

COVID-19 incidence and mortality in Lombardy, Italy: An ecological study on the role of air pollution, meteorological factors, demographic and socioeconomic variables.

Lombardy, the most populated and industrialized Italian region, was the epicentre of the first wave (March and April 2020) of COVID-19 in Italy and it is among the most air polluted areas of Europe. We carried out an ecological study to assess the association between long-term exposure to particulate matter (PM) and nitrogen dioxide (NO2) on COVID-19 incidence and all-cause mortality after accounting for demographic, socioeconomic and meteorological variables. The study was based on publicly available data. Multivariable negative binomial mixed regression models were fitted, and results were reported in terms of incidence rate ratios (IRRs) and standardized mortality ratios (SMR). The effect of winter temperature and humidity was modelled through restricted cubic spline. Data from 1439 municipalities out of 1507 (95%) were included in the analyses, leading to a total of 61,377 COVID-19 cases and 40,401 deaths from all-causes collected from February 20th to April 16th and from March 1st to April 30th, 2020, respectively. Several demographic and socioeconomic variables resulted significantly associated with COVID-19 incidence and all-cause mortality in a multivariable fashion. An increase in average winter temperature was associated with a nonlinear decrease in COVID-19 incidence and all-cause mortality, while an opposite trend emerged for the absolute humidity. An increase of 10 µg/m3 in the mean annual concentrations of PM2.5 and PM10 over the previous years was associated with a 58% and 34% increase in COVID-19 incidence rate, respectively. Similarly, a 10 µg/m3 increase of annual mean PM2.5 concentration was associated with a 23% increase in all-cause mortality. An inverse association was found between NO2 levels and COVID-19 incidence and all-cause mortality. Our ecological study showed that exposure to PM was significantly associated with the COVID-19 incidence and excess mortality during the first wave of the outbreak in Lombardy, Italy.

Late acute aortic dissection following cardiac transplantation in lupus-affected donor aorta.

We report the case of a young woman who underwent cardiac transplantation from systemic lupus erythematosus affected donor and who developed a type A aortic dissection limited only to the graft aortic wall 9 years after.

Symptoms of mental health problems among Italian adolescents in 2017-2018 school year: a multicenter cross-sectional study.

BACKGROUND: Identifying individual and contextual factors that influence adolescent well-being is a research priority. This study aimed to assess the prevalence of symptoms of mental health problems and some related factors in Italian adolescents in 2017-2018. METHODS: The present study was a cross-sectional survey among 3002 students aged 15-16 years who resided in two Italian provinces, in North and South Italy. Symptoms of mental health problems were assessed using the SDQ and CES-DC, and students' risk-taking behaviors and school climate perception were assessed. All information was collected anonymously. Logistic regression models were used to assess the associations of tobacco and alcohol use, screen time, bullying, and school climate with symptoms of mental health problems. RESULTS: One student out of five reported symptoms of mental health problems, with a more than double proportion among girls than boys (28.7% vs 10.4% with depressive symptoms, respectively). Thirty percent and 40% of students smoked tobacco or drank alcoholic beverages at least once in the past month, and more than 40% reported being victims or authors of bullying in the past 6 months. Smoking behavior, alcohol consumption, screen time, bullying, and negative school climate had 1.2- to 3.3-fold increased odds of symptoms of mental health problems without substantial differences between sexes and geographical areas. CONCLUSIONS: Tobacco and alcohol use, screen time, bullying, and school climate were independently associated with symptoms of mental health problems in a large sample of 15-16-year-old Italian adolescents without substantial gender and geographical differences.

[Residential cohort study to assess the impact of emissions released by a cement plant on the health status of the population residing in Pederobba (Veneto Region, Northern Italy)]. / Studio di coorte residenziale per valutare l'impatto delle emissioni di un cementificio sullo stato di salute della popolazione di Pederobba (Treviso).

OBJECTIVES: to assess the impact of a cement plant emissions on mortality, hospitalizations, and cancer incidence in the residents of the municipality of Pederobba (Veneto Region, Northern Italy). DESIGN: retrospective residential cohort study. SETTING AND PARTICIPANTS: the study was conducted in Pederobba and in 7 neighbouring municipalities (Cavaso Del Tomba, Cornuda, Crocetta del Montello, Monfumo, Segusino, Valdobbiadene, Vidor). The cohort included 12,116 residents in Pederobba (151,784 person-years) and 49,004 residents in the neighbouring municipalities (660,268 person-years) in the period 1996-2017. On the basis of the model estimate of the annual average concentration of nitrogen dioxide (NO2), the municipality of Pederobba was divided into an area with higher exposure of NO2 and another one at lower exposure of NO2. Two comparisons were made: the first between the residents in Pederobba and residents in the neighbouring municipalities; the second between people residing in Pederobba in the higher and in the lower exposure areas. MAIN OUTCOME MEASURES: analysis of cause-specific mortality and hospitalization and cancer incidence, with particular attention to the diseases for which there is evidence of association with exposure to air-pollutants. For cancer incidence, available data were limited to the municipalities of Pederobba, Cavaso Del Tomba, Cornuda, Crocetta del Montello, and Monfumo for the period 1996-2015. RESULTS: the comparison among Pederobba and the 7 neighbouring municipalities showed that within Pederobba residents there was:ʉۢ a slight increase in the risk of death from all causes in women, due to circulatory diseases (HR 1.29; 95%CI 1.15-1.45), in particular ischaemic heart disease (HR 1.55; 1.27-1.89) and cerebrovascular diseases (HR 1.35; 1.06-1.72);ʉۢ a moderate increase in hospitalizations for circulatory diseases, such as heart failure (HR 1.17; 1.00-1.37) and cerebrovascular diseases (HR 1.41; 1.17 -1.70), especially in elderly women;ʉۢ a slight increase in hospitalizations for respiratory diseases, especially in older women (HR 1.19; 1.04-1.37);ʉۢ no difference were observed in cancer incidence, neither for all nor for single cancer sites, in both genders.The comparison between residents in the higher exposure area and those in the lower exposure area showed no difference in mortality, hospitalizations, and cancer incidence. CONCLUSIONS: higher mortality and hospitalization rates from circulatory and respiratory causes detected in Pederobba compared to the neighbouring municipalities were not confirmed by the comparison between residents in the higher and in the lower exposure area. Overall, data did not show a clear, well-characterized relationship between the exposure to pollutants emitted by the cement plant and the onset of chronic diseases. The excess of mortality and hospitalization for cardiovascular and cerebrovascular diseases, reported especially in older women, deserves further investigation, because of the complex cause-effect relations of these diseases.

Cation Exchange Protocols to Radiolabel Aqueous Stabilized ZnS, ZnSe, and CuFeS2 Nanocrystals with 64Cu for Dual Radio- and Photo-Thermal Therapy.

Here, cation exchange (CE) reactions are exploited to radiolabel ZnSe, ZnS, and CuFeS2 metal chalcogenide nanocrystals (NCs) with 64Cu. The CE protocol requires one simple step, to mix the water-soluble NCs with a 64Cu solution, in the presence of vitamin C used to reduce Cu(II) to Cu(I). Given the quantitative cation replacement on the NCs, a high radiochemical yield, up to 99%, is reached. Also, provided that there is no free 64Cu, no purification step is needed, making the protocol easily translatable to the clinic. A unique aspect of the approach is the achievement of an unprecedentedly high specific activity: by exploiting a volumetric CE, the strategy enables to concentrate a large dose of 64Cu (18.5 MBq) in a small NC dose (0.18 µg), reaching a specific activity of 103 TBq g-1. Finally, the characteristic dielectric resonance peak, still present for the radiolabeled 64Cu:CuFeS2 NCs after the partial-CE reaction, enables the generation of heat under clinical laser exposure (1 W cm-2). The synergic toxicity of photo-ablation and 64Cu ionization is here proven on glioblastoma and epidermoid carcinoma tumor cells, while no intrinsic cytotoxicity is seen from the NC dose employed for these dual experiments.

Efficacy of cyanoacrylate in the prevention of delayed bleeding after endoscopic mucosal resection of large colorectal polyps: a pilot study.

BACKGROUND: Postoperative bleeding is a common complication after endoscopic polypectomy, particularly after endoscopic mucosal resection (EMR) of large non-pedunculated polyps, despite prophylactic clipping can reduce its occurrence. Cyanoacrylate glue has recently been proposed as a useful tool in reducing bleeding in surgery because of its adhesive and haemostatic properties. The aim of this study is to evaluate the usefulness of endoscopic application of a modified cyanoacrylate glue in the prevention of early or delayed post EMR bleeding. METHODS: This is a pilot study. Inclusion criteria were patients between 18 and 75 years old affected by sessile or flat colonic polyps larger than 2 cm. Patients enrolled in the study were randomized in two groups: group A (EMR) and group B (EMR with the application of 0.3 ml of N-butyl-2-cyanoacrylate + methacryloxysulfolane-Glubran 2®). RESULTS: Fifteen patients in both group A and B were enrolled. There were no intraoperative complications but haemostatic clipping was necessary in 3 patients in each group because of active bleeding. Delayed (after 24 h) bleeding occurred in two patients (13.3%) in group A requiring hospital readmission and re-do endoscopy with apposition of haemostatic clips. No case of bleeding was recorded in group B (p = 0.48). CONCLUSION: The results of this pilot study suggest a potential role of local spray application of Glubran®2 in reducing post-procedural bleeding.

Laparoscopic liver resection in elderly patients: systematic review and meta-analysis.

Laparoscopic liver resection (LLR) is becoming standard practice, replacing the open approach in terms of safety and feasibility. However, few data are available for the elderly. The objective of this study is to assess the feasibility of LLR in elderly patients, by making a comparison with open liver resection (OLR) and with non-elderly patients. Relevant studies found in the Cochrane Library, Embase, PubMed, and Web of Science were used in order to perform a systematic review and meta-analysis. Nine fully extracted comparative studies were included and two groups were identified: Group 1 with a comparison between OLR and LLR in the elderly and Group 2 with a focus on differences after LLR between elderly and non-elderly patients. A total number of 497 elderly patients who underwent LLR were analyzed. A random effect model was used for the meta-analysis. In Group 1, 1025 elderly patients were included: 640 underwent OLR and 385 underwent LLR. LLR was associated with minor blood loss (MD - 240 mL, 95% CI - 416.61, - 63.55; p 0.008; I2 = 96%), less transfusion (8% vs. 13.1%; RR 0.61, 95% CI 0.41, 0.91; p = 0.02; I2 = 0%), fewer postoperative Clavien-Dindo III/IV complications (RR 0.48 in favor of LLR; 95% CI 0.29, 0.77; p = 0.003; I2 = 0%). On the other hand, no significant difference was observed in terms of bile leakage, ascites, mortality, liver failure, or R0 resection. Group 2 included 112 elderly and 276 non-elderly patients who underwent LLR. The meta-analysis showed no significant difference in terms of blood loss, transfusions, liver failure, Clavien-Dindo III/IV complications, postoperative mortality, ascites, bile leak, hospital stay, R0 resection, and operative time. Laparoscopic liver resection is a safe and feasible procedure for elderly patients. However, further randomized studies are required to confirm this.

Longitudinal association between tobacco use and the onset of depressive symptoms among Swedish adolescents: the Kupol cohort study.

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.