Association of sedentary time with risk of cardiovascular diseases and cardiovascular mortality: A systematic review and meta-analysis of prospective cohort studies.

Given the high prevalence of cardiovascular disease (CVD), we meta-analysed CVD relative risk (RR) in relation to high vs. low categories of self-reported and objectively assessed sedentary behaviours from cohort studies; in a sub-sample (n = 4 studies), the theoretical substitution of one hour spent sedentary with the same amount of time spent in light-intense physical activity was evaluated. Based on 19 studies (60,526 fatal and non-fatal CVD, 1,473,354 individuals and 13,559,139 persons-year) we estimated a 30% increased CVD risk for high vs. low categories of sedentary behaviour (RR = 1.29, confidence interval (CI) = 1.22;1.37). Every hour spent sedentary corresponds to a 5% increased fatal and non-fatal CVD risk (RR = 1.05, CI = 1.02;1.07). Dose-response meta-analysis revealed that sedentary behaviour is statistically significantly associated to fatal and non-fatal CVD risk following a J-shaped relation. Substituting one hour spent sedentary with physical activity of light intensity reduced the risk of fatal and non-fatal CVD events by one-fifth (RR =0.84, CI = 0.73;0.97). In meta-regression analysis, potential influential factors such as age, sex, and medical condition did not essentially alter the results.

Evaluation of a large set of patients with Autoimmune Polyglandular Syndrome from a single reference centre in context of different classifications.

PURPOSE: To characterize patients with APS and to propose a new approach for their follow-up. Query ID="Q1" Text="Please check the given names and familynames." METHODS: Monocentric observational retrospective study enrolling patients referred to the Outpatients clinic of the Units of Endocrinology, Diabetology, Gastroenterology, Rheumatology and Clinical Immunology of our Hospital for Autoimmune diseases. RESULTS: Among 9852 patients, 1174 (11.9%) [869 (73.9%) female] were diagnosed with APS. In 254 subjects, the diagnosis was made at first clinical evaluation (Group 1), all the other patients were diagnosed with a mean latency of 11.3 ± 10.6 years (Group 2). Group 1 and 2 were comparable for age at diagnosis (35.7 ± 16.3 vs. 40.4 ± 16.6 yrs, p = .698), but different in male/female ratio (81/173 vs 226/696, p = .019). In Group 2, 50% of patients developed the syndrome within 8 years of follow-up. A significant difference was found after subdividing the first clinical manifestation into the different outpatient clinic to which they referred (8.7 ± 8.0 vs. 13.4 ± 11.6 vs. 19.8 ± 8.7 vs. 7.4 ± 8.1 for endocrine, diabetic, rheumatologic, and gastroenterological diseases, respectively, p < .001). CONCLUSIONS: We described a large series of patients affected by APS according to splitters and lumpers. We propose a flowchart tailored for each specialist outpatient clinic taking care of the patients. Finally, we recommend regular reproductive system assessment due to the non-negligible risk of developing premature ovarian failure.

Line-field confocal optical coherence tomography of cutaneous vascular lesions: Morphological assessment and histopathological correlations.

BACKGROUND: Cutaneous vascular lesions (VLs) are benign or malignant processes involving blood and/or lymphatic vessels, usually readily diagnosed with dermoscopy. However, cases showing unclear clinical/dermoscopic findings may require further investigations. Line-field confocal optical coherence tomography (LC-OCT) is a new, non-invasive imaging technique displaying high resolution and deep penetration. The aim of this study was to describe the LC-OCT features of the most common benign and malignant VLs and to correlate them with histopathological substrates. METHODS: Clinical, dermoscopic, LC-OCT and histopathological images of VLs were retrospectively collected. Detailed LC-OCT description and histopathological correlations were produced for different types of VLs. RESULTS: The study included 71 VLs belonging to 50 caucasian patients [31 (62%) females; median age 56.8 (30-83) years] study lesions included 25 cherry haemangiomas, 15 angiokeratomas, 10 thrombosed haemangiomas, six pyogenic granulomas, five venous lakes, four targetoid haemosiderotic haemangiomas, four Kaposi's sarcomas and two extraungual glomus tumours. LC-OCT detected increased dermal vascularity, assuming different size and shape according to the particular type of VLs. LC-OCT criteria correlated well to established histopathologic findings. CONCLUSION: The results of our preliminary observations indicate that in vivo evaluation with LC-OCT may provide practical clues for the identification of the vascular nature of a lesion and its differential diagnosis.

Predictors of disease recurrence after curative surgery for nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNENs): a systematic review and meta-analysis.

PURPOSE: Patients submitted to curative surgery for non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs) exhibit a variable risk of disease relapse. Aims of this meta-analysis were to estimate the rate of disease recurrence and to investigate the risk factors for disease relapse in patients submitted to curative surgery for NF-PanNENs. METHODS: Medline/Pubmed and Web of Science databases were searched for relevant studies. A meta-regression analysis was performed to investigate the source of recurrence rate heterogeneity. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CI) were used to assess the effect of each possible prognostic factor on disease-free survival. RESULTS: Fifteen studies, involving 2754 patients submitted to curative surgery for NF-PanNENs, were included. The pooled rate of disease recurrence was 21% (95% CI 15-26%). Study quality (Odds ratio, OR 0.94, P = 0.016) and G3-PanNENs rate (OR 2.18, P = 0.040) independently predicted the recurrence rate variability. Nodal metastases (HR 1.63, P < 0.001), tumor grade G2-G3 (G1 versus G2: HR 1.72, P < 0.001, G1 versus G3 HR 2.57, P < 0.001), microvascular (HR 1.25, P = 0.046) and perineural (HR 1.29, P = 0.019) invasion were identified as significant prognostic factors. T stage (T1-T2 versus T3-T4, P = 0.253) and status of resection margins (R0 versus R1, P = 0.173) did not show any significant relationship with NF-PanNENs recurrence. CONCLUSION: Disease relapse occurs in approximately one out of five patients submitted to curative surgery for NF-PanNENs. Nodal involvement, tumor grade, microvascular and perineural invasion are relevant prognostic factors, that should be taken into account for follow-up and for possible trials investigating adjuvant or neoadjuvant treatments.

Computerized tomography texture analysis of pheochromocytoma: relationship with hormonal and histopathological data.

OBJECTIVES: Pheochromocytomas are rare tumors which can present with heterogeneous secretion profiles, clinical manifestations, and radiologic appearance. Under a histopathological point of view, they can be characterized as more or less aggressive with the Pheochromocytoma of the Adrenal gland Scaled Score (PASS) and the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) score. The aim of this study is to analyze the texture analysis characteristics of pheochromocytoma and identify whether the texture analysis can yield information aiding in the diagnosis and the characterization of those tumors. METHODS: Radiological, biochemical, and histopathological data regarding 30 consecutive patients with histologically confirmed pheochromocytoma were analyzed. Images obtained in the unenhanced, late arterial, venous, and delayed phases were used for the texture analysis. RESULTS: Urinary epinephrine and metanephrine levels showed a significant correlation (R2 = 0.946; R2 = 699) in the multivariate linear model with texture features, as well as Ki-67 (R2 = 0.397), PASS score (R2 = 0.182), GAPP score (R2 = 0.705), and cellularity showed a significant correlation (R2 = 0.389). The cluster analysis based on radiomic features resulted in 2 clusters, with significative differences in terms of systolic and diastolic blood pressure values at the time of diagnosis (p = 0.025), GAPP score (4 vs 6, p = 0.05), histological pattern (1-2, p = 0.039), and comedonecrosis (0% vs 50%, p = 0.013). CONCLUSION: In conclusion, our study provides the proof of concept for the use of texture analysis on contrast-enhanced CT images as a noninvasive, quantitative tool for helping in the characterization of the clinical, biochemical, and histopathological features of pheochromocytoma.

Sporadic non-functioning pancreatic neuroendocrine tumours: multicentre analysis.

BACKGROUND: Outcomes after surgery for sporadic pancreatic neuroendocrine neoplasms (Pan-NENs) were evaluated. METHODS: This multicentre study included patients who underwent radical pancreatic resection for sporadic non-functioning Pan-NENs. In survival analysis, the risk of mortality in this cohort was analysed in relation to that of the matched healthy Italian population. Relative survival (RS) was calculated as the rate between observed and expected survival. Factors related to RS were investigated using multivariable modelling. RESULTS: Among 964 patients who had pancreatic resection for sporadic non-functioning Pan-NENs, the overall RS rate was 91.8 (95 per cent c.i. 81.5 to 96.5) per cent. 2019 WHO grade (hazard ratio (HR) 5.75 (s.e. 4.63); P = 0.030) and European Neuroendocrine Tumour Society (ENETS) TNM stage (6.73 (3.61); P < 0.001) were independent predictors of RS. The probability of a normal lifespan for patients with G1, G2, G3 Pan-NENS, and pancreatic neuroendocrine carcinomas (Pan-NECs) was 96.7, 54.8, 0, and 0 per cent respectively. The probability of a normal lifespan was 99.8, 99.3, 79.8, and 46.8 per cent for those with stage I, II, III, and IV disease respectively. The overall disease-free RS rate was 73.6 (65.2 to 79.5) per cent. 2019 WHO grade (HR 2.10 (0.19); P < 0.001) and ENETS TNM stage (HR 2.50 (0.24); P < 0.001) significantly influenced disease-free RS. The probability of disease-free survival was 93.2, 84.9, 45.2, and 6.8 per cent for patients with stage I, II, III, and IV disease, and 91.9, 45.2, 9.4, and 0.7 per cent for those with G1, G2, G3 Pan-NENS, and Pan-NECs, respectively. CONCLUSION: A surgical approach seems without benefit for Pan-NECs, and unnecessary for small G1 sporadic Pan-NENs. Surgery alone may be insufficient for stage III-IV and G3 Pan-NENs.

Diabetes mellitus induced by immune checkpoint inhibitors: type 1 diabetes variant or new clinical entity? Review of the literature.

Immune Check-Point Inhibitors (CPIs) have improved long-term patients' outcomes in several advanced cancers. Diabetes mellitus induced by CPIs (CPI-DM) is considered the second most frequent endocrine CPIs' side effects with a variable prevalence up to 2%. The aim of our study was to identify CPI-DM characteristics and differences from the classical form of diabetes. Therefore, we conducted a structured Pubmed® search collecting publications dated from January 2015 to December 2019. A total of 642 citations were identified and 121 publications met our study criteria. We analyzed 200 case reports, including our 3 cases under publication. The majority of CPI-DM occurred with anti-Programmed cell Death-1 in monotherapy or in combination, although few cases with Programmed cell Death Ligand-1 and Cytotoxic T Lymphocyte Antigen 4 were reported. Generally, CPI-DM arose early (an average of 9 weeks after CPIs starting), but also after the end of CPIs treatment. In all patients, CPI-DM has an acute onset and in 67.5% of cases diabetic ketoacidosis occurs. C-peptide levels were usually and permanently compromised, requiring lifelong insulin therapy. Moreover, autoimmunity and genetic profile was not always helpful. In particular, anti-glutamic acid decarboxylase (anti-GAD) antibodies and Human Leukocyte Antigen (HLA) DR4 were present in only 43.0% and 51.3% of cases respectively. In 51.0% of subjects a mild exocrine impairment coexisted. In short, though CPI-DM has similarities to type 1 diabetes mellitus, it represents a new, largely unknown, clinical entity. In addition, as CPI-DM is a relative frequent side-effect under CPI, a close monitoring of the glucose levels and early signs and symptoms of diabetes in patients affected by neoplasm is recommended.

Mortality in relation to profiles of clinical features in Ghanaian severely undernourished children aged 0-59 months: an observational study.

Severe acute malnutrition (SAM) is associated with a complex pattern of various clinical conditions. We investigated how risk factors cluster in children with SAM, the relationship between clusters of risk factors and mortality as well as length of stay in children with SAM. A prospective observational study design was used. Data were extracted from medical records of 601 infants and children aged 0-59 months admitted and treated for SAM in three Ghanaian referral hospital between June 2013 and June 2018. Among the 601 medical records extracted, ninety-nine died. Three clusters of medical features clearly emerged from data analyses. Firstly, an association was defined by eye signs, pallor, diarrhoea and vomiting with gastrointestinal infections and malaria. In this cluster, pallor and eye signs were related to 2- to 5-fold increased mortality risk. Secondly, HIV, oedema, fast pulse, respiratory infections and tuberculosis; among those features, HIV increased child mortality risk by 2-fold. Thirdly, shock, convulsions, dermatitis, cold hands and feet, weak pulse, urinary tract infections and irritability were clustered. Among those features, cold hands and feet, dermatitis, convulsions and shock increased child mortality risk in a range of 2- to 9-fold. Medical conditions and clinical signs in children diagnosed with SAM associate in patterns and are related to clinical outcomes.

Searching for novel multimodal treatments in oligometastatic pancreatic cancer.

BACKGROUND: Metastatic pancreatic cancer has a median overall survival of less than 12 months, even if treated with chemotherapy. Selected patients with oligometastatic disease could benefit from multimodal treatments connecting chemotherapy and surgical treatment or radiofrequency ablation (RFA) of metastases. CASE PRESENTATION: We present a patient with oligometastatic pancreatic cancer recurrence who was successfully treated with a multimodal therapeutic approach. A 57-year-old male initially presenting with resectable pancreatic cancer underwent pancreatoduodenectomy. The histopathological diagnosis revealed ductal pancreatic adenocarcinoma with positive surgical resection margins and negative lymph nodes. He completed six cycles of adjuvant therapy with gemcitabine (1000 mg/mq 1,8,15q 28), followed by external radiotherapy (54 Gy in 25 fractions) associated with gemcitabine 50 mg/mq twice weekly. Three years later, the patient developed multiple liver metastases, and he started FOLFIRINOX (oxaliplatin 85 mg/mq, irinotecan 180 mg/mq, leucovorin 400 mg/mq and fluorouracil 400 mg/mq given as a bolus followed by 2400 mg/mq as a 46 h continuous infusion,1q 14) as a first-line treatment. The CT scan showed a partial response after 6 cycles. After multidisciplinary discussion, the patient underwent a laparotomic metastasectomy of the three hepatic lesions. After additional postsurgical chemotherapy with 4 cycles of the FOLFIRINOX schedule, the patient remained free of recurrence for 12 months. A CT scan showed a new single liver metastasis, which was treated with radiofrequency ablation (RFA). A second radiofrequency ablation was performed when the patient developed another single liver lesion 12 months after the first RFA; currently, the patient is free from recurrence with an overall survival of 6 years from the diagnosis. CONCLUSIONS: Our case has benefited from successful multimodal treatment, including surgical and local ablative techniques and systemic chemotherapy. A multimodal approach may be warranted in selected patients with oligometastatic pancreatic cancer and could improve overall survival. Further research is needed to investigate this approach.

Prospective observational study on the complications and tolerability of a peripherally inserted central catheter (PICC) in neuro-oncological patients.

PURPOSE: The use of central venous catheters with peripheral insertion (PICC) has increased rapidly in recent years, particularly in cancer patients. The benefits provided may occasionally be affected by relevant complications, such as infections and thrombotic events, especially in neuro-oncological patients. To date, the risk of PICC-related complications in this subset of patients is unknown, as is tolerability. As a primary objective, this study aimed to collect complications related to PICCs in primary neuro-oncological patients. As a secondary objective, the study aimed to evaluate PICC tolerability. METHODS: Neuro-oncological patients with PICCs that were placed as part of normal clinical practice at IRCCS Neurologico C. Besta were consecutively enrolled in the study. PICC-related complications were recorded immediately (during the procedure), early (within 1 week after PICC insertion), and late (1-3-5 months after PICC placement). At the same time points, all patients were also evaluated for tolerability through interviews with semi-structured, open-ended questions. RESULTS: Sixty patients were enrolled (41 males and 19 females, with a median age of 56.2 years). Excluding loss to follow-up, 33/49 patients developed at least one complication related to the PICC. Immediate complications mainly included hematoma (8), accidental arterial puncture (4), and primary malpositioning (3). Regarding early and late complications, 3 device-related infections, 8 thrombotic events, and 20 mechanical complications were registered. Semi-structured interviews revealed an overall positive experience with the device. The most negative impact was on hygiene habits, with 34 patients becoming caregiver-dependent. Over time, almost all patients became used to the device and perceived greater security during chemotherapy. A strongly negative issue was the difficulty of relying on competently trained healthcare personnel in outpatient setting. CONCLUSION: The results showed a nonnegligible increased thromboembolic risk in neuro-oncological patients with PICCs, almost double that in historical oncological populations. It is essential to extend the study to a greater number of patients to achieve reliable results and to identify patients at high risk. The device seems to be positively accepted by the majority of patients, without affecting activities of daily living.

Thr92Ala polymorphism in the type 2 deiodinase gene: an evolutionary perspective.

PURPOSE: In the past, a role of thyroid hormones in human evolution has been hypothesized. T3, the metabolically active form, derives from extrathyroidal conversion of T4 by deionidase 2 (D2) enzyme encoded by DIO2 gene. In thyroid-deficient patients, decreased levels of free T3 have been associated with the polymorphism rs225014 A/G in DIO2, which causes the substitution of Threonine with Alanine (p.Thr92Ala) at protein level. METHODS: We compared DNA and protein sequences of D2 from archaic human subspecies with those of contemporary humans. RESULTS: Neanderthals and Denisovans displayed only the G allele at the rs225014 polymorphism, which encodes for an Alanine on the amino acid level. These data suggest that these hominines were homozygous for the Ala amino acid. These arcaic humans often lived in condition of iodine deficiency and thus, defective mechanisms of T3 biosynthesis could be life threatining. A reduced D2 activity is likely to cause decreased T3 levels, which could be critical for those individuals. Neanderthals and Denisovans were hunters/gatherers, and their diet was mainly based on the consumption of meat, with a low intake of carbohydrates. The need for circulating T3 is reduced at such alimentary conditions. On the basis of our genome comparisons the A allele, corresponding to Threonine and associated with higher levels of circulating T3 in thyroid-deficient patients, appeared for the first time during evolution in Anatomically Modern Humans during the Upper Pleistocene and has been conserved during the Neolithic age. With the advent of agriculture and herding, individuals carrying A allele might have a higher probability for surviving and reproducing. Thus, the variant was positively selected during the evolution. CONCLUSION: Here we present an evolutionary perspective for p.Thr92Ala variant of D2 from Neanderthals to Anatomically Modern Humans.

Locally advanced cervical cancer complicating pregnancy: A case of competing risks from the Catholic University of the Sacred Heart in Rome.

A case of stage IB2 cervical cancer at 27 weeks of pregnancy, treated with neoadjuvant chemotherapy followed by radical Cesarean hysterectomy with full pelvic and infra-mesenteric lymphadenectomy, and adjuvant chemo-radiation is described. While she remains without disease, her baby was diagnosed with acute myelogenous leukemia. We highlight the pre-operative work-up, treatment options, safety, feasibility, and outcomes for the mother and her fetus.

Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort.

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1 = 1.26; 95% CI 1.00-1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1 = 1.29; 95% CI 1.02-1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.

An overview of different health indicators used in the European Health Systems.

INTRODUCTION: In the European Union three different health systems could be defined according to service delivery, financing, and economic policies: Beveridge, Bismarck and Mixed system. Although health systems are hardly to compare, various organizations are developing methods assessing performance. In the present work the performance of the three systems were evaluated using European Community Health Indicators according to Organization for Economic Cooperation and Development. METHODS: The study has been conducted among the 28 states of the European Union using the following indicators: Standardized death rate for diseases of the circulatory system, standardized death rate of malignant neoplasms, road traffic accidents with injury, life expectancy at birth, incidence of Human Immunodeficiency Virus (HIV), infant deaths, pure alcohol consumption, infants vaccinated against Diphtheria Tetanus Pertussis (DTP), public and total expenditure on health over the period 2001-2010. RESULTS: The variation of health indicators over the observational time shows similar trend of circulatory system diseases and malignant neoplasms death rates, road accidents with injury, infant deaths, life expectancy at birth, public and total health expenditure. Some differences in the trend of HIV incidence, alcohol intake and DTP vaccination rates arise among systems. Grouping countries by health system paradigm and geographical area, resulted in a relevant heterogeneity (I2 ≥ 90%, Pvalue < 0.0001). No clear superiority of a given health delivery system was found with respect to other paradigms. CONCLUSIONS: In accordance with the evidence of our study, it can be stated that best performances are more likely to be linked to country specific economic factors. In conclusion, it was not possible to identify the best health system model.

European cardiovascular mortality over the last three decades: evaluation of time trends, forecasts for 2016.

BACKGROUND: The circulatory diseases, in particular ischemic heart diseases and stroke, represent the main causes of death worldwide both in high income and in middle and low income countries. Our aim is to provide a comprehensive report to depict the circulatory disease mortality in Europe over the last 30 years and to address the sources of heterogeneity among different countries. METHODS: Our study was performed using the WHO statistical information system - mortality database - and was restricted to the 28 countries belonging to the European Union (EU-28). We evaluated gender and age time series of all circulatory disease mortality, ischemic heart diseases, cerebrovascular diseases, pulmonary and other circulatory diseases and than we performed forecast for 2016. Mortality heterogeneity was evaluated by countries using the Cochrane Q statistic and the I-squared index. RESULTS: Between 1985 and 2011 SDR for deaths attributable to all circulatory system diseases decreased from 440.9 to 212.0 x 100,000 in EU-28 and a clear uniform reduction was observed. Heterogeneity among countries was found to be consistent, therefore different analysis were carried out considering geographical area. CONCLUSIONS: We forecast a reduction in European cardiovascular mortality. Heterogeneity among countries could only in part be explained by both geographical and health expenditure factors.

Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas).

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

Upregulation of inflammasome activity and increased gut permeability are associated with obesity in children and adolescents.

BACKGROUND: Immune activation contributes to the persistent state of inflammation associated with metabolic dysfunction in obesity. The specific immune receptors that sense metabolic stress signals and trigger inflammation are nevertheless largely unknown, and little is known on inflammatory and immune gene regulation in obesity. METHODS: The study includes a cross-sectional and a longitudinal arm. Forty children and adolescents were enrolled: 22 obese subjects and 18 age-matched normal weight controls. Obese subjects participated in an 18-month therapeutic protocol, based on intensive lifestyle modification (dietary regimen, physical activity and behavioral interventions). Expression of genes involved in the inflammasome pathway, plasma concentration of the inflammasome-associated pro-inflammatory cytokines (interleukin (IL)-1ß and IL-18) and indexes of microbial translocation (lipopolysaccharide (LPS), soluble CD14 (sCD14) and intestinal fatty acid-binding protein) were analyzed at baseline in obese subjects compared with controls, and after 18 months in obese subjects. RESULTS: Cross-sectional analyses showed that the LPS-induced expression of genes involved in inflammasome (NLRP3, caspase 5 and NAIP), Nod-like receptors (NLRX1 and NOD1), downstream signaling (P2RX7, RAGE, RIPk2, TIRAP and BIRC2) and effector molecules (IFN-γ, IL-12ß, IL-1ß, CCL2, CCL5, IL-6 and TNFα) was significantly increased in obese subjects at baseline as compared with normal weight controls. The baseline plasma concentration of inflammasome-related cytokines (IL-1ß and IL-18) and of microbial translocation markers (LPS and sCD14) was augmented in obese subjects as compared with controls as well. Longitudinal analyses indicated that intensive lifestyle modification resulted in a normalization of parameters in subjects with a significant reduction of BMI after 18 months. CONCLUSIONS: In children and adolescents, obesity is characterized by the activation of the inflammasome and by an alteration of gut permeability. Successful lifestyle modification is effective in reducing inflammation, suggesting that inhibition of the inflammasome may be a potential therapeutic strategy in obesity.

Violence and unsafety in a major Italian hospital: experience and perceptions of health care workers.

UNLABELLED: Workers' experience of violence and perceived unsafety can have a profound impact on job satisfaction, job performance, and workers' decision to leave. OBJECTIVES: The aim of the study was to assess the prevalence of physical and non-physical violence among hospital workers, explore the complaints and reactions of victims, assess the relationship between violence and psychosocial/work factors and analyze the levels of perceived unsafety. METHODS: A cross-sectional study was conducted, via a structured self-administered questionnaire given to all the employees of a major hospital in Italy. Cronbach's alpha coefficient was used to assess the internal consistency of the questionnaire. A logistic regression model was used for data analysis. RESULTS: 903 questionnaires out of 1853 (48.7%) were correctly returned; 11.5% had experience of physical violence and 40.2% had been victims of verbal violence in the previous 12 months. The most common consequences were fear, anger, frustration, and anxiety. Verbal violence was influenced by age, role, department, night/holiday shift work and experience in the current ward. Experiences of physical violence were related to gender, role, and department; 469 responders (51.9%) reported feelings of unsafety, which were related to their professional role, department, shift work, experience of physical or psychological violence, having seen episodes of violence and having received specific training. CONCLUSIONS: Our findings suggest that several factors are associated with workplace violence in health care settings and some of these also influenced the levels of perceived unsafety.

New parameters for identifying subclinical atherosclerosis in patients with primary Sjögren's syndrome: a pilot study.

OBJECTIVES: We investigated sub-clinical cardiovascular involvement in primary Sjögren's syndrome (pSS) patients by means of ADMA, coronary flow reserve (CFR), intima media thickness (cIMT), pulse wave velocity (PWV) and myocardial deformation. METHODS: The study involved 22 outpatients with pSS (6 males, 16 females; mean age 60.14±7.81 years) and no documentable cardiovascular disease, and 22 age- and gender-matched controls. Dipyridamole transthoracic stress echocardiography was used to evaluate wall motion and CFR. A CFR value of <2.5 was considered a sign of impaired coronary function. We also evaluated cIMT arterial stiffness PWV and plasma ADMA levels, and made a speckle tracking echocardiography (STE) analysis. RESULTS: All of the patients were affected by pSS. Although within the normal range, the patients' CFR was lower than that of the controls (median 2.70; IQR 2.40-2.90 vs. 3.20; IQR 3.06-3.33; p<0.0001), whereas their ADMA levels were significantly higher (median 0.81 µM; IQR 0.79-0.85 µM vs. 0.54 µM; IQR 0.52-0.58 µM; p<0.0001). Both left and right PWV values were significantly higher in the patients than in the controls (median 8.8 m/s right and 8.9 m/s left vs. 6.86 and 6.89 m/s), whereas QIMT was substantially similar in the two groups. CONCLUSIONS: Higher ADMA levels suggest the presence of endothelial dysfunction and sub-clinical atherosclerosis in pSS patients, even in the case of a normal CFR. This finding is supported by the PWV values, which were higher in the pSS patients. ADMA levels and PWV values may be useful markers for identifying early endothelial dysfunction in pSS patients.

Familial aggregation of moderate to severe plaque psoriasis.

BACKGROUND: Psoriasis is a highly heritable disease. It has been suggested that psoriasis is preferentially transmitted from fathers. AIM: To evaluate the degree of familial aggregation of psoriasis; to determine the recurrence risk ratio (λR ) of psoriasis in first, second and third degree relatives of patients with psoriasis; and to investigate the transmission patterns of the disease and their relationships with the clinical profiles of patients. METHODS: A cross-sectional study on 640 consecutive, unrelated adult patients with chronic plaque psoriasis was performed. The prevalence of psoriasis in first, second and third degree relatives of the patients was determined, and the λR was calculated under the assumption of a population prevalence of 2%. Age of onset and presence of facial, hand and foot psoriasis were evaluated in probands with paternal vs. maternal transmission. RESULTS: A positive familial history of psoriasis was found in 380 patients (59.37%). Of these, 174 (27.18%) had at least one parent with psoriasis, with a λR of 13.59, while 106 patients (16.56%) had at least one second degree relative with psoriasis, and 34 patients (5.31%) had one third degree relative with psoriasis. No parent-of-origin effect in transmission of psoriasis from affected parent to offspring was observed, and there were no significant differences in the clinical profiles of the disease between patients grouped by transmission pattern of psoriasis. CONCLUSIONS: These results show a high familial recurrence risk of psoriasis, and suggest a balanced parental transmission of the disease.