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Background. Atrial fibrillation (AF) often occurs after cardiac surgery and is associated to increased risk of stroke and mortality. Several evidence support the important role of inflammation in the pathogenesis of postoperative atrial fibrillation (POAF). It is known that an increased volume and a pro-inflammatory phenotype of epicardial adipose tissue (EAT) are both associated with AF onset in non surgical context. In the present study, we aim to evaluate whether also POAF occurrence may be triggered by an exalted production of inflammatory mediators from EAT.Methods. The study population was composed of 105 patients, with no history of paroxysmal or permanent AF, undergoing elective cardiac surgery. After clinical evaluation, all patients performed an echocardiographic study including the measurement of EAT thickness. Serum samples and EAT biopsies were collected before surgery. Levels of 10 inflammatory cytokines were measured in serum and EAT conditioned media. After surgery, cardiac rhythm was monitored for 7 days.Results. Forty-four patients (41.3%) developed POAF. As regard to cardiovascular therapy, only statin use was significantly lower in POAF patients (65.1% vs. 84.7%; p-0.032). Levels of Monocyte Chemoattractant Protein-1 (MCP-1), in both serum and EAT, were significantly higher in POAF patients (130.1 pg/ml vs. 68.7 pg/ml; p = ConclusionHigher EAT levels of IL6 and MCP1 are significantly associated with the occurrence of POAF. Statin therapy seems to play a role in preventing POAF. These results might pave the way for a targeted use of these drugs in the perioperative period.

Background Quality of bowel cleansing in hospitalized patients undergoing colonoscopy is often unsatisfactory. No study has investigated the inpatient or outpatient setting as cause of inadequate cleansing. Aims To assess degree of bowel cleansing in inpatients and outpatients and to identify possible predictors of poor bowel preparation in the two populations. Methods Prospective multicentre study on consecutive colonoscopies in 25 regional endoscopy units. Univariate and multivariate analysis with odds ratio estimation were performed. Results Data from 3276 colonoscopies were analyzed (2178 outpatients, 1098 inpatients). Incomplete colonoscopy due to inadequate cleansing was recorded in 369 patients (11.2%). There was no significant difference in bowel cleansing rates between in- and outpatients in both colonic segments. In the overall population, independent predictors of inadequate cleansing both at the level of right and left colon were: male gender (odds ratio, 1.20 [1.02–1.43] and 1.27 [1.05–1.53]), diabetes mellitus (odds ratio, 2.35 [1.68–3.29] and 2.12 [1.47–3.05]), chronic constipation (odds ratio, 1.60 [1.30–1.97] and 1.55 [1.23–1.94]), incomplete purge intake (odds ratio, 2.36 [1.90–2.94] and 2.11 [1.68–2.65]) and a runway time >12 h (odds ratio, 3.36 [2.40–4.72] and 2.53 [1.74–3.67]). Conclusions We found no difference in the rate of inadequate bowel preparation between hospitalized patients and outpatients.

Background Intestinal dysbiosis has been described in Cystic Fibrosis (CF) and probiotics have been proposed to restore microbial composition. Aim of the study was to investigate the effects of Lactobacillus rhamnosus GG (LGG) on clinical outcomes in children with cystic fibrosis (CF). Methods A multicentre, randomised double-blind, clinical trial was conducted in children with CF. After 6 months of baseline assessment, enrolled children (2 to 16 years of age) received Lactobacillus GG (6 × 10 9 CFU/day) or placebo for 12 months. Primary outcomes were proportion of subjects with at least one pulmonary exacerbation and hospitalisation over 12 months. Secondary endpoints were total number of exacerbations and hospitalisations, pulmonary function, and nutritional status. Results Ninety-five patients were enrolled (51/95 female; median age of 103 ± 50 months). In a multivariate GEE logistic analysis, the odds of experiencing at least one exacerbation was not significantly different between the two groups, also after adjusting for the presence of different microbial organisms and for the number of pulmonary exacerbations within 6 months before randomisation (OR 0.83; 95% CI 0.38 to 1.82, p = 0.643). Similarly, LGG supplementation did not significantly affect the odds of hospitalisations (OR 1.67; 95% CI 0.75 to 3.72, p = 0.211). No significant difference was found for body mass index and FEV1. Conclusions LGG supplementation had no effect on respiratory and nutritional outcomes in this large study population of children with CF under stringent randomised clinical trial conditions. Whether earlier interventions, larger doses, or different strains of probiotics may be effective is unknown.

Background Sarcopenia is a condition characterized by decreased skeletal muscle mass due to physiological ageing or to a concomitant disease such as neoplasia. In cancer patients, a low lean body mass is suggested to be a negative prognostic factor for survival and for the development of dose-limiting chemotherapy toxicities irrespective of disease stage. Aim To evaluate the prognostic role of sarcopenia in patients with metastatic colorectal cancer (mCRC) undergoing first-line chemotherapy. Methods Our retrospective analysis included 56 mCRC patients who received first-line chemotherapy from 2014 to 2017 at the Medical Oncology Unit of our hospital. Computerized scans were performed before starting chemotherapy and at the first disease reassessment. Sarcopenia was assessed using the skeletal mass index = muscle area in cm2/(height in m2) calculated at the L3 vertebra. Overall survival and objective response rate were evaluated. Toxicities were analyzed during the first four cycles of therapy and graded according to Common Terminology Criteria for Adverse Events version 4.0. A loss of skeletal muscle mass ≥ 5% was considered indicative of deterioration in muscle condition. Results Median age was 67 years and 35.7% of patients were ≥ 70 years old. Fourteen patients (25%) were sarcopenic at baseline computed tomography (CT) scan (7/33 men; 7/23 women); 5/14 sarcopenic patients were ≥ 70 years old. Median follow-up was 26.8 mo (3.8-66.8 mo) and median overall survival was 27.2 mo (95%CI: 23.3-37.3). Sarcopenia was not correlated to overall survival (P = 0.362), to higher toxicities reported during the first 4 cycles of chemotherapy (P = 1.0) or to response to treatment (P = 0.221). At the first disease reassessment, a skeletal muscle loss (SML) ≥ 5% was found in 17 patients (30.3%) 3 of whom were already sarcopenic at baseline CT scan, while 7 patients became sarcopenic. SML was not correlated to overall survival (P = 0.961). No statistically significant correlation was found between baseline sarcopenia and age (P = 1.0), body mass index (P = 0.728), stage at diagnosis (P = 0.355) or neutrophil/lymphocyte ratio (P = 0.751). Conclusion Neither baseline sarcopenia nor SML affected survival. In addition, baseline sarcopenia was not related to worse treatment toxicity. However, these results must be interpreted with caution due to the limited sample size.

Background Excessive adiposity provides an inflammatory environment. However, in people with severe obesity, how systemic and local adipose tissue (AT)-derived cytokines contribute to worsening glucose tolerance is not clear. Methods Ninty-two severely obese (SO) individuals undergoing bariatric surgery were enrolled and subjected to detailed clinical phenotyping. Following an oral glucose tolerance test, participants were included in three groups, based on the presence of normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D). Serum and subcutaneous AT (SAT) biopsies were obtained and mesenchymal stem cells (MSCs) were isolated, characterized, and differentiated in adipocytes in vitro. TNFA and PPARG mRNA levels were determined by qRT-PCR. Circulating, adipocyte- and MSC-released cytokines, chemokines, and growth factors were assessed by multiplex ELISA. Results Serum levels of IL-9, IL-13, and MIP-1β were increased in SO individuals with T2D, as compared with those with either IGT or NGT. At variance, SAT samples obtained from SO individuals with IGT displayed levels of TNFA which were threefold higher compared to those with NGT, but not different from those with T2D. Elevated levels of TNFα were also found in differentiated adipocytes, isolated from the SAT specimens of individuals with IGT and T2D, compared to those with NGT. Consistent with the pro-inflammatory milieu, IL-1β and IP-10 secretion was significantly higher in adipocytes from individuals with IGT and T2D. Moreover, increased levels of TNFα, both mRNA and secreted protein were detected in MSCs obtained from IGT and T2D, compared to NGT SO individuals. Exposure of T2D and IGT-derived MSCs to the anti-inflammatory flavonoid quercetin reduced TNFα levels and was paralleled by a significant decrease of the secretion of inflammatory cytokines. Conclusion In severe obesity, enhanced SAT-derived inflammatory phenotype is an early step in the progression toward T2D and maybe, at least in part, attenuated by quercetin.

Gustatory perception has been poorly explored in Parkinson's disease (PD). Aim of this study was to assess the flavor ability in PD patients, using the "flavor test" (FT), a new standardized and validated tool to examine the flavor perception. Thirty-eight patients (17 F and 21 M) and 36 control subjects (15 F and 21 M) comparable for age and gender were enrolled. All the subjects underwent the flavor test (FT), the Sniffin' Sticks test (SST), and the gustometry test (GT), based on the basic four tastants ("salty," "sour," "sweet," and "bitter"). PD patients presented a FT score significantly lower than controls (p

Aims Recent evidence supports the occurrence of multiple hormonal and metabolic deficiency syndrome (MHDS) in chronic heart failure (CHF). However, no large observational study has unequivocally demonstrated its impact on CHF progression and outcome. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure) Registry has been specifically designed to test the hypothesis that MHDS affects morbidity and mortality in CHF patients. Methods and Results The T.O.S.CA. Registry is a prospective, multicentre, observational study involving 19 Italian centres. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydropianoandrosterone sulfate, insulin resistance, and the presence of diabetes were evaluated. A MHDS was defined as the presence of ≥2 hormone deficiencies (HDs). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Four hundred and eighty heart failure patients with ejection fraction ≤45% were enrolled. MHDS or diabetes was diagnosed in 372 patients (77.5%). A total of 271 events (97 deaths and 174 cardiovascular hospitalizations) were recorded, 41% in NO-MHDS and 62% in MHDS (P Conclusion MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target. Trial registration ClinicalTrials.gov identifier: NCT023358017

BackgroundThymic epithelial tumors (TETs) are rare thoracic malignancies, commonly divided into two different histopathological entities, thymoma (T) and thymic carcinoma (TC). To date, there are no specific biomarkers for monitoring the biological course of these rare tumors. We carried out a single center study aiming at the detection of circulating cell-free DNA (ccfDNA) and the correlation of its levels with metastatic dissemination and histological subtype in patients with TETs.MethodsFrom July 2018 to January 2020, 5-ml blood samples from 26 patients with advanced TET (aTET) (11 patients with TC and 15 patients with T) and from six patients with completely resected TET (cr-TET), were prospectively obtained before the initiation of systemic therapy. Blood samples from 10 healthy donors were used as control. The QIAamp MinElute ccfDNA Kits was used for ccfDNA isolation from plasma; real-time PCR was used for cfDNA quantification.ResultsWe found significantly higher ccfDNA amount in patients with T and TC compared to controls, with median ccfDNA level of 3.3 ng/µl, 11.4 ng/µl and 25.6 ng/µl, for healthy donors, T and TC patients, respectively (pConclusionsTo the best of our knowledge, this is the first study that prospectively explores detection and quantification of ccfDNA in TETs. Higher baseline cfDNA levels have been observed in both advanced T and TC comparing to the control group.

Background and Aim: Echocardiography is a promising technique for the assessment of epicardial adipose tissue (EAT). Increased EAT thickness is associated with different cardiac diseases, including; coronary artery disease (CAD). Since several different echocardiographic approaches have been proposed to measure EAT, the identification of a standardized method is needed. We propose the assessment of EAT maximal thickness at the Rindfleisch fold, the reproducibility of this measurement and its correlation with EAT thickness and volume assessed at cardiac magnetic resonance (CMR). Finally, we will test the predictive role of this measurement on the presence of significant CAD. Methods and Results: In 1061 patients undergoing echocardiography, EAT thickness was measured at the level of the Rindfleisch fold. In 70 patients, we tested the relationship between echo-EAT thickness and EAT thickness and volume assessed at CMR. In 499 patients with suspected CAD, undergoing coronary artery angiography, we tested the predictive value of EAT on the presence of significant CAD. Echo-EAT thickness measurements had an excellent reliability as indicated by the inter-observer (ICC:0.97; 95% C.I. 0.96 to 0.98) and intra-observer (ICC:0.99; 95% C.I. 0.98 to 0.99) reliability rates. Echo-EAT thickness significantly correlated with CMR-EAT thickness and volume (p < 0.001). An EAT thickness value >10 mm discriminated patients with significant CAD at coronary angiography (p < 0.001). At multivariable analysis, including demographic data and cardiovascular risk factors, EAT thickness was an independent predictor of significant CAD and showed an additive predictive value over common atherosclerotic risk factors. Conclusions: Echocardiographic assessment of EAT thickness at the level of the Rindfleisch fold represents a simple and trustworthy method. An increased EAT thickness shows an additive predictive value on CAD over common atherosclerotic risk factors, thus suggesting its potential clinical use for CAD risk stratification.

IntroductionGrowth impairment has often been described in children who develop coeliac disease (CD). Based on data from the multicentre, longitudinal PreventCD study, we analysed the growth patterns of infants at genetic risk of CD, comparing those who developed CD by 6 years of age (CD ‘cases’, 113 infants) versus those who did not develop CD by 6 years (no CD ‘controls’, 831 infants).MethodsWeight and length/height were measured using a longitudinal protocol. Raw measurements were standardised, computing z-scores for length/height and weight; a linear mixed model was fitted to the data in order to compare the rate of growth in the two cohorts.ResultsNeither cases nor controls had significant growth failure. However, when the mean z-scores for weight and height were analysed, there was a difference between the two groups starting at fourth month of life. When the growth pattern in the first year was analysed longitudinally using mixed models, it emerged that children who develop CD had a significantly lower growth rate in weight z-score (−0.028/month; 95% CI −0.038 to −0.017; pConclusionThe growth of children at risk of CD rarely fell below ‘clinical standards’. However, growth rate was significantly lower in cases than in controls. Our data suggest that peculiar pathways of growth are present in children who develop CD, long before any clinical or serological signs of the disease appear.

Objective: Despite a substantial consistency in recommendations for the management of children with acute gastroenteritis (AGE), a high variability in clinical practice and a high rate of inappropriate medical interventions persist in both developing and developed countries. The aim of this study was to develop a set of clinical recommendations for the management of nonseverely malnourished children with AGE to be applied worldwide. Methods: The Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN) Working Group (WG) selected care protocols on the management of acute diarrhea in infants and children aged between 1 month and 18 years. The WG used a 3-step approach consisting of: systematic review and comparison of published guidelines, agreement on draft recommendations using Delphi methodology, and external peer-review and validation of recommendations. Results: A core of recommendations including definition, diagnosis, nutritional management, and active treatment of AGE was developed with an overall agreement of 91% (range 80%–96%). A total of 28 world experts in pediatric gastroenterology and emergency medicine successively validated the set of 23 recommendations with an agreement of 87% (range 83%–95%). Recommendations on the use of antidiarrheal drugs and antiemetics received the lowest level of agreement and need to be tailored at local level. Oral rehydration and probiotics were the only treatments recommended. Conclusions: Universal recommendations to assist health care practitioners in managing children with AGE may improve practitioners’ compliance with guidelines, reduce inappropriate interventions, and significantly impact clinical outcome and health care-associated costs.

Objectives Given their inclusion and exclusion criteria, randomized clinical trials (RCT) might not include a population that truly mirrors real life (RL). This raises concerns about the applicability of RCT results in clinical practice. We evaluated the efficacy of anti-HER2 treatment with pertuzumab combined with trastuzumab and a taxane as first-line treatment for HER2-positive metastatic breast cancer in a RL setting, and compared the safety results obtained in our population versus the experimental cohort of the CLEOPATRA RCT, which led to the approval of this therapy. Materials and methods Patients treated with trastuzumab, pertuzumab and a taxane were enrolled in this retrospective study. We compared the tumor features and the patients' characteristics of the RL cohort to those of the CLEOPATRA cohort. We also compared the median progression-free survival (PFS) in the RL population versus specific patients' subgroups. Results RL patients were more frequently HR-positive, less likely to have visceral metastases (P

Background and purpose The aim of our study was to describe, by a case-control and cross-sectional design, the correlation between clinical impairment and age in Charcot-Marie-Tooth type 1A (CMT1A) patients. Methods Seventy CMT1A patients and 70 sex- and age-matched healthy controls were enrolled. Motor performance was assessed through the 10-m walk test, the 6-min walk test and the 9-hole peg test of the dominant and non-dominant side, and muscle strength was measured by using the Medical Research Council score. In the CMT1A group, disability and quality of life were evaluated using the Charcot-Marie-Tooth Neuropathy Score (CMTNS) and the Short Form 36 (SF-36) questionnaire. Cross-sectional relationships between age and all clinical measures were analyzed and differences in the slopes between cases and controls were calculated. The occurrence of a structural change in the age-related progression of clinical measures was explored. Results The deterioration of motor performance correlated with age in both groups with a greater slope in CMT1A patients than controls. The deterioration of CMTNS and SF-36 correlated with age in the CMT1A group. The deterioration of all clinical measures with the exception of the SF-36 questionnaire showed a structural change at the 50th year of age. The rate of deterioration was no different between patients and controls until 50 years of age, whereupon it became significantly greater in CMT1A patients. Conclusion Our study supports that the disease progression in CMT1A patients is an age-related process and the 50th year of age represents a critical moment after which the clinical decline becomes faster.

Background Patients on standard dialysis, in particular those on high-flux and high-efficiency dialysis, are exposed to hundreds of liters of dialysis-water per week. The quality of dialysis-water is a factor responsible for inflammation in dialysis patients. Inflammation is a potent trigger of atherosclerosis and a pathogenetic factor in anemia, increasing mortality and morbidity in dialysis patients. Current systems for water treatment do not completely eliminate bacteria and endotoxins. This prospective study tested whether improved dialysis-water purity by an additional ultrafilter can reduce inflammation and ameliorate hemoglobin levels, with a consequent reduction in erythropoietin-stimulating agents (ESA). Methods An ultrafilter, composed of two serially positioned devices with polysulfone membranes of 2.0 and 1.0 m2, respectively, was positioned within the fluid pathway before the dialysis machine. Prevalent dialysis patients were assigned either to continue dialysis with conventional dialysis-water (control phase) or to initiate dialysis sessions with improved dialysis-water purity (study phase). After 6 months, patients were crossed over. Total study duration was 1 year. Routine chemistry, bacterial count, endotoxin levels in dialysis-water as well as blood levels of pro- and anti-inflammatory cytokines, human serum amyloid A, C-reactive protein and fraction 5 of complement were measured. Results Thirty-two patients completed the study. Mean bacterial count was lower and endotoxin levels were absent in dialysis-water obtained with the ultrafilter. At the end of the study-phase, C-reactive protein and pro-inflammatory cytokines decreased while anti-inflammatory ones increased. Hemoglobin levels were improved with lower ESA doses. Conclusions An additional ultrafilter improved dialysis-water purity, reduced levels of inflammation markers, ameliorated hemoglobin concentration with reduced ESA doses. These results remain speculative but they may generate studies to assess whether improved dialysis-water quality with an ultrafilter can reduce inflammation and improve survival of dialysis patients. Electronic supplementary material The online version of this article (doi:10.1007/s40620-017-0422-x) contains supplementary material, which is available to authorized users.

The objective of this study was to identify early clinical, biochemical and electrophysiological prognostic factors of disability in CIDP. We evaluated a dataset from 60 CIDP patients that included sex, age of onset, type of onset, phenotype, disease duration, response to treatment, disability at the time of diagnosis assessed using the modified Rankin Scale (baseline mRS), cerebrospinal fluid protein levels and electrophysiological data. All patients had clinical assessment of disability through the mRS within the last 6 months (last mRS) before enrollment in the study. Stepwise forward logistic regression model was applied to evaluate the impact of clinical, biochemical and electrophysiological parameters on the last mRS, considered as binary outcome (absence or presence of severe disability, i.e.

We tested the hypothesis that a narrative approach may enhance a bio-psycho-social model (BPS) in caring for chronically ill children. Forty-eight narratives were collected from 12 children with six different medical conditions, their mothers, physicians, and nurses. By a textual analysis, narratives were classified on their predominant focus as disease (biological focus), illness (psychologic focus), or sickness (social focus). Sixty-one percent of narrative’ text were classified as illness, 28% as disease and 11% as sickness. All narratives had a degree of illness focus. Narratives by patients and physicians on the one hand, and nurses’ and mothers’ on the other were disease focused. Narratives were also evaluated with respect to the type of medical condition: Illness was largely prevalent in all but Crohn’s disease and HIV infection, the latter having a predominance of sickness most probably related to stigma. Narrative exploration proved a valuable tool for understanding and addressing the needs of children with complex conditions. Narrative approaches allow identification of the major needs of different patients according to health conditions and story tellers. In the narratives, we found a greater illness and disease focus and surprisingly a low sickness focus, except with HIV stories. Narrative medicine provides a tool to strengthen the BPS model in health care.

Background and objectives: Progressive nephropathy is one of the main features of Fabry disease (FD). It has been supposed that an early phase, clinically silent disease occurs in childhood and adolescence and is characterized by glomerular hyperfiltration (HF). Surprisingly, although HF has been reported in several studies, its prevalence is at present unknown. The focus of our study was to determine the prevalence of HF in a cohort of patients with FD and to identify the factors associated with a high risk of HF. Methods: To address this issue, a retrospective observational study of 87 patients with genetically confirmed FD was performed. HF was defined as an estimated glomerular filtration rate (eGFR) > 130 mL/min/1.73 m2 corrected for age (> 40 years: –1 mL/min/1.73 m2/year). Results: HF occurred in 21 patients (24% of our population), and increased to 50% when only young adults were considered. Hyperfiltrating patients were younger and had lower proteinuria levels than those without HF. The prevalence of cardiovascular and other manifestations of FD was significantly lower in hyperfiltering patients. Conclusions: Our study showed a negative correlation between eGFR and age, and with proteinuria levels and the presence of cardiovascular and other manifestations of FD. These data favor the view that HF in Fabry patients could be related predominantly to a predisease state. Even in the absence of a “measured” GFR, HF should be regarded as an early marker of Fabry nephropathy, and its recognition and confirmation by true GFR seems a relevant feature to address the issue of the potential benefit of nephroprotective treatments at the early stage of Fabry nephropathy.

Cancer-related fatigue (CRF) is a complex condition that is reported in > 50% of cancer patients. In men with castration-resistant prostate cancer (CRPC), CRF was reported in 12–21% of patients. Approved systemic therapy against CRPC is commonly administered in combination with androgen-deprivation treatment (ADT) and, in some cases, with daily, low-dose corticosteroids. Importantly, the use of low-dose corticosteroids is associated with multiple negative effects, including reduced muscle mass. On these grounds, we hypothesized that the chronic use of corticosteroids may increase the incidence of fatigue in patients with prostate cancer. We reviewed all randomized trials published during the last 15 years conducted in patients with prostate cancer receiving systemic treatment and we performed a sub-group analysis to gather insights regarding the potential differences in the incidence of fatigue in patients receiving vs. not receiving daily corticosteroids as part of their systemic anti-neoplastic regimen. Overall, 22,734 men enrolled in prospective randomized phase II and III trials were evaluable for fatigue. Estimated pooled incidence of grade 1–2 fatigue was 30.89% (95% CI = 25.34–36.74), while estimated pooled incidence of grade 3–4 fatigue was reported in 3.90% (95% CI = 2.91–5.02). Sub-group analysis showed that grade 3–4 fatigue was approximately double in patients who received daily corticosteroids as part of their anti-neoplastic treatment (5.58; 95% CI = 4.33–6.98) vs. those who did not (2.67%; 95% CI = 1.53–4.11). Our findings highlight the need for ad hoc-designed prospective clinical trials to investigate whether the benefits associated with low-dose, daily corticosteroids outweigh the risks associated with corticosteroid-related adverse events such as fatigue.

Background/aims Functional constipation (FC) is aa frequent functional gastrointestinal disorder, diagnosed according to the Rome criteria. In this study, we compared Rome III and Rome IV criteria for the diagnosis of FC, and determined the prevalence of FC according to these criteria. Methods Consecutive children between infancy and 17 years old were recruited for the study, excluding those with a known organic gastrointestinal disease. A prospective longitudinal design has beenused. For the diagnosis of FC, questionnaires on Pediatric Gastrointestinal Symptoms (QPGS) based on the Rome III and Rome IV criteria (QPGS-RIII and QPGS-RIV) were used. The agreement between these 2 questionnaires was measured by Cohen's kappa coefficient. Results Two hundred fourteen children (mean age, 77.4 ± 59.5 months; 103 males) were screened. There was no statistically significant difference in the prevalence of FC evaluated using the QPGS-Rome IV vs the QPGS-Rome III in the overall sample (39/214 [18.2%] vs 37/214 [17.3.0%]; P = 0.831) as well as in any of the groups. The Cohen's kappa test showed a good agreement between the 2 criteria (κ = 0.65; 95% CI, 0.51 to 0.78). Conclusion Our study demonstrates that the new Rome IV criteria have a good agreement with the Rome III criteria for the diagnosis of FC, without an increase in the number of potential diagnoses, despite the reduction in the duration of the symptoms. This conclusion is important in the management of childhood FC, since a late diagnosis negatively affects the prognosis.

After skin cancer, prostate cancer (PC) is the most common cancer among men. The gold standard for PC diagnosis is based on the PSA (prostate-specific antigen) test. Based on this preliminary screening, the physician decides whether to proceed with further tests, typically prostate biopsy, to confirm cancer and evaluate its aggressiveness. Nevertheless, the specificity of the PSA test is suboptimal and, as a result, about 75% of men who undergo a prostate biopsy do not have cancer even if they have elevated PSA levels. Overdiagnosis leads to unnecessary overtreatment of prostate cancer with undesirable side effects, such as incontinence, erectile dysfunction, infections, and pain. Here, we used artificial neuronal networks to develop models that can diagnose PC efficiently. The model receives as an input a panel of 4 clinical variables (total PSA, free PSA, p2PSA, and PSA density) plus age. The output of the model is an estimate of the Gleason score of the patient. After training on a dataset of 190 samples and optimization of the variables, the model achieved values of sensitivity as high as 86% and 89% specificity. The efficiency of the method can be improved even further by training the model on larger datasets.

The basement membrane collagen IV-degrading matrix metalloproteinases -2 and -9 (MMPs) are most often linked to the malignant phenotype of tumor cells by playing a critical role in invasion, metastasis, angiogenesis, and vasculogenesis. We verified the activity of these two MMPs in the sera of patients affected by brain tumors (20 gliomas, 28 meningiomas and 20 metastasis) by zymography. The sera of 25 healthy volunteers with no concomitant illnesses were used for controls. Zymography showed four dominant gelatinolytic bands of 240, 130, 92 (MMP-9) and 72 (MMP-2) kDa. No statistically significant variations of MMP-2 proteolytic activity between patients and healthy individuals were observed. On the contrary, MMP-9 (both monomeric and multimeric forms) lytic activities were significantly higher in tumors specimens compared to healthy controls (p < 0.001). Moreover, MMP-9 immunohistochemistry revealed: (1) a strong reactivity in neoplastic vessels of high-grade gliomas showing an inverse correlation with serum multimeric gelatinolytic activity; (2) a cytoplasmatic reactivity in meningiomas with a significantly increase in atypical meningioma compared with low-grade ones (p = 0.036); (3) a positive correlation between MMP-9 and Ki-67 (Sperman Rho coefficient r = 0.418 and p = 0.034). Our results suggest that serum and tissue MMP-9 might provide clinicians additional objective information in intracranial neoplasms. Finally, it should be possible to use MMP-9 as a target for new forms of therapy. Nevertheless, due to the small number of patients included in the study, the conclusion may not be transferable to the general population and therefore further evaluations are needed.

Background Autosomal dominant polycystic kidney disease (ADPKD) accounts for 8–10% of end-stage chronic kidney disease (CKD) patients worldwide. In the last decade, the advanced knowledge in genetics and molecular pathobiology of ADPKD focused some aberrant molecular pathways involved in the pathogenesis of the disease leading to controlled clinical trials aimed to delay its progression with the use of mTOR inhibitors, somatostatin or tolvaptan. Preclinical studies suggests an effective role of metformin in ADPKD treatment by activating AMPK sensor. Clinical trials are currently recruiting participants to test the metformin use in ADPKD patients. Methods We retrospectively examined the records of our ADPKD patients, selecting 7 diabetic ADPKD patients under metformin treatment and 7 matched non-diabetic ADPKD controls, to test the effect of metformin on renal progression during a 3 year follow-up. Results During the first year, the GFR decreased by 2.5% in Metformin Group and by 16% in Controls; thereafter, renal function remained stable in Metformin Group and further decreased in Controls, reaching a 50% difference after 3 years of observation. Accordingly, the overall crude loss of GFR, estimated by a linear mixed model, resulted slower in the Metformin than in Control Group (− 0.9; 95% C.I.: -2.7 to 0.9 vs - 5.0; 95% C.I.: -6.8 to − 3.2 mL/min/1.73 m2 per year, p = 0.002). Conclusions Our data are suggestive of a beneficial effect of metformin on progression of ADPKD. Large, randomized, prospective trials are needed to confirm this hypothesis.

Accommodative esotropia (AE) is a convergent deviation due to an excess of the convergence linked to the innervational stimulus for accommodation and it is usually associated to the presence of hyperopia. The development of hyperopia over time has been widely described but the lack of comparative analysis among accommodative esotropia subtypes, does not allow to verify the existence of different developmental patterns. In this study we aimed to describe the long term changes of refractive error in patients affected by accommodative esotropia as a function of the strabismus type: refractive (RAE), non-refractive (NRAE) and partially accommodative esotropia (PAE). The medical records of 66 patients (24 RAE, 22 PAE, 20 NRAE), who wore the full correction of their cycloplegic refraction error during the entire follow up period, were retrospectively reviewed. Mean outcome was the analysis of the variations, among groups, of refractive error over time; differences between mild (≤3.00D) and high (≥5.00D) hyperopia, effects of amblyopia and relationship with AC/A ratio were also investigated. All patients were followed up from approximately 4 years of age to 20, with mean follow up of 16.06±0.29 years. Our results described similar non-linear trend of refractive error development among groups. The initial increase of hyperopia (up to 7-8 years) was followed by a decreasing trend persisting up to adulthood (approximately 20 years of age). During this period, spherical equivalent decreased at a lower mean annual rate in patients affected by RAE (-0.07D) compared to other groups (NRAE -0.11D, p = 0.003 and PAE 0.13D, p = 0.002). In all groups, however, significant amount of hyperopia was found at last examination; indeed the observed difference in SE values from baseline to the end of follow up, was not significant (RAE: +0.27D, 95% C.I. -0.49 to +1.04D, p = 0.472; PAE: -0.69D, 95% C.I. -1.67 to +0.28D, p = 0.154; NRAE: -0.39D, 95% C.I. -1.11 to +0.34D, p = 0.278). AC/A ratio, amblyopia and amount of initial hyperopia appeared to have no significant role in longitudinal change of the refractive error. In conclusion, this study provides a complete overview, from childhood to adulthood, of refractive error development in different form of accommodative esotropia.

No robust biomarkers have been yet validated to identify the recurrence of disease in classical Hodgkin Lymphoma (cHL) patients upon induction treatment. The relevance of the inflammatory microenvironment in cHL prompted us to investigate the key immunomodulator myeloid dendritic cells type-1 (mDC1), type-2 (mDC2) and plasmacytoid dendritic cells (pDC). Blood DC levels were assessed in 52 newly diagnosed patients through multiparametric flow-cytometry. All but two patients received ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine). The median counts of all DC subsets were lower in cHL patients than in healthy controls (P < 0·001). Median mDC counts were inferior for the advanced vs early stage patients for both mDC1s and mDC2s (P = 0·008; P = 0·0007 respectively). Also, median mDC2 counts were reduced in case of bulky (P = 0·0004) and extra-nodal (P = 0·046) disease. Patients with B symptoms had lower levels for mDC1s (P = 0·046), mDC2s (P = 0·009) and pDCs (P = 0·040). All the DC subtypes increased at the end of treatment in 26 patients (P < 0·001): 4·6-fold for mDC1, 2·4-fold for mDC2, 4·5-fold for pDC and aligned DCs subsets with the reference frequencies and the interquartile ranges of the controls. In conclusion, DCs may contribute to the disturbed immunological interplay typical of cHL, prompting a further evaluation of their value as a potential new biomarker.

Sunitinib is the most commonly prescribed drug for advanced renal cell carcinoma in the first-line setting and has been associated with multiple adverse events related to its on–and off–target effects, including hand and foot syndrome and fatigue. It was hypothesized that sunitinib-induced fatigue may be related to off target inhibition of the AMPK enzyme, which results in impairment of energy-producing processes at a systemic level. Quercetin is a naturally occurring flavonol with established AMPK-stimulating activity. While clinical use of quercetin is limited by its poor bio-availability, quercetin-3-O-β-d-glucopyranoside, that is isoquercetin, has an improved pharmacokinetic profile. On the grounds of the in vitro stimulatory activity with respect to AMPk, we hypothesized that oral isoquercetin could improve fatigue in kidney cancer patients receiving sunitinib. Given the lack of data on the safety of isoquercetin given concomitantly with sunitinib, we conducted a phase I trial to assess the safety of GMP manufactured isoquercetin given at two dose levels (450 and 900 mg a day). In the 12-patient study cohort included in this study, isoquercetin was administered concomitantly with 50 mg sunitinib for a median 81 days (IQR, 75.5, 86.5). None of the 12 patients required isoquercetin suspension or isoquercetin dose reduction because of adverse events. No abnormalities in ECG, heart or lower limbs doppler ultrasound were detected. A statistically significant improvement was reported for the FACIT fatigue score (6.8 points; 95% CI: 2.8–10.8; p = 0.002) and for the FACIT Adverse Events score (18.9 points; 95% CI: 9.1–28.8; p < 0.001) after isoquercetin consumption vs. baseline. In this phase I trial, isoquercetin was remarkably safe, with a preliminary signal of activity in terms of improvement of sunitinib adverse events.

The accurate stratification of infants with congenital cytomegalovirus (CMV) infection at risk for more severe outcome may help in the management of patients. Aim of this study was to investigate the ability of a comprehensive neuroimaging investigation in predicting the long-term neurodevelopmental outcome in patients with congenital CMV. We analyzed the prognostic accuracy of a traditional score and a recently proposed scale applied to head ultrasound (HUS), computed tomography (CT) and magnetic resonance imaging (MRI).All consecutive neonates born from 2002 to 2015 with congenital CMV infection were considered eligible for the study. Neuroimaging findings were scored according to both scores.One hundred seventy infants were included (112 symptomatic patients). One-hundred eighteen infants received both HUS, CT and MRI. CT and MRI were normal in all 56 asymptomatic patients, while 32% of them presented an abnormal HUS. The prevalence of abnormal findings differed according to the neuroimaging study. The sensitivity of the new neuroimaging score in detecting patients at risk for poor neurologic outcome was higher than the traditional one for all neuroimaging examinations. CT and MRI showed higher positive predictive value compared with HUS. No neuroimaging examination showed a negative predictive value equal to 100%.Although HUS is the safest neuroimaging technique, it performs less well in detecting some brain abnormalities that can be associated with a poor neurodevelopmental outcome. A comprehensive neuroimaging evaluation is mandatory in infants with congenital CMV infection to decide for treatment and make a prognostic evaluation.

Background Fabry's disease (FD) is a rare, multi-organ lysosomal disease, caused by the deficiency of the enzyme α-galactosidase A, and is difficult to diagnose. Although parapelvic cysts (PC) were previously associated with FD, their prevalence and significance are unclear. Methods The present study aimed to: (i) evaluate, by renal ultrasound, the real prevalence of PC and of their determinants in a multicentre, nationwide cohort of FD patients (n = 173, Study 1) and (ii) ascertain whether a greater accuracy of PC detection improved their identification, in FD patients from a single centre (n = 67, Study 2). In both studies, for each FD patient, an age- and renal function-matched subject was selected for comparison (1:1). Results In Study 1, PC were detected in 28.9% of FD subjects and in only 1.1% of control subjects (P

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy. The Rotterdam criteria indicate four distinct phenotypes. In phenotypes with the typical ovarian morphology (ovarian volume ≥10 ml) the sensibility to clomiphene citrate (CC) ovulation therapy was demonstrated inversely proportional to the ovarian volume. In this retrospective study we evaluated the influence of ovarian volume on the success rate of CC ovulation induction in women with anovulatory phenotype 2 characterized only by the presence of hyperandrogenism and anovulation (ANOV + HA). Statistical analysis was conducted by stratifying patients both on the basis of CC dose (Group 1: n = 37, 50 mg; Group 2: n = 9, 100 mg; and Group 3: n = 12, 150 mg) and on the basis of response to therapy. Eighty women were evaluated but overall only 58 women (72.5%) reached ovulation. In the phenotype studied, we didn't find any correlations between ovarian volume and the chance of ovulation with the gradient increase in CC; furthermore, ovarian volume was comparable in CC responders and non-responders. Our study has shown that in the phenotype 2 examined, ovarian volume did not have any predictive value of the dosage required to induce ovulation. The significance of this result is discussed.

PURPOSE: To evaluate glucose homeostasis in children with growth hormone (GH) deficiency (GHD) receiving long-term replacement therapy. METHODS: We evaluated glucose, insulin, HOmeostasis Model Assessment (HOMA-IR), and HbA1c in 100 GHD children at diagnosis and during 5 years of therapy. One hundred healthy children comparable to patients were evaluated at baseline and after 1 and 5 years. RESULTS: No difference was detected at baseline between GHD patients and controls in glucose (79.58 ± 9.96 vs. 77.18 ± 8.20 mg/dl), insulin (4.50 ± 3.24 vs. 4.30 ± 2.60 µU/ml), HbA1c (5.20 ± 0.31 vs. 5.25 ± 0.33%) levels, and HOMA-IR (0.93 ± 0.72 vs. 0.86 ± 0.61). One year of GH was associated with a significant increase in insulin (7.21 ± 4.84, p

Objectives To assess and compare the ovarian reserve in patients with different-sized endometriomas undergoing cystectomy or ablative surgery in order to determine the best surgical approach to safeguard healthy ovarian tissue. Study design Prospective randomized study on 48 patients with unilateral single ovarian endometriomas. Patients were allocated into two groups based on endometrioma size: n = 26, Group A, small endometriomas) and ≥5 cm ( n = 22, Group B, large endometriomas). Each group was randomized to coagulation or excision treatment (1:1 ratio) before the procedure. Anti-Mullerian hormone (AMH) levels were evaluated before surgery and 3 months after surgery. Results Both ablation and excision resulted in a significant reduction in AMH level regardless of endometrioma size. A significant interaction effect was observed between endometrioma size and type of surgical technique (analysis of covariance p for interaction = 0.039): in Group A, no significant difference was found between the two surgical techniques (−17.6 ± 4.7% vs −18.2 ± 10.6%), whereas in Group B, the excision group showed a significantly greater percentage decrease in AMH level compared with the ablation group (−24.1 ± 9.3% vs −14.8 ± 6.7%, p = 0.011). Conclusions Both ablative and excision treatment of endometriomas have a negative effect on ovarian function. Endometrioma size is associated with the magnitude of ovarian reserve damage following excision treatment, but in the case of ablative treatment, the decrease in AMH serum level is independent of the size of the cyst. In surgical treatment of large endometriomas, the decrease in AMH level is more consistent and much more severe following cystectomy than ablation.

Weight gain and metabolic changes have been related to survival of early breast cancer patients (EBC). ‘’However, factors influencing metabolism post-diagnosis are not fully understood. We measured anthropometric [body mass index (BMI), body weight, waist and hip circumferences, and waist-to-hip ratio] and metabolic (levels of insulin, glucose, H1Ac, total, HDL, and LDL cholesterol, triglycerides, and the homeostasis model assessment score [HOMA]) parameters in 433 pre- and post-menopausal women with EBC at diagnosis and 3, 6, 9, 12, and 24 months thereafter. At diagnosis, compared with post-menopausal women, pre-menopausal patients were more likely to be leaner and to have a lower BMI, smaller waist and hip circumferences, and waist-to-hip ratio. They had also lower glucose, HbA1c, and triglyceride levels and a lower HOMA score. Furthermore, they were more likely to have an estrogen- and/or progesterone-positive tumor and a higher proliferating breast cancer. During the first two post-diagnosis years, all women showed a significant increase of weight (+0.72 kg/year, P

OBJECTIVES The aims of this retrospective study were to describe ulcerative colitis (UC) phenotype at diagnosis and follow-up and to identify possible predictors of severe disease course. METHODS This was a retrospective, single-center study. We reviewed the charts of patients with UC diagnosed between 2 and 18 years at our referral center from January 2007 to January 2016. Laboratory and clinical features at diagnosis, such as disease extent, atypical phenotypes, extraintestinal manifestations, and therapies, and pattern changes during the follow-up, including relapse rate, disease extension, and the cumulative risk for colectomy were collected. RESULTS One hundred eleven patients were enrolled. Atypical phenotypes were identified at diagnosis in 55 out of 111 patients (49.5%). Extraintestinal manifestations were detected in 16 out of 111 (14.4%) at the diagnosis. During the follow-up 60 out of 111 (54%) patients needed to start azathioprine, 9 out of 111 (8.1%) patients started biologic therapy and 10 out of 111 (patients underwent surgery, resulting in a cumulative risk of 8% at 5 years and 16% at 10 years. Steroid refractoriness (hazard ratio: 13.9) and starting of biologic therapy (hazard ratio: 25.3) represented the best predictors for surgery. The cumulative probability of first relapse was 47% at 6 months and 63% at 1 year. Disease extension was reported in 21 out of 70 patients (30%). CONCLUSION Pediatric UC is associated with a severe phenotype and a high percentage of atypical features. Surgery rate seems to be decreased from early reports.

The urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored cell membrane receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. Its expression is increased in many human cancers, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), and correlates with a poor prognosis and early invasion and metastasis. uPAR is able to control, through a cross-talk with tyrosine kinase receptors, the shift between tumor dormancy and proliferation, that usually precedes metastasis formation. Therefore, we investigated the role of uPAR expression in RAS mutated NSCLC and CRC cells. In this study we provided evidence, for the first time, that RAS mutational condition is functionally correlated to uPAR overexpression in NSCLC and CRC cancer cell lines and patient-derived tissue samples. Moreover, oncogenic features related to uPAR overexpression in RAS mutated NSCLC and CRC, such as adhesion, migration and metastatic process may be targeted, in vitro and in vivo, by new anti-uPAR small molecules, specific inhibitors of uPAR-vitronectin interaction. Therefore, anti-uPAR drugs could represent an effective pharmacological strategy for NSCLC and CRC patients carrying RAS mutations.

BACKGROUND: The accumulation of p-cresol, a metabolic product of aromatic amino acids generated by intestinal microbiome, increases the cardiovascular risk in chronic kidney disease (CKD) patients. Therefore, therapeutic strategies to reduce plasma p-cresol levels are highly demanded. It has been reported that the phosphate binder sevelamer (SEV) sequesters p-cresol in vitro, while in vivo studies on dialysis patients showed controversial results. Aim of our study was to evaluate the effect of SEV on p-cresol levels in non-dialysis CKD patients. METHODS: This was a single-blind, randomized placebo-controlled trial (Registration number NCT02199444) carried on 69 CKD patients (stage 3-5, not on dialysis), randomly assigned (1:1) to receive either SEV or placebo for 3 months. Total p-cresol serum levels were evaluated at baseline (T0), and 1 (T1) and 3 months (T3) after treatment start. The primary end-point was to evaluate the effect of SEV on p-cresol levels. RESULTS: Compared to baseline (T0, 7.4 ± 2.7 mg/mL), p-cresol mean concentration was significantly reduced in SEV patients after one (- 2.06 mg/mL, 95% CI - 2.62 to - 1.50 mg/mL; p < 0.001) and 3 months of treatment (- 3.97 mg/mL, 95% CI - 4.53 to - 3.41 mg/mL; p < 0.001); no change of plasma p-cresol concentration was recorded in placebo-treated patients. Moreover, P and LDL values were reduced after 3 months of treatment by SEV but not placebo. CONCLUSIONS: In conclusion, our study represents the first evidence that SEV is effective in reducing p-cresol levels in CKD patients in conservative treatment, and confirms its beneficial effects on inflammation and lipid pattern.

BACKGROUND: Recent studies of the correlation between breast cancer (BC) and vitamin D yielded contrasting results. Although preclinical and clinical evidence has implicated vitamin D in BC prevention and outcome, little is known about the link between vitamin D and specific BC histologically defined subtypes. In the attempt to clarify this association we correlated vitamin D levels with BC characteristics. PATIENTS AND METHODS: We enrolled 220 pre- and postmenopausal women with early BC in this prospective observational trial. Data on the patients' clinical and specific BC pathological characteristics were collected and related to vitamin D levels, stratified in deficient (< 20 ng/mL), insufficient (20-30 ng/mL), and sufficient (> 30 ng/mL). BC subtypes were defined according to the 14th St Gallen Breast Cancer Conference. RESULTS: Deficient vitamin D levels were correlated with Grade 3 (P = .015) and node-positive (P = .043) BC, and with a higher body mass index (P = .017). Insufficient vitamin D levels were associated with estrogen receptor expression in the primary tumor (P = .033). Vitamin D levels were unrelated to the histological molecular subtypes of BC. CONCLUSION: Deficient vitamin D levels were correlated with more aggressive disease, namely, node-positive high grade BC, and with obesity. Should our findings be confirmed in larger prospective studies, nutritional programs designed to reduce body weight, and vitamin D supplementation might be considered a BC prevention strategy.

Reliable immunologic biomarkers able to monitor disease course during multiple sclerosis (MS) are still missing. We aimed at identifying possible immunometabolic biomarkers able to predict the clinical outcome in MS patients during treatment with interferon (IFN)-beta-1a. We measured in 45 relapsing-remitting (RR) MS patients, blood circulating levels of several immunometabolic markers, at enrolment, and correlated their levels to disease activity and progression over time. Higher levels of interleukin (IL)-6, soluble-CD40-ligand (sCD40L) and leptin at baseline associated with a higher relapse rate and a greater risk of experiencing at least one relapse in the following year. Higher values of soluble tumor necrosis factor receptor (sTNF-R) and leptin at baseline were predictive of a higher number of lesions in the following one-year of follow up. In conclusion, our data suggest that an immunometabolic profiling measuring IL-6, sCD40L, leptin and sTNF-R at baseline, could represent a useful tool to predict disease course in RRMS patients during treatment with IFN-beta-1a.

Active surveillance (AS) is currently a widely accepted treatment option for men with clinically localized prostate cancer (PCa). Several reports have highlighted the association of low serum testosterone levels with high-grade, high-stage PCa. However, the impact of serum testosterone as a predictor of progression in men with low-risk PCa has been little assessed. In this study, we evaluated the association of circulating testosterone concentrations with a staging/grading reclassification in a cohort of low-risk PCa patients meeting the inclusion criteria for the AS protocol but opting for radical prostatectomy. Radical prostatectomy (RP) was performed in 338 patients, eligible for AS according to the following criteria: clinical stage T2a or less, PSApT2) and upgrading (GS=7; primary Gleason pattern 4) disease. Unfavorable disease was defined as the occurrence of pathological stage>pT2 and predominant Gleason score 4. Total testosterone was measured before surgery. Low serum testosterone levels (

Background Drugs are the most important treatment option for most diseases, and the majority of medical consultations result in a prescription. Women and men receive different drug prescriptions and differ in therapeutic response to pharmacological therapy. This disparity is due to biological factors (sex differences) or/and behavior, lifestyle and life experience (gender differences). Sex differences in drug use have been demonstrated in several therapeutic areas; however, there is a lack of overviews on sex and gender differences of drug use in an entire population. Methods We conducted a descriptive cross - sectional drug use study, involving the entire Italian population in 2012, aimed at showing and analyzing differences between men and women as regards their exposure to drugs. The data source was IMS LifeLink Treatment DynamicsTMLRx Database and it included all prescribed drugs reimbursed by the Italian National Healthcare System in 2012 and covered 90% of the entire Italian population. The information about the prescriptions was stratified by men and women and age. Drug consumption was expressed as DDD/ 1000 ab die. Exposure to drug prescriptions was expressed as period prevalence (the proportion of the population dispensed ≥1 prescription in 2012 per 1000 inhabitants). Differences of prevalence between men and women were expressed as crude and age adjusted risk ratios with 95% CI. Results Our findings suggested that the largest differences in drug prescriptions regarded drugs affecting bone structure and mineralization (RR 15.9), calcium (RR 8.6) and thyroid therapy (RR 5.4), dispensed more to women than men. Otherwise ACE inhibitors were more commonly used in men. Conclusions This is the first study exploring difference in drug use between men and women and carried out on the entire Italian population. Our findings showed substantial differences between men and women in term of prevalence of drug prescriptions. Some differences in drug use may be explained by sex differences (variations in disease prevalence and severity, pathophysiology, or by other biological differences), other differences need further investigation to explain the apparent lack of a rational medical explanation for some findings. The findings may subsequently be used to plan future studies to address differences suggesting inequity in treatment approaches. Electronic supplementary material The online version of this article doi:(10.1186/s12905-017-0424-9) contains supplementary material, which is available to authorized users.

Background The efficacy of risk model scores to predict venous thromboembolism (VTE) in ambulatory cancer patients is under investigation, aiming to stratify on an individual risk basis the subset of the cancer population that could mostly benefit from primary thromboprophylaxis. Materials and Methods We prospectively assessed 843 patients with active cancers, collecting clinical and laboratory data. We screened all the patients with a duplex ultrasound (B-mode imaging and Doppler waveform analysis) of the upper and lower limbs to evaluate the right incidence of VTE (both asymptomatic and symptomatic). The efficacy of the existing Khorana risk model in preventing VTE was also explored in our population. Several risk factors associated with VTE were analyzed, leading to the construction of a risk model. The Fine and Gray model was used to account for death as a competing risk in the derivation of the new model. Results The risk factors significantly associated with VTE at univariate analysis and further confirmed in the multivariate analysis, after bootstrap validation, were the presence of metastatic disease, the compression of vascular/lymphatic structures by tumor, a history of previous VTE, and a Khorana score >2. Time-dependent receiving operating characteristic (ROC) curve analysis showed a significant improvement in the area under the curve of the new score over the Khorana model at 3 months (71.9% vs. 57.9%, p = .001), 6 months (75.4% vs. 58.6%, p Conclusion ONKOTEV score steps into history of cancer-related-VTE as a promising tool to drive the decision about primary prophylaxis in cancer outpatients. The validation represents the goal of the prospective ONKOTEV-2 study, endorsed and approved by the European Organization for Research and Treatment of Cancer Young Investigators Program.

Background: Although guidelines do not recommend computerised tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI) for the staging or follow-up of asymptomatic patients with non-metastatic breast cancer, they are often requested in routine clinical practice. The aim of this study was to determine the staging and follow-up patterns, and relative costs in a large population of breast cancer patients living and treated in a Southern Italian region. Methods: We analysed the clinical computerised information recorded by 567 primary-care physicians assisting about 650 000 inhabitants in the Campania region. Patients with non-metastatic breast cancer were identified and divided into calendar years from 2001 to 2010. The number of diagnostic tests prescribed per 100 patients (N/Pts) and the mean cost per patient was determined 3 months before diagnosis and up to 1 year after diagnosis. Costs are expressed in constant 2011 euros. Results: We identified 4680 newly diagnosed cases of asymptomatic non-metastatic breast cancer. N/Pts increased significantly (P

Background Infant colic (IC) is a prevalent physiological event of infants, which can disrupt the child's home environment. We aimed to investigate the effectiveness of a mixture of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) compared with Lactobacillus reuteri DSM 17938 and with simethicone for the treatment of IC. Methods A multicenter randomized comparative study was conducted in infants with colic, according to Rome III criteria, who were randomly assigned to receive M. chamomilla L., M. officinalis L. and tyndallized L. acidophilus (HA122) (Colimil® Plus®; Milte Italia Spa, Milan, Italy) (Group A), L. reuteri DSM 17938 (Group B) and simethicone (Group C). Treatment was given to subjects for 28 days. Key Results One-hundred and seventy-six patients completed the study. Mean daily crying time at day 28 was significantly lower in group A (−44, 95% CI: −58 to −30, P

Background and aims: EndoCuff is a disposable device applied to standard colonoscopes to improve mucosal visualization. Randomized parallel trials have shown that EndoCuff increases the adenoma detection rate (ADR). The primary aim of this study was to compare the ADR between EndoCuff-assisted colonoscopies (EAC) and standard colonoscopies within a randomized back-to-back trial. Methods: This was a single-center randomized crossover study (NCT02374515) involving adult patients undergoing screening, surveillance, or diagnostic colonoscopy. Participants received back-to-back standard colonoscopies and EACs in a random order, performed by the same endoscopist. All polyps were excised, but only those proven at histology to be adenomas were considered for analysis. Results: From February 2015 to March 2016, a total of 288 patients were enrolled, and 274 were included in the per-protocol analysis. Compared with standard colonoscopies, EACs increased the ADR (29.6% vs 26.3%; P < .01) and the number of diagnosed adenomas (176 vs 129; P < .01), particularly in the left (73 vs 46; P < .01) and right sides of the colon (83 vs 63; P < .01). EAC increased the detection of adenomas

Environmental pollutants, including endocrine disruptor chemicals (EDCs), interfere on human health, leading to hormonal, immune and metabolic perturbations. Bisphenol-A (BPA), a main component of polycarbonate plastics, has been receiving increased attention due to its worldwide distribution with a large exposure. In humans, BPA, for its estrogenic activity, may have a role in autoimmunity, inflammatory and allergic diseases. To this aim, we assessed the effect of low BPA doses on functionality of human peripheral blood mononuclear cells (PBMCs), and on in vitro differentiation of dendritic cells from monocytes (mDCs). Fresh peripheral blood samples were obtained from 12 healthy adult volunteers. PBMCs were left unstimulated or were activated with the mitogen phytohemagglutinin (PHA) or the anti-CD3 and anti-CD28 antibodies and incubated in presence or absence of BPA at 0.1 and 1nM concentrations. The immune-modulatory effect of BPA was assessed by evaluating the cell proliferation and the levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13) secreted by PBMCs. mDCs were differentiated with IL-4 and GC-CSF with or without BPA and the expression of differentiation/maturation markers (CD11c, CD1a, CD86, HLA-DR) was evaluated by flow cytometry; furthermore, a panel of 27 different cytokines, growth factors and chemokines were assayed in the mDC culture supernatants. PBMCs proliferation significantly increased upon BPA exposure compared to BPA untreated cells. In addition, a significant decrease in IL-10 secretion was observed in PBMCs incubated with BPA, either in unstimulated or mitogen-stimulated cells, and at both 0.1 and 1nM BPA concentrations. Similarly, IL-13 was reduced, mainly in cells activated by antiCD3/CD28. By contrast, no significant changes in IFN-γ and IL-4 production were found in any condition assayed. Finally, BPA at 1nM increased the density of dendritic cells expressing CD1a and concomitantly decreased the expression of HLA-DR and CD86 activation markers. In conclusion, in humans the exposure to BPA causes on PBMCs a significant modulation of proliferative capacity and cytokine production, and on mDCs alteration in differentiation and phenotype. These immune cell alterations suggest that low dose chronic exposure to BPA could be involved in immune deregulation and possibly in the increased susceptibility to develop inflammatory and autoimmune diseases.

Background:In 2009, the agalsidase beta shortage resulted in switching to agalsidase alfa treatment for many Fabry disease patients, offering the unique opportunity to compare the effects of the two drugs. Because single studies describing effects of switching on the disease course are limited and inconclusive, we performed a systematic review and meta-Analysis of existing data.Methods:Relevant studies were identified in the PubMed, Cochrane, ISI Web, and SCOPUS databases from July 2009 to September 2015. The following parameters were analyzed: clinical events, changes in organ function or structure, disease-related symptoms, lyso-Gb3 plasma levels, and adverse effects.Conclusions:The nine studies (217 patients) included in our systematic review showed only marginal differences in most of the evaluated parameters. Seven of these studies were included in the meta-Analysis (176 patients). The pooled incidence rate of major adverse events was reported for five studies (150 patients) and was equal to 0.04 events per person-year. No significant change was observed after the shift in glomerular filtration rate, whereas left ventricular mass index, left ventricular posterior wall dimension, and ejection fraction were significantly reduced over time. Our data showed that the switch to agalsidase alfa was well tolerated and associated with stable clinical conditions.

The aim of this study was to evaluate the influence of somatosensory impairment, distal muscle weakness and foot deformities on the balance in 21 CMT1A patients using a baropodometric platform. Stabilometric analysis by measuring sway area and velocity of a centre of pressure (CoP) both at open and closed eyes were used to assess postural imbalance. Static analysis, by measuring the load and the plantar surface of forefoot, midfoot and hindfoot was used to define the footprint shape and to assess as a whole foot deformities. Stabilometric and static results were compared with those of a control group. In CMT1A patients, stabilometric findings were correlated with static parameters, Achilles' tendon retraction, distal muscle strength and CMT examination score (CMTES). CMT1A patients compared to controls had lower plantar surface and load on midfoot, and higher load on a forefoot. CMT1A patients had a greater postural instability, since they had a higher CoP velocity, both at open and closed eyes. Moreover, the CoP velocity correlated inversely with the strength of ankle dorsi-flexion muscles and directly with CMTES as whole and with the item "motor symptoms legs". Postural imbalance was not correlated with sensory impairment and foot deformities as expressed by static analysis and Achilles' tendon retraction. In this study we demonstrated an altered balance in CMT1A patients during upright standing. The imbalance in our CMT patients seems to be related to the weakness of ankle dorsi-flexor muscles rather than sensory impairment or foot deformities. These results could be due to a mildly affected CMT1A population, evaluated in an early stage of the disease.

Chronic Obstructive Pulmonary Disease (COPD) is a chronic and progressive lung disease characterized by irreversible airflow obstruction, airway inflammation, oxidative stress and, often, mucus hypersecretion. The aim of this study is to determine if carbocisteine, a mucolytic and antioxidant agent, administered daily for 12 months, can reduce exacerbation frequency in COPD patients.This observational study was conducted in Naples (population approximately 1000,000), Italy. It included 85 out-patients (mean age of 67.8 ± 8.6 years) followed by Clinic of Respiratory Diseases of the University Federico II. Every patient underwent spirometry demonstrating airflow obstruction not fully reversible according to ERS/ATS criteria for COPD diagnosis (Tiffenau index less than 70% after administration of salbutamol, a beta2 agonist drug). Patients enrolled had diagnosed COPD since 2 years and suffered at least one exacerbation in the previous year. None of the patients had been treated with carbocisteine or other mucolytic agent for a longer period of time than 7 days and no more than 4 times in the previous year to the enrollment. All of them assumed daily 2.7 g of carbocisteine lysine salt for a year in addition to their basic therapy.The comparison of exacerbation frequency between the previous year (T0) and the end of study treatment (T12), documents a statistically significant reduction of exacerbations(number of exacerbations at T0: 2 [1,3] vs number of exacerbations at T12: 1 [1,2]; p 0.001).Quality of life was also reported and showed a statistically significant improvement at the end of the study (p 0.001).We did not find correlation between reducing exacerbation frequency and exposure to cigarette smoking, passive smoking exposure in childhood, the use of inhaled steroids, the level of education of our patients and the GOLD stadium.Daily administration of a mucolytic drug such as carbocisteine for prolonged periods in addition to the bronchodilator therapy can be considered a good strategy for reducing exacerbation frequency in COPD.