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Background: Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP., Methods: BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions., Results: Results in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06-2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk., Conclusions: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP., Trial Registration: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212., (© 2024. The Author(s).)

Oxidative stress (OS) is implicated in several chronic diseases. Extra-cellular superoxide dismutase (ec-SOD) catalyses the dismutation of superoxide anions with a protective role in endothelial cells. In chronic kidney disease (CKD), OS and thyroid dysfunction (low fT3 syndrome) are frequently present, but their relationship has not yet been investigated. This cohort study evaluated ec-SOD activity in CKD patients during haemodialysis, divided into "acute haemodialytic patients" (AH, 1-3 months of treatment) and "chronic haemodialytic patients" (CH, treated for a longer period). We also evaluated plasmatic total antioxidant capacity (TAC) and its relationships with thyroid hormones. Two basal samples ("basal 1", obtained 3 days after the last dialysis; and "basal 2", obtained 2 days after the last dialysis) were collected. On the same day of basal 2, a sample was collected 5 and 10 min after the standard heparin dose and at the end of the procedure. The ec-SOD values were significantly higher in CH vs. AH in all determinations. Moreover, the same patients had lower TAC values. When the CH patients were divided into two subgroups according to fT3 levels (normal or low), we found significantly lower ec-SOD values in the group with low fT3 in the basal, 5, and 10 min samples. A significant correlation was also observed between fT3 and ec-SOD in the basal 1 samples. These data, confirming OS and low fT3 syndrome in patients with CKD, suggest that low fT3 concentrations can influence ec-SOD activity and could therefore potentially contribute to endothelial oxidative damage in these patients.

Background/objectives: We investigated whether behavioral precautions adopted during Coronavirus disease (COVID-19) pandemic also influenced the spreading and multidrug resistance (MDR) of ESKAPEEc (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii [AB], Pseudomonas aeruginosa, Enterobacter spp and Escherichia Coli, [EC]) among Intensive Care Unit (ICU) patients., Subjects/methods: We performed a single-center retrospective study in adult patients admitted to our COVID-19-free surgical ICU. Only patients staying in ICU for more than 48 hours were included. The ESKAPEEc infections recorded during the COVID-19 period (June 1, 2020 - February 28, 2021) and in the corresponding pre-pandemic period (June 1, 2019 - February 28, 2020) were compared. An interrupted time series analysis was performed to rule out possible confounders., Results: Overall, 173 patients in the COVID-19 period and 132 in the pre-COVID-19 period were investigated. The ESKAPEEc infections were documented in 23 (13.3%) and 35 (26.5%) patients in the pandemic and the pre-pandemic periods, respectively (p = 0.005). Demographics, diagnosis, comorbidities, type of surgery, Simplified Acute Physiology Score II, length of mechanical ventilation, hospital and ICU length of stay, ICU death rate, and 28-day hospital mortality were similar in the two groups. In comparison with the pre-pandemic period, no AB was recorded during COVID-19 period, (p = 0.017), while extended-spectrum beta-lactamase-producing EC infections significantly decreased (p = 0.017). Overall, the ESKAPEEc isolates during pandemic less frequently exhibited multidrug-resistant (p = 0.014)., Conclusions: These findings suggest that a robust adherence to hygiene measures together with human contact restrictions in a COVID-19 free ICU might also restrain the transmission of ESKAPEEc pathogens., (© 2021 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: The aim of this study is to identify miRNAs able to predict the outcomes in breast cancer patients after neoadjuvant chemotherapy (NAC)., Patients and Methods: We retrospectively analyzed 24 patients receiving NAC and not reaching pathologic complete response (pCR). miRNAs were analyzed using an Illumina Next-Generation-Sequencing (NGS) system., Results: Event-free survival (EFS) and overall survival (OS) were significantly higher in patients with up-regulation of let-7a-5p (EFS p = 0.006; OS p = 0.0001), mirR-100-5p (EFS s p = 0.01; OS p = 0.03), miR-101-3p (EFS p = 0.05; OS p = 0.01), and miR-199a-3p (EFS p = 0.02; OS p = 0.01) in post-NAC samples, independently from breast cancer subtypes. At multivariate analysis, only let-7a-5p was significantly associated with EFS ( p = 0.009) and OS ( p = 0.0008)., Conclusion: Up-regulation of the above miRNAs could represent biomarkers in breast cancer.

Objective: To develop a deep learning-based decision tree for the primary care setting, to stratify adult patients with confirmed and unconfirmed coronavirus disease 2019 (COVID-19), and to predict the need for hospitalization or home monitoring., Patients and Methods: We performed a retrospective cohort study on data from patients admitted to a COVID hospital in Rome, Italy, between 5 March 2020 and 5 June 2020. A confirmed case was defined as a patient with a positive nasopharyngeal RT-PCR test result, while an unconfirmed case had negative results on repeated swabs. Patients' medical history and clinical, laboratory and radiological findings were collected, and the dataset was used to train a predictive model for COVID-19 severity., Results: Data of 198 patients were included in the study. Twenty-eight (14.14%) had mild disease, 62 (31.31%) had moderate disease, 64 (32.32%) had severe disease, and 44 (22.22%) had critical disease. The G2 value assessed the contribution of each collected value to decision tree building. On this basis, SpO2 (%) with a cut point at 92 was chosen for the optimal first split. Therefore, the decision tree was built using values maximizing G2 and LogWorth. After the tree was built, the correspondence between inputs and outcomes was validated., Conclusions: We developed a machine learning-based tool that is easy to understand and apply. It provides good discrimination in stratifying confirmed and unconfirmed COVID-19 patients with different prognoses in every context. Our tool might allow general practitioners visiting patients at home to decide whether the patient needs to be hospitalized.

Background : Although secukinumab and ixekizumab both act by inhibiting IL-17A, some scientific evidence suggests that there are differences in efficacy between the two agents. Objective : The aim of this study was to compare the short- and long-term effectiveness of ixekizumab and secukinumab in clinical practice. Methods : A retrospective study was conducted on a cohort of 245 psoriatic patients receiving secukinumab or ixekizumab during the period from September 2016 to December 2019. The proportion of patients achieving PASI75, PASI90, and PASI100 at weeks 12 and 24 was calculated. We recorded the 12- and 24-month drug survival as a measure to assess long-term effectiveness. Results : A higher proportion of patients in the secukinumab group achieved PASI75, 90, and 100 at 12 weeks. The Kaplan-Meier survival curve for any reason of discontinuation showed no differences between the two groups. Instead, the multivariate analysis for ineffectiveness, adjusted for potential confounders, showed a lower drug survival rate in the secukinumab group, with an adjusted HR of 2.57 (95% CI 1.05-6.28, p 0.038). Conclusion : This real-life study demonstrated that ixekizumab and secukinumab are both highly effective in short- and long-term treatment of psoriasis, even though few differences exist concerning speed of action and long-term effectiveness.

Objective: Kisspeptin, neuropeptide involved in puberty beginning and regulation of pituitary-gonadal axis, has been shown to stimulate antioxidant defenses in murine models. Its levels are greater in females than males and also in obese prepubertal girls. Therefore, our aim was to evaluate sex-related differences in prepubertal obese patients and the relationships of Kisspeptin with metabolic/hormonal parameters., Patients and Methods: We studied Kisspeptin concentrations in 54 children (22 males and 32 females, Tanner stage 1), 5-12 ys, classified according to Cole's criteria into 17 overweight and 37 obese; 25 normal-weight children, aged 6-12 years, were studied as controls. We evaluated metabolic (glucose and insulin levels after oral glucose load, total- LDL- HDL-cholesterol, triglycerides, uric acid) and hormonal (fT3, fT4, TSH, IGF-1, leptin) parameters. Moreover, total antioxidant capacity (TAC) was evaluated by spectrophotometric method, using the system H202-metmyoglobin-ABTS. Kisspeptin levels were measured by RIA., Results: We did not find significant differences between obese and normal-weight children, but obese males presented significantly lower levels than females. Kisspeptin did not correlate with BMI, HOMA-IR, Insulin peak levels and TAC; a significant correlation was found between Kisspeptin and fT3 (r2=0.25; p=0.003) in the obese group; leptin levels, significantly greater in obese vs. overweight and control children, significantly correlated with TAC (r2=0.39; p=0.03)., Conclusions: These data suggest that both hormones could modulate antioxidants, Kisspeptin indirectly via influence on thyroid hormones, and Leptin by a direct effect. This mechanism seems to be sex-related, not attributable to peripheral steroid levels. Further studies can clarify the complex interrelationship between central and peripheral Kisspeptin secretion and oxidative stress in children obesity.

Repeated red blood cell (RBC) transfusions in preterm neonates are associated with poor outcome and increased risk for prematurity-associated diseases. RBC transfusions cause the progressive replacement of fetal haemoglobin (HbF) by adult haemoglobin (HbA). We monitored HbF levels in 25 preterm neonates until 36 weeks of post-menstrual age (PMA); patients received RBC units from allogeneic cord blood (cord-RBCs) or from adult donors (adult-RBCs), depending on whether cord-RBCs were available. Primary outcome was HbF level at PMA of 32 weeks. Twenty-three neonates survived until this age: 14 received no transfusions, two only cord-RBCs, three only adult-RBCs and four both RBC types. HbF levels in neonates transfused with cord-RBCs were significantly higher than in neonates receiving adult-RBCs (P < 0·0001) or both RBC types (P < 0·0001). Superimposable results were obtained at PMA of 36 weeks. Every adult-RBCs transfusion increased the risk for an HbF in the lowest quartile by about 10-fold, whereas this effect was not evident if combined adult- and cord-RBCs were evaluated. Overall, these data show that transfusing cord-RBCs can limit the HbF depletion caused by conventional RBC transfusions. Transfusing cord blood warrants investigation in randomised trials as a strategy to mitigate the severity of retinopathy of prematurity (NCT03764813)., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: Segmental resection has been generally associated with increased peri-operative risk of major complications. While major complications are widely acknowledged, minor complications, such as slight, to moderate infections, peripheral sensory disturbances, bladder voiding dysfunction, postoperative urinary obstruction, and sexual disorders are less reported. The aim of this study is to investigate the surgery-related complications and functional disorders, as well as to evaluate their persistence after long-term follow-up in women undergone segmental resection for deep infiltrating endometriosis. Special attention is given to evaluating impairments of bowel, bladder, and sexual function., Methods: All clinical data obtained from medical records of women who underwent segmental resection for intestinal endometriosis between October 2005, and November 2017, in Catholic University Institutions. Perioperative morbidity was classified by Extended Clavien-Dindo classification. Postoperative intestinal, voiding, and sexual morbidity was estimated by the compilation of specific questionnaires., Results: Fifty women were included in the study. Forty-three high colorectal resections (86%), 6 low resections (12%), and 1 ultra-low resection (2%) were performed, while in 3 cases (6%) multiple resections were needed. The overall complication rate was 44%. Nineteen women (38%) experienced early complications and 3 women (6%) late complications. Long-term functional postoperative complications were composed of intestinal in 30%, urinary in 50%, and sexual in 64% of the study population. Median follow-up was 55.5 months., Conclusions: Segmental resection, when indicated, offers a radical and feasible approach for bowel deep infiltrating endometriosis, resulting in an improved general quality of life. The bowel and bladder complications appear to be acceptable and often reversible. Postoperative sexual dysfunctions, such as anorgasmia and insufficient vaginal lubrication, appear to persist over time. Surgeons and women have to be aware of the incidence of this kind of complications.

Background: Computerized Clinical Decision Support Systems (CCDSS) have become increasingly important in ensuring patient safety and supporting all phases of clinical decision making. The aim of this study is to evaluate, through a CCDSS, the rate of the laboratory tests overuse and to estimate the cost of the inappropriate requests in a large university hospital., Method: In this observational study, hospital physicians submitted the examination requests for the inpatients through a Computerized Physician Order Entry. Violations of the rules in tests requests were intercepted and counted by a CCDSS, over a period of 20 months. Descriptive and inferential statistics (Student's t-test and ANOVA) were made. Finally, the monthly comprehensive cost of the laboratory tests was calculated., Results: During the observation period a total of 5,716,370 requests were analyzed and 809,245 violations were counted. The global rate of overuse was 14.2% ± 3.0%. The most inappropriate exams were Alpha Fetoprotein (85.8% ± 30.5%), Chlamydia trachomatis Nucleic Acid Amplification (48.7% ± 8.8%) and Alkaline Phosphatase (20.3% ± 6.5%). The monthly cost of over-utilization was 56,534€ for basic panel, 14,421€ for coagulation, 4,758€ for microbiology, 432€ for immunology exams. All the exams, generated an estimated avoidable cost of 1,719,337€ (85,967€ per month) for the hospital., Conclusions: The study confirms the wide variability in over-utilization rates of laboratory tests. For these reasons, the real impact of inappropriateness is difficult to assess, but the generated costs for patients, hospitals and health systems are certainly high and not negligible. It would be desirable for international medical communities to produce a complete panel of prescriptive rules for all the most common laboratory exams that is useful not only to reduce costs, but also to ensure standardization and high-quality care., Competing Interests: We have no conflicts of interest to report.

Objective: The recent outbreak of SARS-CoV-2 infection in Italy has resulted in a sudden and massive flow of patients into emergency rooms, and a high number of hospitalizations with the need for respiratory isolation. Massive admission of patients to the Policlinico "Agostino Gemelli" Foundation of Rome, Italy, determined the need for reengineering the entire hospital., Materials and Methods: In this article, we consider some of the structural and organizational changes that have been necessary to deal with the emergency, with particular reference to non-intensive medicine wards, and the preventive measures aimed at limiting the spread of SARS-CoV-2 infection among hospital staff and patients themselves., Results: 577 staff members were subjected to molecular tests in 1-month period and 3.8% of the total were positive. 636 patients admitted to the COVID-19 pathway were included and analyzed: 45.4% were identified as SARS-CoV-2 positive. More SARS-CoV-2 negative patients were discharged in comparison to SARS-CoV-2 positive patients (59% vs. 41%, respectively). On the other hand, more SARS-CoV-2 positive patients were transferred to ICUs in comparison to SARS-CoV-2 negative patients (16% vs. 1%, respectively). Occurrence of death was similar between the two groups, 11% vs. 7%, for SARS-CoV-2 negative and positive patients, respectively. 25% of ≥80 years old SARS-CoV-2 positive patients died during the hospitalization, while death rate was lower in other age groups (5% in 70-79 years old patients and 0% in remaining age groups)., Conclusions: Rapid hospital reengineering has probably had an impact on the management of patients with and without SARS-CoV-2 infection, and on in-hospital mortality rates over the reporting period.

Background: While anabolic hormone deficit is a common finding in heart failure with reduced ejection fraction (HFrEF), few data are available in heart failure with preserved ejection fraction (HFpEF)., Methods: Blood samples were collected for metabolic (total cholesterol, HDL cholesterol, LDL cholesterol, creatinine, and glucose) and hormonal (IGF-1, DHEA-S, TSH, fT3, fT4, and T) determination, comparing 30 patients with HFpEF and 20 patients with HFrEF. Total antioxidant capacity was evaluated by using the spectrophotometric method using the latency time in the appearance of the radical species of a chromogen (LAG, sec) as a parameter proportional to antioxidant content of the sample. Echocardiographic parameters were also assessed in the two groups., Results: A high prevalence of testosterone (32% in HFrEF and 72% in HFpEF, p < 0.05) and DHEA-S deficiencies was observed in HFpEF patients. Echocardiographic parameters did not correlate with hormone values. A significant direct correlation between T ( r 2  = 0.25, p < 0.05) and DHEA-S ( r 2  = 0.19, p < 0.05) with LAG was observed only in HFpEF., Conclusion: Anabolic hormone deficiency is clearly shown in HFpEF, as already known in HFrEF. Although longitudinal studies are required to confirm the prognostic value of this observation, our data suggest different mechanisms in modulating antioxidants in the two conditions, with possible therapeutic implications., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Antonio Mancini et al.)

Purposes: The primary objective is to assess the long-term quality of life (QoL) and gastrointestinal well-being in patients with endometriosis (DIE) who underwent segmental resection (SR), through specific questionnaires focused on endometriosis and specific gastrointestinal evaluation. The secondary objectives are represented by the evaluation of peri-operative and post-operative outcomes of the procedure., Methods: This observational cohort study ENDO-RESECT (ClinicalTrials.gov ID: NCT03824054) reports all clinical data about women who underwent SR for DIE between October 2005 and November 2017. In the part of the study dedicated to the QoL assessment, the questionnaires adopted were the Endometriosis Health Profile (EHP30), the Psychological General Well-Being Index and the Hospital Anxiety and Depression Scale, the Gastrointestinal Well-being questionnaire and the Bristol Stool chart. Major post-surgical morbidity and obstetric outcomes were also collected., Results: 50 women (18% stage III and 82% stage IV rAFS) were considered for enrollment. EHP-30 interpretation demonstrated a significant improvement in all continuous variables, except for fertility concerns. The overall gastrointestinal QoL and most of the specific symptoms improved after surgery. Frequent bowel movements appeared in the 13% of the series not resulting in an impairment of general and gastrointestinal QoL. Constipation remained unchanged. Patients with depressive mood managed with laparoscopy, benefited the most from SR; moreover, patients with multinodular bowel localizations experienced a greater reduction in abdominal pain. Median FU after SR was 42.5 months (range 12-157 months). Only three (6%) cases of late major grade III complications were documented. The pregnancy rate was 50%., Conclusions: Improvement of general QoL and most of gastrointestinal symptoms was documented after SR.

(1) Background: There is growing interest in the assessment of muscular mass in inflammatory bowel disease (IBD) as sarcopenia is associated with important outcomes. The aim of the study was to evaluate the percentage of sarcopenia in IBD patients, characterizing methods for assessment and clinical symptoms associated to it. (2) Methods: Consecutive IBD patients accessing the Fondazione Policlinico Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) were enrolled. Healthy patients, elderly or elderly sarcopenic patients, were enrolled as controls. Skeletal muscle mass was evaluated by Dual Energy X-ray Absorptiometry (DEXA) or Bio-Impedensometric Analysis (BIA). Asthenia degree was assessed by subjective visual analogue scales (VAS). Quality of life was measured by the EQ-5D questionnaire. (3) Results: Patients with IBD showed a significant reduction in skeletal muscle mass than healthy controls with lower DEXA and BIA parameters. Moreover, IBD patients presented a lower perception of muscle strength with a higher incidence of asthenia and reduction in quality of life when compared with healthy controls. A significant association between loss in skeletal muscle mass and high asthenia degree was found, configuring a condition of sarcopenia in about one third of patients with IBD. (4) Conclusions: Sarcopenia is common in IBD patients and it is associated with fatigue perception as well as a reduction in quality of life. Therefore, routine assessment of nutritional status and body composition should be a cornerstone in clinical practice, bringing gastroenterologists and nutritionists closer together for a compact, defined picture.

Aim: To investigate the association between a hospital palliative care unit assessment and hospital outcome., Methods: This was a prospective cohort study. Data were assessed from all patients treated and followed by the hospital palliative care team (HPCT) from November 2016 until December 2017., Results: The mean age of the 588 patients was 73.15±13.6 years. All of the patients included in the study were referred to palliative care. A large proportion of patients were affected by cancer, 69.7% (410), while 30.3% (178) were affected by an advanced chronic illness. The three most frequent cancers were: gastrointestinal (n=81, 19.8%), gynaecological (n=66, 16.1%) and lung (n=63, 15.4%); the three most frequent chronic advanced diseases were: advanced dementia (n=45, 25.3%), severe ischaemic/haemorrhagic stroke (n=36, 20.2%) and severe heart failure (n=25, 15.3%). The majority of patients were in clinical wards (n=476, 81.0%) and the average length of stay was 22.9 days. Hospital outcome trends were evaluated in terms of length of stay and number of deaths that occurred in the hospital. In particular, length of stay decreased from 25.8 days to 18.1 days, hospital death from 13 to 0 during the time that the HPCT assessed patients for an appropriate discharge., Conclusion: The HPCT is an effective means of managing patients affected by severe illness, reducing the number of deaths that occur within the hospital, long periods of hospitalisation and instances of readmission. However, further studies are required to fully assess the impact of an HPCT on hospital outcomes.

Background: Postoperative respiratory failure (PRF, namely mechanical ventilation >48 hours) significantly affects morbidity and mortality in liver transplantation (LTx). Previous studies analyzed only one or two categories of PRF risk factors (preoperative, intraoperative or postoperative ones). The aims of this study were to identify PRF predictors, to assess the length of stay (LoS) in ICU and the 90-day survival according to the PRF in LTx patients., Methods: Two classification approaches were used: systematic classification (recipient-related preoperative factors; intraoperative factors; logistic factors; donor factors; postoperative ICU factors; postoperative surgical factors) and patient/organ classification (patient-related general factors; native-liver factors; new-liver factors; kidney factors; heart factors; brain factors; lung factors). Two hundred adult non-acute patients were included. Missing analysis was performed. The competitive role of each factor was assessed., Results: PRF occurred in 36.0% of cases. Among 28 significant PRF predictors at univariate analysis, 6 were excluded because of collinearity, 22 were investigated by ROC curves and by logistic regression analysis. Recipient age (OR = 1.05; p = 0.010), female sex (OR = 2.75; p = 0.018), Model for End-Stage Liver Disease (MELD, OR = 1.09; p<0.001), restrictive lung pattern (OR = 2.49; p = 0.027), intraoperative veno-venous bypass (VVBP, OR = 3.03; p = 0.008), pre-extubation PaCO2 (OR = 1.11; p = 0.003) and Model for Early Allograft Function (MEAF, OR = 1.37; p<0.001) resulted independent PRF risk factors. As compared to patients without PRF, the PRF-group had longer LoS (10 days IQR 7-18 versus 5 days IQR 4-7, respectively; p<0.001) and lower day-90 survival (86.0% versus 97.6% respectively, p<0.001)., Conclusion: In conclusion, MELD, restrictive lung pattern, surgical complexity as captured by VVBP, pre-extubation PaCO2 and MEAF are the main predictors of PRF in non-acute LTx patients., Competing Interests: The authors have declared that no competing interests exist.

Irisin, a recently discovered myokine, has been considered a prognostic factor in several cardiovascular diseases. Nevertheless, no data are available on the role of irisin in patients with heart failure (HF), both with preserved (HFpEF) or reduced (HFrEF) ejection fraction. We have therefore evaluated the circulating irisin levels in HFpEF and HFrEF patients, correlating them with metabolic parameters and total antioxidant capacity (TAC), as index of oxidative stress. Irisin was significantly higher in HFpEF than in HFrEF patients (7.72 ± 0.76 vs 2.77 ± 0.77 ng/ml, respectively). An inverse correlation between irisin and TAC was found in HFpEF, but not in HFrEF. Conversely, no correlation was present with HOMA index. These data support the hypothesis that a different pathophysiological mechanism is involved in the two HF subtypes, and oxidative stress modulates irisin secretion., Competing Interests: The authors have declared that no competing interests exist.

OBJECTIVE To provide an overview of the economic aspects of needlestick and sharps injury (NSI) management among healthcare personnel (HCP) within a Health Technology Assessment project to evaluate the impact of safety-engineered devices on health care METHODS A systematic review of economic analyses related to NSIs was performed in accordance with the PRISMA statement and by searching PubMed and Scopus databases (January 1997-February 2015). Mean costs were stratified by study approach (modeling or data driven) and type of cost (direct or indirect). Costs were evaluated using the CDC operative definition and converted to 2015 International US dollars (Int$). RESULTS A total of 14 studies were retrieved: 8 data-driven studies and 6 modeling studies. Among them, 11 studies provided direct and indirect costs and 3 studies provided only direct costs. The median of the means for aggregate (direct + indirect) costs was Int$747 (range, Int$199-Int$1,691). The medians of the means for disaggregated costs were Int$425 (range, Int$48-Int$1,516) for direct costs (9 studies) and Int$322 (range, Int$152-Int$413) for indirect costs (6 studies). When compared with data-driven studies, modeling studies had higher disaggregated and aggregated costs, but data-driven studies showed greater variability. Indirect costs were consistent between studies, mostly referring to lost productivity, while direct costs varied widely within and between studies according to source infectivity, HCP susceptibility, and post-exposure diagnostic and prophylactic protocols. Costs of treating infections were not included, and intangible costs could equal those associated with NSI medical evaluations. CONCLUSIONS NSIs generate significant direct, indirect, potential, and intangible costs, possibly increasing over time. Economic efforts directed at preventing occupational exposures and infections, including provision of safety-engineered devices, may be offset by the savings from a lower incidence of NSIs. Infect Control Hosp Epidemiol 2016;37:635-646.

Objectives: Tobacco packaging represents an important form of promotion of tobacco products and for this reason plain packaging (PP) can be considered an additional tobacco control measure. In Italy the current tobacco packaging is branded with textual warnings. The study investigated the perception of PP with textual warnings (PPTWs) and pictorial warnings (PPPWs) in Italy., Study Design: Cross-sectional., Methods: The study was conducted on adults who were current, never and former smokers. The participants watched out three types of packages (current packaging, PPTWs and PPPWs) and eight pictorial warnings, and indicated which they considered the most effective ones to motivate smoking cessation or reduction and to prevent the onset., Results: 1065 subjects were recruited. The PPPWs were considered the most effective in motivating to quit, reduce and prevent the smoking habits (ranged 83.4%-96.1%) in all tobacco users and age groups (≤40/>40 years) (P < 0.005). In general PP does not seem to be very effective in quitting for three-quarters of the smokers and 60% declared that they would have still started smoking with PP. The younger group believed less than the older one that PP gives a motivation to quit (29.4% vs 39.1%, P = 0.002). The pictures perceived as most effective in communicating the smoking effects were lung cancer and gangrene (about one-third of the sample)., Conclusions: The textual warnings on tobacco products are a measure of control now outdated. Countries still using them should consider the idea of replace them with pictorial warnings that seem to be more effective. It is also desirable in the near future that these countries introduce the PPPWs., (Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Oxidative stress (OS) could play a role in metabolic syndrome-related manifestations contributing to insulin resistance (IR). The aim of the present study was to gain insight the relationships between OS, IR and other hormones involved in caloric balance, explaining the effects of a natural antioxidant-enriched diet in patients affected by metabolic syndrome., Methods: We investigated the effects of dietary antioxidants on IR, studying 53 obese (20 males and 33 females, 18-66 years old, BMI 36.3 ± 5.5 kg/m 2 ), with IR evaluated by Homeostasis Model Assessment (HOMA)-index, comparing 4 treatments: hypocaloric diet alone (group A) or plus metformin 1000 mg/daily (group B), natural antioxidants-enriched hypocaloric diet alone (group C) or plus metformin (group D). A personalized program, with calculated antioxidant intake of 800-1000 mg/daily, from fruit and vegetables, was administered to group C and D. The glycemic and insulinemic response to oral glucose load, and concentrations of total-, LDL- and HDL-cholesterol, triglycerides, uric acid, C reactive protein, fT3, fT4, TSH, insulin-like growth factor 1 were evaluated before and after 3-months. Plasma Total antioxidant capacity was determined by H 2 O 2 -metmyoglobin system, which interacting with the chromogen ABTS generates a radical with latency time (LAG) proportional to antioxidant content., Results: Despite a similar BMI decrease, we found a significant decrease of HOMA and insulin peak only in group B and D. Insulin response (AUC) showed the greatest decrease in group D (25.60  ±  8.96%) and was significantly lower in group D vs B. No differences were observed in glucose response, lipid metabolism and TAC (expressed as LAG values). TSH values were significantly suppressed in group D vs B., Conclusions: These data suggest that dietary antioxidants ameliorate insulin-sensitivity in obese subjects with IR by enhancing the effect of insulin-sensitizing drugs albeit with molecular mechanisms which remain yet to be elucidated., (Copyright © 2014 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Objective: The Health Technology Assessment (HTA) approach was applied to denosumab in the prevention of osteoporotic fractures in postmenopausal women., Method: Epidemiological, clinical, technical, economic, organizational, and ethical aspects were considered. Medical electronic databases were accessed to evaluate osteoporosis epidemiology and therapeutical approaches. A budget impact and a cost-effectiveness analyses were performed to assess economic implications. Clinical benefits and patient needs were considered with respect to organizational and ethical evaluation., Results: In Italy around four millions women are affected by osteoporosis and have a higher risk for fractures with 70,000 women being hospitalized every year. Bisphosphonates and strontium ranelate are recommended as first line treatment for the prevention of osteoporotic fractures. Denosumab is effective in reducing vertebral, nonvertebral, and hip/femoral fractures with an advantage of being administered subcutaneously every six months. The budget impact analysis estimated a reduction in costs for the National Health Service with the introduction of denosumab. Furthermore, the economic analysis demonstrated that denosumab is cost-effective in comparison to oral bisphosphonates and strontium ranelate. Denosumab can be administered in outpatients by involving General Practitioners in the management. Ethical evaluation is positive because of its efficacy and compliance., Conclusion: Denosumab could add value in the prevention of osteoporotic fractures.

Objective: Systemic lupus erythematosus (SLE) is treated with anti-inflammatory and immunosuppressive drugs and off-label biologics. Belimumab is the first biologic approved after 50 years as an add-on therapy for active disease. This paper summarizes a health technology assessment performed in Italy., Methods: SLE epidemiology and burden were assessed using the best published international and national evidences and efficacy and safety of belimumab were synthesized using clinical data. A cost-effectiveness analysis was performed by a lifetime microsimulation model comparing belimumab to standard of care (SoC). Organizational and ethical implications were discussed., Results: Literature review showed that SLE affects 47 per 100,000 people for a total of 28,500 patients in Italy, 50% of whom are affected by active form of the disease despite SoC. These patients, if autoantibodies and anti-dsDNA positive with low complement, are eligible for belimumab. SLE determines work disability and a 2-5-fold increase in mortality. Belimumab with SoC may prevent 4,742 flares in three years being cost-effective with an incremental cost-effectiveness ratio of €32,859 per quality adjusted life year gained. From the organizational perspective, the development of clear and comprehensive clinical pathways is crucial., Conclusions: The assessment supports the use of belimumab into the SLE treatment paradigm in Italy.

The aims of the present research are to investigate the possible predictors of pancreatic cancer, in particular smoking status, alcohol consumption, hypercholesterolemia, and diabetes mellitus, in patients with histologically confirmed pancreatic carcinoma and to examine the synergism between risk factors. A case-control study (80 patients and 392 controls) was conducted at the Teaching Hospital "Agostino Gemelli" in Rome. A conditional logistic regression was used for the statistical analysis and results were presented as odds ratio (OR) and 95% confidence intervals (95% CI). We also investigated the possible interactions between risk factors and calculated the synergism index (SI). The multivariate analysis revealed that hypercholesterolemia and alcohol consumption resulted in important risk factors for pancreatic cancer even after the adjustment for all variables (OR: 5.05, 95% CI: 2.94-8.66; OR: 2.25, 95% CI: 1.30-3.89, resp.). Interestingly, important synergistic interactions between risk factors were found, especially between ever smoking status and alcohol consumptions (SI = 17.61) as well as alcohol consumption and diabetes (SI = 17.77). In conclusion, the study confirms that hypercholesterolemia and alcohol consumption represent significant and independent risk factors for pancreatic cancer. Moreover, there is evidence of synergistic interaction between diabetes and lifestyle factors (drinking alcohol and eating fatty foods).

Genetic and environmental factors interact in determining the risk of venous thromboembolism (VTE). The risk associated with the polymorphic variants G1691A of factor V (Factor V Leiden, FVL), G20210A of prothrombin (PT20210A) and C677T of methylentetrahydrofolate reductase (C677T MTHFR) genes has been investigated in many studies. We performed a pooled analysis of case-control and cohort studies investigating in adults the association between each variant and VTE, published on Pubmed, Embase or Google through January 2010. Authors of eligible papers, were invited to provide all available individual data for the pooling. The Odds Ratio (OR) for first VTE associated with each variant, individually and combined with the others, were calculated with a random effect model, in heterozygotes and homozygotes (dominant model for FVL and PT20210A; recessive for C677T MTHFR). We analysed 31 databases, including 11,239 cases and 21,521 controls. No significant association with VTE was found for homozygous C677T MTHFR (OR: 1.38; 95 % confidence intervals [CI]: 0.98-1.93), whereas the risk was increased in carriers of either heterozygous FVL or PT20210 (OR = 4.22; 95 % CI: 3.35-5.32; and OR = 2.79;95 % CI: 2.25-3.46, respectively), in double heterozygotes (OR = 3.42; 95 %CI 1.64-7.13), and in homozygous FVL or PT20210A (OR = 11.45; 95 %CI: 6.79-19.29; and OR: 6.74 (CI 95 % 2.19-20.72), respectively). The stratified analyses showed a stronger effect of FVL on individuals ≤ 45 years (p value for interaction = 0.036) and of PT20210A in women using oral contraceptives (p-value for interaction = 0.045). In this large pooled analysis, inclusive of large studies like MEGA, no effect was found for C677T MTHFR on VTE; FVL and PT20210A were confirmed to be moderate risk factors. Notably, double carriers of the two genetic variants produced an impact on VTE risk significantly increased but weaker than previously thought.

Background: We examined the methodological quality of guidelines on colorectal cancer genetic susceptibility syndromes., Methods: PubMed, EMBASE, and Google were searched up to July 2010. Adjourned guidelines in English were included. The Appraisal of Guidelines, Research and Evaluation (AGREE) instrument was used to assess their quality, and the reported evidence base of the guidelines was evaluated., Results: The search yielded 17 eligible guidelines: 11 were developed by independent associations, while 6 had national\state endorsement. Only three guidelines performed satisfactorily, achieving a score >50% in all 6 AGREE domains. Mean standardized scores for the 6 AGREE domains were: 'scope and purpose', 83.9 ± 22.5%; 'stakeholder involvement', 35.6 ± 24.9%; 'rigour of development', 48.6 ± 25.3%; 'clarity and presentation', 71.6 ± 19.3%; 'applicability', 33.8 ± 30.1%; 'editorial independence', 42.2 ± 39.7%. Guidelines with national endorsement performed better in all the domains, with a statistically significant difference in three domains. Fifteen guidelines out of 17 were found to be based on research evidence., Conclusions: There is scope, in many areas, for improving the guidelines analysed, among which are the involvement of various professional figures and patients' representatives, and policies for their application. The AGREE instrument is a useful tool and could also be used profitably by guideline developers to improve the quality of recommendations.

Background: We examined the methodological quality of guidelines on syndromes conferring genetic susceptibility to breast cancer., Methods: PubMed, EMBASE, and Google were searched for guidelines published up to October 2010. All guidelines in English were included. The Appraisal of Guidelines, Research and Evaluation (AGREE) instrument was used to assess the quality of the guidelines, and their reported evidence base was evaluated., Results: Thirteen guidelines were deemed eligible: seven had been developed by independent associations, and the other six had national/state endorsements. Four guidelines performed satisfactorily, achieving a score of greater than 50% in all six AGREE domains. Mean ± SD standardized scores for the six AGREE domains were: 90 ± 9% for 'scope and purpose', 51 ± 18% for 'stakeholder involvement', 55 ± 27% for 'rigour of development', 80 ± 11% for 'clarity and presentation', 37 ± 32% for 'applicability', and 47 ± 38% for 'editorial independence'. Ten of the thirteen guidelines were found to be based on research evidence., Conclusions: Given the ethical implications and the high costs of genetic testing for hereditary breast cancer, guidelines on this topic should provide clear and evidence-based recommendations. Our analysis shows that there is scope for improving many aspects of the methodological quality of current guidelines. The AGREE instrument is a useful tool, and could be used profitably by guidelines developers to improve the quality of recommendations.

Only patients with Model for End-stage Liver Disease (MELD) scores ≥18 or ≥17 experience a survival benefit (SB) at 12 and 36 months after liver transplantation (OLT). The SB calculation estimates the difference after stratification for risk categories between the survival rate of transplanted versus waiting list patients. The aim of this study was to perform a short- and long-term (60 months) SB analyses of a Italian OLT program. One-hundred seventy-one patients were stratified into four MELD classes (6-14, 15-18, 19-25, 26-40), and two groups: namely, waiting list (WL) and transplanted groups (TX). The median waiting time for transplanted patients was 4.4 months (range, 0-35). SB was expressed as mortality hazard ratio (MHR) as obtained through a Cox regression analysis using as a covariate the status of each patient in the waiting list (WL = 0, reference group) or the TX group (TX = 1). Values over 1 indicated the MHR in favor of the WL with the values below 1 indicating MHR in favor of Tx. In the MELD class 6 to 14, the MHR was above 1 at 3 and 6 months, indicating an SB in favor of WL; subsequently, the MHR dropped below 1, indicating an SB in favor of TX (P < .05). In the MELD class 15 to 18 the MHR was above 1 at 3 months, but below 1 subsequently (P < .05). For MELD classes 19 to 25 and 26 to 40, the MHR was always below 1 (P < .01). According to the SB approach, patients in the MELD class 6 to 14 could safely wait for at least 36 months; patients in the MELD class 15 to 18 should likely remain no longer than 12 months on the waiting list, and all the remaining patients with MELD > 18 should be transplanted as soon as possible. OLT should not be precluded but only postponed for MELD < 19 patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Donor-recipient match is a matter of debate in liver transplantation. D-MELD (donor age × recipient biochemical model for end-stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3-year patient survival. D-MELD cutoff predictive of 5-year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (http://www.D-MELD.com). Differences among D-MELD deciles allowed their regrouping into three D-MELD classes (A < 338, B 338-1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44-2.85) in D-MELD class C versus B. The OR was 0.40 (95% CI, 0.24-0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11-1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51-0.93), retransplant (OR = 1.82; 95% CI, 1.16-2.87) and low-volume center (OR = 1.48; 95% CI, 1.11-1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59-2.43) for D-MELD class C versus class B and 0.42 (95% CI, 0.29-0.60) for D-MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D-MELD ≥ 1750). The innovative approach offered by D-MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients., (©Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: The World Health Organization (WHO) estimates that about 180 million people, 3% of the world population, are infected with the hepatitis C virus (HCV). In Italy, the prevalence in the general population is reported to be greater than 5% and 9% among households of HCV-positive patients., Objectives: The aim of this study was to estimate the trends of HCV infection in Italy in the period 1996-2006., Materials and Methods: The formula ln (rate) = b × years was applied for logarithmic transformation of the incidence rates to obtain time trends of HCV infection, using the join-point regression program software version 3.3.1. Linear graphs representing trends and the annual percentage change (APC) were considered for each joinpoint. Time changes are expressed as expected annual percentage change (EAPC) with the respective 95% confidence intervals (CIs); significance levels of time trends are also reported. The null hypothesis was tested using a maximum of 3 changes in slope with an overall significance level of 0.05 divided by the number of joinpoints in the final model., Results: Considering all age groups, the incidence rate decreased from 2.02 to 0.55 per 100,000. The join-point analysis showed a statistically significant decrease in the incidence rates of HCV infection. No join-points were found in any age groups. Our data show that the incidence rates of HCV infections have considerably decreased in each age group throughout the studied period (1996-2006)., Conclusions: This decreasing trend in HCV infections is, in part, attributable to behavioral and social changes. Improved hygiene, use of precautions in medical settings, blood screening, and sexual educational campaigns seem to have contributed to reduce the transmission of infection during the last 10 years.

Increasing evidence suggests that physical activity could prevent cancer, but scanty data is available on head and neck cancer (HNC). The aim of our study is to clarify the effect of recreational physical activity (rPA) on HNC. We analyzed data from four case-control studies, including 2,289 HNC cases and 5,580 controls. rPA was classified as: none/low (reference group), moderate and high. We calculated summary Odds Ratios (ORs) by pooling study-specific ORs. Overall, moderate rPA was associated with 22% lower risk of HNC compared to those with none or very low rPA levels [OR = 0.78, 95% Confidence Interval (95% CI): 0.66, 0.91]. Moderate rPA is associated with reduced risk of oral (OR = 0.74, 95% CI: 0.56, 0.97) and pharyngeal cancer (OR = 0.67, 95% CI: 0.53, 0.85), as well as high rPA levels (OR = 0.53, 95% CI: 0.32, 0.88 for oral cavity, OR = 0.58, 95% CI: 0.38, 0.89 for pharynx). High rPA levels, however, is associated with higher risk of laryngeal cancer (OR = 1.73, 95% CI: 1.04, 2.88). Stratified analyses showed that such inverse association between moderate rPA and HNC was more evident among males (OR = 0.75, 95% CI: 0.62, 0.90), subjects ≥45 years (OR = 0.78, 95% CI: 0.66, 0.93), and ever smokers and ever drinkers (OR = 0.72, 95% CI: 0.59, 0.88). High rPA significantly reduces HNC risk among subject ≥45 years (OR = 0.66, 95% CI: 0.48, 0.91). Promoting rPA might be inversely associated with HNC.

Intestinal parasites account for the majority of parasitic diseases, particularly in endemic areas. Most are transmitted via contaminated food. Because of increased immigration and travel, enteric parasitoses are now distributed worldwide. Between May 2006 and December 2008, we examined stool specimens from 5,351 patients (4,695 Italians, 656 non-Italians) for ova and parasites using microscopy, culture techniques, and molecular methods. Stools from 594 patients (11.1%) were contaminated and for all patients samples combined, a total of 700 intestinal parasites were counted. Ninety of the 594 infected patients had more than one parasite in their stools. Parasites causing intestinal disease occurred in 8.8% of patients. The prevalence was over twice as high among non-Italians (26.8% vs 8.9% in Italians, p<0.001) and higher in males (13.0% vs 9.5% in females, p=0.003). Most isolates were pathogenic protozoa, including in decreasing order of frequency: Blastocystis hominis, Giardia intestinalis, Entamoeba histolytica, and Cyclospora cayetanensis. The latter two species tended to be more common in Italians, although not at significant level (3.6% (15/418) vs 1.7% (3/176) in non-Italians, OR: 2.15; 95%CI: 0.60–11.70, p=0.22). Helminthes were found in 28 patients, mainly non-Italians (5.7% (10/176) vs 4.3% (18/418), OR: 1.34; 95%CI: 0.54–3.13, p=0.47). Ascaris lumbricoides and Hymenolepis nana were the most common. Strongyloides stercoralis, Enterobius vermicularis, Taenia spp. and Trichuris trichiura were also found. Intestinal parasites are a serious problem in developing countries, but should not be underestimated in industrialised countries.

Background: The apolipoprotein E gene (apoE) has three major isoforms encoded by the ε2, ε3, and ε4 alleles, with the ε4 allele associated with hypercholesterolemia and the ε2 allele with the opposite effect. An inverse relationship between cholesterolemia and head and neck cancer (HNC) has been previously reported, although the relationship between apoE genotypes and HNC has not been explored to date., Methods: Four hundred and seventeen HNC cases and 436 hospital controls were genotyped for apoE polymorphisms. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) from logistic regression were used to explore the relationship between HNC and putative risk factors. A gene-environment interaction analysis was done., Results: A borderline significant 40% decreased HNC risk (OR, 0.58; 95% CI, 0.31-1.05) was observed for individuals carrying at least one ε2 allele. Females carrying at least one ε2 allele showed a 60% risk reduction (OR, 0.43; 95% CI, 0.21-0.90) for HNC compared with ε3 homozygotes. A statistically significant interaction was found between alcohol use and the ε4 allele (P for interaction = 0.04), with a 2-fold increased risk (OR, 2.06; 95% CI, 0.95-4.48) among ever drinkers with an ε4 allele, with respect to ε3 homozygote nondrinkers., Conclusions: Our study provides novel evidence of a possible protective effect of the ε2 allele against HNC, probably due to its increased antioxidant properties., Impact: According to our results, apolipoprotein E may play a different role in carcinogenesis other than its well-known role in regulating blood serum cholesterol levels., (©2010 AACR.)

Infertility is associated with oxidative stress, normally counterbalanced by different antioxidant systems. In order to explore the hormonal control of seminal plasma total antioxidant capacity (TAC) we evaluated TAC and hormone patterns in a group of unselected infertile patients and control subjects. One hundred and ten infertile patients (divided into 3 groups: inflammation, varicocele, and other etiologies) and 31 fertile men were examined, evaluating blood serum gonadotropins, testosterone, estradiol, free tri-iodothyronine, free tetraiodothyronine (FT4), thyrotropin, prolactin (PRL), seminal parameters, and TAC. TAC was measured using the H(2)O(2)-metmyoglobin system, which generates the spectroscopically detectable radical cation of the chromogenous compound 2,2(I)-azinobis (3-ethylbenzothiazoline-6-sulfonate). The "lag time" of its appearance is proportional to the antioxidant activity. Lag phase was significantly higher in varicocele vs controls, whereas it was lower in patients with inflammation vs varicocele or other kinds of infertility. The correlation analysis between hormones and seminal parameters showed an inverse correlation between PRL and sperm motility, and a direct correlation of TAC with PRL and FT4, but not with gonadotropins or gonadal steroids. Our data suggest that systemic hormones may play a role in regulating seminal antioxidant capacity. This is interesting also because some hormones, such as thyroid and pituitary hormones, are not usually tested in the first-level evaluation of male patients with fertility problems.

Background and Purpose: A systematic review and meta-analysis was performed to assess the impact of radiotherapy on both 3- and 5-year survival in patients with resectable gastric cancer., Methods: Randomized Clinical Trials (RCTs) in which radiotherapy, (preoperative, postoperative and/or intraoperative), was compared with surgery alone or surgery plus chemotherapy in resectable gastric cancer were identified by searching web-based databases and supplemented by manual examination of reference lists. Meta-analysis was performed using Risk Ratios (RRs). Random or fixed effects models were used to combine data. The methodological quality was evaluated by Chalmers' score., Results: Radiotherapy had a significant impact on 5-year survival. Using an intent to treat (ITT) and a Per Protocol (PP) analysis, the overall 5-year RR was 1.26 (95% CI: 1.08-1.48; NNT=17) and 1.31 (95% CI: 1.04-1.66; NNT=13), respectively. Although the quality of the studies was variable, the data were consistent and no clear publication bias was found., Conclusion: This meta-analysis showed a statistically significant 5-year survival benefit with the addition of radiotherapy in patients with resectable gastric cancer. Radiotherapy remains a standard component in the treatment of resectable gastric cancer and new RCTs need to address the impact of new conformal radiotherapy technologies.

Objectives: A meta-analysis of observational studies on association between cigarette smoking and pancreatic cancer was performed to focus, particularly, on the role of the studies' quality in affecting meta-analysis results., Methods: A bibliographic search was carried out on PubMed and EMBASE databases until February 15, 2008. Key words were "pancreatic neoplasms," "pancreatic cancer," "smoking," "smoke," "cigarette," "case-control studies," and "cohort studies." Studies about cigarette smoking and pancreatic cancer were selected and assessed on quality. STATA 9.0 was used., Results: Six cohort studies and 24 case-control studies were selected, with median quality scores of 8 (range, 3) and 10 (range, 8), respectively. Pooled case-control studies' odds ratio (OR) and cohort studies' risk ratio were, respectively, 1.45 (95% confidence interval [CI], 1.33-1.57) and 1.78 (95% CI, 1.64-1.92). After stratifying for quality scoring, high-quality-scored case-control studies yielded an OR of 1.38 (95% CI, 1.27-1.49), whereas the others gave an OR of 1.52 (95% CI, 1.34-1.73). The results of meta-analysis for cohort studies showed a risk ratio of 1.74 (95% CI, 1.61-1.90) and of 2.10 (95% CI, 1.64-2.67), respectively, for high- and low-quality score studies., Conclusions: There is evidence that cigarette smoking is an important risk factor for pancreatic cancer, but the estimate of the association greatly relies on the studies' quality.

Liver transplantation may be performed using extended criteria donor grafts (ECDg). The characteristics of ECDg include age >60 years, long intensive care unit (ICU) stay, history of malignancy or steatosis. Grafts are often discarded due to steatosis, which can be macrovesicular (MaS) or microvesicular (MiS). MaS is the variety most frequently involved with unfavorable outcomes due to primary nonfunction (PNF) or primary dysfunction (PDF). As of January 2000, all livers referred to our institution were considered potentially transplantable. Steatosis was defined as the presence of fat droplets in more than 5% of hepatocytes. We observed 35 steatotic grafts. Grafts were stratified according to MaS and MiS as follows: low steatosis (5%-15%), mild steatosis (16%-30%), moderate steatosis (31%-60%), or severe steatosis (>60%). Fifteen grafts with moderate (n = 2) or severe (n = 13) MaS were discarded. Twenty grafts were harvested: 18 of them were transplanted at our institution, the remaining 2, discarded by our donor team, were transplanted by other Italian centers. Low MaS was detected in 10 grafts (50%), mild MaS in 4 (20%), and moderate MaS in 2 (10%). Low MiS was detected in 8 grafts (40%), mild MiS in 5 (25%), and moderate MiS in 1 (5%). Steatotic grafts were transplanted only into recipients with model for end-stage liver disease (MELD) scores <27. The 6-month graft survival was 80%; the PNF rate was 10%; and the PDF rate was 15%. The careful use of ECDg with low to moderate steatosis is possible if particular care is taken to avoid additional risk factors related to the recipient.

Background: Hepatitis B (HBV) infection is an important cause of morbidity and mortality and it is associated to a higher risk of chronic evolution in infected children. In Italy the anti-HBV vaccination was introduced in 1991 for newborn and twelve years old children. Our study aims to evaluate time trends of HBV incidence rates in order to provide an assessment of compulsory vaccination health impact., Method: Data concerning HBV incidence rates coming from Acute Viral Hepatitis Integrated Epidemiological System (SEIEVA) were collected from 1985 to 2006. SEIEVA is the Italian surveillance national system that registers acute hepatitis cases. Time trends were analysed by joinpoint regression using Joinpoint Regression Program 3.3.1 according to Kim's method. A joinpoint represents the time point when a significant trend change is detected. Time changes are expressed in terms of the Expected Annual Percent Change (EAPC) with 95% confidence interval (95% CI)., Results: The joinpoint analysis showed statistically significant decreasing trends in all age groups. For the age group 0-14 EAPC was -39.0 (95% CI: -59.3; -8.4), in the period up to 1987, and -12.6 (95% CI: -16.0; -9.2) thereafter. EAPCs were -17.9 (95% CI: -18.7; -17.1) and -6.7 (95% CI: -8.0; -5.4) for 15-24 and > or =25 age groups, respectively. Nevertheless no joinpoints were found for age groups 15-24 and > or =25, whereas a joinpoint at year 1987, before compulsory vaccination, was highlighted in 0-14 age group. No joinpoint was observed after 1991., Discussion: Our results suggest that the introduction of compulsory vaccination could have contribute partly in decreasing HBV incidence rates. Compulsory vaccination health impact should be better investigated in future studies to evaluate the need for changes in current vaccination strategy.

Over the past two decades, scientific research has led to the development of a huge number of new health technologies, among which new vaccines. The decision process underlying the introduction of a new vaccine will be of particular concern in the future and a useful tool is needed to orientate decision makers towards better allocation of economic resources. Health Technology Assessment (HTA) is a multidisciplinary tool that aims to examine the clinical, economic, organizational, ethical, juridical, social and cultural implications of the introduction or the implementation of a specific technology; it could so represent an innovative and effective approach in order to support decision-making processes.