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Introduction The longitudinal trajectories of functional brain dynamics and the impact of genetic risk factors in individuals at risk for Alzheimer's disease are poorly understood. Methods In a large-scale monocentric cohort of 224 amyloid stratified individuals at risk for Alzheimer's disease, default mode network (DMN) resting state functional connectivity (FC) was investigated between two serial time points across 2 years. Results Widespread DMN FC changes were shown in frontal and posterior areas, as well as in the right hippocampus. There were no cross-sectional differences, however, apolipoprotein E e4 (APOE e4) carriers demonstrated slower increase in FC in frontal lobes. There was no impact of individual brain amyloid load status. Discussion For the first time, we demonstrated that the pleiotropic biological effect of the APOE e4 allele impacts the dynamic trajectory of the DMN during aging. Dynamic functional biomarkers may become useful surrogate outcomes for the development of preclinical targeted therapeutic interventions.

Background Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer’s disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE ε4 allele, comorbidities, brain amyloid-β (Aβ) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development. Methods Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study). Results We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE ε4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of Aβ deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score. Conclusion We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood.

β-Secretase1 (BACE1) protein concentrations and rates of enzyme activity, analyzed in human bodily fluids, are promising candidate biological markers for guidance in clinical trials investigating BACE1 inhibitors to halt or delay the dysregulation of the amyloid-β pathway in Alzheimer’s disease (AD). A robust body of evidence demonstrates an association between cerebrospinal fluid/blood BACE1 biomarkers and core pathophysiological mechanisms of AD, such as brain protein misfolding and aggregration, neurodegeneration, and synaptic dysfunction.In pharmacological trials, BACE1 candidate biomarkers may be applied to a wide set of contexts of use (CoU), including proof of mechanism, dose-finding, response and toxicity dose estimation. For clinical CoU, BACE1 biomarkers show good performance for prognosis and disease prediction.The roadmap toward validation and qualification of BACE1 biomarkers requires standardized pre-analytical and analytical protocols to reduce inter-site variance that may have contributed to inconsistent results.BACE1 biomarker-drug co-development programs, including biomarker-guided outcomes and endpoints, may support the identification of sub-populations with a higher probability to benefit from BACE1 inhibitors with a reduced risk of adverse effects, in line with the evolving precision medicine paradigm.

Introduction: Successful development of effective beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)-targeted therapies for early stages of Alzheimer's disease requires biomarker-guided intervention strategies. Methods: We investigated whether key biological factors such as sex, apolipoprotein E (APOE epsilon 4) allele, and age affect longitudinal plasma BACE1 concentrations in a large monocenter cohort of individuals at risk for Alzheimer's disease. We explored the relationship between plasma BACE1 concentrations and levels of brain amyloid-beta (A beta) deposition, using positron emission tomography global standard uptake value ratios. Results: Baseline and longitudinal mean concentrations of plasma BACE1 were significantly higher in women than men. We also found a positive significant impact of plasma BACE1 on baseline A beta-positron emission tomography global standard uptake value ratios. Discussion: Our results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain A beta production and deposition. We argue that plasma BACE1 should be considered in further biomarker validation and qualification studies as well as in BACE1 clinical trials. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.

Why Is a research Methods Handbook Needed? Why is this work needed, and who would benefit from it? First of all, we must realize that this work is on a high but at the same time moderate level. The aim is to put together a Research Methods Handbook that can be of practical help to those writing manuscripts for submission to Arthroscopy and similar journals. We are referring to people working full time, taking care of patients, with busy outpatient clinics and fully booked surgical schedules. These are persons who do not devote the majority of their time to research. And in most cases they do not have any major training in scientific research methods. Since sound research methods are the backbone of a good study, the methods must be solid to ensure that the results are valid. If the methods are not good from the beginning, the outcome will not be good either, and the manuscript will not be published despite the investigator's best effort. The purpose of this Research Methods Handbook is to provide basic information about common research techniques, how to conduct a good study, how to write a manuscript and, we hope, how to get it published. The work is divided into several sections, starting with an overview on evidence-based medicine; much-needed information for all clinicians. The second section is concerned with study methods, with special focus on study designs. Important scientific methods, like CONSORT and STROBE, are explained in greater detail. The third section is on biostatistics. This section is very practical, written with the clinician in mind. Common statistical methods are explained and the aim is to stay practical and pragmatic. We are still clinicians and not statisticians. And the idea is to help clinicians who are conducting a study and not to make them statisticians. The last section is on manuscript writing. Pearls and pitfalls are discussed and tips are given. We dare say that if you follow these simple guidelines, you will have a much greater chance of getting your manuscript published. A few words of thanks. First and foremost we thank Michele Johnson, ISAKOS Executive Director, who helped out with all practical details and negotiated all necessary contracts. At Arthroscopy, Managing Editor Hank Hackett and Jason Miller from Elsevier made things happen. Special thanks to Hank for his professional editing work on all chapters, keeping track of the time frame, and all other practical details. This work is an ISAKOS project, done on behalf of the ISAKOS Scientific Committee, and we would like to thank all Committee members, many of them co-authors, for their part in getting this done. Special thanks to Mario Ferretti, Stephan Lyman, Rob LaPrade, Bruce Levy, Nick Mohtadi, Kevin Shea, Michael Soudry, and Stefano Zaffagnini. We also extend our thanks to all other co-authors, with special thanks to Sabine Goldhahn. Mohit Bhandari, one of the greatest clinician researchers we have ever met, deserves special thanks; without his work, this project would never have been possible. Finally, Gary Poehling and James Lubowitz, Editor-in-Chief and Assistant Editor-in-Chief of Arthroscopy, supported the project from the start and shared their knowledge and vast experience in the section on manuscript writing. Thank you both. We hope that the readers of Arthroscopy as well as other journals will benefit from this work.

Background and purposes: To determine the prevalence of SLC2A1 mutations inchildren with early-onset absence epilepsy (EOAE) and to investigate whether therewere differences in demographic and electroclinical data between patients whobecame seizure-free with anti-epileptic drug (AED) monotherapy (group I) andthose who needed add-on treatment of a second AED (group II).Methods: We reviewed children with EOAE attended different Italian epilepsy cen-ters. All participants had onset of absence seizures within the first 3 years of life butotherwise conformed to a strict definition of childhood absence epilepsy. Mutationanalysis of SLC2A1 was performed in each patient.Results: Eighty-four children (57 in group I, 27 in group II) fulfilled the inclusioncriteria. No mutation in SLC2A1 was found. There were no statistical differencesbetween the two groups with regard to F/M ratio, age at onset of EOAE, early his-tory of febrile seizures, first-degree family history for genetic generalized epilepsy,duration of AED therapy at 3 years after enrollment, use of AEDs at 3 years, failedwithdrawals at 3 years, terminal remission of EOAE at 3 years, and 6-month fol-low-up EEG data. Mean duration of seizures/active epilepsy was significantlyshorter in group I than in group II (P = 0.008).Conclusions: We demonstrate that in a large series of children with rigorous diag-nosis of EOAE, no mutations in SLC2A1 gene are detected. Except for duration ofseizures/active epilepsy, no significant differences in demographic and electroclinicalaspects are observed between children with EOAE who responded well to AEDmonotherapy and those who became seizure-free with add-on treatment of a secondAED.

SUMMARY BACKGROUND: More and more people with severe hemophilia reach an old age thanks to an effective treatment. There is no information on the health status and quality of life of elderly people with hemophilia born at a time when replacement therapy was hardly available. METHODS: Italian patients with severe hemophilia, aged >or=65 years and hence born in 1942 or earlier, were compared with elderly men without bleeding disorders matched for age, sex, geography and social status. The following aspects were evaluated: concomitant illness, orthopedic status, physical functioning and cognitive status. Measurements of generic and disease-specific health-related quality of life were also obtained, together with the presence or absence of depression. RESULTS: Thirty-nine patients, aged 65-78 years, were investigated; 33 had hemophilia A. All patients had started regular treatment on demand only when they were already 25-30 years of age. Patients were compared with 43 men without hemophilia, aged 65-79 years. More patients with hemophilia had chronic hepatitis B and C, HIV infection and hypertension. On the other hand, their elderly peers without hemophilia were more frequently hypercholesterolemic and had more cardiovascular diseases. Most hemophiliacs had arthropathy and worse values for physical functioning, but their cognitive status was similar to that of elderly non-hemophiliacs. Hemophiliacs reported greater depression and lower health-related quality of life. CONCLUSIONS: Elderly patients with hemophilia have more co-morbidities and problems in daily living, but similar cognitive status as age-matched non-hemophilic peers. They have more chronic viral infections and hypertension but fewer cardiovascular diseases. These observations should help to optimize health care delivery in this increasing and neglected population of people with hemophilia.

Malignancies, antiproliferative drug treatment, cancer-related conditions like immobilization, perioperative status and radiotherapy are risk factors for hypercoagulability. Setting aside mass or invasion-related venous thrombosis, the differential diagnosis regarding the etiopathogenesis (paraneoplastic syndrome or antiproliferative treatment) is usually problematic. The authors report a case of combined malignant hemangiopericytoma and recurrent deep venous thrombosis in the right inferior limb. Through a literature review, the following issues are discussed: 1) the criteria for cyto-histopathologic assessment; 2) the involvement of pericytes both in coagulation and platelet aggregation; 3) the importance of discriminating true paraneoplastic syndromes from other tumor-related clinical manifestations; 4) the response to external radiotherapy of malignant hemangiopericytoma as limited disease; 5) the poor results of doxorubicin-ifosfamide polychemotherapy and dacarbazine monochemotherapy in metastatic disease. Although doxorubicin-ifosfamide treatment was in progress in the reported case, the authors conclude that the recurrent deep venous thrombosis is likely to be paraneoplastic, even if such a diagnosis has not been previously reported in the literature.

Background Depression is a frequently observed and disabling condition in primary care, mainly treated by Primary Care Physicians with antidepressant drugs. Psychological interventions are recommended as first-line treatment by the most authoritative international guidelines but few evidences are available on their efficacy and effectiveness for mild depression. Methods/Design This multi-center randomized controlled trial was conducted in 9 Italian centres with the aim to compare the efficacy of Inter-Personal Counseling, a brief structured psychological intervention, to that of Selective Serotonin Reuptake Inhibitors. Patients with depressive symptoms referred by Primary Care Physicians to psychiatric consultation-liaison services were eligible for the study if they met the DSM-IV criteria for major depression, had a score ≥13 on the 21-item Hamilton Depression Rating Scale, and were at their first or second depressive episode. The primary outcome was remission of depressive symptoms at 2-months, defined as a HDRS score ≤ 7. Secondary outcome measures were improvement in global functioning and recurrence of depressive symptoms at 12-months. Patients who did not respond to Inter-Personal Counseling or Selective Serotonin Reuptake Inhibitors at 2-months received augmentation with the other treatment. Discussion This trial addresses some of the shortcomings of existing trials targeting major depression in primary care by evaluating the comparative efficacy of a brief psychological intervention that could be easily disseminated, by including a sample of patients with mild/moderate depression and by using different outcome measures. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12608000479303

This work assesses the factors affecting a firm’s adoption of the Internet of Things (IoT) in the transport and logistics (T&L) industry. This study uses mixed methods research to explore the determinants of IoT. First, we gathered information on firms’ structural characteristics through a questionnaire. Then, we used an OLS regression analysis to determine which factors drive IoT adoption. The results suggested that the level of IoT technologies’ adoption within firms in T&L is positively affected by firm size, the firm’s absorptive capacity, and entrepreneurs’ perception of the benefits of related technologies. Implications and limitations of the study are also provided.

Background - Antineutrophil cytoplasmic antibodies (ANCAs) from patients with vasculitidis can induce neutrophils to release oxygen radicals in vitro. ANCAs with a perinuclear pattern of immunofluorescence are found in most patients with ulcerative colitis, but several findings are against ANCAs having a pathogenetic role in this disease. Aims - To evaluate the influence of ANCAs associated with ulcerative colitis on the respiratory burst activity of neutrophils. Patients - Serum samples were obtained from 14 patients with ulcerative colitis, seven of whom showed positivity for p-ANCAs, three patients with vasculitidis, two with positivity for p-ANCAs, and one for c-ANCAs, and seven healthy volunteers. Methods - A positive ANCA serology was determined with a standard indirect immunofluroescence assay. Purified immunoglobulins (IgGs) were prepared from serum samples by DEAE-Affigel blue chromatography. Human neutrophils were prepared by dextran-Ficoll-Hypaque separation. Superoxide anion (O2-. generation was measured by following the superoxide dismutase inhibitable reduction of ferricytochrome. Results - There were no significant differences among samples from ulcerative colitis IgG p-ANCA positive, ulcerative colitis IgG p-ANCA negative patients, and controls on O2-6. production, whereas ANCA positive IgG from vasculitidis significantly enhanced O2-. release (p < 0.001). Conclusions - p-ANCAs associated with ulcerative colitis have no effect on the respiratory burst activity of normal human neutrophils in vitro. These results reinforce the hypotheses that ANCAs are unlikely to contribute to the pathogenesis of ulcerative colitis.

PurposeA stringent outcome assessment is a key aspect for establishing evidence-based clinical guidelines for anterior cruciate ligament (ACL) injury treatment. The aim of this consensus statement was to establish what data should be reported when conducting an ACL outcome study, what specific outcome measurements should be used and at what follow-up time those outcomes should be assessed.MethodsTo establish a standardized approach to assessment of clinical outcome after ACL treatment, a consensus meeting including a multidisciplinary group of ACL experts was held at the ACL Consensus Meeting Panther Symposium, Pittsburgh, PA; USA, in June 2019. The group reached consensus on nine statements by using a modified Delphi method.ResultsIn general, outcomes after ACL treatment can be divided into four robust categories—early adverse events, patient-reported outcomes, ACL graft failure/recurrent ligament disruption and clinical measures of knee function and structure. A comprehensive assessment following ACL treatment should aim to provide a complete overview of the treatment result, optimally including the various aspects of outcome categories. For most research questions, a minimum follow-up of 2 years with an optimal follow-up rate of 80% is necessary to achieve a comprehensive assessment. This should include clinical examination, any sustained re-injuries, validated knee-specific PROs and Health-Related Quality of Life questionnaires. In the mid- to long-term follow-up, the presence of osteoarthritis should be evaluated.ConclusionThis consensus paper provides practical guidelines for how the aforementioned entities of outcomes should be reported and suggests the preferred tools for a reliable and valid assessment of outcome after ACL treatment.Level of evidenceV.

Social media are nowadays used by people to talk about any kind of topic, either private or not, and among others health problems. Concerning health, on social media one can find large communities discussing about chronic diseases. Here people look for advise, information, support, and so on. In this paper we take into consideration the Italian Twitter community interested in diabetes, a chronic blood disease. Our aim is to understand which are the main conversation topics in this community. Thus, we analyzed about 9K tweets written in Italian that contained the world {\em diabete} (diabetes) and performed both a hashtag analysis and a lexicon analysis, the latter by means of ad-hoc dictionaries. Results show that this is a calm community interested into several distinct topics (e.g., disease related information gathering, recipes for diabetes patients, fundraising campaigns), none of which is really predominant over the others.

Introduction Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. Methods The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). Results We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau 181 concentrations. Discussion Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.

POI is a relevant late complication after HSCT and occurring more frequently after MAC than after RIC regimens. Reports on the frequency of POI after RIC in a large pediatric and adolescent population are lacking. In this study, we describe a girl affected by CML diagnosed at the age of 15 yr and treated with oncarbide and interferon followed by imatinib and dasatinib. She had two pregnancies shortly after RIC performed according to the CML-SCT I-BFM protocol including TT, FLU, and MEL. Hypergonadotropic hypogonadism occurred four months after HSCT; menstruations resumed regularly six months after HSCT. Eight and 20 months after HSCT, the patient became pregnant and then delivered, respectively, two babies at term by cesarean section. Both newborns had no neonatal complications. Donor chimerism at time of two pregnancies and five yr after transplantation demonstrated complete donor engraftment. These findings suggest that I-BFM CML-SCT protocol could be a promising treatment option for adolescents or young adults with CML eligible for HSCT.

Alternative bearing surfaces for total hip arthroplasty, such as metal-on-metal and ceramic-on-ceramic, offer the potential to reduce mechanical wear and osteolysis. In the short and medium term, the second generation of metal-on-metal bearings demonstrated high systemic metal ion levels, whereas ceramic-on-ceramic bearings showed the lowest ones. We aimed to verify whether the long-term ion release in metal-on-metal subjects was still relevant at a median 10-year follow-up, and whether a fretting process at the modular junctions occurred in ceramic-on-ceramic patients and induced an ion dissemination. Serum levels were measured in 32 patients with alumina-on-alumina implants (group A), in 16 subjects with metal-on-metal implants (group B), and in 47 healthy subjects (group C). Group B results were compared with medium-term findings. Cobalt and chromium levels were significantly higher in metal-on-metal implants than in ceramic-on-ceramic ones and controls. Nevertheless, ion levels showed a tendency to decrease in comparison with medium-term content. In ceramic-on-ceramic implants, ion values were not significantly different from controls. Both in groups A and B, aluminum and titanium release were not significantly different from controls. In conclusion, negligible serum metal ion content was revealed in ceramic-on-ceramic patients. On the contrary, due to the higher ion release, metal-on-metal coupling must be prudently considered, especially in young patients, in order to obtain definitive conclusions.

International audience; Key messageFew integration steps (adding low-cost ozone measurements, link to existing conventional monitors, joint data processing) transformed the traditional forest monitoring network into a multifunctional infrastructure producing information relevant for estimating risk to vegetation and human health Context Traditionally, forest monitoring networks have been designed to assess status and trends of forest condition. We argue that they can help providing answers to a much broader range of questions for science, policy, and society. Here, we concentrate on the example of ground-level ozone pollution. Aims The aim of this study is to demonstrate the value of present forest monitoring networks as infrastructures that—with few integration steps—can provide important data and information to estimate the risk posed by ground-level ozone to vegetation and human health. Methods We measured ozone concentration by passive samplers at the local (Trentino, northern Italy) plots of the ICP Forests Level I network over the period 2007–2011. By integrating these data with those from conventional ozone monitors (mostly located in urban areas), we (i) obtained an even distribution of air quality measurements over the investigated area, (ii) estimated international exposure indicators for vegetation and human population, and (iii) obtained data allowing geostatistical modeling and mapping of ozone concentrations, exposure, and associated potential risk.Results Mean May–July ozone concentration ranged from 58 to 169 μg m−3, depending on forest site and year. Modeling and mapping (root-mean-square deviation (RMSD) = 12.31 μg m−3) provided evidence that the risk threshold for vegetation in terms of AOT40 was exceeded in large parts (90 %) of the study area, and frequently even by two times, depending on the year. With respect to population, up to 43 % of the dwellers were exposed to medium–high risk of exceedances of the information threshold. Conclusion Ozone measurements carried out at the ICP Forests Level I forest monitoring network permitted mapping ozone levels and the estimation of possible risk for vegetation and human health. Forest monitoring networks can be seen as infrastructures that can be useful to address a wide range of environmental issues and with a much broader scope than their original one.

Simultaneous assessment of epiphytic lichen diversity by teams from six European countries, following the procedures defined in the recently adopted European standard, revealed several sources of error (e.g. location of plot, selection of trees, identification of taxa). Routine training and further improvement of Standard Operating Procedures (SOPs) are suggested to boost the harmonization process of the European guidelines, which promises to be an effective tool for standardizing the assessment of lichen diversity. © 2014 Elsevier Ltd.

PURPOSE: The aim of our study was to compare the efficacy and safety of oral mesalazine with mesalazine suppositories in patients with active ulcerative proctitis. PATIENTS AND METHODS: A four-week, randomized, single- blind trial was performed in 58 patients with active, histologically confirmed ulcerative proctitis (≤ 15 cm) to evaluate the efficacy and safety of oral 800-mg mesalazine tablets taken three times per day (n = 29) compared with 400 mg of mesalazine suppositories administered three times per day (n = 29). Patients were evaluated at study entry and after two and four weeks. Efficacy evaluations included a disease activity index, which represents a score with four variables: stools frequency, rectal bleeding, mucosal appearance, and physician's assessment of disease severity. Histologic activity was also assessed at study entry and after two and four weeks in accordance with the criteria by Truelove and Richard. Safety assessment included clinical laboratory parameters and adverse event reports. RESULTS: There were no significant differences with regard to baseline comparisons of demographics and severity between the two treatment groups. Improvement in mean disease activity index score was significantly greater with suppositories compared with oral mesalazine, both at two-week and four-week visits (mean disease activity index scores at baseline, two, and four weeks: suppositories = 7.7, 2.59, and 1.48; tablets = 7.42, 5.72, and 3.48, respectively (P < 0.001)). The rate of histologic remission was significantly greater with suppositories compared with tablets both at two and four weeks (P < 0.01). There were no significant differences in adverse events or clinical laboratory results between treatment groups. CONCLUSIONS: Results of this study indicate that treatment with mesalazine suppositories produces earlier and significantly better results than oral mesalazine in the treatment of active ulcerative proctitis.

Background: Mucosal inflammation of the ileal pouch (pouchitis) is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. Broad-spectrum antibiotics are the mainstay of treatment, however, 15% of patients with pouchitis have a chronic, treatment-resistant disease. Aim: To determine the safety and efficacy of bismuth carbomer enemas in achieving and maintaining remission in treatment-resistant chronic pouchitis. Methods: Twelve patients with treatment-resistant chronic pouchitis were treated nightly for 45 days with enemas containing elemental bismuth complexed with carbomer. Diagnosis of pouchitis and response to treatment were evaluated with the Pouchitis Disease Activity Index (PDAI), which includes clinical, sigmoidoscopic and histological criteria. Serum bismuth concentrations were determined by atomic absorption. Results: Ten of 12 patients (83%) went into remission, with a significant decrease of mean total PDAI score from 12 (range 9–15) to 6 (4–15) (P

Background: Rectal treatment with mesalazine enemas is the first-line therapy for distal ulcerative colitis. In order to improve the benefits of rectal therapy, a new 60 mL 5-ASA rectal gel enema preparation has been developed using a device which excludes direct contact of the inert propellant gas with the active drug. The purpose of the present study was to assess by scintigraphy the colonic distribution of this new mesalazine rectal gel enema. Methods: Twelve patients with active ulcerative colitis were administered 4 g of the mesalazine rectal enema labelled with 100 MBq technetium sulphur colloid (99mTc-SC). Anterior scans of the abdomen were acquired at intervals for 4 h. Scans were analysed to evaluate the extent of retrograde flow and homogeneity of distribution of the radiolabelled enema in the rectum, sigmoid, descending and transverse colon. In addition, plasma levels of 5-ASA and Ac-5-ASA were measured for 6 h. Results: All patients retained the entire rectal gel throughout the course of the study without reporting adverse events. In 11 out of 12 patients (92%) the gel had spread homogeneously beyond the sigmoid colon and had reached the upper limit of disease in all cases. The maximum spread (splenic flexure) was observed in 6 out of 12 patients (50%) within the first 2 h. The systemic absorption of mesalazine and its metabolite Ac-5-ASA was low. Conclusions: The new mesalazine enema represents an adequate alternative and a further technological improvement in the topical treatment of distal ulcerative colitis.

Background Several guidelines on adeno-tonsillar disease have been proposed in recent years and some discrepancies in relation both to clinical manifestations and indications for surgical treatment have emerged. The aim of the study was to verify what influence (adeno)-tonsillectomy guidelines have had on the clinical behaviour of ENT specialists in Italy. Our study is a retrospective and multi-centre case series with chart review. Methods The survey involved 14,770 children, aged between the ages of 2 and 11, who had undergone adeno-tonsillar surgery between 2002 and 2008 in fourteen Italian tertiary and secondary referral centres. Anova test was used for the statistical analysis, assuming p < 0.05 as the minimum statistical significance value. Results The frequency of adeno-tonsillar surgeries did not change significantly (p>0.05) during the study period and following the Italian policy document publication. Overall, adeno-tonsillectomy was the most frequent intervention (64.1%), followed by adenoidectomy (31.1%) and tonsillectomy (4.8%). The indications for surgery did not change significantly for each of the operations (p>0.05), with the exception of adeno-tonsillectomy in case of feverish episodes due to acute recurrent tonsillitis ≥ 5 without nasal obstruction (decreased p= 0.010) , even when the feverish episodes due to acute recurrent tonsillitis were < 5 over the last year. Nasal obstruction was associated with feverish episodes due to acute recurrent tonsillitis in 65.2% of operated cases, while otitis media had been diagnosed in 43.3% of the patients studied. Conclusions The recommendations first developed in Italy in a 2003 policy document and then resumed in guidelines in 2008, were not implemented by ENT units involved in the survey. The study highlights the fact that the indications for adeno-tonsillar operations are based on the overall clinical presentation (comorbidity) rather than on a single symptom. Guidelines are necessary to give coherent recommendations based on both the findings obtained through randomized controlled trials and the data collected from observational studies.

Epiphytic lichens have long been used as ecological indicators. Lichen biomonitoring surveys were carried out by five experienced teams and the results compared across the entire process, from sampling design planning to species counting. The five teams received the same background information and worked in parallel but independently in the same area. European standard operating procedures (SOPs), which are still in preparation, were followed in order to identify possible critical issues and improve consistency. Five exercises with progressive reduction in the degree of operational freedom were carried out by the teams. The results revealed differences between teams on each exercise and showed that investigations run by different teams in the same area and at the same time may not be entirely comparable. This was partly due to inherent differences between crews (skills, familiarity with local flora, and accuracy in applying SOPs), partly to ambiguities in the SOPs, and partly to insufficient training with the SOPs. The results may be valuable in improving biomonitoring procedures and in achieving high-quality, consistent lichen diversity data. © 2012 Elsevier Ltd.

Concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were determined by solid-phase ELISA in tissue homogenates of mucosal biopsy specimens obtained from pelvic ileal pouches in 13 patients with pouchitis (reservoir ileitis) and 17 with pouches without pouchitis. Normal ileal mucosa was used as a control. IL-1β was detected in all tissue homogenates from patients with pouchitis compared with only 29% from pouches without pouchitis and none from controls. IL-6 and IL-8 were present in all pouchitis specimens, in 70% of the specimens from nonpouchitis and only 30% of specimens from controls. TNF-α was undetectable in all specimens examined. The concentrations of IL-1β, IL-6, and IL-8 were significantly greater (P

The aim of this study was to investigate the suitability of the North Star Ambulatory Assessment as a possible outcome measure in multicentric clinical trials. More specifically we wished to investigate the level of training needed for achieving a good interobserver reliability in a multicentric setting. The scale was specifically designed for ambulant children with Duchenne Muscular Dystrophy and includes 17 items that are relevant for this cohort. Thirteen Italian centers participated in the study. In the first phase of the study we provided two training videos and an example of the scale performed on a child. After the first session of training, all the 13 examiners were asked to send a video with an assessment performed in their centre and to score all the videos collected. There were no difficulties in performing the items and in obtaining adequate videos with a hand held camera but the results showed a poor interobserver reliability (

The finding of thyroid nodules is a very common occurrence in routine clinical practice. Approximately 5% to 7% of the entire population have thyroid nodules. Vascular lesions are one of the most controversial issues in thyroid pathology. These include benign lesions such as hemangiomas and, rarely, malignant tumors such as angiosarcomas or undifferentiated angiosarcomatoid carcinomas. In particular, angiosarcoma of the thyroid gland is a rare, highly aggressive malignant vascular tumor and in Italy the greatest geographical incidence of this lesion is witnessed near the Alps. Here, a case of thyroid angiosarcoma in a 71-year-old man with a history of goiter for about 20 years is described. The unusual localization of this lesion, the difficulties in reaching a definitive diagnosis for this particular histological type of primary tumor and a history of long-standing multinodular goiter in thyroid of an older man from outside the Alpine region prompted us to report this case of thyroid angiosarcoma mainly to discuss surgical, histopathological and immunohistochemical features.

The activation of circulating polymorphonuclear leukocytes was determined in terms of superoxide radical generation and granulocyte elastase release in untreated patients with ulcerative colitis (N=10) and Crohn's disease (N=9) in remission and in control subjects (N=10). Superoxide radical generation was determined by monitoring spectro-photometrically the reduction of ferricytochrome, after stimulation of cells with phorbol myristate acetate. Plasma elastase concentration was measured by a solid-phase enzyme immunoassay technique as the complex with alpha-1-proteinase inhibitor. Superoxide formation by polymorphonuclear leukocytes from patients with ulcerative colitis and Crohn's disease was significantly lower compared with controls [median (range) nmol/min/mg protein: Crohn's disease 7.8 (7.1-9.6); ulcerative colitis 8.25 (7.4-10.3); controls 14.7 (13.6-15.8)] (P < 0.001), while no difference was found between the two groups of patients. In contrast plasma elastase levels in patients with ulcerative colitis and Crohn's disease were similar to that of controls. This defective respiratory burst of polymorphonuclear leukocytes in patients with inflammatory bowel disease in remission, in absence of an altered degranulation, could represent an important factor for the pathogenesis of these diseases. © 1994 Plenum Publishing Corporation.

Background: Mesalazine suppositories at 500 mg b.d. are a safe and effective treatment for patients with ulcerative proctitis or distal proctosigmoiditis. Recently a mesalazine 1 g suppository (Pentasa) has been developed. Methods: Fifty patients with active ulcerative colitis extending not beyond 20 cm from the anus on sigmoidoscopy, participated in a randomized single-blind study comparing the efficacy, tolerance and acceptance of the new Pentasa mesalazine 1 g suppository, given once daily versus Claversal mesalazine 500 mg suppository b.d. Results: After 2 weeks, clinical remission was observed in 16 of 25 (64%) in the Pentasa group and in 7 of 25 (28%) in the Claversal 500 mg b.d. treated group; sigmoidoscopic remission occurred in 13 of 25 (52%) in the Pentasa group and in six of 25 (24%) in the Claversal group (P