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Neuroinflammation is the earliest stage of several neurological and neurodegenerative diseases. In the case of neurodegenerative disorders, it takes place about 15-20 years before the appearance of specific neurodegenerative clinical symptoms. Constitutive microglial COX-1 is one of the pro-inflammatory players of the neuroinflammation. Novel compounds 3, 14 and 15 (Galmof 0 , Galmof 5 and Galmof 11 , respectively) were projected, and their synthetic methodologies developed, by linking by an ester bond, directly or through a C5 or C11 unit linker the highly selective COX-1 inhibitor mofezolac (COXs selectivity index > 6000) to galactose in order to obtain substances capable to cross blood-brain barrier (BBB) and control the CNS inflammatory response. 3, 14 and 15 (Galmofs) were prepared in good to fair yields. Galmof 0 (3) was found to be a selective COX-1 inhibitor (COX-1 IC 50  = 0.27 μM and COX-2 IC 50  = 3.1 μM, selectivity index = 11.5), chemically and metabolically stable, and capable to cross Caco-2 cell monolayer, resembling BBB, probing that its transport is GLUT-1-mediated. Furthermore, Galmof 0 (3) powerfully inhibits PGE 2 release higher than mofezolac (1) in LPS-stimulated mouse BV2 microglial cell line, a worldwide recognized neuroinflammation model. In addition, Fingerprints for Ligands and Proteins (FLAP) was used to explain the different binding interactions of Galmofs with the COX-1 active site., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Introduction: Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disorder of the brain and spinal cord characterized by inflammation, demyelination, and axonal degeneration. Area covered: Even though the pharmacological armamentarium for MS treatment is considerably improved in the last 20 years, safety data especially for the second-line and innovative treatments are lacking. In order to analyze the safety profile of drugs used for the treatment of MS, a literature review of pre-marketing, post-marketing studies and case reports was performed. Expert opinion: Nowadays, the numerous drugs approved in the last years for the treatment of MS allow a better control of the disease and a better patient compliance. The main advantages of the new disease-modifying agents for MS (DMTs), in fact, derive from the new oral administration and the prolonged half-life with consequent improvement in compliance compared to first-line therapy which required subcutaneous administrations. However, DMTs can cause serious, sometimes life-threatening or fatal, drug adverse reactions. Due to the lack of safety data and given the recent marketing approval of the last DMTs for MS, observational studies and post-marketing surveillance activities will be necessary in order to improve the knowledge about the safety profile of these drugs and the improvement of their use in clinical practice.

Introduction: With the aim to reduce inappropriate procedures and antibiotic therapy in the management of acute otitis media (AOM) in children, the Italian Society of Preventive and Social Pediatrics (SIPPS) proposed a top five list of recommendations for clinical practice. Areas covered: AOM is one of the most frequent reasons for antibiotic prescription in pediatric age. The over-estimation of AOM is associated with inappropriate treatment, increased costs, adverse events and spread of antibiotic resistance. Thus, the most recent guidelines provided stringent diagnostic criteria and considered the 'watchful waiting' approach, limiting the immediate antibiotic therapy to a well-characterized subgroup of children. Expert commentary: The five recommendations proposed are: 1) Do not diagnose AOM without having documented the presence of middle ear effusion 2) Do not diagnose AOM without examining the entire tympanic membrane; 3) Do not treat immediately all cases of AOM with antibiotics; 4) Do not administer ear analgesic drops until examining the whole tympanic membrane 5) Do not use macrolides in the AOM therapy. This list of top five recommendations could be a novel tool to spread the key messages on the guidelines and to promote the correct diagnostic procedures as well as a rational use of antibiotics in children.

The diarylisoxazole molecular scaffold is found in several NSAIDs, especially those with high selectivity for COX-1. Here, we have determined the structural basis for COX-1 binding to two diarylisoxazoles: mofezolac, which is polar and ionizable, and 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6) that has very low polarity. X-ray analysis of the crystal structures of COX-1 bound to mofezolac and 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole allowed the identification of specific binding determinants within the enzyme active site, relevant to generate structure/activity relationships for diarylisoxazole NSAIDs., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Polymer-based nanodiscs are valuable tools in biomedical research that can offer a detergent-free solubilization of membrane proteins maintaining their native lipid environment. Herein, we introduce a novel ca. 1.6 kDa SMA-based polymer with styrene:maleic acid moieties that can form nanodiscs containing a planar lipid bilayer which are useful to reconstitute membrane proteins for structural and functional studies. The physicochemical properties and the mechanism of formation of polymer-based nanodiscs are characterized by light scattering, NMR, FT-IR, and TEM. A remarkable feature is that nanodiscs of different sizes, from nanometer to sub-micrometer diameter, can be produced by varying the lipid-to-polymer ratio. The small-size nanodiscs (up to ca. 30 nm diameter) can be used for solution NMR spectroscopy studies whereas the magnetic-alignment of macro-nanodiscs (diameter of > ca. 40 nm) can be exploited for solid-state NMR studies on membrane proteins., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: To investigate the occurrence of adverse events (AEs) in naïve patients receiving biotech drugs. Design: A prospective observational study. Setting: Onco-hematology, Hepato-gastroenterology, Rheumatology, Dermatology, and Neurology Units in Campania Region (Italy). Participants: 775 patients (53.81% female) with mean age 56.0 (SD 15.2). The mean follow-up/patient was 3.48 (95% confidence interval 3.13-3.84). Main outcome measures: We collected all AEs associated to biotech drugs, including serious infections and malignancies. Serious AEs were defined according to the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, clinical safety data management: definitions and standards for expedited reporting E2A guideline. Results: The majority of the study population was enrolled in Onco-hematology and Rheumatology Units and the most common diagnosis were hematological malignancies, followed by rheumatoid arthritis, colorectal cancer, breast cancer, and psoriatic arthritis. The most commonly prescribed biotech drugs were rituximab, bevacizumab, infliximab, trastuzumab, adalimumab, and cetuximab. Out of 775 patients, 320 experienced at least one AE. Most of patients experienced AEs to cetuximab therapy, rituximab and trastuzumab. Comparing female and male population, our findings highlighted a statistically significant difference in terms of AEs for adalimumab (35.90% vs. 7.41%, p < 0.001) and etanercept (27.59% vs. 10.00%, p = 0.023). Considering all biotech drugs, we observed a peak for all AEs occurrence at follow-up 91-180 days category. Bevacizumab, brentuximab, rituximab, trastuzumab and cetuximab were more commonly associated to serious adverse events; most of these were possibly related to biotech drugs, according to causality assessment. Three cases of serious infections occurred. Conclusions: The results of our study demonstrated that the majority of AEs were not serious and expected. Few cases of serious infections occurred, while no case of malignancy did. Overall, the safety profile of biotech drugs used in our population was similar to those observed in pivotal trials. Notwithstanding the positive results of our study, some safety concerns still remain unresolved. In order to collect more effectiveness and safety data on biotech drugs, the collection and analysis of real world data should be endorsed as well as the management of post-authorization studies.

Causality assessment is a fundamental biomedical technique for the signal detection performed by Pharmacovigilance centers in a Spontaneous reporting system. Moreover, it is a crucial and important practice for detecting preventable adverse drug reactions. Among different methods for causality assessment, algorithms (such as the Naranjo, or Begaud Methods) seem for their operational procedure and easier applicability one of the most commonly used methods. With the upcoming of the new European Pharmacovigilance legislation including in the definition of the adverse event also effects resulting from abuse, misuse and medication error, all well-known preventable causes of ADRs, there was an emerging need to evaluate whether algorithms could fulfill this new definition. In this review, twenty-two algorithmic methods were identified and none of them seemed to fulfill perfectly the new criteria of adverse event although some of them come close. In fact, several issues were arisen in applying causality assessment algorithms to these new definitions as for example the impossibility to answer the rechallenge question in case of medication error or AEFI (Adverse Event Following Immunization). Moreover, the exact conditions at which events occurred, as for example dosage or mode of administration should be considered to better assess causality in conditions of abuse/overdose, or misuse as well as in conditions of lack of expected efficacy reports for biotechnological drugs and adverse event occurring after mixing of vaccines. Therefore, this review highlights the need of updating algorithmic methods to allow a perfect applicability in all possible clinical scenarios accordingly or not with the terms of marketing authorization., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The preparation of substituted aminooxazoles and aminoimidazoles from α-arylamides and α-aminoamides through triflic anhydride-mediated amide activation is reported. These reactions proceed via the intermediacy of nitrilium adducts and feature N-oxide-promoted umpolung of the α-position of amides as well as a mechanistically intriguing sequence that results in sulfonyl migration from nitrogen to carbon. Quantum-chemical mechanistic analysis sheds light on the intricacies of the process.

Purpose: This study aims to investigate preventability criteria of adverse drug reactions (ADRs) involving non-steroidal anti-inflammatory drugs (NSAIDs) by analyzing individual case safety reports (ICSRs) sent through Campania region (Italy) spontaneous reporting system from July 2012 to October 2016. Methods: For all the ICSRs that reported NSAIDs as suspected drug, a trained multidisciplinary team of Campania Pharmacovigilance Regional Centre composed of clinical pharmacologists and pharmacists with pluriannual experience in Pharmacovigilance assessed preventability by using the P-method. Results: In all 19,039 ICSRs were sent to Campania Pharmacovigilance Regional Centre, of which 550 reported NSAIDs as suspected drug. In total, 94 cases (17.1%) out of 550 ICSRs were preventable. In the 94 preventable cases, 201 critical criteria were detected of which 182/201 (90.5%) related to healthcare professionals' practices, 0/201 (0.0%) to drug quality, and 19/201 (9.5%) to patient behavior. The most detected critical criteria were the necessary medication not given (52/182; 28.6%), labeled drug-drug interaction (36/182; 19.7%), incorrect drug administration duration (31/182; 16.9%), wrong indication (26/182; 14.2%), therapeutic duplication (18/182; 10.0%), and documented hypersensitivity to administered drug or drug class (10/182; 5.6%). In seventeen (18.1%) preventable cases, there were 19 critical criteria involving non-compliance (15/19 critical criteria; 78.9%) and self-medication with the non-over-the-counter drugs (4/19 critical criteria; 21.1%). In all, 17 out 94 (18.1%) preventable cases involved over-the-counter drugs. Conclusion: A call for action for Campania Pharmacovigilance Regional Centre is necessary in order to promote initiatives to increase the awareness of healthcare professionals and citizens on the risk associated with inappropriate use of NSAIDs.

Purpose: With the aim to reduce waste in the health care system and avoid risks associated with unnecessary treatment, the Italian Panel of the National Guidelines for the Management of Acute Pharyngitis in Children joined the Choosing Wisely initiative., Methods: An ad hoc Choosing Wisely task force was selected to develop a candidate list of items for the top-5 list on pharyngitis medicine. Through a process of literature review and consensus, the final list of 5 items was chosen. Drafted recommendations were formulated and then reviewed by the task force members until a final consensus was reached., Findings: The 5 recommendations approved are: blood exams should not be performed; antibiotics should not be administrated unless microbiologic confirmation of streptococcal infection has been carried out; if a throat culture is performed, susceptibility tests on isolates should not be executed; antibiotic course should not be shortened; because penicillin V is not available in Italy, amoxicillin (50 mg/kg/d in 2-3 doses orally) for 10 days is the first choice treatment; and steroids should not be administered for the risk of masking possible underlying severe condition., Implications: This top-5 list can be a novel tool to spread the key messages of guidelines and to avoid unnecessary diagnostic procedures, and to promote a rational use of antibiotics in children., (Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.)

Background: Sleep in childhood and adolescence is crucial for mental and physical health; however several researches reported an increasing trend towards a sleep deprivation in this age. Due to the lack of recent epidemiological studies in Italy, the aim of our study was to depict sleep habits and patterns in Italian children aged 1-14 years and to evaluate their relationships with video devices use (TV, tablet, smartphone, PC) and evening/night child activities., Methods: A structured interview was conducted during 2015 by 72 Family Pediatricians in 2030 healthy children aged 1-14 years by a cross-sectional survey named "Ci piace sognare". Total sleep duration was calculated, 2015 National Sleep Foundation Recommendations were used as reference. Optimal sleepers were defined children sleeping in own bed all night without awakenings. Multivariable median regression was performed to identify predictors of sleep duration and multivariable logistic regression for predictors of optimal sleep., Results: Total sleep duration and numbers of awakenings decreased with age. Only 66.9% of children had sleep duration in agreement with Recommendations (50% in 10-14 years group). Before sleeping 63.5% of children used video devices (39.6% at 1-3 years), 39.1% read, 27.5% drank and 19.5% ate. Bottle users at bedtime were 30.8% at 1-3 years, 16.6% at 3-5 years and 4.9% at 5-7 years. Overall, 23.4% of children changed sleeping place during the night, 22.4% referred sleeping problems in the first year of life. Video devices use was negative predictor of sleep duration (-0.25 h [95%CI:-0.35,-0.14], p < 0.001). Optimal sleep was inversely related with bedroom TV (OR 0.63 [0.50,0.79], p < 0.001), with sleeping disorders in the first year (OR 0.62 [0.48,0.80], p < 0.001)), with bottle use (OR 0.64 [0.44,0.94], p < 0.05) and posivively related with high mother's education level (OR 1.44 [1.11,1.88], p < 0.01)., Conclusions: About one third of 1 to 14 year Italian children sleep less than recommended, one half in teenage. Modifiable risk factors for sleep abnormalities such as video devices use, bedroom TV and bottle use should be target of preventive strategies for a correct sleep. Pediatricians should give priority to the identification of sleep disorders early in life.

Background: Allergic sensitization in children and allergic diseases arising therefrom are increasing for decades. Several interventions, functional foods, pro- and prebiotics, vitamins are proposed for the prevention of allergies and they can't be uncritically adopted., Objective: This Consensus document was developed by the Italian Society of Preventive and Social Paediatrics and the Italian Society of Paediatric Allergy and Immunology. The aim is to provide updated recommendations regarding allergy prevention in children., Methods: The document has been issued by a multidisciplinary expert panel and it is intended to be mainly directed to primary care paediatricians. It includes 19 questions which have been preliminarily considered relevant by the panel. Relatively to each question, a literature search has been performed, according to the Italian National Guideline Program. Methodology, and a brief summary of the available literature data, has been provided. Many topics have been analyzed including the role of mother's diet restriction, use of breast/formula/hydrolyzed milk; timing of introduction of complementary foods, role (if any) of probiotics, prebiotics, vitamins, exposure to dust mites, animals and to tobacco smoke., Results: Some preventive interventions have a strong level of recommendation. (e.g., the dehumidifier to reduce exposure to mite allergens). With regard to other types of intervention, such as the use of partially and extensively hydrolyzed formulas, the document underlines the lack of evidence of effectiveness. No preventive effect of dietary supplementation with polyunsaturated fatty acids, vitamins or minerals has been demonstrated. There is no preventive effect of probiotics on asthma, rhinitis and allergic diseases. It has demonstrated a modest effect, but steady, in the prevention of atopic dermatitis., Conclusions: The recommendations of the Consensus are based on a careful analysis of the evidence available. The lack of evidence of efficacy does not necessarily imply that some interventions may not be effective, but currently they can't be recommended.

Objectives: Under physiological conditions, cerumen (Ce) is regularly extruded from the ear canal by a self-cleaning mechanism. Failure of this mechanism leads to excessive accumulation or impaction of Ce. Limited data are available concerning the prevalence of cerumen in healthy and sick infants and children. We assessed the prevalence of Ce in a large population of infants and children and compared the Ce removal attitudes of paediatricians (PEDs) and otorhinolaryngologists (ENTs)., Methods: Children seen in November 2014 for acute respiratory infections, including suspected acute otitis media, or well-being visits, were enrolled. The following data were recorded: presence, laterality, and amount of Ce; presenting complaints and final diagnosis; attempt to remove Ce during the visit; and type of physician., Results: Among 819 children aged 1 month to 12 years, Ce was present in 594 (72.5%), of whom 478 (80.5%) had bilateral Ce, and 261 (43.9%) had Ce in a relevant amount (cerumen obstructing at least 50% of the ear canal). Presence of Ce was more common in younger and in African or Asian children. PEDs were less likely to remove cerumen than ENTs (28.8% vs 91.0%, p < 0.001) irrespective of age, gender, race and reason for visit. Ce was removed by PEDs in less than one-third of sick children with a final diagnosis of acute otitis media (AOM) (31.6%) compared with almost all the children by ENTs (95.6%, p < 0.001)., Conclusion: Ce is highly prevalent in healthy and sick children but is quite neglected by PEDs. Educational programs to reinforce the importance of Ce removal and to improve the techniques for removal in case of suspected AOM should be implemented and rigorously evaluated in order to avoid incorrect diagnosis and erroneous treatments., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Functional gastrointestinal disorders (FGIDs) are chronic or recurrent gastrointestinal symptoms without structural or biochemical abnormalities. FGIDs are multifactorial conditions with different pathophysiologic mechanisms including altered motility, visceral hyperalgesia, brain-gut disturbance, genetic, environmental and psychological factors. Although in most cases gastrointestinal symptoms are transient and with spontaneous resolution in infancy multiple dietary changes and pharmacological therapy are often started despite a lack of evidence-based data. Our aim was to update and critically review the current literature to assess the effects and the clinical appropriateness of drug treatment in early (occurring in infants and toddlers) FGIDs., Methods: We systematically searched the Medline and GIMBE (Italian Group on Medicine Based on Evidence) databases, according to the methodology of the Critically Appraised Topics (CATs). We included reviews, clinical studies, and evidence-based guidelines reporting on pharmacological treatments. Systematic reviews and randomized controlled trials (RCTs) concerning pharmacologic therapies in children with early FGIDs were included, and data were extracted on participants, interventions, and outcomes., Results: We found no evidence-based guidelines or systematic reviews about the utility of pharmacological therapy in functional regurgitation, infant colic and functional diarrhea. In case of regurgitation associated with marked distress, some evidences support a short trial with alginate when other non pharmacological approach failed (stepped-care approach). In constipated infants younger than 6 months of age Lactulose is recommended, whilst in older ages Polyethylene glycol (PEG) represents the first-line therapy both for fecal disimpaction and maintenance therapy of constipation. Conversely, no evidence supports the use of laxatives for dyschezia. Furthermore, we found no RCTs regarding the pharmacological treatment of cyclic vomiting syndrome, but retrospective studies showed a high percentage of clinical response using cyproheptadine, propanolol and pizotifen., Conclusion: There is some evidence that a pharmacological intervention is necessary for rectal disimpaction in childhood constipation and that PEG is the first line therapy. In contrast, for the other early FGIDs there is a lack of well-designed high-quality RCTs and no evidence on the use of pharmacological therapy was found.

Our knowledge of the molecular events underlying type 2 diabetes mellitus-a protein conformational disease characterized by the aggregation of islet amyloid polypeptide (IAPP) in pancreatic β cells-is limited. However, amyloid-mediated membrane damage is known to play a key role in IAPP cytotoxicity, and therefore the effects of lipid composition on modulating IAPP-membrane interactions have been the focus of intense research. In particular, membrane cholesterol content varies with aging and consequently with adverse environmental factors such as diet and lifestyle, but its role in the development of the disease is controversial. In this study, we employ a combination of experimental techniques and in silico molecular simulations to shed light on the role of cholesterol in IAPP aggregation and the related membrane disruption. We show that if anionic POPC/POPS vesicles are used as model membranes, cholesterol has a negligible effect on the kinetics of IAPP fibril growth on the surface of the bilayer. In addition, cholesterol inhibits membrane damage by amyloid-induced poration on membranes, but enhances leakage through fiber growth on the membrane surface. Conversely, if 1:2 DOPC/DPPC raft-like model membranes are used, cholesterol accelerates fiber growth. Next, it enhances pore formation and suppresses fiber growth on the membrane surface, leading to leakage. Our results highlight a twofold effect of cholesterol on the amyloidogenicity of IAPP and help explain its debated role in type 2 diabetes mellitus., (Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Cervical lymphadenopathy is a common disorder in children due to a wide spectrum of disorders. On the basis of a complete history and physical examination, paediatricians have to select, among the vast majority of children with a benign self-limiting condition, those at risk for other, more complex, diseases requiring laboratory tests, imaging and, finally, tissue sampling. At the same time, they should avoid expensive and invasive examinations when unnecessary. The Italian Society of Preventive and Social Pediatrics, jointly with the Italian Society of Pediatric Infectious Diseases, the Italian Society of Pediatric Otorhinolaryngology, and other Scientific Societies, issued a National Consensus document, based on the most recent literature findings, including an algorithm for the management of cervical lymphadenopathy in children., Methods: The Consensus Conference method was used, following the Italian National Plan Guidelines. Relevant publications in English were identified through a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception through March 21, 2014., Results: Basing on literature results, an algorithm was developed, including several possible clinical scenarios. Situations requiring a watchful waiting strategy, those requiring an empiric antibiotic therapy, and those necessitating a prompt diagnostic workup, considering the risk for a severe underling disease, have been identified., Conclusion: The present algorithm is a practice tool for the management of pediatric cervical lymphadenopathy in the hospital and the ambulatory settings. A multidisciplinary approach is paramount. Further studies are required for its validation in the clinical field.

Background: Several guidelines for the management of respiratory tract infections in children are available in Italy, as well as in other European countries and the United States of America. However, poor adherence to guidelines and the sustained inappropriate use of antibiotics have been reported. In the outpatient setting, almost half of antibiotics are prescribed for the treatment of common respiratory tract infections. In Italy the antibiotic prescription rate is significantly higher than in other European countries, such as Denmark or the Netherlands, and also the levels of antibiotic resistance for a large variety of bacteria are higher. Therefore, the Italian Society of Preventive and Social Paediatrics organised a consensus conference for the treatment of respiratory tract infections in children to produce a brief, easily readable, evidence-based document., Methods: The conference method was used, according to the National Institute of Health and the National Plan Guidelines. A literature search was performed focusing on the current guidelines for the treatment of airway infections in children aged 1 month-18 years in the ambulatory setting., Results: Recommendations for the treatment of acute pharyngitis, acute otitis media, sinusitis, and pneumonia have been summarized. Conditions for which antibiotic treatment should not be routinely prescribed have been highlighted., Conclusion: This evidence-based document is intended to accessible to primary care pediatricians and general practice physicians in order to make clinical practice uniform, in accordance with the recommendations of the current guidelines., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Metallated meso-tetrakis(N-methyl-4-pyridyl)porphyrin (MTMPyP) and 5,11,17,23-tetrasulfonato-25,26,27,28-tetrakis-(hydroxylcarbonylmethoxy)-calix[4]arene (C(4)TsTc) were used as key components for building up discrete supramolecular entities starting from the formation of the template species MTMPyP:C(4)TsTc (1 : 4, M = Cu, Zn). The stepwise addition of further amount of porphyrin allows the facile non-covalent synthesis of discrete supramolecular entities (2 : 4 and 3 : 4) which can be built up just by programming the right stoichiometric addition of the proper porphyrin. The redox potentials of these supramolecular complexes in aqueous media, as well as those of the parent metalloporphyrins, have been characterized by using square wave voltammetry technique. The use of the simulation procedure leads us to establish the electrochemical steps involved in the redox processes for each supramolecular species, evidencing multistep electron reductions which were not experimentally resolved clearly because of their closeness. The most striking result is that the electrochemistry of each of these supramolecular complexes is different from that of the parent components. This "anomalous" behavior can be explained only considering each of these supramolecular complexes as a unique entity, in which such an internal electronic communication might occur. The formation of the 1 : 4 supramolecular complex produces a negative shift as to the metallated porphyrin redox potentials of about 30 mV. In the case of 2 : 4 and 3 : 4 species, the redox potentials progressively shifts towards more positive values by about 10-15 mV for each complexation step.

Acute otitis media (AOM) is the most common disease occurring in infants and children and has major medical, social and economic effects. If we consider the Italian pediatric population and the incidence rates in different age ranges it can be calculated that almost one million cases of AOM are diagnosed in Italy every year. Various attempts have been made internationally to clarify the most appropriate ways in which AOM should be managed. In Italy, this has been done at local or regional level but there have so far been no national initiatives. The objective of this guideline is to provide recommendations to pediatricians, general practitioners and otolaryngologists involved in the clinical management of acute otitis media in healthy children aged 2 months to 12 years. After a systematic review and grading of evidences from the literature, the document was drafted by a multidisciplinary panel with identified key clinical questions related to diagnosis, treatment of the acute episode, management of complications and prevention., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Medical education and guidelines have been advocated as major means of improving the management of otitis media. Limited data are available concerning medical education in acute otitis media (AOM), and the association between medical education and attitudes about AOM guidelines has never been explored., Objectives: To assess the prevalence of medical education concerning AOM, of a positive attitude toward AOM guidelines and of appropriate diagnostic methods in a large sample of Italian pediatricians (PEDs) and otolaryngologist (ENTs) and to look for possible associations between them., Subjects and Methods: This cross-sectional survey was based on the responses of 2012 physicians (1160 PEDs and 852 ENTs) to a mailed anonymous questionnaire., Results: Very few (9%) of the responders had received any AOM medical education during medical school, but the number increased during residency (38%) and peaked in the postresidency period (53%) with slight differences between PEDs and ENTs. Forty percent reported a positive attitude toward AOM guidelines, with PEDs having a better attitude than ENTs (46% vs. 32%, P < 0.001). An appropriate diagnostic method for AOM was reported by only 21% of the physicians (PEDs 11% vs. ENTs 35%, P < 0.001). AOM medical education during postresidency and reporting the use of appropriate diagnostic methods were significantly associated with a positive attitude about AOM guidelines., Conclusions: Specific educational programs concerning AOM should be implemented and rigorously evaluated, before physicians become fully trained PEDs and ENTs, and maintained during postresidency. Evidence-based guidelines should be further incorporated into everyday practice of both PEDs and ENTs.

Background: Minimally invasive esophagectomy has the potential to minimize the morbidity of esophageal resection and is particularly suited to the transhiatal approach. This report details our experience with this technique and the lessons we have learned., Methods: A retrospective analysis of patients who underwent minimally invasive transhiatal esophagectomy was performed. Parameters assessed included patient demographics, tumor pathology, operative and postoperative course, and survival., Results: Eighteen patients underwent minimally invasive transhiatal esophagectomy [median age = 69 years (range = 36-79)]. Seventeen were operated on for cancer, including 13 adenocarcinomas and 4 squamous cell carcinomas (median histological stage = 2, range = 1-3), and 1 for high-grade dysplasia in Barrett's. One patient had neoadjuvant chemotherapy. Two patients underwent nonemergency conversion to open surgery. The median duration of operation was 300 min (range = 180-450). All anastomoses were end-to-side hand-sewn. No patients received a red cell transfusion. The 30-day mortality was zero. Complications developed in 15 patients, including 7 respiratory and 10 recurrent laryngeal nerve injuries. There were two anastomotic leaks. Six patients developed stenosis requiring dilatation. The median length of stay was 15 days (range = 10-39). The median number of nodes harvested was 10 (range = 2-26). At a median follow-up of 13 months (range = 4-42), 13 patients were alive., Conclusions: Minimally invasive transhiatal esophagectomy is feasible in our unit, with acceptable mortality. The high rate of anastomotic stenosis has resulted in a change to a semimechanical, side-to-side isoperistaltic technique. The high rate of recurrent laryngeal nerve injuries has resulted in the avoidance of metal retractors at the tracheo-esophageal groove.

Introduction: We evaluated the peri- and postoperative effects of the lack of a temporary portocaval anastomosis (TPCA) during orthotopic liver transplantation (OLT) in 84 patients with cirrhosis., Patients and Methods: From December 1996 to December 2002, 156 liver transplant recipients included (54%; 60 men and 24 women) of mean age 52 +/- 9 years with portal hypertension. In whom peri- and postoperative data were analyzed., Results: The median fall in mean arterial pressure upon vascular clamping and unclampings was 20 mm Hg (range 15 to 75), while the median duration of portal vein clamping was 77 minutes. The median amount of blood autotransfusion was 1100 mL (range 0 to 5400). The median number of red blood cell and fresh-frozen plasma units transfused were 5 and 6.5, respectively. The median intraoperative urinary output was 72 mL/h (range 11 to 221). Three patients (3.5%) presented a perioperative complication, but no perioperative death was observed. Six patients experienced an early postoperative complication (<10 days): five hemodynamic complications and one transient renal failure, which did not require hemodialysis. One patient (1%) died at 12 hours after OLT from acute pulmonary edema., Conclusion: This study shows that systematic TPCA during OLT with preservation of the native retrohepatic vena cava in cirrhotic patients does not appear to be justified. In contrast, peri- and postoperative hemodynamic parameters as well as blood component requirements were comparable to those of the literature reporting OLT with straightforward TPCA.

The authors report their experience on surgical treatment of peptic bleeding lesions. From January 1994 till April 1999 they observed and surgically treated 35 patients (mean age 65) suffering from bleeding gastroduodenal ulcer. Complications linked to surgical treatment had an incidence of 17.5%, while those ones linked to the patient's general conditions of 21%; mortality was 20%. Surgery has been gradually substituted by endoscopy which represent the principal examination for diagnosis of bleeding gastroduodenal ulcer with the aid of different hemostatic techniques, so that surgery has been relegated to the last place in uncontrollable bleeding treatment. Observed results, following those ones of other authors, show the unfavourable prognosis linked to patient's different conditions when surgeon operates.

The authors guided by their personal experience (612 abdominal hernioplasties performed between 1992 and 1998) after using for the cure of inguinal and femoral hernias diverse prosthesis illustrate the characteristics of the polipropene prosthesis which in their opinion possesses every requirement necessary to enable it to become the defining ideal prosthesis. The authors underline again the use of this routinely applied prosthesis, also in a local anaesthesia it has favoured the development of the tension-free and suture-less technique which hes allowed hernioplasty to spread in day-surgery.

The technique of a liver autograft in the pig has three advantages: (1) It provides an excellent training model of liver transplantation, (2) it provides an experimental model for cancer research, and (3) it is more economical than liver allotransplant. We describe a facilitated technique of liver autograft, which can be employed to develop experimental models without the use of a biopump. Mean blood arterial pressure, heart rate, pH, and lactates were tested during the liver grafting and at the end of the procedure in pigs that underwent autografting of the liver and compared with pigs that underwent an orthotopic liver allotransplantation. The cell damage was assessed in the same two groups of animals by monitoring aspartate aminotransferase (AST) and alanine aminotransferase (ALT) blood levels and with the MEGX test, 15 min after the beginning of reperfusion. The surgical procedure may be divided into three parts: hepatectomy, side-to-side portocaval shunt with passive caval-jugular shunt, and reimplantation. This procedure could have a clinical indication for otherwise unresectable liver tumors.

The aims of this investigation are: 1) to assess the function of the hepatocyte in transplanted porcine liver, immediately after reperfusion, by monitoring both LFTs and the MEGX levels; 2) to search for correlation between MEGX and LFTS, in an effort to evaluate the metabolic mechanisms occurring in the early liver transplantation revascularization phase. The MEGX test was found to be less than 50 micrograms/ml in all the recipients and all the LFTS tested have been reported to be out the normal range. Furthermore our data has shown a statistically significant correlationship between the MEGX values and those of alkaline phosphatase and prothrombin and a highly significant correlationship with cholinesterase.

Data from twelve patients who had hepatic resections for colorectal liver metastases were retrospectively analyzed to determine: 1) whether the use of the ultrasonic surgical dissector and the Argon laser can significantly simplify major hepatic resections and decrease both perioperative blood loss and postoperative morbidity and mortality, and 2) whether an adequate patients selection for surgery can effectively determine an improvement in recurrence rate. We performed 4 bisegmentectomies (2 of V and VI; 2 of VI and VII); 1 trisegmentectomy (V, VI, VII); 2 left lobectomies; 1 right hepatectomy and 4 wedge resections, using both the ultrasonic surgical dissector to fractionate and aspirate the hepatic parenchyma and to clear major vascular and biliary structures and the Argon laser for the coagulation of minor vascular and biliary vessels. The resected metastases averaged 5.5 cm (range: 1.5-7.5); blood transfusion requirements were significantly reduced from previous reports, averaging only 1.25 units (range: 0.3); the average operative time was 238 minutes (110 to 420 minutes). There were no operative deaths, operative morbidity rate was 16.6. The results indicate that the ultrasonic surgical dissector and the Argon laser have made a significant contribution to our marked decrease in the average blood loss and transfusion requirement. The long-term results seems to be improved by an adequate patients selection.

The prevention of sudden cardiac death remains one of the greatest challenges in the field of cardiovascular medicine today. Despite the difficulty in predicting which individuals are going to die suddenly, much knowledge has accumulated in recent years in regard to independent risk factors for SCD and moreover, different pharmacological interventions have been evaluated for the prevention of sudden coronary death. Currently, the beta-blockers are the only pharmacological agents that have been shown to reduce sudden cardiac deaths in clinical trials. The reduction in sudden death may involve several mechanisms that include antiatherosclerotic effects, antithrombotic effects, cardiac anti-ischemic effects and antifibrillatory effects.

The analysis of records collected during long-term ambulatory electrocardiographic monitoring has traditionally involved the review of massive data, either manually or with the aid of interactive scanning computers. Many factors complicate this analysis, including the use of analog tape for storage of electrocardiographic waveforms, the need to analyze 100,000 waveforms from an average 24-hour study, and the need to deal with an interface that compresses 24 hours of data into as little as 6 minutes on a screen. Today, the computer incorporated in the monitor can scrutinize each cardiac cycle in real time. The system produces a statistical report based on every heart beat and also performs data reduction and storage of electrocardiograph samples. To assess real-time analysis we examined data collected from the Circadian CircaMed ambulatory electrocardiography system. We found that it could detect and quantify simple or complex ventricular ectopic beats, brady- or tachyarrhythmic events, and ST-segment deviation. One hundred fifty patients 21 to 85 years old with symptoms or clinical finding suggestive of ischemia, cardiac arrhythmia, or conductive defects were referred to our electrocardiography laboratory for ambulatory monitoring. The results demonstrate that this system can detect the full range of cardiac disease found with the traditional method. Of the 150 patients, ambulatory electrocardiographic tests were positive in 93 (62%). In addition, we developed a methodology for lead placement when using two bipolar leads, as is typical for ambulatory electrocardiography. We present a procedure for determining the optimum lead placement that is based on the patient's history and a 12-lead electrocardiogram.

The synthesis of 1,3,3-trimethyl-N-(2-pyridyl)-2-oxabicyclo-[2.2.2]octan-6-amine (cis, trans mixture) starting from 1,3,3-trimethyl-N-nitro-2-oxabicyclo[2.2.2]octan-6-imine, as well as of a series of amides (V) derived from the above amine, is described. Some compounds (V) showed strong hypotensive activity in rats. Effects on heart rate and antiarrhythmic activity in rats, as well as local anesthetic activity in mice, are also reported.

The synthesis of 1-phenyl- and 1-methyl-5-dialkylamino-methyl-1,5,6,7-tetrahydroindazol-4-ones (III) and (IV) by Mannich reaction of the corresponding 1-substituted 1,5,6,7-tetrahydroindazol-4-ones (I) and (II) is described. Some compounds (III) showed a good antiinflammatory and analgesic activity in rats and mice, respectively. Infiltration anesthesia in mice and antiacetylcholine activity in vitro are also reported.

A clinically and sonographically identified case of atrial myxoma with no prolapse due to its short peduncle is described with emphasis on the importance of 2D echocardiography given the lack of both clinical symptoms and Time Motion ultrasound data in atrial myxomas prolapsing through the mitral anulus into the ventricular cavity. In fact 2D echocardiography shows up the systolic-diastolic swing of the tumour mass between the lower third of the left atrium and the atrioventricular valvular plane.